Aspirin use and risk of cholangiocarcinoma: External validation with big data

Altaii, Haider; Al‐Kindi, Sadeer G.; Oliveira, Guilherme H.; Yaqoob, Zaid; Romero‐Marrero, Carlos

doi:10.1002/hep.28920

Cited by 15 publications

(13 citation statements)

References 4 publications

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“…68 The results supported the conclusion of the Mayo-based study, that is, the adjusted OR (aOR) for CCA was lower in aspirin users compared to nonusers (aOR, 0.86; 95% CI, 0.82-0.90; P < .001). 68 However, given the retrospective nature of case-control studies, both analyses were affected by recall bias, and therefore large-scale prospective studies are needed in the future to elucidate the chemopreventive effects of aspirin on CCA.…”

Section: Aspirin and Reduced Risk For Ccasupporting

confidence: 82%

“…These authors reported that aspirin use was associated with a significantly reduced risk of developing any of the three CCA subtypes, with an adjusted OR of 0.35 (95% CI, 0.29‐0.42; P < .001) for iCCA, 0.34 (95% CI, 0.27‐0.42; P < .001) for pCCA, and 0.29 (95% CI, 0.19‐0.44; P < .001) for dCCA 30 . To validate these results in a real‐world cohort, another group of researchers repeated the analysis in a larger clinical registry involving 8 108 530 patients across the United States 68 : 39% of these patients (3153600) used aspirin, and a total of 8460 (0.001%) cases with CCA were identified 68 . The results supported the conclusion of the Mayo‐based study, that is, the adjusted OR (aOR) for CCA was lower in aspirin users compared to nonusers (aOR, 0.86; 95% CI, 0.82‐0.90; P < .001) 68 .…”

Section: Evidence For An Anticancer Effect Of Aspirin On Ccamentioning

confidence: 92%

“…To validate these results in a real‐world cohort, another group of researchers repeated the analysis in a larger clinical registry involving 8 108 530 patients across the United States 68 : 39% of these patients (3153600) used aspirin, and a total of 8460 (0.001%) cases with CCA were identified 68 . The results supported the conclusion of the Mayo‐based study, that is, the adjusted OR (aOR) for CCA was lower in aspirin users compared to nonusers (aOR, 0.86; 95% CI, 0.82‐0.90; P < .001) 68 . However, given the retrospective nature of case‐control studies, both analyses were affected by recall bias, and therefore large‐scale prospective studies are needed in the future to elucidate the chemopreventive effects of aspirin on CCA.…”

Section: Evidence For An Anticancer Effect Of Aspirin On Ccamentioning

confidence: 99%

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A potential role for aspirin in the prevention and treatment of cholangiocarcinoma

Shen

2020

Intl Journal of Cancer

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Cholangiocarcinoma is the second most common primary hepatic cancer, with a rising incidence worldwide. Owing to late diagnosis and limited treatment options, the prognosis for cholangiocarcinoma remains dismal, compelling a search for new treatments. As aspirin exhibits a well‐supported chemopreventive effect on common cancers, researchers have proposed using aspirin as a potential preventive and adjuvant agent for cholangiocarcinoma. In the present review of the literature, we provide a background on cholangiocarcinoma and potential mechanisms of action underlying the anticancer effect of aspirin. Although the exact mode of action remains unclear, multiple downstream effects of aspirin may interfere with cholangiocarcinogenesis, tumour growth and metastasis—including inhibiting the COX‐2 pathway, preventing platelet aggregation and modulating certain proteins and signalling. This review also summarises evidence to support the chemopreventive effects of aspirin on common cancers, particularly colorectal cancer and discusses studies that report a positive outcome of aspirin in cholangiocarcinoma. Regular use of aspirin is associated with a reduced incidence of colorectal cancers as well as cholangiocarcinomas, and improved survival. Aspirin thus appears to play a role in the primary prevention and treatment of cholangiocarcinoma. However, further studies are needed to confirm these benefits and to establish a cause‐and‐effect relationship.

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Section: Aspirin and Reduced Risk For Ccasupporting

confidence: 82%

Section: Evidence For An Anticancer Effect Of Aspirin On Ccamentioning

confidence: 92%

Section: Evidence For An Anticancer Effect Of Aspirin On Ccamentioning

confidence: 99%

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A potential role for aspirin in the prevention and treatment of cholangiocarcinoma

Shen

2020

Intl Journal of Cancer

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“…For example, aspirin treatment was associated with a reduction of morbidity in patients with colorectal adenoma [26,27], and NSAIDs were reported to improve patient survival for PIK3CA-altered head and neck cancer [28]. Regarding CCA, aspirin use was demonstrated to decrease the risk for all the three CCA subtypes [29]. The molecular mechanisms of how NSAIDs suppress tumor progression have also been widely examined in previous studies [30].…”

