Kuen-Yuan Chen

Glutamine Supplementation Attenuates Expressions of Adhesion Molecules and Chemokine Receptors on T Cells in a Murine Model of Acute Colitis

Background. Migration of T cells into the colon plays a major role in the pathogenesis in inflammatory bowel disease. This study investigated the effects of glutamine (Gln) supplementation on chemokine receptors and adhesion molecules expressed by T cells in mice with dextran sulfate sodium- (DSS-) induced colitis. Methods. C57BL/6 mice were fed either a standard diet or a Gln diet replacing 25% of the total nitrogen. After being fed the diets for 5 days, half of the mice from both groups were given 1.5% DSS in drinking water to induce colitis. Mice were killed after 5 days of DSS exposure. Results. DSS colitis resulted in higher expression levels of P-selectin glycoprotein ligand- (PSGL-) 1, leukocyte function-associated antigen- (LFA-) 1, and C-C chemokine receptor type 9 (CCR9) by T helper (Th) and cytotoxic T (Tc) cells, and mRNA levels of endothelial adhesion molecules in colons were upregulated. Gln supplementation decreased expressions of PSGL-1, LFA-1, and CCR9 by Th cells. Colonic gene expressions of endothelial adhesion molecules were also lower in Gln-colitis mice. Histological finding showed that colon infiltrating Th cells were less in the DSS group with Gln administration. Conclusions. Gln supplementation may ameliorate the inflammation of colitis possibly via suppression of T cell migration.

Computerized Detection and Quantification of Microcalcifications in Thyroid Nodules

To improve the ultrasonographic detection rates of thyroid cancers with microcalcifications, we propose to enhance the sensitivity of sonographic calcifications detection and to avoid interobserver variation by a computerized quantification method in a prospective setting. A total of 227 participants with 258 nodules were evaluated. Among them, two nodules were excluded for suspicious aspiration cytology results without pathologic proof. Among the remaining 256 nodules, the diagnosis of 181 nodules was verified by surgical pathology and the diagnosis of 75 was based on fine needle aspiration (FNA) biopsy results. There were 173 benign thyroid nodules and 83 malignant thyroid nodules, which included 74 papillary carcinomas. Patient clinical data were collected and the presence of calcifications on conventional gray-scale ultrasound images was retrospectively reviewed by a thyroid specialist. Quantification of cystic components and calcifications was automatically performed by a proprietary program (AmCAD-UT) implemented with methods proposed in this article. The calcification index (CI) was calculated after the cystic component was excluded. The CI between benign and malignant nodules diagnosed by combined FNA biopsy and surgical pathology results (total number, 256) showed a significant difference (p < 0.0001, AUC = 0.746). Furthermore, we excluded patients without surgical pathology results for further validation and the CI between benign and malignant nodules confirmed by pathology results (total number, 181) showed a significant difference (p < 0.0001, AUC = 0.763). To learn whether our computer program increased our diagnostic capabilities, we analyzed human investigators and their abilities to detect and evaluate. In this study, calcifications were noted in 48.19% (40 of 83) of malignant thyroid nodules and in 10.98% (19 of 173) of benign nodules. This new computer-aided diagnosis method to evaluate the sonographic calcifications of thyroid nodules is a more sensitive and more objective method. It can provide better sensitivity than conventional methods in the diagnosis of thyroid malignancies containing microcalcifications.

Modulatory Effects of Astragalus Polysaccharides on T-Cell Polarization in Mice with Polymicrobial Sepsis.

Background. This study evaluated the impact of different doses of Astragalus polysaccharides (APS) on the functional status and phenotype of T cells during polymicrobial sepsis. Methods. On day 1 after cecal ligation and puncture, mice were treated with either saline, 100 (A100), 200 (A200), or 400 mg APS/kg body weight (BW) (A400) by an intraperitoneal injection daily for 4 days. All mice were sacrificed 5 days after the operation. Results. APS treatment reversed the sepsis-induced decrement in the T helper (Th) cell population, and the percentage of activated Th cells also increased in the spleen and Peyers patches. APS administration downregulated the percentages of circulating Th2 cells and regulatory T cells (Treg), and the percentage of Th17 cells in blood was upregulated in the A400 group. Weight loss and kidney injury were attenuated in the A100 and A200 groups but not in the A400 group at the end of the study. Conclusions. Treatments with 100 and 200 mg APS/kg BW reduced Treg populations and elicited a more-balanced Th1/Th2 response that consequently attenuated immunosuppression in polymicrobial sepsis. High-dose APS administration led to excessive responses of Th17 cells which may have adverse effects in sepsis-induced organ injury.

