Genomic Profiles and Current Therapeutic Agents in Neuroendocrine Neoplasms

2020 ◽  
Vol 21 (4) ◽  
pp. 389-405
Author(s):  
Akihiro Ohmoto ◽  
Chigusa Morizane
Keyword(s):  
Current Knowledge ◽  
Treatment Strategies ◽  
Phase Iii ◽  
World Health ◽  
Standards Of Care ◽  
Neuroendocrine Neoplasms ◽  
Targeted Agents ◽  
Poorly Differentiated ◽  
Molecular Targeted Agents ◽  
Well Differentiated

Neuroendocrine neoplasms (NENs) are rare tumors that mainly occur in the gastroenteropancreatic (GEP) tract and lungs. According to the current World Health Organization classification for GEP-NENs and lung NENs, treatment strategies differ for well-differentiated and poorly differentiated subtypes. For well-differentiated GEP-NENs, somatostatin analogues (SSA), peptide receptor radionuclide therapy, and molecular-targeted agents are approved as the standards of care based on phase III clinical trial data. Promising data regarding the use of everolimus and the novel SSA pasireotide for lung NENs are emerging, though additional studies are required to confirm these effects. For poorly differentiated tumors from the GEP tract and lung, a platinum-based cytotoxic regimen is widely used. Genomic analysis has recently revealed a diverse pattern of primary organ-dependent mutations, and the use of traditional treatment strategies versus organ-specific strategies is currently under discussion. In addition, clinical trials for several molecular-targeted agents and immune checkpoint inhibitors for the treatment of NENs are currently underway. Accumulating genomic information is expected to contribute to the development of novel therapies for other organ-derived NENs or poorly differentiated neuroendocrine carcinomas (NECs). Here, we provide an updated overview of the current knowledge regarding genomic profiles and representative agents for NENs and highlight the prospects for future investigations.

scholarly journals HIGH-GRADE GASTROENTEROPANCREATIC NEUROENDOCRINE NEOPLASMS. MODERN CLASSIFICATION, DIAGNOSTICS AND TREATMENT

2018 ◽  
Vol 8 (3) ◽  
pp. 13-20
Author(s):  
A. A. Kolomeytseva ◽  
V. A. Gorbunova ◽  
N. F. Orel ◽  
G. S. Emelianova ◽  
A. M. Ivanov ◽  
...  
Keyword(s):  
World Health ◽  
Neuroendocrine Neoplasms ◽  
Ki 67 ◽  
First Line Therapy ◽  
Gastroenteropancreatic Neuroendocrine Neoplasms ◽  
Platinum Based Chemotherapy ◽  
Poorly Differentiated ◽  
Net G3 ◽  
Well Differentiated ◽  
Health Organization

Poorly differentiated gastroenteropancreatic neuroendocrine neoplasms (GEP NENs) are rare malignancies, most of which are characterized by aggressiveness, a tendency to rapid metastasis and an unfavorable prognosis even when localized. In 2017 World Health Organization (WHO) updated classification of GEP NENs and recognized the category of well-differentiated pancreatic NET G3, associated with Ki‑67 index usually over 20%. The upper level of Ki‑67 is not defined. Usually it is 55%. Highgrade poorly differentiated pancreatic NENs are defined as pancreatic neuroendocrine carcinomas (panNECs). Although the NET G3 category is recognized for pancreatic neuroendocrine neoplasms only, many specialists consider it reasonable to apply this term to all well-differentiated GEP NETs with Ki‑67 index in the 20 to 55 percent range. Clinical behavior and therapeutic approaches for advanced GEP NECs and NETs G3 are different. Standard palliative chemotherapy for GEP NECs consists of cisplatin or carboplatin combined with etoposide. The second-line regimens include irinotecan-, oxaliplatin, fluoropyrimidine- and temozolomide-based regimens. Temozolomide-based chemotherapy regimens, as well as targeted therapy are more preferable as first line therapy for patients with NETs G3. The platinum-based chemotherapy regimens are considered at the time of disease progression. Further clinical studies with the inclusion of much more patients will determine the optimal treatment strategy for this category of patients.

scholarly journals Non-Vertical Exposures to HIV, HBV and HCV Infection in Children and Adolescents—Risk of Infection, Standards of Care and Postexposure Prophylaxis

2021 ◽  
Vol 13 (4) ◽  
pp. 566-575
Author(s):  
Anna Tomasik ◽  
Maria Pokorska-Śpiewak ◽  
Magdalena Marczyńska
Keyword(s):  
Current Knowledge ◽  
Pediatric Population ◽  
Hcv Infection ◽  
World Health ◽  
Standards Of Care ◽  
Post Exposure Prophylaxis ◽  
Risk Of Infection ◽  
Postexposure Prophylaxis ◽  
Hepatitis C Infection

