Cholangiocarcinoma: Recent Advances in Molecular Pathobiology and Therapeutic Approaches
Open accessAbstract
Cholangiocarcinomas (CCA) pose a complex challenge in oncology due to diverse etiologies, necessitating tailored therapeutic approaches. This review discusses the risk factors, molecular pathology, and current therapeutic options for CCA and explores the emerging strategies encompassing targeted therapies, immunotherapy, novel compounds from natural sources, and modulation of gut microbiota. CCA are driven by an intricate landscape of genetic mutations, epigenetic dysregulation, and post-transcriptional modification, which differs based on geography (e.g., for liver fluke versus non-liver fluke-driven CCA) and exposure to environmental carcinogens (e.g., exposure to aristolochic acid). Liquid biopsy, including circulating cell-free DNA, is a potential diagnostic tool for CCA, which warrants further investigations. Currently, surgical resection is the primary curative treatment for CCA despite the technical challenges. Adjuvant chemotherapy, including cisplatin and gemcitabine, is standard for advanced, unresectable, or recurrent CCA. Second-line therapy options, such as FOLFOX (oxaliplatin and 5-FU), and the significance of radiation therapy in adjuvant, neoadjuvant, and palliative settings are also discussed. This review underscores the need for personalized therapies and demonstrates the shift towards precision medicine in CCA treatment. The development of targeted therapies, including FDA-approved drugs inhibiting FGFR2 gene fusions and IDH1 mutations, is of major research focus. Investigations into immune checkpoint inhibitors have also revealed potential clinical benefits, although improvements in survival remain elusive, especially across patient demographics. Novel compounds from natural sources exhibit anti-CCA activity, while microbiota dysbiosis emerges as a potential contributor to CCA progression, necessitating further exploration of their direct impact and mechanisms through in-depth research and clinical studies. In the future, extensive translational research efforts are imperative to bridge existing gaps and optimize therapeutic strategies to improve therapeutic outcomes for this complex malignancy.
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Most patients do not respond to the chemotherapy.
“However, most patients do not respond to the chemotherapy [33].”
From Overexpression of TBX3 suppresses tumorigenesis in experimental and human cholangiocarcinoma (2024) · cites this paper as [33]
The Introduction (page unavailable) says cholangiocarcinoma’s tumor characteristics and therapeutic resistance have led to refractoriness to chemotherapy. That supports poor chemotherapy response, but the paper does not establish that most patients fail to respond; §4.2 instead reports benefits from some regimens. (LLM, conf=0.82)
Experimental — accuracy not yet measuredChemotherapy, consisting of Gemcitabine and Cisplatin-based therapies, is still the mainstream treatment option for advanced, unresectable, or recurrent iCCA.
“Chemotherapy, consisting of Gemcitabine and Cisplatin-based therapies, is still the mainstream treatment option for advanced, unresectable, or recurrent iCCA [33].”
From Overexpression of TBX3 suppresses tumorigenesis in experimental and human cholangiocarcinoma (2024) · cites this paper as [33]
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“Studies such as BCAT [98] and PRODIGE 12-ACCORD 18 [99] found that both gemcitabine monotherapy and gemcitabine with oxaliplatin therapy did not significantly enhance OS compared to observation.”
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“[91].”
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“From the whole-exome sequencing of 102 iCCA patients, Zou and co-workers [39] observed a prevalence of marked strand-biased SBS22 in the CTG sequence context, which is consistent with the aforementioned AA-UTUC.”
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“…speculation is further consolidated by the finding of significantly increased infiltration of activated natural killer (NK) cells and enhanced CD160 expression (a marker for cytotoxic NK cell) in intrahepatic CCA tumors harboring the SBS22 signature and with a high TMB and neoantigen load [43].”
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“Studies such as BCAT [98] and PRODIGE 12-ACCORD 18 [99] found that both gemcitabine monotherapy and gemcitabine with oxaliplatin therapy did not significantly enhance OS compared to observation.”
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“…was associated with a 35% relative reduction in the risk of death risk (HR:0.65, 95% CI: 0.54–0.78, p 0.001) and a 36% reduced risk for disease progression (HR:0.64, 95% CI: 0.53–0.76, p 0.001) and this benefit was present irrespective of the location (CCA vs. gallbladder carcinoma) [88].”
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“These DNA adducts are repaired by transcription-coupled nucleotide excision repair (TC-NER) but are resistant to global genome nucleotide excision repair (GG-NER), thus leading to a marked non-transcribed strand bias with enriched A:T to T:A transversion events [35,36].”
BackgroundSelf-citationPathological classification of intrahepatic cholangiocarcinoma based on a new concept
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“[48].”
BackgroundSurgical Management of Hilar Cholangiocarcinoma
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“The intrahepatic bile duct margin assessment usually occurs later in the procedure, and if necessary, additional tissue is excised to ensure negative margins based on frozen section analysis [84].”
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“A phase III trial has reported that the combination of gemcitabine with S-1 (Gem-S1) is non-inferior to Gem-Cis with a median overall survival (OS) of 15.1 and 13.4 months, respectively (HR = 0.945, 90% CI: 0.78–1.15, non-inferiority p = 0.046) [89].”
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“Clinical trials have shown that durvalumab in combination with chemotherapy significantly improves OS and PFS for these patients [144].”
BackgroundInfluentialImpact of Dietary Resistant Starch on the Human Gut Microbiome, Metaproteome, and Metabolome
Maier, T. V., Lucio, M., Lee, L. H., VerBerkmoes, N. C., Brislawn, C. J., Bernhardt, J., Lamendella, R., McDermott, J. E., Bergeron, N., Heinzmann, S. S., et al. (2017) · mBio · doi:10.1128/mbio.01343-17 · Cited by 316 · cited 1× · see citing works
“Several studies in recent years have found that prebiotics increase the abundance of specific probiotics in the gut, particularly beneficial bacteria, such as Lactobacillus, Bifidobacterium, Faecalibacterium, Akkermansia, Ruminococcus, and Rosebura species [184–187].”
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“Based on results by the University of Nebraska [132], the Mayo Clinic [85] developed a neoadjuvant protocol for patients with unresectable, stage I and II perihilar CCA comprising external beam radiotherapy (EBRT) combined with radio-sensitizing chemotherapy with bolus fluorouracil, followed by…”
MethodMolecular classification and therapeutic targets in extrahepatic cholangiocarcinoma
Montal, R., Sia, D., Montironi, C., Leow, W. Q., Esteban-Fabró, R., Pinyol, R., Torres‐Martín, M., Bassaganyas, L., Moeini, A., Peix, J., et al. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.03.008 · Cited by 304 · see citing works
Harding, J. J., Fan, J., Oh, D., Choi, H. J., Kim, J. W., Chang, H.-M., Bao, L., Sun, H., Macarulla, T. M., Xie, F., et al. (2023) · The Lancet Oncology · doi:10.1016/s1470-2045(23)00242-5 · Cited by 300 · cited 1× · see citing works
“In a Phase 2b HERIZON-BTC-01 trial, zanidatamab has been reported to show an objective response rate of 41.3% in patients with previously treated HER2 amplified and expressing CCA [151].”
BackgroundInfluentialCorvera, C. U., Blumgart, L. H., Akhurst, T., DeMatteo, R. P., D'Angelica, M. I., Fong, Y., & Jarnagin, W. R. (2007) · Journal of the American College of Surgeons · doi:10.1016/j.jamcollsurg.2007.07.002 · Cited by 289 · cited 1× · see citing works
“PET or PET/CT does not provide any additional information with respect to the staging of tumors but leads to a change in surgical management due to upstaging in 20–25% of patients [61].”
BackgroundGenome-Wide Mutational Signatures of Aristolochic Acid and Its Application as a Screening Tool
Poon, S. L., Pang, S., McPherson, J. R., Yu, W., Huang, K. K., Guan, P., Weng, W., Siew, E. Y., Liu, Y., Heng, H. L., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3006086 · Cited by 287 · cited 1× · see citing works
“Strikingly, genomic profiling of UTUC and hepatocellular carcinoma (HCC) samples from Taiwan, the Balkans, and Belgium have consistently revealed an enriched SBS22 signature (AA-UTUC), including the well-known tumor suppressor gene TP53, implicating the strong mutagenic effect by AA [36–38].”
BackgroundSelf-citationRecurrence after operative management of intrahepatic cholangiocarcinoma
Hyder, O. N., Hatzaras, I. S., Sotiropoulos, G. C., Paul, A., Alexandrescu, S. T., Marques, H. P., Pulitanò, C., Barroso, E., Clary, B. M., Aldrighetti, L. A., et al. (2013) · Surgery · doi:10.1016/j.surg.2012.12.005 · Cited by 283 · cited 1× · see citing works
“The most common site of relapse in intrahepatic CCA is the liver (accounting for approximately 60%), with associated extrahepatic relapse in 18.6%, followed by extrahepatic recurrence in 21% [105,106].”
BackgroundInfluentialSurgical treatment of hilar cholangiocarcinoma in the new era: the Asan experience
Lee, S., Song, G., Hwang, S., Ha, T., Moon, D. B., Jung, D., Kim, K. H., Ahn, C. S., Kim, M. H., Lee, S. K., et al. (2009) · Journal of Hepato-Biliary-Pancreatic Sciences · doi:10.1007/s00534-009-0204-5 · Cited by 259 · cited 2× · see citing works
“The lymph nodes and other extravascular soft tissue may be removed en bloc with the eventual surgical specimen [82].”
