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.

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.

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.

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.

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.

BRAF mutation in follicular variant of papillary thyroid carcinoma is associated with unfavourable clinicopathological characteristics and malignant features on ultrasonography.

OBJECTIVE: Follicular variant of papillary thyroid carcinoma (FVPTC) is a common variant of papillary thyroid carcinoma (PTC), but the association between BRAF mutation and the clinicopathological and ultrasonographical characteristics of FVPTC has not been well studied. The aim of this study was to determine the significance of BRAF mutation in FVPTC. PATIENTS: The medical records of the 137 patients with >5 mm FVPTCs and known BRAF mutation status in the interested nodule were reviewed. BRAF mutation analysis was performed routinely and prospectively by Sanger sequencing. Clinicopathological and ultrasonographical characteristics were compared between BRAF mutation-positive and BRAF mutation-negative groups. RESULTS: BRAF mutation was detected in 35 (25·5%) patients. The BRAF mutation-positive group was associated with smaller tumour size (P = 0·022), extrathyroidal extension (P = 0·001), multifocality (P = 0·046) and higher (III/IV) TNM stages (P = 0·005). In multivariable analysis, higher (III/IV) TNM stage was an independent predictive factor for BRAF mutation-positive status (adjusted OR 2·966, 95% CI 1·321-6·663). In diagnosis of FVPTC, the presence of BRAF mutation was associated with malignant features on ultrasonography (P < 0·001) and higher incidence of suspicious for malignancy or malignant diagnosis on the fine needle aspiration cytology (P = 0·023). Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of US for detecting BRAF mutation were 82·9%, 57·8%, 40·3%, 90·8% and 64·2%, respectively. Conclusions BRAF mutation in FVPTC is associated with unfavourable clinicopathological characteristics and malignant features on ultrasonography and may be a potential prognostic factor as it is in classical PTC.

Current status of robotic thyroid surgery in South Korea: a web-based survey.

BACKGROUND: More than 8,000 cases of robotic thyroidectomy (RoT) were performed in South Korea from 2007 to 2011 using either a transaxillary approach (TAA) or a bilateral axillo-breast approach (BABA). However, there is no consensus regarding patient selection for RoT. This study used a web-based survey questionnaire to examine the current status of RoT in South Korea. METHODS: Thirty-two of 50 surgeons (64.0 %) who had performed RoT in South Korea participated in the web-based survey in August 2011. The questionnaires comprised four main domains: surgeon characteristics, surgical approach, patient selection, and future prospects. RESULTS: In terms of surgical approach, 43.8 % respondents used the TAA method and 53.1 % used the BABA method. The main advantage cited by surgeons using the TAA method was that it made lateral lymph node dissection easier (35.7 %), whereas those using the BABA method cited more cosmesis (100 %) and ease of performing a contralateral thyroidectomy (88.2 %). Papillary thyroid cancer ≤2 cm (65.3 %), intracapsular lesion (76.7 %), nonposterior location (53.6 %), and no clinical evidence of lateral lymph node metastasis (76.7 %) were cited as main indications for RoT. Of respondents, 87.5 % agreed that RoT would play a future role as a treatment modality for thyroid disease. CONCLUSIONS: Opinions differed regarding the advantages and disadvantages of two approaches for RoT. This may be due to differences in surgical procedure itself between two approach methods. Accumulation of RoT surgeon's experiences might establish consensus regarding patient selection and indications for the RoT will need to be further investigated.

Papillary thyroid carcinoma located in the isthmus or upper third is associated with Delphian lymph node metastasis.

