[Show abstract][Hide abstract] ABSTRACT: Despite the favorable therapeutic outcomes reported in differentiated thyroid cancer (DTC), a significant proportion of DTC patients present with refractory behavior to conventional therapy. The sirtuin (Sirt) family has recently been implicated in the maintenance of cellular homeostasis under genotoxic stress. Here, we investigated the induction of Sirt1 expression by etoposide-induced genotoxic stress to gain insights into thyroid carcinogenesis and identify novel therapeutic targets. Immunohistochemical staining analyses of Sirt1 and Sirt3 were performed using human thyroid cancer tissues and matched normal tissues, and bioinformatic analyses were done using public repositories, including the Human Protein Atlas, BioGPS, NCBI Gene Expression Omnibus (GEO) profiles, and GeneNetwork. TPC1, FTC133 and FRO cells were used for molecular biological experiments including apoptosis assays, MTT, immunofluorescence staining and qRT-PCR assays. The IHC data and public repositories data consistently showed variable Sirt1 and Sirt3 expression patterns in normal thyroid follicular cells and papillary thyroid cancer cells. The induction of Sirt1 and Sirt3 was cell type-specific and the expression levels of these genes correlated with apoptotic cell death and cell viability after etoposide-induced genotoxic stress. Sirt1‑Foxp3 signaling-mediated regulation of Bax and p21 mRNA expression was a signature molecular event in TPC1 cells, which showed remarkable resistance to etoposide-induced genotoxic stress. The induction of Sirt1 and Sirt3 may be a determinant of thyroid cancer cell survival under genotoxic stress conditions. Further examination of the Sirt1-Foxp3 signal may improve our understanding of thyroid carcinogenesis and help identify new druggable targets.
[Show abstract][Hide abstract] ABSTRACT: Tumor multifocality is frequently observed in papillary thyroid carcinoma (PTC), but its prognostic value is controversial. We investigated the prognostic significance of multifocality in PTCs larger than 1 cm and papillary thyroid microcarcinomas (PTMC).
Annals of Surgical Oncology 08/2014; · 4.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: This study assessed the results of robotic thyroidectomy by fellowship-trained surgeons in their initial independent practice, and whether standard fellowship training for robotic surgery shortens the learning curve.Materials & Methods: This prospective cohort study evaluated outcomes in 125 patients who underwent robotic thyroidectomy using gasless transaxillary single-incision technique by two recently graduated fellowship-trained surgeons. Learning curves were analyzed by operation time, with proficiency defined as the point at which the slope of the time curve became less steep.Results: Of the 125 patients, 113 underwent robotic less-than-total thyroidectomy (LT), 9 underwent robotic total thyroidectomy (TT) and 3 underwent robotic TT with modified radical neck dissection (MRND). Mean total times for these three operations were 100.8 ±20.6 min, 134.2 ± 38.7 min, and 284.7 ± 60.4 min respectively. For both surgeons, the operation times gradually decreased, reaching a plateau after 20 robotic LTs.Conclusions: The surgical learning curve for robotic thyroidectomy performed by recently graduated fellowship-trained surgeons with little or no experience in endoscopic surgery showed excellent results compared with those in a large series of more experienced surgeons. Head Neck, 2014
[Show abstract][Hide abstract] ABSTRACT: Background
Body image is associated with self-esteem and identity and has a close relationship with quality of life (QoL). We compared the impact of surgical scars on patient body image between conventional open thyroidectomy (OT) and robotic thyroidectomy (RT) in female papillary thyroid carcinoma (PTC) patients.
From October 2009 to December 2010, 116 PTC patients who underwent total thyroidectomy at the Yonsei University Health System (Seoul, Korea) were prospectively enrolled. Of these 116 patients, 56 had OT, and 60 had RT. Their scars were assessed using the Vancouver Scar Scale (VSS), and psychometric properties were evaluated using the body image scale (BIS) questionnaire postoperatively. Both groups were compared using cross-sectional and time series methods.
The mean age was significantly younger in the RT group. Regarding scar quality, the OT group showed superiority in scar pigmentation and the total VSS score during the early postoperative period, but the VSS score improved over time and was similar between both groups at 9 months. The RT group received better scores regarding most of the BIS items, a trend that remained relatively constant over time. In patients with noticeable scars (VSS ≥2) at 9 months, the RT group received better BIS scores regarding almost all items, including “self-conscious,” “physical attractiveness,” “feeling of less feminine,” “sexual attractiveness,” “dissatisfaction with body, scar and appearance when dressed,” and “avoidance of people due to appearance.”
