Ju Won Seok

Postoperative-stimulated serum thyroglobulin measured at the time of 131I ablation is useful for the prediction of disease status in patients with differentiated thyroid carcinoma

BACKGROUND This study was conducted to identify the relevant cutoff value and to evaluate the usefulness of postoperative-stimulated serum thyroglobulin (Tg) at the time of (131)I ablation for the prediction of disease status in patients with differentiated thyroid carcinoma (DTC) who received high-dose (131)I ablation therapy after total thyroidectomy. METHODS We analyzed 218 consecutively enrolled patients who were diagnosed with DTC and underwent total thyroidectomy. All patients underwent (131)I ablation at doses of 100-200 mCi, and stimulated serum Tg was measured at the time of (131)I ablation therapy. To assess disease-free status after (131)I ablation therapy, stimulated serum Tg levels, diagnostic whole-body scan (DxWBS) and neck ultrasonography (US) were performed 6-12 months after (131)I ablation. RESULTS The relevant cutoff value of postoperative stimulated Tg for the prediction of disease-free status was 2 ng/mL. A total of 138 patients (63.3%) showed values of <2 ng/mL. Postoperative-stimulated Tg < 2 ng/mL had a negative predictive value of 94.9%, which increased to 97.7% when low Tg was combined with negative neck US findings. CONCLUSION Postoperative-stimulated Tg at the time of (131)I remnant ablation is a useful biochemical marker for the prediction of disease status in patients with DTC. When high-dose (131)I remnant ablation is performed after total thyroidectomy, the stimulated Tg measurement and DxWBS that are usually performed 6-12 months after (131)I ablation therapy may be skipped, at least in low- and intermediate-risk patients with postoperative stimulated Tg of < 2 ng/mL and negative neck US findings.

Clinical significance of the BRAFV600E mutation in multifocal papillary thyroid carcinoma in Korea

BACKGROUND We examined the frequency of the BRAF(V600E) mutation and compared the clinicopathologic features based on the BRAF(V600E) mutation status in multifocal papillary thyroid carcinoma (PTC). METHODS A total 85 patients who were diagnosed with multifocal PTC were enrolled. We confirmed the status of the BRAF(V600E) mutation in each tumor focus by the real-time polymerase chain reaction technique. RESULTS Among the 85 patients, 49 (57.6%), 34 (40.0%), and 2 (2.4%) patients were determined to have all BRAF(V600E)-positive, mixed BRAF(V600E), and all BRAF(V600E)-negative in their tumor foci, respectively. When we compared clinicopathologic features according to the BRAF(V600E) mutation status of the dominant tumor, the BRAF(V600E) -positive group (n = 70) showed more extrathyroidal invasion in the dominant tumor (32.9% vs 6.7%, P = .041) and more lymph node metastasis (67.2% vs 40.0%, P = .049) than the BRAF(V600E) -negative group (n = 15). Considering all tumor foci, the all BRAF(V600E) mutation group exhibited a younger population (P = .039), showed increased extrathyroidal invasion (38.8% vs 14.7%, P = .017) and lymph node metastasis (71.4% vs 48.4%, P = .038), and received more radioactive iodine therapy (79.2% vs 52.9%, P = .012) than the mixed BRAF(V600E) mutation group. A larger tumor size and heavier preoperative body weight was positively correlated with the relative expression of BRAF(V600E) mutation calculated by 2(-△△Ct) method. CONCLUSION Most of the Korean patients with multifocal PTC had the BRAF(V600E) mutation in one or more tumor foci, and all BRAF(V600E)-positive multifocal PTC showed more aggressive features.

Protein-losing enteropathy detected on Tc-99m HSA and Tc-99m MDP scintigraphy

The authors describe a patient with protein-losing enteropathy in whom abnormal intestinal accumulation of tracer occurred during Tc-99m human serum albumin scintigraphy. Abnormal leakage of the radiotracer was observed in the left upper abdomen and was confirmed by Tc-99m MDP scintigraphy. Both Tc-99m HSA scintigraphy and Tc-99m MDP scintigraphy are useful in the detection of protein-losing enteropathy.

Tracing of the Bile-chemotactic migration of juvenile Clonorchis sinensis in rabbits by PET-CT.

