Showing papers by "Seung-Mo Hong published in 2016"

Recent Updates on Neuroendocrine Tumors From the Gastrointestinal and Pancreatobiliary Tracts

Abstract: Context.—Gastrointestinal (GI) and pancreatobiliary tracts contain a variety of neuroendocrine cells that constitute a diffuse endocrine system. Neuroendocrine tumors (NETs) from these organs are heterogeneous tumors with diverse clinical behaviors. Recent improvements in the understanding of NETs from the GI and pancreatobiliary tracts have led to more-refined definitions of the clinicopathologic characteristics of these tumors. Under the 2010 World Health Organization classification scheme, NETs are classified as grade (G) 1 NETs, G2 NETs, neuroendocrine carcinomas, and mixed adenoneuroendocrine carcinomas. Histologic grades are dependent on mitotic counts and the Ki-67 labeling index. Several new issues arose after implementation of the 2010 World Health Organization classification scheme, such as issues with well-differentiated NETs with G3 Ki-67 labeling index and the evaluation of mitotic counts and Ki-67 labeling. Hereditary syndromes, including multiple endocrine neoplasia type 1 syndrome, von Hip...

Validation of the 2012 International Consensus Guidelines Using Computed Tomography and Magnetic Resonance Imaging: Branch Duct and Main Duct Intraductal Papillary Mucinous Neoplasms of the Pancreas.

Abstract: Objective:To validate the 2012 guidelines for intraductal papillary mucinous neoplasm (IPMN) of the pancreas and to compare diagnostic performances of computed tomography (CT) and magnetic resonance imaging (MRI) for differentiating malignant from benign IPMN.Background:As IPMN has variable risks of

Alpha-synuclein in gastric and colonic mucosa in Parkinson's disease: Limited role as a biomarker.

Abstract: Background Gastric and colonic alpha-synuclein immunoreactivity has been reported in patients with Parkinson's disease (PD). However, enteric alpha-synuclein also has been reported in healthy individuals. Objectives We aimed to investigate the utility of alpha-synuclein immunoreactivity from gastric and colonic mucosal tissues obtained by routine endoscopy to detect PD, and to correlate the pathological burden of alpha-synuclein with motor and nonmotor features of PD. Methods We recruited 104 study subjects, consisting of 38 patients with PD, 13 patients with probable multiple system atrophy (MSA), and 53 healthy controls. Gastric and colonic mucosal tissues obtained by endoscopic gastroduodenoscopy and colonoscopy were assessed using alpha-synuclein immunohistochemistry. Detailed motor and nonmotor features of PD were correlated with enteric alpha-synuclein immunoreactivity. Results No difference was seen in the enteric α-SYN immunoreactivity among patients with PD (31.6% for stomach and 10.4% for colon), patients with MSA (40.0% for stomach and 8.0% for colon), and healthy controls (33.3% for stomach and 18.5% for colon). The frequency of positive alpha-synuclein immunoreactivity was higher in gastric biopsy tissues than in colonic biopsy tissues in all of the study groups (P < 0.05). No significant correlation was found between the presence of alpha-synuclein immunoreactivity and the motor and nonmotor features of PD. Conclusions The presence of alpha-synuclein immunoreactivity in gastric and colonic mucosa was detected in a similar manner in patients with PD, patients with MSA, and controls, thus suggesting a limited role of enteric mucosal alpha-synuclein as a diagnostic biomarker for PD. Future studies are warranted to detect pathological alpha-synuclein strains. © 2015 International Parkinson and Movement Disorder Society

Generation and molecular characterization of pancreatic cancer patient-derived xenografts reveals their heterologous nature.

