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Pancreatic Neoplasms: HELP
Articles by Dr. R Hruban
Based on 283 articles published since 2009
(Why 283 articles?)
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Between 2009 and 2019, R. Hruban wrote the following 283 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9 · 10 · 11 · 12
1 Guideline Pathologic Evaluation and Reporting of Intraductal Papillary Mucinous Neoplasms of the Pancreas and Other Tumoral Intraepithelial Neoplasms of Pancreatobiliary Tract: Recommendations of Verona Consensus Meeting. 2016

Adsay, Volkan / Mino-Kenudson, Mari / Furukawa, Toru / Basturk, Olca / Zamboni, Giuseppe / Marchegiani, Giovanni / Bassi, Claudio / Salvia, Roberto / Malleo, Giuseppe / Paiella, Salvatore / Wolfgang, Christopher L / Matthaei, Hanno / Offerhaus, G Johan / Adham, Mustapha / Bruno, Marco J / Reid, Michelle D / Krasinskas, Alyssa / Klöppel, Günter / Ohike, Nobuyuki / Tajiri, Takuma / Jang, Kee-Taek / Roa, Juan Carlos / Allen, Peter / Fernández-del Castillo, Carlos / Jang, Jin-Young / Klimstra, David S / Hruban, Ralph H / Anonymous6200823. ·*Department of Pathology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA †Department of Pathology, Massachusetts General Hospital, Boston, MA ‡Department of Pathology, Tokyo Women's Medical University, Tokyo, Japan §Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY ¶Department of Pathology, University of Verona, Verona, Italy ||Department of Surgery, Massachusetts General Hospital, Boston, MA **Department of Surgery, University of Verona, Verona, Italy ††Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD ‡‡Departments of Surgery, University of Bonn, Bonn, Germany §§Departments of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands ¶¶Department of Surgery, Edouard Herriot Hospital, HCL, Lyon, France ||||Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands ***Departments of Pathology, Technical University, Munich, Germany †††Department of Pathology, Showa University Fujigaoka Hospital, Yokohama, Japan ‡‡‡Department of Pathology, Tokai University Hachioji Hospital, Tokyo, Japan §§§Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea ¶¶¶Department of Pathology, Pontificia Universidad Católica de Chile, Santiago, Chile ||||||Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY ****Department of Surgery, Massachusetts General Hospital, Boston, MA ††††Department of Surgery, Seoul National University Hospital, Seoul, Korea ‡‡‡‡Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD. ·Ann Surg · Pubmed #25775066.

ABSTRACT: BACKGROUND: There are no established guidelines for pathologic diagnosis/reporting of intraductal papillary mucinous neoplasms (IPMNs). DESIGN: An international multidisciplinary group, brought together by the Verona Pancreas Group in Italy-2013, was tasked to devise recommendations. RESULTS: (1) Crucial to rule out invasive carcinoma with extensive (if not complete) sampling. (2) Invasive component is to be documented in a full synoptic report including its size, type, grade, and stage. (3) The term "minimally invasive" should be avoided; instead, invasion size with stage and substaging of T1 (1a, b, c; ≤ 0.5, > 0.5-≤ 1, > 1 cm) is to be documented. (4) Largest diameter of the invasion, not the distance from the nearest duct, is to be used. (5) A category of "indeterminate/(suspicious) for invasion" is acceptable for rare cases. (6) The term "malignant" IPMN should be avoided. (7) The highest grade of dysplasia in the non-invasive component is to be documented separately. (8) Lesion size is to be correlated with imaging findings in cysts with rupture. (9) The main duct diameter and, if possible, its involvement are to be documented; however, it is not required to provide main versus branch duct classification in the resected tumor. (10) Subtyping as gastric/intestinal/pancreatobiliary/oncocytic/mixed is of value. (11) Frozen section is to be performed highly selectively, with appreciation of its shortcomings. (12) These principles also apply to other similar tumoral intraepithelial neoplasms (mucinous cystic neoplasms, intra-ampullary, and intra-biliary/cholecystic). CONCLUSIONS: These recommendations will ensure proper communication of salient tumor characteristics to the management teams, accurate comparison of data between analyses, and development of more effective management algorithms.

2 Guideline Utilization of ancillary studies in the cytologic diagnosis of biliary and pancreatic lesions: the Papanicolaou Society of Cytopathology guidelines for pancreatobiliary cytology. 2014

Layfield, Lester J / Ehya, Hormoz / Filie, Armando C / Hruban, Ralph H / Jhala, Nirag / Joseph, Loren / Vielh, Philippe / Pitman, Martha B / Anonymous3010788. ·Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, Missouri. ·Diagn Cytopathol · Pubmed #24639398.

