70 results on '"Seung-Mo Hong"'
Search Results
2. Enhancing the shelf life of epoxy monoacrylate resins using acryl phosphate as a reactive additive
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Seung-Mo Hong, Oh Young Kim, and Seok-Ho Hwang
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General Chemical Engineering - Published
- 2022
3. Granulocytic epithelial lesion (GEL) in heterotopic pancreas
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Sun-Young Jun, Jihyun Chun, Sung Joo Kim, Dongwook Oh, Jin Hee Kim, Myung-Hwan Kim, and Seung-Mo Hong
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Pancreatic Neoplasms ,Hepatology ,Endocrinology, Diabetes and Metabolism ,Gastroenterology ,Humans ,Fibrosis ,Pancreas ,Carcinoma, Pancreatic Ductal - Abstract
The diagnosis of type 2 autoimmune pancreatitis (AIP) is dependent on typical radiologic imaging and the presence of the granulocytic epithelial lesion (GEL), which is characterized by ductal neutrophilic infiltration with or without neutrophilic acinar infiltration.We evaluated GEL and related clinicopathologic factors in 165 resected heterotopic pancreata (HPs) [57 gastric (35%), 56 duodenal (34%), 30 omental (18%), and 22 jejunal (13%)] and 29 matched orthotopic pancreata routinely examined during surgery.GEL was noted in 8% (13/165) of HPs, including ductal epithelial (6/13, 46%) and intraluminal (8/13, 62%) neutrophilic infiltrations. However, there was no GEL in orthotopic pancreata. Abdominal pain was observed in 6 (46%) patients with GEL-positive HPs. GEL was more commonly observed in HPs having symptoms (p = 0.029), a larger size (p = 0.028), and an infiltrative growth pattern (p = 0.006). In addition, periductal lymphoplasmacytic infiltration and fibrosis (both p 0.001), interstitial fibrosis (p = 0.017), acinar neutrophilic infiltration (p = 0.032), venulitis (p = 0.050), acinar ductal metaplasia (ADM; p = 0.040), and pancreatic intraepithelial neoplasia/intraductal papillary mucinous neoplasms (PanIN/IPMN; p 0.001) were more commonly seen in HPs with GEL than in those without GEL. Inflammatory bowel disease was present only in one patient with GEL-negative HP.GELs are detected in a subset of HPs without clinical evidence of AIP. Therefore, for the diagnosis of AIP, GEL should be carefully interpreted with the context of other histologic, clinical, and radiologic findings.
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- 2022
4. Large tumor size, lymphovascular invasion, and synchronous metastasis are associated with the recurrence of solid pseudopapillary neoplasms of the pancreas
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Song Cheol Kim, Seung-Mo Hong, Ki Byung Song, Dae Wook Hwang, Jae Hoon Lee, Jihun Kim, You-Na Sung, Sang Soo Lee, Goeun Lee, and Sung Joo Kim
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Surgical resection ,medicine.medical_specialty ,Large tumor ,Lymphovascular invasion ,030230 surgery ,03 medical and health sciences ,Pancreatectomy ,0302 clinical medicine ,Text mining ,medicine ,Humans ,Pancreas ,Retrospective Studies ,Hepatology ,business.industry ,Gastroenterology ,PT category ,Prognosis ,Carcinoma, Papillary ,Lymphovascular ,Pancreatic Neoplasms ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Synchronous metastasis ,Radiology ,Neoplasm Recurrence, Local ,business - Abstract
Solid pseudopapillary neoplasms (SPNs) of the pancreas have low malignant potential. However, malignant SPNs are not fully understood.To evaluate risk factors affecting malignant potential, the clinicopathologic features of 375 surgically resected SPNs were compared.Fifty (13.3%) had malignant histologic features. Twenty-seven and 22 had perineural and lymphovascular invasions, respectively. Adjacent organ invasion was noted in 9 cases. Recurrence occurred in 8 cases. The median recurrence time after surgical resection was 67 months and was associated with a higher pT category (P = 0.001), lymphovascular invasion (P 0.001), and synchronous metastasis (P 0.001). SPN patients with malignant histologic features had worse recurrence-free survival (RFS; 10-year survival rate, 73.2%) than those without malignant histologic features (96.3%; P = 0.01). Patients with a higher pT category (P = 0.04), synchronous metastasis (P 0.01), and lymphovascular invasion (P 0.01) had worse RFS. Lymphovascular invasion (P = 0.042) and a higher T category (P = 0.002) were poor prognostic factors for recurrence.Lymphovascular invasion and a higher T category were worse prognostic factors for recurrence in SPN patients with malignant histologic features. For SPN patients with malignant histologic features, a longer follow-up may be required.
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- 2021
5. Frequent Intraluminal Growth of Large Muscular Veins in Surgically Resected Colorectal Cancer Tissues: A 3-Dimensional Pathologic Reconstruction Study
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Dongjun Jung, Junyoung Shin, Jihyun Park, Jaehoon Shin, You-Na Sung, Yeseul Kim, Seungyeon Yoo, Byong-Wook Lee, Sung-Wuk Jang, In Ja Park, Laura D. Wood, Chan-Gi Pack, Ralph H. Hruban, and Seung-Mo Hong
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Pathology and Forensic Medicine - Published
- 2023
6. Distribution pattern of tumor infiltrating lymphocytes and tumor microenvironment composition as prognostic indicators in anorectal malignant melanoma
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Seung-Mo Hong, Jin Cheon Kim, Mi Ju Kim, Bilal Mustafa, Young Il Kim, Gowun Jeong, Sung-Min Ahn, So-Woon Kim, Seok-Byung Lim, Chang Sik Yu, and In Ja Park
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Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Pathology ,CD3 Complex ,Databases, Factual ,medicine.medical_treatment ,Antigens, Differentiation, Myelomonocytic ,CD8-Positive T-Lymphocytes ,B7-H1 Antigen ,Pathology and Forensic Medicine ,03 medical and health sciences ,Lymphocytes, Tumor-Infiltrating ,0302 clinical medicine ,Antigens, CD ,Internal medicine ,Tumor-Associated Macrophages ,Biomarkers, Tumor ,Tumor Microenvironment ,medicine ,Humans ,Melanoma ,Aged ,Retrospective Studies ,Extracellular Matrix Proteins ,Tumor microenvironment ,CD68 ,Tumor-infiltrating lymphocytes ,business.industry ,FOXP3 ,Forkhead Transcription Factors ,Immunotherapy ,Middle Aged ,Anus Neoplasms ,Prognosis ,medicine.disease ,Hyaluronan Receptors ,Phenotype ,030104 developmental biology ,030220 oncology & carcinogenesis ,Immunohistochemistry ,Female ,Neoplasm Recurrence, Local ,business ,CD163 - Abstract
Anorectal malignant melanoma (ARMM) is a rare disease with poor prognosis. Determining ARMM prognosis precisely is difficult due to the lack of proper assessment techniques. Immunotherapy has proven effective against cutaneous malignant melanoma and may show efficacy in ARMM. Herein, we assessed the immune profile of ARMM to identify possible prognostic biomarkers. Twenty-two ARMM formalin-fixed and paraffin-embedded samples were evaluated using an nCounter® PanCancer Immune Profiling Panel. Validation was performed through immunohistochemical staining for CD3, CD8, Foxp3, CD68, CD163, and PD-L1. RNA analysis revealed significantly decreased scores for pathways involved in cell regulation and function, as well as chemokines, in recurrent patients compared to nonrecurrent patients. In cell-type profiling, the recurrent cases displayed significantly low tumor infiltrating lymphocyte (TIL) scores. Recurrence/death prediction models were defined using logistic regression and showed significantly lower scores in recurrent and deceased patients (all, P
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- 2021
7. Comprehensive histological evaluation with clinical analysis of venous invasion in pancreatic ductal adenocarcinoma: From histology to clinical implications
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Ralph H. Hruban, You Na Sung, Seung-Mo Hong, HyungJun Cho, Sung Joo Kim, Seungbeom Shin, and So Jeong Lee
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Adult ,Male ,medicine.medical_specialty ,Pathology ,Pancreatic ductal adenocarcinoma ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,H&E stain ,Pancreatic Intraepithelial Neoplasia ,Kaplan-Meier Estimate ,Veins ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Neoplasm Invasiveness ,Venous Invasion ,Neoplasm Metastasis ,Stage (cooking) ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Hepatology ,Clinical pathology ,business.industry ,Gastroenterology ,Margins of Excision ,Histology ,Middle Aged ,Prognosis ,Survival Analysis ,Pancreatic Neoplasms ,Lymphatic system ,Regional Blood Flow ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,Female ,030211 gastroenterology & hepatology ,business ,Carcinoma, Pancreatic Ductal - Abstract
Venous invasion is a poor prognostic factor for pancreatic ductal adenocarcinoma (PDAC). However, our understanding of various features of venous invasion is limited. Our aim is to comprehensively evaluate various histopathologic features of venous invasion, including status, type (lymphatic or venous), number of invasion foci, and histologic pattern (pancreatic intraepithelial neoplasia [PanIN]-like, conventional) in PDACs.Various features of venous invasion, including status, number of invasion foci, histologic patterns [pancreatic intraepithelial neoplasia (PanIN)-like, conventional], and size of involved vessels in 471 surgically resected PDACs were evaluated with all available hematoxylin and eosin (HE)-stained slides.Venous invasion was observed in 319 cases (67.7%) and was more frequently associated with increased tumor size, extrapancreatic extension, resection margin involvement, diffuse tumor distribution, lymph node metastasis, and perineural invasion (all Ps .05). High frequency (≥3 foci) of venous invasion was associated with shorter overall survival both in the entire group and in the early stage subgroup (stage I; all Ps .05). Multivariate analysis indicated that a high frequency (≥3 foci) of venous invasion, large tumor size (4 cm), higher histologic grade, and lymph node metastasis, were independent prognostic factors of worse overall survival (all Ps .05).Precise evaluation of venous invasion status, including foci number of invasion, can provide additional prognostic information for patients undergoing surgical resection of PDAC, especially for those with early disease stage.
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- 2020
8. Clinicopathologic analysis of intraductal papillary neoplasm of bile duct: Korean multicenter cohort study
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Jin Seok Heo, Hongbeom Kim, Heejeong Lee, Jung Hoon Kim, Yoo Seok Yoon, Ho-Seong Han, Sang Jae Park, Il Young Park, Yang Won Nah, Jung Hee Lee, Haeryoung Kim, Joo Young Kim, Hong Jin Kim, Wan-Joon Kim, Eun Kyung Hong, Seung-Mo Hong, Wooil Kwon, Chang Ho Cho, Jae Ri Kim, Hee Sung Kim, Hyung Il Seo, Kyu Yeoun Won, Hye-Jeong Choi, In Woong Han, Young Hun Roh, Kyung-Hee Kim, Jeong Mo Bae, Hyeon Kook Lee, Joon Hyuk Choi, Yu Na Kang, Wonae Lee, Chong Woo Chu, Woo Sung Moon, Kee Taek Jang, In Sang Song, Kyungbun Lee, Young Dong Yu, Sungho Jo, Shin Hwang, Seung Eun Lee, Ho Gak Kim, Hee Chul Yu, Jin Sook Jeong, Jong Sil Lee, Chang-Sup Lim, Sun Whe Kim, Min Sun Cho, Hyung Woo Park, Koo Jeong Kang, Sun Hyung Joo, Do Youn Park, Dong-Sik Kim, Kang Min Han, Jin-Young Jang, Chi Young Jeong, and Dong Wook Choi
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medicine.medical_specialty ,Gastroenterology ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Republic of Korea ,medicine ,Humans ,Survival analysis ,Intraductal Papillary Neoplasm ,Hepatology ,Bile duct ,business.industry ,Incidence (epidemiology) ,medicine.disease ,Bile Ducts, Intrahepatic ,medicine.anatomical_structure ,Bile Duct Neoplasms ,Dysplasia ,030220 oncology & carcinogenesis ,Cohort ,030211 gastroenterology & hepatology ,Bile Ducts ,business ,Rare disease ,Cohort study - Abstract
Background IPNB is very rare disease and most previous studies on IPNB were case series with a small number due to low incidence. The aim of this study is to validate previously known clinicopathologic features of intraductal papillary neoplasm of bile duct (IPNB) based on the first largest multicenter cohort. Methods Among 587 patients previously diagnosed with IPNB and similar diseases from each center in Korea, 387 were included in this study after central pathologic review. We also reviewed all preoperative image data. Results Of 387 patients, 176 (45.5%) had invasive carcinoma and 21 (6.0%) lymph node metastasis. The 5-year overall survival was 80.9% for all patients, 88.8% for IPNB with mucosal dysplasia, and 70.5% for IPNB with invasive carcinoma. According to the “Jang & Kim's modified anatomical classification,” 265 (68.5%) were intrahepatic, 103 (26.6%) extrahepatic, and 16 (4.1%) diffuse type. Multivariate analysis revealed that tumor invasiveness was a unique predictor for survival analysis. (p = 0.047 [hazard ratio = 2.116, 95% confidence interval 1.010–4.433]). Conclusions This is the first Korean multicenter study on IPNB through central pathologic and radiologic review process. Although IPNB showed good long-term prognosis, relatively aggressive features were also found in invasive carcinoma and extrahepatic/diffuse type.
