Thyroid segmentation using perithyroidal halo layer on 99mTc-pertechnetate thyroid SPECT/CT: An easy and reliable method for accurate quantification of thyroid activity.

OBJECTIVE: In previous fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) studies, tumor segmentation using peritumoral halo layer (PHL; SegPHL) was shown to be reliable and accurate segmentation method in various malignant tumors. We found that the halo layer also was observed on the 99mTc-pertechnetate (99mTcO4) thyroid single photon emission computed tomography (SPECT)/CT. In the present study, we attempted to apply thyroid segmentation using the perithyroidal halo layer (PTHL; SegPTHL) on 99mTcO4 thyroid SPECT/CT and compared SegPTHL with CT-based thyroid segmentation (SegCT). SUBJECTS AND METHODS: A total of 33 patients (19 females, 14 males; mean age, 46.91±15.7 years old) were enrolled in this study. For SegCT, three-dimensional volume of interest (VOI) of the thyroid was generated via multiple 2-dimensional regions of interest (ROI) along the thyroid margin on transaxial CT images that were manually drawn slice by slice. The PTHL was easily identified by an abrupt increase in layer thickness with minimal or mild distortion of the main thyroid contour, and the thyroid margin for SegPTHL was determined at the innermost portion of PTHL. An automated VOI generation for SegPTHL was performed using the Q. Volumetrix software. The correlation and reliability tests were performed between the quantification parameters of SegPTHL and SegCT. RESULTS: The PTHL threshold adjusted according to maximal SUV of thyroid were similar to the results of previous SegPHLstudies of 18F-FDG PET/CT. A good correlation was observed between the thyroid volumes of SegCT and SegPTHL (r=0.725; P<0.0001), although the thyroid volume of SegPTHL was slightly larger than that of SegCT (P=0.0017). The % thyroid uptake (TcTU), total lesion activity (TLA), and mean standardized uptake value (SUVmean) of SegPTHL correlated well with those of SegCT (r=0.9877, 0.9883, 0.9875, respectively; P<0.0001). No significant error was observed between the parameters (i.e., TcTU, TLA, and SUVmean) of SegPTHL and SegCT. CONCLUSION: Thyroid segmentation PTHL may be a useful method for reliable quantification of thyroid uptake, because the SPECT/CT parameters of SegPTHL were strongly correlated with those of SegCT, as well as the process of SegPTHL is easier and faster than that of SegCT.

Long-Term Recurrence of Small Papillary Thyroid Cancer and Its Risk Factors in a Korean Multicenter Study.

Context: Small papillary thyroid cancer (PTC) generally has an excellent prognosis. However, long-term recurrence is not uncommon and sometimes leads to morbidity or mortality. Objective: To identify high-risk factors for long-term recurrence in patients with small PTC by stratifying their pathologic characteristics. Design, Setting, and Patients: We conducted a nationwide, retrospective, multicenter study of 3282 patients with PTC sized ≤2 cm from 9 high-volume hospitals in Korea. Main Outcome Measures: The maximally selected χ2 method was used to find the best cutoff points of tumor size, the number of metastatic lymph nodes (LNs), and the ratio of metastatic/examined LNs (LNR) to predict recurrence. Kaplan-Meier analysis and the Cox proportional hazards regression model were used to analyze recurrence and risk factors. Results: The optimal tumor size cutoff was 1.8 cm (10-year recurrence rates for tumors sized 0.1 to 1.7 cm and 1.8 to 2.0 cm: 7.7% vs 17.2%, respectively). Metastatic LNs ≤1 and ≥2 provided optimal estimates of recurrence (10-year recurrence rates: 4.0% vs 16.8%, respectively). The LNR of 0.19 was the optimal cutoff point for predicting the risk of recurrence (10-year recurrence rates for LNRs of 0 to 0.18 and 0.19 to 1: 2.7% vs 16.2%, respectively). LN metastasis, lobectomy, tumor size ≥1.8 cm, and bilateral tumors were independent risk factors for recurrence. Conclusions: Long-term recurrence was increased in patients who underwent lobectomy or with tumor sized ≥1.8 cm, 2 or more metastatic LNs, or bilateral tumors. For patients with these high-risk features, total thyroidectomy could be considered to avoid reoperation.

Comparison of monthly ibandronate versus weekly risedronate in preference, convenience, and bone turnover markers in Korean postmenopausal osteoporotic women.

