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Wu GW, Hsieh YH, Chien YC, Bai LY, Yu YL. Novel Insights into PGM2L1 as a Prognostic Biomarker in Cholangiocarcinoma: Implications for Metabolic Reprogramming and Tumor Microenvironment Modulation. Int J Med Sci 2025; 22:1158-1166. [PMID: 40027181 PMCID: PMC11866533 DOI: 10.7150/ijms.106566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Accepted: 01/17/2025] [Indexed: 03/05/2025] Open
Abstract
Cholangiocarcinoma (CCA) is a highly lethal malignancy and the most common adenocarcinoma of the hepatobiliary system. PGM2L1 belongs to the α-D-phosphohexomutase superfamily and functions as a glucose 1,6-bisphosphate (G16BP) synthase. There is growing evidence to provide an association its function to cancer metabolism and progression. However, the molecular mechanisms of PGM2L1 in CCA development remain lacking in evidence. In this study, we found that CCA patients with high PGM2L1 expression had the poorest prognosis. We identified two methylation sites (cg15214137 and cg03699633) within the PGM2L1 gene and their prognostic relevance. We further investigated the relationship between PGM2L1 expression and tumor-infiltrating immune cells, with a particular focus on neutrophils in CCA. Functional enrichment analyses further revealed that high PGM2L1 expression was associated with the Wnt signaling pathway, glycolytic metabolism, and the recruitment of neutrophils. Collectively, these findings suggest that PGM2L1 may serve as an independent prognostic biomarker and is closely linked to tumor immune infiltration and metabolic reprogramming in CCA.
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Affiliation(s)
- Guo-Wei Wu
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung 406040, Taiwan
- Institute of Translational Medicine and New Drug Development, China Medical University, Taichung 406040, Taiwan
- Center for Molecular Medicine, China Medical University Hospital, Taichung 404327, Taiwan
| | - Yi-Hsien Hsieh
- Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
- Department of Medical Research, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
| | - Yi-Chung Chien
- Institute of Translational Medicine and New Drug Development, China Medical University, Taichung 406040, Taiwan
- Center for Molecular Medicine, China Medical University Hospital, Taichung 404327, Taiwan
| | - Li-Yuan Bai
- Division of Hematology and Oncology, China Medical University Hospital, Taichung, 404327, Taiwan
| | - Yung-Luen Yu
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung 406040, Taiwan
- Institute of Translational Medicine and New Drug Development, China Medical University, Taichung 406040, Taiwan
- Center for Molecular Medicine, China Medical University Hospital, Taichung 404327, Taiwan
- Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung 413305, Taiwan
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Supradit K, Prasopdee S, Phanaksri T, Tangphatsornruang S, Pholhelm M, Yusuk S, Butthongkomvong K, Wongprasert K, Kulsantiwong J, Chukan A, Tesana S, Thitapakorn V. Differential circulating miRNA profiles identified miR-423-5p, miR-93-5p, and miR-4532 as potential biomarkers for cholangiocarcinoma diagnosis. PeerJ 2024; 12:e18367. [PMID: 39677943 PMCID: PMC11639864 DOI: 10.7717/peerj.18367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Accepted: 09/30/2024] [Indexed: 12/17/2024] Open
Abstract
Background Cholangiocarcinoma (CCA) is high in morbidity and mortality rates which may be due to asymptomatic and effective diagnostic methods not available. Therefore, an effective diagnosis is urgently needed. Methods Investigation of plasma circulating miRNA (cir-miRNA) was divided into two phases, including the discovery phase (pooled 10 samples each from three pools in each group) and the validation phase (17, 16, and 35 subjects of healthy control (HC), O. viverrini (OV), and CCA groups, respectively). The plasma from healthy control subjects, O. viverrini infected subjects, and CCA subjects was used. In the discovery phase, plasma was pooled by adding an equal volume of plasma, and cir-miRNA was isolated and analyzed with the nCounter® SPRINT Profiler. The significantly different cir-miRNAs were selected for the validation phase. In the validation phase, cir-miRNA was isolated and analyzed using real time-quantitative polymerase chain reaction (RT-qPCR). Subsequently, statistical analysis was conducted, and diagnostic parameters were calculated. Results Differential plasma cir-miRNA profile showed at least three candidates including miR-423-5p, miR-93-5p, and miR-4532 as potential biomarkers. From validation of these cir-miRNAs by RT-qPCR, the result showed that the satisfied sensitivity and specificity to differential CCA group from HC and OV group was obtained from miR-4532 (P < 0.05) while miR-423-5p and miR-93-5p can be used for differential CCA from OV and HC group (P < 0.05) with high specificity but limited the sensitivity. In conclusion, candidate cir-miRNAs have been identified as potential biomarkers including miR-423-5p, miR-93-5p and miR-4532. Screening by miR-4532 and confirmed with miR-423-5p, miR-93-5p were suggested for differential CCA patients in the endemic area of O. viverrini.
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Affiliation(s)
- Kittiya Supradit
- Radiological technology, Faculty of Science, Ramkhamhaeng University, Bangkok, Thailand
| | - Sattrachai Prasopdee
- Chulabhorn International College of Medicine (CICM), Thammasat University, Pathum Thani, Thailand
- Research Group in Multidimensional Health and Disease (MHD), Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, Thailand
- Thammasat Research Unit in Opisthorchiasis, Cholangiocarcinoma, and Neglected parasitic Diseases (TRU-OCN), Thammasat University, Pathum Thani, Thailand
| | - Teva Phanaksri
- Chulabhorn International College of Medicine (CICM), Thammasat University, Pathum Thani, Thailand
| | - Sithichoke Tangphatsornruang
- National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand
| | - Montinee Pholhelm
- Chulabhorn International College of Medicine (CICM), Thammasat University, Pathum Thani, Thailand
- Research Group in Multidimensional Health and Disease (MHD), Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, Thailand
- Thammasat Research Unit in Opisthorchiasis, Cholangiocarcinoma, and Neglected parasitic Diseases (TRU-OCN), Thammasat University, Pathum Thani, Thailand
| | - Siraphatsorn Yusuk
- Thammasat Research Unit in Opisthorchiasis, Cholangiocarcinoma, and Neglected parasitic Diseases (TRU-OCN), Thammasat University, Pathum Thani, Thailand
| | | | - Kanokpan Wongprasert
- Department of Anatomy, Faculty of Science, Mahidol University, Bangkok, Thailand
| | | | | | - Smarn Tesana
- Research Group in Multidimensional Health and Disease (MHD), Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, Thailand
| | - Veerachai Thitapakorn
- Chulabhorn International College of Medicine (CICM), Thammasat University, Pathum Thani, Thailand
- Research Group in Multidimensional Health and Disease (MHD), Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, Thailand
- Thammasat Research Unit in Opisthorchiasis, Cholangiocarcinoma, and Neglected parasitic Diseases (TRU-OCN), Thammasat University, Pathum Thani, Thailand
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Juengsamarn J, Sookthon C, Jeerapradit K, Sriudomporn K, Chansitthichok S, Ouransatien W, Suragul W, Boonpob S, Sarkhampee P, Ngamphaiboon N. Predictive MINT Pathologic Risk Score for Adjuvant Chemotherapy in Resected Cholangiocarcinoma: A Propensity Score-Matched Multicenter Study in Thailand. JCO Glob Oncol 2024; 10:e2400286. [PMID: 39418629 DOI: 10.1200/go-24-00286] [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: 06/21/2024] [Accepted: 08/18/2024] [Indexed: 10/19/2024] Open
Abstract
PURPOSE This study aims to clarify the benefit of adjuvant chemotherapy (AC) in resectable cholangiocarcinoma (CCA) and develop a predictive risk score for treatment selection. METHODS Patients with resected CCA undergoing curative surgery, with or without AC, were identified from three centers in Thailand. Patients with R2 resection and 30 days postoperative death were excluded. Using the largest center as the discovery cohort, we generated propensity score matching (PSM). A predictive model for overall survival (OS) was identified, and a predictive risk score was developed from the PSM discovery cohort, classifying patients into high- and low-risk groups. The proposed risk score was validated in the other two centers. RESULTS In the discovery cohort, 493 patients were identified. After PSM, 328 patients were categorized into surgery (n = 164) and surgery + AC (n = 164) groups. The baseline characteristics in the PSM discovery cohort were well-balanced. In the validation cohort (n = 83), patients with positive lymph node 1 received AC more frequently than those under observation (47% v 18%; P = .02). A MINT pathologic risk score was developed from multivariate analysis for OS. The score includes margin, perineural invasion, pathologic nodal status, and pathologic tumor size. In the PSM discovery cohort, for the low-risk score group, the surgery group had significantly longer OS compared with the surgery + AC group (49.4 v 31.5 months; hazard ratio [HR], 1.78 [95% CI, 1.11 to 2.86]; P = .016). Conversely, for the high-risk score group, the surgery + AC group had better OS than the surgery group (18.8 v 8 months; HR, 0.60 [95% CI, 0.46 to 0.79]; P < .001). The results were comparable in the validation cohort. CONCLUSION Patients with resected CCA with a high-risk MINT pathologic risk score were likely to benefit from AC, whereas those with a low-risk score were not. Further validation in a larger prospective cohort is warranted.