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- 2020
9. Three-dimensional visualization of cleared human pancreas cancer reveals that sustained epithelial-to-mesenchymal transition is not required for venous invasion
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Michaël Noë, Denis Wirtz, Kiyoko Oshima, Elizabeth D. Thompson, Alicia M Braxton, Matthias M. Gaida, Laura D. Wood, Richard A. Burkhart, Seung-Mo Hong, Pei Hsun Wu, Tadashi Yoshizawa, Gemma Lionheart, Ralph H. Hruban, Dong Jun Jung, and Ashley Kiemen
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0301 basic medicine ,CD31 ,Pathology ,medicine.medical_specialty ,Stromal cell ,business.industry ,Cancer ,medicine.disease ,Pathology and Forensic Medicine ,03 medical and health sciences ,Cytokeratin ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Pancreatic cancer ,medicine ,Carcinoma ,Epithelial–mesenchymal transition ,business ,Pancreas - Abstract
Venous invasion is three times more common in pancreatic cancer than it is in other major cancers of the gastrointestinal tract, and venous invasion may explain why pancreatic cancer is so deadly. To characterize the patterns of venous invasion in pancreatic cancer, 52 thick slabs (up to 5 mm) of tissue were harvested from 52 surgically resected human ductal adenocarcinomas, cleared with a modified iDISCO method, and labeled with fluorescent-conjugated antibodies to cytokeratin 19, desmin, CD31, p53 and/or e-cadherin. Labeled three-dimensional (3D) pancreas cancer tissues were visualized with confocal laser scanning or light sheet microscopy. Multiple foci of venous and even arterial invasion were visualized. Venous invasion was detected more often in 3D (88%, 30/34 cases) than in conventional 2D slide evaluation (75%, 25/34 cases, P
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- 2020
10. Pancreatic acinar cell carcinomas and mixed acinar-neuroendocrine carcinomas are more clinically aggressive than grade 1 pancreatic neuroendocrine tumours
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Haeryoung Kim, Soyeon An, Jiyoon Kim, Young Ha Oh, Joo Young Kim, Seung-Mo Hong, Ralph H. Hruban, Kee Taek Jang, Jacqueline A. Brosnan-Cashman, Kyoung Bun Lee, Christopher M. Heaphy, and Do Youn Park
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Adult ,Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Perineural invasion ,Disease-Free Survival ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Carcinoma ,medicine ,Acinar cell ,Humans ,Lymph node ,Aged ,Carcinoma, Acinar Cell ,business.industry ,Significant difference ,Middle Aged ,medicine.disease ,Neuroendocrine Carcinomas ,Pancreatic Neoplasms ,Neuroendocrine Tumors ,stomatognathic diseases ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Immunohistochemistry ,Female ,business ,Pancreas - Abstract
Acinar cell carcinomas (ACCs) and mixed acinar-neuroendocrine carcinomas (MAcNECs) of the pancreas are extremely rare carcinomas with a significant component with acinar differentiation. To date, the clinicopathological behaviours of these neoplasms remain unclear. In this study, we evaluated the histopathological and molecular characteristics of 20 ACCs and 13 MAcNECs and compared them to a cohort of 269 well-differentiated pancreatic neuroendocrine tumours (PanNETs). Compared to PanNETs, both ACCs and MAcNECs had an advanced pT classification (p
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- 2020
11. Prognostic implications of immune classification in a multicentre cohort of patients with small intestinal adenocarcinoma
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Sun-Young Jun, Dae-Woon Eom, Seung-Mo Hong, and Byeong-Joo Noh
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Adult ,Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Adenocarcinoma ,B7-H1 Antigen ,Pathology and Forensic Medicine ,03 medical and health sciences ,Lymphocytes, Tumor-Infiltrating ,0302 clinical medicine ,Immune system ,Internal medicine ,PD-L1 ,Intestinal Neoplasms ,Intestine, Small ,Tumor Microenvironment ,medicine ,Humans ,Aged ,Retrospective Studies ,Aged, 80 and over ,Tissue microarray ,biology ,business.industry ,Patient Selection ,Microsatellite instability ,Small Intestinal Adenocarcinoma ,Middle Aged ,Prognosis ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cohort ,biology.protein ,Immunohistochemistry ,Female ,Immunotherapy ,business ,CD8 - Abstract
The diagnosis of small intestinal adenocarcinoma (SIAC) is usually determined at an advanced stage due to non-specific symptoms and the difficulty of exploring the small intestine. Therefore, the majority of SIAC patients have limited chemotherapeutic options. Until recently, the development of novel and effective therapies for SIAC have been limited owing to the low number of samples that have been collected and the low incidence of SIAC. Immunotherapies are becoming a focus. However, in SIAC, only a few studies to identify immunotherapy-responsive subgroups and their prognostic indicators have been reported. In the present study, we categorise primary SIAC into four types of tumour immune microenvironments and propose a strategy for identifying patient subgroups that are most likely to be immunotherapy-responsive. Formalin-fixed, paraffin-embedded tissue samples of a multicentre cohort of patients with SIAC (n=195) were collected using tissue microarrays. Immunohistochemical (IHC) stains for PD-L1, PD-1, and CD8 were performed, and microsatellite instability was evaluated using an IHC stain. Tumour microenvironment immune type (TMIT) I [PD-L1-positive tumour cells and CD8-high tumour-infiltrating lymphocytes (TILs)] and TMIT III (PD-L1-positive tumour cells and CD8-low TILs) show the best and worse prognoses, respectively. PD-L1 expression was significantly associated with high microsatellite instability (MSI) status. CD8-high TILs were positively correlated with PD-1-high TILs and high MSI. The TMIT I subgroup demonstrated a more patent CD8/PD-L1/PD-1 signalling pathway compared to other TMITs. Therefore, the TMIT I subgroup can be expected to have an effective response to immune checkpoint inhibitor therapies in SIAC. Such classification of SIACs into four immune types can be useful in predicting the prognosis of patients and the identification of immunotherapy-responsive subgroups.
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- 2020
12. Therapeutic relevance of targeted sequencing in management of patients with advanced biliary tract cancer: DNA damage repair gene mutations as a predictive biomarker
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Ki-Hun Kim, Seung-Mo Hong, Tae Jun Song, Heung-Moon Chang, Jae Hoon Lee, Changhoon Yoo, Sang Soo Lee, Song Cheol Kim, Se Jin Jang, Gi-Won Song, Deokhoon Kim, Chul Soo Ahn, Jae Ho Jeong, Baek-Yeol Ryoo, Kyu-Pyo Kim, Tae Won Kim, Do Hyun Park, Shin Hwang, Dae Wook Hwang, and Heejung Chae
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Adult ,Male ,0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Gene mutation ,medicine.disease_cause ,Targeted therapy ,Cholangiocarcinoma ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Exome Sequencing ,Biomarkers, Tumor ,medicine ,Humans ,Gallbladder cancer ,Exome sequencing ,Survival analysis ,Aged ,Platinum ,Retrospective Studies ,Aged, 80 and over ,Chemotherapy ,Predictive marker ,business.industry ,High-Throughput Nucleotide Sequencing ,Middle Aged ,Prognosis ,medicine.disease ,Combined Modality Therapy ,Gene Expression Regulation, Neoplastic ,Survival Rate ,Biliary Tract Surgical Procedures ,Bile Ducts, Intrahepatic ,Biliary Tract Neoplasms ,DNA Repair Enzymes ,030104 developmental biology ,Bile Duct Neoplasms ,030220 oncology & carcinogenesis ,Mutation ,Female ,KRAS ,business ,DNA Damage ,Follow-Up Studies - Abstract
Purpose In biliary tract cancer (BTC), standard chemotherapy has limited benefit and no molecular targeted agents have been approved. This study investigated the genetic profile of BTC to identify potential new therapeutic targets and predictive biomarkers. Methods Targeted exome sequencing was performed for 124 patients with BTC [gallbladder cancer (GBC), 25; intrahepatic cholangiocarcinoma (ICC), 55; extrahepatic cholangiocarcinoma (ECC), 44]. Survival analysis was performed in 112 patients who received palliative chemotherapy for locally unresectable or metastatic disease. Results Genetic alterations were observed in 104 patients (83.8%); the most commonly mutated genes were TP53 (44.4%), KRAS (29.0%), ARID1A (12.1%) and IDH1 (9.7%). IDH1/2 mutations appeared more frequently in ICC (23.6%, P = 0.0002) than in GBC (4.0%) or ECC (2.3%), while ERBB2/3 mutations were found only in GBC (20.0%) and ECC (11.4%). Patients harbouring TP53 mutations had shorter overall survival (OS; median 15.2 vs. 37.8 months, P = 0.018), while IDH1 mutations showed a tendency for longer progression-free survival (PFS; 10.6 vs. 6.1 months, P = 0.124). Potentially actionable genetic alterations were found in 54.8%, and 7.1% received appropriate molecular targeted therapy in the clinical trial setting. Germline or somatic mutations in DNA damage repair (DDR) genes were found in 63.5% of patients and were significantly associated with longer PFS (6.9 vs. 5.7 months, P = 0.013) and OS (21.0 vs. 13.3 months, P = 0.009) in patients who received first-line platinum-containing chemotherapies (n = 88). Conclusions A subgroup of patients with BTC may benefit from targeted therapy by the aid of genetic information. In particular, DDR alterations may be a predictive biomarker for response to platinum-containing chemotherapy in patients with BTC.
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- 2019
13. Poorer Oncologic Outcome of Good Responders to PCRT With Remnant Lymph Nodes Defies the Oncologic Paradox in Patients With Rectal Cancer
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Yong Sik Yoon, Chan Wook Kim, Seung-Mo Hong, Jin Cheon Kim, Eunhae Cho, Jong Lyul Lee, In Ja Park, Seok-Byung Lim, and Chang Sik Yu
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Oncology ,medicine.medical_specialty ,Colorectal cancer ,Kaplan-Meier Estimate ,Disease ,Radiation Tolerance ,Disease-Free Survival ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Humans ,Medicine ,Stage (cooking) ,Aged ,Neoplasm Staging ,Retrospective Studies ,Preoperative chemoradiotherapy ,Proctectomy ,Rectal Neoplasms ,business.industry ,Hazard ratio ,Gastroenterology ,Chemoradiotherapy, Adjuvant ,Middle Aged ,Prognosis ,medicine.disease ,Neoadjuvant Therapy ,Confidence interval ,Drug Resistance, Neoplasm ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,Female ,030211 gastroenterology & hepatology ,Lymph Nodes ,Lymph ,Neoplasm Recurrence, Local ,business - Abstract
We evaluated the oncologic outcome of (y)pT0-2N+ rectal cancer and investigated the impact of metastatic lymph nodes (LNs) on oncologic outcome in the setting of preoperative chemoradiotherapy (PCRT).The records of 1403 patients who underwent surgery for rectal cancer between January 2005 and December 2012 were analyzed. The patients were categorized according to the pathologic stage, including 728 patients with ypT0-2 and 675 with ypT3-4 disease. The oncologic outcomes in terms of the 5-year recurrence-free survival (RFS) and overall survival (OS) were analyzed.Metastatic LNs were observed in 11.5% (n = 84) of patients with ypT0-2 and 42.9% (n = 290) of patients with ypT3-4 disease. The RFS and OS were stratified according to ypT and ypN stage as ypT0-2N0, T0-2N+, T3-4N0, and T3-4N+. The ypT0-2N+ group had slightly lower RFS and OS than those in the ypT3-4N0 group. LN metastasis was significantly associated with RFS in both ypT0-2 and ypT3-4 disease, with a stronger association for ypT0-2 disease (hazard ratio, 3.473, 95% confidence interval, 2.058-5.261; P .001 for ypT0-2 and hazard ratio, 2.038; 95% confidence interval, 1.601-2.684; P .001 for ypT3-4, respectively).The oncologic outcomes of ypT0-2N+ disease were not favorable compared with those of ypT3-4N0 disease. These outcomes dispute the survival paradox traditionally believed for non-PCRT-treated patients with rectal cancer, and highlight the underestimated significance of post-PCRT nodal involvement. The prognostic importance of metastatic LNs should be considered when deciding the surgical strategy after PCRT. Further studies including larger numbers of patients with sufficient follow-up are needed to verify the oncologic impact of metastatic LNs within tumors contained within the bowel wall after PCRT.
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- 2019
14. Signet ring cell component predicts aggressive behaviour in colorectal mucinous adenocarcinoma
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Seung-Mo Hong, In Ja Park, Seok-Byung Lim, Chang Sik Yu, Eunsil Yu, Jin Cheon Kim, Yong Sik Yoon, Jihun Kim, and In Hye Song
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Adult ,Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Perineural invasion ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Signet ring cell carcinoma ,medicine ,Humans ,Aged ,Signet ring cell ,business.industry ,Mucin ,Mucins ,Histology ,Colorectal Mucinous Adenocarcinoma ,Middle Aged ,Prognosis ,medicine.disease ,Adenocarcinoma, Mucinous ,digestive system diseases ,Lymphovascular ,030104 developmental biology ,030220 oncology & carcinogenesis ,Adenocarcinoma ,Female ,Colorectal Neoplasms ,business ,Carcinoma, Signet Ring Cell - Abstract
Mucinous adenocarcinoma (MAC) is defined by the presence of extracellular mucin covering more than 50% of the tumour area; however, MAC is histologically heterogeneous and some cases exhibit signet ring cell components. The aim of this study was to determine the prognostic impact of such variable morphology. A total of 299 consecutive MAC patients who underwent curative surgery were included. MACs were classified into four categories according to the predominant pattern of floating tumour cells: strips (27.1%), clusters (51.8%), signet ring cells (6.7%), and mixed clusters and signet ring cells (14.4%). In addition, we categorised MACs according to the relative amount of mucin. MACs with signet ring cell component were clearly associated with poor overall and recurrence-free survivals. Moreover, MACs with more than 50% signet ring cell component showed particularly poor clinical outcome just like non-mucinous signet ring cell carcinoma. MACs with a greater amount of extracellular mucin were associated with poor recurrence-free survival, independent of the pathological stage. In addition, lymphovascular and perineural invasion, advanced pathological stage, and old age at diagnosis were also prognostic factors for poor overall survival. MACs with more than 50% signet ring cell component should be classified as signet ring cell carcinoma and the presence of signet ring cells should be included in the pathology report of MACs with 10-50% signet ring cell component.
