Selective inhibition of V600E-mutant BRAF gene induces apoptosis in thyroid carcinoma cell lines.

PURPOSE: Papillary thyroid cancer (PTC) has a high incidence of BRAFV600E mutation. The purpose of this study was to evaluate the potential relationship between thyroiditis and BRAFV600E mutation status in patients with PTC. We investigated how a selective inhibitor of BRAFV600E PLX4032 affects the proliferation and inflammatory cytokine levels of thyroid cancer. METHODS: Two thyroid cancer cell lines TPC1 and 8505C were treated with PLX4032, an analysis was done on cell growth, cell cycle, the degree of apoptosis, and levels of inflammatory cytokines. To identify the functional links of BRAF, we used the STRING database. RESULTS: Docking results illustrated PLX4032 blocked the kinase activity by exclusively binding on the serine/threonine kinase domain. STRING results indicated BRAF is functionally linked to mitogen-activated protein kinase. Both cell lines showed a dose-dependent reduction in growth rate but had a different half maximal inhibitory concentration value for PLX4032. The reaction to PLX4032 was more sensitive in the 8505C cells than in the TPC1 cells. PLX4032 induced a G2/M phase arrest in the TPC1 cells and G0/G1 in the 8505C cells. PLX4032 induced apoptosis only in the 8505C cells. With PLX4032, the TPC1 cells showed decreased levels of vascular endothelial growth factor, granulocyte-macrophage colony-stimulating factor, chemokine (C-C motif) ligand 2/monocyte chemoattractant protein 1, whereas the 8505C cells showed significantly decreased levels of IL-8, serpin E1/plasminogen activator inhibitor-1, and matrix metalloproteinase (MMP)-3. CONCLUSION: PLX4032 was cytotoxic in both TPC1 and 8505C cells and induced apoptosis. In the 8505C cells, inflammatory cytokines such as IL-8 and MMP-3 were down-regulated. These findings suggest the possibility that the BRAFV600E mutation needs to target inflammatory signaling pathways in the treatment of thyroid cancer.

Comparative study of bilateral axillo-breast approach endoscopic and robotic thyroidectomy: propensity score matching analysis of large multi-institutional data.

PURPOSE: The aim of this study was to compare the large multi-institutional data of surgical outcomes of bilateral axillo-breast approach (BABA) robotic (RT) and endoscopic thyroidectomy (ET) and to evaluate the merits of robotic thyroidectomy. METHODS: From 2004 to 2015, 1,029 patients underwent BABA ET, and from 2008 to 2015, 2003 patients underwent BABA RT in 3 large volume centers in Korea. Two groups were retrospectively compared in terms of clinicopathologic characteristics, complications, surgical completeness, and long-term outcomes using propensity score matching analysis. RESULTS: Both groups had similar demographic characteristics including age, sex, tumor size, pathologic stage, and hospital stay after matching. Each group had similar rate of transient hypoparathyroidism, however, ET showed significantly higher rate of permanent hypoparathyroidism (ET 5.2% vs. RT 2.3%, P = 0.05), and transient vocal cord palsy (ET 14.4% vs. RT 9.1%, P = 0.006). Total operation time was longer in the ET group irrespective of surgical extents, including lobectomy (P = 0.016), total thyroidectomy (P = 0.031), and total thyroidectomy with central lymph node dissection (P = 0.019). The rate of patients with off-Tg under 1.0 ng/mL after 1st ablation was significantly higher in RT than ET group (ET 64.6% vs. RT 92.7%, P < 0.001). In long-term follow-up of cancer patients, 1.4% experienced recurrence after ET (10 cases), while 0.3% cases experienced recurrence after RT (5 cases) (P < 0.001). CONCLUSION: Both ET and RT can be safe and effective methods to treat thyroid diseases. However, the application of robotic system may help to overcome the limitations of the instruments and surgeon's skills.

