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https://www.readbyqxmd.com/read/29451738/well-differentiated-grade-3-pancreatic-neuroendocrine-tumors-compared-with-related-neoplasms-a-morphologic-study
#1
Carlie S Sigel, Vitor Werneck Krauss Silva, Michelle D Reid, David Chhieng, Olca Basturk, Keith M Sigel, Tanisha D Daniel, David S Klimstra, Laura H Tang
BACKGROUND: Pancreatic neuroendocrine neoplasms with a Ki-67 labeling index greater than 20% were reclassified in 2017 by the World Health Organization into well differentiated (WD) and poorly differentiated grade 3 neuroendocrine carcinoma (NEC). The authors describe the cytologic features of grade 3 WD pancreatic neuroendocrine neoplasms compared with grade 2 neoplasms and NEC. METHODS: Fine-needle aspirates from 65 pancreatic neuroendocrine neoplasms were reviewed, and their cytomorphologic features were compared across grade 2, WD grade 3, and PD small cell type (PD-S), large cell type (PD-L), and type not otherwise specified (PD-NOS) neoplasms...
February 16, 2018: Cancer Cytopathology
https://www.readbyqxmd.com/read/29439012/immediate-post-ablation-fdg-injection-and-corresponding-standardized-uptake-value-is-a-surrogate-biomarker-of-local-tumor-progression-after-thermal-ablation-of-colorectal-carcinoma-liver-metastases
#2
Francois Cornelis, Elena N Petre, Efsevia Vakiani, David Klimstra, Jeremy Durack, Midhat Gonen, Joseph R Osborne, Stephen B Solomon, Constantinos T Sofocleous
Purpose: To determine whether intraprocedural fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) is predictor of local tumor progression after percutaneous ablation of colorectal liver metastases. Methods: In this IRB-approved prospective study, 39 patients (19 males, 20 females; median age 56 years) underwent split-dose FDG PET/CT-guided ablation followed by immediate biopsy and contrast-enhanced CT imaging of the ablation zone. Binary categorization of biopsy tissues was performed based on presence of only non-viable coagulation necrosis or viable tumor cells...
February 9, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29438172/gastric-carcinomas-with-lymphoid-stroma-an-evaluation-of-the-histopathologic-and-molecular-features
#3
Erika Hissong, Girish Ramrattan, Pan Zhang, Xi Kathy Zhou, Gloria Young, David S Klimstra, Jinru Shia, Helen Fernandes, Rhonda K Yantiss
Gastric carcinoma with lymphoid stroma is an uncommon variant enriched for mutually exclusive Epstein-Barr virus (EBV) positivity and mismatch repair (MMR) deficiency. We performed this study to evaluate molecular alterations in this morphologically homogeneous subtype and compare them with 295 conventional gastric cancers analyzed in The Cancer Genome Atlas study. We identified 31 study cases and subjected them to in situ hybridization for EBV-encoded RNAs and assessment for MMR status. Immunostains for PD-L1, β-catenin, and HER2 were performed; extracted DNA was sequenced with a Comprehensive Cancer Panel...
February 12, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29387474/gamma-interferon-exerts-a-critical-early-restriction-on-replication-and-dissemination-of-yellow-fever-virus-vaccine-strain-17d-204
#4
L K Metthew Lam, Alan M Watson, Kate D Ryman, William B Klimstra
Live attenuated viruses are historically among the most effective viral vaccines. Development of a safe vaccine requires the virus to be less virulent, a phenotype that is historically arrived by empirical evaluation often leaving the mechanisms of attenuation unknown. The yellow fever virus 17D live attenuated vaccine strain has been developed as a delivery vector for heterologous antigens; however, the mechanisms of attenuation remain elusive. The successful and safe progress of 17D as a vaccine vector and the development of live attenuated vaccines (LAVs) to related flaviviruses requires an understanding of the molecular mechanisms leading to attenuation...
2018: NPJ Vaccines
https://www.readbyqxmd.com/read/29367431/evaluating-mismatch-repair-deficiency-in-pancreatic-adenocarcinoma-challenges-and-recommendations
#5
Zishuo I Hu, Jinru Shia, Zsofia K Stadler, Anna M Varghese, Marinela Capanu, Erin Salo-Mullen, Maeve A Lowery, Luis A Diaz, Diana Mandelker, Kenneth H Yu, Alice Zervoudakis, David P Kelsen, Christine A Iacobuzio-Donahue, David S Klimstra, Leonard Saltz, Ibrahim H Sahin, Eileen M O'Reilly
PURPOSE: Immune checkpoint inhibition has been shown to generate profound and durable responses in MMR-D solid tumors and has elicited interest in detection tools and strategies to guide therapeutic decision-making. Herein we address questions on the appropriate screening, detection methods, patient selection, and initiation of therapy for MMR-D PDAC and assess the utility of NGS in providing additional prognostic and predictive information for MMR-D PDAC. EXPERIMENTAL DESIGN: Archival and prospectively acquired samples and matched normal DNA from N= 833 PDAC cases were analyzed using a hybridization capture based, NGS assay designed to perform targeted deep sequencing of all exons and selected introns of 341- 468 cancer-associated genes...