Section: Discussionmentioning

confidence: 99%

Annexin10 promotes extrahepatic cholangiocarcinoma metastasis by facilitating EMT via PLA2G4A/PGE2/STAT3 pathway

et al. 2019

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BackgroundCholangiocarcinoma (CCA), consisting of intrahepatic (IHCCA), perihilar (PHCCA), and distal (DCCA) CCA, is a type of highly aggressive malignancy with a very dismal prognosis. Potential biomarkers and drug targets of CCA are urgently needed. As a new member of the Annexin (ANXA) family, the role of ANXA10 in the progression and prognosis of CCA is unknown.MethodsPotential PHCCA biomarkers were screened by transcriptome sequencing of 5 pairs of PHCCA and adjacent tissues. The clinical significance of ANXA10 was evaluated by analyzing its correlation with clinicopathological variables, and the prognostic value of ANXA10 was evaluated with univariate and multivariate analyses. The function of ANXA10 in the epithelial-mesenchymal transition (EMT), proliferation, invasion and metastasis was detected with in vitro and in vivo experiments. Moreover, we screened the key molecule in ANXA10-induced CCA progression by mRNA sequencing and evaluated the correlation between PLA2G4A and ANXA10. The effect of PLA2G4A downstream signaling, including Cyclooxygenase 2, Prostaglandin E2(PGE2) and Signal transducer and activator of transcription 3(STAT3), on EMT and metastasis was further detected with in vitro and in vivo experiments.FindingsANXA10 expression was upregulated in PHCCA and DCCA but not in IHCCA. High ANXA10 expression was significantly associated with poor tumor differentiation and prognosis. ANXA10 promoted the proliferation, migration and invasion of the PHCCA cells. PLA2G4A expression was regulated by ANXA10 and high PLA2G4A predicted poor prognosis in PHCCA and DCCA. ANXA10 facilitated EMT and promoted metastasis by upregulating PLA2G4A expression, thus increasing PGE2 levels and activating STAT3.InterpretationANXA10 was an independent prognostic biomarker of PHCCA and DCCA but not IHCCA. ANXA10 promoted the progression of PHCCA and facilitated metastasis by promoting the EMT process via the PLA2G4A/PGE2/STAT3 pathway. ANXA10, PLA2G4A and their downstream molecules, such as COX2 and PGE2, may be promising drug targets of PHCCA and DCCA.

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“…In addition, SNOMED-CT allows for more concepts to be coded per clinical document compared to ICD making it more accurate in terms of documenting diagnoses and pertinent patient information. It is important to highlight that Explorys has been validated previously as a database (59) and in different specialties including gastroenterology (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)60,61).…”

Section: Discussionmentioning

confidence: 99%

Epidemiology of gallbladder cancer in the Unites States: a population-based study

Alkhayyat¹,

Saleh²,

Qapaja³

et al. 2021

Chin Clin Oncol

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Background: Gallbladder cancer (GBC) is the most common neoplasm of the biliary tract with the lowest rates of survival. Most GBCs are adenocarcinomas that arise from the epithelial lining of the gallbladder. There are limited data in the literature regarding the epidemiology of GBC. Using a large database, we aim to describe the epidemiology using a US population database. Methods: A multi-institutional database (Explorys Inc., Cleveland, OH, USA) was surveyed. A cohort of patients with a primary malignant neoplasm of gallbladder between 1999-2019 was identified. The prevalence rate was calculated and age-, race-, and sex-based distributions were described. Multivariate analysis was done to evaluate underlying associations. Results: Of the 56,197,690 individuals in the database, 4,790 individuals with GBC were identified with a prevalence rate of 8.5 per 100,000. Asian race has the highest prevalence of GBC (13.6/100,000). Patients with GBC were also more likely to be smokers, have a history of alcohol abuse, obesity, diabetes, cholelithiasis, chronic cholecystitis, primary sclerosing cholangitis (PSC), and chronic viral hepatitis. Conclusions: This is one of the largest US population studies to date evaluating the epidemiology of GBC. The 20-year period prevalence rate of GBC was 8.5 per 100,000. Patients with GBC were more likely to be elderly, females, obese, diabetic, and have chronic hepatobiliary disorders.

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Aspirin use and risk of cholangiocarcinoma: External validation with big data

Cited by 15 publications

References 4 publications

A potential role for aspirin in the prevention and treatment of cholangiocarcinoma

A potential role for aspirin in the prevention and treatment of cholangiocarcinoma

Annexin10 promotes extrahepatic cholangiocarcinoma metastasis by facilitating EMT via PLA2G4A/PGE2/STAT3 pathway

Epidemiology of gallbladder cancer in the Unites States: a population-based study

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