BackgroundNakachi, K., Ikeda, M., Konishi, M., Nomura, S., Katayama, H., Kataoka, T., Todaka, A., Yanagimoto, H., Morinaga, S., Kobayashi, S., et al. (2023) · The Lancet · doi:10.1016/s0140-6736(22)02038-4 · Cited by 258 · see citing works
Ioka, T., Kanai, M., Kobayashi, S., Sakai, D., Eguchi, H., Baba, H., Seo, S., Taketomi, A., Takayama, T., Yamaue, H., et al. (2023) · Journal of Hepato-Biliary-Pancreatic Sciences · doi:10.1002/jhbp.1219 · Cited by 249 · cited 1× · see citing works
“[92].”
Azcárate-Peril, M. A., Ritter, A. J., Savaiano, D. A., Monteagudo-Mera, A., Anderson, C., Magness, S. T., & Klaenhammer, T. R. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1606722113 · Cited by 246 · see citing works
Intrahepatic cholangiocarcinoma: pathogenesis and rationale for molecular therapies
Sia, D., Tovar, V., Moeini, A., & Llovet, J. M. (2013) · Oncogene · doi:10.1038/onc.2012.617 · Cited by 236 · see citing works
Klein, O., Kee, D., Nagrial, A. M., Markman, B., Underhill, C. R., Michael, M., Jackett, L. A., Lum, C., Behren, A., Palmer, J., et al. (2020) · JAMA Oncology · doi:10.1001/jamaoncol.2020.2814 · Cited by 232 · cited 1× · see citing works
“…studies have explored the combination of anti-PD1/PDL-1 with anti-CTLA 4 to achieve deeper prolonged responses in a phase II trial that combined ipilimumab with nivolumab in patients with recurrent biliary tract MSS tumors and documented median PFS of 2.9 months and OS of 5.7 months [165].”
BackgroundInfluentialLi, L., Masica, D. L., Ishida, M., Tomuleasa, C., Umegaki, S., Kalloo, A. N., Georgiades, C. S., Singh, V. K., Khashab, M. A., Amateau, S. K., et al. (2014) · Hepatology · doi:10.1002/hep.27050 · Cited by 224 · cited 1× · see citing works
“Recent studies have shown that body fluids, such as plasma and bile, contain a significant amount of miRNAs and some of them could be used to differentiate between CCA patients and healthy individuals [73,74].”
BackgroundSurgical Resection of Hilar Cholangiocarcinoma: Analysis of Survival and Postoperative Complications
Hasegawa, S., Ikai, I., Fujii, H., Hatano, E., & Shimahara, Y. (2007) · World Journal of Surgery · doi:10.1007/s00268-007-9001-y · Cited by 219 · cited 1× · see citing works
“The pattern of relapse in perihilar CCA includes both local and distant [96,109].”
BackgroundPetrick, J. L., Yang, B., Altekruse, S. F., Van Dyke, A. L., Koshiol, J., Graubard, B. I., & McGlynn, K. A. (2017) · PLOS ONE · doi:10.1371/journal.pone.0186643 · Cited by 210 · cited 1× · see citing works
“Choledochal cysts, rare congenital anomalies resulting in cystic dilatation of the biliary tree, represent another well-established risk factor for CCA [21,22].”
BackgroundCoelen, R. J. S., Roos, E., Wiggers, J. K., Besselink, M. G., Buis, C. I., Busch, O. R., Dejong, C. H. C., van Delden, O. M., van Eijck, C. H. J., Fockens, P., et al. (2018) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(18)30234-6 · Cited by 204 · see citing works
Søreide, K., Kørner, H., Havnen, J., & Søreide, J. A. (2004) · British journal of surgery · doi:10.1002/bjs.4815 · Cited by 198 · see citing works
Hong, J. C. (2011) · Archives of Surgery · doi:10.1001/archsurg.2011.116 · Cited by 197 · cited 1× · see citing works
“Based on the UCLA experience, for patients with a tumor length ≤ 6 cm, conventional radiotherapy with chemotherapy or stereotactic body radiation therapy (SBRT) of 40 Gy in 5 fractions followed by chemotherapy can be considered [134].”
MethodSelf-citationWeinberg, B. A., Xiu, J., Lindberg, M. R., Shields, A. F., Hwang, J. J., Poorman, K. A., Salem, M. E., Pishvaian, M. J., Holcombe, R. F., Marshall, J. L., et al. (2019) · Journal of Gastrointestinal Oncology · doi:10.21037/jgo.2018.08.18 · Cited by 185 · cited 1× · see citing works
“In patients with CCA, around 2–3% had microsatellite instability (MSI-H) tumors, and 4–6% with a high tumor mutation burden (TMB-H) were noted [158,159].”
BackgroundIntrahepatic Cholangiocarcinoma: New Insights in Pathology
Sempoux, C. L., Jibara, G. A., Ward, S. C., Fan, C., Qin, L., Roayaie, S., Fiel, M. I., Schwartz, M., & Thung, S. N. (2011) · Seminars in Liver Disease · doi:10.1055/s-0031-1272839 · Cited by 184 · cited 2× · see citing works
“It is important to subcategorize, as each of these categories di ff ers in their risk factors, epidemiological features, clinical presentations, and morphologic and molecular characteristics [45,46].”
BackgroundThe Epidemiology, Diagnosis, and Management of Aristolochic Acid Nephropathy
Gökmen, R., Cosyns, J., Arlt, V. M., Stiborová, M., Phillips, D. H., Schmeiser, H. H., Simmonds, M. S. J., Cook, H. T., Vanherweghem, J., Nortier, J., et al. (2013) · Annals of Internal Medicine · doi:10.7326/0003-4819-158-6-201303190-00006 · Cited by 181 · see citing works
The Opisthorchis viverrini genome provides insights into life in the bile duct
Young, N. D., Nagarajan, N., Lin, S. J., Korhonen, P. K., Jex, A. R., Hall, R. S., Safavi-Hemami, H., Kaewkong, W., Bertrand, D., Gao, S., et al. (2014) · Nature Communications · doi:10.1038/ncomms5378 · Cited by 170 · see citing works
Self-citationHayashi, A., Misumi, K., Shibahara, J., Arita, J., Sakamoto, Y., Hasegawa, K., Kokudo, N., & Fukayama, M. (2016) · The American Journal of Surgical Pathology · doi:10.1097/pas.0000000000000670 · Cited by 169 · cited 1× · see citing works
“Several studies have documented distinct immunohistochemical characteristics of LD-iCCA and SD-iCCA [51,52].”
BackgroundJia, X., Lu, S., Zeng, Z., Liu, Q., Dong, Z., Chen, Y., Zhu, Z., Hong, Z., Zhang, T., Du, G., et al. (2019) · Hepatology · doi:10.1002/hep.30852 · Cited by 168 · cited 1× · see citing works
“Lactobacillus, Actinomyces, Peptostreptococcaceae, Alloscardovia, and Bifidobacteriaceae families are found abundant in patients with intrahepatic CCA (iCCA) and can be employed as biomarkers to distinguish iCCA patients from healthy controls [179].”
BackgroundClinical treatment of cholangiocarcinoma: an updated comprehensive review
Elvevi, A., Laffusa, A., Scaravaglio, M., Rossi, R. E., Longarini, R., Stagno, A. M., Cristoferi, L., Ciaccio, A., Cortinovis, D. L., Invernizzi, P., et al. (2022) · Annals of Hepatology · doi:10.1016/j.aohep.2022.100737 · Cited by 168 · see citing works
Pathologic classification of cholangiocarcinoma: New concepts
Nakanuma, Y., & Kakuda, Y. (2015) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/j.bpg.2015.02.006 · Cited by 167 · cited 4× · see citing works
“Intrahepatic CCA can be classi fi ed into a minimum of two primary categories based adenocarcinoma morphological be-tween immunohistochemical [47,49].”
BackgroundInfluentialHan, J., Xian, Z., Zhang, Y., Liu, J., & Liang, A. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00648 · Cited by 166 · cited 1× · see citing works
“Aristolochic acid (AA) is a toxic compound found naturally in plants of genera Aristolochia and Asarum [33].”
BackgroundChen, X., Wu, X., Wu, H., Gu, Y., Shao, Y. W., Shao, Q., Zhu, F., Li, X., Qian, X., Hu, J. X., et al. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-001240 · Cited by 163 · cited 1× · see citing works
“Camrelizumab, an anti-PD1 antibody plus gemcitabine and oxaliplatin combination chemotherapy in first-line treatment of advanced biliary cancers, resulted in a median PFS and median OS of 6.1 months and 11.8 months, respectively [166].”
BackgroundInfluentialKoerkamp, B. G., Wiggers, J. K., Gönen, M., Doussot, A., Allen, P. J., Besselink, M. G., Blumgart, L. H., Busch, O. R., D'Angelica, M. I., DeMatteo, R. P., et al. (2015) · Annals of Oncology · doi:10.1093/annonc/mdv279 · Cited by 158 · cited 1× · see citing works
“The major prognostic factors are margin status, lymph node metastases, vascular invasion, and tumor differentiation [110–112].”
BackgroundTargeted methylation sequencing of plasma cell-free DNA for cancer detection and classification
Liu, L., Toung, J. M., Jassowicz, A., Vijayaraghavan, R., Kang, H. J., Zhang, R., Kruglyak, K. M., Huang, H. J., Hinoue, T., Shen, H., et al. (2018) · Annals of Oncology · doi:10.1093/annonc/mdy119 · Cited by 154 · cited 1× · see citing works
“Additionally, the Circulating Cell-free Genome Atlas (CCGA) consortium published two studies that used NGS-based targeted methylation panels to study bisulfite-converted cfDNA in a variety of cancers, including CCA [71,72].”
BackgroundYoo, C., Oh, D. Y., Choi, H. J., Kudo, M., Ueno, M., Kondo, S., Chen, L.-T., Osada, M., Helwig, C., Dussault, I., et al. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-000564 · Cited by 151 · cited 1× · see citing works
“Currently, a phase I study of bintrafusp alfa in patients with pretreated CCA has promising results and further studies are being planned [148].”