ABSTRACT: The Papanicolaou Society of Cytopathology has developed a set of guidelines for pancreatobiliary cytology including indications for endoscopic ultrasound-guided fine-needle aspiration, terminology and nomenclature of pancreatobiliary disease, ancillary testing, and post-biopsy management. All documents are based on the expertise of the authors, a review of the literature, discussions of the draft document at several national and international meetings, and synthesis of selected online comments of the draft document. This document presents the results of these discussions regarding the use of ancillary testing in the cytologic diagnosis of biliary and pancreatic lesions. Currently, fluorescence in situ hybridization (FISH) appears to be the most clinically relevant ancillary technique for cytology of bile duct strictures. The addition of FISH analysis to routine cytologic evaluation appears to yield the highest sensitivity without loss in specificity. Loss of immunohistochemical staining for the protein product of the SMAD4 gene and positive staining for mesothelin support a diagnosis of ductal adenocarcinoma. Immunohistochemical markers for endocrine and exocrine differentiation are sufficient for a diagnosis of endocrine and acinar tumors. Nuclear staining for beta-catenin supports a diagnosis of solid-pseudopapilary neoplasm. Cyst fluid analysis for amylase and carcinoembryonic antigen aids in the preoperative classification of pancreatic cysts. Many gene mutations (KRAS, GNAS, VHL, RNF43, and CTNNB1) may be of aid in the diagnosis of cystic neoplasms. Other ancillary techniques do not appear to improve diagnostic sensitivity sufficiently to justify their increased costs.

3 Guideline International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. 2013

Canto, Marcia Irene / Harinck, Femme / Hruban, Ralph H / Offerhaus, George Johan / Poley, Jan-Werner / Kamel, Ihab / Nio, Yung / Schulick, Richard S / Bassi, Claudio / Kluijt, Irma / Levy, Michael J / Chak, Amitabh / Fockens, Paul / Goggins, Michael / Bruno, Marco / Anonymous4730741. ·Division of Gastroenterology, Johns Hopkins University, The Sol Goldman Pancreatic Cancer Research Center, 1830 E Monument Street, Baltimore, MD 21205, USA. mcanto@jhmi.edu ·Gut · Pubmed #23135763.

ABSTRACT: BACKGROUND: Screening individuals at increased risk for pancreatic cancer (PC) detects early, potentially curable, pancreatic neoplasia. OBJECTIVE: To develop consortium statements on screening, surveillance and management of high-risk individuals with an inherited predisposition to PC. METHODS: A 49-expert multidisciplinary international consortium met to discuss pancreatic screening and vote on statements. Consensus was considered reached if ≥ 75% agreed or disagreed. RESULTS: There was excellent agreement that, to be successful, a screening programme should detect and treat T1N0M0 margin-negative PC and high-grade dysplastic precursor lesions (pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasm). It was agreed that the following were candidates for screening: first-degree relatives (FDRs) of patients with PC from a familial PC kindred with at least two affected FDRs; patients with Peutz-Jeghers syndrome; and p16, BRCA2 and hereditary non-polyposis colorectal cancer (HNPCC) mutation carriers with ≥ 1 affected FDR. Consensus was not reached for the age to initiate screening or stop surveillance. It was agreed that initial screening should include endoscopic ultrasonography (EUS) and/or MRI/magnetic resonance cholangiopancreatography not CT or endoscopic retrograde cholangiopancreatography. There was no consensus on the need for EUS fine-needle aspiration to evaluate cysts. There was disagreement on optimal screening modalities and intervals for follow-up imaging. When surgery is recommended it should be performed at a high-volume centre. There was great disagreement as to which screening abnormalities were of sufficient concern to for surgery to be recommended. CONCLUSIONS: Screening is recommended for high-risk individuals, but more evidence is needed, particularly for how to manage patients with detected lesions. Screening and subsequent management should take place at high-volume centres with multidisciplinary teams, preferably within research protocols.

4 Editorial Introduction. 2014

Hruban, Ralph H / Klimstra, David S. · ·Semin Diagn Pathol · Pubmed #25441312.

ABSTRACT: -- No abstract --

5 Review A "Clearer" View of Pancreatic Pathology: A Review of Tissue Clearing and Advanced Microscopy Techniques. 2019

Hong, Seung-Mo / Noë, Michaël / Hruban, Carolyn A / Thompson, Elizabeth D / Wood, Laura D / Hruban, Ralph H. ·Departments of Pathology. · Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. · Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD. ·Adv Anat Pathol · Pubmed #30256228.

