scholarly journals Comprehensive review of evaluation and management of cardiac paragangliomas

Heart ◽  
2020 ◽  
Vol 106 (16) ◽  
pp. 1202-1210 ◽  
Author(s):  
Sri Harsha Tella ◽  
Abhishek Jha ◽  
David Taïeb ◽  
Keith A Horvath ◽  
Karel Pacak
Keyword(s):  
Therapeutic Strategy ◽  
Neuroendocrine Tumour ◽  
Optimal Outcomes ◽  
Positron Emission ◽  
Clinical Scenarios ◽  
Dehydrogenase Enzyme ◽  
Genes Encoding ◽  
Enzyme Subunits ◽  
Anatomic Information ◽  
Rule Out

Cardiac paraganglioma (PGL) is a rare neuroendocrine tumour causing significant morbidity primarily due to norepinephrine secretion potentially causing severe hypertension, palpitations, lethal tachyarrhythmias, stroke and syncope. Cardiologists are faced with two clinical scenarios. The first is the elevated norepinephrine, whose actions must be properly counteracted by adrenoceptor blockade to avoid catastrophic consequences. The second is to evaluate the precise location of a cardiac PGL and its spread since compression of cardiovascular structures may result in ischaemia, angina, non-noradrenergic-induced arrhythmia, cardiac dysfunction or failure. Thus, appropriate assessment of elevated norepinephrine by its metabolite normetanephrine is a gold biochemical standard at present. Furthermore, dedicated cardiac CT, MRI and transthoracic echocardiogram are necessary for the precise anatomic information of cardiac PGL. Moreover, a cardiologist needs to be aware of advanced functional imaging using 68Ga-DOTA(0)-Tyr(3)-octreotide positron emission tomography/CT, which offers the best cardiac PGL-specific diagnostic accuracy and helps to stage and rule out metastasis, determining the next therapeutic strategies. Patients should also undergo genetic testing, especially for mutations in genes encoding succinate dehydrogenase enzyme subunits that are most commonly present as a genetic cause of these tumours. Curative surgical resection after appropriate α-adrenoceptor and β-adrenoceptor blockade in norepinephrine-secreting tumours is the primary therapeutic strategy. Therefore, appropriate and up-to-date knowledge about early diagnosis and management of cardiac PGLs is paramount for optimal outcomes in patients where a cardiologist is an essential team member of a multidisciplinary team in its management.

scholarly journals Uncommon testicular metastasis of a primary neuroendocrine tumour of the lung

2013 ◽  
Vol 7 (9-10) ◽  
pp. 614 ◽  
Author(s):  
Ingrid L. Birker ◽  
Johan A. Van der Zee ◽  
Karin M. Keizer
Keyword(s):  
Neuroendocrine Carcinoma ◽  
Neuroendocrine Tumour ◽  
Hepatic Metastases ◽  
Stage Iv ◽  
Salvage Chemotherapy ◽  
Pet Scan ◽  
Testis Cancer ◽  
Palpable Mass ◽  
Testicular Metastasis ◽  
Positron Emission

A 52-year-old male presented with an asymptomatic palpable mass of the right testicle. Ultrasound confirmed the presence of a testicular tumour and a hemicastration was performed. None of the testis cancer-related tumour markers were elevated and histological findings revealed a neuroendocrine carcinoma, possibly a metastasis from another primary site. The radiological findings showed a lesion in the lung, and a positron emission tomography (PET)-scan was made. The PET scan revealed an increased fluorodeoxyglucose (FDG) uptake in the pulmonary lesion. It also showed lymphatic and hepatic metastases. The patient had no complaints besides a palpable testicular mass and was diagnosed with a cT1aN3M1b neuroendocrine carcinoma of the lower left field of the lung, stage IV. To our knowledge, the presentation of testicular metastasis of a neuroendocrine carcinoma of the lung has not been described in the literature. No curative options were available and the patient is being treated with salvage chemotherapy.

scholarly journals Cohesin mutations are synthetic lethal with stimulation of WNT signaling

