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1.  Genome-wide association analysis in East Asians identifies breast cancer susceptibility loci at 1q32.1, 5q14.3 and 15q26.1 
Nature genetics  2014;46(8):886-890.
In a three-stage genome-wide association study among East Asian women including 22,780 cases and 24,181 controls, we identified three novel genetic loci associated with breast cancer risk, including rs4951011 at 1q32.1 (in intron 2 of the ZC3H11A gene, P = 8.82 × 10−9), rs10474352 at 5q14.3 (near the ARRDC3 gene, P = 1.67 × 10−9), and rs2290203 at 15q26.1 (in intron 14 of the PRC1 gene, P = 4.25 × 10−8). These associations were replicated in European-ancestry populations including 16,003 cases and 41,335 controls (P = 0.030, 0.004, and 0.010, respectively). Data from the ENCODE project suggest that variants rs4951011 and rs10474352 may be located in an enhancer region and transcription factor binding sites, respectively. This study provides additional insights into the genetics and biology of breast cancer.
PMCID: PMC4127632  PMID: 25038754
2.  Atypia of undetermined significance on thyroid fine needle aspiration: surgical outcome and risk factors for malignancy 
This study was performed to analyze the surgical pathology results of the "atypia of undetermined significance" (AUS) category from thyroid fine needle aspiration (FNA) and to describe the characteristics to distinguish a malignant from a benign nodule.
A retrospective analysis was done on 116 patients who underwent thyroid surgery from December 2008 to December 2012, following a diagnosis of AUS from preoperative thyroid FNA. We investigated the age, gender, size and site of the nodules, ultrasonographic criteria, cytological features, the number of atypia results after repeated FNAs, surgical method, and final pathologic results.
Sixty-five out of 116 patients underwent total thyroidectomy and the rest had partial thyroidectomy. The final pathologic results were 41 malignancies (35.3%) and 75 benign diseases (64.7%). AUS was divided into group 1: 'cannot rule out malignancy' or group 2: 'cannot rule out follicular neoplasm'. After surgery, group 1 revealed papillary thyroid cancer in most cases and group 2 revealed follicular adenoma in most cases. Age over 40 years, ultrasonographic findings suggestive of malignancy, more than 2 results of atypia from repeated FNAs and nodules less than 2 centimeters were risk factors for malignancy on univariate analysis. Multivariate analysis showed that ultrasonographic findings suggestive of malignancy was a significant risk factor for malignancy.
For proper evaluation of the risk for malignancy in thyroid AUS patients, the ultrasonographic criteria should be considered along with other clinicopathological findings such as age, nodule size, number of atypia, cytologic features.
PMCID: PMC3994624  PMID: 24761418
Atypia of undetermined significance; Fine needle aspiration; Thyroid neoplasms
4.  Analysis of Infections Occurring in Breast Cancer Patients after Breast Conserving Surgery Using Mesh 
Journal of Breast Cancer  2011;14(4):328-332.
Breast conserving surgery using mesh can effectively fill the defective space, but there is the risk of infection.
From June 2007 to August 2010, 243 patients who underwent breast conserving surgery with polyglactin 910 mesh insert for breast cancer at our institution were retrospectively studied.
Infection occurred in 25 (10.3%) of 243 patients. When comparing the infection and non-infection groups in multivariate analysis, there was no significant difference in age, underlying disease, preoperative biopsy methods, mass location, axillary lymph node dissection, operative methods, neoadjuvant or adjuvant chemotherapy use, mass size and removed breast volume. The infection appeared more common only in patients with body mass index (BMI) greater than 25. Infection symptoms occurred, on average, 119.5 days after surgery, and the average duration of the required treatment was 34.4 days. Out of 25 patients with postoperative infection complications, 16 (64%) patients underwent incision and drainage with mesh removal, whereas the remaining 9 (36%) only required conservative treatment.
During breast conserving surgery, the risk of infection is increased in patients with high BMI, and should be taken into account when considering insertion of a polyglactin 910 mesh. Patient's age, underlying disease and perioperative treatment methods were not significant risk factors for developing mesh infection. Given that most infections seem to develop symptoms one month after surgery, a long enough observation period should be initiated. Early detection and appropriate conservative treatments may effectively address infections, thus reducing the need for more invasive therapies.
PMCID: PMC3268931  PMID: 22323921
Breast neoplasms; Breast-conserving surgery; Infection; Polyglactin 910
5.  The Role of Lymphovascular Invasion as a Prognostic Factor in Patients with Lymph Node-Positive Operable Invasive Breast Cancer 
Journal of Breast Cancer  2011;14(3):198-203.
