Urokinase-type plasminogen activator receptor (uPAR) assessed by liquid biopsies and PET/CT for prognostication in head and neck cancer patients.

Strong prognostic biomarkers are lacking regarding the stratification of treatment and surveillance regimens in head and neck squamous cell carcinoma (HNSCC). The study aimed to assess the prognostic value of soluble urokinase-type plasminogen activator receptor in plasma (suPAR) compared to evaluation by uPAR-positron-emission-tomography (PET) in HNSCC patients. Plasma from 19 controls and 49 HNSCC patients referred to curatively intended radiotherapy (2017-2021) was collected pre-treatment and post-treatment (n = 37). Information on uPAR-PET was available from previous evaluation. Patient median suPAR was significantly higher pre- and post-treatment compared to controls (p = 0.013, p = 0.003) and increased significantly during radiotherapy (p = 0.003). Pre-treatment suPAR did not predict survival outcomes. Post-treatment suPAR significantly predicted RFS (HR = 6.67 (95% CI 1.44-30.9) p = 0.015), but not OS (HR = 3.29 (95% CI 0.882-12.3) p = 0.076) in univariate analysis. RFS prediction was maintained for post-treatment suPAR in multivariate analysis, including TNM-stage (HR = 6.62 (95% CI 1.40-31.4) p = 0.017). Pre-treatment uPAR-PET/CT and post-treatment suPAR was available in 24 patients. High uPAR-estimates on both modalities was significantly associated with poor RFS compared to patients with low uPAR-estimates (log-rank, p = 0.008). Patients with discordant uPAR-estimates (one-low/one-high) were at intermediate risk, although non-significant (p = 0.131). In conclusion, pre-treatment suPAR did not predict RFS or OS. Pre-treatment uPAR-PET and post-treatment suPAR predicted RFS.

FDG-PET/CT in the surveillance of head and neck cancer following radiotherapy.

PURPOSE: To examine the time-dependent diagnostic performance of FDG-PET/CT in the follow-up of head and neck cancer (HNC) and to assess the prognostic value of PET-negative and PET-inconclusive findings. MATERIAL AND METHODS: 279 HNC patients primarily treated with radiotherapy from 2006 to 2012 were included. The follow-up PET/CT scans were categorized as benign, malignant or inconclusive by a radiologist and a nuclear physician. The reference standard was histology or verification by progression on imaging. The outcome measures were positive (PPV) and negative predictive value (NPV), and the PET/CT scans were grouped according to time since treatment and compared. An analysis of the diagnostic accuracy was performed with the inconclusive results categorized as both benign and malignant to create ranges for the diagnostic performance. RESULTS: The proportion of inconclusive results declined from 26 to 8.4% and 0% after 0-3, 3-6 and 12-24 months post-treatment. The ranges for diagnostic performance after 0-3, 3-6, 6-12, 12-24 months and overall post-treatment were: PPV 27.3-50, 48.4-58.3, 71.4-100, 100 and 50.5-65.7 and NPV 75.0-84.6, 95.1-96.8, 92.9-100, 100 and 94.8-96.7. Time to recurrence was not statistically different after a PET-negative or a PET-inconclusive result. CONCLUSION: The diagnostic accuracy of a surveillance PET/CT scan after HNC improves with time since treatment, and is very reliable after 1 year. However, the NPV is already high 3 months post-treatment supporting the use of PET/CT for early evaluation of head and neck cancer patients.

Hepatic erythropoietin response in cirrhosis. A contemporary review.

