High Expression of NRF2 and Low Expression of KEAP1 Predict Worse Survival in Patients With Operable Triple-Negative Breast Cancer / 한국유방암학회지

Purpose@#Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer.Currently, no effective treatment options for this condition exist. Nuclear factor erythroid 2-related factor 2 (NRF2), encoded by nuclear factor erythroid-derived 2-like 2 (NFE2L2) gene and its endogenous inhibitor, Kelch-like ECH-associated protein 1 (KEAP1), both participate in cellular defense mechanisms against oxidative stress and contribute to chemoresistance and tumor progression in numerous types of cancers. This study aimed to evaluate the expression patterns of NRF2 and KEAP1 and their prognostic value in operable TNBC. @*Methods@#Tissue microarrays were prepared using tumor tissues collected from 203 patients with TNBC who underwent surgery. Immunohistochemical staining analyses of NRF2 and KEAP1 were performed. The expression of each immunomarker was categorized into two groups (low or high) based on the median H-score. We analyzed the association between the expression of each immunomarker and clinicopathological information to predict survival.A total of 225 TNBC samples from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset were used to validate our results. @*Results@#NRF2 immunoreactivity was detected in the nucleus and was associated with histologic grade and Ki-67 index, whereas KEAP1 immunoreactivity was detected in the cytoplasm and was associated with the Ki-67 index. Survival analyses showed that NRF2 and KEAP1 expressions were independent prognostic factors for overall survival (OS) (hazard ratio [HR], 2.45 and 0.30; p = 0.015 and 0.016, respectively) and disease-free survival (HR, 2.27 and 0.42; p = 0.019 and 0.022, respectively). NFE2L2 mRNA expression was an independent prognostic factor for OS (HR, 0.59; p = 0.009) in the METABRIC dataset. @*Conclusion@#High NRF2 and low KEAP1 expressions independently predicted poor survival in patients with operable TNBC. Further investigations are warranted to examine the possible therapeutic benefits of targeting the KEAP1-NRF2 pathway for TNBC treatment.

Lead, Mercury, and Cadmium Exposure in the Korean General Population

BACKGROUND: Lead (Pb), mercury (Hg), and cadmium (Cd) are well-known environmental pollutants. They are unnecessary in the biological processes of humans. This study was performed to estimate the representative background exposure levels to the metals by measuring concentrations in whole blood of the Korean general population. METHODS: This population-based cross-sectional study included 4,000 subjects (1,886 males and 2,114 females) 0–83 years of age in 2010 and 2011. Adult subjects (≥ 19 years of age) were collected by sex- and age-stratified probability method, and preschool- and school-aged subjects were recruited by a cluster sampling method. Written consent was provided prior to blood sampling. Pb and Cd blood concentrations were determined by a flameless atomic absorption spectrophotometry, and blood Hg was analyzed by a direct Hg analyzer. RESULTS: The geometric mean, median and 95th percentile of blood Pb was 1.82 µg/dL, 1.83 µg/dL, and 3.78 µg/dL, respectively. The respective values were 2.92 µg/L, 2.87 µg/L, 9.12 µg/L for Hg, and 0.56 µg/L, 0.59 µg/L, 2.20 µg/L for Cd. Blood Pb and Hg were higher in males than in females, but no sex difference was observed, respectively, in subjects 0–4 years of age for Pb and in subjects less than 20 years for Hg. However, blood Cd was higher in females than in males and no sex difference was observed in subjects < 30 years of age. CONCLUSION: This study provides representative data of human exposure to Pb, Hg, and Cd covering whole age groups of the general population in Korea.

Eccrine Hidrocystoma in External Auditory Canal / 대한이비인후과학회지

Hidrocystomas, eccrine or apocrine are rare ductal cystic benign lesions of the sweat gland. These uncommon cystic lesions are extremely rare in the external ear. Here, we discuss the clinical features and management of eccrine hydrocystoma in the external ear by describing the clinical, radiographic, pathologic features and management of an external auditory canal eccrine hidrocystoma in a 73-year-old Korean man. To the best of our knowledge, this tumor has not been reported previously in this site. Five month after surgery, there has been no evidence of local recurrence.