Introduction: in the review, we aimed to present current knowledge about the risk of infection, standards of care, and postexposure prophylaxis (PEP) in pediatric patients after non-vertical exposures to HIV, HBV, and HCV infection. Materials and Methods: the latest available literature and recommendations of Centers for Disease Control and Prevention (CDC), World Health Organization (WHO), European recommendations for the management of HIV and administration of non-occupational PEP, and Polish AIDS Society were reviewed. Results: the majority of cases of non-vertical exposure to blood-borne viruses in the pediatric population consist of sexual exposition and injection with unsterilized sharp objects (usually needlestick injuries). The risk HIV, HBV, and HCV transmission depend on several factors, and each exposure should be evaluated individually with consideration of the patient’s medical history. It is crucial to start antiretroviral therapy within 48 h from exposure. Treatment is continued for 28 days, and a 3-drugs regiment is recommended in the majority of cases. Decisions on hepatitis B and tetanus PEP are based on a history of vaccination. There is no PEP for hepatitis C infection, follow-up testing aims for early identification of disease and consideration of treatment options. Conclusion: all children after the non-vertical exposure to HIV, HBV, and HCV infection should be evaluated by the Infectious Disease specialist as soon as possible after the incident and qualified to post-exposure prophylaxis. Systematic diagnostic and follow-up on children after significant needlestick exposure should be maintained. Children after sexual exposure need a multidisciplinary approach. Response to reported event must be rapid and treatment must be comprehensive.

Giant Primary Neuroendocrine Neoplasms of the Liver: Report of 2 Cases With Molecular Characterization

2019 ◽  
Vol 27 (8) ◽  
pp. 893-899
Author(s):  
Laura G. Pastrián ◽  
Ignacio Ruz-Caracuel ◽  
Raul S. Gonzalez
Keyword(s):  
World Health Organization ◽  
Neuroendocrine Tumor ◽  
Large Cell ◽  
The Other ◽  
World Health ◽  
Neuroendocrine Neoplasms ◽  
Molecular Testing ◽  
Well Differentiated ◽  
Grade 3 ◽  
Health Organization

Primary neuroendocrine neoplasms of the liver have occasionally been reported in the liver, though many reports do not convincingly exclude metastases. In this article, we report 2 “giant” hepatic neuroendocrine lesions without evidence of a primary elsewhere after clinical workup. One occurred in a 21-year-old male; the lesion was a large cell neuroendocrine carcinoma measuring 24 cm. The patient died of disease in 10 months. The other occurred in a 25-year-old patient, was 18 cm wide, and was diagnosed as a well-differentiated neuroendocrine tumor, World Health Organization grade 3. The patient died of disease after 30 months. Molecular testing demonstrated only the presence of TP53 mutations in common. These cases expand our knowledge of seemingly primary neuroendocrine neoplasms of the liver, in particular, giant cases measuring more than 8 cm. Guidelines for clinical workup and therapy for these lesions remain unclear, but future thorough workup of such cases is necessary for specific characterization.

scholarly journals INSM1 Is a Highly Specific Marker of Neuroendocrine Differentiation in Primary Neoplasms of the Gastrointestinal Tract, Appendix, and Pancreas

2020 ◽  
Vol 153 (6) ◽  
pp. 811-820 ◽  
Author(s):  
Kelsey E McHugh ◽  
Sanjay Mukhopadhyay ◽  
Erika E Doxtader ◽  
Christopher Lanigan ◽  
Daniela S Allende
Keyword(s):  
Goblet Cell ◽  
Neuroendocrine Differentiation ◽  
Neuroendocrine Neoplasms ◽  
Specific Marker ◽  
Low Grade ◽  
Ki 67 ◽  
Neuroendocrine Markers ◽  
Primary Neoplasms ◽  
Poorly Differentiated ◽  
Well Differentiated

Abstract Objectives INSM1 has been described as a sensitive and specific neuroendocrine marker. This study aims to compare INSM1 with traditional neuroendocrine markers in gastrointestinal neuroendocrine neoplasms. Methods Retrospective review (2008-2018) was used to retrieve paraffin-embedded tissue from 110 gastrointestinal neuroendocrine neoplasms and controls that was subsequently stained with INSM1, synaptophysin, chromogranin, CD56, and Ki-67. Results INSM1 was positive in 16 of 17 (94.1%) gastric, 17 of 18 (94.4%) pancreatic, 13 of 18 (72.2%) small bowel, 17 of 21 (81.0%) colonic, and 26 of 36 (72.2%) appendiceal tumors. INSM1 was positive in 58 of 70 (82.9%) well-differentiated neuroendocrine tumors, 17 of 20 (85.0%) poorly differentiated neuroendocrine carcinomas, 8 of 11 (72.7%) low-grade goblet cell adenocarcinomas (grade 1), and 6 of 9 (66.7%) high-grade goblet cell adenocarcinomas (grade 2/3). INSM1 sensitivity for neuroendocrine neoplasms (80.9%) was less than that of synaptophysin (99.1%), chromogranin (88%), and CD56 (95.3%); specificity was higher (95.7% vs 86.0%, 87.3%, and 86.0%, respectively). Conclusions INSM1 is a useful marker of neuroendocrine differentiation in gastrointestinal neuroendocrine and mixed neuroendocrine neoplasms. Compared with traditional neuroendocrine markers, INSM1 is less sensitive but more specific.

