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1.  Early Colorectal Epithelial Neoplasm in Korea: A Multicenter Survey of Pathologic Diagnosis 
Korean Journal of Pathology  2013;47(3):245-251.
Background
The incidence of early colorectal epithelial neoplasm (ECEN) is increasing, and its pathologic diagnosis is important for patient care. We investigated the incidence of ECEN and the current status of its pathologic diagnosis.
Methods
We collected datasheets from 25 institutes in Korea for the incidence of colorectal adenoma with high grade dysplasia (HGD) and low grade dysplasia in years 2005, 2007, and 2009; and early colorectal carcinoma in the year 2009. We also surveyed the diagnostic terminology of ECEN currently used by the participating pathologists.
Results
The average percentage of diagnoses of adenoma HGD was 7.0%, 5.0%, and 3.4% in years 2005, 2007, and 2009, respectively. The range of incidence rates of adenoma HGD across the participating institutes has gradually narrowed over the years 2005 to 2009. The incidence rate of early colorectal carcinoma in the year 2009 was 21.2%. The participants did not share a single criterion or terminology for the diagnosis of adenoma HGD. The majority accepted the diagnostic terms that distinguished noninvasive, mucosal confined, and submucosal invasive carcinoma.
Conclusions
Further research requirements suggested are a diagnostic consensus for the histopathologic diagnosis of ECEN; and standardization of diagnostic terminology critical for determining the disease code.
doi:10.4132/KoreanJPathol.2013.47.3.245
PMCID: PMC3701820  PMID: 23837017
Colorectal neoplasms; Pathology, surgical; Multicenter study; Incidence; Diagnosis
2.  T2 Relaxation Time Mapping of the Cartilage Cap of Osteochondromas 
Korean Journal of Radiology  2016;17(1):159-165.
Objective
Our aim was to evaluate the cartilage cap of osteochondromas using T2 maps and to compare these values to those of normal patellar cartilage, from age and gender matched controls.
Materials and Methods
This study was approved by the Institutional Review Board and request for informed consent was waived. Eleven children (ages 5-17 years) with osteochondromas underwent MR imaging, which included T2-weighted fat suppressed and T2 relaxation time mapping (echo time = 9-99/repetition time = 1500 msec) sequences. Lesion origins were femur (n = 5), tibia (n = 3), fibula (n = 2), and scapula (n = 1). Signal intensity of the cartilage cap, thickness, mean T2 relaxation times, and T2 spatial variation (mean T2 relaxation times as a function of distance) were evaluated. Findings were compared to those of patellar cartilage from a group of age and gender matched subjects.
Results
The cartilage caps showed a fluid-like high T2 signal, with mean thickness of 4.8 mm. The mean value of mean T2 relaxation times of the osteochondromas was 264.0 ± 80.4 msec (range, 151.0-366.0 msec). Mean T2 relaxation times were significantly longer than the values from patellar cartilage (39.0 msec) (p < 0.0001). These findings were observed with T2 spatial variation plots across the entire distance of the cartilage cap, with the most pronounced difference in the middle section of the cartilage.
Conclusion
Longer T2 relaxation times of the cartilage caps of osteochondromas should be considered as normal, and likely to reflect an increased water content, different microstructure and component.
doi:10.3348/kjr.2016.17.1.159
PMCID: PMC4720804  PMID: 26798229
T2 relaxation time mapping; Osteochondroma; Cartilage cap
5.  Hypoparathyroidism and Subclinical Hypothyroidism with Secondary Hemochromatosis 
Endocrinology and Metabolism  2014;29(1):91-95.
Hemochromatosis is an inherited genetic disorder of iron metabolism which can also occur as a secondary result of iron-overload. It leads to organ damage such as cardiomyopathy, liver cirrhosis, hypogonadism, and diabetes. This paper discusses a case of secondary hemochromatosis associated with repeated transfusions, presenting as asymptomatic hypoparathyroidism and subclinical hypothyroidism with multiple organ involvement. The 29-year-old female, who had severe aplastic anemia, received multiple transfusions totaling approximately 1,400 units of red blood cells over 15 years. During her routine laboratory examination, hypocalcemia was detected with decreased intact parathyroid hormone and increased thyroid stimulating hormone. Serum ferritin, iron, and total iron binding capacity had increased to 27,583.03 ng/mL, 291 µg/dL, and 389 µg/dL, respectively. She had unusually bronze skin and computed tomography revealed iron deposition in the thyroid, liver, and heart. Multiorgan involvement as seen in this case is rare in hemochromatosis associated with secondary transfusions. To the best of the author's knowledge, this is the first case report in Korea of hypoparathyroidism and subclinical hypothyroidism due to iron deposition in the parathyroid and thyroid gland.
doi:10.3803/EnM.2014.29.1.91
PMCID: PMC3970271  PMID: 24741460
Hypoparathyroidism; Hypothyroidism; Hemochromatosis
6.  The Recovery of Hypothalamic-Pituitary-Adrenal Axis Is Rapid in Subclinical Cushing Syndrome 
Endocrinology and Metabolism  2016;31(4):592-597.