Does Tumor Size Influence the Diagnostic Accuracy of Ultrasound-Guided Fine-Needle Aspiration Cytology for Thyroid Nodules?

Background. Fine-needle aspiration cytology (FNAC) is diagnostic standard for thyroid nodules. However, the influence of size on FNAC accuracy remains unclear especially in too small or too large thyroid nodules. The objective of this retrospective cohort study was to investigate the effect of nodule size on FNAC accuracy. Methods. All consecutive patients who underwent thyroidectomy for nodules in 2010 were enrolled. FNAC results (according to the Bethesda system) were compared to pathological diagnosis. The nodules were categorized into groups A-E on the basis of maximal diameter on ultrasound (≤0.5, >0.5-1, >1-2, >2-4, and >4 cm, resp.). Results. There were 502 cases with 690 nodules. Overall FNAC sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 95.4%, 98.2%, 99.4%, 86.4%, and 96.0%, respectively. False-negative rates (FNRs) of groups A-E were 3.2%, 5.1%, 1.3%, 13.3%, and 50%, respectively. Accuracy rates of groups A-E were 96.8%, 94.8%, 99%, 94.7%, and 87.5%, respectively. Conclusion. Although accuracy rates of FNAC in thyroid nodules smaller than 0.5 cm are comparable to the other group, thyroid nodules larger than 4 cm with benign cytology carry a higher risk of malignancy, which suggest that those should be considered for intensive follow-up or repeated biopsy.

Using Transcutaneous Laryngeal Ultrasonography (TLUSG) to Assess Post-thyroidectomy Patients' Vocal Cords: Which Maneuver Best Optimizes Visualization and Assessment Accuracy?

To assess vocal cord (VC) movement with transcutaneous laryngeal ultrasound (TLUSG), three maneuvers, namely passive (quiet respiration), active (phonation), and Valsalva maneuvers have been described. It remains unclear which maneuver or using more maneuvers provides better visualization and assessment accuracy. We prospectively evaluated 342 post-thyroidectomy patients from two centers. They underwent TLUSG with direct laryngoscopic (DL) validation afterwards. During TLUSG, patients were instructed to perform all three maneuvers (passive, active, and Valsalva). VC visualization rate and accuracy between three maneuvers were compared. Visualization rate tended to be higher in Valsalva maneuver than that in other two maneuvers (92.1% vs. passive: 91.5%; active: 89.8%). While 19 patients had post-operative VC palsy, passive maneuver had lower test specificity than active (94.3 vs. 97.6%, p = 0.01) and Valsalva maneuvers (94.3 vs. 97.4%, p = 0.02). In assessable VCs, passive maneuver has a higher ability to differentiate between mobile VCs and VC palsy (Area under ROC curve--passive: 0.942, active: 0.863, Valsalva: 0.893). TLUSG with more maneuvers did not improve sensitivity or specificity. On applying TLUSG as a screening tool (i.e., only selected patient with "unassessable" VCs or VCP on TLUSG for DL), Valsalva maneuver (85.96%) saved more patients from DL than passive (81.87%) or active (84.81%) maneuver. Passive maneuver has a higher ability to differentiate VC palsy from normal. Using TLUSG as a screening tool, Valsalva was the preferred maneuver as it was more specific, had high visualization rate, and saved more patients from DL.

Combined effect of Hashimoto's thyroiditis and BRAF(V600E) mutation status on aggressiveness in papillary thyroid cancer.