RT provides better self-body image and improves QoL compared with conventional OT by avoiding a noticeable cervical scar.
[Show abstract][Hide abstract] ABSTRACT: Background: The aim of this study was to investigate the correlation between B-type Raf kinase (BRAF) mutation and clinicopathological features of follicular variant of papillary thyroid carcinoma (FVPTC). Methods: 84 patients with pathologically confirmed FVPTC, who underwent preoperative BRAF(V600E) study, were analyzed. Clinicopathological parameters and ultrasonographic features were compared between BRAF(V600E) positive and negative groups. Results: 41.7% of patients showed BRAF(V600E) . BRAF(V600E) positive group showed the smaller tumor size (7.3 ± 3.6 mm vs. 10.7 ± 8.9 mm, p = 0.018) and the more frequent multifocality (25.7% vs. 8.2%, p = 0.028). FVPTC with BRAF(V600E) showed suspicious ultrasonographic features (88.6% vs. 57.1%, p = 0.002) more frequently. BRAF(V600E) positivity is associated with multifocality after adjusting for age, sex, the presence of suspicious ultrasonographic features, pathological tumor size, and thyrotropin level. Conclusions: BRAF(V600E) was correlated with smaller tumor size and suspicious ultrasonographic features in FVPTC. BRAF(V600E) was significant parameter for predicting multifocality of FVPTC. Head Neck, 2014.
[Show abstract][Hide abstract] ABSTRACT: Robotic thyroidectomy is ideal for patients with indeterminate, likely benign lesions less than 3 cm, and a body mass index less than 35 kg/mg(2). Proper arm position and padding are important to facilitate exposure and development of the working space from axilla to thyroid bed. The working space is developed using headlight and retractors without robotic assistance, establishing exposure of the thyroid bed from a 5-cm incision in the axilla. Three robotic instruments and a stereoscopic endoscope provide excellent visualization of the associated thyroid neurovasculature anatomy.
Otolaryngologic Clinics of North America 06/2014; 47(3):373-378. · 1.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Transaxillary robotic thyroidectomy is considered a technically feasible and safe treatment option for patients with low-risk papillary thyroid carcinoma (PTC). The aim of the present study was to determine the factors that contribute to the perioperative surgical outcomes of robotic thyroidectomy and to suggest guidelines for patient selection to be used by surgeons inexperienced in the technique.
[Show abstract][Hide abstract] ABSTRACT: Background. The association between the BRAF mutation and persistence/recurrence was investigated in patients with classical papillary thyroid carcinoma (PTC) at a BRAF mutation prevalent area.Methods. A total of 282 patients with total thyroidectomy and prophylactic central neck dissection were included. The BRAF mutation was evaluated with cytology specimen using dual priming oligonucleotide (DPO)-based multiplex PCR and direct sequencing preoperatively.Results. Thirty four patients (12%) had persistence/recurrence. In all PTC, the BRAF mutation on both methods was not associated with persistence/recurrence. In PTC > 10 mm, the BRAF mutation on DPO-based multiplex PCR was significantly associated with persistence/recurrence and a potential predictor for persistence/recurrence. In PTC ≤ 10 mm, none of the covariates were significantly different between patients with and without persistence/recurrence.Conclusions. The BRAF mutation was significantly associated with persistence/recurrence and a potential predictor in patients with classical PTC > 10 mm at a BRAF mutation prevalent area. Head Neck, 2014
[Show abstract][Hide abstract] ABSTRACT: Abstract Background: Epidermal growth factor (EGF) decreases inflammatory cell infiltration and TGF-β expression during wound healing. Several clinical studies show that recovery of various ulcer wounds, such as diabetic and radiation ulcer, is promoted by EGF. Objective: To evaluate effects of recombinant human epidermal growth factor (rhEGF) on cutaneous scar quality after thyroidectomy. Method: Scar quality was evaluated by Vancouver scar scale (VSS) in two groups of female thyroidectomy patients (control, n = 11; rhEGF-treated, n = 10). Scar erythema, pigmentation, elasticity and hydration were measured by mexameter, cutometer and corneometer. Results: Scar pliability (at 4 weeks) and thickness (2 weeks) after surgery were significantly lower in the rhEGF group than control. Total VSS score was significantly lower in the rhEGF group after 4 weeks. However, erythema, pigmentation, elasticity and hydration of the scar were not significantly different between groups. Conclusion: The early use of rhEGF in surgical wound healing may improve cutaneous scar quality.