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Chue Vin Chin ◽  
Jisha Antony ◽  
Sarada Ketharnathan ◽  
Anastasia Labudina ◽  
Gregory Gimenez ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Therapeutic Strategy ◽  
Synthetic Lethality ◽  
Mcf10a Cell ◽  
Synthetic Lethal ◽  
Deletion Mutations ◽  
Damage Repair ◽  
Genes Encoding ◽  
Mutant Cells ◽  
Gsk3 Inhibitor

Mutations in genes encoding subunits of the cohesin complex are common in several cancers, but may also expose druggable vulnerabilities. We generated isogenic MCF10A cell lines with deletion mutations of genes encoding cohesin subunits SMC3, RAD21, and STAG2 and screened for synthetic lethality with 3009 FDA-approved compounds. The screen identified several compounds that interfere with transcription, DNA damage repair and the cell cycle. Unexpectedly, one of the top ‘hits’ was a GSK3 inhibitor, an agonist of Wnt signaling. We show that sensitivity to GSK3 inhibition is likely due to stabilization of β-catenin in cohesin-mutant cells, and that Wnt-responsive gene expression is highly sensitized in STAG2-mutant CMK leukemia cells. Moreover, Wnt activity is enhanced in zebrafish mutant for cohesin subunits stag2b and rad21. Our results suggest that cohesin mutations could progress oncogenesis by enhancing Wnt signaling, and that targeting the Wnt pathway may represent a novel therapeutic strategy for cohesin-mutant cancers.

scholarly journals Mediastinal Staging for Lung Cancer

2014 ◽  
Vol 21 (3) ◽  
pp. 159-161 ◽  
Author(s):  
Jacob Gelberg ◽  
Sean Grondin ◽  
Alain Tremblay
Keyword(s):  
Computed Tomography ◽  
Lung Cancer ◽  
Positron Emission Tomography ◽  
Lymph Nodes ◽  
Emission Tomography ◽  
Mediastinal Staging ◽  
Positron Emission ◽  
Pet Ct ◽  
Diagnosis Of Cancer ◽  
Rule Out

Staging of the mediastinal and hilar lymph nodes plays a crucial role in identifying the best treatment option for patients with confirmed or suspected lung cancer and, in many cases, can simultaneously confirm a diagnosis of cancer. Noninvasive modalities, such as computed tomography (CT), positron emission tomography (PET) and PET-CT, are an important first step in this assessment. Ultimately, invasive staging is frequently required to confirm or rule out the presence of metastatic disease within the lymph nodes. The present focused review describes and compares noninvasive and invasive modalities for mediastinal staging in lung cancer.

Primary hepatic neuroendocrine tumour masquerading as a giant haemangioma: an unusual presentation of a rare disease

2020 ◽  
Vol 13 (9) ◽  
pp. e236153
Author(s):  
Talal Almas ◽  
Faisal Inayat ◽  
Maryam Ehtesham ◽  
Muhammad Kashif Khan
Keyword(s):  
Neuroendocrine Tumour ◽  
Somatostatin Receptor ◽  
Stable Condition ◽  
Clinical History ◽  
Postoperative Recovery ◽  
Pathological Examination ◽  
Resected Specimen ◽  
Right Hemihepatectomy ◽  
Positron Emission ◽  
Gallium 68

Primary hepatic neuroendocrine tumour is an exceedingly rare entity. We hereby delineate the case of a 45-year-old Balti descent woman who hails from a land-locked village situated in the foothills of the Pakistani Himalayas. The patient presented to our medical centre with a hepatic mass. She underwent extensive diagnostic workup. The consistent findings of an abdominal CT scan, coupled with her clinical history, insinuated a preoperative diagnosis of atypical hepatic haemangioma. After a detailed discussion in a multidisciplinary meeting, a standard right hemihepatectomy was performed. She had an uneventful postoperative recovery and was discharged in stable condition after 1 week. Surprisingly, pathological examination and immunohistochemistry of the resected specimen divulged the diagnosis of a grade II primary hepatic neuroendocrine tumour. Her somatostatin-receptor scintigraphy and Gallium-68 DOTATATE positron emission tomography scan excluded residual hepatic or additional body lesions. Regular follow-ups over the past 4 years demonstrated unremarkable radiological findings with no recurrence to date.