Abstract: // Jaeyun Jung 1, * , Cue Hyunkyu Lee 3, * , Hyang Sook Seol 4 , Yeon Sook Choi 4 , Eunji Kim 3, 5 , Eun Ji Lee 1 , Je-Keun Rhee 6 , Shree Ram Singh 7 , Eun Sung Jun 1 , Buhm Han 3 , Seung Mo Hong 8 , Song Cheol Kim 9 , Suhwan Chang 1, 2 1 Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, Korea 2 Department of Physiology, University of Ulsan College of Medicine, Seoul, Korea 3 Department of Convergence Medicine, University of Ulsan College of Medicine, Seoul, Korea 4 Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea 5 Department of Chemistry, Seoul National University, Seoul, Korea 6 Department of Medical Informatics, College of Medicine, The Catholic University of Korea, Seoul, Korea 7 Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA 8 Department of Pathology, Asan Medical Center, Seoul, Korea 9 Department of Surgery, Asan Medical Center, Seoul, Korea * These authors have contributed equally to this work Correspondence to: Song Cheol Kim, email: drksc@amc.seoul.kr Suhwan Chang, email: suhwan.chang@amc.seoul.kr Keywords: pancreatic cancer, patient-derived xenograft, single nucleotide polymorphism, cancer panel, heterogeneity Received: June 01, 2016 Accepted: August 08, 2016 Published: August 23, 2016 ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) is the most challenging type of cancer to treat, with a 5-year survival rate of <10%. Furthermore, because of the large portion of the inoperable cases, it is difficult to obtain specimens to study the biology of the tumors. Therefore, a patient-derived xenograft (PDX) model is an attractive option for preserving and expanding these tumors for translational research. Here we report the generation and characterization of 20 PDX models of PDAC. The success rate of the initial graft was 74% and most tumors were re-transplantable. Histological analysis of the PDXs and primary tumors revealed a conserved expression pattern of p53 and SMAD4; an exome single nucleotide polymorphism (SNP) array and Comprehensive Cancer Panel showed that PDXs retained over 94% of cancer-associated variants. In addition, Polyphen2 and the Sorting Intolerant from Tolerant (SIFT) prediction identified 623 variants among the functional SNPs, highlighting the heterologous nature of pancreatic PDXs; an analysis of 409 tumor suppressor genes and oncogenes in Comprehensive Cancer Panel revealed heterologous cancer gene mutation profiles for each PDX-primary tumor pair. Altogether, we expect these PDX models are a promising platform for screening novel therapeutic agents and diagnostic markers for the detection and eradication of PDAC.

Prognostic value of CT findings to predict survival outcomes in patients with pancreatic neuroendocrine neoplasms: a single institutional study of 161 patients

Abstract: To evaluate the prognostic value of CT to predict recurrence-free and overall survival in patients with pancreatic neuroendocrine neoplasms (PanNENs). Between January 2004 and December 2012, 161 consecutive patients who underwent preoperative triphasic CT and surgical resection with curative intent for PanNENs were identified. The tumour consistency, margin, presence of calcification, pancreatic duct dilatation, bile duct dilatation, vascular invasion, and hepatic metastases were evaluated. The tumour size, arterial enhancement ratio, and portal enhancement ratio were measured. The Cox proportional hazard model was used to determine the association between CT features and recurrence-free survival and overall survival. By multivariate analysis, tumour size (>3 cm) (hazard ratio, 3.314; p = 0.006), portal enhancement ratio (≤1.1) (hazard ratio, 2.718; p = 0.006), and hepatic metastases (hazard ratio, 4.374; p = 0.003) were independent significant variables for worse recurrence-free survival. Portal enhancement ratio (≤1.1) (hazard ratio, 5.951; p = 0.001) and hepatic metastases (hazard ratio, 4.122; p = 0.021) were independent significant variables for worse overall survival. Portal enhancement ratio (≤1.1) and hepatic metastases assessed on CT were common independent prognostic factors for worse recurrence-free survival and overall survival in patients with PanNENs. • CT is useful to predict survival outcomes in patients with PanNENs. • Survival outcomes are associated with portal enhancement ratio and hepatic metastases. • Portal enhancement ratio is prognostic CT biomarker in patients with PanNENs.

Malignant pancreatic serous cystic neoplasms: systematic review with a new case

Abstract: This study analyzes the clinicopathologic and radiologic characteristics of malignant serous cystic neoplasm (SCN) of the pancreas through systematic review and an institutional case report. A comprehensive literature search was performed in the MEDLINE database to identify studies on malignant SCNs of the pancreas that had detailed clinicopathologic and radiologic information. A computerized systematic search of our institutional database was also performed to identify cases of malignant SCN for addition to the systematic review. Using the final included cases, we analyzed the clinicopathologic and radiologic features of malignant SCNs of the pancreas. A review of 136 candidate articles identified 26 studies with 26 cases that had detailed clinical information. Our institutional data search added one case. The systematic review of the 27 cases revealed that primary tumors (mean diameter 10.2 ± 4.0 cm) mainly involved the body and tail of the pancreas (n = 16) and frequently invaded adjacent organs (n = 19). Distant metastases occurred in 14 patients (synchronous, n = 5; metachronous, n = 8; both, n = 1), most commonly in the liver (n = 13). Imaging features of malignant SCNs of the pancreas were identical to the benign counterpart, except local invasion or distant metastases. The prognosis was excellent in that 17 were alive at the time of writing with a median follow-up period of 2 years. The malignant potential of SCNs of the pancreas should be considered in the diagnosis and management of patients with pancreatic SCNs.