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Affiliation(s)
- Jitlada Juengsamarn
- Department of Medicine, Sunpasitthiprasong Hospital, Ubonratchathani, Thailand
| | | | - Kaewta Jeerapradit
- Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
- Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan, Thailand
| | - Kanin Sriudomporn
- Division of Medical Genetics and Molecular Biology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | | | - Weeris Ouransatien
- Department of Surgery, Sunpasitthiprasong Hospital, Ubonratchathani, Thailand
| | - Wikran Suragul
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | | | - Poowanai Sarkhampee
- Department of Surgery, Sunpasitthiprasong Hospital, Ubonratchathani, Thailand
| | - Nuttapong Ngamphaiboon
- Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
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Sakuma M, Takahashi D, Kamei K, Takayama Y, Takahashi T, Aoyama H, Hosoi T, Maeda A. Drug-free remission of immune thrombocytopenic purpura following resection of perihilar cholangiocarcinoma: a case report. J Surg Case Rep 2024; 2024:rjae607. [PMID: 39329010 PMCID: PMC11427118 DOI: 10.1093/jscr/rjae607] [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: 07/12/2024] [Accepted: 09/11/2024] [Indexed: 09/28/2024] Open
Abstract
Immune thrombocytopenic purpura (ITP) is a rare autoimmune disorder. Although secondary ITP, caused by various underlying diseases, including some malignant tumors, has been reported, instances of ITP resolving after successful treatment of the underlying cause are uncommon and noteworthy. Herein, we present a case of a patient with perihilar cholangiocarcinoma (pCCA) and ITP who achieved drug-free remission of ITP following tumor resection. A 76-year-old man presented with pCCA complicated by ITP. Prednisolone treatment successfully managed his thrombocytopenia, allowing for a left hepatopancreatoduodenectomy. ITP relapse did not occur after discontinuation of prednisolone postoperatively. This case suggests that surgical resection of the underlying malignancy may induce remission of secondary ITP associated with pCCA.
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Affiliation(s)
- Masayoshi Sakuma
- Department of Surgery, Ogaki Municipal Hospital, 4-86, Minaminokawa-cho, Ogaki city, Gifu, Japan
| | - Daigoro Takahashi
- Department of Surgery, Ogaki Municipal Hospital, 4-86, Minaminokawa-cho, Ogaki city, Gifu, Japan
| | - Keitaro Kamei
- Department of Surgery, Ogaki Municipal Hospital, 4-86, Minaminokawa-cho, Ogaki city, Gifu, Japan
| | - Yuichi Takayama
- Department of Surgery, Ogaki Municipal Hospital, 4-86, Minaminokawa-cho, Ogaki city, Gifu, Japan
| | - Takamasa Takahashi
- Department of Surgery, Ogaki Municipal Hospital, 4-86, Minaminokawa-cho, Ogaki city, Gifu, Japan
| | - Hiroki Aoyama
- Department of Surgery, Ogaki Municipal Hospital, 4-86, Minaminokawa-cho, Ogaki city, Gifu, Japan
| | - Takahiro Hosoi
- Department of Surgery, Ogaki Municipal Hospital, 4-86, Minaminokawa-cho, Ogaki city, Gifu, Japan
| | - Atsuyuki Maeda
- Department of Surgery, Ogaki Municipal Hospital, 4-86, Minaminokawa-cho, Ogaki city, Gifu, Japan
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Zhang B, Jin B, Wu X, Xing J, Liu X, Wan X, Xu H, Xu Y, Mao Y, Chen Q, Bai Y, Guan M, Du S. Investigation of transcriptional and immunological disparities among patient groups with varied prognostic risk factors in cholangiocarcinoma. Cancer Med 2024; 13:e70135. [PMID: 39206584 PMCID: PMC11358702 DOI: 10.1002/cam4.70135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Revised: 06/13/2024] [Accepted: 08/09/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND This study explores molecular features associated with better prognosis in cholangiocarcinoma (CCA). METHODS AND RESULTS The transcriptomic and whole-exome sequencing data obtained from paired tissues of 70 were analyzed, grouping them based on progression-free survival (PFS), differentiation degree, and lymph node metastasis. Among the 70 patients, the TP53 gene mutation frequency was the highest (53%), while FLG gene mutation occurred exclusively in the long PFS group. In the comparison between long and short survival groups, the short PFS group exhibited higher monocyte infiltration levels (p = 0.0287) and upregulation of genes associated with cancer-related transcriptional misregulation, chemokine signaling, and cytokine-cytokine receptor interactions. Differences in immune cell infiltration and gene expression were significant across differentiation and lymph node metastasis groups. Particularly noteworthy was the marked increase in CD8 T cell and NK cell infiltration (p = 0.0291, 0.0459) in the lymph node metastasis group, significantly influences prognosis. Additionally, genes related to platinum resistance, Th17 cell differentiation, and Th1 and Th2 cell differentiation pathways were overexpressed in this group. In summary, higher monocyte infiltration levels in the short PFS group, along with elevated expression of genes associated with cancer-related pathways, suggest a poorer prognosis. The significant increase in CD8 T cell and NK cell infiltration reflects an enhanced anti-tumor immune response, underscoring the relevance of immune infiltration levels and gene expression in predicting outcomes for CCA patients. CONCLUSIONS In this study, we elucidated the pertinent molecular mechanisms and pathways that influence the prognosis of CCAs through comprehensive multi-omics analysis.
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Affiliation(s)
- Baoluhe Zhang
- Department of Liver SurgeryPeking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Bao Jin
- Department of Liver SurgeryPeking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Xiang'an Wu
- Department of Liver SurgeryPeking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Jiali Xing
- Department of Liver SurgeryPeking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Xiao Liu
- Department of Liver SurgeryPeking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Xueshuai Wan
- Department of Liver SurgeryPeking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Haifeng Xu
- Department of Liver SurgeryPeking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Yiyao Xu
- Department of Liver SurgeryPeking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Yilei Mao
- Department of Liver SurgeryPeking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | | | | | - Mei Guan
- Department of Medical OncologyPeking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical collegeBeijingChina
| | - Shunda Du
- Department of Liver SurgeryPeking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
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Yang C, Xu J, Wang S, Wang Y, Zhang Y, Piao C. Machine learning to predict the early recurrence of intrahepatic cholangiocarcinoma: A systematic review and meta‑analysis. Oncol Lett 2024; 28:385. [PMID: 38966582 PMCID: PMC11222917 DOI: 10.3892/ol.2024.14518] [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: 11/30/2023] [Accepted: 04/12/2024] [Indexed: 07/06/2024] Open
Abstract
The prediction of early recurrent of intrahepatic cholangiocarcinoma (ICC) has been widely investigated; however, the predictive value is currently insufficient. To determine the effectiveness of machine learning (ML) for the diagnosis of early recurrent intrahepatic cholangiocarcinoma (ICC), particularly in comparison with clinical models, the present study aimed to determine which ML model had the best diagnostic performance for inpatients with recurrent ICC. In order to search for studies which could be included, three electronic databases were screened from inception to November 2023. A pairwise meta-analysis was performed to evaluate the diagnostic accuracy of the random effects model. A network meta-analysis was performed to identify the most effective ML-based diagnostic model based on the surface under the cumulative ranking curve score. A total of 5 studies of acceptable quality containing 1,247 patients with ICC were included in the present study. Following pairwise meta-analysis, it was found that the ML-based diagnostic accuracy was greater than that of clinical models (surface under the cumulative ranking curve score closer to 1, with significant differences), which initially proved that the ML-based diagnostic power was more optimal than that of clinical models. According to the network meta-analysis, the nomogram performed the best, indicating that this ML model achieved the best diagnostic accuracy for patients with recurrent ICC. In conclusion, the application of ML-based diagnostic models for patients with recurrent ICC was more optimal than the application of the clinical model. The nomogram model ranked first among the models and is therefore recommended for patients with recurrent ICC.