Background
In subclinical Cushing syndrome (SC), it is assumed that glucocorticoid production is insufficient to cause a clinically recognizable syndrome. Differences in hormonal levels or recovery time of the hypothalamic-pituitary-adrenocortical (HPA) axis after adrenalectomy between patients with overt Cushing syndrome (OC) and SC remain unknown.
Methods
Thirty-six patients (10 with OC and 26 with SC) with adrenal Cushing syndrome who underwent adrenalectomy from 2004 to 2014 were reviewed retrospectively. Patients were treated with glucocorticoid after adrenalectomy and were reevaluated every 1 to 6 months using a rapid adrenocorticotropic hormone (ACTH) stimulation test.
Results
Levels of basal 24-hour urine free cortisol (UFC), serum cortisol after an overnight dexamethasone suppression test (DST), and serum cortisol and 24-hour UFC after low-dose DST and high-dose DST were all significantly lower in patients with SC compared with OC. Basal ACTH levels showed significantly higher in patients with SC compared with OC. The probability of recovering adrenal function during follow-up differed significantly between patients with OC and SC (P=0.001), with significant correlations with the degree of preoperative cortisol excess. Patients with OC required a longer duration of glucocorticoid replacement to recover a normal ACTH stimulation test compared with patients with SC (median 17.0 months vs. 4.0 months, P<0.001).
Conclusion
The HPA axis recovery time after adrenalectomy in patients with SC is rapid and is dependent on the degree of cortisol excess. More precise definition of SC is necessary to achieve a better management of patients and to avoid the risk of under- or over-treatment of SC patients.
doi:10.3803/EnM.2016.31.4.592
PMCID: PMC5195837  PMID: 28029028
Subclinical Cushing syndrome; Overt Cushing syndrome; Adrenal incidentaloma; Hydrocortisone; Hypothalamic-pituitary-adrenocortical axis recovery
7.  Efficacy of BRAF Inhibitors in Asian Metastatic Melanoma Patients: Potential Implications of Genomic Sequencing in BRAF-Mutated Melanoma12 
Translational Oncology  2016;9(6):557-564.
BACKGROUND: The BRAF inhibitors vemurafenib and dabrafenib are currently the standard treatment for metastatic melanoma with BRAF V600 mutations. However, given the rarity of noncutaneous melanoma, including acral and mucosal subtypes, the efficacy of BRAF inhibitors for this subset of patients has not been extensively investigated. Acquired resistance generally appears 6 to 8 months after treatment with a BRAF inhibitor, and the mechanism of resistance is not well established. METHODS: We examined treatment outcomes for patients diagnosed with metastatic melanoma and treated with BRAF inhibitors at Samsung Medical Center between April 2013 and December 2015. We analyzed genomic alterations in selected patients using targeted sequencing. RESULTS: Twenty-seven patients with a median age of 49 years (range 23-82 years) with metastatic melanoma and treated with a BRAF inhibitor were identified. Of these patients, 19 (70.3%) had noncutaneous melanoma, including acral and mucosal melanoma. All patients had BRAFV600E mutations. The median progression-free survival of all patients was 9.2 months (95% confidence interval, 1.6-16.7), and the objective response rate was 78.9% in the mucosal/acral melanoma group and 75.0% in the cutaneous melanoma group. Three (11.1%) patients achieved complete response, and 19 (70.4%) showed a partial response. Targeted sequencing in five patients demonstrated NF1 mutations in three patients who did not respond to BRAF inhibitors. CONCLUSION: BRAF inhibitors were an effective therapeutic option for Korean patients with metastatic melanoma harboring a BRAF V600 mutation regardless of melanoma subtype (acral/mucosa versus cutaneous).
doi:10.1016/j.tranon.2016.09.004
PMCID: PMC5122709  PMID: 27883956
8.  Current Trends of the Incidence and Pathological Diagnosis of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) in Korea 2000-2009: Multicenter Study 
Purpose
As a result of various independently proposed nomenclatures and classifications, there is confusion in the diagnosis and prediction of biological behavior of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). A comprehensive nationwide study is needed in order to understand the biological characteristics of GEP-NETs in Korea.