Hypervascular solid-appearing serous cystic neoplasms of the pancreas: Differential diagnosis with neuroendocrine tumours

Abstract: To describe imaging findings of arterial hypervascular solid-appearing serous cystic neoplasms (SCNs) of the pancreas on CT and MR and determine imaging features differentiating them from neuroendocrine tumours (NETs) We retrospectively identified 15 arterial hypervascular solid-appearing SCNs and randomly chose 30 size-matched pancreatic NETs On CT, two radiologists in consensus assessed the size, morphology, and CT attenuation On MR, predominant signal intensity and the amount of the cystic component on T2-weighted images and ADC maps were evaluated and compared using Fisher’s exact and Student’s t-test The mean SCN size was 26 cm (range, 08–83) The CT findings were similar between the two tumours: location, shape, margin, and enhancement pattern SCNs were significantly more hypodense on non-enhanced CT images than NETs (P = 03) They differed significantly on MR: bright signal intensity (P = 01) and more than a 10 % cystic component on T2-weighted images (P = 01) were more common in SCNs than in NETs All SCNs showed a non-restrictive pattern on the ADC map, while NETs showed diffusion restriction (P < 01) Arterial hypervascular solid-appearing SCNs and NETs share similar imaging features Non-enhanced CT and MR images with T2-weighted images and ADC maps can facilitate the differentiation • Frequency of hypervascular solid-appearing SCNs was 73 % among surgically confirmed SCNs • Hypervascular solid-appearing SCN of the pancreas can mimic pancreatic NETs • Unenhanced CT and MR features help to differentiate the two tumours

Prognostic Value of Somatostatin Receptor Subtypes in Pancreatic Neuroendocrine Tumors.

Abstract: ObjectivesStudies on the expression of somatostatin receptor (SSTR) subtypes in pancreatic neuroendocrine tumors (PNETs) are rare. The aim of this study was to determine the expression of the SSTR subtypes via immunohistochemistry analyses and assess the correlation between SSTR subtype expression a

Surgical and Oncological Factors Affecting the Successful Engraftment of Patient-derived Xenografts in Pancreatic Ductal Adenocarcinoma

Abstract: Background: To effectively use pancreatic cancer patient-derived xenograft (PDX) models in translational research, successful PDX engraftment of surgical specimens in immune-deficient mice is needed. Materials and Methods: A total of 102 patients underwent pancreatic cancer resection using various procedures. Tumor tissue from all patents was implanted subcutaneously into mice. Tumor engraftment and growth in mice were determined. Engraftment was tested for correlation with operation type, time, tumor size, and oncogene expression using immunohistoculture. Results: Multivariate analysis showed that a tumor size of more than 3.5 cm in the patient was a significant factor related to successful PDX engraftment. In contrast, there was no correlation of engraftment with surgical procedure, time needed to remove the specimen, tumor differentiation, lymph node metastasis, and protein expression of p53, Receptor tyrosine-protein kinase erbB-2 (CERBB2), or deleted in pancreatic carcinoma locus 4 (DPC4). Conclusion: A minimum tumor size in the patient is an important factor for successful tumor engraftment.

Thread sign in biliary intraductal papillary mucinous neoplasm: a novel specific finding for MRI.