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- 2019
15. Effect of Responsiveness of Lymph Nodes to Preoperative Chemoradiotherapy in Patients With Rectal Cancer on Prognosis After Radical Resection
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Hyun Gu Lee, Jung Bok Lee, Seok-Byung Lim, Jin Cheon Kim, In Ja Park, Chang Sik Yu, Seung-Mo Hong, and Sung Joo Kim
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Adult ,Male ,Oncology ,medicine.medical_specialty ,Colorectal cancer ,medicine.medical_treatment ,Kaplan-Meier Estimate ,Radiation Tolerance ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Rectal Neoplasm ,medicine ,Humans ,Lymph node ,Aged ,Neoplasm Staging ,Retrospective Studies ,Tumor Regression Grade ,Proctectomy ,Rectal Neoplasms ,Proportional hazards model ,business.industry ,Gastroenterology ,Chemoradiotherapy, Adjuvant ,Middle Aged ,Prognosis ,medicine.disease ,Magnetic Resonance Imaging ,Primary tumor ,Neoadjuvant Therapy ,medicine.anatomical_structure ,Drug Resistance, Neoplasm ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,Female ,030211 gastroenterology & hepatology ,Lymph Nodes ,Lymph ,Neoplasm Recurrence, Local ,business ,Adjuvant - Abstract
The influence of lymph node (LN) response to preoperative chemoradiotherapy (PCRT) has not been well evaluated for prognosis and additional use of adjuvant treatment after PCRT in rectal cancer patients. The aim of this study was to evaluate the prognostic effect of LN regression grade (LRG) in rectal cancer after PCRT and radical resection.From 2008 to 2011, 389 patients with rectal cancer treated with PCRT followed by radical resection were identified. The pathologic LRG (pLRG) score was determined on the basis of the proportion of tumor cells and fibrosis. The sum of the pLRG of each evaluated LN was used as the final LRG score, LRG-sum. Cox regression analysis was used to evaluate the association of LRG-sum and recurrence-free survival (RFS).The distribution of LRG-sum was significantly associated with tumor regression grade of the primary tumor (P .001). LRG-sum showed different values even in patients with the same number of metastatic LNs. LRG-sum was confirmed as the most relevant associated factor among LN-related variables with RFS along with ypT stage in multivariate analysis. Patients were categorized according to the cutoff points of LRG-sum distribution: LRG1 (LRG-sum 0 to ≤3), LRG2 (LRG-sum 3 to ≤21), and LRG3 (LRG-sum21). RFS showed a significant difference according to LRG group (P .001) and showed more effective difference in RFS in the same ypN stage subgroup on the basis of the number of metastatic LNs.LRG was a prognostic factor of oncologic outcomes of rectal cancer. LN response to PCRT might help in prognostication and determination of treatments after PCRT.
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- 2019
16. Association of SNCA variants with α-synuclein of gastric and colonic mucosa in Parkinson's disease
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Katja Lohmann, Kee Wook Jung, Mi-Jung Kim, Young Jin Kim, Christine Klein, Seung-Mo Hong, Kiju Kim, Frauke Hinrichs, Seung-Jae Myung, Sun Ju Chung, Ho-Sung Ryu, Sung-Cheol Yun, Jeong Hoon Lee, Inke R. König, Juyeon Kim, and Hyo Jeong Lee
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Parkinson's disease ,Colon ,Single-nucleotide polymorphism ,Polymorphism, Single Nucleotide ,Gastroenterology ,Enteric Nervous System ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,SNP ,Intestinal Mucosa ,Allele ,Aged ,Alpha-synuclein ,business.industry ,Stomach ,Parkinson Disease ,Middle Aged ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Neurology ,chemistry ,Gastric Mucosa ,alpha-Synuclein ,Immunohistochemistry ,Female ,Neurology (clinical) ,Geriatrics and Gerontology ,business ,030217 neurology & neurosurgery ,Immunostaining - Abstract
Background Alpha-synuclein (α-Syn) immunostaining in the enteric nervous system (ENS) has been investigated to determine the role of diagnostic biomarker of Parkinson's disease (PD). However, determining factors for alpha-synuclein (α-Syn) deposition in the ENS of humans are still unclear. We aimed to investigate a possible association between SNCA variants and the presence of α-Syn immunostaining in the ENS in patients with PD and healthy individuals. Methods The study subjects consisted of 38 patients with PD and 46 healthy individuals. α-Syn immunohistochemistry was performed for gastric and colonic mucosal tissues of patients with PD and controls. Mucosal biopsy tissues of the ENS were obtained using standard biopsy forceps by endoscopic gastroduodenoscopy or colonoscopy. Two variants within the SNCA gene (the single nucleotide polymorphism [SNP] rs11931074 and the microsatellite REP1) were genotyped. Results In patients with PD, the rs11931074 (G allele) was significantly associated with the presence of α-Syn immunostaining in the ENS (OR = 5.96, 95% CI = 1.70–20.97, P = 0.01). In an interaction analysis, SNP rs11931074–PD status interaction was significantly associated with positive α-Syn immunostaining in the ENS (OR = 7.33, 95% CI = 1.58–33.88, P = 0.01). Longer SNCA REP1 alleles were not associated with positive α-Syn immunostaining in the ENS. Conclusion This exploratory study demonstrated that α-Syn deposition in the ENS may be associated with SNCA variants in patients with PD.
- Published
- 2019
17. Synthesis and characteristics of novel 2-hydroxy-3-mercaptopropyl terminated polyoxypropylene glyceryl ether as an epoxy hardener of epoxy-based adhesives
- Author
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Seung-Mo Hong and Seok-Ho Hwang
- Subjects
Polymers and Plastics ,Organic Chemistry - Published
- 2022
18. EP1092: GASTRIC NEUROENDOCRINE TUMORS ACCORDING TO GRADING CRITERIA OF 2019 WHO CLASSIFICATION INCLUDING MICRONET: A SINGLE-CENTER, RETROSPECTIVE STUDY
- Author
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Yuri Kim, Bo kyung Ahn, Jeong Hoon Lee, and Seung-Mo Hong
- Subjects
Hepatology ,Gastroenterology - Published
- 2022
19. The sulfiredoxin-peroxiredoxin redox system regulates the stemness and survival of colon cancer stem cells
- Author
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Yu Jeong Jeong, Dae-Woon Eom, Sungbo Shim, Sun-Uk Kim, Sung Joo Kim, Seung-Mo Hong, Yena Jung, Young-Ho Park, Peter C.W. Lee, In-Sung Song, and Sung-Wuk Jang
- Subjects
Medicine (General) ,KI, knock-in ,Srx, sulfiredoxin ,QH301-705.5 ,Colon ,Colorectal cancer ,OXPHOS, oxidative phosphorylation ,Clinical Biochemistry ,PBS, phosphate-buffered saline ,Oxidative phosphorylation ,Biochemistry ,DMEM, Dulbecco’s modified Eagle’s medium ,R5-920 ,ROS, reactive oxygen species ,Downregulation and upregulation ,Cancer stem cell ,FACS, fluorescence-activated cell sorting ,medicine ,OCR, oxygen consumption rate ,Biology (General) ,Stemness ,Chemistry ,Organic Chemistry ,Peroxiredoxin ,ROS ,medicine.disease ,OXPHOS ,CSC, cancer stem cell ,WT, wild-type ,Sulfiredoxin ,MACS, magnetic-activated cell sorting ,Cancer research ,FOXM1 ,Prx, peroxiredoxin ,Stem cell ,Research Paper - Abstract
Cancer stem cells (CSCs) initiate tumor formation and are known to be resistant to chemotherapy. A metabolic alteration in CSCs plays a critical role in stemness and survival. However, the association between mitochondrial energy metabolism and the redox system remains undefined in colon CSCs. In this study, we assessed the role of the Sulfiredoxin-Peroxiredoxin (Srx-Prx) redox system and mitochondrial oxidative phosphorylation (OXPHOS) in maintaining the stemness and survival of colon CSCs. Notably, Srx contributed to the stability of PrxI, PrxII, and PrxIII proteins in colon CSCs. Increased Srx expression promoted the stemness and survival of CSCs and was important for the maintenance of the mitochondrial OXPHOS system. Furthermore, Nrf2 and FoxM1 led to OXPHOS activation and upregulated expression of Srx-Prx redox system-related genes. Therefore, the Nrf2/FoxM1-induced Srx-Prx redox system is a potential therapeutic target for eliminating CSCs in colon cancer., Graphical abstract Image 1, Highlights • CSCs initiate tumor formation and are known to be resistant to chemotherapy. • We assessed the role of the Srx-Prx redox system and OXPHOS in colon CSCs. • Srx contributed to the stability of PrxI, PrxII, and PrxIII proteins in colon CSCs. • Nrf2 and FoxM1 upregulated Srx-Prx redox system-related gene expression. • Nrf2/FoxM1-induced Srx-Prx redox system is a target to eliminate CSCs in colon cancer.
- Published
- 2021
20. Evaluation of Clinicopathological Features of Intraductal Biliay Neoplesm of the Bile Duct Based on New Classification: A Japan-Korea Collaborative Study
- Author
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Toru Furukawa, Haeryoung Kim, Keiichi Kubota, Yuhki Sakuraoka, Jin-Young Jang, N. Fukushima, Seung-Mo Hong, Y. Nakanuma, and Kee Taek Jang
- Subjects
Pathology ,medicine.medical_specialty ,medicine.anatomical_structure ,Hepatology ,business.industry ,Bile duct ,Gastroenterology ,Medicine ,Clinicopathological features ,business - Published
- 2021
21. The efficacy of posterior radical antegrade modular pancreatosplenectomy for left sided pancreatic ductal adenocarcinoma
- Author
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J. Kwon, Yangsoon Park, Seung-Mo Hong, Woojin Lee, Dae Wook Hwang, Ki Byung Song, Sun-Whe Kim, and D. Shin
- Subjects
medicine.medical_specialty ,Pancreatic ductal adenocarcinoma ,Hepatology ,business.industry ,Endocrinology, Diabetes and Metabolism ,Gastroenterology ,medicine ,Radiology ,business ,Left sided - Published
- 2020
22. A strategy for actualization of active targeting nanomedicine practically functioning in a living body
- Author
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Si Yeol Song, Seung-Mo Hong, Young-Ah Suh, Jae Hee Lee, Seol Hwa Shin, Jung Jin Hwang, Seong-Yun Jeong, Jung Shin Lee, Eun Kyung Choi, Yun-Yong Park, Eun Jin Ju, Se Jin Jang, and Kyoung Jin Lee
- Subjects
0301 basic medicine ,Drug ,media_common.quotation_subject ,Biophysics ,Mice, Nude ,Bioengineering ,Peptide ,Pharmacology ,Biomaterials ,Mice ,03 medical and health sciences ,Drug Delivery Systems ,0302 clinical medicine ,Peptide Library ,Stomach Neoplasms ,In vivo ,medicine ,Animals ,Humans ,Doxorubicin ,Peptide library ,media_common ,chemistry.chemical_classification ,Mice, Inbred BALB C ,Antibiotics, Antineoplastic ,business.industry ,Cancer ,medicine.disease ,Nanomedicine ,030104 developmental biology ,chemistry ,Mechanics of Materials ,030220 oncology & carcinogenesis ,Liposomes ,Ceramics and Composites ,Nanoparticles ,Nanocarriers ,Peptides ,business ,medicine.drug - Abstract
Designing nanocarriers with active targeting has been increasingly emphasized as for an ideal delivery mechanism of anti-cancer therapeutic agents, but the actualization has been constrained by lack of reliable strategy ultimately applicable. Here, we designed and verified a strategy to achieve active targeting nanomedicine that works in a living body, utilizing animal models bearing a patient's tumor tissue and subjected to the same treatments that would be used in the clinic. The concept for this strategy was that a novel peptide probe and its counterpart protein, which responded to a therapy, were identified, and then the inherent ability of the peptide to target the designated tumor protein was used for active targeting in vivo. An initial dose of ionizing radiation was locally delivered to the gastric cancer (GC) tumor of a patient-derived xenograft mouse model, and phage-displayed peptide library was intravenously injected. The peptides tightly bound to the tumor were recovered, and the counterpart protein was subsequently identified. Peptide-conjugated liposomal drug showed dramatically improved therapeutic efficacy and possibility of diagnostic imaging with radiation. These results strongly suggested the potential of our strategy to achieve in vivo functional active targeting and to be applied clinically for human cancer treatment.