Is Alcohol Swabbing Sufficient to Clean Otoscopes in Hospitals? / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: An otoscope is a basic instrument used by otorhinolaryngologists. An inappropriately sterilized otoscope has been reported to be a possible bacterial vector for infection. In this regard, we decided to investigate contaminated otoscopes for possible bacterial contamination and evaluate the efficacy of the otoscope disinfection methods. MATERIALS AND METHOD: We randomly drew 22 otoscope cones from university hospitals and 10 from private hospitals. Cones were divided into three groups accordingly to their sterilization methods: group 1 was wiped with 70% isopropyl alcohol, group 2 was soaked for 20 min in 70% isopropyl alcohol, and group 3 was soaked in CIDEX solution. The samples were cultured twice, first before the disinfection process and then after the disinfection process. Otoscopes were cleaned for a week by employing these techniques. RESULTS: Most of the pre-sterilized otoscopes (20/22) were obtained from the hospitals which demonstrated contamination with microorganisms. Staphylococcus was the most common bacteria found (16/22). After a week of cleansing, no bacteria were seen in group 1 (0%, 0/8), whereas group 2 (14.3%, 1/7), and group 3 (28.6%, 2/7) still showed remaining microorganisms. The three methods were significantly effective on sterilizing microorganisms. CONCLUSION: An otoscope can be a vector for spreading infection. We found that disinfection by alcohol-swabbing alone is sufficient for sterilizing otoscope cones. Clinically, this information may be useful to otorhinolaryngologists. However, further studies are required to establish the most appropriate disinfection protocol to prevent infection from microorganisms.

Primary Neurilemmoma of the Thyroid Gland Clinically Mimicking Malignant Thyroid Nodule

No abstract available.

Clinical efficacy of the classic laryngeal mask airway in elderly patients: a comparison with young adult patients / 대한마취과학회지

BACKGROUND: The elderly have been reported to show anatomical and physiologic changes in the upper airway, which might affect the supraglottic airway (SGA) performance in geriatric populations. This study aimed to evaluate the clinical efficacy of the classic laryngeal mask airway (LMA-C) in the elderly compared with young adult patients. METHODS: Fifty patients aged 65-85 years (elderly group) and 50 patients aged 20-40 years (young group) who were scheduled for surgery using the LMA-C for general anesthesia were enrolled in this prospective, non-randomized, comparative study. Manipulations required during insertion, success rate, insertion time, oropharyngeal leak pressure, gastric insufflation, and intraoperative inadequate ventilation with the LMA-C were assessed. Fiberoptic evaluation was used to determine the position of the LMA-C. RESULTS: In the elderly group, the insertion success rate on the first attempt was significantly lower than that in the young group (84 vs. 96%, P = 0.02). The insertion time in the elderly group was significantly longer than that in the young group (28.5 +/- 19.6 vs. 22.2 +/- 6.4 seconds, P = 0.001). However, there was no difference in oropharyngeal leak pressure or fiberoptic grade between the two groups after proper placement of the LMA-C. During the surgery, inadequate ventilation events occurred more frequently in the elderly group than in the young group (31.3 vs. 4.0%, P < 0.001). CONCLUSIONS: The clinical efficacy of the LMA-C in elderly patients was inferior to that in young adult patients. Therefore, further studies are required to determine the type of SGA that can provide excellent clinical efficacy in the geriatric population.

