scholarly journals Bone Metastases in Neuroendocrine Neoplasms: From Pathogenesis to Clinical Management

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1332 ◽  
Author(s):  
Barbara Altieri ◽  
Carla Di Dato ◽  
Chiara Martini ◽  
Concetta Sciammarella ◽  
Antonella Di Sarno ◽  
...  
Keyword(s):  
Bone Metastases ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Imaging Techniques ◽  
Case Reports ◽  
Treatment Options ◽  
Neuroendocrine Neoplasms ◽  
Positron Emission ◽  
Late Event ◽  
Skeletal Complications

Bone represents a common site of metastases for several solid tumors. However, the ability of neuroendocrine neoplasms (NENs) to localize to bone has always been considered a rare and late event. Thanks to the improvement of therapeutic options, which results in longer survival, and of imaging techniques, particularly after the introduction of positron emission tomography (PET) with gallium peptides, the diagnosis of bone metastases (BMs) in NENs is increasing. The onset of BMs can be associated with severe skeletal complications that impair the patient’s quality of life. Moreover, BMs negatively affect the prognosis of NEN patients, bringing out the lack of curative treatment options for advanced NENs. The current knowledge on BMs in gastro-entero-pancreatic (GEP) and bronchopulmonary (BP) NENs is still scant and is derived from a few retrospective studies and case reports. This review aims to perform a critical analysis of the evidence regarding the role of BMs in GEP- and BP-NENs, focusing on the molecular mechanisms underlining the development of BMs, as well as clinical presentation, diagnosis, and treatment of BMs, in an attempt to provide suggestions that can be used in clinical practice.

scholarly journals Degenerative Cervical Myelopathy: Insights into Its Pathobiology and Molecular Mechanisms

2021 ◽  
Vol 10 (6) ◽  
pp. 1214
Author(s):  
Ji Tu ◽  
Jose Vargas Castillo ◽  
Abhirup Das ◽  
Ashish D. Diwan
Keyword(s):  
Cervical Myelopathy ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Imaging Techniques ◽  
Disease Process ◽  
Classification Systems ◽  
Molecular Features ◽  
Formidable Challenge ◽  
Long Term Treatment ◽  
Degenerative Cervical Myelopathy

Degenerative cervical myelopathy (DCM), earlier referred to as cervical spondylotic myelopathy (CSM), is the most common and serious neurological disorder in the elderly population caused by chronic progressive compression or irritation of the spinal cord in the neck. The clinical features of DCM include localised neck pain and functional impairment of motor function in the arms, fingers and hands. If left untreated, this can lead to significant and permanent nerve damage including paralysis and death. Despite recent advancements in understanding the DCM pathology, prognosis remains poor and little is known about the molecular mechanisms underlying its pathogenesis. Moreover, there is scant evidence for the best treatment suitable for DCM patients. Decompressive surgery remains the most effective long-term treatment for this pathology, although the decision of when to perform such a procedure remains challenging. Given the fact that the aged population in the world is continuously increasing, DCM is posing a formidable challenge that needs urgent attention. Here, in this comprehensive review, we discuss the current knowledge of DCM pathology, including epidemiology, diagnosis, natural history, pathophysiology, risk factors, molecular features and treatment options. In addition to describing different scoring and classification systems used by clinicians in diagnosing DCM, we also highlight how advanced imaging techniques are being used to study the disease process. Last but not the least, we discuss several molecular underpinnings of DCM aetiology, including the cells involved and the pathways and molecules that are hallmarks of this disease.

scholarly journals Multimodality imaging in carcinoid heart disease

Open Heart ◽  
2019 ◽  
Vol 6 (1) ◽  
pp. e001060 ◽  
Author(s):  
Ali M Agha ◽  
Juan Lopez-Mattei ◽  
Teodora Donisan ◽  
Dinu Balanescu ◽  
Cezar A Iliescu ◽  
...  
Keyword(s):  
Heart Disease ◽  
Carcinoid Syndrome ◽  
Multimodality Imaging ◽  
Imaging Techniques ◽  
Neuroendocrine Neoplasms ◽  
Carcinoid Heart Disease ◽  
Imaging Studies ◽  
Diagnosis And Prognosis ◽  
Positron Emission ◽  
Integral Role

Neuroendocrine neoplasms arise from the gastrointestinal tract and can lead to carcinoid syndrome. Carcinoid heart disease affects more than half of these patients and is the initial presentation of carcinoid syndrome in up to 20 % of patients. Carcinoid heart disease typically leads to valve dysfunction, but in rare instances, carcinoid tumours can also metastasise to the endocardium and myocardium. Cardiovascular imaging plays an integral role in the diagnosis and prognosis of carcinoid heart disease. The use of multimodality imaging techniques including echocardiography, cardiac MRI, cardiovascular CT and positron emission tomography have allowed for a more comprehensive assessment of carcinoid heart disease. In this review, we discuss the features of carcinoid heart disease observed on multimodality imaging, indications for obtaining imaging studies and their role in carcinoid heart disease management.