Materials and Methods
We collected 4,951 pathology reports from 29 hospitals in Korea between 2000 and 2009. Kaplan-Meier survival analysis was used to determine the prognostic significance of clinicopathological parameters.
Results
Although the GEP-NET is a relatively rare tumor in Korea, its incidence has increased during the last decade, with the most significant increase found in the rectum. The 10-year survival rate for well-differentiated endocrine tumor was 92.89%, in contrast to 85.74% in well differentiated neuroendocrine carcinoma and 34.59% in poorly differentiated neuroendocrine carcinoma. Disease related death was most common in the biliary tract (62.2%) and very rare in the rectum (5.2%). In Kaplan-Meier survival analysis, tumor location, histological classification, extent, size, mitosis, Ki-67 labeling index, synaptophysin expression, lymphovascular invasion, perineural invasion, and lymph node metastasis showed prognostic significance (p<0.05), however, chromogranin expression did not (p=0.148). The 2000 and 2010 World Health Organization (WHO) classification proposals were useful for prediction of the prognosis of GEP-NET.
Conclusion
The incidence of GEP-NET in Korea has shown a remarkable increase during the last decade, however, the distribution of tumors in the digestive system differs from that of western reports. Assessment of pathological parameters, including immunostaining, is crucial in understanding biological behavior of the tumor as well as predicting prognosis of patients with GEP-NET.
doi:10.4143/crt.2012.44.3.157
PMCID: PMC3467418  PMID: 23091441
Gastro-enteropancreatic neuroendocrine tumor; Incidence; Prognosis; Pathology
9.  Thyroid gland metastasis arising from primary liver cholangiocarcinoma: The first case report involving surgical operation 
Introduction
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.
Discussion
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.
Conclusion
To the best of our knowledge, this is the first case report on surgically resected thyroid and lateral neck metastases secondary to cholangiocarcinoma.
doi:10.1016/j.ijscr.2011.11.001
PMCID: PMC3267264  PMID: 22288052
Neoplasm metastasis; Thyroid metastasis; Cholangiocarcinoma
10.  Quantitative Assessment of the T2 Relaxation Time of the Gluteus Muscles in Children with Duchenne Muscular Dystrophy: a Comparative Study Before and After Steroid Treatment 
Korean Journal of Radiology  2010;11(3):304-311.
Objective
To determine the feasibility of using T2 mapping as a quantitative method to longitudinally follow the disease activity in children with Duchenne muscular dystrophy (DMD) who are treated with steroids.
Materials and Methods
Eleven boys with DMD (age range: 5-14 years) underwent evaluation with the clinical functional score (CFS), and conventional pelvic MRI and T2 mapping before and during steroid therapy. The gluteus muscle inflammation and fatty infiltration were evaluated on conventional MRI. The histograms and mean T2 relaxation times were obtained from the T2 maps. The CFS, the conventional MRI findings and the T2 values were compared before and during steroid therapy.
Results
None of the patients showed interval change of their CFSs. On conventional MRI, none of the images showed muscle inflammation. During steroid treatment, two boys showed increased fatty infiltration on conventional MRI, and both had an increase of the mean T2 relaxation time (p < 0.05). The remaining nine boys had no increase in fatty infiltration. Of these, three showed an increased mean T2 relaxation time (p < 0.05), two showed no change and four showed a decreased mean T2 relaxation time (p < 0.05).
Conclusion
T2 mapping is a feasible technique to evaluate the longitudinal muscle changes in those children who receive steroid therapy for DMD. The differences of the mean T2 relaxation time may reflect alterations in disease activity, and even when the conventional MRI and CFS remain stable.
doi:10.3348/kjr.2010.11.3.304
PMCID: PMC2864857  PMID: 20461184
Magnetic resonance (MR); Duchenne muscular dystrophy (DMD); Muscle; T2 relaxation time map
11.  Clinicopathologic Features and Long-Term Outcomes of Elderly Breast Cancer Patients: Experiences at a Single Institution in Korea 
Purpose
The purpose of this study was to assess the tumor characteristics and long-term clinical outcomes of adjuvant treatments after surgery with a curative aim for patients with breast cancer who are 65 years and older.