Lymphovascular invasion (LVI) is an important prognostic factor in patients with lymph node-negative patients with invasive breast cancer. However, the prognostic value of LVI it is unclear and controversial about its prognostic value in patients with lymph node-positive breast cancer patients. So, we report the an analysis of the prognostic significance of LVI in a large cohort study of patients with lymph node-positive patients with invasive breast cancer.
We retrospectively reviewed 967 patients with invasive breast cancer that had undergone surgical treatment at our hospital, from January 2004 to December 2007. Among these thempatients, 349 patients with lymph node-positive breast cancer patients are were included in this study. We evaluated clinical and pathological data in these patients, we compared with 5-year overall survival and disease-free survival between an LVI-present group and an LVI-absent group.
The median follow-up was 48 months (range, 12-78 months), and the mean age of the patients was 48 years (range, 23-78 years). LVI was present in 192 patients (55%) of with tumors and was associated with age ≤40 years (p=0.009), high histologichistological grade (p=0.007), estrogen receptor status (p=0.001), tumor size ≥2 cm (p<0.001), and number of involved lymph nodes (p<0.001), but not with progesterone receptor status, HER2 status, p53 status, or tumor multiplicity. LVI was a significant independent prognostic factor for disease-free survival (p<0.001) and overall survival (p=0.006). By multivariate analysis revealed that LVI (p=0.003), number of involved lymph nodes (≥4; p=0.005), and high histological grade (II and III; p=0.02) was were an independent significant predictors of disease-free survival and overall survival in the whole group of patients.
In this case, we demonstrated that LVI is a significant predictor of poor prognosis in patients with lymph node-positive patients with primary invasive breast cancer, LVI is a significant predictive predictor value of poor prognosis. So, LVI should be considered in the therapeutic strategy as a decision making tool in the adjuvant chemotherapy setting.
PMCID: PMC3200515  PMID: 22031801
Breast neoplasms; Lymph node metastasis; Lymphovascular invasion; Prognostic factor
6.  Alpha-Type 1 Polarized Dendritic Cells Loaded with Apoptotic Allogeneic Breast Cancer Cells Can Induce Potent Cytotoxic T Lymphocytes against Breast Cancer 
Various tumor antigens can be loaded onto dendritic cells (DCs) to induce a potent cytotoxic T lymphocyte (CTL) response in DC-based immunotherapy against breast cancer. However, in the clinical setting, obtaining a sufficient number of autologous tumor cells as a source of tumor antigens is a laborious process. We therefore investigated the feasibility of immunotherapy using breast-cancer-specific CTLs generated in vitro by use of alpha-type 1 polarized DCs (α DC1s) loaded with ultraviolet B-irradiated cells of the breast cancer cell line MCF-7.
Materials and Methods
αDC1s were induced by loading allogeneic tumor antigen generated from the MCF-7 UVB-irradiated breast cancer cell line. Antigen-pulsed αDC1s were evaluated by morphological and functional assays, and the breast-cancer-specific CTL response was analyzed by cytotoxic assay.
The αDC1s significantly increased the expression of several molecules related to DC maturation without differences according to whether the αDC1s were loaded with tumor antigens. The αDC1s showed a high production of interleukin-12 both during maturation and after subsequent stimulation with CD40L, which was not significantly affected by loading with tumor antigens. Breast-cancer-specific CTLs against autologous breast cancer cells were successfully induced by αDC1s loaded with apoptotic MCF-7 cells.
Autologous DCs loaded with an allogeneic breast cancer cell line can generate potent breast-cancer-specific CTL responses. This may be a practical method for cellular immunotherapy in patients with breast cancer.
PMCID: PMC3072536  PMID: 21509164
Dendritic cells; Breast neoplasms; Allogeneic; Cytotoxic T lymphocytes; Immunotherapy
7.  Papillary Thyroglossal Duct Cyst Carcinoma with Synchronous Occult Papillary Thyroid Microcarcinoma 
Yonsei Medical Journal  2010;51(4):609-611.
This is a case report on papillary thyroglossal duct cyst (TGDC) carcinoma along with synchronous occult papillary thyroid microcarcinoma. A 46-year-old woman visited our hospital because she had an anterior midline neck mass below her hyoid bone. Preoperative ultrasound-guided fine-needle aspiration cytology revealed signs of papillary TGDC carcinoma. We performed a Sistrunk operation and a total thyroidectomy. Histopathological examination of the specimen revealed papillary carcinoma arising in the TGDC and papillary microcarcinoma of the thyroid gland without extrathyroidal extension. Surgeons should be aware of TGDC carcinoma during surgical planning and postoperative treatment and should differentiate this carcinoma from an anterior midline neck mass.