ABSTRACT: Although pathologic lesions in the pancreas are 3-dimensional (3D) complex structures, we currently use thin 2D hematoxylin and eosin stained slides to study and diagnose pancreatic pathology. Two technologies, tissue clearing and advanced microscopy, have recently converged, and when used together they open the remarkable world of 3D anatomy and pathology to pathologists. Advances in tissue clearing and antibody penetration now make even dense fibrotic tissues amenable to clearing, and light sheet and confocal microscopies allow labeled cells deep within these cleared tissues to be visualized. Clearing techniques can be categorized as solvent-based or aqueous-based techniques, but both clearing methods consist of 4 fundamental steps, including pretreatment of specimens, permeabilization and/or removal of lipid, immunolabeling with antibody penetration, and clearing by refractive index matching. Specialized microscopes, including the light sheet microscope, the 2-photon microscope, and the confocal microscope, can then be used to visualize and evaluate the 3D histology. Both endocrine and exocrine pancreas pathology can then be visualized. The application of labeling and clearing to surgically resected human pancreatic parenchyma can provide detailed visualization of the complexities of normal pancreatic anatomy. It also can be used to characterize the 3D architecture of disease processes ranging from precursor lesions, such as pancreatic intraepithelial neoplasia lesions and intraductal papillary mucinous neoplasms, to infiltrating pancreatic ductal adenocarcinomas. The evaluation of 3D histopathology, including pathology of the pancreatic lesions, will provide new insights into lesions that previously were seen, and thought of, only in 2 dimensions.

6 Review Pancreatic neuroendocrine tumor: review of heterogeneous spectrum of CT appearance. 2018

Lee, Nam Ju / Hruban, Ralph H / Fishman, Elliot K. ·Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, 601 N. Caroline Street, Baltimore, MD, 21287, USA. nlee54@jhmi.edu. · Department of Pathology, Johns Hopkins School of Medicine, 600 N. Wolfe Street, Baltimore, MD, 21287, USA. · Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, 601 N. Caroline Street, Baltimore, MD, 21287, USA. ·Abdom Radiol (NY) · Pubmed #29594467.

ABSTRACT: OBJECTIVE: Pancreatic neuroendocrine tumors (PanNETs) are uncommon pancreatic neoplasms and can be a diagnostic challenge with heterogeneous spectrum of CT appearance. We review CT findings of PanNETs and other mimics. CONCLUSION: PanNETs are typically hypervascular and have avid enhancement on arterial and venous phase images. However, dedicated pancreas protocol may be needed due to their sometimes atypical appearance including transient enhancement. Careful evaluation of CT findings will help differentiate PanNETs from their mimics, and can be used to establish the diagnosis of a PanNETs. Although an accurate diagnosis can be based on serological, urine, and CT scan findings, confirmation is made via pathological examination.

7 Review Lessons learned from 29 lymphoepithelial cysts of the pancreas: institutional experience and review of the literature. 2018

Groot, Vincent P / Thakker, Sameer S / Gemenetzis, Georgios / Noë, Michaël / Javed, Ammar A / Burkhart, Richard A / Noveiry, Behnoud B / Cameron, John L / Weiss, Matthew J / VandenBussche, Christopher J / Fishman, Elliot K / Hruban, Ralph H / Wolfgang, Christopher L / Lennon, Anne Marie / He, Jin. ·Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Surgery, UMC Utrecht Cancer Center, University Medical Center Utrecht, Utrecht, The Netherlands. · Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Gastroenterology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Radiology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Gastroenterology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Radiology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: jhe11@jhmi.edu. ·HPB (Oxford) · Pubmed #29530477.

ABSTRACT: BACKGROUND: Lymphoepithelial cysts (LECs) are rare pancreatic cystic lesions. Since LECs are benign, preoperative diagnosis is important to differentiate from a cystic neoplasm and avoid unnecessary surgery. The aim of this study was to identify clinical, radiographic and cytopathologic features associated with LECs. METHODS: A retrospective review was performed of patients diagnosed with LEC between 1995 and 2017 at our hospital. Clinicopathologic and radiographic imaging features were documented. RESULTS: Of 29 patients with pancreatic LEC, 22 underwent surgical resection. The majority were male (n = 24) with a median age of 55 years (range, 21-74). During the evaluation, all patients underwent a CT, with endoscopic ultrasound (EUS) guided fine needle aspiration (FNA) biopsy (n = 22) and/or MRI/MRCP (n = 11) performed in a smaller number of patients. A combination of exophytic tumor growth on imaging and the presence of specific cytomorphologic features on the EUS-FNA cytology biopsy led to the correct diagnosis of LEC and prevention of unnecessary surgery in 7 patients. DISCUSSION: Differentiating LECs from premalignant pancreatic cystic neoplasms remains difficult. Findings of an exophytic growth pattern of the lesion on abdominal imaging and the presence of specific cytomorphologic features in the EUS-FNA biopsy could help clinicians diagnose LEC preoperatively.

8 Review New Developments in the Molecular Mechanisms of Pancreatic Tumorigenesis. 2018

Felsenstein, Matthäus / Hruban, Ralph H / Wood, Laura D. ·Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD. ·Adv Anat Pathol · Pubmed #28914620.