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Affiliation(s)
- Chao Yang
- Information Construction Department, Department of Ethnic Culture and Vocational Education, Liaoning National Normal College, Shenyang, Liaoning 110032, P.R. China
| | - Jianhui Xu
- Information Construction Department, Department of Ethnic Culture and Vocational Education, Liaoning National Normal College, Shenyang, Liaoning 110032, P.R. China
| | - Shuai Wang
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, P.R. China
| | - Ying Wang
- Information Construction Department, Department of Ethnic Culture and Vocational Education, Liaoning National Normal College, Shenyang, Liaoning 110032, P.R. China
| | - Yingshi Zhang
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, P.R. China
| | - Chengzhe Piao
- Information Construction Department, Department of Ethnic Culture and Vocational Education, Liaoning National Normal College, Shenyang, Liaoning 110032, P.R. China
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Xu Z, Fan X, Zhang C, Li Y, Jiang D, Hu F, Pan B, Huang Y, Zhang L, Lau WY, Liu X, Chen Z. Residual biliary intraepithelial neoplasia without malignant transformation at resection margin for perihilar cholangiocarcinoma does not require expanded resection: a dual center retrospective study. World J Surg Oncol 2024; 22:161. [PMID: 38907218 PMCID: PMC11191332 DOI: 10.1186/s12957-024-03395-5] [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: 03/02/2024] [Accepted: 04/28/2024] [Indexed: 06/23/2024] Open
Abstract
BACKGROUND Additional resection for invasive cancer at perihilar cholangiocarcinoma (pCCA) resection margins has become a consensus. However, controversy still exists regarding whether additional resection is necessary for residual biliary intraepithelial neoplasia (BilIN). METHOD Consecutive patients with pCCA from two hospitals were enrolled. The incidence and pattern of resection margin BilIN were summarized. Prognosis between patients with negative margins (R0) and BilIN margins were analyzed. Cox regression with a forest plot was used to identify independent risk factors associated with overall survival (OS) and recurrence-free survival (RFS). Subgroup analysis was performed based on BilIN features and tumor characteristics. RESULTS 306 pCCA patients receiving curative resection were included. 255 had R0 margins and 51 had BilIN margins. There was no significant difference in OS (P = 0.264) or RFS (P = 0.149) between the two group. Specifically, 19 patients with BilIN at distal bile ducts and 32 at proximal bile ducts. 42 patients showed low-grade BilIN, and 9 showed high-grade. Further analysis revealed no significant difference in long-term survival between different locations (P = 0.354), or between different grades (P = 0.772). Portal vein invasion, poor differentiation and lymph node metastasis were considered independent risk factors for OS and RFS, while BilIN was not. Subgroup analysis showed no significant difference in long-term survival between the lymph node metastasis subgroup, or between the portal vein invasion subgroup. CONCLUSION For pCCA patients underwent curative resection, residual BilIN at resection margin is acceptable. Additional resection is not necessary for such patients to achieve absolute R0 margin.
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Affiliation(s)
- Zeliang Xu
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Xiaoyi Fan
- Department of Oncology and Southwest Cancer Center, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Chengcheng Zhang
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Yuancheng Li
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Di Jiang
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Feng Hu
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Bi Pan
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Yixian Huang
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Leida Zhang
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Wan Yee Lau
- Faculty of Medicine, the Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China
| | - Xingchao Liu
- Department of Hepatobiliary Surgery, School of Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, No. 32, Qingyang District, Chengdu, 610072, China.
| | - Zhiyu Chen
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
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Kumar A, BharathwajChetty B, Manickasamy MK, Unnikrishnan J, Alqahtani MS, Abbas M, Almubarak HA, Sethi G, Kunnumakkara AB. Natural compounds targeting YAP/TAZ axis in cancer: Current state of art and challenges. Pharmacol Res 2024; 203:107167. [PMID: 38599470 DOI: 10.1016/j.phrs.2024.107167] [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: 02/08/2024] [Revised: 04/01/2024] [Accepted: 04/02/2024] [Indexed: 04/12/2024]
Abstract
Cancer has become a burgeoning global healthcare concern marked by its exponential growth and significant economic ramifications. Though advancements in the treatment modalities have increased the overall survival and quality of life, there are no definite treatments for the advanced stages of this malady. Hence, understanding the diseases etiologies and the underlying molecular complexities, will usher in the development of innovative therapeutics. Recently, YAP/TAZ transcriptional regulation has been of immense interest due to their role in development, tissue homeostasis and oncogenic transformations. YAP/TAZ axis functions as coactivators within the Hippo signaling cascade, exerting pivotal influence on processes such as proliferation, regeneration, development, and tissue renewal. In cancer, YAP is overexpressed in multiple tumor types and is associated with cancer stem cell attributes, chemoresistance, and metastasis. Activation of YAP/TAZ mirrors the cellular "social" behavior, encompassing factors such as cell adhesion and the mechanical signals transmitted to the cell from tissue structure and the surrounding extracellular matrix. Therefore, it presents a significant vulnerability in the clogs of tumors that could provide a wide window of therapeutic effectiveness. Natural compounds have been utilized extensively as successful interventions in the management of diverse chronic illnesses, including cancer. Owing to their capacity to influence multiple genes and pathways, natural compounds exhibit significant potential either as adjuvant therapy or in combination with conventional treatment options. In this review, we delineate the signaling nexus of YAP/TAZ axis, and present natural compounds as an alternate strategy to target cancer.
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Affiliation(s)
- Aviral Kumar
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati, Assam 781039, India
| | - Bandari BharathwajChetty
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati, Assam 781039, India
| | - Mukesh Kumar Manickasamy
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati, Assam 781039, India
| | - Jyothsna Unnikrishnan
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati, Assam 781039, India
| | - Mohammed S Alqahtani
- Radiological Sciences Department, College of Applied Medical Sciences, King Khalid University, Abha 61421, Saudi Arabia; BioImaging Unit, Space Research Centre, Michael Atiyah Building, University of Leicester, Leicester LE1 7RH, United Kingdom
| | - Mohamed Abbas
- Electrical Engineering Department, College of Engineering, King Khalid University, Abha 61421, Saudi Arabia
| | - Hassan Ali Almubarak
- Division of Radiology, Department of Medicine, College of Medicine and Surgery, King Khalid University, Abha 61421, Saudi Arabia
| | - Gautam Sethi
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 16 Medical Drive, Singapore 117600, Singapore; NUS Center for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, 117699, Singapore.
| | - Ajaikumar B Kunnumakkara
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati, Assam 781039, India.