scholarly journals Co-existence of gastric adenocarcinoma and neuroendocrine carcinoma: a rare entity

2017 ◽  
Vol 7 (2) ◽  
pp. 1221-1223 ◽  
Author(s):  
Nirajan Mainali ◽  
Niraj Nepal ◽  
Prabesh Kumar Choudhary ◽  
Amrita Sinha ◽  
Saroj Rajbanshi ◽  
...  
Keyword(s):  
Neuroendocrine Carcinoma ◽  
Partial Gastrectomy ◽  
Endoscopic Biopsy ◽  
World Health ◽  
Neuroendocrine Neoplasms ◽  
World Health Organization Classification ◽  
Well Differentiated ◽  
Health Organization ◽  
Histopathology Examination

A mixed adenoneuroendocrine carcinoma is a tumor composed of both adenocarcinoma and neuroendocrine carcinoma components, with each comprising  at least one-third of the lesion, as defined by the World Health Organization classification of neuroendocrine neoplasms in 2010.. A 67-years-old male was admitted to the hospital with symptoms suggesting gastric cancer. Histopathology examination from endoscopic biopsy revealed adenocarcinoma. Later partial gastrectomy specimen examination the lesion show presence of well differentiated adenocarcinoma along with neuro endocrine carcinoma.

Classification and pathology of gastroenteropancreatic neuroendocrine neoplasms

2011 ◽  
Vol 18 (S1) ◽  
pp. S1-S16 ◽  
Author(s):  
Günter Klöppel
Keyword(s):  
Gastrointestinal Tract ◽  
Neuroendocrine Tumours ◽  
Neuroendocrine Tumour ◽  
Tnm Stage ◽  
Neuroendocrine Neoplasms ◽  
Gastroenteropancreatic Neuroendocrine Neoplasms ◽  
Poorly Differentiated ◽  
Well Differentiated ◽  
Neuroendocrine Carcinomas

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are composed of cells with a neuroendocrine phenotype. The old and the new WHO classifications distinguish between well-differentiated and poorly differentiated neoplasms. All well-differentiated neoplasms, regardless of whether they behave benignly or develop metastases, will be called neuroendocrine tumours (NETs), and graded G1 (Ki67 <2%) or G2 (Ki67 2–20%). All poorly differentiated neoplasms will be termed neuroendocrine carcinomas (NECs) and graded G3 (Ki67 >20%). To stratify the GEP-NETs and GEP-NECs regarding their prognosis, they are now further classified according to TNM-stage systems that were recently proposed by the European Neuroendocrine Tumour Society (ENETS) and the AJCC/UICC. In the light of these criteria the pathology and biology of the various NETs and NECs of the gastrointestinal tract (including the oesophagus) and the pancreas are reviewed.

Report of an International Psychogeriatric Association Special Meeting Work Group; Under the Cosponsorship of Alzheimer's Disease International, the European Federation of Neurological Societies, the World Health Organization, and the World Psychiatric Association

1997 ◽  
Vol 9 (S1) ◽  
pp. 11-38 ◽  
Author(s):  
Barry Reisberg ◽  
Alistair Burns ◽  
Henry Brodaty ◽  
Robin Eastwood ◽  
Martin Rossor ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Current Knowledge ◽  
Work Group ◽  
Treatment Strategies ◽  
Diagnostic Procedures ◽  
World Health ◽  
Diagnostic Process ◽  
European Federation ◽  
The World

Current knowledge with respect to the diagnosis of Alzheimer's disease (AD) is reviewed. There is agreement that AD is a characteristic clinicopathologic entity that is amenable to diagnosis. The diagnosis of AD should no longer be considered one of exclusion. Rather, the diagnostic process is one of recognition of the characteristic features of AD and of conditions that can have an impact on presentation or mimic aspects of the clinicopathologic picture. The present availability of improved prognosis, management, and treatment strategies makes the proper, and state-of-the-art, diagnosis of AD a clinical imperative in all medical settings. Concurrently, information regarding the relevance and applicability of current diagnostic procedures in diverse cultural settings must continue to accrue.

scholarly journals Interaction of Radiation Therapy With Molecular Targeted Agents