Classic Papillary Thyroid Carcinoma with Tall Cell Features and Tall Cell Variant Have Similar Clinicopathologic Features

BACKGROUND: The tall cell variant of papillary thyroid carcinoma (TCVPTC) is more aggressive than classic papillary thyroid carcinoma (PTC), but the percentage of tall cells needed to diagnose TCVPTC remains controversial. In addition, little is known about the clinicopathologic features of classic PTC with tall cell features (TCF). METHODS: We retrospectively selected and reviewed the clinicopathologic features and presence of the BRAF mutation in 203 cases of classic PTC, 149 cases of classic PTC with TCF, and 95 cases of TCVPTCs, which were defined as PTCs having or =50% tall cells, respectively. RESULTS: TCVPTCs and classic PTCs with TCF did not vary significantly in clinicopathologic characteristics such as pathologic (p) T stage, extrathyroidal extension, pN stage, lateral lymph node metastasis, or BRAF mutations; however, these features differed significantly in TCVPTCs and classic PTCs with TCF in comparison to classic PTCs. Similar results were obtained in a subanalysis of patients with microcarcinomas (< or =1.0 cm in size). CONCLUSIONS: Classic PTCs with TCF showed a similar BRAF mutation rate and clinicopathologic features to TCVPTCs, but more aggressive characteristics than classic PTCs.

Immunoglobulin G4-Related Hypertrophic Pachymeningitis with Skull Involvement

Immunoglobulin G4 (IgG4)-related hypertrophic pachymeningitis, defined as focally or diffusely thickened dura mater and lymphoplasmacytic infiltration with increased IgG4 bearing plasma cells, is a rare disease. Moreover, cases involving bone are even rarer. In this report, the authors describe a case of IgG4-related hypertrophic pachymeningitis involving the skull in a 65-year-old man presenting with generalized tonic seizures. There is a 2.4 cm diameter extra-axial mass at the vertex of the left frontal convexity and thickened dura mater with contrast enhancement on magnetic resonance (MR) imaging. In addition, the skull adjacent to the mass was focally enhanced. He underwent surgical resection of the enhanced mass and skull. Histopathological findings revealed chronic inflammation with fibrosis, and idiopathic hypertrophic intracranial pachymeningitis was considered. However, eight months after surgery, partial seizures developed and brain MR imaging revealed a recurrence adjacent to the previous mass. We decided to perform additional immunohistochemical staining of the previous specimen, instead of a re-excision. Immunohistochemical staining showed markedly increased IgG4 (+) plasma cells. Consequently, IgG4-related hypertrophic meningitis was confirmed. Since then, steroids and immunosuppressant medications were started. Follow-up MR imaging at 3 months after medication initiation demonstrated complete remission. In conclusion, IgG4-related hypertrophic pachymeningitis should be considered in the differential diagnosis of hypertrophic cranial pachymeningitis.

Clinicopathological Features of Rare BRAF Mutations in Korean Thyroid Cancer Patients

The most common BRAF mutation in thyroid cancer is c.1799T>A (p.Val600Glu), and other BRAF mutations are rarely reported. We investigated the clinicopathological features of thyroid cancer with rare BRAF mutations. A total of 2,763 patients with thyroid cancer underwent molecular testing by direct DNA sequencing for mutations in BRAF exon 15. Among them, 2,110 (76.4%) had BRAF mutations. The c.1799T>A mutation was found in 2,093 (76.9%) of 2,722 papillary carcinomas and in one of 7 medullary carcinomas. Sixteen cases (0.76%) harbored rare mutation types. Five cases had single-nucleotide substitutions, 5 cases had small in-frame deletion or insertion, and one harbored a two-nucleotide substitution. Of these mutations, 2 were novel (c.1797_1798insGAGACTACA, c.[1799T>A; 1801_1812del]). The c.1801A>C mutation was identified in 4 follicular variant papillary carcinomas and one follicular carcinoma. None of the patients with the c.1801A>C mutation showed extrathyroidal extension or lymph node metastasis. The prevalence of rare BRAF mutations was 0.76% of all BRAF-positive thyroid cancers, and the rare mutations were associated with less aggressive pathologic features. Although BRAF mutations are detected exclusively in papillary carcinoma, they are also found in medullary carcinoma and follicular carcinoma.

Erratum: Correction of Nomenclature of BRAF Mutation

We made a mistake in our recently published article.