Materials and Methods
Patients with breast cancer who underwent curative surgery from 2000 to 2009 were analyzed (n=4,388). Tumor characteristics and survival outcome were compared by dividing the patients into two age groups (< 65 and ≥ 65 years old). The Kaplan-Meier method was used for comparison of survival rates by log-rank test, and a Cox regression model was used to examine the effect of variables.
Results
Among 4,388 patients with invasive breast cancer, 317 patients (7.2%) were 65 years or older and the median age of all patients was 47 years (range, 18 to 91 years). Tumor characteristics were similar between the two age groups, but the older patients were treated less often with adjuvant treatments. During a median follow-up period of 122 months, recurrence-free survival (RFS) was equivalent for patients 65 years and older compared to younger patients, but significantly worse in overall survival (OS) and breast cancer–specific survival (BCSS) (5-year OS, 94.3% vs. 90.5%; p < 0.001 and 5-year BCSS, 94.7% vs. 91.8%; p=0.031). In the multivariate model, age ≥ 65 years old was identified as an independent risk factor for OS and RFS.
Conclusion
Elderly breast cancer appeared to have worse outcomes with very low prevalence in Korea, despite similar tumor characteristics. More active adjuvant therapies would have a role for aggressive subtypes for fit, elderly patients.
doi:10.4143/crt.2015.423
PMCID: PMC5080825  PMID: 26987392
Breast neoplasms; Aged; Population characteristics; Treatment outcome
12.  Risk factors associated with early mortality in patients with multiple myeloma who were treated upfront with a novel agents containing regimen 
BMC Cancer  2016;16:613.
Background
Although the introduction of novel agents improved the survival outcomes in patients with multiple myeloma (MM), some patients died within one year (early mortality, EM) following diagnosis. In this study, we evaluated the EM rate, and investigated the risk factors associated with EM in MM patients.
Methods
Retrospective data from 542 patients who were initially treated with a novel agent-containing regimen were analyzed.
Results
The median overall survival (OS) for the entire cohort was 56.5 months. The median OS in the 2010–2014 group was longer than in the 2002–2009 group (59.2 months vs. 49.1 months, P = 0.054). The rate of EM was 13.8 %, and the most common causes of EM were infection and comorbidity. In multivariate analysis, the age-adjusted Charlson comorbidity index (ACCI ≥ 4), low body mass index (BMI < 20 kg/m2), thrombocytopenia, and renal failure were significantly associated with EM. The presence of none, 1, or ≥ 2 factors was associated with a 4.1 %, 14.3 %, or 27.4 % risk of EM (P < 0.001), respectively. The median OS times were significantly different depending on the presence of factors associated with EM (P < 0.001).
Conclusions
In conclusion, the ACCI (≥ 4), low BMI, thrombocytopenia and renal failure were strong predictors for EM in the novel agent era. The results of this study will help to identify patients at high risk for EM, and may be helpful to more accurately predict prognosis of MM patients in the novel-agent era.
doi:10.1186/s12885-016-2645-y
PMCID: PMC4977683  PMID: 27501959
Early mortality; Comorbidity; Thrombocytopenia; Multiple myeloma
13.  BEZ235 (PIK3/mTOR inhibitor) Overcomes Pazopanib Resistance in Patient-Derived Refractory Soft Tissue Sarcoma Cells 
Translational Oncology  2016;9(3):197-202.
BACKGROUND: Although pazopanib treatment has become the standard chemotherapy in salvage setting for metastatic sarcoma patients, most patients progress after pazopanib treatment in 4 to 6 months. After failure to pazopanib, patients have limited options for treatment. Therefore, subsequent therapy in patients who failed to pazopanib is urgently needed and the use of patient derived cells or patient derived tumors for accompanying testing with various pharmacological inhibitors could offer additional treatment options for these patients. METHODS: Patient derived tumor cells were collected from ascites at the time of progression to pazopanib and a 13-drug panel was tested for drug sensitivity. We confirmed the results using in vitro cell viability assay and immunoblot assay. We also performed the genomic profiling of PDX model. RESULTS: The growth of patient derived tumor cells was significantly reduced by exposure to 1.0 μM AZD2014 compared with control (control versus AZD2014, mean growth = 100.0% vs 16.04%, difference = 83.96%, 95% CI = 70.01% to 97.92%, P = .0435). Similarly, 1.0 μM BEZ235 profoundly inhibited tumor cell growth in vitro when compared to control (control versus BEZ235, mean growth = 100.0% vs 7.308%, difference = 92.69%, 95% CI = 78.87% to 106.5%, P < .0001). Despite the presence of CDK4 amplification in the patient-derived tumor cells, LEE011 did not considerably inhibit cell proliferation when compared with control (control vs LEE011, mean growth = 100.0% vs 80.23%, difference = 19.77%, 95% CI = 1.828% to 37.72%, P = .0377). The immunoblot analysis showed that BEZ235 treatment decreased pAKT, pmTOR and pERK whereas AZD2014 decreased only pmTOR. CONCLUSION: Taken together, upregulation of mTOR/AKT pathway in sarcoma patient derived cells was considerably inhibited by the treatment of AZD2014 and BEZ235 with downregulation of AKT pathway (greater extent for BEZ235). These molecules may be considered as treatment option in STS patient who have failed to pazopanib in the context of clinical trials.