BackgroundChaiteerakij, R., Yang, J. D., Harmsen, W. S., Slettedahl, S. W., Mettler, T. A., Fredericksen, Z. S., Kim, W. R., Gores, G. J., Roberts, R. O., Olson, J. E., et al. (2012) · Hepatology · doi:10.1002/hep.26092 · Cited by 150 · cited 1× · see citing works
“In addition, type 2 diabetes mellitus has been reported to confer a higher risk for CCA, whilst treatment with metformin, in turn, confers a protective role [28].”
BackgroundThongprasert, S., Napapan, S., Charoentum, C., & Moonprakan, S. (2005) · Annals of Oncology · doi:10.1093/annonc/mdi046 · Cited by 141 · cited 1× · see citing works
“With a dearth of effective targeted therapies for fluke-positive CCA, the standard of care for these patients remains resection and chemotherapy [152].”
BackgroundBiliary tract cancer registry in Japan from 2008 to 2013
Ishihara, S., Horiguchi, A., Miyakawa, S., Endo, I., Miyazaki, M., & Takada, T. (2015) · Journal of Hepato-Biliary-Pancreatic Sciences · doi:10.1002/jhbp.314 · Cited by 139 · cited 1× · see citing works
“Approximately a quarter to a third of individuals meet the criteria for resection, and following curative-intent surgical resection, there is a 50% 5-year overall survival (OS) rate [95].”
BackgroundBertuccio, P., Bosetti, C., Levi, F., Decarli, A., Negri, E., & Vecchia, C. L. (2013) · Annals of Oncology · doi:10.1093/annonc/mds652 · Cited by 135 · see citing works
Adjuvant Concurrent Chemoradiation for Adenocarcinoma of the Distal Common Bile Duct
Hughes, M. A., Frassica, D. A., Yeo, C. J., Riall, T. S., Lillemoe, K. D., Cameron, J. L., Donehower, R. C., Laheru, D. A., Hruban, R. H., & Abrams, R. A. (2007) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2006.11.048 · Cited by 134 · cited 1× · see citing works
“Survival benefit and decreased incidence of LRR was seen in high-risk patients treated with adjuvant chemoradiation [119–121].”
BackgroundOtsuji, H., Yokoyama, Y., Ebata, T., Igami, T., Sugawara, G., Mizuno, T., & Nagino, M. (2015) · World Journal of Surgery · doi:10.1007/s00268-015-2988-6 · Cited by 129 · cited 1× · see citing works
“Sarcopenia, characterized by muscle loss, is associated with poor prognosis in liver surgery, and it increases the risk of liver failure in patients undergoing major hepatectomy with extrahepatic bile duct resection for hilar CCA [81].”
BackgroundRecurrence after resection with curative intent for distal cholangiocarcinoma
Komaya, K., Ebata, T., Shirai, K., Ohira, S., Morofuji, N., Akutagawa, A., Yamaguchi, R., Nagino, M., Aoba, T., Kaneoka, Y., et al. (2017) · British journal of surgery · doi:10.1002/bjs.10452 · Cited by 129 · see citing works
Biliary tract cancers: epidemiology, molecular pathogenesis and genetic risk associations
Marcano-Bonilla, L., Mohamed, E. A., Mounajjed, T., & Roberts, L. R. (2016) · Chinese Clinical Oncology · doi:10.21037/cco.2016.10.09 · Cited by 125 · see citing works
Wongjarupong, N., Assavapongpaiboon, B., Susantitaphong, P., Cheungpasitporn, W., Treeprasertsuk, S., Rerknimitr, R., & Chaiteerakij, R. (2017) · BMC Gastroenterology · doi:10.1186/s12876-017-0696-4 · Cited by 125 · cited 1× · see citing works
“A positive association between non-alcoholic fatty liver disease (NAFLD) and CCA has also been suggested, especially for intrahepatic CCA [27].”
BackgroundYe, Y., Zhou, L., Xie, X., Jiang, G., Xie, H., & Zheng, S. (2009) · Journal of Surgical Oncology · doi:10.1002/jso.21376 · Cited by 124 · cited 1× · see citing works
“Increased expression of PD-L1 is associated with the pTNM stage and inferior overall survival and is inversely correlated with CD8+ TILs in CCA [154,155].”
BackgroundKim, S. T., Kang, J.-B., Lee, J., Lee, H. W., Oh, S. Y., Jang, J., Lee, M. A., Sohn, B. S., Yoon, S. Y., Choi, H. J., et al. (2019) · Annals of Oncology · doi:10.1093/annonc/mdz058 · Cited by 124 · see citing works
Self-citationSurgical management of hilar cholangiocarcinoma: the Nagoya experience
Nishio, H., Nagino, M., & Nimura, Y. (2005) · HPB · doi:10.1080/13651820500373010 · Cited by 121 · cited 2× · see citing works
“Surgical drains are commonly used, given bile leaks from the liver parenchyma or biliary-enteric reconstruction [83].”
BackgroundEttrich, T. J., Schwerdel, D., Dolnik, A., Beuter, F., Blätte, T. J., Schmidt, S. A., Stanescu-Siegmund, N., Steinacker, J., Marienfeld, R. B., Kleger, A., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-49860-0 · Cited by 120 · cited 1× · see citing works
“Ettrich et al. [65] analyzed paired plasma cfDNA and tumor samples from CCA patients before and after treatments.”
BackgroundTransplantation for hilar cholangiocarcinoma
Heimbach, J. K., Haddock, M. G., Alberts, S. R., Nyberg, S. L., Ishitani, M. B., Rosen, C. B. B., & Gores, G. J. (2004) · Liver Transplantation · doi:10.1002/lt.20266 · Cited by 117 · cited 1× · see citing works
“A tumor with a radial diameter of more than 3 cm is usually excluded, however, vascular encasement and stricture/mass extension along the duct are not considered contraindications [85,86].”
BackgroundFeng, K., Liu, Y., Zhao, Y., Yang, Q., Dong, L., Liu, J., Li, X., Zhao, Z., Mei, Q., & Han, W. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2019-000367 · Cited by 114 · cited 1× · see citing works
“The median PFS was 6.1 months, and the mOS was 8.5 months, with a manageable toxicity profile [164].”
BackgroundInfluentialArechederra, M., Rullán, M., Amat, I., Oyón, D., Zabalza, L., Elizalde, M., Latasa, M. U., Mercado, M., Ruiz-Clavijo, D., Saldaña, C., et al. (2021) · Gut · doi:10.1136/gutjnl-2021-325178 · Cited by 109 · cited 1× · see citing works
“Shen et al. [68] and Arechederra et al. [69] reported significant concordance between mutations detected in tumors and those found in the corresponding bile cfDNA.”
BackgroundVaquero, J., Lobe, C., Tahraoui, S., Clapéron, A., Mergey, M., Merabtene, F., Wendum, D., Coulouarn, C., Housset, C., Desbois‐Mouthon, C., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-3725 · Cited by 108 · cited 1× · see citing works
“Preclinical studies have shown that EGFR inhibitors, such as erlotinib, can inhibit the growth of CCA cells in vitro [146].”
BackgroundZhou, Y., Zhao, Y., Li, B., Huang, J., Wu, L., Xu, D., Yang, J., & He, J. (2012) · BMC Cancer · doi:10.1186/1471-2407-12-289 · Cited by 107 · cited 1× · see citing works
“Chronic viral infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) may also represent a risk factor for CCA development, with a stronger predilection for intrahepatic CCA [25].”
BackgroundSidorenko, V. S., Yeo, J.-E., Bonala, R., Johnson, F., Schärer, O. D., & Grollman, A. P. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr1095 · Cited by 107 · cited 1× · see citing works
“These DNA adducts are repaired by transcription-coupled nucleotide excision repair (TC-NER) but are resistant to global genome nucleotide excision repair (GG-NER), thus leading to a marked non-transcribed strand bias with enriched A:T to T:A transversion events [35,36].”
BackgroundCholangiocarcinoma: Classification, Histopathology and Molecular Carcinogenesis
Lendvai, G., Szekerczés, T., Illyés, I., Dóra, R., Kontsek, E., Gógl, A., Kiss, A., Werling, K., Kovalszky, I., Schaff, Z., et al. (2018) · Pathology & Oncology Research · doi:10.1007/s12253-018-0491-8 · Cited by 104 · cited 2× · see citing works
“Intrahepatic CCA can be classi fi ed into a minimum of two primary categories based adenocarcinoma morphological be-tween immunohistochemical [47,49].”
BackgroundShroff, R. T., Guthrie, K. A., Scott, A. J., et al. (2023) · Journal of Clinical Oncology · doi:10.1200/jco.2023.41.4_suppl.lba490 · Cited by 100 · see citing works
Stereotactic Body Radiotherapy (SBRT) for Intrahepatic and Hilar Cholangiocarcinoma
Mahadevan, A., Dağoğlu, N., Mancias, J. D., Raven, K. E., Khwaja, K. O., Tseng, J. F., Ng, K., Enzinger, P. C., Miksad, R. A., Bullock, A. J., et al. (2015) · Journal of Cancer · doi:10.7150/jca.13032 · Cited by 99 · cited 1× · see citing works
“Various studies have reported high local control rates with acceptable toxicity [135,136].”
BackgroundZhou, Y., Liu, S., Wu, L., & Wan, T. (2015) · Asian Journal of Surgery · doi:10.1016/j.asjsur.2015.07.002 · Cited by 99 · cited 1× · see citing works
“The major factors predictive of recurrence are margin status, lymphovascular invasion, perineural invasion, pancreatic invasion, and lymph node metastasis [113,114].”
