Metabolic disorders and the risk of cholangiocarcinoma

Ghidini, Michele; Ramai, Daryl; Facciorusso, Antonio; Singh, Jameel; Tai, Waqqas; Rijavec, Erika; Galassi, Barbara; Grossi, Francesco; Indini, Alice

doi:10.1080/17474124.2021.1946393

Cited by 12 publications

(4 citation statements)

References 93 publications

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“…NAFLD/NASH may have a pro-carcinogenic role in the development of iCCA. Thus, recent epidemiological evidence clearly indicates that MetS is a risk factor not only for hepatocellular carcinoma, but also for iCCA [11,17]. However, whereas the mechanisms by which MetS and the related liver involvement, NAFLD/NASH, sustain carcinogenesis towards HCC have drawn attention, underlying the role of the long-lasting inflammatory response induced by the lipotoxicity affecting the hepatocytes [18], how a metabolic derangement may induce pro-oncogenic effects on the cholangiocyte level has not been investigated yet.…”

Section: Discussionmentioning

confidence: 99%

Intrahepatic Cholangiocarcinoma Developing in Patients with Metabolic Syndrome Is Characterized by Osteopontin Overexpression in the Tumor Stroma

Cadamuro

Sarcognato

Camerotto

et al. 2023

IJMS

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Metabolic syndrome (MetS) is a common condition closely associated with non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH). Recent meta-analyses show that MetS can be prodromal to intrahepatic cholangiocarcinoma (iCCA) development, a liver tumor with features of biliary differentiation characterized by dense extracellular matrix (ECM) deposition. Since ECM remodeling is a key event in the vascular complications of MetS, we aimed at evaluating whether MetS patients with iCCA present qualitative and quantitative changes in the ECM able to incite biliary tumorigenesis. In 22 iCCAs with MetS undergoing surgical resection, we found a significantly increased deposition of osteopontin (OPN), tenascin C (TnC), and periostin (POSTN) compared to the matched peritumoral areas. Moreover, OPN deposition in MetS iCCAs was also significantly increased when compared to iCCA samples without MetS (non-MetS iCCAs, n = 44). OPN, TnC, and POSTN significantly stimulated cell motility and the cancer-stem-cell-like phenotype in HuCCT-1 (human iCCA cell line). In MetS iCCAs, fibrosis distribution and components differed quantitatively and qualitatively from non-MetS iCCAs. We therefore propose overexpression of OPN as a distinctive trait of MetS iCCA. Since OPN stimulates malignant properties of iCCA cells, it may provide an interesting predictive biomarker and a putative therapeutic target in MetS patients with iCCA.

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Section: Discussionmentioning

confidence: 99%

Intrahepatic Cholangiocarcinoma Developing in Patients with Metabolic Syndrome Is Characterized by Osteopontin Overexpression in the Tumor Stroma

Cadamuro

Sarcognato

Camerotto

et al. 2023

IJMS

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“…In our case, a potential explanation is that patients tend to be more adherent to medical treatment and lifestyle changes after the diagnosis of CCA, and it would minimize the carcinogenic effect of overweight and altered glucose metabolism in the follow-up. In this regard, the published data have shown that biguanides, such as metformin, promote a 60% reduction in the risk of developing iCCA [ 19 ], while aspirin and statins were shown to reduce the risk of death among patients with CCA [ 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

Association between Metabolic Disorders and Cholangiocarcinoma: Impact of a Postulated Risk Factor with Rising Incidence

Fonseca

Hashizume

Oliveira

et al. 2022

Cancers

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Introduction and objectives: The incidence of cholangiocarcinoma (CCA) has been increasing globally. Although a concomitant increase in the incidence of metabolic disorders might suggest a causal relationship, the data are scarce. We aimed to describe the prevalence of metabolic disorders in patients with CCA and report the clinical features and outcomes. Patients and Methods: Retrospective study including patients with CCA. Patients were divided into: (1) past history of diabetes or/and overweight/obesity (“metabolic disorder group”) and (2) without any of these features (“non-metabolic-disorder group”). A Cox regression model was used to determine the prognostic factors. Results: 122 patients were included. In total, 36 (29.5%) had overweight/obesity, 24 (19.7%) had diabetes, and 8 (6.6%) had both. A total of 29 (23.8%) patients had resectable disease and received upfront surgery. A total of 104 (85.2%) received chemotherapy for advanced/recurrent disease. The overall survival of the cohort was 14.3 months (95% CI: 10.1–17.3). ECOG-PS 0 (p < 0.0001), resectable disease (p = 0.018) and absence of vascular invasion (p = 0.048) were independently associated with better prognosis. The “metabolic disorder group” (n = 52) had a median survival of 15.5 months (95% CI 10.9–33.9) vs. 11.5 months (95% CI 8.4–16.5) in the “non-metabolic-disorder group” (n = 70) (HR: 1.10; 95% CI 0.62–1.94). Patients with resectable disease in the “metabolic group” had longer survival than patients in the “non-metabolic group” (43.4 months (95% CI 33.9-NR) vs. 21.8 months (95% CI 8.6–26.9); HR = 0.12, 95% CI 0.03–0.59). Conclusion: Metabolic disorders are frequent among CCA patients. Underlying metabolic comorbidities may be associated with prognosis in resectable CCA. There is a need to explore the mechanism that drives CCA carcinogenesis in a metabolic background.

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“…Zu den primären Leberkarzinomen zählen nicht nur HCCs, sondern auch die intrahepatischen Cholangiokarzinome. Die intrahepatischen Cholangiokarzinome sind gleichermaßen mit dem MetS assoziiert 31 .…”

Section: Hepatozelluläres Karzinomunclassified

Metabolisches Syndrom und Krebsrisiko

Scherübl¹

2022

Dtsch Med Wochenschr

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Krebs zählt zu den führenden Todesursachen beim metabolischen Syndrom (MetS). Je mehr Komponenten des metabolischen Syndroms jemand hat, desto stärker steigt das Tumorrisiko, z. B. Karzinome des Dickdarms. Bei adipösen MetS-Patienten kann die Gewichtsreduktion das Krebsrisiko senken. Dem MetS vorzubeugen und regelmäßig an Vorsorgeuntersuchungen teilzunehmen ist wichtig und verringert das Risiko, an Krebs zu erkranken und daran zu versterben. HintergrundTumorerkrankungen sind die häufigste Todesursache der deutschen Bevölkerung im Alter von 35-70 Jahren. In dieser Altersgruppe übertreffen die malignombedingten Todesfälle diejenigen infolge von Herz-Kreislauf-Krankheiten um mehr als das Doppelte [1]. Es erkranken in Deutschland jedes Jahr > 500 000 Menschen neu an Krebs. Das statistische Lebenszeitrisiko einer Tumordiagnose beträgt ca. 35 % und dies mit steigender Tendenz. MerkeZusammen mit Herz-Kreislauf-Erkrankungen zählt Krebs zu den 2 führenden Todesursachen bei Menschen mit metabolischem Syndrom (MetS).

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Metabolic disorders and the risk of cholangiocarcinoma

Cited by 12 publications

References 93 publications

Intrahepatic Cholangiocarcinoma Developing in Patients with Metabolic Syndrome Is Characterized by Osteopontin Overexpression in the Tumor Stroma

Intrahepatic Cholangiocarcinoma Developing in Patients with Metabolic Syndrome Is Characterized by Osteopontin Overexpression in the Tumor Stroma

Association between Metabolic Disorders and Cholangiocarcinoma: Impact of a Postulated Risk Factor with Rising Incidence

Metabolisches Syndrom und Krebsrisiko

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