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1.  Systematic Review of Surgical Approaches for Adrenal Tumors: Lateral Transperitoneal versus Posterior Retroperitoneal and Laparoscopic versus Robotic Adrenalectomy 
Background. Laparoscopic lateral transperitoneal adrenalectomy (LTA) has been the standard method for resecting benign adrenal gland tumors. Recently, however, laparoscopic posterior retroperitoneal adrenalectomy (PRA) has been more popular as an alternative method. This systematic review evaluates current evidence on adrenalectomy techniques, comparing laparoscopic LTA with PRA and laparoscopic adrenalectomy with robotic adrenalectomy. Methods. PubMed, Embase, and ISI Web of Knowledge databases were searched systematically for studies comparing surgical outcomes of laparoscopic LTA versus PRA and laparoscopic versus robotic adrenalectomy. The studies were evaluated according to the PRISMA statement. Results. Eight studies comparing laparoscopic PRA and LTA showed that laparoscopic PRA was superior or at least comparable to laparoscopic LTA in operation time, blood loss, pain score, hospital stay, and return to normal activity. Conversion rates and complication rates were similar. Six studies comparing robotic and laparoscopic adrenalectomy found that outcomes and complications were similar. Conclusion. Laparoscopic PRA was more effective than LTA, especially in reducing operation time and hospital stay, but there was no evidence showing that robotic adrenalectomy was superior to laparoscopic adrenalectomy. Cost reductions and further technical advances are needed for wider application of robotic adrenalectomy.
PMCID: PMC4281398  PMID: 25587275
2.  Can Robotic Thyroidectomy Be Performed Safely in Thyroid Carcinoma Patients? 
Endocrinology and Metabolism  2014;29(3):226-232.
Since the adoption of the Da Vinci robotic system for remote access thyroid surgery, robotic thyroidectomy (RT) has become a popular surgical option for patients who want to avoid neck scars. Surgeons in South Korea pioneered this surgical technique and have reported successful outcomes. Although many studies have reported that RT is a feasible and safe therapeutic alternative, concerns over the surgical and oncological safety of RT remain. This article reviews the advantages and disadvantages of RT and compares the surgical safety and oncological completeness of RT with conventional open thyroidectomy.
PMCID: PMC4192813  PMID: 25309779
Thyroid neoplasms; Robotic thyroidectomy; Robot-assisted thyroidectomy; Transaxillary thyroidectomy; Bilateral axillo-breast approach
3.  Antiadhesive effect and safety of sodium hyaluronate-carboxymethyl cellulose membrane in thyroid surgery 
A number of researchers have suggested the use of sodium hyaluronate carboxymethyl cellulose (HA-CMC) membrane for preventing postoperative adhesion. This study evaluated the antiadhesive effect and safety of HA-CMC membrane in thyroidectomy for papillary thyroid cancer.
One hundred sixty-two patients who underwent thyroidectomy were prospectively randomized. In the study group of 80 patients, the 7.5 cm × 13 cm HA-CMC membrane was applied to the operative field after thyroidectomy. The subjects were asked about complications including adhesive symptoms using an 8-item questionnaire at 2 weeks, 3 months, and 6 months after surgery. In addition, items on the appearance of neck wrinkles and scars were evaluated by a physician who had no information about the patient's allocation.
There were no significant differences in complications such as swallowing difficulty, and wrinkles between study and control groups. Both groups presented significantly decreased scores over time in swallowing difficulty, and wrinkles. There were no complications regarding the HA-CMC membrane.
The antiadhesive effect of HA-CMC membrane in thyroid surgery is still uncertain, although it is biologically safe. Further investigation is needed to confirm the antiadhesive effect of HA-CMC membrane in thyroid surgery.
PMCID: PMC3834017  PMID: 24266009
Sodium hyaluronate carboxymethyl cellulose; HA-CMC; Seprafilm; Adhesion; Thyroid
4.  Role of charcoal tattooing in localization of recurred papillary thyroid carcinoma: initial experiences 
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.
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.
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.
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.
PMCID: PMC4347043  PMID: 25741493
Thyroid neoplasms; Charcoal; Tattooing; Reoperation; Recurrence
5.  Optimal Cutoff Age for Predicting Mortality Associated with Differentiated Thyroid Cancer 
PLoS ONE  2015;10(6):e0130848.
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.