BackgroundThe Mutational Features of Aristolochic Acid–Induced Mouse and Human Liver Cancers
Lu, Z., Luo, Q., Zhao, L., Shi, Y. Y., Wang, N., Wang, L., & Han, Z. (2019) · Hepatology · doi:10.1002/hep.30863 · Cited by 97 · cited 1× · see citing works
“The tumor-promoting effect of AA in CCA was further supported by a mouse study that investigated the mutational features of AA [44].”
BackgroundThorotrast-Induced Liver Neoplasia: A Collective Review
Lipshutz, G. S., Brennan, T. V., & Warren, R. S. (2002) · Journal of the American College of Surgeons · doi:10.1016/s1072-7515(02)01287-5 · Cited by 95 · cited 1× · see citing works
“Previously, thorotrast, a radiographic contrast agent now banned from clinical use, has been strongly suggested to increase the risk of CCA development [29].”
BackgroundMakawita, S., Abou‐Alfa, G. K., Roychowdhury, S., Sadeghi, S., Borbath, I., Goyal, L., Cohn, A. L., Lamarca, Á., Oh, D., Macarulla, T. M., et al. (2020) · Future Oncology · doi:10.2217/fon-2020-0299 · Cited by 93 · cited 1× · see citing works
“Other clinical trials have shown that infigratinib is effective for pretreated patients and in the first-line setting [141].”
BackgroundMutational spectrum and precision oncology for biliary tract carcinoma
Lin, J., Cao, Y., Yang, X., Li, G., Shi, Y., Wang, D., Long, J., Song, Y., Mao, J., Xie, F., et al. (2021) · Theranostics · doi:10.7150/thno.56539 · Cited by 89 · cited 2× · see citing works
“In a separate study by Lin et al. [41], 35.8% of the intrahepatic CCA patients had a SBS22 mutational signature and presented with a significantly higher tumor mutational burden (TMB) than the non-AA intrahepatic CCA patients ( p < 0.001).”
BackgroundInfluentialFisher, S. B., Patel, S. H., Kooby, D. A., Weber, S. M., Bloomston, M., Cho, C. S., Hatzaras, I. S., Schmidt, C. R., Winslow, E. R., Staley, C. A., et al. (2012) · HPB · doi:10.1111/j.1477-2574.2012.00489.x · Cited by 84 · cited 1× · see citing works
“The risk factors predictive of recurrence are margin status, lymph node metastasis, lymphovascular invasion, perineural invasion, multiplicity of lesions, and a tumor size greater than 5 cm [107,108].”
BackgroundSigel, C., Drill, E. N., Zhou, Y., Baştürk, O., Aşkan, G., Pak, L. M., Vakiani, E., Wang, T., Boerner, T., Do, R. K. G., et al. (2018) · The American Journal of Surgical Pathology · doi:10.1097/pas.0000000000001118 · Cited by 80 · cited 1× · see citing works
“Furthermore, they display a significant presence of desmoplastic stroma [50].”
BackgroundBonet, M., Allal, A. S., Gich, I. J., Solé, J. M., & Carrió, I. (2011) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2011.05.003 · Cited by 80 · see citing works
Cytotoxic Pentacyclic and Tetracyclic Aromatic Sesquiterpenes from Phomopsis archeri
Hemtasin, C., Kanokmedhakul, S., Kanokmedhakul, K., Hahnvajanawong, C., Soytong, K., Prabpai, S., & Kongsaeree, P. (2011) · Journal of Natural Products · doi:10.1021/np100632g · Cited by 79 · see citing works
Gallstones and cholecystectomy in relation to risk of intra- and extrahepatic cholangiocarcinoma
Nordenstedt, H., Mattsson, F., El‐Serag, H. B., & Lagergren, J. (2012) · British Journal of Cancer · doi:10.1038/bjc.2011.607 · Cited by 78 · cited 1× · see citing works
“Liver cirrhosis, as well as cholelithiasis and choledocholithiasis, have been identified as strong risk factors for CCA, particularly intrahepatic and extrahepatic CCA subtypes, respectively [9,24].”
BackgroundZheng, Y., Tu, X., Zhao, P., Jiang, W., Liu, L., Tong, Z., Zhang, H., Yan, C., Fang, W. J., & Wang, W. (2018) · British Journal of Cancer · doi:10.1038/s41416-018-0138-2 · Cited by 78 · cited 1× · see citing works
“Other agents used in this setting are a combination of capecitabine and irinotecan (XELIRI) [103] and 5FU-based regimens [104].”
BackgroundXu, D., Ma, Y., Zhao, B., LI, S., Zhang, Y., Pan, S., Wu, Y., Wang, J., Wang, D., Pan, H., et al. (2014) · Oncology Reports · doi:10.3892/or.2014.3059 · Cited by 77 · see citing works
Infection with the carcinogenic human liver fluke, Opisthorchis viverrini
Smout, M. J., Sripa, B., Laha, T., Mulvenna, J. P., Gasser, R. B., Young, N. D., Bethony, J. M., Brindley, P. J., & Loukas, A. C. (2011) · Molecular BioSystems · doi:10.1039/c0mb00295j · Cited by 76 · see citing works
Shen, N., Zhang, D., Yin, L., Qiu, Y., Liu, J., Yu, W., Fu, X., Zhu, B., Xu, X., Duan, A., et al. (2019) · Oncology Reports · doi:10.3892/or.2019.7177 · Cited by 75 · cited 1× · see citing works
“Shen et al. [68] and Arechederra et al. [69] reported significant concordance between mutations detected in tumors and those found in the corresponding bile cfDNA.”
BackgroundNAD+ Homeostasis and NAD+-Consuming Enzymes: Implications for Vascular Health
Campagna, R., & Vignini, A. (2023) · Antioxidants · doi:10.3390/antiox12020376 · Cited by 74 · cited 1× · see citing works
“As the master regulator of NAD homeostasis, it will potentially affect all NAD-dependent enzyme activity [149].”
BackgroundThe genomic landscape of cholangiocarcinoma reveals the disruption of post-transcriptional modifiers
Zhang, Y., Ma, Z., Li, C., Wang, C., Jiang, W., Chang, J., Han, S., Lu, Z., Shao, Z., Wang, Y., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-30708-7 · Cited by 74 · see citing works
The Landmark Series: Hilar Cholangiocarcinoma
Soares, K. C., & Jarnagin, W. R. (2021) · Annals of Surgical Oncology · doi:10.1245/s10434-021-09871-6 · Cited by 68 · cited 1× · see citing works
“Only about 30% of patients are eligible for successful resection, and even after surgery, there is a high likelihood of disease recurrence, resulting in variable 5-year survival rates of 10–50% depending on the tumor stage and location [76].”
BackgroundKim, B. J., Yoo, C., Kim, K., Hyung, J., Park, S., Ryoo, B., & Chang, H.-M. (2017) · British Journal of Cancer · doi:10.1038/bjc.2016.446 · Cited by 66 · cited 1× · see citing works
“Other agents used in this setting are a combination of capecitabine and irinotecan (XELIRI) [103] and 5FU-based regimens [104].”
BackgroundCorrea‐Gallego, C., Maddalo, D., Doussot, A., Kemeny, N. E., Kingham, T. P., Allen, P. J., D'Angelica, M. I., DeMatteo, R. P., Betel, D., Klimstra, D. S., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0163699 · Cited by 65 · cited 1× · see citing works
“Recent studies have shown that body fluids, such as plasma and bile, contain a significant amount of miRNAs and some of them could be used to differentiate between CCA patients and healthy individuals [73,74].”
BackgroundAntimalarial and Cytotoxic Depsidones from the Fungus Chaetomium brasiliense
Khumkomkhet, P., Kanokmedhakul, S., Kanokmedhakul, K., Hahnvajanawong, C., & Soytong, K. (2009) · Journal of Natural Products · doi:10.1021/np9003189 · Cited by 64 · cited 1× · see citing works
“…alkaloid (tiliacorinine), sesquiterpenes (phomoarcherin B, phomoarcherin C), and depsidones (mollicelline K, mollicelline N, mollicelline C, mollicelline F) emerged as promising hits with half-maximal inhibitory concentration (IC 50 ) 10 µ g/mL against CCA cell-lines [169–173].”
BackgroundDeng, T., Li, J., He, B., Chen, B., Liu, F., Chen, Z., Zheng, J., Shi, Z., Zhang, T., Deng, L., et al. (2022) · Hepatology International · doi:10.1007/s12072-021-10279-3 · Cited by 63 · cited 1× · see citing works
“Deng et al. [177] investigated the gut microbiota differences between patients with CCA, hepatocellular carcinoma (HCC), and healthy controls.”
BackgroundThanan, R., Pairojkul, C., Pinlaor, S., Khuntikeo, N., Wongkham, C., Sripa, B., Ma, N., Vaeteewoottacharn, K., Furukawa, A., Kobayashi, H., et al. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.07.034 · Cited by 62 · see citing works
Plasma mi R ‐21 is a novel diagnostic biomarker for biliary tract cancer
Kishimoto, T., Eguchi, H., Nagano, H., Kobayashi, S., Akita, H., Hama, N., Wada, H., Kawamoto, K., Tomokuni, A., Tomimaru, Y., et al. (2013) · Cancer Science · doi:10.1111/cas.12300 · Cited by 62 · cited 1× · see citing works
“Other studies have shown that the expression of miR-21, a known CCA-promoting miRNA, was correlated with tumor stage (late clinical stage) and poorer survival [75].”
BackgroundZhang, T., Zhang, S., Chen, J., Lin, Z., Deng, T., Xie, X., Deng, L., Li, X., Ma, J., Ding, X., et al. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.751795 · Cited by 62 · cited 1× · see citing works
“Zhang et al. [178], reported that Burkholderia, Cabelleronia, Paraburkholderia, Faecalibacterium, and Ruminococcus-1 genera in gut microbiota are significantly enriched in the gut microbiota of CCA patients.”