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Pei F, Tao Z, Lu Q, Fang T, Peng S. Octamer-binding transcription factor 4-positive circulating tumor cell predicts worse treatment response and survival in advanced cholangiocarcinoma patients who receive immune checkpoint inhibitors treatment. World J Surg Oncol 2024; 22:110. [PMID: 38664770 PMCID: PMC11044354 DOI: 10.1186/s12957-024-03369-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Accepted: 03/28/2024] [Indexed: 04/29/2024] Open
Abstract
BACKGROUND Octamer-binding transcription factor 4-positive circulating tumor cell (OCT4+CTC) exhibits high stemness and invasive potential, which may influence the efficacy of immune checkpoint inhibitors (ICI). This study aimed to assess the prognostic role of OCT4+CTC in advanced cholangiocarcinoma (CCA) patients who received ICI treatment. METHODS In total, 40 advanced CCA patients who received ICI treatment were included, and CTC and OCT4 counts were detected via a Canpatrol system and an RNA in situ hybridization method before ICI treatment. Patients were subsequently divided into none CTC, OCT4-CTC, and OCT4+CTC groups. Patients were followed up for a median of 10.4 months. RESULTS The percentages of patients in none CTC, OCT4-CTC, and OCT4+CTC groups were 25.0%, 30.0%, and 45.0%, respectively. The proportion of patients with lymph node metastasis was highest in OCT4+CTC group, followed by none CTC group, and lowest in OCT4-CTC group (P = 0.025). The objective response rate (ORR) was lowest in OCT4+CTC group, moderate in OCT4-CTC group, and highest in none CTC group (P = 0.009), while disease control rate was not different among three groups (P = 0.293). In addition, progression-free survival (PFS) (P < 0.001) and overall survival (OS) (P = 0.001) were shorter in the OCT4+CTC group than in none CTC & OCT4-CTC group. Moreover, OCT4+CTC (versus none CTC) was independently linked with poorer PFS [hazard ratio (HR) = 6.752, P = 0.001] and OS (HR = 6.674, P = 0.003) in advanced CCA patients. CONCLUSION OCT4+CTC relates to lymph node metastasis and shows a good predictive value for poor treatment response and survival in advanced CCA patients who receive ICI treatment.
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Affiliation(s)
- Fei Pei
- Department of Hepatobiliary Pancreatic Surgery, Hubei Key Laboratory of Kidney Disease Pathogenesis and Intervention, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, No. 141 Tianjin Road, Huangshi, 435200, Hubei, China
| | - Zhen Tao
- Department of Hepatobiliary Pancreatic Surgery, Hubei Key Laboratory of Kidney Disease Pathogenesis and Intervention, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, No. 141 Tianjin Road, Huangshi, 435200, Hubei, China.
| | - Qi Lu
- Department of Hepatobiliary Pancreatic Surgery, Hubei Key Laboratory of Kidney Disease Pathogenesis and Intervention, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, No. 141 Tianjin Road, Huangshi, 435200, Hubei, China
| | - Tao Fang
- Department of Hepatobiliary Pancreatic Surgery, Hubei Key Laboratory of Kidney Disease Pathogenesis and Intervention, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, No. 141 Tianjin Road, Huangshi, 435200, Hubei, China
| | - Shasha Peng
- Department of Hepatobiliary Pancreatic Surgery, Hubei Key Laboratory of Kidney Disease Pathogenesis and Intervention, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, No. 141 Tianjin Road, Huangshi, 435200, Hubei, China
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10
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Makki M, Bentaleb M, Abdulrahman M, Suhool AA, Al Harthi S, Ribeiro Jr MAF. Current interventional options for palliative care for patients with advanced-stage cholangiocarcinoma. World J Clin Oncol 2024; 15:381-390. [PMID: 38576598 PMCID: PMC10989261 DOI: 10.5306/wjco.v15.i3.381] [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: 12/11/2023] [Revised: 01/18/2024] [Accepted: 02/27/2024] [Indexed: 03/22/2024] Open
Abstract
Primary biliary tract tumors are malignancies that originate in the liver, bile ducts, or gallbladder. These tumors often present with jaundice of unknown etiology, leading to delayed diagnosis and advanced disease. Currently, several palliative treatment options are available for primary biliary tract tumors. They include percutaneous transhepatic biliary drainage (PTBD), biliary stenting, and surgical interventions such as biliary diversion. Systemic therapy is also commonly used for the palliative treatment of primary biliary tract tumors. It involves the administration of chemotherapy drugs, such as gemcitabine and cisplatin, which have shown promising results in improving overall survival in patients with advanced biliary tract tumors. PTBD is another palliative treatment option for patients with unresectable or inoperable malignant biliary obstruction. Biliary stenting can also be used as a palliative treatment option to alleviate symptoms in patients with unresectable or inoperable malignant biliary obstruction. Surgical interventions, such as biliary diversion, have traditionally been used as palliative options for primary biliary tract tumors. However, biliary diversion only provides temporary relief and does not remove the tumor. Primary biliary tract tumors often present in advanced stages, making palliative treatment the primary option for improving the quality of life of patients.
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Affiliation(s)
- Maryam Makki
- Department of Surgery, Division of Trauma, Critical Care and Acute Care Surgery, Sheikh Shakhbout Medical City, Abu Dhabi 11001, United Arab Emirates
| | - Malak Bentaleb
- Department of Surgery, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi 11001, United Arab Emirates
| | - Mohammed Abdulrahman
- Department of Surgery, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi 11001, United Arab Emirates
| | - Amal Abdulla Suhool
- Department of Surgery, Division of Hepato-Pancreato-Biliary (HPB) Surgery, Sheikh Shakhbout Medical City, Abu Dhabi 91888, United Arab Emirates
| | - Salem Al Harthi
- Department of Surgery, Division of Hepato-Pancreato-Biliary (HPB) Surgery, Sheikh Shakhbout Medical City, Abu Dhabi 91888, United Arab Emirates
| | - Marcelo AF Ribeiro Jr
- Department of Surgery, Division of Trauma, Critical Care and Acute Care Surgery, Sheikh Shakhbout Medical City, Abu Dhabi 11001, United Arab Emirates
- Department of Surgery, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi 11001, United Arab Emirates
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11
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Elshami M, Ammori JB, Hardacre JM, Selfridge JE, Bajor D, Mohamed A, Chakrabarti S, Mahipal A, Winter JM, Ocuin LM. Surgical Resection Alone is Associated With Higher Long-Term Survival Than Multiagent Chemotherapy Alone for Patients With Localized Biliary Tract Cancers. J Surg Res 2024; 295:705-716. [PMID: 38141457 DOI: 10.1016/j.jss.2023.11.067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 07/17/2023] [Accepted: 11/12/2023] [Indexed: 12/25/2023]
Abstract
INTRODUCTION We compared long-term survival of patients with localized biliary tract cancers (BTCs) treated with either surgical resection or multiagent chemotherapy. METHODS Patients with localized BTC [gallbladder adenocarcinoma, extrahepatic cholangiocarcinoma, intrahepatic cholangiocarcinoma] were identified within the National Cancer Database (2010-2017). Piecewise-constant hazard modeling was used to estimate hazard ratios (HRs) at prespecified intervals: 0-30 d, 31-60 d, 61-90 d, and >90 d post-treatment. RESULTS A total of 5988 patients with localized BTC were identified: 2697 (45.0%) received multiagent chemotherapy and 3291 (55.0%) underwent surgical resection. Patients with gallbladder adenocarcinoma or extrahepatic cholangiocarcinoma who were treated with surgical resection had an associated decline in overall survival (OS) as compared to those treated with multiagent chemotherapy within 0-30 d of treatment initiation (gallbladder adenocarcinoma [adjusted HR = 3.94, 95% confidence interval [CI]: 1.77-8.80]; extrahepatic cholangiocarcinoma [adjusted HR = 4.88, 95% CI: 2.76-8.61]). However, there was an associated improvement in OS for patients treated with surgical resection after 90 d from treatment initiation (gallbladder adenocarcinoma [adjusted HR = 0.36, 95% CI: 0.28-0.46]; extrahepatic cholangiocarcinoma [adjusted HR = 0.27, 95% CI: 0.24-0.32]). Among patients with intrahepatic cholangiocarcinoma, those who underwent surgical resection had an associated improvement in OS at 31-60 d (adjusted HR = 0.63, 95% CI: 0.40-0.99) and a further associated increase in OS at 61-90 d (adjusted HR = 0.34, 95% CI: 0.21-0.54) and after 90 d (HR = 0.23, 95% CI: 0.21-0.27) of treatment initiation. CONCLUSIONS For patients with localized BTC, surgical resection alone is associated with improved long-term survival outcomes compared to multiagent chemotherapy alone.