scholarly journals The Clinical Need for New Diagnostics in the Identification and Management of Patients with Suspected Sepsis in UK NHS Hospitals: A Survey of Healthcare Professionals

Antibiotics ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 737
Author(s):  
Amanda Winter ◽  
William Stephen Jones ◽  
A. Joy Allen ◽  
D. Ashley Price ◽  
Anthony Rostron ◽  
...  
Keyword(s):  
Healthcare Professionals ◽  
Care Pathway ◽  
Cross Sectional Survey ◽  
Suspected Sepsis ◽  
Cross Sectional ◽  
Blood Tests ◽  
Clinical Scenarios ◽  
Initial Identification ◽  
Uk National Health Service ◽  
Rule Out

Development of a new diagnostic is ideally driven by an understanding of the clinical need that the test addresses and the optimal role the test will have within a care pathway. This survey aimed to understand the clinical need for new sepsis diagnostics and to identify specific clinical scenarios that could be improved by testing. An electronic, cross-sectional survey was circulated to UK National Health Service (NHS) doctors and nurses who care for patients with suspected sepsis in hospitals. Two hundred and sixty-five participants completed the survey, representing 64 NHS Trusts in England. Sixty-seven percent of respondents suggested that the major cause of delay was during the initial identification of sepsis and the subsequent recognition of patients who were deteriorating. Existing blood tests did not enhance the confidence of consultants making their diagnoses. Those surveyed identified a role for a near-patient test to “rule out” suspected sepsis and, thereby, stop or postpone use of antibiotics. Current diagnostic tests are slow, non-specific, and do not reliably identify patients with a high suspicion of sepsis. As a result, they have a limited use in patient management and antibiotic stewardship. Future development of sepsis diagnostics should focus on overcoming these limitations.

New advances in the management of pulmonary sarcoidosis

BMJ ◽  
2019 ◽  
pp. l5553 ◽  
Author(s):  
Daniel A Culver ◽  
Marc A Judson
Keyword(s):  
New Technologies ◽  
Granulomatous Inflammation ◽  
Needle Aspiration ◽  
Pulmonary Sarcoidosis ◽  
Endobronchial Ultrasound ◽  
Transbronchial Needle Aspiration ◽  
Optimal Outcomes ◽  
Disease States ◽  
Positron Emission ◽  
Immunosuppressive Medications

AbstractSarcoidosis is a highly variable granulomatous multisystem syndrome. It affects individuals in the prime years of life; both the frequency and severity of sarcoidosis are greater in economically disadvantaged populations. The diagnosis, assessment, and management of pulmonary sarcoidosis have evolved as new technologies and therapies have been adopted. Transbronchial needle aspiration guided by endobronchial ultrasound has replaced mediastinoscopy in many centers. Advanced imaging modalities, such as fluorodeoxyglucose positron emission tomography scanning, and the widespread availability of magnetic resonance imaging have led to more sensitive assessment of organ involvement and disease activity. Although several new insights about the pathogenesis of sarcoidosis exist, no new therapies have been specifically developed for use in the disease. The current or proposed use of immunosuppressive medications for sarcoidosis has been extrapolated from other disease states; various novel pathways are currently under investigation as therapeutic targets. Coupled with the growing recognition of corticosteroid toxicities for managing sarcoidosis, the use of corticosteroid sparing anti-sarcoidosis medications is likely to increase. Besides treatment of granulomatous inflammation, recognition and management of the non-granulomatous complications of pulmonary sarcoidosis are needed for optimal outcomes in patients with advanced disease.

scholarly journals Dopamine agonist resistant prolactinomas: any alternative medical treatment?

