Increased Screening Rates for Thyroid Cancer Among Residents Living Near Nuclear Power Plants

Frequent screening for thyroid cancer has been suggested as a probable explanation for the observed high risk of thyroid cancer in nuclear power plant (NPP) areas. We aimed to compare thyroid cancer screening rates of residents living near NPPs to those of the general population. This study utilized data from two national survey-based studies in 2016 and in 2014, respectively, for residents (n = 1,200) living in administrative districts within 5 km of NPP sites as the interest group, and the general population (n = 228,712) including distantliving residents (n = 19,100) in administrative districts within 30 km of NPP sites as reference groups. We observed an increase in screening rates in residents near NPPs, which may lead to a higher possibility of thyroid cancer detection. Therefore, further epidemiological studies investigating radiation-induced thyroid cancer risk among residents near NPPs should be carefully designed and interpreted considering possible detection bias.

Reliability and Validity of a Nationwide Survey (the Korean Radiation Workers Study)

Background@#This study aimed to evaluate the reliability and validity of the self-administered questionnaire for Korean radiation workers. @*Methods@#From May 24, 2016, to June 30, 2017, 20,608 participants completed the questionnaire, providing information on sociodemographics, lifestyle, work history and practices, medical radiation exposure, and medical history, which was linked to the National Dose Registry and the National Cancer Registry. The validity of the questionnaire was evaluated using the responses of 20,608 workers, and reliability was evaluated using the responses of 3043 workers who responded to the survey twice. @*Results@#Responses concerning demographic characteristics and lifestyle showed reliability with a moderate-to-high agreement (kappa: 0.43–0.99), whereas responses concerning occupation and medical radiation exposure had a wide range of agreement (kappa: 0.05–0.95), possibly owing to temporal variability during employment. Regarding validity, responses to the question about the first year of employment had an excellent agreement with the national registry (intraclass correlation coefficient = 0.9); however, responses on cancer history had a wide range of agreement (kappa: 0.22–0.85). @*Conclusion@#Although the reliability and validity of the questionnaire were not distinguished by demographic characteristics, they tended to be low among participants whose occupational radiation exposure was minimal. Overall, the information collected can be reliable for epidemiological studies; however, caution must be exercised when using information such as medical exposure and work practices, which are prone to temporal variability.

Radiation-related occupational cancer and its recognition criteria in South Korea

Ionizing radiation is a well-known carcinogen, and is listed as one carcinogenic agent of occupational cancer. Given the increase in the number of workers exposed to radiation, as well as the increase in concern regarding occupational cancer, the number of radiation-related occupational cancer claims is expected to increase. Unlike exposure assessment of other carcinogenic agents in the workplace, such as asbestos and benzene, radiation exposure is usually assessed on an individual basis with personal dosimeters, which makes it feasible to assess whether a worker's cancer occurrence is associated with their individual exposure. However, given the absence of a threshold dose for cancer initiation, it remains difficult to identify radiation exposure as the root cause of occupational cancer. Moreover, the association between cancer and radiation exposure in the workplace has not been clearly established due to a lack of scientific evidence. Therefore, criteria for the recognition of radiation-related occupational cancer should be carefully reviewed and updated with new scientific evidence and social consensus. The current criteria in Korea are valid in terms of eligible radiogenic cancer sites, adequate latent period, assessment of radiation exposure, and probability of causation. However, reducing uncertainty with respect to the determination of causation between exposure and cancer and developing more specific criteria that considers mixed exposure to radiation and other carcinogenic agents remains an important open question.

Cytological Features That Differentiate Follicular Neoplasm from Mimicking Lesions

BACKGROUND: It is difficult to correctly diagnose follicular neoplasms (FNs) on fine-needle aspiration cytology (FNAC) because it shares many cytological features with other mimicking lesions. The aim of this study was to identify the cytological features that differentiate FNs from mimicking lesions. METHODS: We included the cytological slides from 116 cases of thyroid FN diagnosed on FNAC, and included their subsequent histological diagnoses. We evaluated the cytological architectural pattern and nuclear features of the lesions according to their histological groups. RESULTS: The final histological diagnoses of the 116 cases varied, and included 51 FNs (44%), 47 papillary thyroid carcinomas (40%) including follicular variant, and seventeen cellular nodular hyperplasias (15%). Regardless of the final histological diagnosis, microfollicular pattern was observed in most cases. On the other hand, trabecular pattern was identified in 34% of FNs, but not in any other lesions. Additionally, elongated nuclei and ground glass chromatin were found in only some papillary thyroid carcinomas. CONCLUSIONS: This study shows that the trabecular pattern is a representative cytological feature of FNs that can be used to distinguish FNs from mimicking lesions. In addition, nuclear shape and chromatin pattern can be used to further confirm the diagnosis of FNs from mimicking lesions through FNAC.