ABSTRACT: Pancreatic cancer is an aggressive disease with a dismal prognosis in dire need of novel diagnostic and therapeutic approaches. The past decade has witnessed an explosion of data on the genetic alterations that occur in pancreatic cancer, as comprehensive next-generation sequencing analyses have been performed on samples from large cohorts of patients. These studies have defined the genomic landscape of this disease and identified novel candidates whose mutations contribute to pancreatic tumorigenesis. They have also clarified the genetic alterations that underlie multistep tumorigenesis in precursor lesions and provided insights into clonal evolution in pancreatic neoplasia. In addition to these important insights into pancreatic cancer biology, these large scale genomic studies have also provided a foundation for the development of novel early detection strategies and targeted therapies. In this review, we discuss the results of these comprehensive sequencing studies of pancreatic neoplasms, with a particular focus on how their results will impact the clinical care of patients with pancreatic cancer.

9 Review Classification, Morphology, Molecular Pathogenesis, and Outcome of Premalignant Lesions of the Pancreas. 2017

Pittman, Meredith E / Rao, Rema / Hruban, Ralph H. · ·Arch Pathol Lab Med · Pubmed #29189063.

ABSTRACT: CONTEXT: - Invasive pancreatic ductal adenocarcinoma has a greater than 90% mortality rate at 5 years. Understanding noninvasive, curable precursor lesions gives us the best hope for reducing mortality from pancreatic ductal adenocarcinoma. The 3 pancreatic precursor lesions that have been well studied include intraductal papillary mucinous neoplasm, mucinous cystic neoplasm, and pancreatic intraepithelial neoplasia. OBJECTIVE: - To give an update on the latest clinical, molecular, and pathologic advances in intraductal papillary mucinous neoplasm, mucinous cystic neoplasm, and pancreatic intraepithelial neoplasia for the general surgical pathologist. DATA SOURCES: - The current literature was analyzed and the authors' experiences with institutional and consult material were incorporated. CONCLUSIONS: - Our understanding of the molecular alterations that lead from pancreatic precursor lesion to invasive carcinoma continues to evolve. These advances aid clinicians in their treatment decisions and researchers in their search for actionable, druggable targets.

10 Review Abdominal schwannomas: review of imaging findings and pathology. 2017

Lee, Nam Ju / Hruban, Ralph H / Fishman, Elliot K. ·Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, 601 N. Caroline Street, Baltimore, MD, 21287, USA. nlee54@jhmi.edu. · Department of Pathology, Johns Hopkins School of Medicine, 600 N. Wolfe Street, Baltimore, MD, 21287, USA. · Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, 601 N. Caroline Street, Baltimore, MD, 21287, USA. ·Abdom Radiol (NY) · Pubmed #28265705.

ABSTRACT: Schwannomas are typically slow growing, encapsulated benign neoplasms. Visceral schwannomas are rare, and preoperative diagnosis is challenging, as they are often confused with other neoplasms even with advanced imaging studies. Surgical excision is usually needed to establish a definitive diagnosis, as pathology is the "gold standard." We review the imaging findings of abdominal schwannomas focusing on pancreatic, gastrointestinal, and retroperitoneal/adrenal schwannomas with pathology correlation. We conclude that schwannoma should be included in the broad differential diagnosis of an abdominal mass and that when it is unnecessary radical resection can be avoided.

11 Review The many faces of pancreatic serous cystadenoma: Radiologic and pathologic correlation. 2017

Chu, L C / Singhi, A D / Haroun, R R / Hruban, R H / Fishman, E K. ·The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital, 600 North Wolfe Street, Halsted B168, 21287 Baltimore, MD, USA. Electronic address: lindachu@jhmi.edu. · Department of Pathology, University of Pittsburgh Medical Center, 15213 Pittsburgh, PA, USA. · The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital, 600 North Wolfe Street, Halsted B168, 21287 Baltimore, MD, USA. · The Sol Goldman Pancreatic Cancer Research Center, The Department of Pathology, Johns Hopkins Hospital, 401 North Broadway, 21231 Baltimore, MD, USA. ·Diagn Interv Imaging · Pubmed #27614585.

ABSTRACT: Pancreatic serous cystadenoma can be categorized into microcystic, honeycomb, oligocystic, and solid patterns based on imaging appearance. The presence of typical computed tomography (CT) features helps to differentiate serous cystadenomas from other cystic and solid pancreatic masses. Cases with atypical features present a diagnostic challenge as they can mimic malignant neoplasms. This article reviews pathophysiology, prevalence, CT features, mimickers and recommendations for management of pancreatic serous cystadenoma.

12 Review Current concepts in the diagnosis and pathobiology of intraepithelial neoplasia: A review by organ system. 2016

Voltaggio, Lysandra / Cimino-Mathews, Ashley / Bishop, Justin A / Argani, Pedram / Cuda, Jonathan D / Epstein, Jonathan I / Hruban, Ralph H / Netto, George J / Stoler, Mark H / Taube, Janis M / Vang, Russell / Westra, William H / Montgomery, Elizabeth A. ·Assistant Professor of Pathology, Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD. · Associate Professor of Pathology, Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD. · Professor of Pathology, Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD. · Assistant Professor of Dermatology, Department of Dermatology, Johns Hopkins Medical Institutions, Baltimore, MD. · Professor of Urology, Brady Urological Institute, Johns Hopkins Hospital, Baltimore, MD. · Professor of Pathology, Department of Pathology, University of Virginia Health System, Charlottesville, VA. · Associate Professor of Dermatology and Pathology, Department of Dermatology, Johns Hopkins Medical Institutions, Baltimore, MD. ·CA Cancer J Clin · Pubmed #27270763.