BACKGROUND: Delphian lymph node (DLN) metastasis is a recognized indicator of further lymph node involvement in papillary thyroid carcinoma (PTC). The aim of this study was to evaluate the clinicopathological significance of and risk factors for DLN metastasis. METHODS: The medical records of 1,436 patients who underwent primary thyroidectomy for classical PTC with a tumor size of 2 cm or less were reviewed. Of these, 370 patients from whom the DLN was harvested were enrolled. Metastasis in DLN was present in 46 patients and absent in 324 patients. Clinicopathological features were compared according to DLN metastasis. RESULTS: In univariate analysis, DLN metastasis was associated with suspected lymph node metastasis on preoperative ultrasonography, tumor location in the isthmus or upper third of the thyroid, larger tumor size, extrathyroid extension, lymphovascular invasion, and further lymph node metastasis. Multivariable analysis revealed that DLN metastasis was associated with tumor location in the isthmus or upper third of the thyroid (odds ratio [OR] = 2.420; 95 % confidence interval [CI] 1.193-4.910) and further lymph node metastasis (OR = 4.746; 95 % CI 2.065-10.908). CONCLUSIONS: DLN metastasis in PTC is associated with tumor location in the isthmus or upper third of the thyroid and unfavorable clinicopathological characteristics. Careful consideration and patient management are warranted when preoperative ultrasonography indicates that the tumor is located in the isthmus or upper third of the thyroid.

Use of spiral computed tomography volumetry for determining the operative approach in patients with Graves' disease.

BACKGROUND: The purposes of the present study were to assess (1) the correlation between the weight of the postoperative thyroid specimen and the spiral computed tomography (CT) volumetry results of the thyroid gland in patients with Graves' disease, and (2) the utility of CT volumetry for determining the operative approach. METHODS: From 2009 to 2010, a total of 56 patients with Graves' disease underwent total or subtotal thyroidectomy. An enhanced spiral CT was taken in all patients prior to the operation. From 2.5 mm-thick slices of the thyroid gland, the surface area was calculated to measure the volume of the thyroid gland. The glandular volume was compared to the weight of the postoperative thyroid specimen. RESULTS: A total of 42 and 14 patients underwent total and subtotal thyroidectomy, respectively. The mean weight of the postoperative thyroid specimen was 43.9 ± 33.4 g, and the mean volume obtained by CT volumetry was 44.2 ± 32.8 mL. A good correlation was observed between the weight of the postoperative thyroid specimen and the volume calculated by CT (r = 0.98, p < 0.001). When 100 mL was set as the higher cut-off value of the thyroid volume for minimally invasive thyroid surgery, the estimated blood loss showed a significant difference between the >100 mL and the ≤100 mL groups (608.3 ± 540.8 vs. 119.7 ± 110.4 mL; p = 0.036). CONCLUSIONS: Spiral CT volumetry may be used to measure the thyroid volume reliably in patients with Graves' disease. For cases in which surgery is indicated in patients with Graves' disease, CT volumetry provides useful information from which to determine the operative approach. One hundred milliliter or less of thyroid volume in CT volumetry is recommended to perform minimally invasive thyroid surgery.

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.

Activation of NF-κB pathway in oral buccal mucosa during small intestinal ischemia-reperfusion injury.

BACKGROUND: Intestinal ischemia-reperfusion injury induces intestinal mucosal barrier disruption, systemic inflammatory response syndrome, multiorgan failure, and death. The major pathway for the systemic inflammatory responses depends on nuclear factor kappa B (NF-κB). However, direct measuring of NF-κB in injured tissues is not routinely available. Our aim was to determine whether NF-кB pathway in buccal mucosa is activated during intestinal ischemia-reperfusion injury. MATERIALS AND METHODS: Male Sprague-Dawley rats were prepared for the animal experiment. Superior mesenteric artery (SMA) was exposed and clamped for 30 min in the intestinal ischemia-reperfusion (IR) group. SMA was exposed only in control group. Serum, buccal mucosa, and small intestinal mucosa were harvested in 90 min after reperfusion in IR or 120 min after SMA exposure in control group. Serum cytokine levels and tissue NF-κB pathway activities were measured. RESULTS: Serum TNF-α (5.49 ± 2.72 versus 1.77 ± 1.20 pg/mL, P = 0.002) and interleukin-6 (232.32 ± 29.98 versus 115.92 ± 17.81 pg/mL, P = 0.002) levels were significantly higher in IR than control group. Intestinal mucosal cytoplasmic phosphorylated inhibitor kappa B (IκB)/IκB ratio, nuclear NF-κB expression, and NF-κB DNA-binding activity were significantly higher in IR than control group. Buccal mucosal cytoplasmic phosphorylated IκB/IκB ratio, nuclear NF-κB expression, and NF-κB DNA-binding activity were also higher in IR than control group. CONCLUSION: Buccal mucosal NF-κB pathway was activated by intestinal ischemia-reperfusion injury. The present study suggests that buccal mucosal may be considered as an indicator for the assessment of intestinal ischemia-reperfusion injury.