Histologic Disorderliness in the Arrangement of Tumor Cells as an Objective Measure of Tumor Differentiation

BACKGROUND: Inter-observer and intra-observer variation in histologic tumor grading are well documented. To determine whether histologic disorderliness in the arrangement of tumor cells may serve as an objective criterion for grading, we tested the hypothesis the degree of disorderliness is related to the degree of tumor differentiation on which tumor grading is primarily based. METHODS: Borrowing from the statistical thermodynamic definition of entropy, we defined a novel mathematical formula to compute the relative degree of histologic disorderliness of tumor cells. We then analyzed a total of 51 photomicrographs of normal colorectal mucosa and colorectal adenocarcinoma with varying degrees of differentiation using our formula. RESULTS: A one-way analysis of variance followed by post hoc pairwise comparisons using Bonferroni correction indicated that the mean disorderliness score was the lowest for the normal colorectal mucosa and increased with decreasing tumor differentiation. CONCLUSIONS: Disorderliness, a pathologic feature of malignant tumors that originate from highly organized structures is useful as an objective tumor grading proxy in the field of digital pathology.

Performance Measurement of Siemens Inveon PET Scanner for Small Animal Imaging / 의학물리

Inveon PET is a recently developed preclinical PET system for small animal. This study was conducted to measure the performance of Inveon PET as recommended by the NEMA NU 4-2008. We measured the spatial resolution, the sensitivity, the scatter fraction and the NECR using a F-18 source. A 3.432 ns coincidence window was used. A 1 mm3 sized F-18 point source was used for the measurement of spatial resolution within an energy window of 350~625 keV. PET acquisition was performed to obtain the spatial resolution from the center to the 5 cm offset toward the edge of the transverse FOV. Sensitivity, scatter fraction, and NECR were measured within an energy window of 350~750 keV. For measuring the sensitivity, a F-18 line source (length: 12.7 cm) was used with concentric 5 aluminum tubes. For the acquisition of the scatter fraction and the NECR, two NEMA scatter phantoms (rat: 50 mm in diameter, 150 mm in length; mouse: 25 mm in diameter, 70 mm in length) were used and the data for 14 half-lives (25.6 hr) was obtained using the F-18 line source (rat: 316 MBq, mouse: 206 MBq). The spatial resolution of the F-18 point source was 1.53, 1.50 and 2.33 mm in the radial, tangential and axial directions, respectively. The volumetric resolution was 5.43 mm3 in the center. The absolute sensitivity was 6.61%. The peak NECR was 486 kcps @121 MBq (rat phantom), and 1056 kcps @128 MBq (mouse phantom). The values of the scatter fraction were 20.59% and 7.93% in the rat and mouse phantoms, respectively. The performances of the Inveon animal PET scanner were measured in this study. This scanner will be useful for animal imaging.

The Evaluation of Scattering Effects for Various Source Locations within a Phantom in Gamma Camera / 의학물리

(131)I is a radiological isotope being used widely for treatment of cancer as emitting gamma-ray and it is also applied to estimate the function of thyroid for its accumulation in thyroid. However, (131)I is more difficult to quantitate comapred to (99m)Tc, because (131)I has multiple energy gamma-ray emissions compared to (99m)Tc which is a mono energetic gamma-ray source. Especially, scattered ray and septal penetration resulted by high energy gamma ray have a bad influence upon nuclear medicine image. The purpose of this study was to estimate scatter components depending on the different source locations within a phantom using Monte Carlo simulation (GATE). The simulation results were validated by comparing with the results of real experiments. Dual-head gamma camera (ECAM, Chicago, Illinois Siemens) with high energy, general-purpose, and parallel hole collimators (hole radius: 0.17 cm, septal thickness: 0.2 cm, length: 5.08 cm) was used in this experiment. The NaI crystal is 44.5x59.1 cm in height and width and 0.95 cm in thickness. The diameter and height of PMMA phantom were 16 cm and 15 cm, respectively. The images were acquired at 5 different locations of (131)I point source within the phantom and the images of (99m)Tc were also acquired for comparison purpose with low energy source. The simulation results indicated that the scattering was influenced by the location of source within a phantom. The scattering effects showed the same tendency in both simulation and actual experiment, and the results showed that the simulation was very adequate for further studies. The results supported that the simulation techniques may be used to generalize the scattering effects as a function of a point source location within a phantom.