PMCID: PMC4477980  PMID: 26102084
6.  Feasibility of implementing a surgical student internship program in South Korea 
Despite recommendations for introducing student internships (SI) in undergraduate medical education in Korea, the feasibility of surgical SIs has not been demonstrated in the Korean context. We thus identified tasks that could be performed by surgical student interns in a Korean education hospital.
The opinions of surgery clerkship directors of medical schools nationwide, regarding the tasks, symptoms and signs, disease entities, and procedures that student interns could perform in their hospitals, were subjected to descriptive analysis.
Out of the 41 medical schools in Korea, 32 responded. Five implemented an optimal-quality SI program. Two schools considered third-year clerkship as SI. The respondents replied that student interns could be involved in basic nonspecific tasks such as history taking, physical examination, medial recording, reporting patients' status, and assisting during surgery. However, more surgery-specific tasks such as perioperative management or caring for a patient with acute abdominal pain were considered difficult for student interns to encounter in the Korean context.
Surgical educators should determine a specific role for student interns and encourage them to perform surgery-specific tasks. We recommend societal and system support, and curriculum renovation to establish an SI program in Korea.
PMCID: PMC4384287  PMID: 25844351
Undergraduate medical education; Clinical competence; Clinical clerkship
7.  The Frequency and Clinical Implications of the BRAFV600E Mutation in Papillary Thyroid Cancer Patients in Korea Over the Past Two Decades 
Endocrinology and Metabolism  2014;29(4):505-513.
Over the past several decades, there has been a rapid worldwide increase in the prevalence of papillary thyroid cancer (PTC) as well as a number of changes in the clinicopathological characteristics of this disease. BRAFV600E, which is a mutation of the proto-oncogene BRAF, has become the most frequent genetic mutation associated with PTC, particularly in Korea. Thus, the present study investigated whether the prevalence of the BRAFV600E mutation has increased over the past two decades in the Korean population and whether various PTC-related clinicopathological characteristics have changed.
The present study included 2,624 patients who underwent a thyroidectomy for PTC during two preselected periods; 1995 to 2003 and 2009 to 2012. The BRAFV600E mutation status of each patient was confirmed using the polymerase chain reaction-restriction fragment length polymorphism method or by the direct sequencing of DNA.
The prevalence of the BRAFV600E mutation in Korean PTC patients increased from 62.2% to 73.7% (P=0.001) over the last two decades. Additionally, there was a greater degree of extrathyroidal extension (ETE) and lymph node metastasis in 2009 to 2012 patients with the BRAFV600E mutation and a higher frequency of thyroiditis and follicular variant-PTC in 2009 to 2012 patients with wild-type BRAF. However, only the frequency of ETE was significantly higher in 1995 to 2003 patients with the BRAFV600E mutation (P=0.047). Long-term recurrence rates during a 10-year median follow-up did not differ based on BRAFV600E mutation status.
The BRAFV600E mutation rate in Korean PTC patients has been persistently high (approximately 70%) over the past two decades and continues to increase. The present findings demonstrate that BRAFV600E-positive PTC was associated with more aggressive clinicopathological features, especially in patients who were recently diagnosed, suggesting that BRAFV600E mutation status may be a useful prognostic factor for PTC in patients recently diagnosed with this disease.
PMCID: PMC4285045  PMID: 25325273
Thyroid cancer, papillary; BRAFV600E mutation; Prognosis
8.  Diabetes Mellitus and Risk of Thyroid Cancer: A Meta-Analysis 
PLoS ONE  2014;9(6):e98135.
Diabetes mellitus (DM) is an important risk factor for endocrine cancers; however, the association with thyroid cancer is not clear. We performed a systematic review and meta-analysis to clarify the association between thyroid cancer and DM.
We searched MEDLINE, PUBMED and EMBASE databases through July 2012, using search terms related to diabetes mellitus, cancer, and thyroid cancer. We conducted a meta-analysis of the risk of incidence of thyroid cancer from pre-existing diabetes. Of 2,123 titles initially identified, sixteen articles met our inclusion criteria. An additional article was identified from a bibliography. Totally, 14 cohort and 3 case-control studies were selected for the meta-analysis. The risks were estimated using random-effects model and sensitivity test for the studies which reported risk estimates and used different definition of DM.
