Intrahepatic cholangiocarcinoma: pathogenesis, current staging, and radiological findings

Saleh, Mohammed; Virarkar, Mayur; Bura, Vlad; Valenzuela, Raúl; Javadi, Sanaz; Szklaruk, Janio; Bhosale, Priya

doi:10.1007/s00261-020-02559-7

Cited by 35 publications

(21 citation statements)

References 113 publications

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“…Radiologic criteria can only suggest a possible iCCA diagnosis, and a definitive diagnosis can only be based on histology. In particular, histological confirmation of iCCA on liver biopsy is mandatory in cases of unresectable disease, to determine subsequent patient management 1 , 2 , 17 .…”

Section: Intrahepatic Cholangiocarcinomamentioning

confidence: 99%

“…Other non-specific symptoms, typically seen in advanced disease, include fatigue, abdominal pain, malaise, nausea, anorexia, and weight loss. CA19-9 is characteristically elevated 1 , 2 , 4 , 5 , 17 .…”

Section: Intrahepatic Cholangiocarcinomamentioning

confidence: 99%

“…Morphology and clinical history is usually helpful in differentiating iCCA from benign lesions 17 . However, the distinction between a well-differentiated iCCA and its benign mimics can be challenging, particularly in small biopsies with scant cellularity.…”

Section: Intrahepatic Cholangiocarcinomamentioning

confidence: 99%

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Cholangiocarcinoma

et al. 2021

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Summary Liver cancer represents the third leading cause of cancer-related death worldwide. Cholangiocarcinoma (CCA) is the second most common type of liver cancer after hepatocellular carcinoma, accounting for 10-15% of all primary liver malignancies. Both the incidence and mortality of CCA have been steadily increasing during the last decade. Moreover, most CCAs are diagnosed at an advanced stage, when therapeutic options are very limited. CCA may arise from any tract of the biliary system and it is classified into intrahepatic, perihilar, and distal CCA, according to the anatomical site of origin. This topographical classification also reflects distinct genetic and histological features, risk factors, and clinical outcomes. This review focuses on histopathology of CCA, its differential diagnoses, and its diagnostic pitfalls.

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Section: Intrahepatic Cholangiocarcinomamentioning

confidence: 99%

Section: Intrahepatic Cholangiocarcinomamentioning

confidence: 99%

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Cholangiocarcinoma

et al. 2021

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“…The age-specific mortality rate of this disease has increased in almost all countries across all continents, albeit at different rates [ 3 ]. The rising incidence and high mortality of iCCA have aroused growing worldwide concerns, especially over the last two decades [ 6 ]. The significant increase in the mortality rate of this primary hepatobiliary cancer coincides with the rapidly growing interest of clinicians and investigators [ 3 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

ESR1 as a recurrence-related gene in intrahepatic cholangiocarcinoma: a weighted gene coexpression network analysis

Chen

Yang

et al. 2021

Cancer Cell Int

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Background Intrahepatic cholangiocarcinoma (iCCA) is the second most common malignant hepatic tumor and has a high postoperative recurrence rate and a poor prognosis. The key roles of most tumor recurrence-associated molecules in iCCA remain unclear. This study aimed to explore hub genes related to the postsurgical recurrence of iCCA. Method Differentially expressed genes (DEGs) between iCCA samples and normal liver samples were screened from The Cancer Genome Atlas (TCGA) database and used to construct a weighted gene coexpression network. Module-trait correlations were calculated to identify the key module related to recurrence in iCCA patients. Genes in the key module were subjected to functional enrichment analysis, and candidate hub genes were filtered through coexpression and protein–protein interaction (PPI) network analysis. Validation studies were conducted to detect the “real” hub gene. Furthermore, the biological functions and the underlying mechanism of the real hub gene in iCCA tumorigenesis and progression were determined via in vitro experiments. Results A total of 1019 DEGs were filtered and used to construct four coexpression modules. The red module, which showed the highest correlations with the recurrence status, family history, and day to death of patients, was identified as the key module. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses demonstrated that genes in the red module were enriched in genes and pathways related to tumorigenesis and tumor progression. We performed validation studies and identified estrogen receptor 1 (ESR1), which significantly impacted the prognosis of iCCA patients, as the real hub gene related to the recurrence of iCCA. The in vitro experiments demonstrated that ESR1 overexpression significantly suppressed cell proliferation, migration, and invasion, whereas ESR1 knockdown elicited opposite effects. Further investigation into the mechanism demonstrated that ESR1 acts as a tumor suppressor by inhibiting the JAK/STAT3 signaling pathway. Conclusions ESR1 was identified as the real hub gene related to the recurrence of iCCA that plays a critical tumor suppressor role in iCCA progression. ESR1 significantly impacts the prognosis of iCCA patients and markedly suppresses cholangiocarcinoma cell proliferation, migration and invasion by inhibiting JAK/STAT3 signaling pathway.

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“…In all enrolled patients, we confirmed that a center of tumor was located in the periphery of hilar bile duct, and evaluated presence or absence of tumor extent to hilar bile duct with preoperative image studies. Based on UICC 8 th , hilar bile duct was defined as the duct located between the right side of the umbilical portion of the left portal vein and the left side of the origin of the right posterior portal vein [25][26][27].…”

Section: Preoperative Managementmentioning

confidence: 99%

The prognostic impact of lymphocyte-to-C-reactive protein score in patients undergoing surgical resection for intrahepatic cholangiocarcinoma: A comparative study of major representative inflammatory / immunonutritional markers

et al. 2021

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Background In many malignancies including intrahepatic cholangiocarcinoma (iCCA), prognostic significance of host-related inflammatory / immunonutritional markers have attracted a lot of attention. However, it is unclear which is the strongest prognostic indicator for iCCA among these markers. The aim of this study was to firstly evaluate the prognostic utility of inflammatory / immunonutritional markers in resected iCCA patients using a multiple comparison in addition to a new marker, lymphocyte-to-C-reactive protein (CRP) score. Methods A total of sixty iCCA patients, who underwent surgical resection between October 2004 and April 2019, were enrolled in this study. Their clinical and pathological data were retrospectively assessed using univariate and multivariate analysis to determine prognostic predictors for disease specific survival (DSS). Moreover, these patients, who were divided into high and low groups based on lymphocyte-to-CRP score, were compared these survival outcomes using Kaplan-Meier analysis with a log-rank test. Results In multivariate analysis, the significant prognostic factors were preoperative lymphocyte-to-CRP score (p = 0.008), preoperative CRP-to-albumin ratio (CAR; p = 0.017), pathological T category (p = 0.003), and pathological vascular invasion (p < 0.001). Resected iCCA patients with a low lymphocyte-to-CRP score (score 0) had significant better prognosis than patients with a high score (score 1 or 2) (p = 0.016). Notably, the mortality of the high lymphocyte-to-CRP score group did not show statistically difference from the poor mortality of unresected iCCA patients (p = 0.204). Conclusions Preoperative lymphocyte-to-CRP score was the strongest prognostic indicator in iCCA patients with surgical resection. In these patients, early intervention with nutritional support should be considered prior to operation.

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Intrahepatic cholangiocarcinoma: pathogenesis, current staging, and radiological findings

Cited by 35 publications

References 113 publications

Cholangiocarcinoma

Cholangiocarcinoma

ESR1 as a recurrence-related gene in intrahepatic cholangiocarcinoma: a weighted gene coexpression network analysis

The prognostic impact of lymphocyte-to-C-reactive protein score in patients undergoing surgical resection for intrahepatic cholangiocarcinoma: A comparative study of major representative inflammatory / immunonutritional markers

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