ABSTRACT: Answer questions and earn CME/CNE In this report, a team of surgical pathologists has provided a review of intraepithelial neoplasia in a host of (but not all) anatomic sites of interest to colleagues in various medical specialties, namely, uterine cervix, ovary, breast, lung, head and neck, skin, prostate, bladder, pancreas, and esophagus. There is more experience with more readily accessible sites (such as the uterine cervix and skin) than with other anatomic sites, and the lack of uniform terminology, together with divergent biology in various sites, makes it difficult to paint a unifying, relevant portrait. The authors' aim was to provide a framework from which to move forward as we care for patients with such precancerous lesions. CA Cancer J Clin 2016;66:408-436. © 2016 American Cancer Society.

13 Review Surgical and molecular pathology of pancreatic neoplasms. 2016

Hackeng, Wenzel M / Hruban, Ralph H / Offerhaus, G Johan A / Brosens, Lodewijk A A. ·Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. · Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. l.a.a.brosens@umcutrecht.nl. ·Diagn Pathol · Pubmed #27267993.

ABSTRACT: BACKGROUND: Histologic characteristics have proven to be very useful for classifying different types of tumors of the pancreas. As a result, the major tumor types in the pancreas have long been classified based on their microscopic appearance. MAIN BODY: Recent advances in whole exome sequencing, gene expression profiling, and knowledge of tumorigenic pathways have deepened our understanding of the underlying biology of pancreatic neoplasia. These advances have not only confirmed the traditional histologic classification system, but also opened new doors to early diagnosis and targeted treatment. CONCLUSION: This review discusses the histopathology, genetic and epigenetic alterations and potential treatment targets of the five major malignant pancreatic tumors - pancreatic ductal adenocarcinoma, pancreatic neuroendocrine tumor, solid-pseudopapillary neoplasm, acinar cell carcinoma and pancreatoblastoma.

14 Review Pancreatic cancer. 2016

Kleeff, Jorg / Korc, Murray / Apte, Minoti / La Vecchia, Carlo / Johnson, Colin D / Biankin, Andrew V / Neale, Rachel E / Tempero, Margaret / Tuveson, David A / Hruban, Ralph H / Neoptolemos, John P. ·NIHR Pancreas Biomedical Research Unit, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Duncan Building, Daulby Street, Liverpool L69 3GA, UK. · Department of General, Visceral and Pediatric Surgery, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany. · Departments of Medicine, and Biochemistry and Molecular Biology, Indiana University School of Medicine, the Melvin and Bren Simon Cancer Center, and the Pancreatic Cancer Signature Center, Indianapolis, Indiana, USA. · SWS Clinical School, University of New South Wales, and Ingham Institute for Applied Medical Research, Sydney, New South Wales, Australia. · Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy. · University Surgical Unit, University Hospital Southampton, Southampton, UK. · Institute of Cancer Sciences, Wolfson Wohl Cancer Research Centre, University of Glasgow, Garscube Estate, Bearsden, Glasgow, Scotland, UK. · QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. · UCSF Pancreas Center, University of California San Francisco - Mission Bay Campus/Mission Hall, San Francisco, California, USA. · Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, New York, USA. · The Sol Goldman Pancreatic Cancer Research Center, Departments of Pathology and Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. ·Nat Rev Dis Primers · Pubmed #27158978.

ABSTRACT: Pancreatic cancer is a major cause of cancer-associated mortality, with a dismal overall prognosis that has remained virtually unchanged for many decades. Currently, prevention or early diagnosis at a curable stage is exceedingly difficult; patients rarely exhibit symptoms and tumours do not display sensitive and specific markers to aid detection. Pancreatic cancers also have few prevalent genetic mutations; the most commonly mutated genes are KRAS, CDKN2A (encoding p16), TP53 and SMAD4 - none of which are currently druggable. Indeed, therapeutic options are limited and progress in drug development is impeded because most pancreatic cancers are complex at the genomic, epigenetic and metabolic levels, with multiple activated pathways and crosstalk evident. Furthermore, the multilayered interplay between neoplastic and stromal cells in the tumour microenvironment challenges medical treatment. Fewer than 20% of patients have surgically resectable disease; however, neoadjuvant therapies might shift tumours towards resectability. Although newer drug combinations and multimodal regimens in this setting, as well as the adjuvant setting, appreciably extend survival, ∼80% of patients will relapse after surgery and ultimately die of their disease. Thus, consideration of quality of life and overall survival is important. In this Primer, we summarize the current understanding of the salient pathophysiological, molecular, translational and clinical aspects of this disease. In addition, we present an outline of potential future directions for pancreatic cancer research and patient management.

