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1.  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
2.  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
3.  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
4.  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
5.  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
6.  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
7.  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
8.  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
9.  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
10.  Changes in the Clinicopathological Characteristics and Outcomes of Thyroid Cancer in Korea over the Past Four Decades 
Thyroid  2013;23(7):797-804.
Thyroid cancer has increased globally, with a prominent increase in small, papillary thyroid cancers (PTC). The Korean population has a high iodine intake, high prevalence of BRAF V600E mutations, and family histories of thyroid cancer. We examined the clinicopathological characteristics and outcomes of thyroid cancers in Korean patients over four decades.
The medical records of 4500 thyroid cancer patients, between 1962 and 2009 at a single center, including 3147 PTC patients, were reviewed.
The mean age of the patients was 46.8±13.2 years; women accounted for 82.9% of the patients, and the median follow-up duration was 4.8 years (mean 7.0±5.8 years, range 1–43 years). The number of patients visiting the clinic increased from 411 during 1962–1990 to 2900 during 2000–2009. Age at diagnosis increased from 39.6±12.9 to 48.6±12.4 years. The male to female ratio increased from 1:6 to 1:4.5. The proportion of small (<1 cm) tumors increased from 6.1% to 43.1%, and the proportion of cancers with lymph node (LN) involvement or extrathyroidal extension (ETE) decreased from 76.4% to 44.4% and from 65.5% to 54.8% respectively. Although there were decreases in the proportion of LN involvement and ETE, these decreasing rates were not proportional to the expected rates based on the decreased proportion of large tumors. The overall recurrence and mortality rates were 13.3% and 1.4%. The five-year recurrence rate significantly decreased (from 11% to 5.9%), and the five-year mortality also improved (from 1.5% to 0.2%).
The incidence of thyroid cancer has rapidly increased, with a decrease in tumors of large size, LN involvement, and ETE, although the decreasing rates of LN involvement and ETE were not as prominent as decreasing rates of large size tumors. The mortality and recurrence rates have also decreased. Future long-term follow-up of patients diagnosed in the most recent decade is needed to confirm the prognostic characteristics of Korean PTC patients.
PMCID: PMC3704118  PMID: 23427907
11.  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
12.  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
14.  Antiproliferation and Redifferentiation in Thyroid Cancer Cell Lines by Polyphenol Phytochemicals 
Journal of Korean Medical Science  2011;26(7):893-899.
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.
PMCID: PMC3124719  PMID: 21738342
Thyroid Neoplasms; F9 Embryonal Carcinoma Cell; Redifferentiation; Polyphenols; Phytochemical; CD97; Sodium-Iodine Symporter
15.  Young age: an independent risk factor for disease-free survival in women with operable breast cancer 
BMC Cancer  2004;4:82.
The incidence of breast cancer in young women (age < 35) is low. The biology of the disease in this age group is poorly understood, and there are conflicting data regarding the prognosis for these women compared to older patients.
We retrospectively analyzed 2040 consecutive primary invasive breast cancer patients who underwent surgical procedures at our institution between 1990 and 1999. The younger age group was defined as patients aged <35 years at the time of diagnosis. The clinicopathological characteristics and treatment outcomes were compared between younger and older age groups.
A total of 256 (12.5%) patients were aged <35. There was a significantly higher incidence of nuclear grade 3 and medullary histological-type tumors in younger patients compared to older patients. Axillary lymph node status, T stage, histological grade, c-erbB2 expression and estrogen receptor status did not differ significantly between the two age groups. Younger patients had a greater probability of recurrence and death at all time periods. Although there was no significant difference in disease-free survival between the two age groups in lymph node-negative patients, the younger group showed worse prognosis among lymph node-positive patients (p < 0.001). In multivariate analysis, young age remained a significant predictor of recurrence (p = 0.010).
Young age (<35) is an independent risk factor for relapse in operable breast cancer patients.
PMCID: PMC545947  PMID: 15546499
16.  Combined administration of glutamine and growth hormone synergistically reduces bacterial translocation in sepsis. 
We investigated the combined effect of glutamine (GLN) and growth hormone (GH) on bacterial translocation (BT) in sepsis. After single intraperitoneal injection of lipopolysaccharide (10 mg/kg), 48 rats were divided randomly into four groups of 12 animals each: the control group received chow orally; the GLN group received chow plus 10% GLN; GH group received chow plus GH; and the GLN/GH group received chow, 10% GLN, and GH. Twenty-four and 96 hr later, rats were sacrificed. Portal blood culture, bacterial colony counts of cultured mesenteric lymph nodes, mucosal thickness, malondialdehyde (MDA), and glutathione (GSH) levels in the gut mucosa were measured. There was no significant change of the rate of portal blood culture between all treatment groups at 24 and 96 hr. At 24 hr, the rats receiving combined treatment of GLN and GH showed lower bacterial colony counts and mucosal MDA levels than the control rats, and higher mucosal GSH levels than the control and GLN-treated rats. At 96 hr, rats treated with both GLN and GH exhibited lower bacterial colony counts and mucosal MDA levels, and higher mucosal thickness and GSH levels than control, GLN, or GH-treated rats. This study suggests that the combination of GLN and GH may synergistically reduce BT over time in sepsis.
PMCID: PMC3055004  PMID: 12589081
17.  The effects of antioxidants and nitric oxide modulators on hepatic ischemic-reperfusion injury in rats. 
Journal of Korean Medical Science  2002;17(4):502-506.
Ischemic-reperfusion injury (IRI) is thought to be caused by oxygen radicals. Nitric oxide (NO) also has been thought to play a key role in IRI. This experiment was designed to evaluate the effects of antioxidants and NO supplement on hepatic IRI. Male Sprague-Dawley rats were divided into five groups: a sham operation group, a group with IRI, and three groups with vitamin C combined with vitamin E (VC&VE), L-arginine and N(G)-nitro-L-arginine (NNLA) injected after IRI. IRI was induced by clamping of the porta hepatis for 30 minutes and then by declamping. To prevent mesenteric blood congestion, a porto-systemic shunt had been made four weeks before the portal clamping. Biochemical assays of TNF-alpha level and NO2- level in the blood, malondialdehyde level, catalase activity and NO synthase activity in the liver tissue were performed. The results were as follows: IRI increased the malondialdehyde level and exhausted the catalase activity remarkably. VC&VE lowered the malondialdehyde levels and protected against catalase exhaustion, but had no significant effect on the NO production. L-arginine had a definite antioxidant effect, which was much weaker than that of VC&VE. In conclusion, antioxidants and a supplement of NO protected the liver tissue against IRI.
PMCID: PMC3054897  PMID: 12172046

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