Journal of Dermatological Treatment 04/2014; · 1.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In 2001, the authors developed a novel method of gasless transaxillary endoscopic thyroidectomy (ET) and have now performed >1000 operations. This review was performed to document surgical outcomes after 10 years of experience with this technique and to determine what the role of ET has in the current era.
All patients who underwent elective ET using the gasless transaxillary approach from November 2001 to December 2010 were evaluated. Patient demographics, surgical data, histologic analysis results, and complications were recorded and analyzed.
A total of 1085 patients underwent ET during the study period. Mean patient age was 36.9±9.7 years; the gender ratio was 1:49 (male:female). There were 228 benign thyroid tumor cases and 857 thyroid malignancies. Trend analysis showed a progressive increase in case numbers per month until the end of 2007, followed by a steady decline. There were 175 total thyroidectomy cases and 910 cases of less-than-total thyroidectomy. Mean overall operating time was 132.92±48.6 minutes, and the overall complication rate was 13.5%. The most common complications were: transient hypocalcemia (6.3%), transient hoarseness (3.9%), hematoma (0.4%), permanent hypocalcemia (0.1%), and permanent recurrent laryngeal nerve injury (0.2%).
Gasless ET is comparable to open thyroidectomy in terms of early surgical outcomes and complications, and it bridges the gap between conventional open surgery and robotic transaxillary thyroidectomy.
[Show abstract][Hide abstract] ABSTRACT: Robotic thyroidectomy (RT), a new gasless, transaxillary approach developed by the Yonsei University group in Seoul, Korea, eliminates the need for a cervical incision. Since RT is technically complex and has a steep learning curve, the surgical complication rate may initially be higher than with conventional surgery. This study evaluated the complication rates of transaxillary RT and assessed ways to prevent surgical complications.
Between October 2007 and March 2013, 3,000 patients underwent RT for thyroid cancer in the Department of Surgery, Yonsei University College of Medicine at Severance Hospital, Seoul. The medical records of these patients were reviewed retrospectively, and surgical complications were assessed on the basis of clinical findings.
The most common surgical complication was symptomatic hypocalcemia, of which 37.43 % cases were transient and 1.10 % permanent. Other surgical complications included recurrent laryngeal nerve injury (1.23 % transient, 0.27 % permanent), seroma (1.73 %), hematoma (0.37 %), chyle leakage (0.37 %), trachea injury (0.2 %), Horner's syndrome (0.03 %), carotid artery injury (0.03 %), and brachiocephalic vein injury (0.03 %). The technique-related complications, which were never seen in conventional open thyroidectomy, were axillary skin flap perforation (0.1 %), and traction injury of the arm on the side the lesion was located (0.13 %).
Surgeons who have mastered standardized robotic surgical procedures and who understand potential complications and how to prevent them can perform RT safely.
[Show abstract][Hide abstract] ABSTRACT: Thyroid hormone withdrawal (THW) for postoperative radioiodine adjuvant therapy or diagnostic radioiodine whole body scan in patients with differentiated thyroid cancers results in acute thyroid hormone deficiency and abnormal lipid profiles. To better clarify the clinical pattern of dyslipidemia occurring after THW, we retrospectively analyzed the association between serum total cholesterol level after THW and various clinical factors in a total of 61 patients who underwent total thyroidectomy due to papillary thyroid cancers from January 2010 to March 2012, in Severance Hospital, Seoul, Korea. Preoperative baseline total cholesterol was significantly correlated with post-THW total cholesterol level; however, age, gender, or elevated TSH level after THW itself was not correlated with post-THW total cholesterol level. A significant correlation between preoperative measured BMI and post-THW total cholesterol level was found (r = 0.263, P = 0.041). In multiple logistic analysis, BMI was an independent determining factor of post-THW total cholesterol level (P = 0.012).
International journal of endocrinology. 01/2014; 2014:649016.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to evaluate the diagnostic utility of PAI at detecting thyroid microcalcifications at 700 nm laser wavelengths.