Background Adult Clonorchis sinensis live in the bile duct and cause clonorchiasis. It is known that the C. sinensis metacercariae excyst in the duodenum and migrate up to the bile duct through the common bile duct. However, no direct evidence is available on the in vivo migration of newly excysted C. sinensis juveniles (CsNEJs). Advanced imaging technologies now allow the in vivo migration and localization to be visualized. In the present study, we sought to determine how sensitively CsNEJs respond to bile and how fast they migrate to the intrahepatic bile duct using PET-CT. Methodology/Principal Findings CsNEJs were radiolabeled with 18F-fluorodeoxyglucose (18F-FDG). Rabbits with a gallbladder contraction response to cholecystokinin-8 (CCK-8) injection were pre-screened using cholescintigraphy. In these rabbits, gallbladders contracted by 50% in volume at an average of 11.5 min post-injection. The four rabbits examined were kept anesthetized and a catheter inserted into the mid duodenum. Gallbladder contraction was stimulated by injecting CCK-8 (20 ng/kg every minute) over the experiment. Anatomical images were acquired by CT initially and dynamic PET was then carried out for 90 min with a 3-min acquisition per frame. Twelve minutes after CCK-8 injection, about 3,000 18F-FDG-labeled CsNEJs were inoculated into the mid duodenum through the catheter. Photon signals were detected in the liver 7–9 min after CsNEJs inoculation, and these then increased in the whole liver with stronger intensity in the central area, presenting that the CsNEJs were arriving at the intrahepatic bile ducts. Conclusion In the duodenum, CsNEJs immediately sense bile and migrate quickly with bile-chemotaxis to reach the intrahepatic bile ducts by way of the ampulla of Vater.

DICOM-based intravascular ultrasound signal intensity analysis: an Echoplaque Medical Imaging Bench study.

BackgroundMost intravascular ultrasound (IVUS) data are stored digitally using the Digital Imaging and Communications in Medicine (DICOM) standard. This allows random access to studies and improves on the major limitation of conventional grayscale IVUS. MethodsWe harvested 129 coronary arteries from 43 autopsied cases. Grayscale IVUS and virtual histology-IVUS imaging were performed beginning 30 mm distal to the ostium of each coronary artery. Grayscale IVUS was processed; and the signal intensity was determined from DICOM-stored images using a new Medical Imaging Bench system (Echoplaque-MIB). We compared 436 regions of interest. The accuracy rate was expressed using the interpolation method and 95% confidence interval (CI). ResultsPatients’ mean age was 49±9 years and 82% were men. Four patients succumbed to sudden cardiac death and 39 to noncardiac death. Grayscale IVUS signal intensity of dense calcium was 215±21.1 (95% CI: 207–223), that of fibrotic plaque was 75±17.8 (95% CI: 72–79), and that of fibrofatty plaque was 55±11.3 (95% CI: 52–59); however, the signal intensity of the necrotic core was between fibrotic plaque and dense calcium of 161±27.4 (95% CI: 153–168). Using the interpolation method, the cutoff values were as follows: fibrofatty plaque 0–65, fibrotic plaque 66–105, necrotic core 106–187, and dense calcium of at least 188. Overall, MIB grayscale had a 78.1% sensitivity and a 91.9% specificity versus histopathology. ConclusionPlaque characterization using DICOM-based grayscale IVUS signal intensity analysis may improve on the major limitation of conventional grayscale IVUS: its inability to assess plaque composition.

Anti-proliferative Effect and Action Mechanism of Dexamethasone in Human Medullary Thyroid Cancer Cell Line

Introduction. Dexamethasone is known to inhibit the cell proliferation of certain transformed cell lines. In this study, the effect and action mechanism of dexamethasone were examined in the human medullary thyroid cancer cell line, TT cells. Methods. TT cells were treated with or without dexamethasone. 5-Bromo-2′-deoxyuridine uptake assay was used to evaluate cell proliferation. Cell cycle and its regulatory proteins were assessed by flow cytometry and western blot analysis, respectively. Apoptosis was analyzed by Hoechst staining and Annexin V assay. Results. Dexamethasone significantly reduced TT cell proliferation by 60% (p < 0.01). A substantial portion of cells was arrested at the G1 phase. The expression levels of cyclin D1, cyclin-dependent kinase (CDK)4, and CDK2 were decreased. In addition, the phosphorylation of retinoblastoma protein, which is a critical checkpoint protein in the transition of G1 to S phase, was decreased. On the other hand, the expression level of p27Kip1, which is a cyclin/CDK inhibitor, was enhanced. Hoechst staining showed many fragmented nuclei in the dexamethasone-treated cells. The proportion of early apoptotic cells was also increased in the Annexin V assay. Conclusion. Dexamethasone inhibited the proliferation of TT cells through cell cycle arrest at the G1 phase and increased apoptosis.

