The Prognostic Role of Mitotic Index in Hepatocellular Carcinoma Patients after Curative Hepatectomy

하상윤,최미선,이태범,박철근 대한암학회 2016 Cancer Research and Treatment Vol.48 No.1

Purpose High proliferation rate is a hallmark of cancer. The mitotic index is a useful and simple method for analysis of cell proliferation. However, the practical utility of mitotic index as a predictor of prognosis in patients with hepatocellular carcinoma (HCC) has not been deter- mined. Therefore, we examined mitotic index as a prognostic marker in HCC patients. Materials and Methods We counted the number of mitotic cells in 10 high-power fields of the tumor area on hema- toxylin and eosin–stained slides representing 282 surgically resected HCCs. The highest number of mitotic cells was defined as the mitotic index. Results High mitotic index was observed in 127 of 282 HCCs. High mitotic index showed significant association with younger age, larger tumor size, higher Edmondson grade, microvascular invasion, major portal vein invasion, intrahepatic metastasis, higher American Joint Com- mittee on Cancer (AJCC) T-stage, higher Barcelona Clinic Liver Cancer (BCLC) stage, higher alpha-fetoprotein level, hepatitis B virus etiology, and liver cirrhosis. Patients with high mitotic index had shorter disease-specific survival (DSS) (p < 0.001) and tended to have shorter recurrence-free survival (p=0.112). In subgroup analysis among patients with a larger tumor size, microvascular invasion, intrahepatic metastasis, higher AJCC T-stage, and higher BLCL stage, high mitotic index showed unfavorable influences on DSS (p=0.001, p=0.008, p=0.003, p=0.012, and p < 0.001, respectively). In addition, high mitotic index was an independent predictor of shorter DSS (p=0.004). Conclusion High mitotic index may be a novel predictor of DSS in patients with HCC and may have utility as an auxiliary prognostic factor in HCC.

Mucoepidermoid Carcinoma of Tracheobronchial Tree: Clinicopathological Study of 31 Cases

하상윤,한정호,이재준,김영은,최윤라,김홍관 대한병리학회 2011 Journal of Pathology and Translational Medicine Vol.45 No.2

Background: All aspects of mucoepidermoid carcinoma (MEC) of the lung including histologic grading, clinical behavior and its differentiation from adenosquamous cell carcinoma are still not fully understood. Methods: We reviewed the hematoxylin-eosin stained slides and medical re­cords of 31 cases of MEC of the lungs. The cases were classified as low and high grade accord­ing to the quantitative grading system formulated for MEC. High grade tumors were tested for an epidermal growth factor receptor (EGFR) mutation. Results: Twenty eight cases were classified as low grade and 3 cases as high grade. Histologically, lower glandular component, cellular atyp­ia, necrosis, mitoses >4/10 high power fields, and endolymphatic tumor emboli were typical char­acteristics of a high grade tumor. Although some tumors showed histologic features mimicking high grade tumors, they were classified as low grade tumors according to this quantitative grad­ing system. Low grade tumors showed no recurrence or metastasis. However, among three pa­tients with a high grade tumor, two had distant metastases and one died of disease. Additionally, an EGFR mutation was not detected. Conclusions: A high grade MEC was consistently different from a low grade tumor with regard to malignant histologic features and poor prognosis. There­fore, correct histologic grading is important in predicting the prognosis to avoid unnecessary treat­ment.

3차원 재구성법을 이용한 수복물의 정량적 미세누출도 측정

하상윤,신동훈 大韓齒科保存學會 2004 Restorative Dentistry & Endodontics Vol.29 No.5

Established microleakage tests have their own disadvantages. In this study, 3D reconstruction method was tried to overcome these disadvantages. Four types of microleakage tests were used and relationships among them were estimated: penetrated dye volume: marginal adaptability: degree of dye penetration and relative penetrated length to cavity wall. Twenty-four Class V cavities were bulk filled with composite (Esthet X) following surface treatments: N group (no treatment): E group (etching only): T group (etching + Prime & Bond NT). 50% silver nitrate was used as a dye solution after thermocycling (5℃ & 55℃, 1.000 times). Teeth were serially ground with a thickness of 0.2 mm. Volume of dye penetration was estimated from a three-dimensionally reconstructed image with a software (3D-DOCTOR). Percentage of margin without gap was estimated from SEM and degree of dye penetration and the relative length of dye penetration to overall cavity wall were also estimated. ANOVA and Scheffe test for dye volume, Kruskal-Wallis and Mann-Whitney test for marginal quality, Spearman's rho test for checking of relationships among methods were used. The results were as follows: 1. Dye penetration could be seen from several directions, furthermore, its volumetric estimation was possible. 2. Reverse relationship was found between dye volume and marginal quality (r = -0.881/ p = 0.004). 3. Very low relationship was seen between dye volume and two-dimensional tests (degree of dye penetration and relative length). However, 2D evaluation methods showed high relationship (p = 0.002-0.054) each other. 4. Three times vertical section could be recommended as a 2D test.

