Relative Observer and Technical Error in the Ultrasonic Monitoring of Thyroid Nodular Growth Using Nodular Volume (VOL), vs. Longest Dimension (LD), vs. the Sum of the 3 Nodular Dimensions (SUM3D)

Though not a reliable indicator of malignancy, ultrasonic monitoring of nodule growth still has a role in the evaluation of nodules, e.g. indicating when a nodule may require biopsy or re-biopsy. Observer and technical limitations, however, limit the precision of ultrasonic determination of simple growth, vs. stability or shrinkage. Ultrasonic parameters used for this purpose all have their own limitations. Monitoring nodule growth by VOL frequently exhibits wide and conflicting swings in apparent size compared to the penultimate size, doubtlessly reflecting measurement limitations. As a growth parameter, LD typically exhibits a smoother time course but does not address growth in the other two dimensions. SUM3D includes changes in all dimensions but, like LD, is not a true measure of nodule mass or volume. This study was to determine the relative error of these three growth parameters and how it relates to their relative efficacy for nodular growth monitoring. The anterior-posterior (AP), left-right (LR) and superior-inferior (SI) dimensions of 34 benign nodules were determined ultrasonographically by four pairs of trained observers. One observer of a pair was regarded as a Time-1 observer and the other as a Time-2 observer, simulating the process for determining growth change over time. All observers measured the same image of each of the 34 nodules but were unaware of the measurements obtained by any other observer. For each image for each pair of observers, the dimensions were used to calculate the VOL, LD and SUM3D and the perceived changes thereof from Time-1 to Time-2. Since only one image for each nodule was distributed, differences between the Time-1 vs Time-2 measurements for each nodule could only reflect observer-based differences. “S”-curves plotting the nominal %-change in a parameter reported by the Time-2 observer compared to that reported by the Time-1 observer (x-axis) were rank-ordered from negative to positive changes (y-axis). The %-change in each parameter due to observer/technical error ranging from the highest over-estimate to the lowest were, in order from Top 10%, Middle 40%, and Bottom 10%, respectively: LD: 19-36%, -4 to 6%, -15 to -42%; SUM3D: 15 to 28%, -4 to 4%, -11 to -43%; VOL: 48 to 105%, -13 to 15%, -33 to -81%. The magnitude of %-change from Time-1 to Time-2 for the VOL parameter were 2 to 3 times greater than that of the LD or SUM3D parameters for the top 10% of values, the middle 40% of values, and the bottom 10% of values. These degrees of difference coincide with the wide variability seen in nodular growth curves [not illustrated here] when nodular VOL (y-axis) is plotted as a function of length of observation (x-axis). This study helps explain why monitoring nodular growth by LD or by the SUM3D usually provides a clearer, less fluctuant illustration of thyroid nodule growth over time than does VOL.

Clinical course of asymptomatic small enhancing brain nodules in patients with nonsmall cell lung cancer: do we have to follow them up?

AimsBrain magnetic resonance imaging (MRI) is recommended during the initial work-up for nonsmall cell lung cancer (NSCLC). Although small enhancing brain nodules not radiologically confirmed as metastatic lesions have often been detected, their clinical course has not been well studied.MethodsThis nested case–control study included NSCLC patients who had small enhancing brain nodules detected by serial brain MRIs from January 2014 through December 2018 at a tertiary university hospital. Small enhancing brain nodules were defined as round enhancing nodules of ≤10 mm diameter without oedema in thin-section (1 mm) contrast MRIs. The incidence, natural course and risk factors of growing nodules were evaluated.ResultsA total of 171 small enhancing brain nodules in 123 patients were observed over an average of 22.1 months. The incidence of nodule growth was 49.1% with mean growth rate of 11 mm·year−1. We found that 25.0% of the growing nodules contributed to clinical upstaging compared to the initial stage. Cerebral events were more common in growing nodules; therefore, local therapy was performed more often. However, there was no difference in the cerebral event-related mortality. Nodule growth was more frequent in younger individuals, multiple nodules, advanced disease, poorly differentiated carcinoma, rim enhancement and larger initial size. In multivariable analysis, predictors of growth were N stage ≥1, existence of epidermal growth factor receptor mutation and larger initial size.ConclusionConsidering the clinical course of small enhancing brain nodules, more intensive evaluation is required for early detection and pre-emptive intervention when accompanied by risk factors.