- Published
- 2017
23. Recent updates on grading and classification of neuroendocrine tumors
- Author
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Joo Young Kim, Seung-Mo Hong, and Jae Y. Ro
- Subjects
Pathology ,medicine.medical_specialty ,Lung Neoplasms ,Proliferation index ,Neuroendocrine tumors ,Pathology and Forensic Medicine ,Diagnosis, Differential ,03 medical and health sciences ,0302 clinical medicine ,Stomach Neoplasms ,Intestinal Neoplasms ,medicine ,Humans ,Endocrine system ,Grading (education) ,Gastrointestinal tract ,Lung ,business.industry ,General Medicine ,medicine.disease ,Pancreatic Neoplasms ,Neuroendocrine Tumors ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Neoplasm Grading ,Differential diagnosis ,Pancreas ,business - Abstract
Neuroendocrine tumors (NETs) are originating from neuroendocrine cells in diffuse endocrine systems. NETs are diagnosed by characteristic histologic features and immunoprofiles. Recent 2010 WHO classification for gastroenteropancreatic NETs introduced grading system based on mitotic count and Ki-67 proliferation index. Gastroenteropancreatic NETs are classified as NET grade 1, NET grade 2, and neuroendocrine carcinoma (NET grade 3). However, the carcinoid is still used in classification of NETs of the lung and uterine cervix. Some issues with grading system such as methodologies for evaluation of Ki-67 index and subclassification of neuroendocrine carcinoma (NET grade 3) are arising. The importance of Ki-67 labeling index is emerging in differential diagnosis of lung carcinoids. In this review, we focus on recent grading and classification of NETs and related issues in various organs, including gastrointestinal tract, pancreas, lung, and female reproductive organs.
- Published
- 2017
24. KRAS and PIK3CA mutations in colorectal adenocarcinomas correlate with aggressive histological features and behavior
- Author
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Tae Im Kim, Hyung-Sik Shin, Mineui Hong, Byung Chun Kim, Jeong Won Kim, Young Woong Ko, Seung-Mo Hong, Eunsil Yu, Jihun Kim, Mi Kyung Shin, Sung-Min Chun, Se-Jin Jang, and Kyung-Chan Choi
- Subjects
Male ,Proto-Oncogene Proteins B-raf ,0301 basic medicine ,Oncology ,Neuroblastoma RAS viral oncogene homolog ,medicine.medical_specialty ,Time Factors ,Class I Phosphatidylinositol 3-Kinases ,Colorectal cancer ,DNA Mutational Analysis ,Perineural invasion ,Kaplan-Meier Estimate ,Adenocarcinoma ,Biology ,medicine.disease_cause ,Disease-Free Survival ,Pathology and Forensic Medicine ,Proto-Oncogene Proteins p21(ras) ,03 medical and health sciences ,Exon ,0302 clinical medicine ,Growth factor receptor ,Tumor budding ,Internal medicine ,Peripheral Nervous System ,Biomarkers, Tumor ,medicine ,Humans ,Genetic Predisposition to Disease ,Neoplasm Invasiveness ,neoplasms ,Retrospective Studies ,Exons ,Middle Aged ,medicine.disease ,Phenotype ,digestive system diseases ,Treatment Outcome ,030104 developmental biology ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,Mutation ,Cancer research ,Female ,KRAS ,Neoplasm Grading ,Colorectal Neoplasms - Abstract
Summary Tumor budding (TB) in colorectal carcinoma (CRC) is related to epithelial-mesenchymal transition and has been recently characterized as an indicator of poor prognosis along with lymphovascular tumor emboli, perineural invasion, and an infiltrative growth pattern. Mutations in the genes of the Ras–mitogen-activated protein kinase and phosphatidylinositol-4,5-bisphosphate 3-kinase pathways are associated with epithelial-mesenchymal transition and an aggressive CRC phenotype and have been used in patient stratification for anti–epidermal growth factor receptor therapies; however, the impact of these mutations on CRC morphology and behavior remains unclear. In this study, using a multigene panel, we detected KRAS , NRAS , BRAF , PIK3CA , TP53 , and POLE mutations in 90 CRCs and investigated their associations with clinicopathological parameters, including TB. Our results showed that 21 of 34 tumors with high-grade TB had KRAS mutations ( P =.001) and KRAS G12D and PIK3CA exon 9 variants were significantly associated with high-grade TB ( P =.002 and .006, respectively); furthermore, tumors with KRAS mutations in exons 3 and 4 tended to have lymphovascular tumor emboli and perineural invasion ( P =.044 and .049, respectively). PIK3CA exon 9 mutations indicated a tendency for shorter disease-free survival ( P =.030), whereas BRAF mutations were associated with extracellular mucin deposition ( P =.016). Our study revealed a correlation of KRAS mutations with high-grade TB, an association of certain KRAS and PIK3CA variants with aggressive clinicopathological features, as well as a possible relationship between BRAF mutations and mucin production in CRC.
- Published
- 2017
25. CD133 expression in well-differentiated pancreatic neuroendocrine tumors: a potential predictor of progressive clinical courses
- Author
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Seung-Mo Hong, Yonson Ku, Masayuki Akita, Yoh Zen, Joo Young Kim, Kohei Fujikura, Takumi Fukumoto, Denis Corbeil, Kyoko Otani, Soyeon An, Yoshihide Nanno, Yasuhiro Sakai, Takanori Hirose, Jana Karbanová, Hirochika Toyama, Ki Byung Song, Tomoo Itoh, and Song Cheol Kim
- Subjects
Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Pathology ,Time Factors ,Multivariate analysis ,Lymphovascular invasion ,Biopsy ,Kaplan-Meier Estimate ,Biology ,Neuroendocrine tumors ,Gastroenterology ,Disease-Free Survival ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Neoplasm Invasiveness ,Clinical significance ,AC133 Antigen ,Grading (tumors) ,Aged ,Neoplasm Staging ,Keratin-19 ,Tissue microarray ,Cell Differentiation ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Pancreatic Neoplasms ,Neuroendocrine Tumors ,Phenotype ,030104 developmental biology ,Tissue Array Analysis ,030220 oncology & carcinogenesis ,embryonic structures ,Cohort ,Female ,Neoplasm Grading ,Neoplasm Recurrence, Local - Abstract
The present study aimed to elucidate whether the stemness molecule, CD133, is expressed in well-differentiated pancreatic neuroendocrine tumors (PanNETs; World Health Organization grades 1 and 2) and establish its clinical relevance using 2 separate cohorts. In the first series (n = 178) in which tissue microarrays were available, immunohistochemistry revealed that CD133 was expressed in 14 cases (8%). CD133+ PanNETs had higher TNM stages (P < .01), more frequent lymphovascular invasion (P = .01), and higher recurrence rates (P = .01). In the second cohort (n = 56), the expression of CD133 and CK19 was examined in whole tissue sections. CD133 and CK19 were positive in 10 (18%) and 36 (64%) cases, respectively. CD133 expression correlated with higher pT scores (P < .01), the presence of microscopic venous infiltration (P = .03), and shorter disease-free periods (P < .01). When cases were divided into grade 1 and 2 neoplasms, patients with CD133+ PanNET continued to have shorter disease-free periods than did those with CD133- tumors in both groups (P < .01 and P = .02, respectively). Although CK19+ cases had shorter disease-free periods than did CK19- cases in the whole cohort (P = .02), this difference was less apparent in subanalyses of grade 1 and 2 cases. CD133 expression also appeared to be an independent predictive factor for tumor recurrence in a multivariate analysis (P = .018). The CD133 phenotype was identical between primary and metastatic foci in 17 of 18 cases from which tissues of metastatic deposits were available. In conclusion, the combination of CD133 phenotyping and World Health Organization grading may assist in stratifying patients in terms of the risk of progressive clinical courses.
- Published
- 2017
26. Nonductal Pancreatic Cancers
- Author
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Seung-Mo Hong and Sun-Young Jun
- Subjects
Pathology ,medicine.medical_specialty ,Pancreatoblastoma ,Tumor cells ,Pathology and Forensic Medicine ,Diagnosis, Differential ,03 medical and health sciences ,0302 clinical medicine ,Stroma ,Biomarkers, Tumor ,Acinar cell ,Humans ,Medicine ,Pancreas ,beta Catenin ,Carcinoma, Acinar Cell ,business.industry ,Cadherin ,Cadherins ,medicine.disease ,Immunohistochemistry ,Carcinoma, Papillary ,Gene Expression Regulation, Neoplastic ,Pancreatic Neoplasms ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Surgery ,Differential diagnosis ,business - Abstract
Nonductal pancreatic neoplasms, including solid pseudopapillary neoplasms, acinar cell carcinomas, and pancreatoblastomas, are uncommon. These entities share overlapping gross, microscopic, and immunohistochemical features, such as well-demarcated solid neoplasms, monotonous cellular tumor cells with little intervening stroma, and abnormal beta-catenin expression. Each tumor also has unique clinicopathologic characteristics with diverse clinical behavior. To differentiate nonductal pancreatic neoplasms, identification of histologic findings, such as pseudopapillae, acinar cell features, and squamoid corpuscles, is important. Immunostainings for acinar cell or neuroendocrine markers are helpful for differential diagnosis. This article describes the clinicopathologic and immunohistochemical features of nonductal pancreatic cancers.
- Published
- 2016
27. A melanin-bleaching methodology for molecular and histopathological analysis of formalin-fixed paraffin-embedded tissue
- Author
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Kevin M. Brown, Joon-Yong Chung, Kris Ylaya, John D. Sears, Candice Perry, Chel Hun Choi, Seung-Mo Hong, Hanbyoul Cho, Jiyeon Choi, and Stephen M. Hewitt
- Subjects
0301 basic medicine ,Tris ,Hot Temperature ,Biology ,Article ,Pathology and Forensic Medicine ,Melanin ,03 medical and health sciences ,chemistry.chemical_compound ,Formaldehyde ,Humans ,Molecular Biology ,Melanins ,Tricine ,Paraffin Embedding ,030102 biochemistry & molecular biology ,Histological Techniques ,RNA ,Hydrogen Peroxide ,Cell Biology ,Molecular biology ,Blot ,chemistry ,Nucleic acid ,sense organs ,DNA ,Immunostaining - Abstract
Removal of excessive melanin from heavily pigmented formalin-fixed paraffin-embedded (FFPE) melanoma tissues is essential for histomorphological and molecular diagnostic assessments. Although there have been efforts to address this issue, current methodologies remain complex and time-consuming, and are not suitable for multiple molecular applications. Herein, we have developed a robust and rapid melanin-bleaching methodology for FFPE tissue specimens. Our approach is based on quick bleaching (15 min) at high temperature (80 °C) with 0.5% diluted hydrogen peroxide (H(2)O(2)) in Tris-HCl, PBS, or Tris/Tricine/SDS buffer. Immunostaining for Ki-67 and HMB45 was enhanced by bleaching with 0.5% H(2)O(2) in Tris/Tricine/SDS and Tris-HCl, respectively. In addition to histopathological applications, our approach also facilitates recovery of protein and nucleic acid from archival melanin-rich FFPE tissue sections. Protein extracted from bleached FFPE tissues was compatible with western blotting using anti-human GAPDH and AKT antibodies. Our bleaching condition significantly improved RNA quality compared with unbleached tissues without compromising the yield. Notably, the RNA/DNA obtained from bleached tissues was suitable for end point PCR and real-time quantitative RT–PCR. In conclusion, this improved melanin-bleaching method enhances and simplifies immunostaining procedures, and facilitates the use of melanin-rich FFPE tissues for histomorphological and PCR amplification-based molecular assays.
- Published
- 2016
28. Shear Wave Elastography for Assessment of Steatohepatitis and Hepatic Fibrosis in Rat Models of Non-Alcoholic Fatty Liver Disease
- Author
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Seung-Mo Hong, Bo-Kyeong Kang, Hyunhee Cheong, Moon-Gyu Lee, Seung Soo Lee, and Kiseok Jang
- Subjects
Liver Cirrhosis ,Male ,medicine.medical_specialty ,Pathology ,Acoustics and Ultrasonics ,Biophysics ,Disease ,Severity of Illness Index ,digestive system ,Gastroenterology ,Rats, Sprague-Dawley ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,Nonalcoholic fatty liver disease ,Animals ,Medicine ,Radiology, Nuclear Medicine and imaging ,Stage (cooking) ,Shear wave elastography ,Radiological and Ultrasound Technology ,Receiver operating characteristic ,business.industry ,Fatty liver ,nutritional and metabolic diseases ,medicine.disease ,digestive system diseases ,Rats ,Fatty Liver ,Disease Models, Animal ,Liver ,ROC Curve ,Elasticity Imaging Techniques ,Steatohepatitis ,business ,Hepatic fibrosis - Abstract
The purpose of this study was to evaluate shear wave elastography (SWE) as a method for determining the severity of non-alcoholic fatty liver disease (NAFLD) and the stage of hepatic fibrosis, as well as the major determinants of liver elasticity among the various histologic and biomolecular changes associated with NAFLD. Rat NAFLD models with various degrees of NAFLD severity were created and imaged using SWE. The explanted livers were subjected to histopathologic evaluation and RNA expression analysis. Among the histologic and biomolecular findings, the fibrosis stage and the collagen RNA level were significant independent factors associated with liver elasticity (p < 0.001). Liver elasticity was effective in detecting non-alcoholic steatohepatitis (NASH) and in determining fibrosis stage, and the corresponding areas under the receiver operating characteristic curves were 0.963 and 0.927-0.997, respectively. In conclusion, SWE is a potential non-invasive method for the detection of NASH and staging of hepatic fibrosis in patients with NAFLD.