Compared with individuals without DM, the patients with DM were at 1.34-fold higher risk for thyroid cancer (95% CI 1.11–1.63). However, there was heterogeneity in the results (p<0.0001). Sensitivity tests and studies judged to be high quality did not show heterogeneity and DM was associated with higher risk for thyroid cancer in these sub-analyses (both of RRs = 1.18, 95% CIs 1.08–1.28). DM was associated with a 1.38-fold increased risk of thyroid cancer in women (95% CI 1.13–1.67) after sensitivity test. Risk of thyroid cancer in men did not remain significant (RR 1.11, 95% CI 0.80–1.53).
Compared with their non-diabetic counterparts, women with pre-existing DM have an increased risk of thyroid cancer.
PMCID: PMC4057085  PMID: 24927125
9.  Clinical Effect of Surgical Correction for Nasal Pathology on the Treatment of Obstructive Sleep Apnea Syndrome 
PLoS ONE  2014;9(6):e98765.
This study aimed to evaluate the hypothesis that relief of nasal obstruction in subjects with obstructive sleep apnea (OSA) would lead to reduce OSA severity and to discuss the available evidence on the clinical efficacy of nasal surgery as a treatment modality for OSA.
Study Design
Twenty-five subjects who had reduced patency of nasal cavity and narrowing of retroglossal or retropalatal airways were diagnosed with OSA and underwent nasal surgery, such as septoplasty or turbinoplasty to correct nasal pathologies. The effect of the surgery on nasal patency was quantified by measuring minimal cross-sectional area (MCA) using acoustic rhinometry. The watch-PAT-derived respiratory disturbance index (RDI), apnea and hypopnea index (AHI), lowest oxygen saturation, and valid sleep time were measured before and after nasal surgery.
The present study shows that the AHI and RDI decreased significantly and the lowest oxygen saturation and valid sleep time rose after nasal surgery in 25 OSA subjects. In addition, a reduction in subjective symptoms was observed in subjects and mean MCA increased after nasal surgery. Fourteen subjects were classified as responders and 11 subjects as non-responders. Responders showed considerable improvement of their subjective symptoms and the AHI and RDI were significantly lower after surgery. We found that the changes between pre- and post-operative AHI and RDI values were minimal in 11 non-responders. However, daytime somnolence and REM sleep time improved after nasal surgery in non-responders.
Our study provides evidence that the surgical treatment of nasal pathology improves nasal airway patency and reduces OSA severity in 56% subjects. Furthermore, correction of nasal pathology appears to result in improved sleep quality in both responder and non-responders OSA subjects.
PMCID: PMC4045850  PMID: 24896824
10.  Role of adjuvant postoperative external beam radiotherapy for well differentiated thyroid cancer 
Radiation Oncology Journal  2013;31(3):162-170.
To analyze the outcome of adjuvant postoperative external beam radiotherapy (EBRT) in well-differentiated thyroid cancer (WDTC).
Materials and Methods
We identified 84 patients treated with EBRT for WDTC from February 1981 to December 2010. Among them, we analyzed 39 patients who received EBRT after initial radical surgery. Twenty-four females and 15 males were included. The median age was 49 years (range, 16 to 72 years). There were 34 papillary thyroid carcinomas and 5 follicular thyroid carcinomas. Most patients showed pathologic T3/T4 stage (54%/26%). Ten patients (25.6%) had gross residual tumors. Five patients (12.8%) had tumor cells at the margin. The median EBRT dose and fraction size were 62.6 Gy and 1.8 to 2.0 Gy, respectively.
The median follow-up was 73 months (range, 21 to 372 months). The five-year overall survival (OS) and locoregional recurrence free survival (LRFS) were 97.4% and 86.9%, respectively. Locoregional failures occurred in 5 and all failure sites were the neck node area. In univariate analysis, OS was significantly influenced by invasion of the trachea (p = 0.016) or esophagus (p = 0.006). LRFS was significantly decreased by male (p = 0.020), gross residuum after resection (p = 0.002), close or positive tumor at surgical margin involvement (p = 0.044), and tracheal invasion (p = 0.040). No significant prognostic factor was identified in the multivariate analysis. No patient experienced the Radiation Therapy Oncology Group grade 3 or more toxicity.
Our locoregional control rate of 87.2% is comparable to historical controls with surgery alone, even though our study had a large proportion of advanced stage. Adjuvant EBRT may an effective and safe treatment option in patients with WDTC.