scholarly journals The Role of Imaging in Radiation Therapy Planning: Past, Present, and Future

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Gisele C. Pereira ◽  
Melanie Traughber ◽  
Raymond F. Muzic
Keyword(s):  
Treatment Planning ◽  
Planning Process ◽  
Imaging Modality ◽  
Imaging Techniques ◽  
Treatment Options ◽  
Three Dimensional ◽  
Dose Calculation ◽  
Positron Emission ◽  
Tissue Contrast ◽  
Anatomical Information

The use of ionizing radiation for cancer treatment has undergone extraordinary development during the past hundred years. The advancement of medical imaging has been critical in helping to achieve this change. The invention of computed tomography (CT) was pivotal in the development of treatment planning. Despite some disadvantages, CT remains the only three-dimensional imaging modality used for dose calculation. Newer image modalities, such as magnetic resonance (MR) imaging and positron emission tomography (PET), are also used secondarily in the treatment-planning process. MR, with its better tissue contrast and resolution than those of CT, improves tumor definition compared with CT planning alone. PET also provides metabolic information to supplement the CT and MR anatomical information. With emerging molecular imaging techniques, the ability to visualize and characterize tumors with regard to their metabolic profile, active pathways, and genetic markers, both across different tumors and within individual, heterogeneous tumors, will inform clinicians regarding the treatment options most likely to benefit a patient and to detect at the earliest time possible if and where a chosen therapy is working. In the post-human-genome era, multimodality scanners such as PET/CT and PET/MR will provide optimal tumor targeting information.

scholarly journals How I treat extramedullary myeloma

Blood ◽  
2016 ◽  
Vol 127 (8) ◽  
pp. 971-976 ◽  
Author(s):  
Cyrille Touzeau ◽  
Philippe Moreau
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Median Overall Survival ◽  
Molecular Mechanisms ◽  
Plasma Cells ◽  
Imaging Techniques ◽  
Lactate Dehydrogenase Level ◽  
Altered Expression ◽  
Positron Emission ◽  
Extramedullary Relapse

Abstract Extramedullary myeloma (EMM) is defined by the presence of plasma cells (PCs) outside the bone marrow in a patient with multiple myeloma (MM). Using sensitive imaging techniques including magnetic resonance imaging and positron emission tomography/computed tomography, EMM may be found in up to 30% of MM patients across the overall disease course. The molecular mechanisms underlying the hematogenous spread of PCs outside the bone marrow are only partially known and involve hypoxia and an altered expression of adhesion molecules. Extramedullary disease is associated with adverse prognostic factors (ie, high lactate dehydrogenase level, 17p deletion, and high-risk gene expression profile). The prognosis of EMM is poor, and the median overall survival of patients who experience an extramedullary relapse is <6 months. The adverse prognosis is less pronounced in patients with bone-related plasmacytomas than in those with hematogenous EMM. EMM patients should be considered as having high-risk myeloma and treated accordingly. However, EMM clinical situations are extraordinarily heterogeneous, and their management is particularly challenging. In the present review, a case-and-comment format is used to describe our approach to the management of EMM.

Gastroenteropancreatic Neuroendocrine Neoplasms (GEP NENs) : The Role of Checkpoint Inhibitors

2022 ◽  
Vol 22 ◽  
Author(s):  
Giulia Arrivi ◽  
Nicola Fazio
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Response Assessment ◽  
Neuroendocrine Neoplasms ◽  
Precision Oncology ◽  
Disease Characteristics

Background: The treatment options for GEP-NENs includes various drugs and is based on grading, morphology and location of the primary Objective: The aim of our work is to investigate the clinical impact of new immune checkpoint inhibitors in order to define a new possible strategy of use within GEP-NENs. Method: A scientific literature search from 2015 to January 2020 was performed by using PubMed and Embase: reviews and prospective or retrospective studies with a minimum of twenty patients were selected; conference proceedings were included Results: several studies have been conducted to assess the role of immune checkpoint inhibitors in NENs, but nowadays the current knowledge in this field is mainly based on a phase I-II studies. Immunotherapy showed limited antitumor activity, but higher response rate was reported in poor-differentiated neuroendocrine tumors. No specific biomarkers were identified for patient selection and response assessment Conclusion: Immunotherapy appears as a powerful possibility to help our patients, but nowadays we see many gaps in this field. We must balance therapeutic possibility offered by precision oncology with the understanding the limitations of application of testing and treatment in clinical practice. Future efforts should focus on research of the best patients to candidate for immunotherapy in term of disease characteristics and previous treatments, and how to select them with accurate biomarkers.