BACKGROUND: The purpose of this study was to evaluate the association between Hashimoto's thyroiditis and BRAF(V600E) mutation status in patients with papillary thyroid cancer (PTC) and to determine their combined association with tumor aggressiveness in PTC. METHODS: A total of 1780 patients with PTC who underwent surgery were enrolled in this study. Simple and multiple analyses were performed to determine the association between Hashimoto's thyroiditis and the BRAF(V600E) mutation in PTC. RESULTS: Hashimoto's thyroiditis was present in 11.5% of patients (204/1780) with PTC. Multiple logistic regressions showed that BRAF(V600E) (odds ratio [OR] = 0.493; 95% confidence interval [CI] = 0.360-0.678) and the female sex (OR = 7.146; 95% CI = 3.408-18.347) were independent factors associated with Hashimoto's thyroiditis in PTC. BRAF(V600E) mutation and the Hashimoto's thyroiditis-negative PTC group were associated with aggressive disease (OR = 3.069; 95% CI = 1.654-5.916). CONCLUSION: Hashimoto's thyroiditis was associated less frequently with BRAF(V600E) , and frequently with the female sex in patients with PTC. Hashimoto's thyroiditis and BRAF(V600E) status may help to predict clinical outcome of PTC.

Prospective, randomized controlled trial on use of ropivacaine after robotic thyroid surgery: Effects on postoperative pain.

BACKGROUND: We evaluated the effects of ropivacaine for pain relief after robotic thyroid surgery. METHODS: One hundred eight patients scheduled for robotic thyroid surgery were randomized into ropivacaine (n = 54) or control (n = 54) groups. After surgery, 40 mL of 0.25% ropivacaine or 0.9% saline (control) was instilled into the skin flap. Postoperative pain intensity (visual analog scale [VAS]), analgesic requirements (fentanyl), and adverse events were assessed at 1, 2, 4, 8, 16, and 24 hours postoperatively. RESULTS: One hundred three patients completed the study protocol. VAS scores were lower in the ropivacaine group than the control group (p = .010); however, VAS scores were not significantly different after 8 hours postoperatively. Total analgesic consumption was higher in controls than ropivacaine-treated patients (p = .01). Adverse events did not differ between the 2 groups. CONCLUSION: Ropivacaine instillation after robotic thyroid surgery reduces acute postoperative pain and analgesic requirements without adverse events. © 2015 Wiley Periodicals, Inc. Head Neck 38: E-E, 2016.

Postoperative biochemical remission of serum calcitonin is the best predictive factor for recurrence-free survival of medullary thyroid cancer: a large-scale retrospective analysis over 30 years.

CONTEXT: The increase in thyroid screening in the general population may lead to earlier detection of medullary thyroid carcinoma (MTC). OBJECTIVE: We aimed to evaluate secular trends in clinicopathological characteristics and long-term prognosis of MTC and its prognostic factors. DESIGN: This was a retrospective analysis from 1982 to 2012. PATIENTS: Three hundred and thirty-one patients with MTC were included and grouped based on the year of diagnosis (1982-2000, 2001-2005, 2006-2010 and 2011-2012). MEASUREMENTS: These included recurrence and mortality as well as biochemical remission (BCR) of serum calcitonin. RESULTS: Mean tumour size (from 2·5 cm to 1·7 cm, P < 0·001) and percentage of extrathyroidal extension (from 52·0% to 26·0%, P = 0·026) decreased. The percentage of patients achieving BCR within six postoperative months (po-BCR) increased with time (from 39·6% to 76·1%, P < 0·001). The 5-year overall recurrence rate significantly decreased in 2006-2012 compared to 1982-2005 (10% vs 18%, respectively, P = 0·031), although the 5-year survival rate did not improve (92% vs 92%, P = 0·929). Failure to achieve po-BCR was the strongest predictive factor associated with recurrence (hazard ratio [HR] = 58·04, 95% CI 7·14-472·11; P < 0·001). Male gender (HR = 3·18, 95% CI 1·18-8·56; P = 0·022), tumour size >2 cm (HR = 18·33, 95% CI 2·35-143·06; P = 0·006) and distant metastasis (HR = 4·00, 95% CI 1·31-12·21; P = 0·015) were significant prognostic factors for mortality. CONCLUSIONS: Clinicopathological characteristics and recurrence of MTC improved with time. Po-BCR was the best predictive factor for recurrence-free survival.

Intraoperative neuromonitoring of the external branch of the superior laryngeal nerve during robotic thyroid surgery: a preliminary prospective study.