January 24, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29360137/chcc-cca-consensus-terminology-for-primary-liver-carcinomas-with-both-hepatocytic-and-cholangiocytic-differentation
#6
Elizabeth Brunt, Shinichi Aishima, Pierre-Alain Clavien, Kathryn Fowler, Zachary Goodman, Gregory Gores, Annette Gouw, Alex Kagen, David Klimstra, Mina Komuta, Fukuo Kondo, Rebecca Miksad, Masayuki Nakano, Yasuni Nakanuma, Irene Ng, Valerie Paradis, Young Nyun Park, Alberto Quaglia, Massimo Roncalli, Tania Roskams, Michiie Sakamoto, Romil Saxena, Christine Sempoux, Claude Sirlin, Ashley Stueck, Swan Thung, W M S Tsui, Xin-Wei Wang, Aileen Wee, Hirohisa Yano, Matthew Yeh, Yoh Zen, Jessica Zucman-Rossi, Neil Theise
Primary liver carcinomas with both hepatocytic and cholangiocytic differentiation have been referred to as "combined (or mixed) hepatocellular-cholangiocarcinoma." These tumors, although described over 100 years ago, have attracted greater attention recently because of interest in possible stem cell origin and perhaps because of greater frequency and clinical recognition. Currently, due to lack of common terminology in the literature, effective treatment and predictable outcome data have been challenging to accrue...
January 23, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29357472/age-related-erosion-of-obstacle-avoidance-reflexes-evoked-with-electrical-stimulation-of-tibial-nerve-during-walking
#7
Sandra R Hundza, Amit Gaur, Ryan Brodie, Drew Commandeur, Marc D Klimstra
In young healthy adults, characteristic obstacle avoidance reflexes have been demonstrated in response to electrical stimulation of cutaneous afferents of the foot during walking. It is unknown whether there is an age-related reflex erosion of this obstacle avoidance reflex with stimulation to the tibial nerve (Tibn) innervating the sole of the foot. The purpose of this study was to identify age-dependent differences in obstacle avoidance reflexes evoked with electrical stimulation of the Tibn at the ankle during walking in healthy young and older (70 years and older) adults with no history of falls...
December 20, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/29281739/lower-temperatures-reduce-type-i-interferon-activity-and-promote-alphaviral-arthritis
#8
Natalie A Prow, Bing Tang, Joy Gardner, Thuy T Le, Adam Taylor, Yee S Poo, Eri Nakayama, Thiago D C Hirata, Helder I Nakaya, Andrii Slonchak, Pamela Mukhopadhyay, Suresh Mahalingam, Wayne A Schroder, William Klimstra, Andreas Suhrbier
Chikungunya virus (CHIKV) belongs to a group of mosquito-borne alphaviruses associated with acute and chronic arthropathy, with peripheral and limb joints most commonly affected. Using a mouse model of CHIKV infection and arthritic disease, we show that CHIKV replication and the ensuing foot arthropathy were dramatically reduced when mice were housed at 30°C, rather than the conventional 22°C. The effect was not associated with a detectable fever, but was dependent on type I interferon responses. Bioinformatics analyses of RNA-Seq data after injection of poly(I:C)/jetPEI suggested the unfolded protein response and certain type I interferon responses are promoted when feet are slightly warmer...
December 27, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29239037/well-differentiated-pancreatic-neuroendocrine-tumours-pannets-and-poorly-differentiated-pancreatic-neuroendocrine-carcinomas-pannecs-concepts-issues-and-a-practical-diagnostic-approach-to-high-grade-g3-cases
#9
REVIEW
Aatur D Singhi, David S Klimstra
With increasing accessibility and advancements in abdominal imaging modalities, the incidence of pancreatic neuroendocrine neoplasms has increased steadily during the past few decades. By definition, neuroendocrine neoplasms of the pancreas show neuroendocrine differentiation, but they represent a broad and heterogeneous group of neoplasms with diverse clinical and pathological characteristics. The majority of pancreatic neuroendocrine neoplasms can be classified as well-differentiated pancreatic neuroendocrine tumours (PanNETs) or poorly differentiated pancreatic neuroendocrine carcinomas (PanNECs)...