Robotic thyroidectomy by bilateral axillo-breast approach: review of 1,026 cases and surgical completeness.

BACKGROUND: Good postoperative and excellent cosmetic results have been achieved with bilateral axillo-breast approach (BABA) robotic thyroidectomy (RoT). This study was performed to analyze the surgical outcomes and evaluate the surgical completeness and safety of BABA RoT. METHODS: Between February 2008 and February 2012, a total of 1026 cases of BABA RoT were performed. The clinicopathologic characteristics, operation types, and postoperative outcomes of patients were analyzed. RESULTS: Of the 1026 cases analyzed, 968 cases were a malignant tumor and 58 cases were benign thyroid disease. Mean operating times for BABA total RoT with central lymph node dissection included 38 ± 13 min (range 20-90 min) of working space creation and 75 ± 26 min (range 25-175) of console time. Among the 872 patients who underwent total thyroidectomy with central lymph node dissection, transient hypoparathyroidism occurred in 39.1 %, transient vocal cord palsy occurred in 14.2 %, and permanent hypoparathyroidism and permanent vocal cord palsy occurred in 1.5 % and 0.2 % of patients, respectively. The median stimulated thyroglobulin (Tg) level of patients after their first radioactive iodine therapy was 0.4 ng/mL, with 65.1 % of patients having a stimulated Tg level of <1.0 ng/mL. The median suppressed Tg level at 3 postoperative months of patients without radioactive iodine therapy was <0.1 ng/mL, with 99.4 % of patients showing a suppressed Tg level of< 1.0 ng/mL. There was no recurrence or mortality after a median follow-up of 23 months. CONCLUSIONS: BABA RoT is a safe and effective method that provides good surgical completeness and has low rates of postoperative complications and recurrence.

Bilateral axillo-breast approach robotic thyroidectomy for Graves' disease: an initial experience in a single institute.

BACKGROUND: Bilateral axillo-breast approach (BABA) robotic thyroidectomy has shown excellent cosmetic and surgical outcomes. The aim of the present study was to evaluate the safety, feasibility, and initial outcome of this procedure in patients with Graves' disease. METHODS: From June 2008 to July 2001, a total of 30 patients with Graves' disease were reviewed retrospectively. Patient demographics, operative indications, and surgical variables, including operative time, blood loss, excised thyroid weight, and complications, were collected and investigated. RESULTS: The thyroidectomies were classified as total (n = 21), near-total (n = 6), or subtotal (n = 3). There were five indications for surgery: concomitant thyroid carcinoma or suspicious nodule (n = 22), recurrence after antithyroid medication (n = 2), local compressive symptoms (n = 1), patient's preference (n = 4), and side effects of antithyroid medication (n = 1). The mean operative time, console time, blood loss, and excised thyroid weight were 190 min (range: 105-298 min), 113 min (range: 60-227 min), 229 mL (range: 50-550 mL), and 36.6 g (range: 7.8-123.0 g), respectively. There were no cases of postoperative bleeding or conversions to open surgery. Postoperative transient hypoparathyroidism and vocal cord palsy occurred in 13 (43.3 %) and 4 (13.3 %) cases. Permanent hypoparathyroidism occurred in 1 (3.3 %) case. All patients were satisfied with the cosmetic outcomes. CONCLUSIONS: BABA robotic thyroidectomy is a feasible and safe treatment for Graves' disease. It is recommended as an alternative for patients who are concerned by the cosmetic effects of traditional thyroidectomy.