15 Review Genetics of pancreatic neuroendocrine tumors: implications for the clinic. 2015

Pea, Antonio / Hruban, Ralph H / Wood, Laura D. ·a 1 Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. ·Expert Rev Gastroenterol Hepatol · Pubmed #26413978.

ABSTRACT: Pancreatic neuroendocrine tumors (PanNETs) are a common and deadly neoplasm of the pancreas. Although the importance of genetic alterations in PanNETs has been known for many years, recent comprehensive sequencing studies have greatly expanded our knowledge of neuroendocrine tumorigenesis in the pancreas. These studies have identified specific cellular processes that are altered in PanNETs, highlighted alterations with prognostic implications, and pointed to pathways for targeted therapies. In this review, we will discuss the genetic alterations that play a key role in PanNET tumorigenesis, with a specific focus on those alterations with the potential to change the way patients with these neoplasms are diagnosed and treated.

16 Review Postoperative Omental Infarct After Distal Pancreatectomy: Appearance, Etiology Management, and Review of Literature. 2015

Javed, Ammar A / Bagante, Fabio / Hruban, Ralph H / Weiss, Matthew J / Makary, Martin A / Hirose, Kenzo / Cameron, John L / Wolfgang, Christopher L / Fishman, Elliot K. ·Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, 600 North Wolfe St, Halsted 608, Baltimore, MD, 21287, USA. · Department of Surgery, Chirurgia Generale e Epatobiliare, G.B. Rossi University Hospital,, University of Verona, Verona, Italy. · Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. · Department of Radiology, The Johns Hopkins Hospital, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD, 21287, USA. efishman@jhmi.edu. ·J Gastrointest Surg · Pubmed #26302877.

ABSTRACT: INTRODUCTION: The clinico-radiological characteristics and the natural history of postoperative omental infarct (OI) in patients who underwent distal pancreatectomy (DP) and splenectomy have not been defined. MATERIALS AND METHODS: Twelve patients who underwent DP over a period of 2 years and were postoperatively diagnosed with OI based on computed tomography (CT) findings were identified. RESULTS: A total of 12 patients were diagnosed with an OI based on their postoperative imaging. Seven (58.3 %) patients had previously undergone laparoscopic DP, one (8.3 %) had undergone a robotic DP, and in one (8.3 %), a laparoscopic DP was converted to an open procedure. The remaining three (25.1 %) were treated with open DP. In five (41.6 %) patients, the diagnosis of OI was made during routine follow-up. One patient underwent surgical resection of OI, and two had drains placed in the mass. Nine patients were managed conservatively. During the study period, on review of CT imaging, the minimum prevalence of postoperative OI after DP was found to be 22.8 %. A review of literature identified nine articles that reported a total of 34 patients who were diagnosed with OI after abdominal surgery. CONCLUSION: The management of an asymptomatic postoperative OI should be conservative while an early invasive intervention should be performed in patients who are symptomatic or have infected OI.

17 Review Genomic landscapes of pancreatic neoplasia. 2015

Wood, Laura D / Hruban, Ralph H. ·The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. ·J Pathol Transl Med · Pubmed #25812653.

ABSTRACT: Pancreatic cancer is a deadly disease with a dismal prognosis. However, recent advances in sequencing and bioinformatic technology have led to the systematic characterization of the genomes of all major tumor types in the pancreas. This characterization has revealed the unique genomic landscape of each tumor type. This knowledge will pave the way for improved diagnostic and therapeutic approaches to pancreatic tumors that take advantage of the genetic alterations in these neoplasms.

18 Review Pathological and molecular evaluation of pancreatic neoplasms. 2015

Rishi, Arvind / Goggins, Michael / Wood, Laura D / Hruban, Ralph H. ·Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD. · Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD. · Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD. Electronic address: rhruban@jhmi.edu. ·Semin Oncol · Pubmed #25726050.

ABSTRACT: Pancreatic neoplasms are morphologically and genetically heterogeneous and include a wide variety of tumors ranging from benign to malignant with an extremely poor clinical outcome. Our understanding of these pancreatic neoplasms has improved significantly with recent advances in cancer sequencing. Awareness of molecular pathogenesis brings new opportunities for early detection, improved prognostication, and personalized gene-specific therapies. Here we review the pathological classification of pancreatic neoplasms from the molecular and genetic perspectives.

19 Review The genetic classification of pancreatic neoplasia. 2015

Matthaei, Hanno / Semaan, Alexander / Hruban, Ralph H. ·Department of General, Visceral, Thoracic and Vascular Surgery, University of Bonn, Bonn, Germany, hannomatthaei@gmail.com. ·J Gastroenterol · Pubmed #25605630.

ABSTRACT: Cancer is caused by the accumulation of inherited and/or acquired alterations in specific genes. The recent decline in the cost of DNA sequencing has allowed tumor sequencing to be conducted on a large scale, which, in turn, has led to an unprecedented understanding of the genetic events that drive neoplasia. This understanding, when integrated with meticulous histologic analyses and with clinical findings, has direct clinical implications. The recent sequencing of all of the major types of cystic and noncystic neoplasms of the pancreas has revealed opportunities for molecular diagnoses and for personalized treatment. This review summarizes the results from these recent studies focusing on the clinical relevance of genomic data.