This study included 36 resected samples in 18 patients. To evaluate the PA manifestation of microcalcifications in PAI, gray level histogram and co-occurrence matrix (COM) texture parameters were extracted from the 3 fixed ROI US and PA images, respectively, per sample. We compared the textural parameters obtained from specimen PAIs between samples with punctate microcalcifications on specimen radiography and those without microcalcifications.
On specimen US, the mean value (2748.4±862.5) of samples with microcalcifications on specimen radiography was higher than that (1961.9±780.2) of those without microcalcifications (P = 0.007). However, there were no significant differences in textural parameters obtained from specimen PAIs between samples with punctate microcalcifications on specimen radiography and those without when applying both the mean value of the three slices of thyroid specimens and the value of the thyroid specimen slice which had the highest value of the mean values in specimen US.
PAI did not show significant PA contrast on thyroid microcalcifications indicating that the experimental setup and protocols should be enhanced, e.g., method of complete blood rejection from ex vivo specimens, the multi-wavelength spectroscopic PA imaging method which can solely extract the PA signal from microcalcifications even with high spectral interferences, or PA imaging with narrower slice thickness using 2-dimensional array transducer, etc.
PLoS ONE 01/2014; 9(11):e113358. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The present study was designed to investigate the necessity of completion thyroidectomy for patients who underwent thyroid lobectomy for low-risk papillary thyroid microcarcinoma (PTMC) that was later pathologically diagnosed as central lymph node (CLN) metastasis.
Between 1986 and 2001, we assessed 551 patients who underwent thyroidectomy with prophylactic ipsilateral central compartment neck dissection, and 409 patients were followed-up completely. Thyroid lobectomy were performed in 281 and 128 patients, respectively. The patients were divided into two groups according to CLN metastasis. Clinicopathological profiles and follow-up details were investigated by retrospective chart review.
The CLN-positive and -negative groups were comprised of 43 (15.2 %) and 238 patients (84.8 %), respectively. The mean ages of the two groups were not significantly different (p > 0.05). The mean tumor size of the CLN-positive group (6.8 mm) was significantly larger than that of the CLN-negative group (5.6 mm; p < 0.05). Microscopic capsular invasion was significantly higher in the CLN-positive group (51.2 vs. 23.9 %; p < 0.05). Overall, 21 patients (7.4 %, 21/281) experienced recurrence. Among these, 2 (4.7 %, 2/43) and 19 (8.0 %, 19/238) were in the CLN-positive and -negative groups, respectively. There was no significant correlation between CLN metastasis and tumor recurrence.
Postoperative recurrence was lower in the CLN-positive group, and there was no significant correlation between CLN metastasis and tumor recurrence. Our results suggest that it is not necessary to perform completion thyroidectomy for PTMC patients who have undergone thyroid lobectomy and who have been pathologically diagnosed with CLN metastasis.
World Journal of Surgery 12/2013; · 2.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Using the da Vinci(®) robotic system, surgeons can complete secure thyroidectomy without noticeable neck scarring. This study compared the surgical completeness of transaxillary robotic thyroidectomy (RT) with conventional open procedures (OT) in treating papillary thyroid carcinoma (PTC) patients.
From April 2009 through February 2011, 94 PTC patients underwent total thyroidectomy with central compartment neck dissection (CCND) at Yonsei University College of Medicine. All patients received 1.1 GBq radioactive iodine (RAI) ablation, post-therapy whole-body scans (TxWBS), and diagnostic WBS (DxWBS) 1 year later. We prospectively compared patient clinicopathologic characteristics and surgical completeness between the two groups.
Fifty-one patients underwent OT and 43 underwent RT. Mean age was significantly younger in the RT group. Tumor size, capsular-invasion frequency, multifocality, bilaterality, and central nodal metastasis were not different between the two groups. The number of retrieved nodes during CCND did not significantly differ between the groups. There was no significant difference between the OT and RT groups in stimulated thyroglobulin levels acquired during TxWBS and DxWBS. The RAI uptake ratios at TxWBS were significantly higher in the RT group compared with the OT group; however, follow-up DxWBS showed no difference in RAI uptake ratios. Also, the ablation success rate was similar between the two groups. There were no abnormal findings in follow-up neck ultrasonography in either group.
Remnant thyroid tissue ablation after transaxillary RT was successfully managed by 1.1 GBq RAI. RT showed similar surgical completeness versus conventional OT, and provides a safe and feasible surgical option for PTC patients.