Pituitary ◽  
2019 ◽  
Vol 23 (1) ◽  
pp. 27-37 ◽  
Author(s):  
P. Souteiro ◽  
N. Karavitaki
Keyword(s):  
Kinase Inhibitors ◽  
Mammalian Target Of Rapamycin ◽  
Somatostatin Analogues ◽  
Cytotoxic Agents ◽  
Tumor Control ◽  
Medical Treatments ◽  
Secondary Resistance ◽  
Optimal Outcomes ◽  
Clinical Scenarios

Abstract Consensus guidelines recommend dopamine agonists (DAs) as the mainstay treatment for prolactinomas. In most patients, DAs achieve tumor shrinkage and normoprolactinemia at well tolerated doses. However, primary or, less often, secondary resistance to DAs may be also encountered representing challenging clinical scenarios. This is particularly true for aggressive prolactinomas in which surgery and radiotherapy may not achieve tumor control. In these cases, alternative medical treatments have been considered but data on their efficacy should be interpreted within the constraints of publication bias and of lack of relevant clinical trials. The limited reports on somatostatin analogues have shown conflicting results, but cases with optimal outcomes have been documented. Data on estrogen modulators and metformin are scarce and their usefulness remains to be evaluated. In many aggressive lactotroph tumors, temozolomide has demonstrated optimal outcomes, whereas for other cytotoxic agents, tyrosine kinase inhibitors and for inhibitors of mammalian target of rapamycin (mTOR), higher quality evidence is needed. Finally, promising preliminary results from in vitro and animal reports need to be further assessed and, if appropriate, translated in human studies.

scholarly journals Chest Pain: The Need to Consider Less Frequent Diagnosis

2016 ◽  
Vol 2016 ◽  
pp. 1-5
Author(s):  
Pedro Magalhães ◽  
Anabela Morais ◽  
Sofia Carvalho ◽  
Joana Cunha ◽  
Ana R. Lima ◽  
...  
Keyword(s):  
Chest Pain ◽  
Takayasu Arteritis ◽  
Temporal Artery ◽  
Lower Limbs ◽  
Temporal Artery Biopsy ◽  
Acute Phase Reactants ◽  
Granulomatous Vasculitis ◽  
Positron Emission ◽  
Clinical Scenarios ◽  
Underlying Causes

Chest pain is one of the most frequent patient’s complaints. The commonest underlying causes are well known, but, sometimes, in some clinical scenarios, it is necessary to consider other diagnoses. We report a case of a 68-year-old Caucasian male, chronically hypertensive, who complained of recurrent episodes of chest pain and fever with elevated acute phase reactants. The first investigation was negative for some of the most likely diagnosis and he quickly improved with anti-inflammatory drugs. Over a few months, his symptoms continued to recur periodically, his hypertension was aggravated, and he developed headaches and lower limbs claudication. After a temporal artery biopsy that was negative for vasculitis, he underwent a positron emission tomography suggestive of Takayasu Arteritis. Takayasu Arteritis is a rare chronic granulomatous vasculitis of the aorta and its first-order branches affecting mostly females up to 50 years old. Chest pain is experienced by >40% of the patients and results from the inflammation of the aorta, pulmonary artery, or coronaries.

Whole-Body Positron Emission Tomography (PET) Using 2-18Fluoro-2-Deoxy-D-Glucose (FDG) for Monitoring Lymphadenopathy in Autoimmune Lymphoproliferative Syndrome (ALPS).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3850-3850
Author(s):  
V. Koneti Rao ◽  
Jorge A. Carrasquillo ◽  
Janet K. Dale ◽  
Stephen Bacharach ◽  
Millie Whatley ◽  
...  
Keyword(s):  
Lymph Node ◽  
Burkitt Lymphoma ◽  
Lymph Node Biopsy ◽  
Whole Body ◽  
Fdg Uptake ◽  
Type Iii ◽  
Invasive Test ◽  
Standardized Uptake Values ◽  
Positron Emission ◽  
Genes Encoding