PURPOSE: The aim of this study was to evaluate the feasibility of monitoring external branch of the superior laryngeal nerve (EBSLN) during robotic thyroid surgery. METHODS: A total of 10 patients undergoing bilateral axillo-breast approach (BABA) robotic thyroid surgery were enrolled. The nerve integrity monitor (NIM Response 2.0 System) was used for EBSLN monitoring. We performed voice assessments preoperatively and at 1 and 3 months postoperatively using Voice Handicap Index-10 (VHI-10), maximal phonation time (MPT), phonation efficient index (PEI), and laryngeal electromyography (EMG). RESULTS: A total of 19 EBSLNs were at risk and 14 EBSLNs (73.7%) were identified using neuromonitoring. VHI-10 showed a change of voice over time (0.1 vs. 3.6 vs. 1.3); however, this was not statistically significant. VHI-10 scores normalized at 3 months postoperatively compared to the preoperative scores. MPT (a) (16.0 vs. 15.6 vs. 15.4), and MPT (e) (20.1 vs. 15.4 vs. 18.5) showed no significant differences preoperatively compared to the values obtained 1 and 3 months postoperatively. There was a significant change of PEI over time (4.8 vs. 1.1 vs. 4.6) (P = 0.036); however, the values normalized at 3 months postoperatively. Laryngeal EMG results showed 4 cases (21.2%) of neuropathy of EBSLNs at 1 month postoperatively, and electrodiagnostic studies revealed nearly complete recovery of the function of EBSLNs in 4 patients at 3 months postoperatively. CONCLUSION: It is suggested that neuromonitoring of EBSLNs during BABA robotic thyroid surgery is feasible and might be helpful to preserve voice quality.

A Possible Association Between Thyroid Cancer and Breast Cancer.

BACKGROUND: Several lines of evidence suggest that breast cancer (BC) and thyroid cancer (TC) occur together in the same female patients more frequently than would be expected by chance. This study investigated the prevalence and clinicopathological characteristics of second primary BC in TC patients and second primary TC in BC patients. METHODS: A retrospective case-controlled study was performed in 4243 patients with differentiated TC and 6833 patients with BC. Age-matched control groups without second malignancies were selected. RESULTS: Of the 4243 patients with TC, 55 patients developed subsequent BC during a five-year follow-up (range 2-40 years); the standardized incidence ratio (SIR) was 2.45 [confidence interval (CI) 1.83-2.96]. Among the 6833 patients with BC, 81 patients developed subsequent TC during a 6.2-year follow-up (range 2-40 years); the SIR was 2.18 [CI 1.43-2.82]. Subsequent second BC or TC diagnosed within five years of the initial primary malignancy showed more clinical characteristics consistent with early-stage cancer than did control BC or TC patients. Notably, the expression of both the estrogen and progesterone receptors was significantly higher in the tissues of BC patients with coexisting TC compared with those with BC alone. CONCLUSIONS: The overall risk of second primary TC or BC is increased in patients with prior BC or TC, respectively. The early detection of second cancer might have contributed to these findings. However, BC that coexisted with TC had a higher expression of hormone receptors, suggesting an association between the molecular pathogenesis of TC and BC.

In-Depth Survey of Scarring and Distress in Patients Undergoing Bilateral Axillo-Breast Approach Robotic Thyroidectomy or Conventional Open Thyroidectomy.

