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Case Study
Multiple Neuroendocrine Tumors in Stomach and Duodenum in a Multiple Endocrine Neoplasia Type 1 Patient
Bohyun Kim, Han-Kwang Yang, Woo Ho Kim
J Pathol Transl Med. 2018;52(2):126-129.   Published online December 21, 2017
DOI: https://doi.org/10.4132/jptm.2017.09.16
  • 6,333 View
  • 139 Download
  • 1 Web of Science
  • 1 Crossref
AbstractAbstract PDF
A 67-year-old woman with a history of subtotal parathyroidectomy, distal pancreatectomy, and total splenectomy 23 years prior underwent surgical gastric resection for neuroendocrine tumors of the stomach and duodenum. Meticulous examination of the entire stomach and duodenum revealed multiple scattered, minute neuroendocrine tumors. To the best of our knowledge, this is the first case report of a patient diagnosed with gastroduodenal neuroendocrine tumors associated with multiple endocrine neoplasia type 1 (MEN 1) in whom complete histologic mapping of the whole gastrectomy specimen was performed. The presence of MEN 1–associated neuroendocrine tumors in the stomach is very rare, but should be considered in patients diagnosed with MEN 1 who present with a new tumor in the stomach.

Citations

Citations to this article as recorded by  
  • A Case of Asymptomatic Multiple Endocrine Neoplasia Type I with Thymic Carcinoid
    Suk Ki Park, Moon Won Lee, In Sub Han, Young Joo Park, Sung Yong Han, Joon Woo Park, Bong Eun Lee, Gwang Ha Kim, Sang Soo Kim
    The Korean Journal of Helicobacter and Upper Gastrointestinal Research.2019; 19(1): 65.     CrossRef
Original Article
Loss of Progesterone Receptor Expression Is an Early Tumorigenesis Event Associated with Tumor Progression and Shorter Survival in Pancreatic Neuroendocrine Tumor Patients
Sung Joo Kim, Soyeon An, Jae Hoon Lee, Joo Young Kim, Ki-Byung Song, Dae Wook Hwang, Song Cheol Kim, Eunsil Yu, Seung-Mo Hong
J Pathol Transl Med. 2017;51(4):388-395.   Published online June 8, 2017
DOI: https://doi.org/10.4132/jptm.2017.03.19
  • 6,421 View
  • 131 Download
  • 14 Web of Science
  • 13 Crossref
AbstractAbstract PDF
Background
Pancreatic neuroendocrine tumors (PanNETs) are the second most common pancreatic neoplasms and there is no well-elucidated biomarker to stratify their detection and prognosis. Previous studies have reported that progesterone receptor (PR) expression status was associated with poorer survival in PanNET patients.
Methods
To validate previous studies, PR protein expression was assessed in 21 neuroendocrine microadenomas and 277 PanNETs and compared with clinicopathologic factors including patient survival.
Results
PR expression was gradually decreased from normal islets (49/49 cases, 100%) to neuroendocrine microadenoma (14/21, 66.6%) to PanNETs (60/277, 21.3%; p < .001). PanNETs with loss of PR expression were associated with increased tumor size (p < .001), World Health Organization grade (p = .001), pT classification (p < .001), perineural invasion (p = .028), lymph node metastasis (p = .004), activation of alternative lengthening of telomeres (p = .005), other peptide hormonal expression (p < .001) and ATRX/DAXX expression (p = .015). PanNET patients with loss of PR expression (5-year survival rate, 64.1%) had significantly poorer recurrence-free survival outcomes than those with intact PR expression (90%) by univariate (p = .012) but not multivariate analyses. Similarly, PanNET patients with PR expression loss (5-year survival rate, 76%) had significantly poorer overall survival by univariate (p = .015) but not multivariate analyses.
Conclusions
Loss of PR expression was noted in neuroendocrine microadenomas and was observed in the majority of PanNETs. This was associated with increased grade, tumor size, and advanced pT and pN classification; and was correlated with decreased patient survival time by univariate but not multivariate analyses. Loss of PR expression can provide additional information on shorter disease-free survival in PanNET patients.