PMCID: PMC2880280  PMID: 20499433
Thyroglossal duct cyst carcinoma; synchronous; occult; thyroid microcarcinoma
8.  A Phase I/II Trial to Evaluate the Technical Feasibility of Partial Breast Irradiation with Three-Dimensional Conformal Radiation Therapy in Korean Women with Stage I Breast Carcinoma: An Initial Report of the Korean Radiation Therapy Oncology Group (KROG) Study 0804 
This prospective study was designed to verify the technical feasibility of partial breast irradiation in breast cancer patients with small breasts, which are commonly encountered in Korean women.
Materials and Methods
A total of 40 Gy, administered in 10 fractions on consecutive days (one fraction per day), was prescribed to the isocenters of the fields using three-dimensional conformal radiotherapy (3-DCRT). For all patients, treatment planning and dose parameters strictly adhered to the constraints set forth in the Radiation Therapy Oncology Group (RTOG) 0319 protocol. This study was designed such that if fewer than five of the first 42 evaluable patients received unacceptable scores, the treatment would be considered reproducible.
Ten treatment plans (23.8%) were determined to have major variations. There was no major variation in planning target volume (PTV) coverage. The ipsilateral and contralateral breast dose limitations were not met in four (9.5%) and four cases (9.5%), respectively. Major variations in ipsilateral and contralateral lung dose limitations were observed in two cases (4.8%). Major variations in the heart and thyroid dose limitations were observed in one (2.4%) and one case (2.4%), respectively. In multivariate analysis, a ratio of PTV to ipsilateral breast volume (PTV/IB) > 0.16 was the only significant factor that statistically affected major variations.
We concluded that partial breast irradiation using 3-DCRT could not be reproduced in Korean breast cancer patients, particularly small-volumed breast surrogated as PTV/IB > 0.16. The dominant cause was the major variation in surrounding normal breast tissues.
PMCID: PMC4296846  PMID: 25143050
Breast neoplasms; Partial breast irradiation; Conformal radiotherapy
9.  Expression of matrix metalloproteinases and their inhibitors in different immunohistochemical-based molecular subtypes of breast cancer 
BMC Cancer  2014;14(1):959.
Metalloproteinases (MMPs) and their tissue inhibitors of metalloproteinases (TIMPs) are involved in several key pathways of tumor growth, invasion and metastasis, but little is known about their expression according to different molecular subtypes of breast cancer. The aims of this study were to assess the prevalence and clinical significance of MMP and TIMP expression in invasive breast cancer and to determine its association with immunohistochemical-based molecular classification.
Tissue microarray sections were immunostained for estrogen receptor-α (ER-α), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), cytokeratin (CK) 5/6, epidermal growth factor receptor (EGFR) and with specific antibodies against MMP-1, 2, 7, 9, 11, 13, and 14 and TIMP-1, 2, and 3. Based on the immunostaining data from five of the markers used (ER-α, PR, HER2, EGFR and CK5/6), three major subtypes (123 luminal A, 31 basal-like, and 17 HER2-overexpressing) were selected.
Statistically significant differences in the expression of MMPs and TIMPs among the three subtypes were found in tumoral MMP7 (P = 0.005), tumoral MMP-9 (P = 0.000), tumoral MMP-13 (P = 0.016) and stromal MMP-13 (P = 0.016). The incidence of tumoral MMP-9 expression in the HER2-overexpressing subtype was significantly higher than in the luminal A subtype (P = 0.021). Tumoral MMP-9 and stromal MMP-13 expression were significantly higher in the HER2-overexpressing subtype than in the basal-like subtype (P = 0.000 and P = 0.016, respectively). Tumoral MMP-7 expression was significantly higher in the basal-like subtype compared to luminal A (P = 0.007) and HER2-overexpressing subtype (P = 0.004). Tumoral MMP-13 showed a higher expression in the basal-like subtype than in the HER2-overexpressing subtype (P = 0.010). In multivariate analysis, stage and stromal MMP-1 expression were significantly related to overall survival. Stage was of independent prognostic significance for disease-free survival.
We found some variations in MMP and TIMP expression among the immunohistochemical-based molecular subtypes of breast carcinomas, suggesting differences in their tumor pathophysiology. Additional studies are needed to determine the mechanisms underlying the differences of MMP and TIMP expression in the molecular subtypes for the development of specific therapeutic targets for breast cancer subtypes.
PMCID: PMC4301952  PMID: 25510449
Breast cancer; Molecular subtype; Immunohistochemistry; Matrix metalloproteinase; Tissue inhibitor of metalloproteinase
10.  Tumorigenesis of Papillary Thyroid Cancer Is Not BRAF-Dependent in Patients with Acromegaly 
PLoS ONE  2014;9(10):e110241.