PURPOSE: Oncologic and surgical outcomes of bilateral axillo-breast approach (BABA) robotic thyroidectomy (RoT) are comparable with those of open thyroidectomy (OT). We compared degree of scarring and psychological/physical distress between OT and BABA RoT. MATERIALS AND METHODS: Study included 129 cases of thyroidectomy (78 OT, 51 BABA RoT). Patients were evaluated by psychology consultant using 5-point scale questionnaire. RESULTS: BABA RoT was associated with lower degree of scarring than OT (7.8 vs. 11.7, P<0.001). Psychological distress immediately after operation and during surveillance period was higher in OT than in BABA RoT (3.1 vs. 2.6, P=0.009 and 2.4 vs. 1.9, P<0.001). Physical distress (pain and exercise limitation) did not differ between groups (2.5 vs. 2.6, P=0.321 and 2.0 vs. 1.9, P=0.0175). CONCLUSIONS: BABA RoT was associated with less scarring and psychological distress than OT. BABA RoT might be alternative for patients who are concerned about neck scar.

Radioactive Iodine Therapy Did Not Significantly Increase the Incidence and Recurrence of Subsequent Breast Cancer.

CONTEXT: Previous studies on the extent to which radioactive iodine (RAI) therapy for thyroid cancer increases the risk of subsequently developing breast cancer have given conflicting results. OBJECTIVE: This study aimed to evaluate the effect of RAI treatment on breast cancer development and recurrence among female patients with primary thyroid cancer. DESIGN: This was a retrospective cohort study. The risk of subsequent breast cancer associated with RAI and its dose in hazard ratios (HRs) with 95% confidential intervals (CIs) were calculated using time-dependent Cox proportional hazard models. PATIENTS: A total of 6150 patients with thyroid cancer enrolled between 1973 and 2009 were followed until December 2012. Of these, 3631 (59.0%) received RAI therapy. During the follow-up period, 99 primary breast cancers were diagnosed. MAIN OUTCOME MEASURE: Risk of breast cancer development according to RAI therapy and RAI dose during treatment for primary thyroid cancer. RESULTS: RAI therapy did not significantly increase the incidence of subsequent breast cancer among female patients (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.22-1.06) when a 2-year latency period was accounted for. High-dose RAI (≥120 mCi) was associated with a reduced incidence of subsequent breast cancer (HR, 0.17; 95% CI, 0.05-0.62) in the cohort with a 2-year latency period. CONCLUSIONS: The long-term follow-up results of this study suggest that RAI treatment for patients with thyroid cancer may not increase the risk or recurrence of breast cancer.

Optimal Cutoff Age for Predicting Mortality Associated with Differentiated Thyroid Cancer.

Patient's age at the time of diagnosis is an important prognostic factor for differentiated thyroid cancer (DTC) as reflected in various staging and risk stratification systems. However, discrepancies exist among the different staging systems on an optimal cut-off age for predicting the clinical outcome of patients with DTC. To determine the age at diagnosis most predictive of clinical outcomes of DTC, a population-based cohort study was performed composed of 35,323 patients with DTC between 1988 and 2010 using the Surveillance, Epidemiology, and End Results (SEER) database. The Youden index J was used to determine the most predictive age-at-diagnosis for thyroid-cancer-specific death. The multivariate Cox proportional hazards model was used to determine the hazard ratios (HRs) for each age group. With a median follow-up of 5.4 years (range, 0-22.9 years), DTC-associated mortality was 1.5% (n = 533) and the rate of death from overall cause was 7.0% (n = 2482). The optimal cutoff age at diagnosis for thyroid-cancer-specific death was 57. Multivariate analysis found that the age-at-diagnosis is the most prognostic factor for thyroid-cancer-specific death (HR 10.02, 95% CI 8.18-12.28). Age at diagnosis is the most important prognostic factor for DTC patients. Based on our analysis, age at diagnosis of 57 might be the optimal predictor of thyroid-cancer-specific death. This finding might be used as consideration in revision of the risk stratification system for treatment of DTC patients.

Efficacy and Safety of Radiofrequency Ablation for Treatment of Locally Recurrent Thyroid Cancers Smaller than 2 cm.