Congenital hyperinsulinism: recent updates on molecular mechanisms, diagnosis and management

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Dinesh Giri ◽  
Katherine Hawton ◽  
Senthil Senniappan
Keyword(s):  
Molecular Genetics ◽  
Intrauterine Growth Restriction ◽  
Molecular Mechanisms ◽  
Imaging Techniques ◽  
Birth Asphyxia ◽  
Maternal Diabetes ◽  
Congenital Hyperinsulinism ◽  
Positron Emission ◽  
Computed Tomography Scanning ◽  
Tomography Scanning

Abstract Congenital hyperinsulinism (CHI) is a rare disease characterized by an unregulated insulin release, leading to hypoglycaemia. It is the most frequent cause of persistent and severe hypoglycaemia in the neonatal period and early childhood. Mutations in 16 different key genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, UCP2, HNF4A, HNF1A, HK1, KCNQ1, CACNA1D, FOXA2, EIF2S3, PGM1 and PMM2) that are involved in regulating the insulin secretion from pancreatic β-cells have been described to be responsible for the underlying molecular mechanisms of CHI. CHI can also be associated with specific syndromes and can be secondary to intrauterine growth restriction (IUGR), maternal diabetes, birth asphyxia, etc. It is important to diagnose and promptly initiate appropriate management as untreated hypoglycaemia can be associated with significant neurodisability. CHI can be histopathologically classified into diffuse, focal and atypical forms. Advances in molecular genetics, imaging techniques (18F-fluoro-l-dihydroxyphenylalanine positron emission tomography/computed tomography scanning), novel medical therapies and surgical advances (laparoscopic pancreatectomy) have changed the management and improved the outcome of patients with CHI. This review article provides an overview of the background, clinical presentation, diagnosis, molecular genetics and therapy for children with different forms of CHI.

scholarly journals Evolving Castration Resistance and Prostate Specific Membrane Antigen Expression: Implications for Patient Management

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3556
Author(s):  
Katharina Kessel ◽  
Christof Bernemann ◽  
Martin Bögemann ◽  
Kambiz Rahbar
Keyword(s):  
Prostate Cancer ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Treatment Options ◽  
Antigen Expression ◽  
Diagnostic Process ◽  
Prostate Specific Membrane Antigen ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance ◽  
Specific Membrane

Metastatic castration-resistant prostate cancer (mCRPC) remains an incurable disease, despite multiple novel treatment options. The role of prostate-specific membrane antigen (PSMA) in the process of mCRPC development has long been underestimated. During the last years, a new understanding of the underlying molecular mechanisms of rising PSMA expression and its association with disease progression has emerged. Accurate understanding of these complex interactions is indispensable for a precise diagnostic process and ultimately successful treatment of advanced prostate cancer. The combination of different novel therapeutics such as androgen deprivation agents, 177LU-PSMA radioligand therapy and PARP inhibitors promises a new kind of efficacy. In this review, we summarize the current knowledge about the most relevant molecular mechanisms around PSMA in mCRPC development and how they can be implemented in mCRPC management.

scholarly journals Functional Evaluation of KEL As An Oncogenic Gene in The Progression of Acute Erythroleukemia

2021 ◽  
Author(s):  
Zijuan Wu ◽  
Wenjie Liu ◽  
Yan Yu ◽  
Chun Qiao ◽  
Han Zhu ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Treatment Options ◽  
Biological Significance ◽  
Erythroid Differentiation ◽  
Regulation Mechanism ◽  
Functional Evaluation ◽  
Aberrant Expression ◽  
Promising Therapeutic Target ◽  
Luciferase Activity Assay

Abstract Background Acute erythroleukemia (AEL) is an infrequent subtype of acute myeloid leukemia (AML) with worse prognosis. Though the last decade has seen major advances in the novel features and genomic landscape in AEL, there is still a lack of specific therapeutic targets and effective treatment approaches for this disease. MethodsTCGA database was used to screen out the oncogene with specifically aberrant expression in AEL. Protein array was performed to explore the activated signaling pathways and targets that undergo phosphorylation modulation. A series of functional analyses in cell lines and mice models were performed to investigate the biological significance and clinical relevance of KEL regulation in AEL. CHIP, EMSA and dual-luciferase activity assay were performed to explore the upstream regulation mechanism of KEL.ResultsIn this study, the results showed that KEL promoted cell proliferation and its downregulation reversed drug resistance in AEL cells to JQ1. Our findings suggested that KEL contributed to gain of H3K27 acetylation and promoted erythroid differentiation induced by GATA1. Additionally, GATA1 and TAL1 as co-Transcription factors (TFs) modulated the expression of KEL. Maintaining cell viability and differentiation, KEL also played parts in the immune evasion of tumor cells. ConclusionsOur work expands the current knowledge regarding molecular mechanisms involved in cancer onset and progression, offering promising therapeutic target to broaden the treatment options.