January 2018: Histopathology
https://www.readbyqxmd.com/read/29184698/case-report-primary-acinar-cell-carcinoma-of-the-liver-treated-with-multimodality-therapy
#10
Emmet J Jordan, Olca Basturk, Jinru Shia, David S Klimstra, William Alago, Michael I D'Angelica, Ghassan K Abou-Alfa, Eileen M O'Reilly, Maeve A Lowery
We describe a case of primary acinar cell carcinoma (ACC) originating in the liver in a 54-year-old female, diagnosed following persistent abnormal elevated liver function. Imaging revealed two masses, one dominant lesion in the right hepatic lobe and another in segment IVA. A right hepatectomy was performed to remove the larger lesion, while the mass in segment IVA was unresectable due to its proximity to the left hepatic vein. Immunohistochemical staining showed positivity for trypsin and chymotrypsin. Postoperatively the patient underwent hepatic arterial embolization of the other unresectable lesion followed by FOLFOX chemotherapy...
October 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/29094972/identity-exploration-and-commitment-in-early-adolescence-genetic-and-environmental-contributions
#11
Noam Markovitch, Koen Luyckx, Theo Klimstra, Lior Abramson, Ariel Knafo-Noam
Identity formation is a key developmental task in adolescence. Although many adolescents in modern societies face issues of identity, there are substantial individual differences in identity exploration and commitment. Little is known about the origins of these individual differences. The current study investigated the genetic and environmental contributions to identity formation. In total, 571 11-year-old twins (85 monozygotic complete pairs and 176 dizygotic complete pairs) reported on their identity formation, using the Dimensions of Identity Development Scale (DIDS; Luyckx, Schwartz, Berzonsky, et al...
November 2017: Developmental Psychology
https://www.readbyqxmd.com/read/29094969/a-theoretical-framework-for-the-associations-between-identity-and-psychopathology
#12
Theo A Klimstra, Jaap J A Denissen
Identity research largely emerged from clinical observations. Decades of empirical work advanced the field in refining existing approaches and adding new approaches. Furthermore, the existence of linkages of identity with psychopathology is now well established. Unfortunately, both the directionality of effects between identity aspects and psychopathology symptoms, and the mechanisms underlying associations are unclear. In the present paper, we present a new framework to inspire hypothesis-driven empirical research to overcome this limitation...
November 2017: Developmental Psychology
https://www.readbyqxmd.com/read/29045506/clinical-and-molecular-characterization-of-patients-with-cancers-of-unknown-primary-in-the-modern-era
#13
A M Varghese, A Arora, M Capanu, N Camacho, H H Won, A Zehir, J Gao, D Chakravarty, N Schultz, D S Klimstra, M Ladanyi, D M Hyman, D B Solit, M F Berger, L B Saltz
Background: On the basis of historical data, patients with cancers of unknown primary (CUP) are generally assumed to have a dismal prognosis with overall survival of less than one year. Treatment is typically cytotoxic chemotherapy guided by histologic features and the pattern of metastatic spread. The purpose of this study was to provide a clinical and pathologic description of patients with CUP in the modern era, to define the frequency of clinically actionable molecular alterations in this population, to determine how molecular testing can alter therapeutic decisions, and to investigate novel uses of next generation sequencing in the evaluation and treatment of patients with CUP...
September 26, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29044913/assessment-of-cytologic-differentiation-in-high-grade-pancreatic-neuroendocrine-neoplasms-a-multi-institutional-study
#14
Carlie S Sigel, Vitor Werneck Krauss Silva, Michelle D Reid, David Chhieng, Olca Basturk, Keith M Sigel, Tanisha D Daniel, David S Klimstra, Laura H Tang
BACKGROUND: Well-differentiated (WD) and poorly differentiated (PD) pancreatic neuroendocrine neoplasms are biologically distinct entities with different therapies and prognoses. WD neoplasms with elevated proliferation (Ki-67 > 20%) have been shown to have an overlapping histology with PD neuroendocrine carcinomas. This study compared expert cytomorphologic assessments of differentiation in pancreatic neuroendocrine neoplasms in a multi-institutional study. METHODS: Fine-needle aspiration specimens from pancreatic neuroendocrine neoplasms (grade 2 [G2] and grade 3 [G3] according to the 2017 World Health Organization classification; n = 72) were diagnosed independently by 3 cytopathologists as WD or PD (poorly differentiated large cell type [PD-L] or poorly differentiated small cell type [PD-S]) purely on the basis of cytomorphology...