2014 ◽  
Vol 32 (26) ◽  
pp. 2886-2893 ◽  
Author(s):  
Zachary S. Morris ◽  
Paul M. Harari
Keyword(s):  
Clinical Investigation ◽  
Growth Factor Receptor ◽  
Clinical Trial Design ◽  
Systematic Investigation ◽  
Phase Iii ◽  
Targeted Therapeutics ◽  
Targeted Agents ◽  
Clinical Value ◽  
Cellular Mechanics ◽  
Molecular Targeted Agents

The development of molecular targeted therapeutics in oncology builds on many years of scientific investigation into the cellular mechanics of malignant transformation and progression. The past two decades have brought an accelerating pace to the clinical investigation of new molecular targeted agents, particularly in the setting of metastatic disease. The integration of molecular targeted agents into phase III clinical trial design has lagged in the curative treatment setting, particularly in combination with established therapeutic modalities such as radiation. In this review, we discuss the interaction of radiation and molecular targeted therapeutics. The dynamics of cellular and tumor response to radiation offer unique opportunities for beneficial interplay with molecular targeted agents that may go unrecognized with conventional screening and monotherapy clinical testing of novel agents. By using epidermal growth factor receptor (EGFR) as a primary example, we discuss recent clinical studies that illustrate the potential synergy of molecular targeted agents with radiation and highlight the clinical value of such interactions. For various molecular targeted agents, their greatest clinical impact may rest in combination with radiation, and efforts to facilitate systematic investigation of this approach appear highly warranted.

scholarly journals An Overview of the Epidemiologic, Diagnostic and Treatment Approaches of COVID-19: What do We Know?

2021 ◽  
Vol 42 ◽  
Author(s):  
Hanieh Beyrampour-Basmenj ◽  
Morteza Milani ◽  
Abbas Ebrahimi-Kalan ◽  
Ziyad Ben Taleb ◽  
Kenneth D Ward ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
World Health ◽  
Treatment Approaches ◽  
Number Of Patients ◽  
Control And Prevention ◽  
History Of ◽  
Health Organization ◽  
Available Information

Background: In late December 2019, a new infectious respiratory disease (COVID-19) was reported in a number of patients with a history of exposure to the Huanan seafood market in China. The World Health Organization officially announced the COVID-19 pandemic on March 11, 2020. Here, we provided an overview of the epidemiologic, diagnostic and treatment approaches associated with COVID-19.Methods: We reviewed the publications indexed in major biomedical databases by December 20, 2020 or earlier (updated on May 16, 2021). Search keywords included a combination of: COVID-19, Coronavirus disease 2019, SARS-CoV-2, Epidemiology, Prevention, Diagnosis, Vaccine, and Treatment. We also used available information about COVID-19 from valid sources such as WHO.Results and Conclusion: At the time of writing this review, while most of the countries authorized COVID-19 vaccines for emergency use starting December 8, 2020, there is no a definite cure for it. This review synthesizes current knowledge of virology, epidemiology, clinical symptoms, diagnostic approaches, common treatment strategies, novel potential therapeutic options for control and prevention of COVID-19 infection, available vaccines, public health and clinical implications.

scholarly journals Pancreatic Neuroendocrine Neoplasms: Landscape and Horizon

2020 ◽  
Vol 144 (7) ◽  
pp. 816-828
Author(s):  
Laura H. Tang
Keyword(s):  
Neuroendocrine Neoplasms ◽  
Specific Gene ◽  
Important Distinction ◽  
Pancreatic Neuroendocrine Neoplasms ◽  
Poorly Differentiated Neuroendocrine Carcinoma ◽  
Poorly Differentiated ◽  
Well Differentiated ◽  
Initial Description ◽  
Definition Of ◽  
Hereditary Conditions

Context.— Since the initial description of pancreatic endocrine physiology and the recognition of islet cell tumors in the 1800s, there have been noteworthy advances in the pathobiology of pancreatic neuroendocrine neoplasms (PanNENs), and definition of the important distinction between well-differentiated neuroendocrine tumor (PanNET) and poorly differentiated neuroendocrine carcinoma (PanNEC). The evolving knowledge has resulted in a continuous update in terminology, classification, and grading system for this group of neoplasms. Pancreatic neuroendocrine tumors associated with hereditary conditions have been linked to unique molecular and genetic events, and sporadic PanNETs have specific gene signatures. Based on accumulative experience and knowledge, therapeutic strategies have been defined for this group of neoplasms. Objective.— To review the evolution and description of the pathologic-genomic evolution of PanNENs, and to facilitate accurate pathologic interpretation for the corresponding clinical management. Data Sources.— Literature review of published studies and author's own work. Conclusions.— Evolving experience and knowledge have established subtypes of pancreatic neuroendocrine neoplasms, based on their genotype and phenotype. Accurate pathologic interpretation of the specific neoplasm has significant implications for therapy and prognosis.

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