- Published
- 2015
29. A Combination of Molecular Markers and Clinical Features Improve the Classification of Pancreatic Cysts
- Author
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Volkan Adsay, Herbert J. Zeh, David S. Klimstra, Oscar W. Cummings, Jean Murphy, Bert Vogelstein, John L. Cameron, Jorge Paulino, Marco Dal Molin, Giuseppe Zamboni, Carlos Fernandez-del Castillo, Tyler M. Tomita, Song Cheol Kim, Michele T. Yip-Schneider, Nita Ahuja, Janine Ptak, Anne Marie Lennon, Siva P. Raman, C. Max Schmidt, Justin Geoghegan, Christopher L. Wolfgang, Kenji Yamao, Noushin Niknafs, Isaac Kinde, Mari Mino-Kenudson, Giuseppe Malleo, Jeanin E. van Hooft, Rachel Karchin, Kenneth W. Kinzler, Yuxuan Wang, Niall Swan, Seung-Mo Hong, James R. Eshleman, Christopher Douville, William R. Brugge, Lisa Dobbyn, Sun Whe Kim, Schalk Van der Merwe, Wooil Kwon, Mark A. Schattner, Matthew J. Weiss, Nickolas Papadopoulos, Barish H. Edil, Yuchen Jiao, Kenzo Hirose, Aldo Scarpa, Susuma Hijioka, Marcia I. Canto, Martin A. Makary, Shinichi Yachida, Roberto Salvia, Simeon Springer, Luis A. Diaz, Amanda L. Blackford, Aatur D. Singhi, David L. Masica, Nobuyoshi Hiraoka, Michael Goggins, Meredith E. Pittman, Satoshi Nara, Ki Byung Song, Randall E. Brand, Massimo Falconi, Peter J. Allen, Ralph H. Hruban, Jin-Young Jang, Richard D. Schulick, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, CCA -Cancer Center Amsterdam, Gastroenterology and Hepatology, Springer, Simeon, Wang, Yuxuan, Dal Molin, Marco, Masica David, L, Jiao, Yuchen, Kinde, Isaac, Blackford, Amanda, Raman Siva, P, Wolfgang Christopher, L, Tomita, Tyler, Niknafs, Noushin, Douville, Christopher, Ptak, Janine, Dobbyn, Lisa, Allen Peter, J, Klimstra David, S, Schattner Mark, A, Schmidt C., Max, Yip Schneider, Michele, Cummings Oscar, W, Brand Randall, E, Zeh Herbert, J, Singhi Aatur, D, Scarpa, Aldo, Salvia, Roberto, Malleo, Giuseppe, Zamboni, Giuseppe, Falconi, Massimo, Jang Jin, Young, Kim Sun, Whe, Kwon, Wooil, Hong Seung, Mo, Song Ki, Byung, Kim Song, Cheol, Swan, Niall, Murphy, Jean, Geoghegan, Justin, Brugge, William, Fernandez Del Castillo, Carlo, Mino Kenudson, Mari, Schulick, Richard, Edil Barish, H, Adsay, Volkan, Paulino, Jorge, van Hooft, Jeanin, Yachida, Shinichi, Nara, Satoshi, Hiraoka, Nobuyoshi, Yamao, Kenji, Hijioka, Susuma, van der Merwe, Schalk, Goggins, Michael, Canto Marcia, Irene, Ahuja, Nita, Hirose, Kenzo, Makary, Martin, Weiss Matthew, J, Cameron, John, Pittman, Meredith, Eshleman James, R, Diaz Luis A., Jr, Papadopoulos, Nickola, Kinzler Kenneth, W, Karchin, Rachel, Hruban Ralph, H, Vogelstein, Bert, and Lennon Anne, Marie
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,diagnosis ,medicine.disease_cause ,Article ,chemistry.chemical_compound ,Predictive Value of Tests ,CDKN2A ,Molecular marker ,Biomarkers, Tumor ,GNAS complex locus ,medicine ,Humans ,Genetic Predisposition to Disease ,Cyst ,molecular ,Genetic Testing ,Pancreas ,neoplasms ,IPMN ,pancreatic cyst ,Retrospective Studies ,Hepatology ,biology ,Intraductal papillary mucinous neoplasm ,Gastroenterology ,Middle Aged ,Prognosis ,medicine.disease ,Phenotype ,medicine.anatomical_structure ,chemistry ,Mutation ,biology.protein ,Female ,KRAS ,Pancreatic Cyst ,Pancreatic cysts ,Algorithms - Abstract
Background & Aims The management of pancreatic cysts poses challenges to both patients and their physicians. We investigated whether a combination of molecular markers and clinical information could improve the classification of pancreatic cysts and management of patients. Methods We performed a multi-center, retrospective study of 130 patients with resected pancreatic cystic neoplasms (12 serous cystadenomas, 10 solid pseudopapillary neoplasms, 12 mucinous cystic neoplasms, and 96 intraductal papillary mucinous neoplasms). Cyst fluid was analyzed to identify subtle mutations in genes known to be mutated in pancreatic cysts ( BRAF , CDKN2A , CTNNB1 , GNAS , KRAS , NRAS , PIK3CA , RNF43 , SMAD4 , TP53 , and VHL ); to identify loss of heterozygozity at CDKN2A , RNF43 , SMAD4 , TP53 , and VHL tumor suppressor loci; and to identify aneuploidy. The analyses were performed using specialized technologies for implementing and interpreting massively parallel sequencing data acquisition. An algorithm was used to select markers that could classify cyst type and grade. The accuracy of the molecular markers was compared with that of clinical markers and a combination of molecular and clinical markers. Results We identified molecular markers and clinical features that classified cyst type with 90%−100% sensitivity and 92%−98% specificity. The molecular marker panel correctly identified 67 of the 74 patients who did not require surgery and could, therefore, reduce the number of unnecessary operations by 91%. Conclusions We identified a panel of molecular markers and clinical features that show promise for the accurate classification of cystic neoplasms of the pancreas and identification of cysts that require surgery.
- Published
- 2015
30. Prognostic Comparison of the Longitudinal Margin Status in Distal Bile Duct Cancer: R0 on First Bile Duct Resection vs. R0 After Additional Resection
- Author
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Young-Joo Lee, Seung-Mo Hong, Jin Hee Kim, Eun Sung Jun, Yejong Park, Jae Hoon Lee, Sang Hyun Shin, Kwang-Min Park, Dae Wook Hwang, Ki Byung Song, Song Cheol Kim, and Sun-Young Jun
- Subjects
medicine.medical_specialty ,business.industry ,Bile duct ,medicine.medical_treatment ,Carcinoma in situ ,medicine.disease ,Pancreaticoduodenectomy ,Institutional review board ,Margin status ,Surgery ,Bile duct cancer ,medicine.anatomical_structure ,Dysplasia ,Carcinoma ,Medicine ,business - Abstract
Background: This study investigated survival differences following intra-operative frozen-section examination of bile duct resection margins and final longitudinal margin status (LMS) in distal bile duct cancer confined to the intra-pancreatic portion. No studies have examined the relationship between LMS and survival for distal bile duct cancer. Methods: Overall, 193 patients underwent Whipple's operation for curative resection of distal bile duct cancer from 2008 to 2016 at the Asan Medical Center, Seoul, Republic of Korea. Patients were sorted into 2 and 3 groups according to LMS of frozen-sections and LMS of the final pathological specimen results: R0 on first bile duct resection (Primary R0), R0 after additional resection (Secondary R0), and no evidence of residual carcinoma (FR0), carcinoma in situ or high-grade dysplasia (FR1-CIS/HGD), or invasive carcinoma (FR1-INV). Survival and prognostic factors according to LMS were analyzed. Findings: There were no differences between primary R0 and secondary R0 in 5-year overall survival (OS) (60.8% vs. 46.1%, P = 0.969) or diseasefree survival (DFS) (54·6% vs. 54·9%, P = 0·903). The 5-year OS after FR0, FR1-CIS/HGD, FR1-INV were 59·3%, 59·5%, 14·3%, respectively. There was no difference between FR0 and FR1-CIS/HGD (P = 0·842). Final margin status of the bile duct was an independent prognostic factor by multivariable analyses. Interpretation: If R0 of final longitudinal margin status was achieved, it would help to improve survival regardless of R0 through additional resection. And, it should be avoided remaining invasive cancer at the longitudinal margin whenever possible. Funding Statement: This study was supported by the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (grant number: HI14C2640). Declaration of Interests: The authors declare no competing interests in relation to this study. Ethics Approval Statement: Data collection and analysis were performed according to the institutional guidelines, which conformed to the ethical standards of the Declaration of Helsinki. Institutional Review Board approval was obtained on December 22, 2017 (No. 2017-1407).
- Published
- 2018
31. 1124 A MULTI-MODALITY TEST TO GUIDE THE MANAGEMENT OF PATIENTS WITH PANCREATIC CYSTS
- Author
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C. Max Schmidt, Bert Vogelstein, Ralph H. Hruban, Aatur D. Singhi, Christopher Douville, Alison P. Klein, Walter G. Park, Michael Goggins, Christopher J. Thoburn, Randall Brand, Aldo Scarpa, Shinichi Yachida, Marcia I. Canto, Martin A. Makary, David L. Masica, Simeon Springer, Michele T. Yip-Schneider, Niall Swan, Christopher L. Wolfgang, Jorge Paulino, Carlos Fernandez-Del Castillo, Mark A. Schattner, Rachel E. Simpson, William R. Brugge, Mari Mino-Kenudson, Cristian Tomasetti, Nickolas Papadopoulos, Matthew J. Weiss, Rachel Karchin, Kenneth W. Kinzler, Bahman Asfari, Jin-Young Jang, Marco Dal Molin, Stefano Crippa, Giuseppe Zamboni, Susuma Hijioka, Elizabeth D. Thompson, Massimo Falconi, Jin He, Seung-Mo Hong, Joshua D. Cohen, David S. Klimstra, Dae Wook Hwang, Richard D. Schulick, Jeanin E. Van Hooft, Peter J. Allen, Wooil Kwon, Anne Marie Lennon, Lu Li, Barish H. Edil, Claudio Doglioni, Roberto Salvia, Richard A. Burkhart, Rita Teresa Lawlor, and Justin Geoghegan
- Subjects
medicine.medical_specialty ,business.industry ,Gastroenterology ,medicine ,Radiology, Nuclear Medicine and imaging ,Radiology ,Pancreatic cysts ,medicine.disease ,business ,Multi modality ,Test (assessment) - Published
- 2019
32. Pathological Features and Long-term Post-resection Prognosis of Primary Neuroendocrine Tumors of the Liver
- Author
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Tae-Yong Ha, Chul-Soo Ahn, Seung-Mo Hong, Gi-Won Song, Shin Hwang, Jay Jung, Ki-Hun Kim, and Deok-Bog Moon
- Subjects
Pathology ,medicine.medical_specialty ,Primary (chemistry) ,Hepatology ,business.industry ,Gastroenterology ,medicine ,Neuroendocrine tumors ,medicine.disease ,business ,Pathological ,Resection ,Term (time) - Published
- 2019
33. Granular cell tumor of the gastrointestinal tract: histologic and immunohistochemical analysis of 98 cases
- Author
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Hosub Park, Kwangseon Min, Soyeon An, Ho June Song, Young Soo Park, Eunsil Yu, Min-Sun Kim, Jaejung Jang, Jeong Hoon Lee, Kyung-Jo Kim, Jihun Kim, and Seung-Mo Hong
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pathology ,Esophageal Neoplasms ,Gastroenterology ,Pathology and Forensic Medicine ,Stomach Neoplasms ,Infiltrative Growth Pattern ,Submucosa ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Esophagus ,Aged ,Gastrointestinal tract ,Granular cell tumor ,business.industry ,Stomach ,S100 Proteins ,Sigmoid colon ,Middle Aged ,medicine.disease ,Immunohistochemistry ,medicine.anatomical_structure ,Granular Cell Tumor ,Female ,Colorectal Neoplasms ,business - Abstract
Granular cell tumors (GCTs) are uncommon benign neoplasms in the gastrointestinal (GI) tract, and our current understanding of GCT in GI tract is limited. A total of 98 GCTs were retrieved from 95 patients, and the clinicopathological and immunohistochemical features were compared. The male-to-female ratio was 2.2:1 and with a mean age of 49 years. The mean tumor size was 0.37 cm. Seventy-three esophageal (75%), 21 colorectal (21%), and 4 gastric (4%) GCTs were included. Gastric (mean, 0.75 cm) and colorectal (0.6 cm) GCTs were significantly larger than esophageal tumors (0.27 cm; P
- Published
- 2015
34. Oxidation behavior of austenitic stainless steels as fuel cladding candidate materials for SCWR in superheated steam
- Author
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Hiroshi Abe, Seung Mo Hong, and Yutaka Watanabe
- Subjects
Cladding (metalworking) ,Austenite ,Nuclear and High Energy Physics ,Materials science ,Mechanical Engineering ,Superheated steam ,Kinetics ,Metallurgy ,Oxide ,Recrystallization (metallurgy) ,Atmospheric temperature range ,Microstructure ,chemistry.chemical_compound ,Nuclear Energy and Engineering ,chemistry ,General Materials Science ,Safety, Risk, Reliability and Quality ,Waste Management and Disposal - Abstract
Oxidation behavior of austenitic stainless steels as fuel cladding candidate materials for supercritical-water-cooled reactor (SCWR), including three types of 15Cr–20Ni stainless steels (1520 SSs), in the temperature range of 700–780 °C superheated steam have been investigated. Effect of temperature, dissolved oxygen (DO), degree of cold work (CW), and machined layer by cold drawing process on the oxidation kinetics assuming power-law kinetics are discussed. Characteristics of oxide layers and its relation to oxidation behaviors are also discussed. The effect of DO on the weight gain behavior in superheated steam at 700 °C was minor for all specimens at least up to 200 ppb DO. The tube-shaped specimens of 1520 SSs showed very good oxidation resistance at 700–780 °C. There was no clear difference in the oxidation kinetics among the three investigated types of 1520 SSs. The machined layer formed at the tube surface has a significant role to mitigate oxidation in superheated steam. A fine-grained microstructure near the surface due to recrystallization by cold drawing process is effective to form the protective Cr 2 O 3 layer. It has been suggested that since Cr diffusion in the outside surface of tubes is accelerated as a result of an increased dislocation density and/or grain refinement by cold drawing, tube specimens show very slow oxidation kinetics. Breakdown of the protective Cr 2 O 3 layer and nodule oxide formation were partly observed on the tube-shaped specimens of 15Cr–20Ni SSs. The reliability of Cr 2 O 3 layer has to be carefully examined to predict the oxidation kinetics after long-term exposure.