[Show abstract][Hide abstract] ABSTRACT: Purpose: During the past decade, various endoscopic thyroid surgeries have been conducted, each with its own benefits. The incorporation of robotic systems to endoscopic thyroid surgery has improved the visualization and precision of endoscopic techniques. We previously reported our initial experience with robotic modified radical neck dissection (MRND) of papillary thyroid carcinoma (PTC) with lateral neck node metastasis (LNM). The aim of this study was to compare surgical outcomes of robotic vs. conventional open MRND of PTC with LNM using propensity score matching. Methods: From January 2008 to February 2011, 515 patients with PTC with LNM were enrolled. One hundred patients underwent robotic MRND, and 415 patients underwent conventional open MRND. These two groups were retrospectively compared with respect to their clinicopathological characteristics, surgical outcomes, and surgical completeness. Furthermore, to avoid selection bias, propensity score matching analysis was used to compare surgical outcomes of each group without any compounding factors. Results: The operative time for the robotic MRND was longer than for the open MRND (297.9±60.2 min vs. 212.1±55.6 min, P=0.089). However, the mean numbers of retrieved lymph nodes and mean hospital stay after surgery were similar in the two groups (36.0±12.9 vs. 40.8±13.3, P=0.235), (6.1±1.6 days vs. 6.1±2.1 days, P=0.577). The complication rates were similar between the two groups, and there was no statistical difference in postoperative thyroglobulin levels between groups (0.51±0.83 ng/ml vs. 0.89±2.46 ng/ml, P=0.593). Conclusion: According to our study, robotic MRND shows similar surgical outcomes to conventional open MRND after case-matched analyses. We suggest that robotic MRND is an acceptable alternative as an operative method for PTC with LNM, resulting in excellent cosmesis and patient satisfaction.
The Korean journal of endocrine surgery. 11/2013; 13:1598-1703227.
[Show abstract][Hide abstract] ABSTRACT: Estrogen metabolism may be associated with the pathophysiological development of papillary thyroid carcinoma (PTC).
To evaluate the differential estrogen metabolism between benign and malignant PTCs, estrogen profiling by gas chromatography--mass spectrometry was applied to urine samples from postmenopausal patients with 9 benign tumors and 18 malignant stage I and III/IV PTCs.
The urinary concentration of 2-methoxyestradiol was significantly lower in the stage I malignant patients (3.5-fold; P < 0.025) than in the benign group. The metabolic ratios of 16alpha-OH-estrone/estrone and estriol/estradiol, which are responsible for 16alpha-hydroxylase activity, were increased more than 2.5-fold in the advanced-stage malignant PTC (P < 0.02 each). The more than 6.2-fold decrease in the urinary 2-/16alpha-hydroxylase ratio in stage III/IV malignant PTC was consistent with the ratio in postmenopausal patients with endocrine gland cancers. In addition, reductive 17beta-hydroxysteroid dehydrogenase (17beta-HSD; estradiol/estrone or estriol/16alpha-OH-estrone) was present at significantly higher levels in subjects with stage III/IV malignant PTCs than in benign subjects (>3.5-fold difference; P < 0.002). In particular, the estriol/16alpha-OH-estrone ratio differentiated between the benign and early-stage malignant patients (P < 0.01).
Increased 16alpha-hydroxylation and/or a decreased 2-/16alpha-ratio, as well increased reductive 17beta-HSD, with regard to estrogen metabolism could provide potential biomarkers. The devised profiles could be useful for differentiating malignant thyroid carcinomas from benign adenomas in postmenopausal women.
[Show abstract][Hide abstract] ABSTRACT: Background: This study examined whether the time required for recovery from transient hypoparathyroidism is correlated with the onset of hypocalcemic symptoms in patients with total thyroidectomy (TT). Methods: Medical records of 54 patients were retrospectively reviewed. The correlation between the onset of hypocalcemic symptoms and the recovery time were compared for all patients divided into three groups based on first appearance of hypocalcemic symptoms; group 1, onset within 24 hours; group 2, onset at 24-48 hours; and group 3, onset more than 48 hours. Results: There was a negative correlation between onset and recovery times (P < 0.001). Serum parathyroid hormone levels one year after surgery were significantly lower in group 1, than in groups 2 or 3 (P < 0.001). Conclusions: Recovery time can be predicted by time of onset of hypocalcemic symptoms and signs. Earlier onset leads to longer recovery times. Head Neck, 2013.