Prognostic Value of Extranodal Extension in Thyroid Cancer: A Meta-Analysis

Purpose Thyroid cancer is the most common endocrine cancer and its incidence has continuously increased in the last three decades all over the world. We aimed to evaluate the prognostic value of extranodal extension (ENE) of thyroid cancer. Materials and Methods We performed a systematic search of MEDLINE (from inception to June 2014) and EMBASE (from inception to June 2014) for English-language publication. The inclusion criteria were studies of thyroid cancer that reported the prognostic value of ENE in thyroid cancer. Reviews, abstracts, and editorial materials were excluded, and duplicate data were removed. Two authors performed the data extraction independently. Results 6 studies including 1830 patients were eligible for inclusion in the study. All patients included in the meta-analysis had papillary thyroid cancer (PTC). Recurrence-free survival was analyzed based on 3 studies. The pooled hazard ratio for recurrence was 2.01 [95% confidence interval (CI) 1.19–3.40, p=0.009]. Disease-specific survival was analyzed based on 3 studies with 973 patients. Patients of PTC with ENE showed 3.37-fold higher risk of death from the disease (95% CI 1.55–7.32, p=0.002). Conclusion ENE should be considered to be a poor prognostic marker in thyroid cancer; such knowledge might improve the management of individual patients. This might facilitate the planning of appropriate ablation therapy and tailored patient follow-up from the beginning of treatment.

Comparison of Visceral Fat Measures with Cardiometabolic Risk Factors in Healthy Adults.

We aimed to evaluate the associations of visceral adiposity with cardiometabolic risk factors in normal subjects with integrated 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT). A total of 58 normal subjects who underwent 18F-FDG PET/CT scan for cancer screening were included in this study. Volume and average Hounsfield unit (HU) of visceral adipose tissue (VAT) was measured from CT components of integrated PET/CT. Standardized uptake values (SUVmax) of liver, spleen, lumbar spine and ascending aorta (AA) were measured from PET components of integrated PET/CT. Body mass index (coefficient 78.25, p = 0.0259), glucose (37.62, p<0.0001), insulin (348.90, p = 0.0011), logarithmic transformation of homeostatic model assessment index-insulin resistance (-2118.37, p = 0.0007), and VAT HU (-134.99, p<0.0001) were independently associated with VAT volume. Glucose (0.1187, p = 0.0098) and VAT volume (-0.004, p<0.0001) were found to be associated with VAT HU. Both VAT volume and VAT HU of whole abdominal cavity is significantly associated with cardiometabolic risk factors.

Effect of Temperature-Sensitive Poloxamer Solution/Gel Material on Pericardial Adhesion Prevention: Supine Rabbit Model Study Mimicking Cardiac Surgery

Objective We investigated the mobility of a temperature-sensitive poloxamer/Alginate/CaCl2 mixture (PACM) in relation to gravity and cardiac motion and the efficacy of PACM on the prevention of pericardial adhesion in a supine rabbit model. Methods A total of 50 rabbits were randomly divided into two groups according to materials applied after epicardial abrasion: PACM and dye mixture (group PD; n = 25) and saline as the control group (group CO; n = 25). In group PD, rabbits were maintained in a supine position with appropriate sedation, and location of mixture of PACM and dye was assessed by CT scan at the immediate postoperative period and 12 hours after surgery. The grade of adhesions was evaluated macroscopically and microscopically two weeks after surgery. Results In group PD, enhancement was localized in the anterior pericardial space, where PACM and dye mixture was applied, on immediate post-surgical CT scans. However, the volume of the enhancement was significantly decreased at the anterior pericardial space 12 hours later (P < .001). Two weeks after surgery, group PD had significantly lower macroscopic adhesion score (P = .002) and fibrosis score (P = .018) than did group CO. Inflammation score and expression of anti-macrophage antibody in group PD were lower than those in group CO, although the differences were not significant. Conclusions In a supine rabbit model study, the anti-adhesion effect was maintained at the area of PACM application, although PACM shifted with gravity and heart motion. For more potent pericardial adhesion prevention, further research and development on the maintenance of anti-adhesion material position are required.

Severe Spastic Trismus without Generalized Spasticity after Unilateral Brain Stem Stroke

A 62-year-old female patient diagnosed with left brain stem stroke 2 months ago was admitted to our clinic for rehabilitation. She had no generalized spasticity on both extremities, but could open her mouth only approximately 2 mm between her upper and lower teeth due to severe trismus. On needle electromyography, the left masseter muscle showed paradoxically increased muscle activity during mouth opening. We injected 50 units of type A botulinum toxin (Botox®) into the left masseter muscle, and 20 units into the left temporalis muscle with guidance of ultrasonography. The interincisal distance increased to 8 mm on the 3rd day after injection, and 9 mm on the 4th day. One month later, the interincisal distance increased to 14 mm. The increased interincisal distance was maintained for 13 months after injection, and the quality of hygienic care and compliance of oral stimulation therapy also improved.