Several studies have reported a high frequency of papillary thyroid cancer (PTC) in patients with acromegaly. The aim of this study was to determine the prevalence and predictors of thyroid cancer in patients with acromegaly and to investigate the frequency of the BRAFV600E mutation in PTC patients with and without acromegaly.
Materials and Methods
We conducted a retrospective study of 60 patients with acromegaly. Thyroid ultrasonography (US) and US-guided fine needle aspiration were performed on nodules with sonographic features of malignancy. We selected 16 patients with non-acromegalic PTC as a control group. The BRAFV600E mutation was analyzed in paraffin-embedded surgical specimens of PTC by real-time polymerase chain reaction, and tumor specimens from patients with PTC were stained immunohistochemically with an antibody against insulin-like growth factor-1 receptor β (IGF-1Rβ).
Thyroid cancer was found in 15 (25.0%) patients. No differences in age, sex, initial growth hormone (GH) and IGF-1 percentage of the upper limit of normal values or treatment modalities were observed between patients with and without PTC. Acromegaly was active in 12 of 15 patients at the time of PTC diagnosis; uncontrolled acromegaly had a significantly higher frequency in the PTC group (60%) than in the non-PTC group (28.9%) (p = 0.030). The BRAFV600E mutation was present in only 9.1% (1/11) of PTC patients with acromegaly, although 62.5% (10/16) of control patients with PTC had the mutation (p = 0.007). IGF-1Rβ immunostaining showed moderate-to-strong staining in all malignant PTC cells in patients with and without acromegaly. Significantly less staining for IGF-1Rβ was observed in normal adjacent thyroid tissues of PTC patients with acromegaly compared with those without (p = 0.014).
The prevalence of PTC in acromegalic patients was high (25%). An uncontrolled hyperactive GH-IGF-1 axis may play a dominant role in the development of PTC rather than the BRAFV600E mutation in patients with acromegaly.
PMCID: PMC4201528  PMID: 25329702
11.  Iatrogenic Intraspinal Epidermoid Cyst 
Korean Journal of Spine  2014;11(3):195-197.
Epidermoid cyst is generally regarded as congenital disease, and commonly related to other congenital spinal anomalies. However, it also develops iatrogenically. We report one rare case of epidermoid cyst that we experineced among intradural extramedullary tumors. A 21-year-old female patient was admitted to the hospital due to low back pain with radiating pain into a right lower extremity that initiated about a month ago. She complained sensory lose and motor weakness (grade 4+) on her right extremity as well as urinary dysfunction and sphincter dysfunction. She had a lumbar puncture three times due to Pneumococcal meningitis when she was 13 years old. The well-circumscribed intradural extramedullary mass of 1.8×1.6×4 cm size was found on the L4-5 in a magnetic resonance image. Gross total tumor removal was garried out after the total laminectomy L5 and partial laminectomy L4. The tumor mass was gray-colored and so fragile that it was easy to be removed. The histological diagnosis confirmed epidermoid cyst without malignancy. After the operation, the patient progressively showed remarkable neurological recovery. In this case, the cause of epidermoid cyst is considered iatrogenic concerning history of several times of lumbar puncture as meningitis.
PMCID: PMC4206976  PMID: 25346768
Epidermoid cyst; Lumbar puncture; Iatrogenic
12.  Prototype Nerve-Specific Near-Infrared Fluorophores 
Theranostics  2014;4(8):823-833.
Nerve preservation is an important issue during most surgery because accidental transection or injury results in significant morbidity, including numbness, pain, weakness, or paralysis. Currently, nerves are still identified only by gross appearance and anatomical location during surgery, without intraoperative image guidance. Near-infrared (NIR) fluorescent light, in the wavelength range of 650-900 nm, has the potential to provide high-resolution, high-sensitivity, and real-time avoidance of nerve damage, but only if nerve-specific NIR fluorophores can be developed. In this study, we evaluated a series of Oxazine derivatives to highlight various peripheral nerve structures in small and large animals. Among the targeted fluorophores, Oxazine 4 has peak emission near into the NIR, which provided nerve-targeted signal in the brachial plexus and sciatic nerve for up to 12 h after a single intravenous injection. In addition, recurrent laryngeal nerves were successfully identified and highlighted in real time in swine, which could be preserved during the course of thyroid resection. Although optical properties of these agents are not yet optimal, chemical structure analysis provides a basis for improving these prototype nerve-specific NIR fluorophores even further.
PMCID: PMC4063980  PMID: 24955143
Real-time intraoperative identification; nerve targeting; recurrent laryngeal nerve; contrast agents; targeted agents; near-infrared imaging.