doi:10.1016/j.tranon.2016.03.008
PMCID: PMC4907899  PMID: 27267837
14.  A Korean single-center, real-world, retrospective study of first-line weekly paclitaxel in patients with metastatic angiosarcoma 
Background
Angiosarcoma is a rare subgroup of soft tissue sarcomas associated with poor prognosis, but paclitaxel has been shown to be active in pretreated metastatic disease. We investigated the efficacy and safety of weekly paclitaxel as first-line chemotherapy in adult patients with metastatic angiosarcoma.
Methods
A retrospective study using the Samsung Medical Center (Seoul, Korea) cancer chemotherapy registry was performed on 21 consecutive patients with angiosarcoma who were treated with weekly paclitaxel as first-line therapy for metastatic disease between Oct. 2008 and Dec. 2014. We excluded patients who were enrolled in clinical trials to ensure the results would reflect the real-world outcomes obtained in a daily clinical setting. Endpoints included efficacy in terms of response rate, progression-free survival (PFS), overall survival (OS) and safety.
Results
Among 21 patients, 15 (71 %) were male and the median age was 53 years (range, 24–76). Primary sites of angiosarcoma were the visceral organs (33 %), scalp (29 %) and heart (23 %). The median number of metastatic sites was two (range, 1–5) with the lungs being the most frequently involved site. Weekly paclitaxel was generally well tolerated: the major hematologic toxicity was grade 1/2 anemia (24 %). Among non-hematologic toxicities, grade 1/2 peripheral neuropathy was most commonly observed (67 %). Objective response was observed in 11 (52 %) patients (4 complete and 7 partial responses). With a median follow-up of 21 months, the estimated median PFS and OS were 5.7 months (95 % CI 5.1–6.3) and 18.6 months (95 % CI 9.9–27.3), respectively.
Conclusions
In this retrospective study, first-line chemotherapy with weekly paclitaxel demonstrated clinically relevant efficacy and tolerability in unselected Korean patients with metastatic angiosarcoma. It is encouraging that response rate and PFS for Korean patients were similar to those reported in Western reports.
doi:10.1186/s13569-016-0048-0
PMCID: PMC4864900  PMID: 27175275
Angiosarcoma; Chemotherapy; Paclitaxel; Retrospective
15.  Immunoprevention of chemical carcinogenesis through early recognition of oncogene mutations 
Prevention of tumors induced by environmental carcinogens has not been achieved. Skin tumors produced by polyaromatic hydrocarbons, such as 7,12-dimethylbenzanthracene (DMBA) often harbor an H-ras point mutation, suggesting that it is a poor target for early immune surveillance. The application of pyrosequencing and allele-specific PCR techniques established that mutations in the genome and expression of the Mut H-ras gene could be detected as early as one day after DMBA application. Further, DMBA sensitization raised Mut H-ras epitope-specific CTLs capable of eliminating Mut H-ras+ pre-neoplastic skin cells, demonstrating that immunosurveillance is normally induced but may be ineffective due to insufficient effector pool size and/or immune suppression. To test whether selective pre-expansion of CD8 T cells with specificity for the single Mut H-ras epitope was sufficient for tumor prevention, MHC class I-epitope-focused lentivector-infected dendritic cell (DC)- and DNA-based vaccines were designed to bias toward CTL rather than Treg induction. Mut H-ras but not wild-type H-ras epitope-focused vaccination generated specific CTL and inhibited DMBA-induced tumor initiation, growth and progression in preventative and therapeutic settings. Transferred Mut H-ras-specific effectors induced rapid tumor regression, overcoming established tumor suppression in tumor bearing mice. These studies support further evaluation of oncogenic mutations for their potential to act as early tumor-specific, immunogenic epitopes to expand relavent immunesurviellance effectors in order to block tumor formation, rather than treating established tumors.
doi:10.4049/jimmunol.1402125
PMCID: PMC4355080  PMID: 25694611
16.  Pineal Diffuse Large B-Cell Lymphoma Concomitant With Pituitary Prolactinoma: Possible Correlation Between 2 Distinguished Pathologies 
Medicine  2016;95(8):e2923.