Risk factors of hypoparathyroidism following total thyroidectomy for thyroid cancer.

BACKGROUND: The risk factors responsible for hypoparathyroidism after total thyroidectomy have not been completely defined. The present study evaluated one surgeon's personal experience of postoperative hypoparathyroidism after total thyroidectomy for thyroid cancer and predisposing risk factors of postoperative hypoparathyroidism. METHODS: We performed a retrospective analysis of 531 consecutive total thyroidectomy cases for thyroid cancer operated by single surgeon at the Center for Thyroid Cancer, National Cancer Center, Korea, from March 2003 to August 2006. RESULTS: Postoperative hypoparathyroidism occurred in 135 patients (25.4 %), 19 of whom (3.6 % of total patients) experienced permanent hypoparathyroidism. Parathyroid autotransplantation, bilateral central lymph node dissection, gross extrathyroidal extension, and the presence of parathyroid gland in the pathologic specimen were associated with postoperative hypoparathyroidism in multivariate analysis (p < 0.05, respectively). The presence of parathyroid gland in the pathologic specimen and the early period of surgeon's practice were statistically significant risk factors for permanent hypoparathyroidism in multivariate analysis (p < 0.05, respectively). CONCLUSIONS: Careful surgical technique for in situ preservation of parathyroid gland and autotransplantation of inadvertently removed parathyroid gland are important, especially in case of gross extrathyroidal extension. Adequate surgical experience is also an important factor. And routine bilateral central lymph node dissection should be done thoughtfully for its effect on postoperative hypoparathyroidism.

Prospective study of sensation in anterior chest areas before and after a bilateral axillo-breast approach for endoscopic/robotic thyroid surgery.

BACKGROUND: The bilateral axillo-breast approach for endoscopic/robotic thyroid surgery (BABA) shows good oncologic and surgical outcomes and does not result in neck scars. However, there is concern about potential sensory changes of the skin flaps after BABA, especially of the breast areas. This prospective study was undertaken to evaluate sensory changes in the skin flaps after BABA. PATIENTS AND METHODS: A total of 19 women (mean age 36.9 ± 8.7; age range 21-51 years) who underwent BABA were enrolled. Skin flap sensory assessments were performed for each patient preoperatively and again at 1 and 3 months postoperatively. The Semmes-Weinstein monofilament test was used to evaluate the cutaneous light-pressure thresholds, a biothesiometer was used to evaluate the vibration thresholds, and an infrared thermometer was used to measure skin temperatures of the skin flaps. RESULTS: There were changes in the sensations of the anterior chest areas over time, as determined by the Semmes-Weinstein monofilament test (1.5 vs 4.3 versus 1.4; P < 0.05) and the biothesiometer (26.8 vs 31.2 vs 22.3; P < 0.05). The sensations in the anterior chest areas normalized to preoperative levels at 3 months postoperatively. No significant differences were seen in the infrared thermometer test at any of the time points (36.2 vs 36.2 vs 36.3 °C; P = 0.9927). CONCLUSIONS: While anterior chest area sensations were changed at 1 month postoperatively, the sensations normalized at 3 months after BABA. These results suggest that BABA has minimal adverse effects on anterior chest area sensation.

The association of the BRAF(V600E) mutation with prognostic factors and poor clinical outcome in papillary thyroid cancer: a meta-analysis.