BackgroundBrandi, G., Girolamo, S. D., Farioli, A., Rosa, F. D., Curti, S., Pinna, A. D., Ercolani, G., Violante, F. S., Biasco, G., & Mattioli, S. (2013) · Cancer Causes & Control · doi:10.1007/s10552-013-0167-3 · Cited by 61 · cited 1× · see citing works
“These findings were similarly demonstrated in a population-based case-control study nested on the Nordic Occupational Cancer cohort, where an increased risk of intrahepatic CCA, but not of extrahepatic CCA, was observed by cumulative exposure to asbestos [30,31].”
ResultProteogenomic characterization of cholangiocarcinoma
Deng, M., Ran, P., Chen, L., Wang, Y., Yu, Z., Cai, K., Feng, J., Qin, Z., Yin, Y., Tan, S., et al. (2022) · Hepatology · doi:10.1002/hep.32624 · Cited by 61 · see citing works
Lee, J., Yoon, W. S., Koom, W. S., & Rim, C. H. (2018) · Strahlentherapie und Onkologie · doi:10.1007/s00066-018-1367-2 · Cited by 60 · cited 1× · see citing works
“The most common side effects were duodenal ulcer and gastric ulcer (incidence of grade ≥ 3 acute toxicity 10 percent) and a late toxicity incidence of 10–20% in most studies [137].”
BackgroundGenetics of Opisthorchis viverrini-related cholangiocarcinoma
Jusakul, A., Kongpetch, S., & Teh, B. T. (2015) · Current Opinion in Gastroenterology · doi:10.1097/mog.0000000000000162 · Cited by 59 · see citing works
Self-citationDiagnosis of Cholangiocarcinoma
Shin, D. W., Moon, S., & Kim, J. H. (2023) · Diagnostics · doi:10.3390/diagnostics13020233 · Cited by 59 · cited 1× · see citing works
“Table 3 describes the radiological findings of CCA with USG, CT, and MRI [62].”
BackgroundWasenang, W., Chaiyarit, P., Proungvitaya, S., & Limpaiboon, T. (2019) · Clinical Epigenetics · doi:10.1186/s13148-019-0634-0 · Cited by 59 · cited 1× · see citing works
“Wasenang et al. [70] used a qPCR-based methylation-sensitive high-resolution melting (MS-HRM) approach to assess for the presence of CCA-specific methylated sites on OPCML, HOXA9, and HOXD9 genes in serum-derived cfDNA.”
MethodBile-Based Cell-Free DNA Analysis Is a Reliable Diagnostic Tool in Pancreatobiliary Cancer
Driescher, C., Fuchs, K., Häberle, L., Goering, W., Frohn, L., Opitz, F. V., Haeussinger, D., Knoefel, W. T., Keitel, V., & Esposito, I. (2020) · Cancers · doi:10.3390/cancers13010039 · Cited by 57 · cited 1× · see citing works
“Driescher et al. [67] showed that bile cfDNA was more sensitive than plasma cfDNA in detecting mutations re-ported in the matched tumors (96.2% vs. 31.6%).”
BackgroundInfluentialGkika, E., Hallauer, L., Kirste, S., Adebahr, S., Bartl, N., Neeff, H. P., Fritsch, R., Brass, V., Nestle, U., Grosu, A., et al. (2017) · BMC Cancer · doi:10.1186/s12885-017-3788-1 · Cited by 56 · cited 1× · see citing works
“Various studies have reported high local control rates with acceptable toxicity [135,136].”
BackgroundLack of Targetable FGFR2 Fusions in Endemic Fluke-Associated Cholangiocarcinoma
Kongpetch, S., Jusakul, A., Lim, J. Q., Ng, C. C. Y., Chan, J. Y., Rajasegaran, V., Lim, T. H., Lim, K. H., Choo, S. P., Dima, S., et al. (2020) · JCO Global Oncology · doi:10.1200/go.20.00030 · Cited by 55 · cited 2× · see citing works
“Furthermore, FGFR fusions were detected only exclusively in intrahepatic CCA, and the fusions were found to be mutually exclusive with FGFR/BRAF/ERBB2/KRAS mutations [56].”
BackgroundSelf-citationViganò, L., Soldani, C., Franceschini, B., Cimino, M., Lleò, A., Donadon, M., Roncalli, M. G., Aghemo, A., Tommaso, L. D., & Torzilli, G. (2019) · Journal of Gastrointestinal Surgery · doi:10.1007/s11605-019-04111-5 · Cited by 55 · cited 1× · see citing works
“CD3+ and CD8+ T lymphocyte infiltration have resulted in superior survival with reduced local recurrences and Tregs infiltration co-related with inferior survival in patients with CCA who underwent resection [156].”
BackgroundKe, Q., Lin, N., Deng, M., Wang, L., Zeng, Y., & Liu, J. (2020) · PLoS ONE · doi:10.1371/journal.pone.0229292 · Cited by 53 · see citing works
Deng, M., Li, S., Fu, X., Yan, X., Chen, J., Qiu, Y., & Guo, R. (2021) · Cancer Cell International · doi:10.1186/s12935-021-02081-w · Cited by 52 · cited 1× · see citing works
“Increased expression of PD-L1 is associated with the pTNM stage and inferior overall survival and is inversely correlated with CD8+ TILs in CCA [154,155].”
BackgroundEpigallocatechin‐gallate modulates chemotherapy‐induced apoptosis in human cholangiocarcinoma cells
Lang, M., Henson, R., Braconi, C., & Patel, T. C. (2009) · Liver International · doi:10.1111/j.1478-3231.2009.01984.x · Cited by 51 · see citing works
Chen, X., Qin, S., Gu, S., Ren, Z., Chen, Z., Xiong, J., Liu, Y., Meng, Z., Zhang, X., Wang, L., et al. (2021) · International Journal of Cancer · doi:10.1002/ijc.33751 · Cited by 50 · cited 1× · see citing works
“Another chemoim-munotherapy combination of camrelizumab with FOLFOX or GEMOX showed an ORR of 16.6%, and the median PFS and OS were 5.3 months and 12.4 months, respectively [167].”
BackgroundInfluentialPathogenesis of cholangiocarcinoma: From genetics to signalling pathways
Kongpetch, S., Jusakul, A., Ong, C. K., Lim, W. K., Rozen, S., Tan, P. B. O., & Teh, B. T. (2015) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/j.bpg.2015.02.002 · Cited by 46 · cited 1× · see citing works
“Infestation of liver flukes called Opisthorchis viverrini (Ov) has been associated with the highest incidence of CCA in the northeast region of Thailand and neighboring Laos and Cambodia [12,13].”
BackgroundSelf-citationMoro, C. F., Fernandez-Woodbridge, A., D'souza, M. A., Zhang, Q., Bozóky, B., Vasan, S. K., Catalano, P., Heuchel, R. L., Shtembari, S., Chiaro, M. D., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0166067 · Cited by 46 · see citing works
Nassour, I., Mokdad, A. A., Porembka, M. R., Choti, M. A., Polanco, P. M., Mansour, J. C., Minter, R. M., Wang, S. C., & Yopp, A. C. (2018) · Annals of Surgical Oncology · doi:10.1245/s10434-018-6388-7 · Cited by 45 · see citing works
SEOM clinical guidelines for pancreatic and biliary tract cancer (2020)
Gómez‐España, M. A., Montés, A. F., García‐Carbonero, R., Macarulla, T. M., Maurel, J., Martín, Á., Pazo-Cid, R., Vera, R., Carrato, A., & Feliú, J. (2021) · Clinical & Translational Oncology · doi:10.1007/s12094-021-02573-1 · Cited by 45 · see citing works
The role of the hepatitis viruses in cholangiocarcinoma
Ralphs, S., & Khan, S. A. (2013) · Journal of Viral Hepatitis · doi:10.1111/jvh.12093 · Cited by 44 · cited 1× · see citing works
“Notably, the increased risk of CCA amongst HBV and HCV patients not only depends on the presence of liver cirrhosis but also on the direct oncogenic effects exerted by these viruses on the liver [26].”
BackgroundRen, B., Guo, Q., Yang, Y., Liu, L., Wei, S., Chen, W., & Tian, Y. (2020) · Radiation Oncology · doi:10.1186/s13014-020-1459-x · Cited by 44 · cited 1× · see citing works
“However, various retrospective studies and meta-analyses have supported the role of adjuvant chemoradiation in patients with positive resection margins and lymph node involvement [97,115–118].”
BackgroundRole of molecular genetics in the clinical management of cholangiocarcinoma
Normanno, N., Martinelli, E., Melisi, D., Pinto, C., Rimassa, L., Santini, D., & Scarpa, A. (2022) · ESMO Open · doi:10.1016/j.esmoop.2022.100505 · Cited by 44 · cited 1× · see citing works
“CCA encompasses a highly heterogeneous genomic mutational landscape that is associated with poor outcomes in patients [2,6,7,54,55].”
BackgroundFarioli, A., Straíf, K., Brandi, G., Curti, S., Kjærheim, K., Martinsen, J. I., Sparén, P., Tryggvadóttír, L., Weiderpass, E., Biasco, G., et al. (2017) · Occupational and Environmental Medicine · doi:10.1136/oemed-2017-104603 · Cited by 42 · cited 1× · see citing works
“These findings were similarly demonstrated in a population-based case-control study nested on the Nordic Occupational Cancer cohort, where an increased risk of intrahepatic CCA, but not of extrahepatic CCA, was observed by cumulative exposure to asbestos [30,31].”
ResultIDH inhibitors in advanced cholangiocarcinoma: Another arrow in the quiver?