QUANTITATIVE ANALYSIS OF DYNAMIC POWER DOPPLER SONOGRAMS FOR PATIENTS WITH THYROID NODULES

To clarify and determine whether power Doppler sonograms are useful for the detection of malignant thyroid nodules, a computerized quantification method was used to evaluate the vascular density of a thyroid nodule in a prospective setting. Sonographic power Doppler images were collected in consecutive frames (45 frames of images), and a proprietary program (AmCAD-UV) was implemented using methods proposed in this article automatically calculated a quantified power Doppler vascular index (PDVI). The minimum PDVI value (PDVImin) was suggested as a measure of the vascular density of the nodule. The vascular densities of the peripheral and central areas of the nodule, referred to as central PDVImin and Ring PDVImin, respectively, were also evaluated. For 238 tumors (79 malignant and 159 benign) from 208 patients, all of the proposed indices of benign lesions were significantly higher than those of the malignant lesions. The area under the receiver operating characteristic curve (AUC) reaches 71% with the PDVImin. When the vascular patterns were further classified into intra-nodular and peripheral vascularity types, no vascularity type was observed significantly more frequently in malignant nodules than in benign nodules. These proposed computerized vascular indices provide a quantification method to objectively evaluate thyroid nodules and have potential as predictors of thyroid malignancy. The conventional vascular characterizations of malign nodules, that is, more vessels are observed in malignant nodules than in benign nodules, are shown to be unreliable in our study. Instead, a higher value of the quantified power Doppler vascular density was observed in benign nodules.

Serum vascular endothelial growth factor-D levels correlate with cervical lymph node metastases in papillary thyroid carcinoma

The aim of this multicenter study was to evaluate the clinical relevance of serum vascular endothelial growth factor-D (VEGF-D) in papillary thyroid carcinoma (PTC). This prospective study consisted of 74 patients with primary PTC and 15 patients with benign thyroid nodules treated from 2008 to 2009. VEGF-D concentration was compared with patient clinicopathologic features and lymph node metastases. There was no significant difference in mean serum VEGF-D levels between the PTC and benign thyroid nodule groups. Within the PTC group, serum VEGF-D levels were significantly higher in patients with lymph node metastases than in patients without metastases (241.92 vs. 213.89 pg/ml, respectively; P = 0.035). Receiver operating characteristic curve analysis revealed that preoperative serum VEGF-D levels were predictive of lymph node metastases in the patients >45 years. Serum VEGF-D level that was correlated with the presence of cervical lymph node metastases in PTC patients might be a useful prognostic indicator.

Primary Intrathoracic Goiter

Nodular goiter is a common disease in Taiwan, and substernal or intrathoracic goiters are not infrequent. However, intrathoracic goiters are mainly of the secondary type and primary intrathoracic goiters are rarely seen. We report a 55-year-old woman who was incidentally found to have an ectopic goiter located in the anterior upper mediastinum with the initial presenting symptom of productive cough. Imaging studies including chest X-ray and computed tomography identified the lesion, and 131I-uptake scan showed weak uptake in the thorax. Surgical removal via thoracotomy was performed and the diagnosis was confirmed by pathology. A primary intrathoracic goiter, although rare, should also be considered in the differential diagnosis of mediastinal tumor.

COMPUTERIZED QUANTIFICATION OF ULTRASONIC HETEROGENEITY IN THYROID NODULES

To test whether computerized quantification of ultrasonic heterogeneity can be of help in the diagnosis of thyroid malignancy, we evaluated ultrasonic heterogeneity with an objective and quantitative computerized method in a prospective setting. A total of 400 nodules including 271 benign thyroid nodules and 129 malignant thyroid nodules were evaluated. Patient clinical data were collected, and the grading of heterogeneity on conventional gray-scale ultrasound images was retrospectively reviewed by a thyroid specialist. Quantification of ultrasonic heterogeneity (heterogeneity index, HI) was performed by a proprietary program implemented with methods proposed in this article. HI values differed significantly between benign and malignant nodules, diagnosed by a combination of fine-needle aspiration and surgical pathology results (p < 0.001, area under the curve = 0.714). The ultrasonic heterogeneity of these samples, as assessed by an experienced clinician, could not significantly differentiate between benign and malignant thyroid nodules. However, nodules with marked ultrasonic heterogeneity had higher HI values than nodules with homogeneous nodules. These results indicate that the new computer-aided diagnosis method for evaluation of the ultrasonic heterogeneity of thyroid nodules is an objective and quantitative method that is correlated with conventional ultrasonic heterogeneity assessment, but can better aid in the diagnosis of thyroid malignancy.