Citations

Citations to this article as recorded by  
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    Archives of Pathology & Laboratory Medicine.2023; 147(1): 100.     CrossRef
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    Lingaku Lee, Tetsuhide Ito, Robert T Jensen
    Expert Review of Anticancer Therapy.2019; 19(12): 1029.     CrossRef
  • Immunohistochemistry, carcinomas of unknown primary, and incidence rates
    Edward B. Stelow, Hadi Yaziji
    Seminars in Diagnostic Pathology.2018; 35(2): 143.     CrossRef
  • Carbonic anhydrase 9 expression in well-differentiated pancreatic neuroendocrine neoplasms might be associated with aggressive behavior and poor survival
    Joo Young Kim, Sang Hwa Lee, Soyeon An, Sung Joo Kim, You-Na Sung, Ki-Byung Song, Dae Wook Hwang, Song Cheol Kim, Seung-Mo Hong
    Virchows Archiv.2018; 472(5): 739.     CrossRef
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    BMC Gastroenterology.2018;[Epub]     CrossRef
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Review
Neuroendocrine Tumors of the Female Reproductive Tract: A Literature Review
Yi Kyeong Chun
J Pathol Transl Med. 2015;49(6):450-461.   Published online October 13, 2015
DOI: https://doi.org/10.4132/jptm.2015.09.20
  • 13,673 View
  • 210 Download
  • 18 Web of Science
  • 21 Crossref
AbstractAbstract PDF
Neuroendocrine tumors of the female reproductive tract are a heterogeneous group of neoplasms that display various histologic findings and biologic behaviors. In this review, the classification and clinicopathologic characteristics of neuroendocrine tumors of the female reproductive tract are described. Differential diagnoses are discussed, especially for non-neuroendocrine tumors showing high-grade nuclei with neuroendocrine differentiation. This review also discusses recent advances in our pathogenetic understanding of these disorders.

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Original Articles
Clinical and Prognostic Significances of Cytokeratin 19 and KIT Expression in Surgically Resectable Pancreatic Neuroendocrine Tumors
Eun-Mi Son, Joo Young Kim, Soyeon An, Ki-Byung Song, Song Cheol Kim, Eunsil Yu, Seung-Mo Hong
J Pathol Transl Med. 2015;49(1):30-36.   Published online January 15, 2015
DOI: https://doi.org/10.4132/jptm.2014.10.23
  • 10,343 View
  • 83 Download
  • 18 Web of Science
  • 17 Crossref
AbstractAbstract PDF
Background
Pancreatic neuroendocrine tumors (PanNETs) are malignant endocrine neoplasms that present diverse clinical behaviors. Therefore, identification of biomarkers of PanNETs is important for stratification of the prognosis of PanNET patients. Recently, cytokeratin 19 (CK19) and KIT expression were reported to have prognostic significance in PanNET patients. Methods: To identify their prognostic significance, CK19 and KIT protein expression were assessed in 182 surgically resected PanNETs and compared with clinicopathologic factors. Results: Of 182 PanNETs cases, CK19 and KIT expression was noted in 97 (53.3%) and 16 (8.8%) cases, respectively. PanNET patients with CK19 expression had larger tumors (p=.006), higher World Health Organization (WHO) grade (p=.002) and pT classification (p<.001), increased distant metastasis (p=.004), and lymphovascular (p=.012) and perineural (p=.019) invasion. Similarly, those with KIT expression had larger tumors (p=.030), higher WHO grade (p=.001), advanced pT classification (p<.001), distant metastasis (p=.001), and lymphovascular invasion (p=.014). The 5-year survival rate for PanNET patients with KIT expression was significantly lower (62%) than that of patients without KIT expression (77%, p=.011), as determined by univariate but not by multivariate analyses. Conclusions: CK19 and KIT expression correlate with higher metastatic potential and advanced disease stage, and KIT expression is associated with worse survival in PanNET patients.