- Published
- 2014
35. Prognostic significance of CDX2 and mucin expression in small intestinal adenocarcinoma
- Author
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Sun-Young Jun, Hosub Park, Kee-Taek Jang, Dae Woon Eom, Seung-Mo Hong, Eunsil Yu, and Young Kyung Bae
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Perineural invasion ,Kaplan-Meier Estimate ,Adenocarcinoma ,Mucin 5AC ,digestive system ,Immunophenotyping ,Pathology and Forensic Medicine ,Young Adult ,Intestinal Neoplasms ,Biomarkers, Tumor ,medicine ,Humans ,CDX2 Transcription Factor ,CDX2 ,Mucin-6 ,MUC1 ,Aged ,Proportional Hazards Models ,Aged, 80 and over ,Homeodomain Proteins ,business.industry ,Mucin-1 ,Mucin ,Small Intestinal Adenocarcinoma ,Middle Aged ,Prognosis ,medicine.disease ,Immunohistochemistry ,digestive system diseases ,Tissue Array Analysis ,embryonic structures ,Female ,business - Abstract
The clinicopathological and prognostic significance of CDX2 and mucin expression have not been comprehensively evaluated in small intestinal adenocarcinoma. Immunohistochemical microarray analyses of CDX2, MUC1, MUC5AC, and MUC6 protein expressions in 189 surgically resected small intestinal adenocarcinoma cases were examined and compared with various clinicopathologic variables, including survival. CDX2, MUC1, MUC5AC, and MUC6 expressions were observed in 43.4% (82 patients), 37.6% (71), 31.7% (60), and 21.7% (41) of patients, respectively. Whereas CDX2 expression was found to be associated with low-grade tumors (P=0.034), fewer nodal metastases (P=0.019), and less perineural invasion (P=0.049) in small intestinal adenocarcinoma patients, patients expressing MUC1 tended to demonstrate high-grade (P=0.021) and nodular or infiltrative (P=0.020) tumors. On the basis of the combined CDX2, MUC1, MUC5AC, and MUC6 expression patterns, small intestinal adenocarcinoma patients were further classified as intestinal (CDX2+/MUC1-; 29.6%), pancreatobiliary (CDX2-/MUC1+; 23.8%), mixed (CDX2+/MUC1+; 13.8%), gastric (CDX2-/MUC1-/MUC5AC+ or MUC6+; 13.8%), or null (CDX2-/MUC1-/MUC5AC-/MUC6-; 19.0%). Among these immunophenotypes, intestinal-type patients demonstrated more frequent distal (jejunal or ileal; P=0.033), tubular (P=0.039), and low-grade tumors (P=0.004) and significantly better survival according to univariate (P
- Published
- 2014
36. Increased number of metastatic lymph nodes in adenocarcinoma of the ampulla of Vater as a prognostic factor: A proposal of new nodal classification
- Author
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Song Cheol Kim, HyungJun Cho, Seung-Mo Hong, Eunsil Yu, Hyo Jeong Kang, Kwang-Min Park, Young-Joo Lee, Soo-Heang Eo, and Sung Koo Lee
- Subjects
Adult ,Male ,Oncology ,Ampulla of Vater ,medicine.medical_specialty ,Prognostic factor ,Common Bile Duct Neoplasms ,Lymph node metastasis ,Adenocarcinoma ,Metastasis ,Young Adult ,Internal medicine ,Republic of Korea ,medicine ,Humans ,Lymph node ,Aged ,Neoplasm Staging ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Middle Aged ,Prognosis ,medicine.disease ,medicine.anatomical_structure ,Lymphatic Metastasis ,Female ,Surgery ,Lymph Nodes ,Lymph ,NODAL ,business - Abstract
Although the number of metastatic lymph nodes in most gastrointestinal carcinomas is correlated inversely with prognosis, the prognostic value of the number of metastatic lymph nodes in ampullary adenocarcinoma has not been well characterized.Lymph node metastasis was assessed in the Surveillance, Epidemiology and End Results database in 1,057 ampullary adenocarcinomas that were operatively resected and for which at least 12 lymph nodes were examined. A complex pattern of survival versus extent of lymph node metastasis was captured by censored local regression. The impact of the extent of lymph nodes metastasis on survival was investigated by use of the K-adaptive partitioning algorithm to identify the most significant cut-off points of metastatic lymph nodes affecting survival.Two significant cut-off points (0 and 2) for the metastatic lymph node segregated patients into 3 groups with clinically important differences in median survival: patients with no metastatic lymph node (477 cases) had a median survival of 91 months, patients with 1-2 metastatic lymph nodes (279 cases) had a median survival of 29 months, whereas patients with ≥3 metastatic Lymph nodes (301 cases) had a median survival of 19 months (P.0001). These results were validated with additional single institution dataset (318 cases, P.0001).The present results suggest that the nodal classification of ampullary adenocarcinoma should be categorized N0 (no metastatic lymph node), N1 (1-2 metastatic lymph nodes), and N2 (≥3 metastatic lymph nodes).
- Published
- 2014
37. Incipient serous cystic neoplasia of the pancreas is a very rare phenomenon: a systematic prospective observation in pancreatectomy specimens—reply
- Author
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So-Woon Kim and Seung-Mo Hong
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,Pathology and Forensic Medicine ,03 medical and health sciences ,Pancreatectomy ,0302 clinical medicine ,X ray computed ,medicine ,Humans ,Prospective Studies ,Prospective cohort study ,Pancreas ,business.industry ,General surgery ,Cystadenoma, Serous ,medicine.disease ,Pancreatic Neoplasms ,Serous fluid ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Cystadenoma ,030211 gastroenterology & hepatology ,Tomography, X-Ray Computed ,business - Published
- 2017
38. Association Between Expression Level of PD1 by Tumor-Infiltrating CD8+ T Cells and Features of Hepatocellular Carcinoma
- Author
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Deok-Bog Moon, Sukyeong Eo, Seongyeol Park, Hyung-Don Kim, Seung-Mo Hong, Kijong Yi, Kyung Hwan Kim, Young Seok Ju, Min Hwan Kim, Shin Hwang, Min Kyung Jung, Gi-Won Song, Eui-Cheol Shin, Su-Hyung Park, Changhoon Yoo, and Hyo Jeong Kang
- Subjects
0301 basic medicine ,Tumor microenvironment ,Hepatology ,Tumor-infiltrating lymphocytes ,Lymphocyte ,Gastroenterology ,Biology ,HCCS ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,medicine ,Cancer research ,Cytotoxic T cell ,Interferon gamma ,Interleukin-7 receptor ,CD8 ,medicine.drug - Abstract
Background & Aims T-cell exhaustion, or an impaired capacity to secrete cytokines and proliferate with overexpression of immune checkpoint receptors, occurs during chronic viral infections but has also been observed in tumors, including hepatocellular carcinomas (HCCs). We investigated features of exhaustion in CD8+ T cells isolated from HCC specimens. Methods We obtained HCC specimens, along with adjacent nontumor tissues and blood samples, from 90 patients who underwent surgical resection at Asan Medical Center (Seoul, Korea) from April 2016 through April 2018. Intrahepatic lymphocytes and tumor-infiltrating T cells were analyzed by flow cytometry. Tumor-infiltrating CD8+ T cells were sorted by flow cytometry into populations based on expression level of programmed cell death 1 (PDCD1 or PD1): PD1-high, PD1-intermediate, and PD1-negative. Sorted cells were analyzed by RNA sequencing. Proliferation and production of interferon gamma (IFNG) and tumor necrosis factor (TNF) by CD8+ T cells were measured in response to anti-CD3 and antibodies against immune checkpoint receptors including PD1, hepatitis A virus cellular receptor 2 (HAVCR2 or TIM3), lymphocyte activating 3 (LAG3), or isotype control. Tumor-associated antigen-specific CD8+ T cells were identified using HLA-A*0201 dextramers. PDL1 expression on tumor tissue was assessed by immunohistochemistry. Results PD1-high, PD1-intermediate, and PD1-negative CD8+ T cells from HCCs had distinct gene expression profiles. PD1-high cells expressed higher levels of genes that regulate T-cell exhaustion than PD1-intermediate cells. PD1-high cells expressed TIM3 and LAG3, and low proportions of TCF1+, TBEThigh/eomesoderminlow, and CD127+. PD1-high cells produced the lowest amounts of IFNG and TNF upon anti-CD3 stimulation. Differences in the PD1 expression patterns of CD8+ T cells led to the identification of 2 subgroups of HCCs: HCCs with a discrete population of PD1-high cells were more aggressive than HCCs without a discrete population of PD1-high cells. HCCs with a discrete population of PD1-high cells had higher levels of predictive biomarkers of response to anti-PD1 therapy. Incubation of CD8+ T cells from HCCs with a discrete population of PD1-high cells with antibodies against PD1 and TIM3 or LAG3 further restored proliferation and production of IFNG and TNF in response to anti-CD3. Conclusions We found HCC specimens to contain CD8+ T cells that express different levels of PD1. HCCs with a discrete population of PD1-high CD8+ T cells express TIM3 and/or LAG3 and produce low levels of IFNG and TNF in response to anti-CD3. Incubation of these cells with antibodies against PD1 and TIM3 or LAG3 further restore proliferation and production of cytokines; HCCs with a discrete population of PD1-high CD8+ T cells might be more susceptible to combined immune checkpoint blockade–based therapies.
- Published
- 2018
39. Type 1 autoimmune pancreatitis with histologically proven granulocytic epithelial lesions
- Author
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Seung-Mo Hong, Ho Gak Kim, Jimin Han, Jeong Eun Song, and Myung-Hwan Kim
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Disease ,Epithelium ,Autoimmune Diseases ,Lesion ,Young Adult ,medicine ,Humans ,Pancreas ,Autoimmune pancreatitis ,Pancreatic duct ,Pancreatic Disorder ,Hepatology ,business.industry ,Gastroenterology ,Histology ,medicine.disease ,medicine.anatomical_structure ,Pancreatitis ,medicine.symptom ,business ,Granulocytes - Abstract
There are two distinct subtypes of autoimmune pancreatitis (AIP): type 1 and type 2. Type 1 AIP is the pancreatic manifestation of systemic fibroinflammatory disease, which is named as IgG4-related disease. On the other hand, type 2 AIP is a pancreatic disorder that is not associated with IgG4. Type 1 and type 2 AIP have different clinical profiles and histologic findings. We present a 22-year-old man who has been diagnosed as type 1 AIP with histologically proven granulocytic epithelial lesion after surgical resection for pancreatic head mass. Since the patient had no pancreatic duct narrowing, elevation of serum IgG4, and other organ involvement, it was very difficult to diagnose preoperatively. This is a rare and interesting case in which histologic features of type 1 and type 2 AIP coexist.
- Published
- 2015
40. Epithelial-mesenchymal transition phenotype is associated with patient survival in small intestinal adenocarcinoma
- Author
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Hee Jin Lee, Seung-Mo Hong, Han-Ik Bae, Jung Yoen Kim, Kyu Yun Jang, Aeri Kim, Mi Jin Gu, and Young Kyung Bae
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Epithelial-Mesenchymal Transition ,Vimentin ,Kaplan-Meier Estimate ,Adenocarcinoma ,Disease-Free Survival ,Pathology and Forensic Medicine ,Young Adult ,Intestinal Neoplasms ,Intestine, Small ,Biomarkers, Tumor ,medicine ,Carcinoma ,Humans ,Epithelial–mesenchymal transition ,Aged ,Aged, 80 and over ,biology ,Wild type ,Histology ,Middle Aged ,Prognosis ,medicine.disease ,Immunohistochemistry ,Phenotype ,Fibronectin ,Tissue Array Analysis ,embryonic structures ,biology.protein ,Cancer research ,Female - Abstract
We investigated the clinical significance of epithelial-mesenchymal transition (EMT) phenotype in 184 small intestinal adenocarcinomas (SIACs) based on the expression pattern of EMT-related proteins in cancer cells.Immunohistochemistry for epithelial (E-cadherin) and mesenchymal (vimentin and fibronectin) markers were performed and cases of SIAC were classified into four subtypes of EMT: complete type (E-cadherin-, vimentin+ and/or fibronectin+), wild type (E-cadherin+, vimentin-, fibronectin-), incomplete 1 type (hybrid type; E-cadherin+, vimentin+ and/or fibronectin+), and incomplete 2 type (null type; E-cadherin-, vimentin-, fibronectin-).We identified 19 (10.3%) cases of complete EMT type, 86 (46.7%) cases of wild type and 79 (43%) cases of incomplete EMT type [hybrid type, 22 (12%) cases; null type, 57 (31%) cases]. Complete EMT phenotype showed a significant association with undifferentiated histology (p0.001). Overall survival of SIAC patients with complete EMT phenotype was significantly shorter than those of patients with incomplete (p=0.001) and wild (p0.001) types. In multivariate analysis, complete EMT phenotype was an independent prognostic factor in SIAC patients (hazard ratio 2.3; 95% confidence interval 1.15-4.6; p=0.019).Complete EMT phenotype stratifies a specific group representing a poor clinical outcome in patients with SIAC.