PURPOSE: To evaluate the efficacy and safety of radiofrequency ablation (RFA) for localized small recurrent thyroid cancers less than 2 cm by comparing them with those at repeat surgery. MATERIALS AND METHODS: This retrospective study was institutional review board-approved, and informed consent was waived. From December 2008 to December 2011, this study evaluated 73 patients (17 men and 56 women; age, 50.3 years ± 13.6) with recurrent thyroid cancer who had been treated with RFA (n = 27) or repeat surgery (n = 46) who met the following criteria: (a) three or fewer recurrences or lesions with high probability of recurrence at ultrasonography; (b) no tumor other than the target tumors; and (c) at least 1 year of follow-up. RFA was recommended and performed in cases of surgical ineligibility, such as patient refusal and poor medical condition. Recurrence-free survival rates and posttreatment complication rates (eg, hoarseness and hypocalcemia) were compared between RFA and reoperation groups after adjustment with weighted analysis by using inverse probability of treatment weights. RESULTS: After this adjustment, the 1- and 3-year recurrence-free survival rates were comparable (P = .681) for RFA (96.0% and 92.6%, respectively) and reoperation (92.2% and 92.2%, respectively) groups. The posttreatment hoarseness rate did not differ between the RFA (7.3% [1.8 of 24]) and reoperation (9.0% [3.6 of 39.5]) groups (P = .812), and posttreatment hypocalcemia occurred exclusively in the reoperation group (11.6% [4.6 of 39.5]) but not in the RFA group (0% [0 of 24]) (P = .083). CONCLUSION: RFA may be an effective and safe alternative to repeat surgery in patients with locally recurrent small thyroid cancers.

Role of charcoal tattooing in localization of recurred papillary thyroid carcinoma: initial experiences.

PURPOSE: Surgical excision is the definitive treatment for localized recurrence of papillary thyroid carcinoma. Reoperation for recurrence, however, is challenging and associated with increased operative times and complication rates. For safe and effective reoperation, ultrasound-guided charcoal tattooing localization can be used. The aim of this study was to investigate the feasibility and safety of the ultrasound-guided charcoal tattooing localization. METHODS: Between November 2012 and August 2013, ten patients underwent preoperative charcoal tattooing localization for twelve recurrent lesions. Patient demographics, pathologic features, and operation results were reviewed. RESULTS: The technical success rate of charcoal tattooing was 100%. Eight patients had one recurrent lesion, and two patients had double lesions. Among these 12 recurrent lesions, three (25%) were found in level II, four (33%) in level IV, four (33%) in level VI, and one (8%) was found in the thyroidectomy bed site. The mean size of lesions was 0.87 ± 0.35 cm. Of these 10 patients, eight patients underwent selective lymph node dissection, one patient underwent modified radical neck dissection, and one patient underwent recurrent mass excision. Transient hypocalcemia developed in one patient, and no recurrent laryngeal nerve palsy occurred. There were no major complications related to the injection of the charcoal. The mean follow-up period after reoperation was 8.6 ± 2.7 months; in the follow-up ultrasound, there were no remnant lesions in all patients. CONCLUSION: Preoperative ultrasound-guided charcoal tattooing localization for recurrent thyroid cancer appears to be a feasible and safe procedure for reoperation. Further evaluation is warranted in larger patients' cohorts.

Factors Affecting the Locoregional Recurrence of Conventional Papillary Thyroid Carcinoma After Surgery: A Retrospective Analysis of 3381 Patients.