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Altered Expression of PTEN and Its Major Regulator MicroRNA-21 in Pulmonary Neuroendocrine Tumors
Hyoun Wook Lee, Seung Yeon Ha, Mee Sook Roh
Korean J Pathol. 2014;48(1):17-23.   Published online February 25, 2014
DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.1.17
  • 6,571 View
  • 42 Download
  • 10 Crossref
AbstractAbstract PDF
Background

Phosphatase and tensin homolog on chromosome ten (PTEN) is one of the most frequently inactivated tumor suppressors in various tumor types. MicroRNA-21 (miR-21) may affect tumor progression by post-transcriptional repression of expression of tumor suppressors, such as PTEN. This study was conducted to evaluate the significance of PTEN expression in pulmonary neuroendocrine (NE) tumors and to analyze the relationship between PTEN and miR-21 expressions.

Methods

Expressions of PTEN and miR-21 were investigated by immunohistochemistry and real time reverse transcription-polymerase chain reaction, respectively, in 75 resected pulmonary NE tumors (23 typical carcinoids [TCs], nine atypical carcinoids [ACs], 22 large cell NE carcinomas [LCNECs], and 21 small cell lung carcinomas [SCLCs]).

Results

Loss of PTEN expression was observed in four of 23 TCs (17.4%), four of nine ACs (44.4%), 16 of 22 LCNECs (72.7%) and nine of 21 SCLCs (42.9%) (p=.025). The expression level of miR-21 was significantly higher in high-grade NE carcinomas than in carcinoid tumors (p<.001). PTEN expression was inversely correlated with miR-21 expression (p<.001).

Conclusions

This study suggests that aberrant expression of PTEN in relation to miR-21 may represent an important step in the development and progression of pulmonary NE tumors.

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    Song Yan, Gang Liu, Changyan Pei, Wenqing Chen, Pei Li, Qiang Wang, Xintian Jin, Jiajia Zhu, Mengzhu Wang, Xiyu Liu
    Anti-Cancer Drugs.2015; 26(4): 388.     CrossRef
Proposal for a Standardized Pathology Report of Gastroenteropancreatic Neuroendocrine Tumors: Prognostic Significance of Pathological Parameters
Mee-Yon Cho, Jin Hee Sohn, So Young Jin, Hyunki Kim, Eun Sun Jung, Mi-Jung Kim, Kyoung-Mee Kim, Woo Ho Kim, Joon Mee Kim, Yun Kyung Kang, Joon Hyuk Choi, Dae Young Kang, Youn Wha Kim, Eun Hee Choi
Korean J Pathol. 2013;47(3):227-237.   Published online June 25, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.3.227
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AbstractAbstract PDF
Background

There is confusion in the diagnosis and biological behaviors of gastroenteropancreatic neuroendocrine tumors (GEP-NETs), because of independently proposed nomenclatures and classifications. A standardized form of pathology report is required for the proper management of patients.

Methods

We discussed the proper pathological evaluation of GEP-NET at the consensus conference of the subcommittee meeting for the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. We then verified the prognostic significance of pathological parameters from our previous nationwide collection of pathological data from 28 hospitals in Korea to determine the essential data set for a pathology report.

Results

Histological classification, grading (mitosis and/or Ki-67 labeling index), T staging (extent, size), lymph node metastasis, and lymphovascular and perineural invasion were significant prognostic factors and essential for the pathology report of GEP-NET, while immunostaining such as synaptophysin and chromogranin may be optional. Furthermore, the staging system, either that of the 2010 American Joint Cancer Committee (AJCC) or the European Neuroendocrine Tumor Society (ENETS), should be specified, especially for pancreatic neuroendocrine neoplasms.

Conclusions

A standardized pathology report is crucial for the proper management and prediction of prognosis of patients with GEP-NET.

