Scoring system for diagnosis and pretreatment risk assessment of neuroblastoma using urinary biomarker combinations.

The urinary catecholamine metabolites, homovanillic acid (HVA) and vanillylmandelic acid (VMA), are used for the adjunctive diagnosis of neuroblastomas. We aimed to develop a scoring system for the diagnosis and pretreatment risk assessment of neuroblastoma, incorporating age and other urinary catecholamine metabolite combinations. Urine samples from 227 controls (227 samples) and 68 patients with neuroblastoma (228 samples) were evaluated. First, the catecholamine metabolites vanillactic acid (VLA) and 3-methoxytyramine sulfate (MTS) were identified as urinary marker candidates through comprehensive analysis using liquid chromatography-mass spectrometry. The concentrations of these marker candidates and conventional markers were then compared among controls, patients, and numerous risk groups to develop a scoring system. Participants were classified into four groups: control, low risk, intermediate risk, and high risk, and the proportional odds model was fitted using the L2-penalized maximum likelihood method, incorporating age on a monthly scale for adjustment. This scoring model using the novel urine catecholamine metabolite combinations, VLA and MTS, had greater area under the curve values than the model using HVA and VMA for diagnosis (0.978 vs. 0.964), pretreatment risk assessment (low and intermediate risk vs. high risk: 0.866 vs. 0.724; low risk vs. intermediate and high risk: 0.871 vs. 0.680), and prognostic factors (MYCN status: 0.741 vs. 0.369, histology: 0.932 vs. 0.747). The new system also had greater accuracy in detecting missing high-risk neuroblastomas, and in predicting the pretreatment risk at the time of screening. The new scoring system employing VLA and MTS has the potential to replace the conventional adjunctive diagnostic method using HVA and VMA.

Quantitative assessment of viral load in the blood and urine of patients with congenital cytomegalovirus infection using droplet digital PCR.

Congenital cytomegalovirus infection (cCMV) is a common cause of congenital infections, leading to neurodevelopmental sequelae. Real-time quantitative polymerase chain reaction (qPCR) has been widely used for the diagnosis and assessment of cCMV; however, the correlation between CMV DNA load and the severity of cCMV symptoms has been inconclusive. Droplet digital PCR (ddPCR) offers an improvement over the current qPCR methods through the absolute quantification of viral loads. We compared ddPCR and qPCR results for the quantification of CMV DNA in blood and urine specimens from 39 neonates with cCMV (21 symptomatic and 18 asymptomatic). There was no significant difference in blood CMV DNA loads measured by ddPCR and qPCR, with or without any clinical findings. However, developmental delays at 36 months were significantly more frequently observed in patients with high CMV DNA loads (≥2950 copies/ml), as measured by ddPCR at diagnosis, than in those with lower CMV DNA loads. The association of urine CMV DNA load with symptoms and developmental delay was not observed. CMV DNA loads in the blood might be used as a predictor of developmental outcomes in cCMV patients, and absolute quantitation of viral loads by ddPCR assay could contribute to the standardization of CMV load measurement.

Investigation of appropriate semi-quantitative index for assessment of esophageal and breast cancer treatment response in Japanese patients using 18F-FDG PET/CT findings.

OBJECTIVE: To examine the correlation of the quantitative indexes standardized uptake value (SUV), SUV corrected for lean body mass (SUL) and SUV corrected for Japanese lean body mass (SULj) with body weight to develop an appropriate quantitative index independent of body weight fluctuation for assessment of response to cancer treatment in Japanese patients. SUBJECTS AND METHODS: Fifty-six males with esophageal cancer and 30 females with breast cancer underwent fluorine-18-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) scans, once before and once after, receiving neoadjuvant chemotherapy prior to planned surgical resection. The maximum value, peak value, and average value of SUV, SUL and SULj were calculated by setting a spherical volume of interest (3cm diameter) in a normal area of the liver. The correlation between each index and body weight was obtained from the correlation coefficient (r) and the significance of the correlation was tested. RESULTS: Analyses were conducted with all patients (P<0.01), as well as after dividing into those with only esophageal (P<0.05) or breast (P<0.01) cancer. Regarding the correlation coefficient between each index and body weight, a significant difference was seen for SUVmax, SUVpeak and SUVmean. In contrast, there was no correlation with body weight for SULmax, SULpeak, SULmean, SULjmax, SULjpeak, or SULjmean in any of the 3 groups. CONCLUSION: Based on the correlation with body weight, we concluded that both SUL and SULj (SUL corrected for Japanese lean body mass) is useful for assessment of cancer treatment response in Japanese patients.