October 17, 2017: Cancer
https://www.readbyqxmd.com/read/28884748/a-fish-assay-efficiently-screens-for-braf-gene-rearrangements-in-pancreatic-acinar-type-neoplasms
#15
Lu Wang, Olca Basturk, Jiajing Wang, Ryma Benayed, Sumit Middha, Ahmet Zehir, Irina Linkov, Mamta Rao, Ruth Aryeequaye, Long Cao, Juliann Chmielecki, Jeffrey Ross, Philip J Stephens, Volkan Adsay, Gokce Askan, Serdar Balci, David S Klimstra
Approximately 1-2% of pancreatic neoplasms are acinar cell carcinomas. Recently, BRAF gene rearrangements were identified in over 20% of acinar-type neoplasms, which included both pure acinar cell carcinomas and mixed carcinomas with acinar differentiation, using next-generation sequencing-based platforms, providing a potential therapeutic target for patients with these neoplasms. Thus, it is clinically important to develop a rapid, cost- and material-efficient assay to screen for BRAF gene fusions in pancreatic acinar-type neoplasms...
January 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28873162/mutation-detection-in-patients-with-advanced-cancer-by-universal-sequencing-of-cancer-related-genes-in-tumor-and-normal-dna-vs-guideline-based-germline-testing
#16
Diana Mandelker, Liying Zhang, Yelena Kemel, Zsofia K Stadler, Vijai Joseph, Ahmet Zehir, Nisha Pradhan, Angela Arnold, Michael F Walsh, Yirong Li, Anoop R Balakrishnan, Aijazuddin Syed, Meera Prasad, Khedoudja Nafa, Maria I Carlo, Karen A Cadoo, Meg Sheehan, Megan H Fleischut, Erin Salo-Mullen, Magan Trottier, Steven M Lipkin, Anne Lincoln, Semanti Mukherjee, Vignesh Ravichandran, Roy Cambria, Jesse Galle, Wassim Abida, Marcia E Arcila, Ryma Benayed, Ronak Shah, Kenneth Yu, Dean F Bajorin, Jonathan A Coleman, Steven D Leach, Maeve A Lowery, Julio Garcia-Aguilar, Philip W Kantoff, Charles L Sawyers, Maura N Dickler, Leonard Saltz, Robert J Motzer, Eileen M O'Reilly, Howard I Scher, Jose Baselga, David S Klimstra, David B Solit, David M Hyman, Michael F Berger, Marc Ladanyi, Mark E Robson, Kenneth Offit
Importance: Guidelines for cancer genetic testing based on family history may miss clinically actionable genetic changes with established implications for cancer screening or prevention. Objective: To determine the proportion and potential clinical implications of inherited variants detected using simultaneous sequencing of the tumor and normal tissue ("tumor-normal sequencing") compared with genetic test results based on current guidelines. Design, Setting, and Participants: From January 2014 until May 2016 at Memorial Sloan Kettering Cancer Center, 10 336 patients consented to tumor DNA sequencing...
September 5, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28857328/different-aspects-of-emotional-intelligence-of-borderline-personality-disorder
#17
Mathell Peter, Arnoud R Arntz, Theo Klimstra, Ad J J M Vingerhoets
OBJECTIVES: The present study investigated deficiencies in different components of emotional intelligence in borderline personality disorder (BPD). METHOD: The Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) and the Emotional Quotient Inventory (EQ-i) were used to assess EI dimensions. BPD patients (N = 85; 69 women; M = 33.6 years) were compared with Cluster C personality disorder (PD) patients (N = 39; 23 women; M = 36.6 years) and nonpatients (N = 69; 44 women; M = 35...
August 30, 2017: Clinical Psychology & Psychotherapy
https://www.readbyqxmd.com/read/28819720/immunohistochemical-null-phenotype-for-mismatch-repair-proteins-in-colonic-carcinoma-associated-with-concurrent-mlh1-hypermethylation-and-msh2-somatic-mutations
#18
Tao Wang, Zsofia K Stadler, Liying Zhang, Martin R Weiser, Olca Basturk, Jaclyn F Hechtman, Efsevia Vakiani, Lenard B Saltz, David S Klimstra, Jinru Shia
Microsatellite instability, a well-established driver pathway in colorectal carcinogenesis, can develop in both sporadic and hereditary conditions via different molecular alterations in the DNA mismatch repair (MMR) genes. MMR protein immunohistochemistry (IHC) is currently widely used for the detection of MMR deficiency in solid tumors. The IHC test, however, can show varied staining patterns, posing challenges in the interpretation of the staining results in some cases. Here we report a case of an 80-year-old female with a colonic adenocarcinoma that exhibited an unusual "null" IHC staining pattern with complete loss of all four MMR proteins (MLH1, MSH2, MSH6, and PMS2)...