The Significance of TROP2 Expression in Predicting BRAF Mutations in Papillary Thyroid Carcinoma

BACKGROUND: Trophoblast antigen 2 (TROP2) is a human trophoblast cell-surface glycoprotein that is overexpressed in several types of epithelial cancers, and is suggested to be associated with an unfavorable prognosis. BRAF mutations are the most common genetic alteration in papillary thyroid carcinoma (PTC). We evaluated the correlation between TROP2 expression and BRAF mutation in PTC. METHODS: First, we carried out pyrosequencing for BRAF mutations and immunohistochemistry for TROP2 expression with a tissue microarray consisting of 52 PTC cases. Membranous staining in at least 5% of tumor cells was designated as positive staining and we analyzed the relationship between TROP2 expression and diverse clinicopathological factors, including BRAF mutation. Second, we tested TROP2 mRNA expression in three thyroid cancer cell lines with BRAF mutations (BCPAP, SNU790, and 8505C) and a normal thyroid cell line. Additionally, we checked TROP2 protein levels in a normal thyroid cell line after introduction of the BRAF V600E mutation. RESULTS: In this study, 21 of 26 cases with BRAF mutation showed TROP2 immunoreactivity, whereas all 26 cases without BRAF mutation showed no immunoreactivity for TROP2 with a statistically significant difference (p<.001). Upregulation of TROP2 mRNA was observed in all three thyroid cancer cell lines, but not in the normal thyroid cell line. Interestingly, however, the TROP2 expression was increased in the normal thyroid cell line after introduction of the BRAF V600E mutation. CONCLUSIONS: Based on these results, we concluded that TROP2 expression is significantly associated with BRAF mutation and that TROP2 immunohistochemistry could be used for predicting BRAF mutations or diagnosing papillary thyroid carcinoma.

Importance of Individual Ghost Cells in Fine-Needle Aspiration Cytology Diagnosis of Pilomatricoma

BACKGROUND: Although histological diagnosis of pilomatricoma is not difficult because of its unique histological features, cytological diagnosis through fine-needle aspiration cytology (FNAC) is often problematic due to misdiagnoses as malignancy. METHODS: We reviewed the cytological features of 14 cases of histologically-proven pilomatricoma from Korea Cancer Center Hospital, with a discussion on the diagnostic pitfalls of FNAC. RESULTS: Among 14 cases of pilomatricoma, 10 (71.4%) were correctly diagnosed through FNAC, and two (14.3%) were misdiagnosed as carcinoma. Cytologically, all cases had easily recognizable clusters of basaloid cells and foreign body-type multinucleated cells. Although ghost cells were also found in all cases, some were inconspicuous and hardly recognizable due to their small numbers. CONCLUSIONS: An accurate diagnosis of pilomatricoma in FNAC is feasible with consideration of clinical information and close examination of ghost cells.

The Role of Notch1 Signaling in Anaplastic Thyroid Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The Notch signaling pathway is widely expressed in normal, reactive, and neoplastic tissues; however, its role in thyroid tissues has not been fully elucidated. Therefore, this study was conducted to characterize the expression of the Notch signaling pathway in papillary thyroid cancer (PTC) cells and anaplastic thyroid cancer (ATC) cells. MATERIALS AND METHODS: Expression of activated Notch1 in ATC and PTC paraffin-embedded tissues was determined by immunohistochemistry. The small interfering RNA techniquewas employed to knock down Notch1 expression in ATC and PTC cell lines. RESULTS: The expression of activated Notch1 was higher in ATC cases than in PTC cases. Inhibition of Notch1 significantly reduced proliferation and migration of ATC cells, but not PTC cells. In addition, inhibition of Notch1 in ATC cells significantly reduced the expression of key markers of epithelial-mesenchymal transition and cancer stem cells. Conversely, changes in the expression of these proteins were not observed in PTC cells. CONCLUSION: The results of this study suggest that Notch1 expression plays different roles in tumor progression in ATC and PTC cells. We also found that Notch1 expression was significantly related to the highly invasive or proliferative activity of ATC cells.