Accumulation and Distribution of Fertilizer Nitrogen and Nodule-Fixed Nitrogen in Soybeans with Dual Root Systems

The soybean (Glycine max L. Merr.) is a crop with a high demand for nitrogen (N). The root nodules that form in soybeans can fix atmospheric N effectively, yet the goal of achieving high yields cannot be met by relying solely on nodule-fixed N. Nonetheless, the application of N fertilizer may inhibit nodule formation and biological N fixation (BNF), but the underpinning mechanisms are still unclear. In this study, we grafted the roots of non-nodulated soybeans onto nodulated soybeans to generate plants with dual root system. The experiment included three treatments conducted under sand culture conditions with NO 3 − and NH 4 + as N sources. Treatment I: The non-nodulated roots on one side received 50 mg·L−1 15 NO 3 − or 15NH4+, and the nodulated roots on the other side were not treated. Treatment II: The non-nodulated roots received 50 mg·L−1 15 NO 3 − or 15 NH 4 + , and the nodulated roots received 50 mg·L−1 14 NO 3 − or 14 NH 4 + . Treatment III: Both non-nodulated and nodulated roots received 50 mg·L−1 15 NO 3 − or 15 NH 4 + . The results showed the following: (1) Up to 81.5%–87.1% of the N absorbed by the soybean roots and fixed by the root nodules was allocated to shoot growth, leaving 12.9%–18.5% for root and nodule growth. Soybeans preferentially used fertilizer N in the presence of a NO 3 − or NH 4 + supply. After the absorbed fertilizer N and nodule-fixed N was transported to the shoots, a portion of it was redistributed to the roots and nodules. The N required for root growth was primarily derived from the NO 3 − or NH 4 + assimilated by the roots and the N fixed by the nodules, with a small portion translocated from the shoots. The N required for nodule growth was primarily contributed by nodule-fixed N with a small portion translocated from the shoots, whereas the NO 3 − or NH 4 + that was assimilated by the roots was not directly supplied to the nodules. (2) Based on observations of the shoots and one side of the roots and nodules in the dual root system as an N translocation system, we proposed a method for calculating the N translocation from soybean shoots to roots and nodules during the R1–R5 stages based on the difference in the 15N abundance. Our calculations showed that when adding N at a concentration of 50 mg·L−1, the N translocated from the shoots during the R1–R5 stages accounts for 29.6%–52.3% of the N accumulation in nodulated roots (Rootn) and 9.4%–16.6% of the N accumulation in Nodulen of soybeans. Through the study of this experiment, the absorption, distribution and redistribution characteristics of fertilizer N and root nodule N fixation in soybean can be clarified, providing a theoretical reference for analyzing the mechanisms of the interaction between fertilizer N and nodule-fixed N.

THYROID NODULE GROWTH AS A PREDICTOR OF MALIGNANCY

Objective: To assess which measure of thyroid nodule growth on serial neck ultrasound, if any, is associated with malignancy. Methods: Retrospective exploratory chart review of malignant thyroid nodules assessed at Kingston Health Sciences Centre (2006–2016) and benign thyroid nodules (2016), at least 1 cm in diameter and with 2 ultrasounds completed at least 30 days apart. Groups were compared using independent samples Student's t test, chi-square test, or Mann-Whitney U test as appropriate, as well as multivariable logistic and linear regression modelling to adjust for age and baseline volume. Results: One hundred and seventy-eight nodules were included in the study. When growth was defined as >20% increase in 2 dimensions (minimum 2 mm), malignant nodules (MNs) underwent significantly more growth than benign nodules (BNs) (16.8% BN versus 29.8% MN [ P = .026]; odds ratio = 2.49; 95% confidence interval = 1.12 to 5.56). There was no significant difference between the groups when growth was defined as >2 mm/year or ≥50% volume growth. Nodules shrank >2 mm/year in each group and the difference was not statistically significant (24.2% BN versus 20.7% MN [ P = .449]). The median doubling time for the nodules that grew was 1022.1 days in the BN group and 463.2 days in the MN group ( P = .036). The median doubling time for all nodules was 456.5 days in the BN group and 244.2 days in the MN group ( P = .015). Conclusion: Thyroid nodule growth defined as >20% increase in 2 dimensions (minimum 2 mm) is associated with risk of malignancy. Nodule shrinkage did not distinguish between BNs and MNs. Abbreviations: BN = benign nodule; CI = confidence interval; FNA = fine needle aspiration; KHSC = Kingston Health Science Centre; MN = malignant nodule; OR = odds ratio; ROC = receiver operating characteristic