Diffuse Large B-Cell Lymphoma Associated with Chronic Inflammation Manifested as a Soft Tissue Mass: Incidental Discovery on Histological Examination

하상윤,최윤라,김성주,고영혜 대한병리학회 2011 Journal of Pathology and Translational Medicine Vol.45 No.4

We report an extraordinary case of diffuse large B-cell lymphoma arising in a cystic necrotic mass in a 35-year-old man who presented with a soft tissue mass at the site of previous surgery. A benign mass was surgically removed 17 years ago, after which a cystic lesion gradually developed at the same site. The resected mass appeared as a thick-walled cyst filled with brown necrotic and hemorrhagic material. On microscopic examination, the cyst wall was primarily necrotic tissue with some aggregates of large atypical lymphoid cells. These atypical cells were diffusely positive for CD20 and showed a high proliferation index, Epstein-Barr virus positivity, and clonal rearrangement of the immunoglobulin gene. His present condition was diagnosed as Epstein-Barr virus-associated diffuse large B-cell lymphoma arising from chronic inflammation. It is important to be aware of the clinical manifestations and histological features of this rare disease in light of diagnosis and treatment.

The Overexpression of CCAR1 in Hepatocellular Carcinoma Associates with Poor Prognosis

하상윤,김정훈,양정욱,김지민,김빛나리,박철근 대한암학회 2016 Cancer Research and Treatment Vol.48 No.3

Purpose Cell division cycle and apoptosis regulator 1 (CCAR1) plays a dynamic role in regulation of cell growth and apoptosis by serving as a cofactor of steroid/thyroid nuclear receptors, !- catenin, and p53 in a variety of cell types including different cancer cells. However, whether CCAR1 protein is overexpressed in hepatocellular carcinoma (HCC) and the prognostic significance of CCAR1 protein expression in HCC have not been reported. Materials and Methods In 167 HCC patients with long-term follow-up, CCAR1 protein expression was examined by immunohistochemistry. Results High CCAR1 protein expression was observed in 149 of the 167 HCC cases (89.2%) and showed significant correlation with microvascular invasion, intrahepatic metastasis, higher American Joint Committee on Cancer (AJCC) T stage, and early recurrence. High CCAR1 expression showed an unfavorable effect on recurrence-free survival (RFS) (p=0.002). In subgroup analysis, among patients with "-fetoprotein # 20 ng/mL (n=54) and patients with AJCC T stage 1 (n=62), significant differences in RFS were observed between high CCAR1 expression groups and low CCAR1 expression groups (p=0.015 and p=0.004, respectively). High CCAR1 expression tended to be an independent predictor of shorter RFS (p=0.054) and showed an unfavorable effect on overall survival (OS) (p=0.015). In subgroup analysis, among patients with "-fetoprotein # 20 ng/mL (n=54), significant difference in OS was observed between high CCAR1 expression group and low CCAR1 expression group (p=0.046). Conclusion CCAR1 protein could be a potential biomarker predicting RFS in HCC patients after curative hepatectomy. In addition, CCAR1 had prognostic values in HCC patients with normal serum "-fetoprotein levels or early stage HCC.

근관충전방법에 따른 내흡수 치근의 근관충전 효율성 비교

홍찬의,신동훈,하상윤 大韓齒科保存學會 1995 Restorative Dentistry & Endodontics Vol.20 No.2

강원도 지역 군급수원의 수질 노로바이러스 오염실태 조사

하상윤 ( Sangyun Ha ),한현정 ( Hyunjeong Han ),여성원 ( Sungwoon Yeo ),조치환 ( Chihwan Cho ),신현승 ( Hyeonseung Shin ),조상희 ( Sanghee Cho ) 국군의무사령부 2020 대한군진의학학술지 Vol.51 No.1

Objective; This study was conducted to ensure the safety of drinking water for soldiers by surveying on contamination levels of Norovirus in unerground/surface water for Military use in Gangwon Province and to acquire Norovirus analysis technology in water. Method; Among the water sources used by the front unit of the 0 Corps, a total of 67 water supply sources that are found to be vulnerable to microbial contamination, such as those that do not have automatic residual chlorine injection devices installed or where pathogenic microorganisms were detected as a result of regular water quality tests were selected. Samples were collected by filtering and adsorbing more than 500 liters of water with a standard filter apparatus and the pH, temperature, turbidity, and residual chlorine levels of water samples were measured to investigate the characteristics of water quality at the site, but the microbiological examinations for total coliforms and E.coli were conducted in the laboratory independently. We pre-treated the samples and conducted gene analysis(RT-PCR and reverse transcription-PCR process) followed by electrophoresis. After checking the bands that matched the positive control, the positive sample was sent to the specialized institute for sequencing. Results; In this study, Norovirus type GI.10 was detected in one of 67 water sources. The detection rate of Norovirus among the total was 1.5%, of which the detection rate for underground water was 1.7%. Conclusion; In order to ensure the safety of underground/surface water to drink for Military use, it is necessary to steadily conduct monitoring examinations on Norovirus contamination as well as legal inspections. Norovirus analysis technology of water obtained through this study will also help prevent water-borne disease more preemptively and timely.