Establishment of Hepatocellular Cancer Induced Pluripotent Stem Cells Using a Reprogramming Technique

BACKGROUND/AIMS: Cancer is known to be a disease by many factors. However, specific results of reprogramming by pluripotency-related transcription factors remain to be scarcely reported. Here, we verified potential effects of pluripotent-related genes in hepatocellular carcinoma cancer cells. METHODS: To better understand reprogramming of cancer cells in different genetic backgrounds, we used four liver cancer cell lines representing different states of p53 (HepG2, Hep3B, Huh7 and PLC). Retroviral-mediated introduction of reprogramming related genes (KLF4, Oct4, Sox2, and Myc) was used to induce the expression of proteins related to a pluripotent status in liver cancer cells. RESULTS: Hep3B cells (null p53) exhibited a higher efficiency of reprogramming in comparison to the other liver cancer cell lines. The reprogrammed Hep3B cells acquired similar characteristics to pluripotent stem cells. However, loss of stemness in Hep3B-iPCs was detected during continual passage. CONCLUSIONS: We demonstrated that reprogramming was achieved in tumor cells through retroviral induction of genes associated with reprogramming. Interestingly, the reprogrammed pluripotent cancer cells (iPCs) were very different from original cancer cells in terms of colony shape and expressed markers. The induction of pluripotency of liver cancer cells correlated with the status of p53, suggesting that different expression level of p53 in cancer cells may affect their reprogramming.

Therapeutic effect of topical application of curcumin during treatment of radiation burns in a mini-pig model

Curcumin protects the skin against radiation-induced epidermal damage and prevents morphological changes induced by irradiation skin, thereby maintaining the epidermal thickness and cell density of basal layers. In this study, the effects of topical curcumin treatment on radiation burns were evaluated in a mini-pig model. Histological and clinical changes were observed five weeks after radiation exposure to the back (⁶⁰Co gamma-radiation, 50 Gy). Curcumin was applied topically to irradiated skin (200 mg/cm²) twice a day for 35 days. Curcumin application decreased the epithelial desquamation after irradiation. Additionally, when compared to the vehicle-treated group, the curcumin-treated group showed reduced expression of cyclooxygenase-2 and nuclear factor-kappaB. Furthermore, irradiation prolonged healing of biopsy wounds in the exposed area, whereas curcumin treatment stimulated wound healing. These results suggest that curcumin can improve epithelial cell survival and recovery in the skin and therefore be used to treat radiation burns.

Is the Linear No-Threshold Dose-Response Paradigm Still Necessary for the Assessment of Health Effects of Low Dose Radiation?

Inevitable human exposure to ionizing radiation from man-made sources has been increased with the proceeding of human civilization and consequently public concerns focus on the possible risk to human health. Moreover, Fukushima nuclear power plant accidents after the 2011 East-Japan earthquake and tsunami has brought the great fear and anxiety for the exposure of radiation at low levels, even much lower levels similar to natural background. Health effects of low dose radiation less than 100 mSv have been debated whether they are beneficial or detrimental because sample sizes were not large enough to allow epidemiological detection of excess effects and there was lack of consistency among the available experimental data. We have reviewed an extensive literature on the low dose radiation effects in both radiation biology and epidemiology, and highlighted some of the controversies therein. This article could provide a reasonable view of utilizing radiation for human life and responding to the public questions about radiation risk. In addition, it suggests the necessity of integrated studies of radiobiology and epidemiology at the national level in order to collect more systematic and profound information about health effects of low dose radiation.

beta-irradiation (166Ho patch)-induced skin injury in mini-pigs: effects on NF-kappaB and COX-2 expression in the skin

In the present study, the detrimental effect of beta-emission on pig skin was evaluated. Skin injury was modeled in mini-pigs by exposing the animals to 50 and 100 Gy of beta-emission delivered by 166Ho patches. Clinicopathological and immunohistochemical changes in exposed skin were monitored for 18 weeks after beta-irradiation. Radiation induced desquamation at 2~4 weeks and gradual repair of this damage was evident 6 weeks after irradiation. Changes in basal cell density and skin depth corresponded to clinically relevant changes. Skin thickness began to decrease 1 week after irradiation, and the skin was thinnest 4 weeks after irradiation. Skin thickness increased transiently during recovery from irradiation-induced skin injury, which was evident 6~8 weeks after irradiation. Epidermal expression of nuclear factor-kappa B (NF-kappaB) differed significantly between the untreated and irradiated areas. One week after irradiation, cyclooxygenase-2 (COX-2) expression was mostly limited to the basal cell layer and scattered among these cells. High levels of COX-2 expression were detected throughout the full depth of the skin 4 weeks after irradiation. These findings suggest that NF-kappaB and COX-2 play roles in epidermal cell regeneration following beta-irradiation of mini-pig skin.