Abstract
This is the first reported case of pineal lymphoma with concomitant prolactin-producing pituitary adenoma.
A 51-year-old male experienced worsening headaches accompanied by nausea, diplopia, and memory loss for 1 month. Cranial nerve examination revealed bilateral upward gaze limitation with convergence impairment, which is known as Parinaud syndrome. Magnetic resonance images revealed a mass in the pineal gland with a coexisting mass within the enlarged sella fossa. Hormone analysis revealed hyperprolactinemia. The pineal mass was removed without injuring the hypothalamus, brain stem, or any neighboring vessels. Pathology examination confirmed the diagnosis of diffuse large B-cell lymphoma (DLBCL) involving the pineal gland. After further studies, the pineal lymphoma was determined to be a secondary tumor from a gastric primary tumor. The patient died 6 months after diagnosis due to systemic progression of DLBCL.
Although the mechanistic link between hyperprolactinemia and lymphoma progression has not been clarified on a clinical basis, high prolactin levels may contribute to the rapid progression and therapeutic resistance of the lymphoma.
doi:10.1097/MD.0000000000002923
PMCID: PMC4779034  PMID: 26937937
17.  Effect of the amount of thickness reduction on color and translucency of dental monolithic zirconia ceramics 
PURPOSE
This study investigated the effect of amount of thickness reduction on color and translucency of dental monolithic zirconia ceramics.
MATERIALS AND METHODS
One-hundred sixty-five monolithic zirconia specimens (16.3 mm × 16.3 mm × 2.0 mm) were divided into 5 groups (Group I to V) according to the number of A2-coloring liquid applications. Each group was then divided into 11 subgroups by reducing the thickness up to 1.0 mm in 0.1-mm increments (Subgroup 0 to 10, n=3). Colors and spectral distributions were measured according to CIELAB on a reflection spectrophotometer. All measurements were performed on five different areas of each specimen. Color difference (ΔE*ab) and translucency parameter (TP) were calculated. Data were analyzed using one-way ANOVA and multiple comparison Scheffé test (α=.05).
RESULTS
There were significant differences in CIE L* between Subgroup 0 and other subgroups in all groups. CIE a* increased (0.523.7) were obtained between Subgroup 0 and other subgroups. TP values generally increased as the thickness reduction increased in all groups (R2>0.89, P<.001).
CONCLUSION
Increasing thickness reduction reduces lightness and increases a reddish, bluish appearance, and translucency of monolithic zirconia ceramics.
doi:10.4047/jap.2016.8.1.37
PMCID: PMC4769888  PMID: 26949486
Y-TZP ceramic; Color; Dental Prosthesis Coloring
18.  Characteristics of Korean Patients with Antithyroid Drug-Induced Agranulocytosis: A Multicenter Study in Korea 
Endocrinology and Metabolism  2015;30(4):475-480.
Background
Antithyroid drugs (ATDs) can lead to the development of agranulocytosis, which is the most serious adverse effect. Characteristics of ATD-induced agranulocytosis (AIA) have seldom been reported due to the rarity. In this study, we characterized the clinical features for AIA in Korean patients.
Methods
We retrospectively reviewed data from patients with AIA diagnosed between 1997 and 2014 at four tertiary hospitals. Agranulocytosis was defined as an absolute neutrophil count (ANC) below 500/mm3.
Results
The mean age of the patients (11 males, 43 females) was 38.2±14.9 years. Forty-eight patients (88.9%) with AIA had fever and sore throat on initial presentation, 20.4% of patients developed AIA during the second course of treatment, and 75.9% of patients suffered AIA within 3 months after initiation of ATD. The patients taking methimazole (n=39) showed lower levels of ANC and more frequent use of granulocyte-macrophage colony-stimulating factor than propylthiouracil (n=15) users. The median duration of agranulocytosis was 5.5 days (range, 1 to 20). No differences were observed between the long (≥6 days) and short recovery time (≤5 days) groups in terms of age, gender, ATDs, duration of ATDs, or initial ANC levels. Four patients (7.4%) who were taking ATDs for less than 2 months died of sepsis on the first or second day of hospitalization.