PMCID: PMC3797276  PMID: 24137562
Papillary thyroid cancer; Follicular thyroid cancer; Radiotherapy; Adjuvant
11.  The Expression of Tumor-Associated Macrophages in Papillary Thyroid Carcinoma 
Endocrinology and Metabolism  2013;28(3):192-198.
Tumor-associated macrophages (TAMs) play a tumorigenic role related to advanced staging and poor prognosis in many human cancers including thyroid cancers. Yet, a functional role of TAMs in papillary thyroid carcinoma (PTC) has not been established. The aim of this study was to investigate TAM expression in human PTC with lymph node (LN) metastasis.
Thirty-six patients who underwent surgery after being diagnosed with PTC with LN metastasis were included. Primary tumor tissues were immunohistochemically stained with an anti-CD68 antibody and clinical characteristics according to TAM density were evaluated.
The TAM densities (CD68+ cells) varied from 5% to 70%, in all tumor areas, while few cells were stained in adjacent normal tissues. TAMs were identified as CD68+ cells with thin, elongated cytoplasmic extensions that formed a canopy structure over tumor cells. Comparing clinicopathologic characteristics between tumors with low (<25%) and high (25% to 70%) TAM densities, primary tumors were larger in the high density group than in the low density group (2.0±0.1 vs. 1.5±0.1; P=0.009).
TAMs were identified in primary PTC tumors with LN metastasis and higher TAM densities were related to larger tumor sizes, suggesting a tumorigenic role of TAMs in human PTCs.
PMCID: PMC3811699  PMID: 24396678
Tumor-associated macrophages; Thyroid cancer, papillary; Tumor size
12.  Antiadhesive effect and safety of oxidized regenerated cellulose after thyroidectomy: a prospective, randomized controlled study 
To evaluate the antiadhesive effects and safety of an oxidized regenerated cellulose (Interceed) after thyroidectomy.
Seventy-six thyroidectomized patients were prospectively randomized into two groups with regard to the use of Interceed. We evaluated each group for their adhesive symptoms using four subjective and four objective items at the 2nd week, 3rd and 6th month after thyroidectomy. All patients were examined for vocal cord motility by indirect laryngoscope at each period.
Total adhesion scores at each postoperative follow-up period decreased with time, but were not significantly different in each group. The median score for swallowing discomfort for liquid was significantly lower in the Interceed group than in the control group 2 weeks after surgery. In addition, the severity of skin adhesion to the trachea was reduced in the Interceed group compared with the control group 6 months after surgery. During the study, there were no adverse effects or significant differences in postoperative complications between the groups.
Interceed appeared to be safe and effective in improving neck discomfort at early postoperative periods and preventing skin adhesion to the trachea 6 months after thyroidectomy.
PMCID: PMC3671000  PMID: 23741689
Adhesion; Neck discomfort; Oxidized regenerated cellulose; Thyroidectomy
13.  Development of a canine model for recurrent laryngeal injury by harmonic scalpel 
Laboratory Animal Research  2012;28(4):223-228.
Various energy devices had been used in thyroid surgery. Aim of study is to develop canine model for recurrent laryngeal nerve injury by harmonic scalpel and to evaluate feasibility of using this model for evaluating the safety use of harmonic scalpel during thyroid surgery. Nine dogs were divided into 3 groups according to distance between harmonic scalpel application and recurrent laryngeal nerve; group 1 (1 mm), 2 (2 mm), and 3 (3 mm). Vocal cord function was assessed pre- and postoperatively using video laryngoscopy. Harmonic scalpel was applied adjacent to left recurrent laryngeal nerve and, two weeks later, right recurrent laryngeal nerve at assigned distances. Recurrent laryngeal nerves were evaluated for subacute and acute morphologic changes. Laryngoscopy demonstrated 3 abnormal vocal cords in group 1, 1 in group 2, and no in group 3 (P=0.020). Subacute histologic changes were observed in nerves with abnormal function. Acute histologic changes were observed 5/8 (62.5%) in group 1, 1/7 (14.3%) in group 2, and not in group 3. We developed canine model for recurrent laryngeal injury. The functional outcomes matched with the histologic changes. These warrant further study to determine the safety margin for energy device in vicinity of recurrent laryngeal nerve.