A Case of Kinky Hair Disease

Kinky hair disease is X-linked recessive neurodegenerative disorder produced by defects in a gene(ATP7A) that encodes an intracellular copper-transporting ATPase. About 90-95% of the patients have a severe clinical course leading to death in early childhood. ATP7A mutations associated with Menkes disease show great variety from cytogenetic abnormalities to partial gene deletions to single base-pair changes. We experienced a 15 month-old boy with loss of developmental milestones, hypotonia, seizures and failure to thrive. On laboratory findings, the levels of serum copper and ceruloplasmin were low. Electron microscopy of hair illustrated pathognomic pili torti and other abnormalities such as trichorrhexis nodosa and trichoptilosis(longitudinal splitting of the shaft). Brain magnetic resonance image showed diffuse cerebral and cerebellar atrophy with tortousity of cerebral blood vessels. Genetic defect was evaluated. Our sequencing data on the amplified exon 19 of ATP7ase genomic DNA confirmed point mutation, G1255A, resulting in a glycine-to-arginine conversion. So, we report a brief view with the related literatures.

Clonality of Lymphocytic Interstitial Pneumonia in Common Variable Immunodeficiency / 대한소아혈액종양학회지

Common variable immunodeficiency (CVID) is a heterogenous syndrome characterized by hypogammaglobulinemia, various immunologic abnormalities and recurrent bacterial infections. Associated immunologic abnormalities consists of various kinds of autoimmune diseases and lymphoproliferative disorders. The lymphoproliferative disorder take several forms, such as malignant lymphoma, atypical lymphoid hyperplasia, and beniegn lymphoid hyperplasia. Lymphocytic interstitial pneumonia (LIP), which is a kind of atypical lymphoid hyperplasia, develop in young age groups and has controversy on its clonality. We experienced a 14-year-old female patient with LIP and CVID. We analysed the third complementarity-determining region (CDR3) of the immunoglobulin heavy chain gene for clonality analysis. Clonality analysis of lung biopsy specimen revealed that 6 of 13 colony and 4 of 13 colony have identical sequences respectively. We speculate that one of these 2 lymphoid cell clone may develop into malignant lymphoma in the future.

Gastrointestinal Foreign Bodies in Children: Experiences of 60 Cases in Kangwon, Korea / 대한소아소화기영양학회지

PURPOSE: Ingested foreign bodies present a common clinical problem. It is well known that most of them pass uninterrupted through the gastrointestinal tract. We evaluated the role of endoscopy and Foley catheter for removal of foreign bodies in the gastrointestinal tract. METHODS: We investigated retrospectively 60 cases with foreign bodies in the gastrointestinal tract. They had been treated at Wonju Christian Hospital, Yonsei University of Korea, from January, 1996 through December, 1999. RESULTS: The age of the patients ranged from 7 months to 13 years. Patients under 5 years were 57 cases (97%) and there was no significant difference in sex (M : F=1.07 : 1). 45 cases of the patients had no symptom. The most common foreign bodies were coins (43 cases). The most common location was esophagus (31 cases). The number of foreign body removal using flexible endoscopy and Foley catheter was 22 (36.7%) and 18 (30.0%) cases, respectively. In 18 cases (30.0%), foreign bodies passed spontaneously. Only 1 case (1.7%), curtain pin impaction at ileocecal region, required surgery. CONCLUSION: Early foreign body removal from esophagus and stomach is recommended to lessen the morbidity and complication. Fluoroscopic foley catheter technique and flexible endoscopy for removal of esophageal foreign bodies in children is safe and effective.