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Affiliation(s)
- Mohamedraed Elshami
- Division of Surgical Oncology, Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, Ohio
| | - John B Ammori
- Division of Surgical Oncology, Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, Ohio
| | - Jeffrey M Hardacre
- Division of Surgical Oncology, Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, Ohio
| | - J Eva Selfridge
- Division of Hematology and Oncology, Department of Medicine, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, Ohio
| | - David Bajor
- Division of Hematology and Oncology, Department of Medicine, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, Ohio
| | - Amr Mohamed
- Division of Hematology and Oncology, Department of Medicine, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, Ohio
| | - Sakti Chakrabarti
- Division of Hematology and Oncology, Department of Medicine, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, Ohio
| | - Amit Mahipal
- Division of Hematology and Oncology, Department of Medicine, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, Ohio
| | - Jordan M Winter
- Division of Surgical Oncology, Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, Ohio
| | - Lee M Ocuin
- Division of Surgical Oncology, Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, Ohio.
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12
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Gervasi F, Pojero F. Use of Oleuropein and Hydroxytyrosol for Cancer Prevention and Treatment: Considerations about How Bioavailability and Metabolism Impact Their Adoption in Clinical Routine. Biomedicines 2024; 12:502. [PMID: 38540115 PMCID: PMC10968586 DOI: 10.3390/biomedicines12030502] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2024] [Revised: 02/12/2024] [Accepted: 02/18/2024] [Indexed: 11/11/2024] Open
Abstract
The fact that the Mediterranean diet could represent a source of natural compounds with cancer-preventive and therapeutic activity has been the object of great interest, especially with regard to the mechanisms of action of polyphenols found in olive oil and olive leaves. Secoiridoid oleuropein (OLE) and its derivative hydroxytyrosol (3,4-dihydroxyphenylethanol, HT) have demonstrated anti-proliferative properties against a variety of tumors and hematological malignancies both in vivo and in vitro, with measurable effects on cellular redox status, metabolism, and transcriptional activity. With this review, we aim to summarize the most up-to-date information on the potential use of OLE and HT for cancer treatment, making important considerations about OLE and HT bioavailability, OLE- and HT-mediated effects on drug metabolism, and OLE and HT dual activity as both pro- and antioxidants, likely hampering their use in clinical routine. Also, we focus on the details available on the effects of nutritionally relevant concentrations of OLE and HT on cell viability, redox homeostasis, and inflammation in order to evaluate if both compounds could be considered cancer-preventive agents or new potential chemotherapy drugs whenever their only source is represented by diet.
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Affiliation(s)
- Francesco Gervasi
- Specialistic Oncology Laboratory Unit, ARNAS Hospitals Civico Di Cristina e Benfratelli, 90127 Palermo, Italy;
| | - Fanny Pojero
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, 90123 Palermo, Italy
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13
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Pratt CG, Whitrock JN, Shah SA, Fong ZV. How to Determine Unresectability in Hilar Cholangiocarcinoma. Surg Clin North Am 2024; 104:197-214. [PMID: 37953036 DOI: 10.1016/j.suc.2023.09.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2023]
Abstract
Hilar cholangiocarcinoma is considered a biologically aggressive disease for which surgical resection remains the only curative treatment. Preoperative evaluation for resectability is challenging given tumor proximity to the porta hepatis, but minimal benefit and increased morbidity precludes recommendation for margin positive resection. This article reviews the determination of unresectability in hilar cholangiocarcinoma through discussion of the preoperative assessment, the intraoperative assessment, and key steps of surgical resection, as well as treatment options for unresectable tumors. Overall, evaluating patients preoperatively for resectability requires a multidisciplinary, holistic, and individualized approach to accurately determine resectability and optimize clinical outcomes for patients with hilar cholangiocarcinoma.
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Affiliation(s)
- Catherine G Pratt
- Cincinnati Research in Outcomes and Safety in Surgery (CROSS) Research Group, Department of Surgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML 0558, Cincinnati, OH 45267-0558, USA. https://twitter.com/CPrattMD
| | - Jenna N Whitrock
- Cincinnati Research in Outcomes and Safety in Surgery (CROSS) Research Group, Department of Surgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML 0558, Cincinnati, OH 45267-0558, USA. https://twitter.com/JennaWhitrockMD
| | - Shimul A Shah
- Cincinnati Research in Outcomes and Safety in Surgery (CROSS) Research Group, Department of Surgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML 0558, Cincinnati, OH 45267-0558, USA; Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way, MSB 2006C, ML 0519, Cincinnati, OH 45267-0558, USA. https://twitter.com/shimulshah73
| | - Zhi Ven Fong
- Division of Surgical Oncology and Endocrine Surgery, Department of Surgery, Mayo Clinic Arizona, Mayo Clinic College of Medicine, 5777 East Mayo Boulevard, Phoenix, AZ 85054, USA.
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14
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Liu QQ, Yu XH, Tang QB, Chen D, Zhang R, Liu C, Shi XD. Complete response of recurrent perihilar cholangiocarcinoma following sintilimab combined with lenvatinib plus S-1: a case report and review of literature. Anticancer Drugs 2024; 35:81-85. [PMID: 37227031 DOI: 10.1097/cad.0000000000001519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/26/2023]
Abstract
Perihilar cholangiocarcinoma is a refractory malignancy with an unfavorable prognosis and a high probability of recurrence. Systemic chemotherapy is critical for palliative treatment, but effective therapeutic strategies for perihilar cholangiocarcinoma after first-line chemotherapy failure are scarce. Here, we introduced a sustained benefit following sintilimab combined with lenvatinib plus S-1 in a patient with recurrent perihilar cholangiocarcinoma. A 52-year-old female patient was admitted to our hospital due to yellow skin and sclera, and further radiological examination revealed perihilar cholangiocarcinoma. The patient underwent surgery and histopathological results confirmed moderately differentiated adenocarcinoma with metastatic lymph nodes. Postoperative adjuvant chemotherapy with gemcitabine and S-1 was given. One year after surgery, the patient experienced hepatic recurrence. Then, she received radiofrequency ablation combined with gemcitabine and cisplatin. Unfortunately, radiological assessment revealed progressive disease with multiple liver metastases after treatment. Subsequently, she received sintilimab combined with lenvatinib plus S-1 and the lesions were completely regressed following 14 cycles of combination therapy. The patient recovered well without disease recurrence at the last follow-up. Sintilimab combined with lenvatinib plus S-1 may be an alternative therapeutic option for chemotherapy-refractory perihilar cholangiocarcinoma, and further evaluation in a larger number of patients is needed.
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Affiliation(s)
- Qin-Qin Liu
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
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15
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Sucandy I, Marques HP, Lippert T, Magistri P, Coelho JS, Ross SB, Chumbinho B, Di Sandro S, DiBenedetto F. Clinical Outcomes of Robotic Resection for Perihilar Cholangiocarcinoma: A First, Multicenter, Trans-Atlantic, Expert-Center, Collaborative Study. Ann Surg Oncol 2024; 31:81-89. [PMID: 37718337 DOI: 10.1245/s10434-023-14307-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2023] [Accepted: 09/01/2023] [Indexed: 09/19/2023]
Abstract
INTRODUCTION Perihilar cholangiocarcinoma is a difficult cancer to treat with frequent vascular invasion, local recurrence, and poor survival. Due to the need for biliary anastomosis and potential vascular resection, the standard approach is an open operation. Suboptimal outcomes after laparoscopic resection had been sporadically reported by high-volume centers. In this first, Trans-Atlantic, multicenter study, we report our outcomes of robotic resection for perihilar cholangiocarcinoma. This is the largest study of its kind in the Western hemisphere. METHODS Between 2016 and 2023, we prospectively followed patients undergoing robotic resection for perihilar cholangiocarcinoma at three, high-volume, robotic, liver-surgery centers. RESULTS Thirty-eight patients underwent perihilar cholangiocarcinoma utilizing the robotic technique; Klatskin type-3 was the most common. The median age was 72 years, and 82% of the patients underwent preoperative biliary drainage. Median operative time was 481 minutes with a median estimated blood loss of 200 mL. The number of harvested lymph nodes was seven, and 11 (28%) patients yielded positive lymph nodes. Three patients required vascular reconstruction; 18% of patients had >1 biliary anastomosis. R0 resection margins were achieved in 82% of patients. Clavien-Dindo Grade ≥3 complications were seen in 16% of patients. The length of stay was 6 days. Five patients had an unplanned readmission within 30 days. One patient died within 30 days. With a median follow-up of 15 months, 68% of patients are alive without disease, 13% recurred, and 19% died. CONCLUSIONS Application of the robotic platform for perihilar cholangiocarcinoma is safe and feasible with acceptable short-term clinical and oncological outcomes.