Biliary Granular Cell Tumor

No abstract available.

Induced Pluripotent Stem Cells: Next Generation Stem Cells to Clinical Applications / 한양의대학술지

Induced pluripotent stem cells (iPSC) are specially manipulated cells from somatic cells by the introduction of four factors that are reprogrammed. The properties of iPSC are similar to embryonic stem cells (ESC) characteristic of self-renewal and pluripotency. The technology of reprogramming somatic cells to iPSC enables the generation of patient-specific cells that can be used as powerful tools for drug screening, in vitro models for human disease and autologous transplantation. The iPSC technology provides a priceless resource for regenerative medicine but there are still changing obstacles over the safety of iPSC in avoiding induction of tumorigenicity and maintaining high purity of re-differentiated cells from iPSC to produce more functional cells for cell therapy. A variety of methods to overcome the limitation of iPSC application applied in the clinical setting have been developed. In this review, we summarize the recent progress in iPSC generation and differentiation techniques to facilitate clinical application of iPSC with future potential in regenerative medicine.

Radiation-induced eosinophilic, polymorphic, and pruritic eruption in a pig skin model / 한국실험동물학회지

Eosinophilic, polymorphic and pruritic eruption associated with radiotherapy (EPPER) can occur in cancer patients after irradiation. In this study, we characterized the clinical and histopathological features of pig skin that developed widespread polymorphic and pruritic skin lesions following localized 50 Gy gamma-irradiation. The pigs developed pruritus 5-7 weeks after irradiation, and infiltration of the dermis by eosinophils was detected 4-7 weeks after irradiation. The irradiated animals also showed transiently increased numbers of peripheral eosinophils 5-7 weeks after treatment. Irradiation induced desquamation after 2-4 weeks, which and the desquamation gradually resolved after 7 weeks. These pathological changes correspond to those seen in irradiated human skin, indicating that this model could be useful for elucidating the pathogenesis of EPPER and for developing therapeutic and prophylactic methods.

Time-Dependent Effects of Prognostic Factors in Advanced Gastric Cancer Patients

PURPOSE: This study aimed to identify time-dependent prognostic factors and demonstrate the time-dependent effects of important prognostic factors in patients with advanced gastric cancer (AGC). MATERIALS AND METHODS: We retrospectively evaluated 3,653 patients with AGC who underwent curative standard gastrectomy between 1991 and 2005 at the Korea Cancer Center Hospital. Multivariate survival analysis with Cox proportional hazards regression was used in the analysis. A non-proportionality test based on the Schoenfeld residuals (also known as partial residuals) was performed, and scaled Schoenfeld residuals were plotted over time for each covariate. RESULTS: The multivariate analysis revealed that sex, depth of invasion, metastatic lymph node (LN) ratio, tumor size, and chemotherapy were time-dependent covariates violating the proportional hazards assumption. The prognostic effects (i.e., log of hazard ratio [LHR]) of the time-dependent covariates changed over time during follow-up, and the effects generally diminished with low slope (e.g., depth of invasion and tumor size), with gentle slope (e.g., metastatic LN ratio), or with steep slope (e.g., chemotherapy). Meanwhile, the LHR functions of some covariates (e.g., sex) crossed the zero reference line from positive (i.e., bad prognosis) to negative (i.e., good prognosis). CONCLUSIONS: The time-dependent effects of the prognostic factors of AGC are clearly demonstrated in this study. We can suggest that time-dependent effects are not an uncommon phenomenon among prognostic factors of AGC.

Primary Myxoid Leiomyoma of the Liver

Herein, we report a case of primary myxoid leiomyoma of the liver. A 60-year-old woman complained of upper abdominal fullness. Computed tomography showed a solid tumor (8 cm) in the liver. The patient underwent right hepatectomy and histological findings from the resected specimen revealed scattered bland spindle cells in a background of exuberant myxoid material. The tumor cells were immunoreactive for smooth muscle actin and desmin. No other lesions were found elsewhere in the body. Thus, the tumor was diagnosed as a primary myxoid leiomyoma of the liver.