Postoperative Showering for Clean and Clean-contaminated Wounds: A Prospective, Randomized Controlled Trial.

Objective:To evaluate wound infection rates, pain scores, satisfaction with wound care, and wound care costs starting 48 hours after surgery. Background:Showering after surgery is a controversial issue for wound care providers and patients. We investigated the benefits and detriments of showering for postoperative wound care. Methods:Patients undergoing thyroid, lung, inguinal hernia, and face and extremity surgeries with clean or clean-contaminated wounds were included. The patients were randomized to allow showering (shower group) or to keep the wound dry (nonshower group) for postoperative wound care starting 48 hours after surgery. The primary endpoint was the rate of surgical wound infection. The secondary endpoints included the wound pain score, satisfaction with wound care, and cost of wound care. Results:Between May 2013 and March 2014, there were 222 patients randomized to the shower group and 222 to the nonshower group. Two patients in each group were lost to follow-up. There were 4 superficial surgical site infections in the shower group and 6 in the nonshower group (4/220, 1.8% vs 6/220, 2.7%, P = 0.751). Postoperative pain scores were comparable between the 2 groups. Patients in the shower group were more satisfied with their method of wound care, and their wound care costs were lower when compared with the nonshower group. Conclusions:Clean and clean-contaminated wounds can be safely showered 48 hours after surgery. Postoperative showering does not increase the risk of surgical site complications. It may increase patients’ satisfaction and lower the cost of wound care.

Quantitative analysis of echogenicity for patients with thyroid nodules.

Hypoechogenicity has been described qualitatively and is potentially subject to intra- and inter-observer variability. The aim of this study was to clarify whether quantitative echoic indexes (EIs) are useful for the detection of malignant thyroid nodules. Overall, 333 participants with 411 nodules were included in the final analysis. Quantification of echogenicity was performed using commercial software (AmCAD-UT; AmCad BioMed, Taiwan). The coordinates of three defined regions, the nodule, thyroid parenchyma, and strap muscle regions, were recorded in the database separately for subsequent analysis. And the results showed that ultrasound echogenicity (US-E), as assessed by clinicians, defined hypoechogenicity as an independent factor for malignancy. The EI, adjusted EI (EIN-T; EIN-M) and automatic EI(N-R)/R values between benign and malignant nodules were all significantly different, with lower values for malignant nodules. All of the EIs showed similar percentages of sensitivity and specificity and had better accuracies than US-E. In conclusion, the proposed quantitative EI seems more promising to constitute an important advancement than the conventional qualitative US-E in allowing for a more reliable distinction between benign and malignant thyroid nodules.

Using Ion Torrent sequencing to study genetic mutation profiles of fatal thyroid cancers

BACKGROUND/PURPOSE Surgery followed by radioiodine is a mainstay of treatment for thyroid cancers of follicular origins. However, about 5% of the thyroid cancers are non-operable and/or radioiodine-refractory diseases, which are either locally advanced or metastatic and result in a survival of less than 5 years. How to treat this population of thyroid cancer patients becomes a critical issue requiring further understanding of the tumors genetic information. METHODS We used formalin-fixed paraffin-embedded specimens of 22 fatal thyroid cancers and their corresponding non-tumor parts, if available, to yield genomic DNA, and applied the Ion Torrent™ Personal Genome Machine (IT-PGM) System (Life Technologies), a next generation sequencing technology, to interrogate 740 mutational hotspots in 46 oncogenes. We further validated the results by conventional direct sequencing. RESULTS We confirmed 21 mutations of 11 oncogenes in the 22 fatal thyroid cancer samples. Among them, the MET p.N375S and MLH1 p.V384D mutations, each was detected in two cases, and has rarely been found to be involved in thyroid cancer pathogenesis before. We also identified homozygous PDGFRA p.V824V mutation in eight out of the 22 cases, while the non-tumor counterparts carried heterozygous PDGFRA p.V824V mutation. We noted that the Ion Torrent technique unfortunately showed high false positive rates for detecting EGFR mutations in thyroid cancers. CONCLUSION The extensive genetic studies provide new insights to future targeted therapy in these patients. IT-PGM proved to be valuable for comprehensively searching genetic mutations in potentially fatal thyroid cancers.