Citations

Citations to this article as recorded by  
  • Analysis of Prognostic Risk Factors of Endoscopic Submucosal Dissection (ESD) and Curative Resection of Gastrointestinal Neuroendocrine Neoplasms
    Yuan Si, ChaoKang Huang, JingBin Yuan, XianHui Zhang, QingQiang He, ZhiJin Lin, Ling He, ZhongXin Liu, Yuvaraja Teekaraman
    Contrast Media & Molecular Imaging.2022; 2022: 1.     CrossRef
  • Standardization of the pathologic diagnosis of appendiceal mucinous neoplasms
    Dong-Wook Kang, Baek-hui Kim, Joon Mee Kim, Jihun Kim, Hee Jin Chang, Mee Soo Chang, Jin-Hee Sohn, Mee-Yon Cho, So-Young Jin, Hee Kyung Chang, Hye Seung Han, Jung Yeon Kim, Hee Sung Kim, Do Youn Park, Ha Young Park, So Jeong Lee, Wonae Lee, Hye Seung Lee,
    Journal of Pathology and Translational Medicine.2021; 55(4): 247.     CrossRef
  • Preoperative diagnosis of well‐differentiated neuroendocrine tumor in common hepatic duct by brush cytology: A case report
    Jiwoon Choi, Kyong Joo Lee, Sung Hoon Kim, Mee‐Yon Cho
    Diagnostic Cytopathology.2019; 47(7): 720.     CrossRef
  • Primary renal well-differentiated neuroendocrine tumors: report of six cases with an emphasis on the Ki-67 index and mitosis
    Bohyun Kim, Han-Seong Kim, Kyung Chul Moon
    Diagnostic Pathology.2019;[Epub]     CrossRef
  • Primary low‐grade neuroendocrine carcinoma of the skin: An exceedingly rare entity
    Tiffany Y. Chen, Annie O. Morrison, Joe Susa, Clay J. Cockerell
    Journal of Cutaneous Pathology.2017; 44(11): 978.     CrossRef
  • Prognostic Validity of the American Joint Committee on Cancer and the European Neuroendocrine Tumors Staging Classifications for Pancreatic Neuroendocrine Tumors
    Jae Hee Cho, Ji Kon Ryu, Si Young Song, Jin-Hyeok Hwang, Dong Ki Lee, Sang Myung Woo, Young-Eun Joo, Seok Jeong, Seung-Ok Lee, Byung Kyu Park, Young Koog Cheon, Jimin Han, Tae Nyeun Kim, Jun Kyu Lee, Sung-Hoon Moon, Hyunjin Kim, Eun Taek Park, Jae Chul Hw
    Pancreas.2016; 45(7): 941.     CrossRef
  • Early diagnosis and treatment of gastrointestinal neuroendocrine tumors
    Hong Shen, Zhuo Yu, Jing Zhao, Xiu-Zhen Li, Wen-Sheng Pan
    Oncology Letters.2016; 12(5): 3385.     CrossRef
  • Recent Updates on Neuroendocrine Tumors From the Gastrointestinal and Pancreatobiliary Tracts
    Joo Young Kim, Seung-Mo Hong
    Archives of Pathology & Laboratory Medicine.2016; 140(5): 437.     CrossRef
  • Pancreatic neuroendocrine tumors: Correlation between the contrast-enhanced computed tomography features and the pathological tumor grade
    Koji Takumi, Yoshihiko Fukukura, Michiyo Higashi, Junnichi Ideue, Tomokazu Umanodan, Hiroto Hakamada, Ichiro Kanetsuki, Takashi Yoshiura
    European Journal of Radiology.2015; 84(8): 1436.     CrossRef
  • Tumeurs neuroendocrines du tube digestif et du pancréas : ce que le pathologiste doit savoir et doit faire en 2014
    Jean-Yves Scoazec, Anne Couvelard
    Annales de Pathologie.2014; 34(1): 40.     CrossRef
  • Spectrum of Gastroenteropancreatic NENs in Routine Histological Examinations of Bioptic and Surgical Specimen: A Study of 161 Cases Collected from 17 Departments of Pathology in the Czech Republic
    Václav Mandys, Tomáš Jirásek
    Gastroenterology Research and Practice.2014; 2014: 1.     CrossRef
  • p27 Loss Is Associated with Poor Prognosis in Gastroenteropancreatic Neuroendocrine Tumors
    Hee Sung Kim, Hye Seung Lee, Kyung Han Nam, Jiwoon Choi, Woo Ho Kim
    Cancer Research and Treatment.2014; 46(4): 383.     CrossRef
Nuclear Image Analysis Study of Neuroendocrine Tumors
Meeja Park, Taehwa Baek, Jongho Baek, Hyunjin Son, Dongwook Kang, Jooheon Kim, Hyekyung Lee
Korean J Pathol. 2012;46(1):38-41.   Published online February 23, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.38
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AbstractAbstract PDF
Background