20 Review Adenocarcinoma of the pancreas. 2014

Hruban, Ralph H / Klimstra, David S. ·Department of Pathology, the Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Weinberg 2242, 401 N Broadway, Baltimore, Maryland 21231; Department of Oncology, the Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: rhruban@jhmi.edu. · Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York. ·Semin Diagn Pathol · Pubmed #25441308.

ABSTRACT: Infiltrating ductal adenocarcinoma of the pancreas is a real enigma. On one hand, it is one of the most deadly of all of the solid malignancies. On the other hand, the neoplastic glands can be remarkably well-differentiated, and it can be difficult to distinguish between a reactive non-neoplastic gland and a gland of invasive adenocarcinoma. In this review, we will present diagnostic criteria that one can "hang your hat on" when establishing the diagnosis of infiltrating ductal adenocarcinoma of the pancreas. We will also review clinically important features of the disease, and, with the impending incorporation of molecular genetics into everyday practice, we will emphasize clinical applications of cancer genetics.

21 Review Solid-pseudopapillary neoplasm of the pancreas: cytomorphologic findings and literature review. 2014

Bhatnagar, Ramneesh / Olson, Matthew T / Fishman, Elliot K / Hruban, Ralph H / Lennon, Anne M / Ali, Syed Z. ·Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Md., USA. ·Acta Cytol · Pubmed #24969629.

ABSTRACT: BACKGROUND: Solid-pseudopapillary neoplasm (SPN) is a rare pancreatic malignancy with an excellent prognosis. It is most commonly diagnosed in young women. This article comprehensively reviews the clinical, pathological and radiological features of this neoplasm, as well as its clinical management. METHODS: A literature review of SPN was performed of all articles published in the English language in PubMed prior to November 1, 2013. Cytomorphological features, histopathology, immunohistochemistry, patient general demographics, molecular studies, radiologic imaging and clinical management were reviewed. RESULTS: SPN displays distinct cytomorphological features on fine-needle aspiration - thin, delicate, branching vessels in a 'Chinese character' pattern lined by one to several layers of loosely cohesive neoplastic cells. Nuclear features include indented or grooved nuclei with an evenly distributed chromatin pattern and small inconspicuous nucleoli. SPN is characteristically immunoreactive for CD10, β-catenin (in an abnormal nuclear pattern), CD99 in a perinuclear dot-like pattern, α1-antitrypsin, and progesterone receptor. Almost all SPNs harbor an activating point mutation in exon 3 of the β-catenin gene (CTNNB1). Clinicopathological features generally do not correlate with prognosis, and most patients experience excellent long-term survival. CONCLUSIONS: SPN can mimic other neoplasms of the pancreas, which can lead to diagnostic challenges in a limited cytologic specimen. Distinct cytomorphological features can help distinguish SPNs from other pancreatic neoplasms. Complete surgical resection as well as resection of metastatic disease is preferred given a low rate of tumor recurrence and long periods of disease-free intervals.

22 Review The early detection of pancreatic cancer: what will it take to diagnose and treat curable pancreatic neoplasia? 2014

Lennon, Anne Marie / Wolfgang, Christopher L / Canto, Marcia Irene / Klein, Alison P / Herman, Joseph M / Goggins, Michael / Fishman, Elliot K / Kamel, Ihab / Weiss, Matthew J / Diaz, Luis A / Papadopoulos, Nickolas / Kinzler, Kenneth W / Vogelstein, Bert / Hruban, Ralph H. ·Authors' Affiliations: Departments of Medicine; Surgery; · Surgery; Pathology; Oncology; · Authors' Affiliations: Departments of Medicine; · Pathology; Oncology; Department of Epidemiology, the Bloomberg School of Public Health, Baltimore, Maryland. · Oncology; Radiation Oncology; and. · Authors' Affiliations: Departments of Medicine; Pathology; Oncology; · Radiology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine; and. · Surgery; · Oncology; · Pathology; Oncology; · Pathology; Oncology; rhruban@jhmi.edu. ·Cancer Res · Pubmed #24924775.

ABSTRACT: Pancreatic cancer is the deadliest of all solid malignancies. Early detection offers the best hope for a cure, but characteristics of this disease, such as the lack of early clinical symptoms, make the early detection difficult. Recent genetic mapping of the molecular evolution of pancreatic cancer suggests that a large window of opportunity exists for the early detection of pancreatic neoplasia, and developments in cancer genetics offer new, potentially highly specific approaches for screening of curable pancreatic neoplasia. We review the challenges of screening for early pancreatic neoplasia, as well as opportunities presented by incorporating molecular genetics into these efforts.