PMCID: PMC3542380  PMID: 23326282
Recurrent laryngeal nerve; canine model; harmonic scalpel; safety margin; nerve damage; ultrasonic shears
14.  Analysis of patients with anaplastic thyroid cancer expected to have curative surgery 
Anaplastic thyroid cancer (ATC) is rare and has a poor prognosis. The aim of this study was to analyze the clinicopathologic characteristics of patients diagnosed with ATC expected to undergo curative thyroidectomy, with the goal of finding differences between patients surviving ≥6 months and <6 months.
From 1981 to 2010, 24 patients underwent thyroidectomy due to ATC. Among those patients, 12 suspected of distant metastasis preoperatively were excluded. The remaining 12 patients were analyzed by retrospective review of electronic medical records.
Median age was 55 years, and the male to female ratio was 1:5. All patients presented with neck mass at initial diagnosis. Five patients lived <6 months and seven patients lived ≥6 months after operation. In patients surviving ≥6 months, all lesions were <5 cm and all patients underwent total thyroidectomy. In patients surviving <6 months, two of the four lesions were >5 cm, and two of the five patients underwent less than total thyroidectomy (P = 0.287 and 0.152, respectively). All patients with lesion size <5 cm underwent total thyroidectomy and showed a shorter median operation time (P = 0.182 and 0.033, respectively).
ATC showed female predominance. Patients initially presented with neck mass, and median age was 55 years. In patients with ATC who are expected to undergo curative thyroidectomy, surgery should actively be considered as primary therapy for patient survival when the size is <5 cm.
PMCID: PMC3433547  PMID: 22977757
Anaplastic thyroid cancer; Thyroidectomy
15.  An exclusively dopamine secreting paraganglioma in the retroperitoneum: a first clinical case in Korea 
Exclusively dopamine producing retroperitoneal paragangliomas are extremely rare. We have experienced the first Korean case managed successfully based on the proper evaluation. A 26-year-old female patient came to our attention after the accidental detection of an adrenal mass. She had no symptoms and denied any family history. Laboratory evaluations were normal but serum dopamine (425 ng/L) and 24-hour urine dopamine levels (1,565.3 µg/day) were elevated. She underwent laparoscopic right adrenalectomy. Histopathological diagnosis was a paraganglioma. After operation, dopamine levels in serum and 24-hour urine dropped to 0.09 ng/L and 388.4 µg/day. Dopamine producing paraganglioma elicit no clinical symptoms. Only the dopamine level is elevated in serum and 24-hour urine samples. Surgical resection without using preoperative alpha blockage is the treatment of choice. The prognosis for patients with this tumor tends to be poor because the diagnosis is usually delayed due to lack of symptoms.
PMCID: PMC3373991  PMID: 22708103
Pheochromocytoma; Paraganglioma; Adrenal glands; Dopamine; Adrenergic alpha-antagonists
16.  Berberine Inhibited the Growth of Thyroid Cancer Cell Lines 8505C and TPC1 
Yonsei Medical Journal  2012;53(2):346-351.
Thyroid cancer is the most common malignancy in Korean females and can be treated with good prognosis. However, drugs to treat aggressive types of thyroid cancer such as poorly differentiated or anaplastic thyroid cancer have not yet been established. To that end, we analyzed the effects of berberine on human thyroid cancer cell lines to determine whether this compound is useful in the treatment of aggressive thyroid cancer.
Materials and Methods
The two thyroid cancer cell lines 8505C and TPC1, under adherent culture conditions, were treated with berberine and analyzed for changes in cell growth, cell cycle duration, and degree of apoptosis.
Following berberine treatment, both cell lines showed a dose-dependent reduction in growth rate. 8505C cells showed significantly increased levels of apoptosis following berberine treatment, whereas TPC1 cells showed cell cycle arrest at the G0/G1 phase. Immunobloting of p-27 expression following berberine treatment showed that berberine induced a little up-regulation of p-27 in 8505c cells but relatively high up-regulation of p-27 in TPC1 cells.
These results suggest that berberine treatment of thyroid cancer can inhibit proliferation through apoptosis and/or cell cycle arrest. Thus, berberine may be a novel anticancer drug for the treatment of poorly differentiated or anaplastic thyroid cancer.
PMCID: PMC3282951  PMID: 22318822
Berberine; anticancer-drug; thyroid cancer; growth

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