There is a subjective disagreement about nuclear chromatin in the field of pathology. Objective values of red, green, and blue (RGB) light intensities for nuclear chromatin can be obtained through a quantitative analysis using digital images.

Methods

We examined 10 cases of well differentiated neuroendocrine tumors of the rectum, small cell lung carcinomas, and moderately differentiated squamous cell lung carcinomas respectively. For each case, we selected 30 representative cells and captured typical microscopic findings. Using an image analyzer, we determined the longest nuclear line profiles and obtained graph files and Excel data on RGB light intensities. We assessed the meaningful differences in graph files and Excel data among the three different tumors.

Results

The nucleus of hematoxylin and eosin-stained tumor cells was expressed as a combination of RGB light sources. The highest intensity was from blue, whereas the lowest intensity was from green. According to the graph files, green showed the most noticeable change in the light intensity, which is consistent with the difference in standard deviations.

Conclusions

The change in the light intensity for green has an important implication for differentiating between tumors. Specific features of the nucleus can be expressed in specific values of RGB light intensities.

Citations

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  • Difference of the Nuclear Green Light Intensity between Papillary Carcinoma Cells Showing Clear Nuclei and Non-neoplastic Follicular Epithelia in Papillary Thyroid Carcinoma
    Hyekyung Lee, Tae Hwa Baek, Meeja Park, Seung Yun Lee, Hyun Jin Son, Dong Wook Kang, Joo Heon Kim, Soo Young Kim
    Journal of Pathology and Translational Medicine.2016; 50(5): 355.     CrossRef
  • Comparison of diagnostic accuracy between CellprepPlus® and ThinPrep® liquid‐based preparations in effusion cytology
    Yong‐Moon Lee, Ji‐Yong Hwang, Seung‐Myoung Son, Song‐Yi Choi, Ho‐Chang Lee, Eun‐Joong Kim, Hye‐Suk Han, Jin young An, Joung‐Ho Han, Ok‐Jun Lee
    Diagnostic Cytopathology.2014; 42(5): 384.     CrossRef
Case Report
CK20 Negative and CK7 Positive Merkel Cell Carcinoma of the Conjunctiva: Brief Case Report.
Jung Ha Shin, Jae Young Park, Hyun Seung Kim, Ok Ran Shin, Kyo Young Lee
Korean J Pathol. 2010;44(6):675-678.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.6.675
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AbstractAbstract PDF
Merkel cell carcinoma (MCC) is an uncommon but potentially aggressive neuroendocrine carcinoma of the skin. It typically develops on sun-exposed areas of the head and neck, particularly the eyelid, periorbital region, and extremities. We report a case of unusually located MCC, presenting as a conjunctival mass, which has only been reported once in the English literature. An 83-year-old male presented with a 0.8 x 0.7 cm sized mass protruding from the lower fornix of the right conjunctiva. The mass was excised. The tumor was located in the submucosa without connection to the overlying mucosa. Light microscopic findings showed a carcinoma with undifferentiated small round cells and the presence of cytokeratin (CK AE1/3, CK7) and neuroendocrine markers. We established a diagnosis of MCC. As reported in the literature, the majority of MCCs are positive for CK20 but negative for CK7. But, this case showed an uncommon cytokeratin immunohistochemical profile of positive for CK7 and negative for CK20, suggesting a new immunophenotypic MCC variant.
Original Article
Differential Expression of Glut1 in Pulmonary Neuroendocrine Tumors: Correlation with Histological Grade.