BACKGROUND: The effects of the BRAF(V600E) mutation on prognostic factors and poor clinical outcomes in papillary thyroid cancer (PTC) have not been fully quantified. The authors performed comprehensive meta-analysis to assess the strength of associations between these conditions and the BRAF(V600E) mutation. METHODS: The authors identified the clinical studies that examined the association of the BRAF(V600E) mutation in surgical specimens with clinicopathologic outcomes between January 2003 and October 2010 using the Medline database. One hundred thirty-one relevant studies were hand-searched. The authors selected 27 studies that included 5655 PTC patients. They calculated the pooled odds ratios (ORs) or risk ratios with 95% confidence intervals (CIs) for each study using a random effect model. RESULTS: The average prevalence rate of the BRAF(V600E) mutation was 49.4%. In 26 studies, compared with the patients who had the wild-type BRAF genes, the PTC patients with the BRAF(V600E) mutation had increased ORs of an extrathyroidal invasion (OR, 2.14; 95% CI, 1.68-2.73), a lymph node metastasis (OR, 1.54; 95% CI, 1.21-1.97), and an advanced TNM stage (OR, 2.00; 95% CI, 1.61-2.49). In 8 studies, patients with the mutation had 2.14-fold increased risk of recurrent and persistent disease (95% CI, 1.67-2.74). The associations were generally consistent across the different study populations. CONCLUSIONS: This meta-analysis demonstrates that the BRAF(V600E) mutation is closely related to the high-risk clinicopathological factors and poorer outcome of PTC. The results obtained here suggest that the BRAF(V600E) mutation should be considered as a poor prognostic marker in PTC and may lead to better management for individual patients.

Endoscopic thyroidectomy via bilateral axillo-breast approach (BABA): review of 512 cases in a single institute.

BACKGROUND: Various techniques for endoscopic thyroidectomy have been introduced in the past decade, and the cosmetic superiority of these techniques has been universally acknowledged. We developed the endoscopic thyroidectomy via bilateral axillo-breast approach (BABA) and have performed more than 500 operations. The aims of this study are to analyze the surgical outcomes and to evaluate the effectiveness and safety of BABA endoscopic thyroidectomy. PATIENTS AND METHODS: Between February 2004 and March 2008, 512 patients with thyroid diseases underwent BABA endoscopic thyroidectomy. The criteria analyzed were clinicopathologic characteristics, types of operation, operation time, tumor-node-metastasis (TNM) stage on the basis of the 7th edition of the American Joint Committee on Cancer (AJCC), results after radioactive ablation therapy, and recurrence of disease in these patients. RESULTS: Of 512 patients, 397 had a malignant tumor and 115 had benign thyroid disease. Eight patients were diagnosed with Graves' disease, and nine patients underwent completion thyroidectomy. Three cases were subjected to open thyroidectomy due to uncontrolled bleeding. Mean operation time was 151.2 ± 38.1 min for total and near-total thyroidectomy, and 141.7 ± 50.1 min for subtotal thyroidectomy and lobectomy. Regarding postoperative complications, transient hypocalcemia occurred in 31.1% of patients and permanent hypoparathyroidism occurred in 4.2% of patients. Transient hoarseness occurred in 20.3% of patients, and permanent vocal cord palsy occurred in 1.7%. Mean hospital stay after operation was 3.34 ± 0.8 days (range 3-7 days), and mean follow-up period was 57.1 ± 17.6 months (range 38.5-71.7 months). There were eight cases of recurrent thyroid carcinoma, and no mortality has occurred up to the present time. CONCLUSIONS: Endoscopic thyroidectomy via bilateral axillo-breast approach is a safe and effective method that gives good surgical completeness, a low rate of postoperative complications and recurrence, and an excellent cosmetic result. Therefore, this method is a good choice for patients with surgical thyroid diseases.

Value of adrenal venous sampling for lesion localization in primary aldosteronism.

BACKGROUND: Distinguishing between unilateral and bilateral adrenal lesions is mandatory for surgical treatment of primary aldosteronism (PA). Adrenal venous sampling (AVS) is considered the gold standard for identification and localization of the lesion or lesions causing PA. The objective of the present study was to determine the usefulness of AVS in PA patients. PATIENTS AND METHODS: From January 2001 to October 2011, 86 patients with the biochemical diagnosis of PA were retrospectively analyzed. The study group included 45 males and 41 females with a mean age of 50.7 ± 12.6 years, and all patients underwent adrenal computed tomography (CT) and AVS. RESULTS: The catheterization success rate of AVS was 82.69 % (86/104). In addition, AVS revealed bilateral lesions in 15/75 patients with unilateral abnormalities diagnosed by CT. These patients underwent medical treatment instead of surgery. One patient had an adrenal mass on the right side, but AVS localized the lesion on the left side. This patient underwent left adrenalectomy. Furthermore, AVS revealed a unilateral lesion in 2/5 patients with bilateral abnormalities demonstrated by CT. These patients underwent unilateral adrenalectomy. Finally, AVS demonstrated localization in 1/6 of patients with no CT abnormalities who were subjected to surgery. Fifty-three patients with unilateral lesion and one patient with bilateral hypersecretion underwent surgical removal of the affected gland(s). All patients had resolution of hypokalemia and clinical improvement of hypertension. CONCLUSIONS: Many patients (19/86, or 22.09 %) would have been inappropriately managed if decision making had been based solely on CT findings. Therefore, AVS is recommended before determining definitive PA management.