13.  Syringomyelia Coexisting With Guillain-Barre Syndrome 
Annals of Rehabilitation Medicine  2013;37(5):745-749.
Guillain-Barre syndrome (GBS) and syringomyelia are diseases of different entities. GBS is an acute post-infectious autoimmune disease which is mediated by autoantibodies against the myelin of peripheral nerves. Syringomyelia is a chronic disease characterized by a cavity extending longitudinally inside the spinal cord. A 67-year-old man is being hospitalized due to severe numbness and ascending weakness in all limbs. On neurological examination, the motor power of all limbs are decreased and show absence of deep tendon reflexes (DTRs). The patient is being diagnosed with GBS on the basis of the acute clinical course, nerve conduction studies of segmental demyelinating polyneuropathy, and a finding of albuminocytologic dissociation in the cerebrospinal fluid. The patient is presented with a new set of symptoms thereafter, which composes of sensory changes in the upper extremities, the urinary dysfunction including frequency and residual urine, spastic bilateral lower extremities, and increased reflexes of the knee and the biceps at follow-up examinations. The spinal magnetic resonance imaging in the sagittal section revealed a syrinx cavity between the fifth cervical and the first thoracic vertebral segment in the cord. The somatosensory evoked potential show sensory pathway defects between both the brachial plexus and the brain stem. Thus, this patient is being diagnosed with both GBS and syringomyelia. We report a case of symptomatic syringomyelia coexisting with GBS. Since the GBS is presented with a progressive muscle weakness and reduced DTRs, the muscle weakness and stiffness in the extremities suggests a concurrent syringomyelia might be easily overlooked.
PMCID: PMC3825956  PMID: 24236267
Guillain-Barre syndrome; Syringomyelia; Posttraumatic syringomyelia
14.  Malignant thyroid bed mass after total thyroidectomy 
Ultrasonographic (US) criteria on malignant thyroid bed mass have been suggested, including taller than wide shape, loss of echogenic hilum, abnormal vascularity, and microcalcification. The relationship between fine-needle aspiration (FNA) cytology findings and US findings on thyroid bed mass is unknown. We have retrospectively assessed the malignant thyroid bed mass after total thyroidectomy due to papillary thyroid carcinoma (PTC).
We retrospectively evaluated 2,048 patients who underwent total thyroidectomy due to PTC. FNA was performed in 97 patients on the thyroid bed under US surveillance. The 97 suspicious thyroid bed masses were divided into two groups: metastatic thyroid bed group (n = 34) and nonmetastatic group (n = 63). The groups were evaluated according to various clinical, serologic, and US findings.
Within a median 47.0 months of follow-up, the proportion of malignant thyroid bed mass was high in large tumor size (1.37 cm vs. 1.03 cm), isthmic position (10.3% vs. 3.9%), and previous N1a (55.9% vs. 34.9%). US findings revealed that the presence of microcalcification or macrocalcification (47.1% vs. 19.0%) and thyroid bed mass height (5.4 mm vs. 3.9 mm) were the only discriminable criteria for central compartment recurrence. But, degree of echogenicity, loss of hilum, and irregularity of margin failed to discriminate malignant thyroid bed mass.
US findings on malignant thyroid bed mass were different from previously reported general criteria on lateral metastatic nodes. Additional FNA cytology should be performed on patients, even low-risk patients, who present the above findings.
PMCID: PMC3764368  PMID: 24020017
Ultrasonography; Fine-needle biopsy; Thyroidectomy; Papillary thyroid cancer
15.  Invasive Micropapillary Carcinoma of the Breast: MR Imaging Findings 
Korean Journal of Radiology  2013;14(4):551-558.
To analyze the magnetic resonance (MR) imaging findings of invasive micropapillary carcinoma of the breast.
Materials and Methods
MR images were retrospectively evaluated in 14 patients (age range: 37-67, mean age: 49 years) with pathologically confirmed invasive micropapillary carcinoma of the breast. The enhancement type (mass/non-mass), shape, margin, contrast enhancement, and time-intensity curve pattern on the dynamic study were correlated with the histopathologic features. Associated findings, such as edema, nipple change, skin change and enlarged axillary lymph nodes were also studied.
The most common features of the masses were irregular shape (12 of 14 patients, 85.8%) and irregular or spiculated margin (11 of 14 patients, 78.7%). The contrast enhancement was heterogeneous in 11 patients (78.7%), rim enhancement in 2 cases (14.2%), and homogeneous in one patient (7.1%). The predominant kinetic pattern was rapid increase (14 of 14, 100%) in the initial phase and washout (11 of 14, 78.7%) in the delayed phase. Associated non-mass like enhancement was shown in 4 patients, representing ductal carcinoma in situ. MR imaging helped detect additional sites of cancer other than the index lesion in 3 patients (21.4%). Enlarged axillary lymphadenopathy was identified in 7 of the 14 patients (50%).