Conclusion
The majority of AIA incidents occur in the early treatment period. Considering the high fatality rate of AIA, an early aggressive therapeutic approach is critical and patients should be well informed regarding the warning symptoms of the disease.
doi:10.3803/EnM.2015.30.4.475
PMCID: PMC4722401  PMID: 26394729
Graves disease; Antithyroid agents; Agranulocytosis
19.  Endobronchial ALK-Positive Anaplastic Large Cell Lymphoma Presenting Massive Hemoptysis 
Primary anaplastic large cell lymphoma (ALCL) of the lung is highly aggressive and quite rare. We report here a case of anaplastic lymphoma kinase-positive endobronchial ALCL, that was initially thought to be primary lung cancer. A 68-year-old woman presented with hemoptysis, dyspnea, and upper respiratory symptoms persisting since 1 month. The hemoptysis and and bronchial obstruction lead to respiratory failure, prompting emergency radiotherapy and steroid treatment based on the probable diagnosis of lung cancer, although a biopsy did not confirm malignancy. Following treatment, her symptoms resolved completely. Chest computed tomography scan performed 8 months later showed increased and enlarged intra-abdominal lymph nodes, suggesting lymphoma. At that time, a lymph node biopsy was recommended, but the patient refused and was lost to follow up. Sixteen months later, the patient revisited the emergency department, complaining of persistent abdominal pain since several months. A laparoscopic intra-abdominal lymph node biopsy confirmed a diagnosis of ALCL.
doi:10.4046/trd.2015.78.4.390
PMCID: PMC4620337  PMID: 26508931
Large Cell Lymphoma; Respiratory Failure; Hemoptysis
21.  Synchronous Pancreatic Ductal Adenocarcinomas Diagnosed by Endoscopic Ultrasound-Guided Fine Needle Biopsy 
Gut and Liver  2015;9(5):685-688.
Cases of pancreatic ductal adenocarcinoma with multiple masses accompanying underlying pancreatic diseases, such as intraductal papillary mucinous neoplasm, have been reported. However, synchronous invasion without underlying pancreatic disease is very rare. A 61-year-old female with abdominal discomfort and jaundice was admitted to our hospital. Abdominal computed tomography (CT) revealed cancer of the pancreatic head with direct invasion of the duodenal loop and common bile duct. However, positron emission tomography-CT showed an increased standardized uptake value (SUV) in the pancreatic head and tail. We performed endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) for the histopathologic diagnosis of the pancreatic head and the evaluation of the increased SUV in the tail portion of the pancreas, as the characteristics of these lesions could affect the extent of surgery. As a result, pancreatic ductal adenocarcinomas were confirmed by both cytologic and histologic analyses. In addition, immunohistochemical analysis of the biopsy specimens was positive for carcinoembryonic antigen and p53 in both masses. The two masses were ultimately diagnosed as pancreatic ductal adenocarcinoma, stage IIB, based on EUS-FNB and imaging studies. In conclusion, the entire pancreas must be evaluated in a patient with a pancreatic mass to detect the rare but possible presence of synchronous pancreatic ductal adenocarcinoma. Additionally, EUS-FNB can provide pathologic confirmation in a single procedure.
doi:10.5009/gnl14215
PMCID: PMC4562788  PMID: 26087782
Carcinoma; pancreatic ductal; Neoplasms; multiple primary; Endoscopic ultrasound-guided fine needle aspiration; Biopsy; large-core needle
22.  Warfarin skin necrosis mimicking calciphylaxis in a patient with secondary hyperparathyroidism undergoing peritoneal dialysis 
Warfarin skin necrosis (WSN) is an infrequent complication of warfarin treatment and is characterized by painful ulcerative skin lesions that appear a few days after the start of warfarin treatment. Calciphylaxis also appears as painful skin lesions caused by tissue injury resulting from localized ischemia caused by calcification of small- to medium-sized vessels in patients with end-stage renal disease. We report on a patient who presented with painful skin ulcers on the lower extremities after the administration of warfarin after a valve operation. Calciphylaxis was considered first because of the host factors; eventually, the skin lesions were diagnosed as WSN by biopsy. The skin lesions improved after warfarin discontinuation and short-term steroid therapy. Most patients with end-stage renal disease have some form of cardiovascular disease and some require temporary or continual warfarin treatment. It is important to differentiate between WSN and calciphylaxis in patients with painful skin lesions.
doi:10.1016/j.krcp.2015.07.003
PMCID: PMC4811981  PMID: 27069859
Calciphylaxis; End-stage renal disease; Warfarin skin necrosis
23.  Ultrasonographic differentiation of bezoar from feces in small bowel obstruction 
Ultrasonography  2015;34(3):211-216.