Abstract: To evaluate thread sign of biliary intraductal papillary mucinous neoplasm (B-IPMN) on magnetic resonance imaging (MRI). Thread sign was defined as intraductal linear or curvilinear hypointense striations. Two radiologists independently evaluated the presence and location of thread sign on MR cholangiography (thin-slice, thick-slab and 3D MRC) and axial MR images (T2 TSE, T2 HASTE and DWI) in patients with B-IPMN (n = 38) and in matched control groups with benign (n = 36) or malignant (n = 35) biliary diseases. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of thread sign for diagnosing B-IPMN were evaluated. Thread sign was observed only in patients with B-IPMN on MRC (44.7–52.6 % [17/38–20/38], P < 0.001) and axial MR images (31.6 % [12/38], P < 0.001), except in one patient with recurrent pyogenic cholangitis on MRC (2.8 %, 1/36). The sensitivity, specificity, accuracy, PPV and NPV of thread sign for diagnosing B-IPMN on MRC were 0.53, 0.99, 0.83, 0.95 and 0.80, respectively (reader 1) and 0.45, 1.0, 0.81, 1.0 and 0.77, respectively (reader 2). Thread sign was detected mainly at the extrahepatic bile duct (52.6 %, 20/38). B-IPMN can manifest thread sign, a novel specific MR finding, mainly at the extrahepatic bile duct on MRI, especially on MRC. • Some B-IPMNs manifest thread sign within the bile ducts on MRI. • Thread sign is a highly specific finding for B-IPMN on MRI. • MRC is superior to axial T2WI and DWI for detecting thread sign.

Overexpression of ankyrin1 promotes pancreatic cancer cell growth

Abstract: The methylation status of a promoter influences gene expression and aberrant methylation during tumor development has important functional consequences for pancreatic and other cancers. Using methylated CpG island amplification and promoter microarrays, we identified ANK1 as hypomethylated in pancreatic cancers. Expression analysis determined ANK1 as commonly overexpressed in pancreatic cancers relative to normal pancreas. ANK1 was co-expressed with miR-486 in pancreatic cancer cells. Stable knockdown of ANK1 in the pancreatic cancer cell line AsPC1 led to changes in cell morphology, and decreases in colony formation. Stable knockdown of ANK1 also marked reduced the growth of tumors in athymic nude mice. Among patients undergoing pancreaticoduodenectomy, those with pancreatic cancers expressing ANK1 had a poorer prognosis than those without ANK1 expression. These findings indicate a role for ANK1 overexpression in mediating pancreatic cancer tumorigenicity.

Clinicopathological Features and Prognosis of Hepatic Epithelioid Hemangioendothelioma After Liver Resection and Transplantation.

Abstract: BACKGROUND Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor. We present a single-center study on hepatic EHE cases treated by hepatic resection (HR) or liver transplantation (LT). MATERIAL AND METHODS Six HR patients with hepatic EHE were identified during 5 years from 2010 to 2014; EHE represented 0.13% (6 of 4572) of all primary liver tumors. Two LT recipients were also identified during 12 years from 2003 to 2014, who represented 0.06% (2 of 3576) of all adult LT patients. RESULTS Mean age of the patients was 42.3±11.2 years and 7 were female. Preoperative diagnoses based on imaging studies were suspected liver metastasis or EHE; thus, all patients underwent liver biopsy. The extent of HR, which was determined by the location and size of tumors, consisted of right hepatectomy in two patients, right anterior sectionectomy in one, right posterior sectionectomy in one, central bisectionectomy plus partial hepatectomy in one, and right trisectionectomy plus partial hepatectomy in one. All patients recovered uneventfully from surgery. The disease-free survival rate was 83.3% at 1 year and 44.4% at 3 years in HR patients, but all patients are alive to date. Two patients underwent living-donor LT because they had multiple tumors scattered throughout the liver. Of these, one patient died from tumor recurrence at 9 months and the other is alive after 5 years without recurrence. CONCLUSIONS Hepatic EHE is often misdiagnosed as a metastatic tumor. This disease has malignant potential; thus, it requires aggressive treatment including HR, non-surgical treatment, and LT.

Prognostic factors in 151 patients with surgically resected non-functioning pancreatic neuroendocrine tumours.