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Affiliation(s)
| | - Hugo P Marques
- Hepato-Biliary-Pancreatic and Transplantation Center, Lisbon Central Hospitals and University Center/NOVA Medical School, Lisbon, Portugal
| | - Trenton Lippert
- University of South Florida Morsani College of Medicine, Tampa, FL, USA
| | - Paolo Magistri
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University Hospital of Modena "Policlinico", University of Modena and Reggio Emilia, Modena, Italy
| | - Joao Santos Coelho
- Hepato-Biliary-Pancreatic and Transplantation Center, Lisbon Central Hospitals and University Center/NOVA Medical School, Lisbon, Portugal
| | | | - Beatriz Chumbinho
- Hepato-Biliary-Pancreatic and Transplantation Center, Lisbon Central Hospitals and University Center/NOVA Medical School, Lisbon, Portugal
| | - Stefano Di Sandro
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University Hospital of Modena "Policlinico", University of Modena and Reggio Emilia, Modena, Italy
| | - Fabrizio DiBenedetto
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University Hospital of Modena "Policlinico", University of Modena and Reggio Emilia, Modena, Italy
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16
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Kim J, Han DH, Choi GH, Kim KS, Choi JS, Kim SH. The prognostic value of the number of metastatic lymph nodes on the long-term survival of intrahepatic cholangiocarcinoma using the SEER database. J Gastrointest Oncol 2023; 14:2511-2520. [PMID: 38196549 PMCID: PMC10772680 DOI: 10.21037/jgo-23-580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Accepted: 11/10/2023] [Indexed: 01/11/2024] Open
Abstract
Background In the 8th edition of the American Joint Committee on Cancer, the nodal staging of intrahepatic cholangiocarcinoma (ICC) is classified as N0 and N1 in accordance with lymph node (LN) metastases. Recently, several studies have reported that the number of metastatic LNs is associated with prognosis in patients with ICC. However, the majority of these studies were published in Eastern countries, and there are few available data for Western countries. This study aimed to investigate the association between metastatic LN number and prognosis in ICC patients using the Surveillance, Epidemiology, and End Results (SEER) database. Methods Data from 658 ICC patients in the SEER database who underwent hepatectomy with LN dissection from 2000 to 2018 were retrospectively reviewed. Hazard ratios (HRs) according to increasing numbers of metastatic LN were calculated. The patients were then divided into three groups according to their metastatic LN numbers (N0: no metastatic LNs; N+ <4: 1-3 metastatic LNs; N+ ≥4: ≥4 metastatic LNs), and cause-specific survival (CSS) was compared. Results Metastatic LN number was a prognostic factor of oncologic survival [CSS: HR =1.300; 95% confidence interval (CI): 1.225-1.379; P<0.001]. In survival analysis, an increasing number of metastatic LNs was significantly correlated with poorer oncologic outcomes [CSS: N0 vs. N+ <4 vs. N+ ≥4: 40.856 (95% CI: 38.806-42.919) vs. 22.000 (95% CI: 18.283-25.717) vs. 15.000 (95% CI: 11.520-18.480) months, P<0.001]. In post hoc analysis, a significant difference was found between adjacent groups (N0 vs. N+ <4, P<0.001; N+ <4 vs. N+ ≥4, P=0.004). Conclusions Patients with ICC in the SEER database were reaffirmed to have worse prognosis with an increasing number of metastatic LNs.
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Affiliation(s)
- Juwan Kim
- Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Dai Hoon Han
- Department of Hepatobiliary and Pancreatobiliary Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Gi Hong Choi
- Department of Hepatobiliary and Pancreatobiliary Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Kyung Sik Kim
- Department of Hepatobiliary and Pancreatobiliary Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jin Sub Choi
- Department of Hepatobiliary and Pancreatobiliary Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sung Hyun Kim
- Department of Hepatobiliary and Pancreatobiliary Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
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Hu CL, Han X, Gao ZZ, Zhou B, Tang JL, Pei XR, Lu JN, Xu Q, Shen XP, Yan S, Ding Y. Systematic sequential therapy for ex vivo liver resection and autotransplantation: A case report and review of literature. World J Gastrointest Surg 2023; 15:2663-2673. [PMID: 38111758 PMCID: PMC10725551 DOI: 10.4240/wjgs.v15.i11.2663] [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: 08/29/2023] [Revised: 09/30/2023] [Accepted: 10/25/2023] [Indexed: 11/26/2023] Open
Abstract
BACKGROUND Perihilar cholangiocarcinoma (pCCA) is a highly malignant tumor arising from the biliary tree. Radical surgery is the only treatment offering a chance of long-term survival. However, limited by the tumor's anatomic location and peri-vascular invasion, most patients lose the chance for curative treatment. Therefore, more methods to increase the resectability of tumors as well as to improve outcomes are needed. CASE SUMMARY A 68-year-old female patient had a hepatic hilar mass without obvious symptoms. Laboratory results showed hepatitis B positivity. Magnetic resonance imaging indicated that the mass (maximum diameter: 41 mm) invaded the left and right branches of the main portal vein, as well as the middle, left and right hepatic veins; enlarged lymph nodes were also detected in the hilum. The patient was diagnosed with pCCA, and the clinical stage was determined to be T4N1M0 (stage IIIC). Considering the tumor's anatomic location and vascular invasion, systematic conversion therapy followed by ex vivo liver resection and autotransplantation (ELRA) was determined as personalized treatment for this patient. Our original systemic sequential therapeutic strategy (lenvatinib and tislelizumab in combination with gemcitabine and cisplatin) was successfully adopted as conversion therapy because she achieved partial response after three cycles of treatment, without severe toxicity. ELRA, anastomotic reconstruction of the middle hepatic vein, right hepatic vein, root of portal vein, inferior vena cava and right hepatic artery, and lymph node dissection were performed at one month after systemic therapy. Pathological and immunohistochemical examination confirmed the diagnosis of pCCA with lymph node metastasis. Although the middle hepatic vein was partially obstructed four months later, hepatic vein stent implantation successfully addressed this problem. The patient has survived for 22 mo after the diagnosis, with no evidence of recurrence or metastasis. CONCLUSION An effective therapeutic strategy for conversion therapy greatly increases the feasibility and efficiency of ELRA.