Purpose:
To evaluate ultrasonographic accuracy in the differentiation of a bezoar from feces in a small bowel obstruction showing feces-like material just proximal to the transitional zone in abdominal computed tomography (CT).
Methods:
This study included 14 patients who showed feces-like material just proximal to the transitional zone, among 302 patients diagnosed with small bowel obstruction on abdominal CT. The diagnostic signs of a bezoar on ultrasonography included an arc-like surfaced intraluminal mass, posterior acoustic shadow and twinkling artifacts. The diagnostic performance of ultrasonography in each patient was compared with a final diagnosis that was surgically or clinically made.
Results:
Among the 14 patients, seven were ultrasonographically diagnosed as having a bezoar, and five of the seven were surgically diagnosed as having a phytobezoar. The remaining two of the seven showed complete symptomatic improvement before surgery. The other seven patients were ultrasonographically diagnosed as not having a bezoar. Among them, six patients were conservatively treated with symptomatic improvement, suggesting the absence of a bezoar. The remaining one patient was confirmed not to have a bezoar during adhesiolysis. In all patients, the ultrasonographic diagnosis agreed with the clinically confirmed diagnosis.
Conclusion:
Ultrasonography might be an accurate method for the differential diagnosis of feces-like material just proximal to the transitional zone in abdominal CT. It can help radiologists to quickly and easily diagnose a bezoar.
doi:10.14366/usg.14070
PMCID: PMC4484283  PMID: 25868731
Ultrasonography; Bezoars; Intestinal obstruction; Intestine, small
24.  Dissecting metal ion-dependent folding and catalysis of a single DNAzyme 
Nature chemical biology  2007;3(12):763-768.
Protein metalloenzymes use various modes for functions where metal–dependent global conformational change is required in some cases, but not in others. In contrast, most ribozymes appear to require a global folding that almost always precedes enzyme reactions. Herein we studied metal–dependent folding and cleavage activity of the 8–17 DNAzyme using single molecule fluorescence resonance energy transfer (FRET). Addition of Zn2+ and Mg2+ resulted in a folding step followed by cleavage reaction, suggesting that the DNAzyme may require metal–dependent global folding for activation. In the presence of Pb2+, however, cleavage reaction occurred without a precedent folding step, suggesting that the DNAzyme may be prearranged to accept Pb2+ for the activity. This feature may contribute to the remarkably fast Pb2+–dependent reaction of the DNAzyme. These results suggest that DNAzymes can use all modes of activation that metalloproteins use.
doi:10.1038/nchembio.2007.45
PMCID: PMC4376948  PMID: 17965708
25.  Immunoprevention of Chemical Carcinogenesis through Early Recognition of Oncogene Mutations 
Prevention of tumors induced by environmental carcinogens has not been achieved. Skin tumors produced by polyaromatic hydrocarbons, such as 7,12-dimethylbenz(a)anthracene (DMBA), often harbor an H-ras point mutation, suggesting that it is a poor target for early immunosurveillance. The application of pyrosequencing and allele-specific PCR techniques established that mutations in the genome and expression of the Mut H-ras gene could be detected as early as 1 d after DMBA application. Further, DMBA sensitization raised Mut H-ras epitope–specific CTLs capable of eliminating Mut H-ras+ preneoplastic skin cells, demonstrating that immunosurveillance is normally induced but may be ineffective owing to insufficient effector pool size and/or immunosuppression. To test whether selective pre-expansion of CD8 T cells with specificity for the single Mut H-ras epitope was sufficient for tumor prevention, MHC class I epitope–focused lentivector-infected dendritic cell– and DNA-based vaccines were designed to bias toward CTL rather than regulatory T cell induction. Mut H-ras, but not wild-type H-ras, epitope-focused vaccination generated specific CTLs and inhibited DMBA-induced tumor initiation, growth, and progression in preventative and therapeutic settings. Transferred Mut H-ras–specific effectors induced rapid tumor regression, overcoming established tumor suppression in tumor-bearing mice. These studies support further evaluation of oncogenic mutations for their potential to act as early tumor-specific, immunogenic epitopes in expanding relevant immunosurveillance effectors to block tumor formation, rather than treating established tumors.
doi:10.4049/jimmunol.1402125
PMCID: PMC4355080  PMID: 25694611

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