Abstract: Background Recently, non-functioning pancreatic neuroendocrine tumors (NF-PNETs) are increasing. It is important to know about the prognostic factors and long-term survival rates in patients with NF-PNET for the management of these diseases. Methods We retrospectively analysed the records of 151 patients with NF-PNET who had pancreatic resection between January 1995 and December 2010. Result The 10-year overall survival, disease-specific survival and disease-free survival rate of the patients who underwent surgery for NF-PNET were 72.6%, 85.1% and 57.2% respectively. The three staging systems (2004 World Health Organization classification, 2006 European Neuroendocrine Tumor Society stages and 2010 grading system) showed comparable prognostic relevance in disease-specific survival of patients with resected NF-PNETs. Lymph nodes metastasis, high Ki-67 index and mitotic rate were the independent poor prognostic factors for disease-specific survival in the patients with surgically resected NF-PNET on multivariate analysis. Conclusion We suggested that the three staging systems accurately reflect the prognosis in disease-specific survival of patients with resected NF-PNETs. Presence of lymph nodes metastases and high Ki-67 index and mitotic rate were the independent poor prognostic factors after resection of NF-PNET.

Prevalence and clinical significance of cellular and acellular mucin in patients with locally advanced mucinous rectal cancer who underwent preoperative chemoradiotherapy followed by radical surgery

Abstract: Aim The frequent presence of acellular mucin in specimens showing pathological complete response to preoperative chemoradiotherapy (CRT) and the poor response to preoperative CRT in mucinous rectal cancer have been reported. However, the prevalence and prognostic significance of cellular and acellular mucin have not been evaluated in resected specimens from patients with mucinous rectal cancer who undergo preoperative CRT. Method We retrospectively evaluated the clinicopathological features and prognostic significance of mucin in resected specimens from 59 consecutive patients with mucinous rectal cancer who underwent long-course CRT followed by resection between January 2000 and December 2009. Patients were categorized according to the presence of mucin, as identified by pathological analysis. The clinicopathological findings and oncological results were compared. Results Mucin was identified in 25 of 59 patients with mucinous rectal cancer (42.4%). Mucin was more frequent in men (hazard ratio = 23.94, 95% confidence interval = 1.875–305.504, P = 0.015) and in specimens showing a good tumour response grade (hazard ratio = 64.26, 95% confidence interval = 6.940–595.045, P < 0.001). With a median follow-up of 67.7 (range 8.6–133.2) months, the 5-year overall survival (60.7% without mucin vs 51.4% with mucin, P = 0.898) and disease-free survival (59.9% without mucin vs 56.9% with mucin, P = 0.813) did not differ between the groups. Conclusion The presence of mucin in rectal cancer with mucinous differentiation after preoperative CRT and resection is associated with male gender and a good tumour response grade, without significant impact on oncological outcome.

Chronic intractable diarrhea caused by gastrointestinal mastocytosis.

Abstract: As mast cells have been highlighted in the pathogenesis of diarrhea-predominant irritable bowel syndrome, a new term "mastocytic enterocolitis" was suggested by Jakate and colleagues to describe an increase in mucosal mast cells in patients with chronic intractable diarrhea and favorable response to treatment with antihistamines. Although it is not an established disease entity, two cases have been reported in the English medical literature. Here, for the first time in Asia, we report another case of chronic intractable diarrhea caused by gastrointestinal mastocytosis. The patient was a 70-year-old male with chronic intractable diarrhea for 3 months; the cause of the diarrhea remained obscure even after exhaustive evaluation. However, biopsy specimens from the jejunum were found to have increased mast cell infiltration, and the patient was successfully treated with antihistamines.

Correlation of Microsatellite Instability With Clinicopathologic Features and Survival

Abstract: Objectives: To evaluate the association of microsatellite instability (MSI) with clinicopathologic features and oncologic outcomes in patients with poorly differentiated colorectal cancer (PD). Methods: Study patients were divided into well-differentiated colorectal cancer (WD) and PD, which were compared according to histologic differentiation and MSI status. Results: Among 1,941 patients, PD was more frequent among microsatellite-unstable tumors (23.6%) than among microsatellite-stable (MSS) tumors (4.2%, P < .001). Patients with PD had worse 4-year overall survival rates than patients with WD (78.6% vs 88.2%, P = 0.010). Compared with MSS-PD tumors, MSI-PD tumors were characterized by right-colon predilection, larger size, and infrequent lymph node metastasis (P < .001 to P = .007). Conclusions: The clinicopathologic characteristics of PD were closely associated with those of MSI. The outcomes of MSI-PD tumors were better than those of MSS-PD tumors, but this finding did not reach statistical significance. The phenomenon of microsatellite instability (MSI), observed in approximately 15% of sporadic colorectal cancers