- Published
- 2013
41. Loss of expression of the SWI/SNF chromatin remodeling subunit BRG1/SMARCA4 is frequently observed in intraductal papillary mucinous neoplasms of the pancreas
- Author
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Francesca Scrimieri, Ming Tseh Lin, Rajni Sharma, Richard D. Schulick, Sachidanand Hebbar, Hanno Matthaei, Roeland F. de Wilde, Ralph H. Hruban, Christopher L. Wolfgang, Michael Goggins, Anirban Maitra, Seung-Mo Hong, Skye C. Mayo, James R. Eshleman, and Marco Dal Molin
- Subjects
Pathology ,medicine.medical_specialty ,endocrine system diseases ,Biology ,Article ,Chromatin remodeling ,Pathology and Forensic Medicine ,Cell Line, Tumor ,Pancreatic cancer ,medicine ,Humans ,Cyst ,Pancreas ,Retrospective Studies ,Cell Nucleus ,Intraductal papillary mucinous neoplasm ,DNA Helicases ,Nuclear Proteins ,Chromatin Assembly and Disassembly ,medicine.disease ,Adenocarcinoma, Mucinous ,Carcinoma, Papillary ,SWI/SNF ,Pancreatic Neoplasms ,medicine.anatomical_structure ,Tissue Array Analysis ,Disease Progression ,SMARCA4 ,Adenocarcinoma ,Neoplasm Grading ,Carcinoma, Pancreatic Ductal ,Transcription Factors - Abstract
A better molecular characterization of intraductal papillary mucinous neoplasm (IPMN), the most frequent cystic precursor lesion of pancreatic adenocarcinoma, may have a pivotal role in its early detection and in the development of effective therapeutic strategies. BRG1, a central component of the chromatin remodeling complex SWI/SNF regulating transcription, is inactive in several malignancies. In this study, we evaluate the Brg1 expression in intraductal papillary mucinous neoplasm to better understand its role in the pancreatic carcinogenesis. Tissue microarrays of 66 surgically resected IPMNs were immunolabeled for the Brg1 protein. Expression patterns were then correlated with clinicopathologic parameters. Normal pancreatic epithelium strongly immunolabeled for Brg1. Reduced Brg1 expression was observed in 32 (53.3%) of the 60 evaluable IPMN lesions and occurred more frequently in high-grade IPMNs (13 of 17 showed loss; 76%) compared to intermediate-grade (15 of 29 showed loss; 52%) and low-grade IPMNs (4 of 14 showed loss; 28%) (P = .03). A complete loss of Brg1 expression was observed in 5 (8.3%) of the 60 lesions. Finally, a decrease in Brg1 protein expression was furthermore found in a low-passage noninvasive IPMN cell line by Western blot analysis. We did not observe correlation between Brg1 expression and IPMN subtype or with location of the cyst. We provide first evidence that Brg1 expression is lost in noninvasive cystic precursor lesions of pancreatic adenocarcinoma.
- Published
- 2012
42. Prevalence of the Alternative Lengthening of Telomeres Telomere Maintenance Mechanism in Human Cancer Subtypes
- Author
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Elizabeth A. Montgomery, Anirban Maitra, William H. Westra, Jonathan I. Epstein, Michael Goggins, Alan K. Meeker, Michael Torbenson, Edward Gabrielson, Angelo M. De Marzo, Pedram Argani, Robert J. Kurman, Christine A. Iacobuzio-Donahue, Ie Ming Shih, Tamara L. Lotan, Luigi Terracciano, Janis M. Taube, Tzyy Choou Wu, Dinesh Rakheja, Seung-Mo Hong, Richard B.S. Roden, Qing Kay Li, Christopher M. Heaphy, Charles G. Eberhart, Andrea P. Subhawong, and George J. Netto
- Subjects
Male ,Telomerase ,Pathology ,medicine.medical_specialty ,medicine.diagnostic_test ,Short Communication ,Telomere Homeostasis ,Cancer ,Telomere ,Biology ,medicine.disease ,Endometrium ,Phenotype ,digestive system diseases ,Pathology and Forensic Medicine ,medicine.anatomical_structure ,Neoplasms ,medicine ,Cancer research ,Humans ,Female ,Cervix ,Fluorescence in situ hybridization - Abstract
Approximately 10% to 15% of human cancers lack detectable telomerase activity, and a subset of these maintain telomere lengths by the telomerase-independent telomere maintenance mechanism termed alternative lengthening of telomeres (ALT). The ALT phenotype, relatively common in subtypes of sarcomas and astrocytomas, has rarely been reported in epithelial malignancies. However, the prevalence of ALT has not been thoroughly assessed across all cancer types. We therefore comprehensively surveyed the ALT phenotype in a broad range of human cancers. In total, two independent sets comprising 6110 primary tumors from 94 different cancer subtypes, 541 benign neoplasms, and 264 normal tissue samples were assessed by combined telomere-specific fluorescence in situ hybridization and immunofluorescence labeling for PML protein. Overall, ALT was observed in 3.73% (228/6110) of all tumor specimens, but was not observed in benign neoplasms or normal tissues. This is the first report of ALT in carcinomas arising from the bladder, cervix, endometrium, esophagus, gallbladder, kidney, liver, and lung. Additionally, this is the first report of ALT in medulloblastomas, oligodendrogliomas, meningiomas, schwannomas, and pediatric glioblastoma multiformes. Previous studies have shown associations between ALT status and prognosis in some tumor types; thus, further studies are warranted to assess the potential prognostic significance and unique biology of ALT-positive tumors. These findings may have therapeutic consequences, because ALT-positive cancers are predicted to be resistant to anti-telomerase therapies.
- Published
- 2011
43. Adenocarcinoma of the small intestine: a multi-institutional study of 197 surgically resected cases
- Author
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Dae Woon Eom, Soon Won Hong, Gwang Il Kim, Sun-Young Jun, Jung Yeon Kim, Hee Kyung Chang, Seung-Mo Hong, Young Ha Oh, Gyeong Hoon Kang, Jae Bok Park, Mi Jin Gu, Kyu Yun Jang, Soo Jin Jung, Eun Sun Jung, Young Kyung Bae, Kee Taek Jang, Eunsil Yu, Ghil Suk Yoon, Joon Mee Kim, Kye Won Kwon, Jason Y. Park, Jihun Kim, Ji Shin Lee, and Han Ik Bae
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Adenoma ,Lymphovascular invasion ,Perineural invasion ,Ileum ,Kaplan-Meier Estimate ,Adenocarcinoma ,Pathology and Forensic Medicine ,Duodenal Neoplasms ,Intestine, Small ,medicine ,Humans ,Survival rate ,Aged ,Aged, 80 and over ,Jejunal Neoplasms ,business.industry ,Small Intestinal Adenocarcinoma ,Middle Aged ,Prognosis ,medicine.disease ,Ileal Neoplasms ,medicine.anatomical_structure ,Dysplasia ,Lymphatic Metastasis ,Female ,business - Abstract
Small intestinal adenocarcinoma is a rare malignant neoplasm, and its clinicopathologic characteristics have not been well elucidated. A total of 197 small intestinal adenocarcinoma cases were collected from 22 institutions in South Korea and were evaluated for clinicopathologic factors that affect the prognosis of small intestinal adenocarcinoma patients using univariate and multivariate analyses. The mean patient age was 59 years, and the male-to-female ratio was 1.7:1. Tumors were located in the duodenum of 108 cases (55%), the jejunum in 59 (30%), and the ileum in 30 (15%). Predisposing conditions were observed in 23 cases (12%), including 17 cases with sporadic adenomas, 3 with Peutz-Jeghers syndrome, 2 with Meckel diverticulum, and 1 with Crohn disease. Synchronous or metachronous malignant tumors were identified in 31 cases (16%), including 13 colorectal and 10 stomach cancers. About 90% of tumors were classified as either pT3 (63 cases) or pT4 (112 cases). The median survival time for all small intestinal adenocarcinoma patients was 39.7 months. Compared with small intestinal adenocarcinomas without accompanying sporadic adenomas, small intestinal adenocarcinomas with accompanying adenomas were more well differentiated (P < .0001), with a more polypoid growth pattern (P < .0001), a lower pT classification (P < .0001), less perineural invasion (P = .01), and less lymphatic invasion (P = .03). Small intestinal adenocarcinoma patients with associated sporadic adenomas (77%) had a significantly better 5-year survival rate than those without sporadic adenomas (38%, P = .02). By univariate analysis, small intestinal adenocarcinoma patients had significantly different survival based on pT classification (P = .003), lymph node metastasis (P < .0001), distal location (jejunal and ileal carcinomas) (P = .003), retroperitoneal tumor seeding (P < .0001), vascular invasion (P = .007), lymphatic invasion (P = .001), peritumoral dysplasia (P = .004), and radiation therapy (P = .006). By multivariate analysis, lymph node metastasis (P = .01) and distal location (P = .003) were independent predictors of a worse prognosis. In conclusion, (1) small intestinal adenocarcinomas are diagnosed at an advanced disease stage; therefore, the development of strategies for detection at an earlier stage is needed. (2) Small intestinal adenocarcinoma patients with an adenomatous component had a better survival than those without an adenomatous component. (3) Lymph node metastasis and distal location (jejunum and ileum) of tumor are the most important independent prognostic factors.
- Published
- 2010
44. Type 2 autoimmune pancreatitis (idiopathic duct-centric chronic pancreatitis) in an Asian country highlighting patients presenting as clinical acute pancreatitis
- Author
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Jin Hee Kim, Sung Koo Lee, Dong Wan Seo, Tae Jun Song, Dongwook Oh, Myung-Hwan Kim, Sang Soo Lee, Seung-Mo Hong, and Do Hyun Park
- Subjects
medicine.medical_specialty ,Hepatology ,business.industry ,Endocrinology, Diabetes and Metabolism ,Gastroenterology ,medicine.disease ,medicine.anatomical_structure ,Internal medicine ,Asian country ,Medicine ,Pancreatitis ,Acute pancreatitis ,business ,Duct (anatomy) ,Autoimmune pancreatitis - Published
- 2018
45. Tu1951 - Novel Blood-Based Detection of Colorectal Cancer and Adenoma Using a Nanobiosensor Targeting CCSP-2 (Colon Cancer Secreted Protein-2)
- Author
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Sang-Yeob Kim, Sungwook Park, Byong Duk Ye, Eun-Ju Do, Dong-Hoon Yang, Seung-Jae Myung, Minhong Jeun, Kwan Hyi Lee, Seung-Mo Hong, Jaewon Choe, Ja Young Kang, Sang Hyoung Park, Hye-Nam Son, Suk-Kyun Yang, Jinmyoung Joo, Dong-Hee Kim, You-Na Sung, Hyo Jeong Lee, Sung Wook Hwang, and Jeong-Sik Byeon
- Subjects
Hepatology ,Adenoma ,Colorectal cancer ,business.industry ,Gastroenterology ,medicine ,Cancer research ,medicine.disease ,business - Published
- 2018
46. In vivo and in vitro propagation of intraductal papillary mucinous neoplasms
- Author
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Angela Young, Margaret Griffith, Anirban Maitra, Mihoko Kamiyama, Seung-Mo Hong, Hong Liang, Georg Feldmann, Chanjuan Shi, Collins Karikari, Masamichi Mizuma, Ralph H. Hruban, Alexis Norris-Kirby, Michael Goggins, James R. Eshleman, Michael Borges, Conrad Lubek, Hirohiko Kamiyama, and Ming Tseh Lin
- Subjects
Male ,Pathology ,endocrine system diseases ,pancreatic cancer ,precursor lesions ,Mice, SCID ,Gene mutation ,medicine.disease_cause ,Mice ,0302 clinical medicine ,Mice, Inbred NOD ,CDKN2A ,Immunodeficient mice ,Aged, 80 and over ,Mice, Knockout ,Middle Aged ,Adenocarcinoma, Mucinous ,Immunohistochemistry ,3. Good health ,030220 oncology & carcinogenesis ,Cell lines ,Female ,030211 gastroenterology & hepatology ,Carcinoma, Pancreatic Ductal ,Adult ,medicine.medical_specialty ,Transplantation, Heterologous ,Mice, Nude ,Biology ,Article ,Pathology and Forensic Medicine ,03 medical and health sciences ,Cytokeratin ,In vivo ,Cell Line, Tumor ,Pancreatic cancer ,medicine ,Animals ,Humans ,Molecular Biology ,Cyclin-Dependent Kinase Inhibitor p16 ,Aged ,Intraductal papillary mucinous neoplasm (IPMN) ,Cell Biology ,medicine.disease ,DNA Fingerprinting ,Carcinoma, Papillary ,Pancreatic Neoplasms ,Cell culture ,Cancer research ,Carcinogenesis ,Neoplasm Transplantation - Abstract
Background Intraductal papillary mucinous neoplasms (IPMNs) are one of the 3 known curable precursor lesions of invasive pancreatic ductal adenocarcinoma, an almost uniformly fatal disease. Cell lines from IPMNs and their invasive counterparts should be valuable to identify gene mutations critical to IPMN carcinogenesis, and permit high-throughput screening to identify drugs that cause regression of these lesions. Methods To advance the study of the biological features of IPMNs, we attempted in vivo and in vitro growth of selected IPMNs based on the hypothesis that IPMNs could be grown in the most severely immunodeficient mice. We examined fourteen cases by implanting them into nude, severe combined immunodeficient (SCID), and NOD/SCID/IL2Rγnull (NOG) mice, in addition to direct culture, to generate tumor xenografts and cell lines. One sample was directly cultured only. Results Thirteen tumors were implanted into the 3 types of mice, including 10 tumors implanted into the triple immunodeficient NOG mice, where the majority (8 of 10) grew. This included 5 IPMNs lacking an invasive component. One of the explanted IPMNs, with an associated invasive carcinoma, was successfully established as a cell line. Tumorigenicity was confirmed by growth in soft agar, growth in immunodeficient mice, and the homozygous deletion of p16/cdkn2a. Epithelial differentiation of the cell line was documented by cytokeratin expression. Patient origin was confirmed using DNA fingerprinting. Conclusions Most non-invasive IPMNs grow in NOG mice. We successfully established one IPMN cell line, and plan to use it to clarify the molecular pathogenesis of IPMNs.