BACKGROUND: Papillary thyroid carcinoma (PTC) does recur, despite its favorable long-term outcome. The incidence of thyroid cancer in South Korea increased during the 1990s, then increased rapidly after the turn of the century. In 2011, the rate of thyroid cancer diagnoses was 15 times that observed in 1993. The present study aimed to identify factors associated with the locoregional recurrence of recently increasing conventional PTC. METHODS: The records of 3381 patients with conventional PTC were reviewed for this retrospective cohort study. Between January 2004 and January 2012, these patients underwent ultrasonography, computed tomography, and preoperative and total thyroidectomy with central neck dissection. Disease recurrence was defined as structural evidence of disease following the remission period. RESULTS: Median length of follow-up was 5.6 (range 2.1-10.1) years. Of 3381 patients, 75 (2.2 %) experienced recurrence. The univariate analysis suggested that locoregional recurrence was associated with tumor size, multifocality, extrathyroidal extension (ETE), lymph node metastasis, lymphatic invasion, vascular invasion, and positive surgical margin. However, multivariate analysis showed that only tumor size (p < 0.001), bilaterality (p < 0.001), gross ETE (p = 0.049), lymph node metastasis (p < 0.001), and vascular invasion (p = 0.013) were independently associated with locoregional recurrence. CONCLUSIONS: Tumor size, bilaterality, gross ETE, lymph node metastasis, and vascular invasion were associated with locoregional recurrence. Evaluation of these prognostic factors appears to help identify patients who require close monitoring.

Protocol of a thyroid cancer longitudinal study (T-CALOS): a prospective, clinical and epidemiological study in Korea.

INTRODUCTION: Thyroid cancer incidence in Korea is the highest in the world and has recently increased steeply. However, factors contributing to this sudden increase have not been fully elucidated, and few studies have explored the postoperative prognosis. The Thyroid Cancer Longitudinal Study (T-CALOS) was initiated with three aims: (1) to identify factors predicting quality of life, recurrence, and incidence of other diseases after thyroid cancer treatments; (2) to investigate environmental exposure to radiation, toxicants and molecular factors in relation to tumour aggressiveness; and (3) to evaluate gene-environment interactions that increase thyroid cancer in comparison with healthy participants from a pool of nationwide population-based healthy examinees. METHODS AND ANALYSIS: T-CALOS enrols patients with incident thyroid cancer from three general hospitals, Seoul National University Hospital, Seoul National University Bundang Hospital and National Medical Center, Korea. The study is an ongoing project expecting to investigate 5000 patients with thyroid cancer up until 2017. Healthy examinees with a normal thyroid confirmed by sonography have been enrolled at the Healthy Examination Center at Seoul National University Hospital. We are also performing individual matching using two nationwide databases that are open to the public. Follow-up information is obtained at patients' clinical visits and by linkage to the national database. For statistical analysis, we will use conditional logistic regression models and a Cox proportional hazard regression model. A number of stratifications and sensitivity analyses will be performed to confirm the results. ETHICS AND DISSEMINATION: Based on a large sample size, a prospective study design, comprehensive data collection and biobank, T-CALOS has been independently peer-reviewed and approved by the three hospitals and two funding sources (National Research Foundation of Korea and Korean Foundation for Cancer Research). The results of T-CALOS will be published according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) criteria.

Indocyanine green as a near-infrared fluorescent agent for identifying parathyroid glands during thyroid surgery in dogs.

BACKGROUND: Surgical procedures involving the thyroid gland require identification of the parathyroid glands. Indocyanine green (ICG) is a near-infrared (NIR) fluorescent contrast agent used for a variety of procedures such as intraoperative angiography, extrahepatic cholangiography, and lymph node mapping. In this study, we used a canine model to evaluate ICG for NIR fluorescent imaging of the parathyroid gland. METHODS: Three dogs were used for the study. The dogs were administered general anesthesia, and after surgical dissection, each dog received a series of intravenous ICG doses ranging from 12.5 to 100 µg/kg ICG. The excitation light source used to illuminate the operating field was a NIR laser (λ = 785 nm). Intravascular ICG fluorescence (λ = 835/45 nm) was recorded using a charge-coupled device that employed optical filtering to block ambient and laser light. Fluorescent imaging was assessed after injection of each dose of ICG. RESULTS: NIR fluorescent imaging visualized the parathyroid glands. The intensity curves showing the peak and plateau of fluorescence are similar regardless of the concentration of ICG. The time to peak fluorescent intensity was 50.2 ± 2.0 s after injection of ICG. Taking into consideration background fluorescent intensity, the estimated optimal dose of ICG was 18.75 µg/kg. At 106.7 ± 5.8 s, the parathyroid glands lost much of their fluorescence, although they remained sufficiently fluorescent to be distinguishable. There was a positive correlation of fluorescent intensity with ICG dose escalation up to 25 µg/kg. CONCLUSIONS: ICG NIR fluorescent imaging was useful in detecting the parathyroid glands of dogs. By allowing detection of parathyroid glands, the current technique shows promise for use by endocrine surgeons performing thyroidectomies.