간 양성 염증성 병변의 병리 진단

하상윤 ( Sang Yun Ha ) 대한간학회 2017 Postgraduate Courses (PG) Vol.2017 No.1

For diagnosis of Inflammatory lesions of the liver, histologic examination is often not necessary. But histologic confirmation is needed to distinguish it from other tumors when it is found as a nodule or focal lesion. In this lecture, I describe the pathologic findings of inflammatory lesions in the liver, which are found as nodules. In addition, I introduce other rare benign non-tumorous lesions that form nodules and rare tumors that may be mistaken for liver cancer.

Gastroenteropancreatic Neuroendocrine Tumors with Liver Metastases in Korea: A Clinicopathological Analysis of 72 Cases in a Single Institute

신유주,하상윤,현지연,이보람,이지연,장기택,김경미,박영석,박철근 대한암학회 2015 Cancer Research and Treatment Vol.47 No.4

Purpose Management of gastroenteropancreatic (GEP) neuroendocrine tumors with liver metastases(NETLM) presents many clinical challenges. Assessment of the extent of disease and primarytumor site is crucial for management. In this study, we investigated the primary tumor sitesand prognostic factors in GEP NETLM among Korean patients. Materials and MethodsWe reviewed the medical records of 72 Korean patients diagnosed with GEP NETLMbetween January 1999 and May 2013, focusing on their clinical and pathologic characteristics. ResultsThe most frequently encountered primary tumor sites were the pancreas (n=25, 35%), stomach(n=8, 11%), gall bladder (n=4, 6%) and rectum (n=3, 4%). Twenty-five patients (35%)had occult primary tumor. Twelve patients (17%) had histological grade G1 tumors, 30patients (42%) had G2 tumors, and 30 patients (42%) had G3 tumors. The mean follow-upperiod after histological confirmation of hepatic metastases was 11.30±2.44 months forG3 tumors, 19.67±4.09 months for G2 tumors, and 30.67±6.51 months for G1 tumors. Multivariate analyses revealed that an unknown primary tumor site (p=0.001) and higherhistological grade (p < 0.001) were independent prognostic indicators for shorter overallsurvival (OS). Most long-term survivors (OS > 24 months) had received antitumor treatment. ConclusionThe primary tumor site most frequently associated with GEP NETLM was the pancreas. Unknown primary tumor and higher histological grade were independent prognostic indicatorsfor shorter OS. Patients identified as being at a risk of shorter OS should be followedup closely.

Expression of PEG10 Is Associated with Poor Survival and Tumor Recurrence in Hepatocellular Carcinoma

방희진,하상윤,황수현,박철근 대한암학회 2015 Cancer Research and Treatment Vol.47 No.4

Purpose Paternally expressed gene 10 (PEG10), first identified as an imprinted gene, is paternallyexpressed and maternally silenced. In hepatocellular carcinoma (HCC), PEG10 has beenidentified as a potential target gene located within the amplified 7q21 locus. The purposeof this study was to investigate the expression of PEG10 protein in HCC and evaluate itsprognostic significance. Materials and MethodsPEG10 protein expression was examined by immunohistochemistry in tumor tissues from218 HCC patients undergoing curative resection. Furthermore, the relationships betweenPEG10 expression and clinicopathologic features or postoperative survival of HCC patientswere evaluated. The median follow-up period was 119.8 months for survivors. ResultsPEG10 expression was observed in 148 of the 218 HCCs (67.9%) and was significantlycorrelated with younger age, female, higher Edmondson grade, microvascular invasion,intrahepatic metastasis, higher American Joint Committee on Cancer T-stage, and higher!-fetoprotein level. PEG10 expression was an independent predictor of early recurrence(p=0.013), and it showed an unfavorable influence on recurrence-free survival (p < 0.001). A subgroup analysis showed that among patients with !-fetoprotein " 20 ng/mL (80patients), the PEG10-positive group also showed an unfavorable influence on recurrencefreesurvival (p=0.002). Moreover, a multivariate survival analysis identified PEG10 as anindependent predictor of shorter recurrence-free survival (p=0.005). PEG10 expressionshowed an unfavorable influence on overall survival (p=0.007) but was not an independentpredictor of shorter overall survival (p=0.128). ConclusionPEG10 protein could be a potential biomarker predicting early recurrence and recurrencefreesurvival in HCC patients after curative resection, even in those with normal serum!-fetoprotein levels.