August 17, 2017: Familial Cancer
https://www.readbyqxmd.com/read/28777785/erratum-mutational-landscape-of-metastatic-cancer-revealed-from-prospective-clinical-sequencing-of-10-000-patients
#19
Ahmet Zehir, Ryma Benayed, Ronak H Shah, Aijazuddin Syed, Sumit Middha, Hyunjae R Kim, Preethi Srinivasan, Jianjiong Gao, Debyani Chakravarty, Sean M Devlin, Matthew D Hellmann, David A Barron, Alison M Schram, Meera Hameed, Snjezana Dogan, Dara S Ross, Jaclyn F Hechtman, Deborah F DeLair, JinJuan Yao, Diana L Mandelker, Donavan T Cheng, Raghu Chandramohan, Abhinita S Mohanty, Ryan N Ptashkin, Gowtham Jayakumaran, Meera Prasad, Mustafa H Syed, Anoop Balakrishnan Rema, Zhen Y Liu, Khedoudja Nafa, Laetitia Borsu, Justyna Sadowska, Jacklyn Casanova, Ruben Bacares, Iwona J Kiecka, Anna Razumova, Julie B Son, Lisa Stewart, Tessara Baldi, Kerry A Mullaney, Hikmat Al-Ahmadie, Efsevia Vakiani, Adam A Abeshouse, Alexander V Penson, Philip Jonsson, Niedzica Camacho, Matthew T Chang, Helen H Won, Benjamin E Gross, Ritika Kundra, Zachary J Heins, Hsiao-Wei Chen, Sarah Phillips, Hongxin Zhang, Jiaojiao Wang, Angelica Ochoa, Jonathan Wills, Michael Eubank, Stacy B Thomas, Stuart M Gardos, Dalicia N Reales, Jesse Galle, Robert Durany, Roy Cambria, Wassim Abida, Andrea Cercek, Darren R Feldman, Mrinal M Gounder, A Ari Hakimi, James J Harding, Gopa Iyer, Yelena Y Janjigian, Emmet J Jordan, Ciara M Kelly, Maeve A Lowery, Luc G T Morris, Antonio M Omuro, Nitya Raj, Pedram Razavi, Alexander N Shoushtari, Neerav Shukla, Tara E Soumerai, Anna M Varghese, Rona Yaeger, Jonathan Coleman, Bernard Bochner, Gregory J Riely, Leonard B Saltz, Howard I Scher, Paul J Sabbatini, Mark E Robson, David S Klimstra, Barry S Taylor, Jose Baselga, Nikolaus Schultz, David M Hyman, Maria E Arcila, David B Solit, Marc Ladanyi, Michael F Berger
No abstract text is available yet for this article.
August 4, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28776573/pancreatic-intraductal-tubulopapillary-neoplasm-is-genetically-distinct-from-intraductal-papillary-mucinous-neoplasm-and-ductal-adenocarcinoma
#20
Olca Basturk, Michael F Berger, Hiroshi Yamaguchi, Volkan Adsay, Gokce Askan, Umesh K Bhanot, Ahmet Zehir, Fatima Carneiro, Seung-Mo Hong, Giuseppe Zamboni, Esra Dikoglu, Vaidehi Jobanputra, Kazimierz O Wrzeszczynski, Serdar Balci, Peter Allen, Naoki Ikari, Shoko Takeuchi, Hiroyuki Akagawa, Atsushi Kanno, Tooru Shimosegawa, Takanori Morikawa, Fuyuhiko Motoi, Michiaki Unno, Ryota Higuchi, Masakazu Yamamoto, Kyoko Shimizu, Toru Furukawa, David S Klimstra
Intraductal tubulopapillary neoplasm is a relatively recently described member of the pancreatic intraductal neoplasm family. The more common member of this family, intraductal papillary mucinous neoplasm, often carries genetic alterations typical of pancreatic infiltrating ductal adenocarcinoma (KRAS, TP53, and CDKN2A) but additionally has mutations in GNAS and RNF43 genes. However, the genetic characteristics of intraductal tubulopapillary neoplasm have not been well characterized. Twenty-two intraductal tubulopapillary neoplasms were analyzed by either targeted next-generation sequencing, which enabled the identification of sequence mutations, copy number alterations, and selected structural rearrangements involving all targeted (≥300) genes, or whole-exome sequencing...
August 4, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
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