Patient preferences, convenience, and bone turnover markers were evaluated for the monthly ibandronate over the weekly risedronate regimen in Korean postmenopausal osteoporotic women. This was a 6-month, prospective, randomized, open-label, multicenter study with a two-period and two-sequence crossover treatment design. After a 30-day screening period, eligible participants with postmenopausal osteoporosis were randomized to receive either monthly oral ibandronate 150 mg for 3 months followed by weekly oral risedronate 35 mg for 12 weeks (sequence A) or the same regimen in reverse order (sequence B). Patient preference and convenience were evaluated by questionnaire. The changes in serum C-telopeptide after 3 months of treatment were analyzed. A total of 365 patients were enrolled in this study (sequence A 182, sequence B 183). Of patients expressing a preference (83.4%), 74.8% preferred the monthly ibandronate regimen over the weekly regimen (25.2%). More women stated that the monthly ibandronate regimen was more convenient (84.2%) than the weekly regimen (15.8%). There was no significant difference in the change in bone turnover marker between the two treatments. The two regimens were similarly tolerable. There were fewer adverse events in the monthly ibandronate group compared to the weekly risedronate group in terms of gastrointestinal side effects (nausea and abdominal distension). This study revealed a strong preference and convenience for monthly ibandronate over weekly risedronate in Korean postmenopausal osteoporotic women. There was no significant difference in change of bone turnover marker and safety profile between the two regimens.

Characterization of neural cell types expressing peroxiredoxins in mouse brain.

The differential expression patterns of antioxidant enzymes observed in the brains of patients with neurodegenerative diseases suggest an important role for reactive oxygen species and antioxidant enzymes in neurodegeneration. The six mammalian peroxiredoxins (Prxs) comprise a novel family of anti-oxidative proteins that are widely distributed in most tissues, but few studies of Prx in brain tissue have been reported. The specific histology of the neural cell types in which Prxs are expressed is an important issue related to biological function and defense against oxidative stress in the brain. This study analyzed mouse brain neural cell types expressing Prx isoforms using single- or double-label immunohistochemical techniques. In neurons, immunoreactivity for Prx II-V was observed in the cytoplasm. In particular, Prx II was found in the habenular nuclei, and Prx III and V were found in the stratum lucidum of the hippocampus. Astrocytes and microglia were immunoreactive only for Prx VI and Prx I, respectively. Prx I and IV immunoreactivity was apparent in oligodendrocytes, where it was principally localized in the nuclei. The observed distribution of Prx isoforms in the mammalian brain may be indicative of their specific roles in their preferred neural cell types and subcellular locales. The results of this study will help in unraveling the physiological and pathophysiological roles of the different Prx isoforms in neural function.

Thrombin induces expression of cytokine-induced SH2 protein (CIS) in rat brain astrocytes: involvement of phospholipase A2, cyclooxygenase, and lipoxygenase.

Previously we have reported that thrombin induces inflammatory mediators in brain glial cells (Ryu et al. 2000. J Biol Chem 275:29955). In the present study, we found that thrombin induced a negative regulator of a cytokine signaling molecule, cytokine-induced SH2 protein (CIS), in rat brain astrocytes. In response to thrombin, CIS expression was increased at both the mRNA and protein levels. Although STAT5 is known to regulate CIS expression, thrombin did not activate STAT5, and inhibitors of JAK2 (AG490) and JAK3 (WHI-P97 and WHI-P154) had little effect on thrombin-induced CIS expression. In contrast, cytosolic phospholipase A(2) (cPLA(2)), cyclooxygenase (COX), and lipoxygenase (LO) play a role in CIS expression, since inhibitors of cPLA(2), cyclooxygenase (COX), and LO significantly reduced CIS expression. Reactive oxygen species (ROS) scavengers (N-acetyl-cysteine [NAC] and trolox) reduced thrombin-induced CIS expression, and inhibitors of COX and LO reduced ROS produced by thrombin. Furthermore, prostaglandin E(2) (PGE(2)) and leukotriene B(4) (LTB(4)), products of COX and LO, respectively, potentiated thrombin-induced CIS expression, indicating that ROS, and PGE(2) and LTB(4) generated by COX and LO, mediate CIS expression. Since interferon-gamma (IFN-gamma)-induced GAS-luciferase activity and tyrosine phosphorylation of STAT1 and STAT3 were lower in CIS-transfected cells compared to control vector-transfected cells, CIS could have anti-inflammatory activity. These data suggest that thrombin-stimulation of ROS and prostaglandin and leukotriene production via the cPLA(2), COX and LO pathways results in CIS expression. More importantly, CIS expression may be a negative feedback mechanism that prevents prolonged inflammatory responses.