HIV-Associated Gastrointestinal Cancer

Jensen, Björn; Oette, Mark; Haes, Johannes; Häussinger, Dieter

doi:10.1159/000456714

Cited by 14 publications

(10 citation statements)

References 38 publications

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“…Human Immunodeficiency Virus (HIV) infection may increase the risk of ICC [62]. A U.S. case-control study (625 cases, 90,834 controls) found HIV to have an OR of 5.9 (95% CI 1.8-18.8) [63].…”

Section: Risk Factorsmentioning

confidence: 99%

Molecular Pathogenesis of Cholangiocarcinoma

2019

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Background Cholangiocarcinomas are a heterogeneous group of malignancies arising from a number of cells of origin along the biliary tree. Although most cases in Western countries are sporadic, large population-based studies have identified a number of risk factors. This review summarises the evidence behind reported risk factors and current understanding of the molecular pathogenesis of cholangiocarcinoma, with a focus on inflammation and cholestasis as the driving forces in cholangiocarcinoma development. Risk Factors for cholangiocarcinogenesis Cholestatic liver diseases (e.g. primary sclerosing cholangitis and fibropolycystic liver diseases), liver cirrhosis, and biliary stone disease all increase the risk of cholangiocarcinoma. Certain bacterial, viral or parasitic infections such as hepatitis B and C and liver flukes also increase cholangiocarcinoma risk. Other risk factors include inflammatory disorders (such as inflammatory bowel disease and chronic pancreatitis), toxins (e.g. alcohol and tobacco), metabolic conditions (diabetes, obesity and non-alcoholic fatty liver disease) and a number of genetic disorders. Molecular pathogenesis of cholangiocarcinoma Regardless of aetiology, most risk factors cause chronic inflammation or cholestasis. Chronic inflammation leads to increased exposure of cholangiocytes to the inflammatory mediators interleukin-6, Tumour Necrosis Factor-ɑ, Cyclo-oxygenase-2 and Wnt, resulting in progressive mutations in tumour suppressor genes, proto-oncogenes and DNA mismatch-repair genes. Accumulating bile acids from cholestasis lead to reduced pH, increased apoptosis and activation of ERK1/2, Akt and NF-κB pathways that encourage cell proliferation, migration and survival. Other mediators upregulated in cholangiocarcinoma include Transforming Growth Factor-β, Vascular Endothelial Growth Factor, Hepatocyte Growth Factor and several microRNAs. Increased expression of the cell surface receptor c-Met, the glucose transporter GLUT-1 and the sodium iodide symporter lead to tumour growth, angiogenesis and cell migration. Stromal changes are also observed, resulting in alterations to the extracellular matrix composition and recruitment of fibroblasts and macrophages that create a microenvironment promoting cell survival, invasion and metastasis. Conclusion Regardless of aetiology, most risk factors for cholangiocarcinoma cause chronic inflammation and/or cholestasis, leading to the activation of common intracellular pathways that result in reactive cell proliferation, genetic/epigenetic mutations and cholangiocarcinogenesis. An understanding of the molecular pathogenesis of cholangiocarcinoma is vital when developing new diagnostic biomarkers and targeted therapies for this disease.

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Section: Risk Factorsmentioning

confidence: 99%

Molecular Pathogenesis of Cholangiocarcinoma

2019

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“…This is another concern in older adults. About a third of HIV-positive persons are reported to die from cancer in their lifespan (Jensen et al 2017;Ehren et al 2014). HIV-infected patients demonstrate an increased risk of both HIV-related and non-HIV-related malignancies, especially for tumors of the breast, melanoma, pancreas, larynx, prostate, colorectum, and lung cancer.…”

Section: Malignancy In Hivmentioning

confidence: 99%

“…HIV-infected patients demonstrate an increased risk of both HIV-related and non-HIV-related malignancies, especially for tumors of the breast, melanoma, pancreas, larynx, prostate, colorectum, and lung cancer. There is an increase in adjusted cancer-specific mortality for the following GI malignancies: pancreas (hazard ratio (HR) 1.71), colorectum (HR 1.49), and liver (HR 1.1) (Jensen et al 2017;Gotti et al 2014;Coghill et al 2015).…”

Section: Malignancy In Hivmentioning

confidence: 99%

HIV in Older Adults

Pitchumoni¹,

Desai²

2020

Geriatric Gastroenterology

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Human immunodeficiency virus (HIV) infection is the cause of acquired immunodeficiency syndrome (AIDS). HIV disease continues to be a significant public health problem, although highly active antiretroviral therapy (HAART) has changed the dismal prognosis that existed in the 1980s. Life expectancy for people living with HIV (PLHIV) in the USA has significantly improved in the HAART era. Globally, 5.8 million (16%) PLHIV were older than age 50 years in 2015; the proportion of older PLHIV will rise to 22% in 2020. The burden of the epidemic differs between countries and regions within countries. Sub-Saharan Africa remains most severely affected. Older age with

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“…Several studies have reported cancer epidemiology and screening interventions in patients with HIV infection [45678]. However, gastric cancer data have been too limited to allow specific screening recommendations.…”

Section: Introductionmentioning

confidence: 99%

Role of Upper Gastrointestinal Endoscopy in Patients with Human Immunodeficiency Virus Infection in the Era of Combination Antiretroviral Therapy

Kang

Lee

et al. 2019

Infect Chemother

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Background Gastrointestinal (GI) diseases are common in patients with human immunodeficiency virus (HIV) infection. There are few reports on the epidemiology and endoscopic findings of gastric cancer in patients with HIV infection in the era of combination antiretroviral therapy (cART). We retrospectively analyzed upper GI endoscopic findings in patients with HIV infection and investigated their role as gastric cancer screening. Materials and Methods We retrospectively investigated endoscopies conducted in Korean patients with HIV infection referred for endoscopy at a tertiary hospital between January 2004 and December 2018. Endoscopic and pathologic findings were analyzed according to the reason for endoscopy, patient age, and cART duration. All endoscopic findings were reevaluated by gastroenterologists. Results Three hundred ten endoscopies in 201 patients with HIV infection were investigated. Of these, 118 (38.1%) endoscopies in 81 (40.1%) patients were performed for cancer screening purposes. Gastric cancer was found in 4 patients (2.0%); one of them presented with gastric cancer at the time of HIV diagnosis, and the other 3 patients were diagnosed with early gastric cancer on screening endoscopy, which was cured with endoscopic submucosal dissection or surgery. The prevalence of gastric cancer in screening endoscopies was 3.7%. Atrophic gastritis was a more common finding in screening endoscopies than in diagnostic endoscopies ( P <0.001), and was significantly associated with longer durations of cART ( P <0.001). The overall prevalence of gastric cancer, atrophic gastritis, and intestinal metaplasia was 2.0, 57.8, and 25.4%, respectively. The prevalence of atrophic gastritis and intestinal metaplasia increased with age. Conclusion Regular gastric cancer screening might be useful for early diagnosis and treatment of gastric cancer in patients with HIV infection.

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HIV-Associated Gastrointestinal Cancer

Cited by 14 publications

References 38 publications

Molecular Pathogenesis of Cholangiocarcinoma

Molecular Pathogenesis of Cholangiocarcinoma

HIV in Older Adults

Role of Upper Gastrointestinal Endoscopy in Patients with Human Immunodeficiency Virus Infection in the Era of Combination Antiretroviral Therapy

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