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Affiliation(s)
- Chen-Lu Hu
- Department of Nursing, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Xin Han
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Zhen-Zhen Gao
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Bo Zhou
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Jin-Long Tang
- Department of Pathology, Zhejiang University School of Medicine, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Xiang-Ru Pei
- Department of Nursing, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Jie-Nan Lu
- Department of Nursing, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Qin Xu
- Department of Nursing, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Xiao-Ping Shen
- Department of Nursing, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Sheng Yan
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Yuan Ding
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
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Zhu XX, Li JH, Fang P, Qu XF, Liang LJ, Lai JM, Yin XY. Renin-angiotensin system inhibitors improve the survival of cholangiocarcinoma: a propensity score-matched cohort study. BMC Cancer 2023; 23:826. [PMID: 37670280 PMCID: PMC10478452 DOI: 10.1186/s12885-023-11152-2] [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: 04/25/2023] [Accepted: 07/04/2023] [Indexed: 09/07/2023] Open
Abstract
BACKGROUND Hypertension is a risk factor for cholangiocarcinoma (CCA). The effect of anti-hypertensive drugs on the prognosis of CCA is not clear. METHODS This is a retrospective study of 102 patients (56.9% males, median age 66 years) diagnosed with CCA and hypertension concurrently and received radical surgery (R0), with a median follow-up of 36.7 months. Kaplan-Meier analysis, Cox regressions, and propensity score (PS) matching were applied for statistical analysis. RESULTS Results of multivariable cox analysis showed that renin-angiotensin system inhibitors (RASis) usage was a protective factor for progression-free survival (PFS) (hazard ratio [HR] = 0.55, 95% confidence interval [95% CI]: 0.32-0.96) and overall survival (OS) (HR = 0.40, 95% CI: 0.20-0.79), respectively. Calcium channel blockers, diuretics, and β-blockers didn't show significant associations. The association of RASis usage and PFS and OS was derived by PS matching, with a cohort of 28 RASis users and 56 RASis non-users. The median PFS and OS of RASis users (PFS, 17.6 months (9.2-34.4); OS, 24.8 months (16.5-42.3)) were longer than RASis non-users (PFS, 10.5 months (4.1-24.1); OS, 14.6 months (10.6-28.4)). The 1 year, 2 years, and 3 years' survival rates of RASis users (89.1%, 77.0%, and 65.5%) were higher than RASis non-users (70.9%, 54.0%, and 40.0%). CONCLUSIONS RASis usage improves the survival of patients with CCA and hypertension concurrently.
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Affiliation(s)
- Xiao-Xu Zhu
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan 2nd Rd, Guangzhou, Guangdong, 510080, China
| | - Jian-Hui Li
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan 2nd Rd, Guangzhou, Guangdong, 510080, China
| | - Peng Fang
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan 2nd Rd, Guangzhou, Guangdong, 510080, China
| | - Xiao-Fei Qu
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan 2nd Rd, Guangzhou, Guangdong, 510080, China
| | - Li-Jian Liang
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan 2nd Rd, Guangzhou, Guangdong, 510080, China
| | - Jia-Ming Lai
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan 2nd Rd, Guangzhou, Guangdong, 510080, China.
| | - Xiao-Yu Yin
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan 2nd Rd, Guangzhou, Guangdong, 510080, China.
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19
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Criss CR, Makary MS. Recent Advances in Image-Guided Locoregional Therapies for Primary Liver Tumors. BIOLOGY 2023; 12:999. [PMID: 37508428 PMCID: PMC10376862 DOI: 10.3390/biology12070999] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 07/09/2023] [Accepted: 07/10/2023] [Indexed: 07/30/2023]
Abstract
Primary liver cancer is the leading cause of cancer-related deaths worldwide. with incidences predicted to rise over the next several decades. Locoregional therapies, such as radiofrequency or microwave ablation, are described as image-guided percutaneous procedures, which offer either a curative intent for early-stage hepatocellular carcinoma or bridging/downstaging for surgical resection or transplantation. Catheter-driven locoregional therapies, such as transarterial chemoembolization and radioembolization, induce tumor hypoxia, can be palliative, and improve survival for early-to-intermediate hepatocellular carcinoma and unresectable intrahepatic cholangiocarcinoma. Herein, we provide a comprehensive overview of the antineoplastic mechanisms underpinning locoregional therapies, different treatment approaches, and the current state of the literature for the efficacy of locoregional therapies for primary liver cancer. We also discuss emerging advancements, such as the adjuvant use of immunotherapies and molecular targeting agents with locoregional therapy, for the treatment of primary liver cancer.
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Affiliation(s)
- Cody R. Criss
- OhioHealth Riverside Methodist Hospital, Columbus, OH 43214, USA;
| | - Mina S. Makary
- Department of Radiology, The Ohio State University Medical Center, Columbus, OH 43210, USA
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20
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Du H, Hou S, Zhang L, Liu C, Yu T, Zhang W. LncRNA FALEC increases the proliferation, migration and drug resistance of cholangiocarcinoma through competitive regulation of miR-20a-5p/SHOC2 axis. Aging (Albany NY) 2023; 15:3759-3770. [PMID: 37166421 PMCID: PMC10449288 DOI: 10.18632/aging.204709] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 04/17/2023] [Indexed: 05/12/2023]
Abstract
BACKGROUND LncRNA is an important regulatory factor in the human genome. We aim to explore the roles of LncFALEC and miR-20a-5p/SHOC2 axis on the proliferation, migration, and Fluorouracil (5-FU) resistance of cholangiocarcinoma (CCA). METHODS In this study, the expression of FALEC and miR-20a-5p in CCA tissues and cell lines (HuCCT1, QBC939, and Huh-28) was detected by RT-qPCR. The FALEC in 5-FU-resistant CCA cell lines (QBC939-R, Huh-28-R) was knocked down to evaluate its effects on cell proliferation, migration, invasion, and drug resistance. RESULTS Our analysis showed that compared with the adjacent non-tumor tissues, FALEC was significantly higher in the CCA tissues and even higher in the samples from 5-FU-resistant patients. Knockdown FALEC increased the sensitivity of 5-FU and decreased migration and invasion of CCA cells. Dual luciferase reporter confirmed that FALEC sponges miR-20a-5p and down-regulated its expression. Moreover, SHOC2 leucine-rich repeat scaffold protein (SHOC2) was the target gene of miR-20a-5p. We found overexpression of FALEC (FALEC-OE) increased resistance of CCA cells to 5-FU significantly, which might contribute to increased SHOC2 expression and activation of the ERK1/2 signaling pathway. CONCLUSIONS In summary, our study revealed that down-regulation of FALEC could inhibit the proliferation, migration, and invasion of CCA cells in vitro by regulating the miR-20a-5p/SHOC2 axis and participating in 5-FU resistance by mediating the ERK1/2 signaling pathway.
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Affiliation(s)
- Haiming Du
- The Biliopancreatic Endoscopic Surgery Department, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Senlin Hou
- The Biliopancreatic Endoscopic Surgery Department, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Lichao Zhang
- The Biliopancreatic Endoscopic Surgery Department, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Chao Liu
- Department of Anesthesiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Tingting Yu
- The Biliopancreatic Endoscopic Surgery Department, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Wei Zhang
- The Biliopancreatic Endoscopic Surgery Department, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
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21
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Brunese MC, Fantozzi MR, Fusco R, De Muzio F, Gabelloni M, Danti G, Borgheresi A, Palumbo P, Bruno F, Gandolfo N, Giovagnoni A, Miele V, Barile A, Granata V. Update on the Applications of Radiomics in Diagnosis, Staging, and Recurrence of Intrahepatic Cholangiocarcinoma. Diagnostics (Basel) 2023; 13:diagnostics13081488. [PMID: 37189589 DOI: 10.3390/diagnostics13081488] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Revised: 04/14/2023] [Accepted: 04/18/2023] [Indexed: 05/17/2023] Open
Abstract
BACKGROUND This paper offers an assessment of radiomics tools in the evaluation of intrahepatic cholangiocarcinoma. METHODS The PubMed database was searched for papers published in the English language no earlier than October 2022. RESULTS We found 236 studies, and 37 satisfied our research criteria. Several studies addressed multidisciplinary topics, especially diagnosis, prognosis, response to therapy, and prediction of staging (TNM) or pathomorphological patterns. In this review, we have covered diagnostic tools developed through machine learning, deep learning, and neural network for the recurrence and prediction of biological characteristics. The majority of the studies were retrospective. CONCLUSIONS It is possible to conclude that many performing models have been developed to make differential diagnosis easier for radiologists to predict recurrence and genomic patterns. However, all the studies were retrospective, lacking further external validation in prospective and multicentric cohorts. Furthermore, the radiomics models and the expression of results should be standardized and automatized to be applicable in clinical practice.