- Published
- 2010
47. Aberrant MicroRNA-155 Expression Is an Early Event in the Multistep Progression of Pancreatic Adenocarcinoma
- Author
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Ji Kon Ryu, Seung-Mo Hong, Ralph H. Hruban, Michael Goggins, Anirban Maitra, and Collins Karikari
- Subjects
Original Paper ,Pathology ,medicine.medical_specialty ,endocrine system diseases ,Hepatology ,business.industry ,Endocrinology, Diabetes and Metabolism ,Carcinoma in situ ,Gastroenterology ,Pancreatic Intraepithelial Neoplasia ,Adenocarcinoma ,medicine.disease ,Pancreatic Neoplasms ,miR-155 ,MicroRNAs ,microRNA ,Humans ,Medicine ,CA19-9 ,business ,Carcinoma in Situ - Abstract
Pancreatic intraepithelial neoplasia (PanIN) is the most common noninvasive precursor to invasive pancreatic adenocarcinoma. Misexpression of microRNAs (miRNAs) is commonly encountered in invasive neoplasia; however, miRNA abnormalities in PanIN lesions have not been documented.Three candidate miRNAs (miR-21, miR-155, and miR-221) previously reported as overexpressed in pancreatic cancers were assessed in 31 microdissected PanINs (14 PanIN-1, 9 PanIN-2, 8 PanIN-3) using quantitative reverse transcription PCR (qRT-PCR). Subsequently, miR-155 was evaluated by locked nucleic acid in situ hybridization (LNA-ISH) in PanIN tissue microarrays.Relative to microdissected non-neoplastic ductal epithelium, significant overexpression of miR-155 was observed in both PanIN-2 (2.6-fold, p = 0.02) and in PanIN-3 (7.4-fold, p = 0.014), while borderline significant overexpression of miR-21 (2.5-fold, p = 0.049) was observed in PanIN-3 only. In contrast, no significant differences in miR-221 levels were observed between ductal epithelium and PanIN lesions by qRT-PCR. LNA-ISH confirmed the aberrant expression of miR-155 in PanIN-2 (9 of 20, 45%) and in PanIN-3 (8 of 13, 62%), respectively, when compared with normal ductal epithelium (0 of 10) (p0.01).Abnormalities of miRNA expression are observed in the multistep progression of pancreatic cancer, with miR-155 aberrations demonstrable at the stage of PanIN-2, and miR-21 abnormalities at the stage of PanIN-3 lesions. and IAP.
- Published
- 2010
48. Widespread activation of the DNA damage response in human pancreatic intraepithelial neoplasia
- Author
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Chanjuan Shi, Alan K. Meeker, Michael Goggins, Jan Bart M. Koorstra, Anirban Maitra, Ralph H. Hruban, Seung-Mo Hong, Ji Kon Ryu, G. J. A. Offerhaus, and University of Groningen
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Pathology ,endocrine system diseases ,pancreatic cancer ,Pancreatic Intraepithelial Neoplasia ,Cell Cycle Proteins ,PROGRESSION ,Ataxia Telangiectasia Mutated Proteins ,Epithelium ,Histones ,0302 clinical medicine ,pancreatic intraepithelial neoplasia ,ONCOGENE-INDUCED SENESCENCE ,PHOSPHORYLATION ,Checkpoint Kinase 2 ,Oligonucleotide Array Sequence Analysis ,0303 health sciences ,Tissue microarray ,CELLULAR SENESCENCE ,Immunohistochemistry ,CANCER ,3. Good health ,DNA-Binding Proteins ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Disease Progression ,Adenocarcinoma ,medicine.symptom ,EXPRESSION ,medicine.medical_specialty ,DNA damage ,Chk2 ,DUCTAL ADENOCARCINOMA ,Protein Serine-Threonine Kinases ,Biology ,Article ,Pathology and Forensic Medicine ,Lesion ,03 medical and health sciences ,Pancreatic cancer ,Biomarkers, Tumor ,medicine ,Humans ,TISSUE MICROARRAY ,030304 developmental biology ,Analysis of Variance ,LESIONS ,Tumor Suppressor Proteins ,medicine.disease ,Pancreatic Neoplasms ,ATM ,CELLS - Abstract
Pancreatic intraepithelial neoplasia (PanIN) lesions are the most common non-invasive precursors of pancreatic adenocarcinoma. We postulated that accumulating DNA damage within the PanIN epithelium activates checkpoint mechanisms. Tissue microarrays were constructed from 81 surgically resected primary pancreatic adenocarcinomas and an independent set of 58 PanIN lesions (31 PanIN-1, 14 PanIN-2, and 13 PanIN-3). Immunohistochemical labeling was carried out using anti-gammaH2AX(Ser139), anti-phosphoATM(Ser1981), anti-phosphoChk2(Thr68), and anti-p53. A 'histologic score' combining area and intensity of labeling in the nuclear compartment was determined for each lesion. A progressive increase in gammaH2AX(Ser139) labeling, consistent with escalating DNA damage, was observed in the non-invasive precursor lesions (scores of 4.34, 6.21, and 7.50, respectively, for PanIN-1, -2, and -3), compared with the pancreatic ductal epithelium (score 2.36) (ANOVA, P0.0001). In conjunction, activation of the ataxia telangiectasia mutated (ATM)-Chk2 checkpoint pathway was observed in all histological grades of PanIN lesions. Specifically, pATM(Ser1981) histologic scores for PanIN-1, PanIN-2, and PanIN-3 were 4.83, 5.14, and 7.17, respectively, versus 2.33 for the ductal epithelium (ANOVA, P0.0001); the corresponding scores for pChk2(Thr68) were 5.43, 7.64, and 5.44 in PanINs-1, -2, and -3, respectively, versus 2.75 in the ductal epithelium (ANOVA, P0.0001). In contrast, absent to minimal nuclear p53 was observed in the ductal epithelium, and in PanINs-1 and -2 (a histologic score of 0-1.86), with a significant upregulation (corresponding to mutational inactivation) seen only at the stage of PanIN-3 and invasive neoplasia (histologic scores of 4.00 and 4.22). Nuclear p53 accumulation in cancers was associated with attenuation of the ATM-Chk2 checkpoint and a restitution to 'baseline' levels. To conclude, activation of the ATM-Chk2 checkpoint pathway is commonly observed in PanINs, likely in response to the accumulating DNA damage from events such as oncogene mutations and telomere dysfunction. Loss of p53 function appears to be a critical determinant for bypassing this checkpoint and the subsequent progression to invasive adenocarcinoma.
- Published
- 2009
49. Depth of tumor invasion better predicts prognosis than the current American Joint Committee on Cancer T classification for distal bile duct carcinoma
- Author
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Ralph H. Hruban, Bhuvnesh Aggarwal, Seung-Mo Hong, HyungJun Cho, Timothy M. Pawlik, Robert A. Anders, and Michael Goggins
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Adult ,Male ,medicine.medical_specialty ,Bile Duct Neoplasm ,Bile Duct Carcinoma ,Article ,Metastasis ,Cholangiocarcinoma ,medicine ,Carcinoma ,Humans ,Neoplasm Invasiveness ,Survival analysis ,Aged ,Aged, 80 and over ,Bile duct ,business.industry ,Middle Aged ,Prognosis ,medicine.disease ,Survival Analysis ,Distal Bile Duct Carcinoma ,Surgery ,Bile Ducts, Intrahepatic ,medicine.anatomical_structure ,Bile Duct Neoplasms ,Biliary tract ,Female ,Radiology ,business - Abstract
The American Joint Committee on Cancer (AJCC) T classification system for cholangiocarcinoma does not take into account the unique pathologic features of the bile duct. As such, the current AJCC T classification for distal cholangiocarcinoma may be inaccurate.A total of 147 patients with distal cholangiocarcinoma were identified from a single institution database. The prognostic importance of depth of tumor invasion relative to the AJCC T classification system was assessed.The AJCC T classification was T1 (n = 11, 7.5%), T2 (n = 6, 4.1%), T3 (n = 73, 49.7%), or T4 (n = 57, 38.8%). When cases were analyzed according to depth of tumor invasion, most lesions wereor =5 mm (5 mm, 9.5%; range, 5-12, 51.0%;12 mm, 39.5%). The AJCC T classification was not associated with survival outcome (median survival, T1, 40.1 months; T2, 14.8 months; T3, 16.5 months; T4, 20.2 months; P = .17). In contrast, depth of tumor invasion was associated with a worse outcome as tumor depth increased (median survival,5 mm, not reached; range, 5-12, 28.9 months;12 mm, 12.9 months; P = .001). On multivariate analyses, tumor depth remained the factor most associated with outcome (5 mm; hazard ratio [HR] = referent vs 5-12 mm; HR = 3.8 vs12 mm; HR = 6.7 mm; P = .001).The AJCC T classification for distal cholangiocarcinoma does not accurately predict prognosis. Depth of the bile duct carcinoma invasion is a better alternative method to determine prognosis and should be incorporated into the pathologic assessment of resected distal cholangiocarcinoma.
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- 2009
50. Biliary intraepithelial neoplasia: an international interobserver agreement study and proposal for diagnostic criteria
- Author
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Wilson M. S. Tsui, Linda D. Ferrell, Yoh Zen, Prodromos Hytiroglou, Yasuni Nakanuma, Fausto Sessa, Romano Colombari, Hironori Haga, N. Volkan Adsay, Motoko Sasaki, Yutaka Atomi, Gregory Y. Lauwers, Arief A. Suriawinata, Seung-Mo Hong, Kenji Notohara, Kiyoko Oshima, Dirk J. van Leeuwen, Krystof Bardadin, Alberto Quaglia, and Günter Klöppel
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Pathology ,medicine.medical_specialty ,International Cooperation ,Cholangitis, Sclerosing ,Lithiasis ,Pathology and Forensic Medicine ,Primary sclerosing cholangitis ,chemistry.chemical_compound ,Bile Ducts, Extrahepatic ,Terminology as Topic ,Atypia ,Humans ,Medicine ,Choledochal cysts ,Bilin ,Intrahepatic Cholangiocarcinoma ,business.industry ,Bile duct ,Liver Diseases ,medicine.disease ,Bile Ducts, Intrahepatic ,Biliary Tract Neoplasms ,medicine.anatomical_structure ,chemistry ,Choledochal Cyst ,Biliary Intraepithelial Neoplasia ,Hepatolithiasis ,business ,Carcinoma in Situ - Abstract
Cholangiocarcinoma of the intrahepatic and extrahepatic bile ducts develops through a multistep histopathologic sequence. Premalignant or non-invasive neoplastic lesions of bile ducts have been historically called biliary dysplasia or atypical biliary epithelium. To this date, no standard terminology or classification system has been offered for these lesions. In 2005, a conceptual framework and diagnostic criteria for biliary intraepithelial neoplasia (BilIN) were proposed using the livers of patients with hepatolithiasis. We report herein an international interobserver agreement study on the diagnosis of biliary non-invasive neoplastic lesions with the goal to obtain a consensus on the terminology and grading. Seventeen pathologists from the United States, Europe and Asia participated in this study. They shared a digital file containing histological pictures of 30 foci of non-invasive neoplastic lesions selected from the biliary system of patients suffering from primary sclerosing cholangitis, choledochal cyst or hepatolithiasis. In the criteria, we proposed in 2005, BilIN was classified into three categories based on the degree of atypia: BilIN-1, BilIN-2 and BilIN-3. In this study, consensus was reached for the terminology of BilIN and the three-grade classification system. Interobserver agreement on the diagnosis was moderate (kappa-value=0.45). On the basis of the suggestions and opinions obtained from the 17 participants, the original criteria for BilIN were revised. We now propose a new consensus classification of BilIN that may assist in allowing a more uniform terminology for the diagnosis of biliary non-invasive neoplastic lesions. This classification should help to advance clinical and research applications.
- Published
- 2007
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