23 Review A systematic review of solid-pseudopapillary neoplasms: are these rare lesions? 2014

Law, Joanna K / Ahmed, Aadil / Singh, Vikesh K / Akshintala, Venkata S / Olson, Matthew T / Raman, Siva P / Ali, Syed Z / Fishman, Elliot K / Kamel, Ihab / Canto, Marcia I / Dal Molin, Marco / Moran, Robert A / Khashab, Mouen A / Ahuja, Nita / Goggins, Michael / Hruban, Ralph H / Wolfgang, Christopher L / Lennon, Anne Marie. ·From the *Division of Gastroenterology, †Department of Pathology, ‡Department of Radiology, Johns Hopkins University School of Medicine, §Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, and ∥Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD. ·Pancreas · Pubmed #24622060.

ABSTRACT: OBJECTIVE: The aim of the study was to determine if there had been any change in the number of solid-pseudopapillary neoplasm (SPN) cases detected and their evaluation or management over time. METHODS: A systematic review of SPN was performed of all articles published in English in PubMed and Scopus. RESULTS: A total of 2744 patients with SPN were identified in 484 studies published between 1961 and 2012; 87.8% of the cases were reported between 2000 and 2012. A total of 2408 (87.8%) were females, and the mean age was 28.5 (SD, 13.7) years. The most common symptom was abdominal pain in 63.6% of the cases and incidentally detected in 38.1% of the cases. There were 2285 patients who underwent pancreatic resection. The mean tumor size was 8.6 (SD, 4.3) cm. Follow-up was reported for 1952 (90.5%) patients, with a mean follow-up of 36.1 (SD, 32.8) months. Disease-free survival was documented in 1866 (95.6%) patients with recurrence in 86 (4.4%) patients; the median time to recurrence was 50.5 months. CONCLUSIONS: The number of SPNs reported in the literature has seen a 7-fold increase in the number of cases reported since 2000 compared with before. Solid-pseudopapillary neoplasms continue to be primarily found in young women and present with nonspecific symptoms. Surgery remains the mainstay of treatment with an excellent long-term prognosis.

24 Review The diagnosis and surgical treatment of pancreatoblastoma in adults: a case series and review of the literature. 2013

Salman, Bulent / Brat, Gabriel / Yoon, Yoo-Seok / Hruban, Ralph H / Singhi, Aatur D / Fishman, Elliot K / Herman, Joseph M / Wolfgang, Christopher L. ·Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA. ·J Gastrointest Surg · Pubmed #24081396.

ABSTRACT: INTRODUCTION: Pancreatoblastoma is an extremely rare pancreatic neoplasm in adults. The aim of this study is to report our experience with adult pancreatoblastoma as well as review the cases reported in the literature in order to provide guidelines for the management of patients with this rare neoplasm. METHODS: We have encountered three cases of pancreatoblastoma in adults at our institution in addition to the 30 cases reported to date in literature. RESULTS: The median age of pancreatoblastoma in adults is 37 years (range, 18-78 years); men and women are similarly affected (male/female = 16/17). The behavior of pancreatoblastoma is clearly that of a malignant neoplasm, with local invasion, recurrence, and metastasis. Among the adult reported cases, at diagnosis or operation, metastasis and/or local invasion was found in 14 of 31 adult patients (46 %) (2 patients had no data) The survival was significantly higher in patients with resected tumor (resection only and resection + adjuvant chemo/radiotherapy) when compared to unresected patients (palliative chemo/radiotherapy and no treatment), (p = 0.008, HR = 0.20). CONCLUSION: When disease is localized, the treatment of choice is a complete surgical resection. The role of adjuvant chemotherapy or radiotherapy is still unclear based on the very small number of patients treated.

25 Review Advancements in pancreatic neuroendocrine tumors. 2013

Sadaria, Miral R / Hruban, Ralph H / Edil, Barish H. ·Department of Surgery, University of Colorado Anschutz Medical Campus, Division of GI, Tumor and Endocrine Surgery, Academic Office One, 12631 East 17th Avenue, C311, Aurora, CO 80045, USA. ·Expert Rev Gastroenterol Hepatol · Pubmed #23899286.

ABSTRACT: Pancreatic neuroendocrine tumors (PanNETs) have increased in incidence in the USA over the last 20 years. Although PanNETs are often misconceived as being indolent tumors as they have a far more favorable prognosis over pancreatic adenocarcinoma, roughly 60-70% of patients have metastatic disease at the time of diagnosis due to presentation late in the disease process. While improvements in imaging modalities allow for early detection and better tumor localization, recent advancements in basic science, as well as surgical and medical management of PanNETs have further improved the prognosis. The mainstay of therapy for localized PanNETs is surgical intervention, which has become safer and is slowly shifting towards a more minimally invasive approach. However, the prognosis still remains relatively bleak for patients with unresectable disease. Fortunately, novel molecular targeted therapies, such as everolimus and sunitinib, have recently come into the limelight and have shown significant promise for the treatment of locally advanced and metastatic disease.

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