BRAF V600E mutation is associated with tumor aggressiveness in papillary thyroid cancer.

BACKGROUND: The BRAF(V600E) mutation is the most common genetic alteration found in papillary thyroid cancer (PTC). Recent studies show that this mutation occurs more frequently in patients with PTC showing aggressive clinicopathologic features. The aim of the present study was to evaluate the prevalence of the BRAF(V600E) mutation in tumor samples and its association with high-risk clinicopathologic features prospectively. PATIENTS AND METHODS: From February 2009 to January 2010, 547 PTC patients who underwent surgery in Seoul National University Hospital were enrolled in the study. Polymerase chain reaction was used to amplify exon 15 of the BRAF gene from paraffin-embedded thyroid tumor specimens, followed by direct sequencing to detect the BRAF(V600E) mutation. Both univariate and multivariate analyses were performed to analyze associations between the BRAF(V600E) mutation and clinicopathologic features. RESULTS: The BRAF(V600E) mutation was found in 381/547 (69.7%) patients with primary PTC. The BRAF(V600E) mutation was significantly associated with age (≥ 45 years), tumor size (>1 cm), extrathyroidal extension, and cervical lymph node metastases (P < 0.05). Multiple logistic regression showed that it was significantly associated with gender (OR = 1.834; 95% CI 1.021-3.463), tumor size (OR = 1.972; 95% CI 1.250-3.103), and extra-thyroidal extension (OR = 2.428; 95% CI 1.484-3.992), but not with age, multifocality, lymph node metastases, and advanced disease stage. The proportion of BRAF(V600E) mutation was significantly associated with the number of high-risk factors of tumor recurrence (P < 0.001). CONCLUSIONS: The BRAF(V600E) mutation was associated with high-risk clinicopathologic characteristics in patients with PTC. The BRAF(V600E) mutation may be a potential prognostic factor in PTC patients.

Antiproliferation and redifferentiation in thyroid cancer cell lines by polyphenol phytochemicals.

Thyroid carcinogenesis is accompanied by loss of thyroid-specific functions and refractory to radioiodine and thyroid stimulating hormone (TSH) suppression therapy. Redifferentiating agents have been shown to inhibit tumor growth and improve the response to conventional therapy. Polyphenol phytochemicals (PPs) in fruits and vegetables have been reported to inhibit cancer initiation, promotion, progression and induce redifferentiation in selected types. In this study we examined PPs induce redifferentiation in thyroid cancer cell lines. We investigated the effects of genistein, resveratrol, quercetin, kaempferol, and resorcinol on the F9 embryonal carcinoma cell differentiation model. The thyroid cancer cell lines, TPC-1, FTC-133, NPA, FRO, and ARO, displayed growth inhibition in response to genistein, resveratrol, quercetin. We further demonstrated that genistein decreased the dedifferention marker CD97 in NPA cells and resveratrol decreased CD97 in FTC-133, NPA, FRO cells and quercetin decreased CD97 in all cell lines. We observed increased expression of differentiation marker NIS in FTC-133 cells in response to genistein, and resveratrol but no change in NPA, FRO, ARO cells. Quercetin increased or induced NIS in FTC-133, NPA, FRO cells. These findings suggest that PPs may provide a useful therapeutic intervention in thyroid cancer redifferentiation therapy.