Abstract ALPS is associated with mutations in genes that promote apoptosis of lymphocytes leading to accumulation of unwanted cells, including ones that react against self antigens. It is characterized by early childhood onset of chronic lymphadenopathy, hepatosplenomegaly and autoimmune cytopenias. ALPS Types Ia, Ib, IIa and IIb are associated with mutations in the genes encoding the apoptosis signaling proteins Fas, FasL, and Caspases 10 or 8 respectively, while patients in whom no mutations have been identified are classified as ALPS Type III. Patients with intracellular Fas mutations have a significantly increased (14–51 fold) risk of developing non-Hodgkin’s (NHL) and Hodgkin’s lymphoma (HL) relative to SEER data. The diagnosis of lymphoma can be particularly difficult because many ALPS manifestations overlap with those of lymphoma, risking the need for repeated biopsies. A non-invasive test is desired for ALPS patients to help discern whether a biopsy is warranted and decide which node to biopsy. PET using FDG, as a measure of glucose metabolism, has emerged as a useful technique in the staging and follow up of various tumors including lymphomas. We have been exploring the value of PET to determine whether qualitative or quantitative FDG localization can differentiate ALPS patients with benign adenopathy from those with ALPS-associated lymphomas. Patients received 15 mCi of FDG and underwent imaging of their torso using a dedicated PET scanner. Images were analyzed semi-quantitatively to determine the maximum standardized uptake values (SUVmax = mCi/g in node of interest/mCi injected x grams lean body mass) in sites of abnormal nodal uptake. Thus far, 9 male and 7 female patients with ALPS with a median age of 24 years (range 14–47yrs) have been studied. 11 patients have ALPS Type Ia, 1 has ALPS Type IIa, and 4 have ALPS Type III. 5 underwent lymph node biopsy following PET; 4 of them had lymph node histopathology consistent with ALPS. One patient was diagnosed with Burkitt lymphoma (BL) following his initial PET study, and is being followed after chemotherapy. Three subjects had prior diagnoses of lymphoma (2NHL and 1HL) and were in remission at the time of PET study. The patient with Burkitt lymphoma had an SUVmax of 26.9 at diagnosis; whereas the other 15 ALPS patients had a mean SUVmax of 8.2 (SE+0.5; range 4.2–11.3; with significant overlap between the groups. Qualitatively, the patients with ALPS Types Ia and IIa had greater numbers of nodal sites with increased FDG uptake than the patients with ALPS Type III. The biodistribution of FDG in patients with ALPS is abnormal compared to previously studied normal controls who typically exhibit no nodal uptake. With additional subjects studied, it may be possible to determine whether there are sufficient changes in FDG uptake to discriminate among the different subgroups of ALPS or between ALPS associated adenopathy and ALPS associated lymphoma. In the interim, one needs to be aware of the considerable FDG avidity of ALPS related adenopathy while assessing ALPS patients by PET scans for suspected lymphoma.

scholarly journals Hypoxia Signaling Cascade for Erythropoietin Production in Hepatocytes

2015 ◽  
Vol 35 (15) ◽  
pp. 2658-2672 ◽  
Author(s):  
Yutaka Tojo ◽  
Hiroki Sekine ◽  
Ikuo Hirano ◽  
Xiaoqing Pan ◽  
Tomokazu Souma ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Kidney Diseases ◽  
Oxygen Homeostasis ◽  
Nucleosome Structure ◽  
Gene Enhancer ◽  
Genes Encoding ◽  
Oxygen Conditions ◽  
Fatty Livers ◽  
Hif Prolyl Hydroxylase

Erythropoietin (Epo) is produced in the kidney and liver in a hypoxia-inducible manner via the activation of hypoxia-inducible transcription factors (HIFs) to maintain oxygen homeostasis. Accelerating Epo production in hepatocytes is one plausible therapeutic strategy for treating anemia caused by kidney diseases. To elucidate the regulatory mechanisms of hepatic Epo production, we analyzed mouse lines harboring liver-specific deletions of genes encoding HIF-prolyl-hydroxylase isoforms (PHD1, PHD2, and PHD3) that mediate the inactivation of HIF1α and HIF2α under normal oxygen conditions. The loss of all PHD isoforms results in both polycythemia, which is caused by Epo overproduction, and fatty livers. We found that deleting any combination of two PHD isoforms induces polycythemia without steatosis complications, whereas the deletion of a single isoform induces no apparent phenotype. Polycythemia is prevented by the loss of either HIF2α or the hepatocyte-specificEpogene enhancer (EpoHE). Chromatin analyses show that the histones aroundEpoHEdissociate from the nucleosome structure after HIF2α activation. HIF2α also induces the expression of HIF3α, which is involved in the attenuation of Epo production. These results demonstrate that the total amount of PHD activity is more important than the specific function of each isoform for hepaticEpoexpression regulated by a PHD-HIF2α-EpoHEcascadein vivo.

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