Liver Stem Cells / 한양의대학술지

Liver transplantation has been regarded as the definitive curative approach for pathologic liver conditions from the acute stage to the chronic end stage for decades. Recently, translational research has been focused on liver stem cell transplantation, using various cell therapies, due to the potential benefit of natural host liver regeneration. Many studies are ongoing utilizing and evaluating the use of either fetal-liver-derived stem cells or oval cells, however many obstacles still remain. Extensive research identifying and characterizimg stem/progenitor cells for potential application to in vitro cell therapy, whereas many questions remain concerning the isolation and identification of adult liver stem cells with adequate capacity for proliferation and the regeneration of injured liver. Recent approaches to liver regeneration include the production of hepatocyte-like cells from other stem cell sources such as mesenchymal stem cells and embryonic stems cells. Another major target for liver regeneration studies include the generation of liver stem cells from induced pluripotent stem cells (IPSC) We review the current data concerning characterization of stem cells and progenitor cells for their capacity to support their potential for re-population and regeneration of normal adult liver from liver damaged due to injury and/or disease.

Fine Needle Aspiration Cytology of Parathyroid Lesions

BACKGROUND: There has been an increase in the use of fine needle aspiration cytology (FNAC) for the diagnosis of parathyroid lesions (PLs). Differentiation between a thyroid lesion and a PL is not easy because of their similar features. We reviewed parathyroid aspirates in our institution and aimed to uncover trends in diagnostic criteria. METHODS: We selected 25 parathyroid aspirates (from 6 men and 19 women) confirmed surgically or immunohistochemically from 2006 to 2011. RESULTS: Major architectural findings of PLs include scattered naked nuclei, loose clusters, a papillary pattern with a fibrovascular core, tight clusters, and a follicular pattern. These architectures were commonly admixed with one another. Cytological features included anisokaryosis, stippled chromatin, a well-defined cell border, and oxyphilic cytoplasm. Eighteen of the 25 patients were diagnosed with PL using FNAC. Seven patients had been misdiagnosed with atypical cells (n=2), benign follicular cells (n=2), adenomatous goiter (n=2) and metastatic carcinoma (n=1) in FNAC. Using clinicoradiologic data, the sensitivity of the cytological diagnosis was 86.7%. The cytological sensitivity decreased to 50% without this information. CONCLUSIONS: FNAC of PL is easily confused with thyroid lesions. A combination of cytological parameters and clinical data will be required to improve the diagnostic sensitivity of PLs.

Early Colorectal Epithelial Neoplasm in Korea: A Multicenter Survey of Pathologic Diagnosis

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.

Test Execution Variation in Peritoneal Lavage Cytology Could Be Related to Poor Diagnostic Accuracy and Stage Migration in Patients with Gastric Cancer

PURPOSE: Peritoneal lavage cytology is part of the routine staging workup for patients with advanced gastric cancer. However, no quality assurance study has been conducted to show variations or biases in peritoneal lavage cytology results. The aim of this study was to demonstrate a test execution variation in peritoneal lavage cytology between investigating surgeons. MATERIALS AND METHODS: A prospective cohort study was designed for determination of the positive rate of peritoneal lavage cytology using a liquid-based preparation method in patients with potentially curable advanced gastric cancer (cT2~4/N0~2/M0). One hundred thirty patients were enrolled and underwent laparotomy, peritoneal lavage cytology, and standard gastrectomy, which were performed by 3 investigating surgeons. Data were analyzed using the chi-square test and a logistic regression model. RESULTS: The overall positive peritoneal cytology rate was 10.0%. Subgroup positive rates were 5.3% in pT1 cancer, 2.0% in pT2/3 cancer, 11.1% in pT4a cancer, and 71.4% in pT4b cancer. In univariate analysis, positive peritoneal cytology showed significant correlation with pT stage, lymphatic invasion, vascular invasion, ascites, and the investigating surgeon. We found the positive rate to be 2.1% for surgeon A, 10.2% for surgeon B, and 20.6% for surgeon C (P=0.024). Multivariate analysis identified pT stage, ascites, and the investigating surgeon to be significant risk factors for positive peritoneal cytology. CONCLUSIONS: The peritoneal lavage cytology results were significantly affected by the investigating surgeon, providing strong evidence of test execution variation that could be related to poor diagnostic accuracy and stage migration in patients with advanced gastric cancer.