Rizzo, A., Ricci, A. D., & Brandi, G. (2021) · Cancer Treatment and Research Communications · doi:10.1016/j.ctarc.2021.100356 · Cited by 38 · see citing works
Progress in Radiotherapy for Cholangiocarcinoma
Wang, N., Huang, A., Kuang, B., Yu, X., Xiao, Y., & Ma, H. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.868034 · Cited by 38 · cited 2× · see citing works
“The lymph node stations to be included in distal CCA are along the common bile duct, common hepatic artery, hepatoduodenal ligament, superior mesenteric artery (SMA), para-aortic, and retropancreatic nodes [129,130].”
BackgroundApoptotic activity of caged xanthones fromGarcinia hanburyiin cholangiocarcinoma cell lines
Hahnvajanawong, C. (2010) · World Journal of Gastroenterology · doi:10.3748/wjg.v16.i18.2235 · Cited by 37 · cited 1× · see citing works
“…alkaloid (tiliacorinine), sesquiterpenes (phomoarcherin B, phomoarcherin C), and depsidones (mollicelline K, mollicelline N, mollicelline C, mollicelline F) emerged as promising hits with half-maximal inhibitory concentration (IC 50 ) 10 µ g/mL against CCA cell-lines [169–173].”
BackgroundDiagnostic and Prognostic Value of Circulating Cell-Free DNA for Cholangiocarcinoma
Wintachai, P., Lim, J. Q., Techasen, A., Lert-itthiporn, W., Kongpetch, S., Loilome, W., Chindaprasirt, J., Titapun, A., Namwat, N., Khuntikeo, N., et al. (2021) · Diagnostics · doi:10.3390/diagnostics11060999 · Cited by 37 · cited 1× · see citing works
“Both real-time quantitative PCR (qPCR) and next-generation sequencing (NGS) platforms can be used to detect mutations in CCA-associated genes (e.g., ARID1A, PBRM1, MTOR, FGFR2, and TP53) in plasma cfDNA from CCA patients [64].”
MethodSelf-citationZhou, W., Qian, L., Rong, Y., Zhou, Q., Shan, J., Li, P., Shi, L., Liu, H., & Sun, X. (2020) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2020.03.017 · Cited by 37 · cited 1× · see citing works
“The target volume should include tumor bed, anastomosis, and regional lymph nodes [128,131].”
BackgroundLu, S., Ke, S., Wang, C., Xu, Y., Li, Z., Song, K., Bai, M., Zhou, M., Yu, H., Yin, B., et al. (2022) · Oncogenesis · doi:10.1038/s41389-022-00415-5 · Cited by 35 · cited 1× · see citing works
“NNMT has been found to be overexpressed in CCA, which contributes to tumor progression and metastasis [150], thus representing a promising molecular target.”
BackgroundSurgical management of biliary tract cancers
Fairweather, M., Balachandran, V. P., & D'Angelica, M. I. (2016) · Chinese Clinical Oncology · doi:10.21037/cco.2016.10.03 · Cited by 34 · see citing works
Molecular mechanisms of cholangiocarcinoma
Fava, G. (2010) · World Journal of Gastrointestinal Pathophysiology · doi:10.4291/wjgp.v1.i1.12 · Cited by 30 · cited 1× · see citing works
“The tumor cells undergo diverse genetic and epigenetic alterations resulting in enhanced proliferation signaling, dysregulation of apoptosis, angiogenesis, invasion, and stromal proliferation [4].”
BackgroundIn vitro and In vivo Antitumor Activity of Tiliacorinine in Human Cholangiocarcinoma
Janeklang, S., Nakaew, A., Vaeteewoottacharn, K., Seubwai, W., Boonsiri, P., Kısmalı, G., Suksamrarn, A., Okada, S., & Wongkham, S. (2014) · Asian Pacific Journal of Cancer Prevention · doi:10.7314/apjcp.2014.15.17.7473 · Cited by 28 · see citing works
Clinical Target Volume in Biliary Carcinoma: A Systematic Review of Pathological Studies
Marinelli, I., Guido, A., Fuccio, L., Farioli, A., Panni, V., Giaccherini, L., ARCELLI, A., Ercolani, G., Brandi, G., Cammelli, S., et al. (2017) · Anticancer Research · doi:10.21873/anticanres.11404 · Cited by 27 · cited 3× · see citing works
“The lymphatic drainage area in CCA varies with the location of the tumor [128–130].”
BackgroundDecharchoochart, P., Suthiwong, J., Samatiwat, P., Kukongviriyapan, V., & Yenjai, C. (2014) · Journal of Natural Medicines · doi:10.1007/s11418-014-0851-y · Cited by 26 · see citing works
Roussel, E., Brasse‐Lagnel, C., Tuech, J., Montialoux, H., Papet, E., Tortajada, P., Bekri, S., & Schwarz, L. (2021) · World Journal of Surgery · doi:10.1007/s00268-021-06388-7 · Cited by 26 · cited 1× · see citing works
“…were orally administered the mixed probiotics (containing Bifidobacterium lactis, Lactobacillus plantanum, and Lactobacillus salivarius) in the post-operative periods, thereby supporting the use of probiotics to modulate the immune response in reducing complications of infections in patients [182].”
MethodSebastian, N., Tan, Y., Miller, E. D., Williams, T. M., & Diaz, D. A. (2019) · Clinical and Translational Radiation Oncology · doi:10.1016/j.ctro.2019.07.007 · Cited by 25 · cited 1× · see citing works
“SBRT was associated with a better OS compared to chemoradiation and TARE [138].”
ResultDechakhamphu, S., Pinlaor, S., Sitthithaworn, P., Bartsch, H., & Yongvanit, P. (2010) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2010.06.003 · Cited by 24 · see citing works
The rate of cholangiocarcinoma in Caroli Disease A German multicenter study
Fard-Aghaie, M. H., Makridis, G., Reese, T., Feyerabend, B., Wagner, K. C., Schnitzbauer, A. A., Bechstein, W. O., Oldhafer, F., Kleine, M., Klempnauer, J. L., et al. (2021) · HPB · doi:10.1016/j.hpb.2021.06.423 · Cited by 24 · see citing works
Hong, J. H., Yong, C. H., Heng, H. L., Chan, J. Y., Lau, M. C., Chen, J., Lee, J. Y., Lim, A. H., Li, Z., Guan, P., et al. (2023) · Gut · doi:10.1136/gutjnl-2023-330483 · Cited by 24 · cited 1× · see citing works
“More recently, genome-wide changes in DNA methylation and enhancer activities have proven valuable in deciphering different molecular subtypes to guide the therapeutic interventions in many other cancers [57–59].”
BackgroundSelf-citationAnticancer activity of streptochlorin, a novel antineoplastic agent, in cholangiocarcinoma
Kwak, T. W., Shin, H. J., Jeong, Y., Han, M., Oh, S., Kim, H., Kim, D. H., & Kang, D. H. (2015) · Drug Design Development and Therapy · doi:10.2147/dddt.s80205 · Cited by 23 · see citing works
Liang, L., Li, C., Jia, H., Diao, Y., Xing, H., Pawlik, T. M., Lau, W. Y., Shen, F., Huang, D., Zhang, C.-W., et al. (2021) · Therapeutic Advances in Gastrointestinal Endoscopy · doi:10.1177/2631774521993065 · Cited by 20 · see citing works
Southekal, S., Shakyawar, S. K., Bajpai, P., Elkholy, A., Manne, U., Mishra, N. K., & Guda, C. (2023) · Cancers · doi:10.3390/cancers15072134 · Cited by 20 · see citing works
Li, Z., Chu, J., Su, F., Ding, X., Zhang, Y., Dou, L., Liu, Y., Yan, K., Liu, X., Liu, Y., et al. (2022) · PubMed Central · Cited by 18 · see citing works
Evaluation of Tazemetostat as a Therapeutically Relevant Substance in Biliary Tract Cancer
Bekric, D., Neureiter, D., Ablinger, C., Dobias, H., Beyreis, M., Ritter, M., Jakab, M., Bischof, J., Koller, U., Kiesslich, T., et al. (2023) · Cancers · doi:10.3390/cancers15051569 · Cited by 18 · cited 1× · see citing works
“Tazemetostat, an inhibitor of EZH2, commonly found overexpressed in CCA, has shown effectiveness in CCA models in vitro [147].”
BackgroundKamarajah, S. K., Bednar, F., Cho, C. S., & Nathan, H. (2020) · Cancer · doi:10.1002/cncr.33356 · Cited by 16 · cited 2× · see citing works
“In a propensity-matched National Cancer Database analysis in patients with distal CCA by Kamarajah et al. [121], adjuvant radiation after surgical resection was associated with a survival benefit regardless of the margin and lymph nodal status.”
BackgroundPatil, P. A., Taddei, T. H., Jain, D., & Zhang, X. (2021) · Archives of Pathology & Laboratory Medicine · doi:10.5858/arpa.2020-0725-oa · Cited by 16 · see citing works
Alterations in the human oral microbiome in cholangiocarcinoma
Rao, B., Zhang, G., Zou, Y., Ren, T., Ren, H., Liu, C., Yu, Z., & Ren, Z. (2022) · Military Medical Research · doi:10.1186/s40779-022-00423-x · Cited by 16 · cited 1× · see citing works
“Lautropia, Alloprevotella, and Actinomyces families were shown to be particularly common microbiomes in CCA patients compared to healthy controls [181].”
BackgroundHow long should follow-up be continued after R0 resection of perihilar cholangiocarcinoma?
Nakahashi, K., Ebata, T., Yokoyama, Y., Igami, T., Mizuno, T., Yamaguchi, J., Onoe, S., Watanabe, N., & Nagino, M. (2020) · Surgery · doi:10.1016/j.surg.2020.04.068 · Cited by 15 · cited 2× · see citing works
“In a study by Nakahashi et al. [112], 60% of the patients developed recurrence even after R0 resection.”