Invasive micropapillary carcinoma appears as a mass with an irregular shape, irregular or spiculated margin and heterogeneous enhancement on MR imaging. Though these findings are not specific and are also observed with other breast malignancies, invasive micropapillary carcinoma frequently showed multiple lesions, accompanying non-mass enhancement and axillary lymph node enlargement.
PMCID: PMC3725348  PMID: 23901311
Breast neoplasms; Diagnosis; Micropapillary carcinoma; Breast neoplasms; MR
16.  Subcutaneous Panniculitis-Like T-Cell Lymphoma of the Breast 
Korean Journal of Radiology  2013;14(3):391-394.
Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of cutaneous lymphoma. There have been a few case reports describing the radiologic imaging findings of SPTCL. We report a case of SPTCL, rarely presented with a breast mass. Here, we review her clinical history and radiologic (mammography and ultrasound) findings.
PMCID: PMC3655289  PMID: 23690702
Subcutaneous panniculitis-like T-cell lymphoma; Breast; Mammography; Ultrasound
17.  Age and prognosis of papillary thyroid carcinoma: retrospective stratification into three groups 
We investigated the prognosis according to age in papillary thyroid carcinoma (PTC) patients.
We retrospectively evaluated 2,890 patients who underwent thyroidectomy due to PTC between May 2004 and Aug 2008. We divided patients into 3 groups: young (≤35 years old), middle (between 35 and 54 years old), and old (≥55 years old).
Median age was 47.0 years old (range, 15 to 82 years). Within a follow-up period median of 50 months, there were 148 (5.1%) locoregional recurrences, 6 (0.2%) PTC-related deaths, and 18 (0.6%) PTC-unrelated deaths. Outcomes were more favorable in the young group, with no PTC-related death despite the frequent locoregional recurrence. In the old group compared to the middle, there was a higher proportion of male, and more aggressive types as T3 or N1b, higher mean tumor number, more multiplicity, and bilaterality. The old group of ≥55 years did not show a significant difference in PTC-related deaths than other age groups in Cox analysis (OR, 0.9; P = 0.677), but a significant cutoff age in PTC-related deaths at 62.5 years was determined in ROC analysis (area under curve = 0.912).
We showed that the ≤35 years group shows favorable prognosis despite the frequent locoregional recurrence and ≥62.5 years group shows a poor prognosis regardless of other factors such as male sex or tumor aggressiveness. Further multiinstitutional studies are needed to elucidate the prognosis according to patient's age.
PMCID: PMC3491227  PMID: 23166884
Age; Prognosis; Papillary thyroid carcinoma
18.  Observational study of central metastases following thyroid lobectomy without a completion thyroidectomy for papillary carcinoma 
There are no guidelines for the optimal timing of the decision of when to perform completion thyroidectomy, and controversy exists regarding how the timing of completion thyroidectomy impacts survival patterns. We investigated the legitimacy of an observational strategy in central node metastasis after thyroid lobectomy for papillary thyroid cancer (PTC).
We retrospectively evaluated 522 consecutive patients who underwent thyroid lobectomy. Of the 69 patients with central metastasis, 61 patients (88.4%) were included in an observational study under cautious evaluation with informed consent by the patients, and compared with an observation arm of 180 postlobectomy N0 (node negative proven) patients.
Of the 522 patients, six (1.1%) thyroid, five (0.9%) central, and two (0.4%) lateral recurrences were observed. Lateral recurrences occurred in the immediate completion N0 and Nx groups but not in the N1a observation arms. There were two (3.3%) central recurrences without thyroid or lateral recurrence on the observation arm of N1a observation patients. But two (1.1%) thyroid and three (1.7%) central recurrences were on the observation arm of N0 patients. In Kaplan-Meier survival curves for central or lateral recurrences between observation arms for the N1a and N0 groups, no significant difference was found between the N1a and N0 observation arms (P = 0.365).
The timing of when to perform completion thyroidectomy in central metastases-proven patients after lobectomy for PTC should be based on the patient's risk category.
PMCID: PMC3467385  PMID: 23091791
Observation; Lymphatic metastasis; Thyroid neoplasms; Thyroidectomy
19.  Is it possible to predict hypothyroidism after thyroid lobectomy through thyrotropin, thyroglobulin, anti-thyroglobulin, and anti-microsomal antibody? 