Neuroendocrine tumour of the ampulla of Vater: a rare neoplasm at an atypical site

2020 ◽  
pp. 1-10
Author(s):  
Abrar Zahid ◽  
Danish Ali ◽  
Muhammad Zubair ◽  
Irfan Ahmed ◽  
Tauseef Fatima ◽  
...  
Keyword(s):  
Weight Loss ◽  
Immunohistochemical Staining ◽  
Poor Prognosis ◽  
Carcinoid Syndrome ◽  
Neuroendocrine Tumour ◽  
Carcinoid Tumour ◽  
Treatment Options ◽  
Ampulla Of Vater ◽  
Neuroendocrine Neoplasms ◽  
Late Event

Abstract The periampullary neuroendocrine tumour is an infrequently occurring tumour. Its prevalence among gastrointestinal neuroendocrine neoplasms is less than 0.3%, and less than 2% out of periampullary tumours. These neoplasms have relatively poor prognosis. Jaundice and pain in the abdomen are the early and most commonly occurring symptoms with weight loss being a late event. The carcinoid syndrome presents infrequently in periampullary neuroendocrine tumour and happens only if hepatic metastasis occurs. In this scenario, histopathology plays a paramount role in the diagnosis. Specific immunohistochemical staining is used for diagnosis while the treatment options are local excision, endoscopic excision and pancreaticoduodenectomy. Here is a case report of a 42-year-old patient who presented with complaint of obstructive jaundice for one month. Periampullary carcinoid tumour was diagnosed on biopsy, and she underwent Pancreaticoduodenectomy as treatment. Continuou...  

scholarly journals Superioridade da PET/CT com FNa-F18 na Deteção de Metástases Ósseas quando Comparada com Outros Métodos de Diagnóstico por Imagem

2017 ◽  
Vol 30 (1) ◽  
pp. 53 ◽  
Author(s):  
Paula Lapa ◽  
Tiago Saraiva ◽  
Rodolfo Silva ◽  
Margarida Marques ◽  
Gracinda Costa ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Positron Emission Tomography ◽  
Bone Metastases ◽  
Bone Scintigraphy ◽  
Imaging Modality ◽  
Imaging Techniques ◽  
Emission Tomography ◽  
Skeletal Metastases ◽  
Positron Emission ◽  
18F Fdg

Introduction: The 18F-NaF positron emission tomography/computed tomography is being considered as an excellent imaging modalityfor bone metastases detection. This ability was compared with other imaging techniques.Material and Methods: We retrospectively evaluated 114 patients who underwent 18F-NaF positron emission tomography/ computed tomography. Of these, 49 patients also had bone scintigraphy, 61 18F-FDG positron emission tomography/computed tomography and 10 18F-FCH positron emission tomography/computed tomography. We identified the technique that detected the largest number of bone metastases. For the detection of skeletal metastases with the 18F-NaF positron emission tomography/computed tomography study,the contribution of the positron emission tomography component was compared with the contribution of the computed tomography component. Cases in which 18F-NaF positron emission tomography/computed tomography and bone scintigraphy required further additional tests for diagnosis clarification were registered.Results: The 18F-NaF positron emission tomography/computed tomography was superior to bone scintigraphy in 49% of the patients(p < 0.001); it was superior to 18F-FDG positron emission tomography/computed tomography in 59% of the patients (p < 0.001) and it was superior to 18F-FCH positron emission tomography/computed tomography in 40% of the patients (p < 0.001). None of the compared imaging techniques were superior to 18F-NaF positron emission tomography/computed tomography. The positron emission tomography component was superior to computed tomography in 35% of the cases (p < 0.001). Further investigation was suggested in only 3.5% of patients who underwent 18F-NaF positron emission tomography/computed tomography (45% for bone scintigraphy) (p < 0.001).Discussion: As with other authors, our experience also confirms that 18F-NaF positron emission tomography/computed tomography is an excellent imaging modality for the detection of bone metastases, detecting lesions in more patients and more lesions per patient.Conclusion: The 18F-NaF positron emission tomography/computed tomography showed a superior ability for the detection of bone metastases when compared with bone scintigraphy, 18F-FDG positron emission tomography/computed tomography and 18F-FCH positron emission tomography/computed tomography.

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