BackgroundJung, W., Kim, K., Min, S. K., Nam, E. M., & Lee, J. K. (2019) · British Journal of Radiology · doi:10.1259/bjr.20190285 · Cited by 15 · cited 2× · see citing works
“The lymph node stations to be included in distal CCA are along the common bile duct, common hepatic artery, hepatoduodenal ligament, superior mesenteric artery (SMA), para-aortic, and retropancreatic nodes [129,130].”
BackgroundRole of adjuvant (chemo)radiotherapy for resected extrahepatic cholangiocarcinoma: a meta-analysis
Shi, X., Zhang, J., Tian, H., Tang, L.-N., & Li, A.-L. (2020) · Journal of Zhejiang University SCIENCE B · doi:10.1631/jzus.b1900691 · Cited by 12 · cited 1× · see citing works
“However, various retrospective studies and meta-analyses have supported the role of adjuvant chemoradiation in patients with positive resection margins and lymph node involvement [97,115–118].”
BackgroundLi, J., Liang, Y., Fan, J., Xu, C., Guan, B., Zhang, J., Guo, B., Shi, Y. X., Wang, P., Tan, Y., et al. (2022) · BMC Medicine · doi:10.1186/s12916-022-02426-w · Cited by 12 · cited 1× · see citing works
“More recently, genome-wide changes in DNA methylation and enhancer activities have proven valuable in deciphering different molecular subtypes to guide the therapeutic interventions in many other cancers [57–59].”
BackgroundTang, Z., Yang, Y., Zhang, Q., & Liang, T. (2023) · Clinical Epigenetics · doi:10.1186/s13148-022-01413-5 · Cited by 12 · cited 1× · see citing works
“In an epigenetic study by Tang and co-workers [60] on intrahepatic CCA, the collagen type XII alpha 1 chain (COL12A1) was identified as a specific biomarker for enrichment in the epithelial–mesenchymal transition pathway and advanced tumor stage.”
BackgroundMuhamad, N., Plengsuriyakarn, T., & Na‐Bangchang, K. (2022) · PLoS ONE · doi:10.1371/journal.pone.0277614 · Cited by 10 · cited 1× · see citing works
“Significantly, an oral formulation from the standardized extract of Atractylodes lancea rhizomes has completed a Phase I clinical trial with a satisfactory safety profile, and a Phase II clinical trial in patients with advanced-stage CCA is ongoing [168].”
BackgroundOptimal perioperative care in peri-hilar cholangiocarcinoma resection
Quinn, L. M., Dunne, D. F. J., Jones, R. P., Poston, G. J., Malik, H., & Fenwick, S. W. (2018) · European surgery. Supplement/European surgery · doi:10.1007/s10353-018-0529-x · Cited by 6 · cited 1× · see citing works
“Preoperative biliary drainage can enhance postoperative liver regeneration, particularly in patients with high bilirubin levels [79].”
BackgroundGenomic and Transcriptomic Landscape of Tumor Clonal Evolution in Cholangiocarcinoma
Chen, G., Cai, Z., Dong, X., Zhao, J., Lin, S., Hu, X., Liu, F., Liu, X., & Zhang, H. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.00195 · Cited by 5 · cited 1× · see citing works
“CCA encompasses a highly heterogeneous genomic mutational landscape that is associated with poor outcomes in patients [2,6,7,54,55].”
Background[WHO guidelines for governments and consumers regarding the use of alternative therapies].
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Moro, C. F., Fernandez-Woodbridge, A., D'souza, M. A., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0171283 · Cited by 4 · see citing works
Shen, N., Zhang, D., Yin, L., Qiu, Y., Liu, J., Yu, W., Fu, X., Zhu, B., Xu, X., Duan, A., et al. (2019) · Cancer Research · doi:10.1158/1538-7445.am2019-2292
Flagged first, then by citations
Research works printed but not linked: 1
- Chinese Chapter of International Hepato-PancreatoBiliary Association, and Hepatic Surgery Group (2015). Chinese Society of Surgery, Chinese Medical Association. Diagnosis and treatment of cholangiocarcinoma:surgical expert consensus. J. Clin. Hepatol., 31, 12–16.
Cited by
Sorted by citations
Circulating tumor DNA in cholangiocarcinoma: current clinical applications and future perspectives
Wang, J., Li, Y., Liang, Z., Zhang, Y., Li, T., Tian, C., Zhao, J., Jin, B., Cao, J., & Lin, Y. (2025) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2025.1616064 · Cited by 19 · see citing works
Cholangiocarcinoma: The era of liquid biopsy
Kotsifa, E., Saffioti, F., & Mavroeidis, V. K. (2025) · World Journal of Gastroenterology · doi:10.3748/wjg.v31.i11.104170 · Cited by 12 · see citing works
Farhat, J., Alzyoud, L., Alwahsh, M., Acharjee, A., & Al‐Omari, B. (2025) · Cancer Medicine · doi:10.1002/cam4.70853 · Cited by 10 · see citing works
“This reveals the heterogeneous nature of cholangiocarcinoma, emphasizing the need for subtype-specific diagnostic and therapeutic strategies [114].”
Microbiome and gut-liver interactions: From mechanisms to therapies
Anis, M. A., Shahid, Y., Majeed, A. A., & Abid, S. (2025) · World Journal of Gastroenterology · doi:10.3748/wjg.v31.i40.111409 · Cited by 11 · see citing works
Genomic landscape of biliary tract cancer and corresponding targeted treatment strategies
Yamada, D., Kobayashi, S., Doki, Y., & Eguchi, H. (2025) · International Journal of Clinical Oncology · doi:10.1007/s10147-025-02761-x · Cited by 8 · see citing works
2′,4′-dihydroxychalcone induces ferroptosis through ERO1A/GPX4 regulatory axis in cholangiocarcinoma
Wang, T., Zhou, X., Wang, N., Su, Z., Bi, Y., Sun, L., Liu, L., Piao, Y., Piao, J., Lin, Z., et al. (2025) · Phytomedicine · doi:10.1016/j.phymed.2025.157192 · Cited by 5 · see citing works
Bai, M., Wang, R., Huang, C., Zhong, R., Jiang, N., Fu, W., Mi, N., Gao, L., Jin, Y., Ma, H., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-81392-0 · Cited by 5 · see citing works
“Chemotherapy is the standard treatment for patients with metastatic and unresectable disease or recurrent CCA 32 .”
Zhao, R., Han, M., Lin, S., Lin, Z., Yu, M., Zhang, B., Ma, L., Li, D., & Peng, L. (2024) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2024.2380513 · Cited by 5 · see citing works
“5-FU has been extensively employed in the treat-ment of various gastrointestinal malignancies, including CRC [6], cholangiocarcinoma [7], pancreatic cancer [8,9], and gastric cancer [10].”
Endoscopic Ablation in Cholangiocarcinoma
Natha, C. M., Vemulapalli, V., & Thosani, N. C. (2025) · Cancers · doi:10.3390/cancers17172843 · Cited by 4 · see citing works
“The malignancy is often characterized by dense desmoplastic stroma, perineural invasion, and vascular encasement— factors that contribute to its insidious progression and frequent late-stage diagnosis [9].”
Targeting PDGF-CC as a promising therapeutic strategy to inhibit cholangiocarcinoma progression
Luo, Z., Zhou, F., Tan, C., et al. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-05857-6 · Cited by 4 · see citing works
“The molecular mechanisms driving CCA progression are complex and not fully understood, necessitating further exploration to identify potential therapeutic targets that could improve patient outcomes [23].”
Diagnosis of Cholangiocarcinoma: The New Biological and Technological Horizons
Selvaggi, F., Lopetuso, L. R., Pizzi, A. D., Melchiorre, E., Murgiano, M., Taraschi, A. L., Cotellese, R., Diana, M., Vivarelli, M., Mocchegiani, F., et al. (2025) · Diagnostics · doi:10.3390/diagnostics15081011 · Cited by 4 · see citing works
“Based on emerging findings, the differences in gut microbiota composition observed in CCA patients suggest that specific microbial features could serve as a non-invasive diagnostic tool for early CCA detection [87].”
Aziz, B., Bosman, E., van der Wurff‐Jacobs, K. M. G., van Nostrum, C. F., & Khurshid, A. (2025) · Biomedical Materials · doi:10.1088/1748-605x/adaff7 · Cited by 4 · see citing works
Muhammad, Y., Jin, Y., Luo, K., Bai, H., Zhang, X., Sun, X., Maheen, Z., Tanveer, A., Muhammad, S. M., Qu, J., et al. (2026) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.70357 · Cited by 3 · see citing works
“Triplet regimens have been explored to increase efficacy in treating advanced or metastatic biliary system tumors, such as iCCA, at the local level; however, the outcomes are still varied or in the early stages [193].”
New Relevant Evidence in Cholangiocarcinoma Biology and Characterization
Porro, N., Spínola-Lasso, E., Pastore, M., Caligiuri, A., Tommaso, L. D., Marra, F., & Gentilini, A. (2024) · Cancers · doi:10.3390/cancers16244239 · Cited by 3 · see citing works
“Probiotics are microorganisms that helps the host to restore microbial dysbiosis, maintaining intestinal microbial balance and inhibiting the colonization of harmful bacteria [7].”
Li, X., Guan, R., & Zhang, S. (2025) · Biology · doi:10.3390/biology14040351 · Cited by 3 · see citing works
“Other risk factors include inflammatory bowel disease, alcohol consumption, and smoking, and, of course, the controversial factors of obesity and hypertension [36], as seen in Table 1.”