We investigated the incidence and risk factors of hypothyroidism after thyroid lobectomy, and evaluated the possibility to predict hypothyroidism preoperatively with serologic markers, such as thyrotropin (TSH), thyroglobulin (TG), anti-thyroglobulin (ATA), and anti-microsomal antibody (AMA).
We enrolled 123 consecutive patients who underwent thyroid lobectomy due to benign conditions between May 2004 and April 2008. Only preoperative euthyroid patients were included. Patients were divided into two groups by postoperative thyroid function outcomes, into hypothyroid (n = 97) and euthyroid groups (n = 26), and analyzed specially for the preoperative levels of TSH, TG, ATA, and AMA.
Twenty-six (21.1%) patients developed hypothyroidism following thyroid lobectomy within 35.7 months of follow-up. The proportion of post-lobectomy hypothyroidism was high in patients with high-normal preoperative TSH level, and the cut-off value was 2.0 mIU/L, with 67% sensitivity and 75% specificity. The quantitative titer of preoperative TG, ATA, and AMA was not significant, but the outcome of categorical analysis of two or more positivities on these three markers was significantly higher in hypothyroid patients than in euthyroid patients (28.6% vs. 3.9%, P = 0.024). The combined positivity of preoperative TSH and two or more positivities of TG, ATA, and AMA possess 100% positive predictive value and 81% negative predictive value.
The incidence of hypothyroidism following thyroid lobectomy was 21.1%. High-normal preoperative TSH and two or more positivities for TG, ATA, and AMA are good pre-operative predictive markers. Such high-risk patients need close TSH monitoring before the onset of clinical hypothyroidism.
PMCID: PMC3243854  PMID: 22200038
Hypothyroidism; Thyrotropin; Thyroglobulin; Thyroid microsomal antibodies
20.  Primary papillary carcinoma originated from a branchial cleft cyst 
Journal of the Korean Surgical Society  2011;81(Suppl 1):S12-S16.
Although branchial cleft cysts are common, papillary carcinomas arising from them are rare. Here we report a 41-year-old woman with papillary carcinoma originating from a right lateral branchial cleft cyst without any evidence of a papillary carcinoma in the thyroid gland. The patient underwent right lateral neck dissection followed by total thyroidectomy. We then confirmed papillary carcinoma arising from the branchial cleft cyst through microscopic and immunohistochemical staining with thyroglobulin (TG), thyroid-associated transcription factor-1 (TTF-1) and p63. It is the 10th case worldwide describing papillary carcinoma in a branchial cleft cyst with a review of the literature on the features of the disease and discussion of the role of immunohistochemical staining with TG, TTF -1 and p63. In conclusion, it should be emphasized that the surgeon must be cautioned of the possibility of primary papillary carcinoma in the branchial cleft cyst.
PMCID: PMC3267057  PMID: 22319730
Branchioma; Thyroid neoplasms; Papillary carcinoma
21.  Thyroid gland metastasis arising from primary liver cholangiocarcinoma: The first case report involving surgical operation 
A primary cancer causing thyroid metastasis is extremely rare. In western countries, the most common primary tumors causing thyroid metastases include kidney, lung, breast, and gastrointestinal cancers. In contrast, breast is the most common primary site, followed by kidney, colon, and lung cancers in Korea. To the best of our knowledge, surgically confirmed thyroid metastasis from cholangiocarcinoma has not been reported. Herein, we report the first case of thyroid metastasis secondary to cholangiocarcinoma on which surgery was performed.
Presentation of case
A 55-year-old man was diagnosed with hepatic malignancy in December 2008. He subsequently received 2 cycles of transarterial chemoembolization and 4 cycles of radio-frequency ablation between 2008 and 2010. At follow-up in January 2011, brain metastasis was identified in the right parietal area secondary to cholangiocarcinoma. In April 2011, the patient was found to have palpable masses on the left thyroid and lateral neck. The patient subsequently underwent total thyroidectomy followed by left radical neck dissection. Intraoperatively, an ill-defined mass measuring 6.0 cm was found infiltrating the subcutaneous tissue into the prevertebral fascia. Microscopic and immunohistochemical findings confirmed that the thyroid masses and lymph nodes were metastatic cholangiocarcinoma.
Positive immunohistochemical staining for cytokeratin 7, cytokeratin 19, and AFP and negative results for TG, TTF-1, and cytokeratin 20 can be definitely helpful in arriving at a correct diagnosis.
To the best of our knowledge, this is the first case report on surgically resected thyroid and lateral neck metastases secondary to cholangiocarcinoma.
PMCID: PMC3267264  PMID: 22288052
Neoplasm metastasis; Thyroid metastasis; Cholangiocarcinoma
22.  Basal-like breast cancer displays distinct patterns of promoter methylation 
Cancer biology & therapy  2010;9(12):1017-1024.