The main function of erythropoietin (EPO) is to maintain red blood cell mass, but in recent years, increasing evidence has suggested a wider biological role not solely related to erythropoiesis, e.g. angiogenesis and tissue protection. EPO is produced in the liver during fetal life, but the main production shifts to the kidney after birth. The liver maintains a production capacity of up to 10% of the total EPO synthesis in healthy controls, but can be up-regulated to 90-100%. However, the hepatic EPO synthesis has been shown not to be adequate for correction of anemia in the absence of renal-derived EPO. Elevated circulating EPO has been reported in a number of diseases, but data from cirrhotic patients are sparse and the level of plasma EPO in patients with cirrhosis is controversial. Cirrhosis is characterized by liver fibrosis, hepatic dysfunction and the release of proinflammatory cytokines, which lead to arterial hypotension, hepatic nephropathy and anemia. An increase in EPO due to renal hypoperfusion, hypoxia and anemia or an EPO-mediated hepato-protective and regenerative mechanism is plausible. However, poor hepatic synthesis capacity, a decreasing co-factor level and inflammatory feedback mechanisms may explain a potential insufficient EPO response in end-stage cirrhosis. Finally, the question remains as to whether a potential increase in EPO production in certain stages of cirrhosis originates from the kidney or liver. This paper aims to review contemporary aspects of EPO relating to chronic liver disease.

Immunologic, hemodynamic, and adrenal incompetence in cirrhosis: impact on renal dysfunction.

Acute kidney injury (AKI) is one of the most severe complications of cirrhosis and is associated with significant morbidity and mortality. Liver fibrosis and liver insufficiency, portal hypertension, systemic vasodilation, and a subsequent hyperdynamic circulation undermine the renal and cardiac function, making cirrhotic patients more susceptible to hemodynamic incidents. In addition, the immune system is impaired in cirrhosis, leading to an exaggerated production of vasoactive mediators, and the adrenal cortisol response is insufficient, which causes further impairment of the vascular tonus, cardiac output, and renal perfusion. Consequently, the cardiovascular and renal dysfunction is aggravated, resulting in a hepatorenal syndrome (HRS). HRS is seen exclusively in patients with liver disease and has been considered an entirely functional prerenal dysfunction, rather than a structural dysfunction, but is not responsive to volume expansion. Recent research indicates that development of hepatic nephropathy represents a continuous spectrum of functional and structural dysfunction and may be precipitated by the inherent immunologic, adrenal, and hemodynamic incompetence in cirrhosis. New research explores several new markers of renal dysfunction that may replace serum creatinine in the future and give new insight on the hepatic nephropathy. Our understanding of the pathophysiological mechanisms causing the immunologic, adrenal, and hemodynamic incompetence, and the impact on renal dysfunction, has improved in recent years, and in this review we aim to highlight recent achievements in this field.

Risk of breast cancer after false-positive test results in screening mammography.

BACKGROUND: Screening for disease in healthy people inevitably leads to some false-positive tests in disease-free individuals. Normally, women with false-positive screening tests for breast cancer are referred back to routine screening. However, the long-term outcome for women with false-positive tests is unknown. METHODS: We used data from a long-standing population-based screening mammography program in Copenhagen, Denmark, to determine the long-term risk of breast cancer in women with false-positive tests. The age-adjusted relative risk (RR) of breast cancer for women with a false-positive test compared with women with only negative tests was estimated with Poisson regression, adjusted for age, and stratified by screening round and technology period. All statistical tests were two-sided. RESULTS: A total of 58 003 women, aged 50-69 years, were included in the analysis. Women with negative tests had an absolute cancer rate of 339/100 000 person-years at risk, whereas women with a false-positive test had an absolute rate of 583/100 000 person-years at risk. The adjusted relative risk of breast cancer after a false-positive test was 1.67 (95% confidence interval [CI] 1.45 to 1.88). The relative risk remained statistically significantly increased 6 or more years after the false-positive test, with point estimates varying between 1.58 and 2.30. When stratified by assessment technology phase and using equal follow-up time, the false-positive group from the mid 1990s had a statistically significantly higher risk of breast cancer (RR = 1.65, 95% CI = 1.22 to 2.24) than the group with negative tests, whereas the false-positive group from the early 2000s was not statistically significantly different from the group testing negative. CONCLUSIONS: The implementation of new assessment technology coincided with a decrease in the size of excess risk of breast cancer for women with false-positive screening results. However, it may be beneficial to actively encourage women with false-positive tests to continue to attend regular screening.