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Affiliation(s)
- Maria Chiara Brunese
- Department of Medicine and Health Sciences "V. Tiberio", University of Molise, 86100 Campobasso, Italy
| | | | - Roberta Fusco
- Medical Oncology Division, Igea SpA, 80013 Naples, Italy
| | - Federica De Muzio
- Department of Medicine and Health Sciences "V. Tiberio", University of Molise, 86100 Campobasso, Italy
| | - Michela Gabelloni
- Nuclear Medicine Unit, Department of Translational Research, University of Pisa, 56126 Pisa, Italy
| | - Ginevra Danti
- Italian Society of Medical and Interventional Radiology (SIRM), SIRM Foundation, Via della Signora 2, 20122 Milan, Italy
- Department of Emergency Radiology, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy
| | - Alessandra Borgheresi
- Department of Radiology, University Hospital "Azienda Ospedaliera Universitaria delle Marche", 60121 Ancona, Italy
- Department of Clinical, Special and Dental Sciences, Università Politecnica delle Marche, 60121 Ancona, Italy
| | - Pierpaolo Palumbo
- Department of Diagnostic Imaging, Area of Cardiovascular and Interventional Imaging, Abruzzo Health Unit 1, 67100 L'Aquila, Italy
| | - Federico Bruno
- Department of Diagnostic Imaging, Area of Cardiovascular and Interventional Imaging, Abruzzo Health Unit 1, 67100 L'Aquila, Italy
| | - Nicoletta Gandolfo
- Diagnostic Imaging Department, Villa Scassi Hospital-ASL 3, 16149 Genoa, Italy
| | - Andrea Giovagnoni
- Department of Radiology, University Hospital "Azienda Ospedaliera Universitaria delle Marche", 60121 Ancona, Italy
- Department of Clinical, Special and Dental Sciences, Università Politecnica delle Marche, 60121 Ancona, Italy
| | - Vittorio Miele
- Italian Society of Medical and Interventional Radiology (SIRM), SIRM Foundation, Via della Signora 2, 20122 Milan, Italy
- Department of Emergency Radiology, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy
| | - Antonio Barile
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, 67100 L'Aquila, Italy
| | - Vincenza Granata
- Division of Radiology, Istituto Nazionale Tumori IRCCS Fondazione Pascale-IRCCS di Napoli, 80131 Naples, Italy
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22
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Giovinazzo F, Pascale MM, Cardella F, Picarelli M, Molica S, Zotta F, Martullo A, Clarke G, Frongillo F, Grieco A, Agnes S. Current Perspectives in Liver Transplantation for Perihilar Cholangiocarcinoma. Curr Oncol 2023; 30:2942-2953. [PMID: 36975438 PMCID: PMC10047046 DOI: 10.3390/curroncol30030225] [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: 12/02/2022] [Revised: 01/17/2023] [Accepted: 01/30/2023] [Indexed: 03/05/2023] Open
Abstract
Cholangiocarcinoma (CCA) encompasses all malignant neoplasms arising from the epithelial cells of the biliary tree. About 40% of CCAs are perihilar, involving the bile ducts distal to the second-order biliary branches and proximal to the cystic duct implant. About two-thirds of pCCAs are considered unresectable at the time of diagnosis or exploration. When resective surgery is deemed unfeasible, liver transplantation (LT) could be an effective alternative. The overall survival rates after LT at 1 and 3 years are 91% and 81%, respectively. The overall five-year survival rate after transplantation is 73% (79% for patients with underlying PSC and 63% for de novo pCCA). Multicenter case series reported a 5-year disease-free survival rate of ~65%. However, different protocols, including neoadjuvant therapy, have been proposed. The scarcity of organ availability represents a crucial limiting factor in recommending LT preferentially in treating pCCA. Living donor transplantations and marginal cadaveric allografts have proven to be exciting options to overcome organ shortage. Management of jaundice and cholangitis is still challenging for these patients and could impact LT listing. Whether to adopt surgical resection or LT as standard-of-care in pCCA is still a matter of debate, and more prospective studies are needed.
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Affiliation(s)
- Francesco Giovinazzo
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Correspondence:
| | - Marco Maria Pascale
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Francesca Cardella
- Surgical Oncology of Gastrointestinal Tract Unit, Vanvitelli University, 80138 Naples, Italy
| | - Matteo Picarelli
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Serena Molica
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Francesca Zotta
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Annamaria Martullo
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - George Clarke
- Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, UK
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TH, UK
| | - Francesco Frongillo
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Antonio Grieco
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Department of Medicine and Translational Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Salvatore Agnes
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Department of Medicine and Translational Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
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23
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Miura Y, Ashida R, Saiga A, Sugiura T, Ohgi K, Yamada M, Otsuka S, Aramaki T, Sato R, Uesaka K. Secondary Budd-Chiari syndrome occurred after adjuvant radiotherapy for perihilar cholangiocarcinoma: a case report. World J Surg Oncol 2023; 21:9. [PMID: 36647103 PMCID: PMC9841655 DOI: 10.1186/s12957-023-02890-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Accepted: 01/09/2023] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND Budd-Chiari syndrome (BCS) is a rare vascular disorder of the liver, and acute and secondary BCS is even rarer. CASE PRESENTATION A 62-year-old man with perihilar cholangiocarcinoma of Bismuth type IIIa underwent right hemi-hepatectomy with caudate lobectomy and pancreatoduodenectomy. Adjuvant chemoradiotherapy was performed due to a positive hepatic ductal margin. Subsequently, the disease passed without recurrence. The patient visited for acute onset abdominal pain at the 32nd postoperative month. Multidetector-row computed tomography (MDCT) showed stenosis of the left hepatic vein (LHV) root, which was the irradiated field, and thrombotic occlusion of the LHV. The patient was diagnosed with acute BCS caused by adjuvant radiotherapy. Although anticoagulation therapy was performed, the patient complained of sudden upper abdominal pain again. MDCT showed an enlarged LHV thrombus and hepatomegaly. The patient was diagnosed with exacerbated acute BCS, and stenting for the stenotic LHV root was performed with a bare stent. Although stenting for the LHV root was very effective, restenosis occurred twice due to thrombus in the existing stent, so re-stenting was performed twice. The subsequent clinical course was acceptable without recurrence or restenosis of the LHV root as of 6 months after the last stenting using a stent graft. CONCLUSION Although no case of BCS caused by radiotherapy has yet been reported, the present case showed that late side effect of radiotherapy can cause hepatic vein stenosis and secondary BCS.
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Affiliation(s)
- Yuya Miura
- grid.415797.90000 0004 1774 9501Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, Japan
| | - Ryo Ashida
- grid.415797.90000 0004 1774 9501Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, Japan
| | - Atsushi Saiga
- grid.415797.90000 0004 1774 9501Division of Interventional Radiology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, Japan
| | - Teiichi Sugiura
- grid.415797.90000 0004 1774 9501Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, Japan
| | - Katsuhisa Ohgi
- grid.415797.90000 0004 1774 9501Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, Japan
| | - Mihoko Yamada
- grid.415797.90000 0004 1774 9501Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, Japan
| | - Shimpei Otsuka
- grid.415797.90000 0004 1774 9501Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, Japan
| | - Takeshi Aramaki
- grid.415797.90000 0004 1774 9501Division of Interventional Radiology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, Japan
| | - Rui Sato
- grid.415797.90000 0004 1774 9501Division of Interventional Radiology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, Japan
| | - Katsuhiko Uesaka
- grid.415797.90000 0004 1774 9501Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, Japan
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24
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Cristóbal I, Lamarca A. Role of the PP2A Pathway in Cholangiocarcinoma: State of the Art and Future Perspectives. Cancers (Basel) 2022; 14:5422. [PMID: 36358840 PMCID: PMC9657793 DOI: 10.3390/cancers14215422] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Accepted: 10/31/2022] [Indexed: 08/27/2023] Open
Abstract
Cholangiocarcinoma represents a heterogeneous disease at both a clinical and molecular level [...].
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Affiliation(s)
- Ion Cristóbal
- Cancer Unit for Research on Novel Therapeutic Targets, Oncohealth Institute, IIS-Fundación Jiménez Díaz-UAM, 28040 Madrid, Spain
| | - Angela Lamarca
- Medical Oncology Department, Oncohealth Institute, IIS-Fundación Jiménez Díaz-UAM, 28040 Madrid, Spain
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