Recent microarray profiling studies on breast cancer have identified distinct subtypes that are associated with different clinical outcomes. Promoter hypermethylation of several known or putative tumor suppressor genes occurs frequently during the pathogenesis of breast cancer. We proposed that immunohistopathologic subtypes of breast cancer are likely to contain distinct promoter methylation patterns. A panel of ten gene promoters was assessed by quantitative multiplex methylation-specific PCR in 114 invasive ductal carcinomas from Korea representing the three major subtypes [57 luminal, 24 human epidermal growth factor 2 (HER2), and 33 basal-like] based on immunohistochemical findings of estrogen receptor, progesterone receptor, HER2, cytokeratin 5/6 and epidermal growth factor receptor. The median methylation levels of HIN1, RASSF1A and TWIST, and the average methylation ratio were significantly lower in basal-like subtype compared to luminal or HER2 subtypes. In contrast, BRCA1 methylation level was significantly higher in basal-like subtype than in luminal subtype. The methylation status of a panel of four genes (APC1, CDH, BRCA1 and RAR-β) in luminal and HER2 subtypes were dissimilar, where HER2 tumors showed a significantly higher level of methylation compared to luminal tumors. These results suggest that gene methylation in breast cancer can potentially serve as epigenetic biomarkers and may contribute further to current breast cancer classification.
PMCID: PMC3094906  PMID: 20505321
breast cancer; basal-like; luminal; HER2; methylation; quantitation
23.  Plasma 5-Hydroxytryptamine Concentration and Its Correlation with Psychopathology in Patients with Irritable Bowel Syndrome 
Gut and Liver  2009;3(1):26-30.
Irritable bowel syndrome (IBS) is a biopsychosocial disorder. 5-Hydroxytryptamine (5-HT) plays a crucial role in the control of gastrointestinal motility, sensation, and secretion. This study investigated changes in platelet-depleted plasma 5-HT and their correlation with psychopathology in IBS patients and healthy subjects.
This study involved 21 subjects with IBS and 13 healthy subjects. Fasting and 1-hr postprandial plasma 5-HT concentrations were measured. The SCL-90R symptom checklist was used for the assessment of current psychological symptoms.
Fasting and postprandial plasma 5-HT concentrations were significantly higher in IBS patients (15.11±13.51 ng/mL and 16.31±14.21 ng/mL, respectively) than in healthy subjects (5.55±4.14 ng/mL and 6.25±4.82 ng/mL, respectively; p<0.05). There were no significant changes between fasting and 1-hr postprandial 5-HT concentration in IBS subtypes and healthy subjects. Scores on all SCL-90R subscales except for the interpersonal-sensitivity subscale were significantly higher in IBS patients than in healthy subjects. No correlation was found between SCL-90R items and platelet-depleted plasma 5-HT concentration.
5-HT might play a critical role in IBS, and psychopathological factors are correlated with IBS.
PMCID: PMC2871566  PMID: 20479897
Irritable bowel syndrome; 5-hydroxytryptamine; Psychopathology
24.  Growth and siderophore production of staphylococci in human peritoneal dialysate. 
Journal of Korean Medical Science  2003;18(2):158-162.
Although activity of iron uptake system (IUS) was thought to play an important role in staphylococcal growth in human peritoneal dialysate (HPD) solution, siderophore production, one of the well-known IUS, was not yet detected directly in HPD solution. Therefore, we tried to detect siderophore production directly in HPD solution by using a newly developed chrome azurol S (CAS) agar diffusion assay and to investigate the effect of IUS activity on bacterial growth in HPD solution. According to the susceptibility test for streptonigrin and the productivity of siderophore in the iron-deficient (ID) medium, Staphylococcus aureus ATCC 6538 strain and Staphylococcus epidermidis clinical isolate had higher IUS activity and grew better than S. aureus ATCC 25923 strain in the ID medium. These bacteria did not grow and produce siderophore in the unused chronic ambulatory peritoneal dialysis solution. However, these bacteria grew and produced siderophore in the HPD solution. Moreover, S. aureus ATCC 25923 strain with lower activity of IUS grew poorly and produced smaller amount of siderophore in HPD compared to S. aureus ATCC 6538 strain and S. epidermidis clinical isolate with higher activity of IUS like in the ID medium. To the best of our knowledge, this is the first report that siderophore production is directly detected in the HPD by CAS agar diffusion assay. These results indicated that activity of IUS plays an important role in bacterial growth in the HPD solution and pathogenesis of continuous ambulatory peritoneal dialysis peritonitis.
PMCID: PMC3055012  PMID: 12692409

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