Hyun Ju Lee, Seol Bong Yoo, Won Woo Lee, Doo Hyun Chung, Jeong Wook Seo, Jin Haeng Chung
Korean J Pathol. 2009;43(3):201-205.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.3.201
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AbstractAbstract PDF
BACKGROUND
Increased glucose uptake, a process that is mediated by glucose transporter (Glut1) proteins, is an important metabolic feature in a variety of cancer cells. The overexpression of Glut1 in human cancers is known to be related to a variety of histopathological parameters, including histological grade, proliferation rate, and lymphatic invasion. The principal objective of this study was to evaluate Glut1 expression in the spectrum of pulmonary neuroendocrine (NE) tumors including typical carcinoid tumor (TC), atypical carcinoid tumor (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell carcinoma (SCC), and to characterize the relationship between Glut1 expression and the histologic grade of NE tumors.
METHODS
19 TC, 7 AC, 13 LCNEC, and 6 SCC patients were included in this study. The percentages of Glut1-positive tumor cells in these patients were determined. For statistical analysis, Glut1 expression was subdivided into a Glut1-low expression group (0-30%) and a Glut1-high expression group (31-90%).
RESULTS
In our subgroup analyses, the histological grade of pulmonary neuroendocrine (NE) tumors was significantly correlated with Glut1 expression; TC (n=19, 3.6+/-4.2%), AC (n=7, 20.0+/-4.9%), LCNEC (n=13, 60.0+/-21.1%), and SCC (n=6, 74.2+/-16.9%). Glut1-high expression was significantly associated with high-grade NE tumors such as LCNEC and SCC (n=19, 62.6+/-21.0%) (p=0.000).
CONCLUSIONS
The results of this study appear to indicate that Glut1 overexpression is a consistent feature of high-grade NE lung tumors.

Citations

Citations to this article as recorded by  
  • GLUT1: A novel tool reflecting proliferative activity of lung neuroendocrine tumors?
    Nazim Benzerdjeb, Pascal Berna, Henri Sevestre
    Pathology International.2017; 67(1): 32.     CrossRef
  • Oncocytic carcinoid tumor of the lung with intense F-18 fluorodeoxyglucose (FDG) uptake in positron emission tomography–computed tomography (PET/CT)
    Yuki Tanabe, Yoshifumi Sugawara, Rieko Nishimura, Kohei Hosokawa, Makoto Kajihara, Teruhiko Shimizu, Tadaaki Takahashi, Shinya Sakai, Shigeki Sawada, Motohiro Yamashita, Haruhiko Ohtani
    Annals of Nuclear Medicine.2013; 27(8): 781.     CrossRef
Review
Fine Needle Aspiration Cytologic Findings of Pulmonary Neuroendocrine Tumors.
Jae Soo Koh
Korean J Cytopathol. 2008;19(1):9-15.
DOI: https://doi.org/10.3338/kjc.2008.19.1.9
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AbstractAbstract PDF
The major categories of neuroendocrine tumors of lung are typical carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma, and small cell carcinoma. The histologic classification criteria of neuroendocrine tumors are well documented in the "WHO Classification of Tumors" based on mitotic figures and necrosis. Cytologic characteristics of neuroendocrine tumors are trabecular, acinar, and solid arrangement of tumor cells and occasional rosette formation. Nuclear chromatin patterns are characteristically described as "salt and pepper chromatin pattern". Many of cytologic classifications documented in the literature are before the "WHO Classification". In this review, the cytologic features of pulmonary neuroendocrine tumors are documented according to the WHO classification, and recent concepts of neuroendocrine tumors of lung are discussed.

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