Enhancing biliary tract cancer diagnosis using AI-driven 3D optical diffraction tomography
Park, S. W., Moon, H. C., Hong, S. J., et al. (2025) · Methods · doi:10.1016/j.ymeth.2025.06.003 · Cited by 3 · see citing works
Overexpression of TBX3 suppresses tumorigenesis in experimental and human cholangiocarcinoma
Deng, S., Lu, X., Wang, X., Liang, B., Xu, H., Yang, D., Cui, G., Yonemura, A., Paine, H., Zhou, Y., et al. (2024) · Cell Death & Disease · doi:10.1038/s41419-024-06839-8 · Cited by 2 · see citing works
Ahmad, A. V. D., Shaikh, M. S., Khan, S. W., et al. (2025) · Discover Molecules · doi:10.1007/s44345-025-00014-y · Cited by 2 · see citing works
Frozen Section Studies of Gastrointestinal and Hepatobiliary Systems: A Review Article
Zaitoun, A. M., & Almahari, S. A. (2025) · Gastroenterology Insights · doi:10.3390/gastroent16040046 · Cited by 2 · see citing works
Dixit, S., Mahakalkar, C., Kshirsagar, S., et al. (2024) · Cureus · doi:10.7759/cureus.66790 · Cited by 2 · see citing works
Bulut, G., Kayis, M., Gezer, D., et al. (2025) · Medical Oncology · doi:10.1007/s12032-025-02927-7 · Cited by 1 · see citing works
“Despite their routine use, current chemotherapeutic options are insufficient to achieve meaningful long-term outcomes, underscoring the urgent need for more effective and targeted therapeutic approaches [14].”
Cholangiocarcinoma in the Era of Precision Medicine: Emerging Insights and Therapeutic Strategies
Agarwal, A., Rashid, S., James, L., & Mattei, J. (2026) · Current Pharmaceutical Design · doi:10.2174/0113816128428934260307141948 · Cited by 1 · see citing works
Jeeunngoi, J., Senawong, G., Jogloy, S., et al. (2024) · Preprints.org · doi:10.20944/preprints202407.0656.v1
Image-Guided Ablation for Cholangiocarcinoma: Current Evidence and Future Directions
Silva, J. A. M., Paolucci, I., Brock, K. K., et al. (2024) · Digestive Disease Interventions · doi:10.1055/s-0044-1787959
Surgical Decision-Making in Hepatobiliary and Pancreatic Surgery
Chumbinho, B., Custódio, P., Sobral, M., et al. (2024) · Springer eBooks · doi:10.1007/978-3-031-67391-7_17
Role of genomics in liver transplantation for cholangiocarcinoma
Soliman, N., Maqsood, A., & Connor, A. A. (2025) · Current Opinion in Organ Transplantation · doi:10.1097/mot.0000000000001209
Wulandari, F. S., Huang, L.-Y., Crawford, D. R., et al. (2025) · Research Square · doi:10.21203/rs.3.rs-6527097/v1
The Role and Function of Non-Coding RNAs in Cholangiocarcinoma Invasiveness
Meng, Y., Wei, F., Zhang, Y., He, W., Yan, H., & Wu, J. (2025) · Biomedicines · doi:10.3390/biomedicines13061369
Zhang, J., Gong, Y., Li, W., et al. (2025) · Research Square · doi:10.21203/rs.3.rs-7591535/v1
Can flukes cause cancer? Insight into molecular links between parasites and carcinogenesis
Paluch, M., Cudzik, M., Kędra, A., et al. (2025) · Molecular and Biochemical Parasitology · doi:10.1016/j.molbiopara.2025.111707
Nanotheranostics in gastrointestinal cancers
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Braga, V. M., Pereira, P. H. F., Apolinário, L. D. A., da Silva, D. M., Ramalho, L. N. Z., Ali, S., de Oliveira, C. A. F., & Ramalho, F. S. (2025) · Toxins · doi:10.3390/toxins18010014
“…targeted-therapy approaches as well as other molecular strategies, including FGFR2-directed inhibitors, IDH1/2 inhibitors, ERBB2-targeted therapies and selected immunotherapy-based combination [22], and besides that cyclin D1 and Rb status might represent markers of progression or aggressiveness.”
Sitthirak, S., Wangwiwatsin, A., Jusakul, A., Namwat, N., Klanrit, P., Roytrakul, S., Dokduang, H., Duangchan, T., Rattanapan, Y., Titapun, A., et al. (2026) · Medical Sciences · doi:10.3390/medsci14010030
“These modifications augment the flexibility of cancer cells, enabling them to acclimate to environmental stresses and treatment strategies [32,33].”
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“Among all BTC subtypes, the anatomical site and spread pattern are vital reasons why so few patients qualify as candidates for curative surgery [47].”
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“Liver flukes, cholangitis, and stones are the primary risk factors for CCA, while metabolic conditions, excessive alcohol consumption, and hepatitis viruses play lesser, but still not neglectable roles (Khosla et al., 2024; Dolbnya et al., 2024).”
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“At the molecular level, CCA development is driven by genetic and epigenetic alterations, including dysregulation of oncogenic pathways such as MAPK, PI3K/AKT, and Notch signaling, which promote tumor progression, metastasis, and therapeutic resistance [5].”
Bulut, G., Kayis, M., Ozyıldız, Z., et al. (2026) · Bratislavské lekárske listy/Bratislava medical journal · doi:10.1007/s44411-026-00848-z
- Authors
- Khosla, D., Misra, S., Chu, P. L., Guan, P., Nada, R., Gupta, R., Kaewnarin, K., Ko, T. K., Heng, H. L., Srinivasalu, V. K., Kapoor, R., Singh, D., Klanrit, P., Sampattavanich, S., Tan, J., Kongpetch, S., Jusakul, A., Teh, B. T., Chan, J. Y., & Hong, J. H.
- Affiliations
- Post Graduate Institute of Medical Education and Research (IN)
- Sanjay Gandhi Post Graduate Institute of Medical Sciences (IN)
- Duke-NUS Medical School (SG)
- Agency for Science, Technology and Research (SG)
- SingHealth (SG)
- National Cancer Centre Singapore (SG)
- Mazumdar Shaw Medical Centre (IN)
- Khon Kaen University (TH)
- Siriraj Hospital (TH)
- Corresponding author
- Hong, Jing Han
- ORCID
- Khosla, Divya
- Misra, Shagun
- Chu, Pek Lim
- Guan, Peiyong
- Nada, Ritambhra
- Gupta, Rajesh
- Kaewnarin, Khwanta
- Ko, Tun Kiat
- Heng, Hong Lee
- Srinivasalu, Vijay Kumar
- Kapoor, Rakesh
- Singh, Deepika
- Klanrit, Poramate
- Sampattavanich, Somponnat
- Tan, Jing
- Kongpetch, Sarinya
- Jusakul, Apinya
- Teh, Bin Tean
- Chan, Jason Yongsheng
- Hong, Jing Han
- Venue
- Cancers
- Publisher
- MDPI AG
- Published
- 2024-02-16
- Volume
- 16
- Issue
- 4
- Pages
- 801
- ISSN
- 2072-6694 (ISSN-L)
- PMC
- PMC10887007
- OpenAlex
- W4391882308
- Semantic Scholar
- c03076863c4d48c91184b0576db88f65fd165b01
- Cited by
- 44
- References
- 187
- Citations by year
- 2026: 13 · 2025: 22 · 2024: 9
- FWCI
- 4.86
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cancers (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Singapore Therapeutics Development Review Pre-Pilot (H23G1a0009, TA21jun-0005, 08/FY2023/EX/27-A65, MOH-000248-00, MOH-000144, COVID19TUG21-0146, 236B9008)
- Singapore Ministry of Health’s National Medical Research Council Research Transition Award (H23G1a0009, TA21jun-0005, 08/FY2023/EX/27-A65, MOH-000248-00, MOH-000144, COVID19TUG21-0146, 236B9008)
- AM/ACP-Designated Philanthropic Fund Grant Award (H23G1a0009, TA21jun-0005, 08/FY2023/EX/27-A65, MOH-000248-00, MOH-000144, COVID19TUG21-0146, 236B9008)
- National Medical Research Council Singapore Translational Research Investigator Award (H23G1a0009, TA21jun-0005, 08/FY2023/EX/27-A65, MOH-000248-00, MOH-000144, COVID19TUG21-0146, 236B9008)
- National Medical Research Council Open Fund—Individual Research Grant (H23G1a0009, TA21jun-0005, 08/FY2023/EX/27-A65, MOH-000248-00, MOH-000144, COVID19TUG21-0146, 236B9008)
- NCC Cancer Fund (H23G1a0009, TA21jun-0005, 08/FY2023/EX/27-A65, MOH-000248-00, MOH-000144, COVID19TUG21-0146, 236B9008)
- Verdant Foundation (H23G1a0009, TA21jun-0005, 08/FY2023/EX/27-A65, MOH-000248-00, MOH-000144, COVID19TUG21-0146, 236B9008)
- 3rd A*STAR-AMED Joint Grant (H23G1a0009, TA21jun-0005, 08/FY2023/EX/27-A65, MOH-000248-00, MOH-000144, COVID19TUG21-0146, 236B9008)
- Topics
- Health Sciences › Medicine › Surgery › Cholangiocarcinoma and Gallbladder Cancer Studies
- Health Sciences › Medicine › Surgery › Pediatric Hepatobiliary Diseases and Treatments
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Keywords
- cholangiocarcinoma, molecular pathobiology, liver fluke, aristolochic acid, genetic mutations, epigenetic dysregulation, post-transcriptional modification, liquid biopsy, cell-free DNA, surgical resection, adjuvant chemotherapy, cisplatin, gemcitabine, FOLFOX, radiotherapy, targeted therapy, IDH1 mutation, immune checkpoint inhibitors, immunotherapy, natural compounds, gut dysbiosis, precision medicine
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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