Comparison of 4D CT, ultrasonography, and 99mTc sestamibi SPECT/CT in localizing single-gland primary hyperparathyroidism.

OBJECTIVE: The present study was designed to evaluate 4D computerized tomography (CT) as a means of localizing abnormal parathyroid glands in primary hyperparathyroidism (HPT). STUDY DESIGN: Case series with expertized image review. SETTING: Tertiary care hospital. SUBJECTS AND METHODS: A total of 38 patients were recruited for study, all of whom had undergone focused parathyroidectomy for single-lesion primary HPT between June 2011 and September 2013. In each patient, 3 imaging procedures were performed: cervical ultrasonography (US), 99mTc-sestamibi SPECT/CT (SeS), and 4D CT. Collective imaging data were blindly reviewed and compared. RESULTS: 4D CT outperformed US and SeS in terms of sensitivity (P=.27), specificity (P=.01), positive predictive value (PPV) (P<.01), negative predictive value (NPV) (P=.19), and accuracy (P<.01). In 7.9% (3/38) of patients, 4D CT provided specific anatomic information that was unaffordable by US and SeS. Localization by 4D CT correlated with tissue parathyroid hormone level (P=.02), maximum diameter (P=.01), and volume (P<.01) of abnormal parathyroid glands. CONCLUSION: 4D CT proved helpful in localizing target parathyroid glands of primary HPT that were missed by traditional imaging.

Differences in the characteristics of papillary thyroid microcarcinoma ≤5 mm and >5 mm in diameter.

BACKGROUND: The behavior and optimal management of papillary thyroid microcarcinomas (PTMCs) after thyroidectomy remain unclear. The purpose of this study was to compare the clinicopathologic features and tumor recurrence rates of patients with PTMCs ≤5 mm and >5 mm in diameter after total thyroidectomy. METHODS: A group of patients with PTMCs ≤5 mm (n=83) has been compared to a group with >5 mm (n=122). All of these patients had conventional type PTMCs and were followed up for 5 years. Both the histology and the outcome have been compared. RESULTS: Sex (p=.014) and extrathyroidal extension (p=.003) of patients in the ≤5 mm and >5 mm groups differed significantly. Two and 5 patients from these groups, respectively, experienced tumor recurrence within 5 years (2.4% vs 4.1%; p=.634). CONCLUSION: The clinicopathologic features of PTMCs ≤5 mm and >5 mm are similar, except for sex distribution and extrathyroidal extension. The 5-year recurrence rate in the 2 groups did not differ significantly.

Helicopter patient transportation service on the Ulleung Island, South Korea.

INTRODUCTION: Despite numerous studies of helicopter emergency medical services, few reports have examined the outcomes of patients transported by helicopter across the sea from isolated islands. We analyzed helicopter transportation from the isolated Ulleung Island, which lies to the east of the South Korean mainland. METHODS: This study included 284 patients transported from the Ulleung Island to mainland hospitals between January 2007 and March 2013. Emergency Severity Index and Injury Severity Score were calculated. Hospital stay time and flight duration was measured. Data were analyzed using Student's t-test. RESULTS: The mean age of the patients was 53.5 years. Of the transported patients, 19.0% were visitors to the island and 29.6% were traumatically injured. The mortality rate after transportation was 11.6% (33 patients). CONCLUSION: Helicopter transportation has been very beneficial for the treatment of emergency patients on Ulleung Island. A national level of interest and investment is required to improve this service.