Prospective investigation of patent foramen ovale as a mechanism for brain metastasis in patients without prior lung involvement.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e14510-e14510
Author(s):  
Rebecca Levin-Epstein ◽  
Joshua Rusheen ◽  
Preetham Kumar ◽  
Rubine Gevorgyan ◽  
Zoe McWatters ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Brain Metastases ◽  
Patent Foramen Ovale ◽  
Lung Metastases ◽  
Lung Involvement ◽  
Left Heart ◽  
Foramen Ovale ◽  
Positive Study ◽  
The Right ◽  
The Brain

e14510 Background: Brain metastases can lead to significant morbidity and mortality in patients with advanced cancer. Preventing metastatic disease to the brain could thus substantially improve outcomes. The mechanism of brain metastasis is incompletely understood. Circulating tumor cells drain to the right heart and through the pulmonary circulation, where they may manifest as lung metastases, and can circulate further to the left heart and then to the brain. However, in patients who develop brain metastases without prior lung involvement, metastatic cells may take an alternate route. We hypothesized that cancer cells may pass directly from the right to left heart via a patent foramen ovale (PFO), akin to paradoxical embolism. The prevalence of PFO is approximately 20-30% in the general population; if further elevated in this population, PFO may play a role in brain metastasis development, and ultimately, prophylactic PFO closure may provide benefit. We conducted a pilot study to investigate whether PFO is associated with brain metastases in patients without prior lung involvement. Methods: We prospectively identified patients with brain metastases from a non-lung primary cancer with no preceding lung metastases. Participants underwent a transcranial Doppler study to assess for PFO. Agitated saline was injected intravenously at rest and with Valsalva maneuver. High intensity signals were counted in the middle cerebral arteries for 1 minute after each injection. Spencer grade ≥3 indicated a positive study, consistent with the presence of PFO. Results: We accrued 9 participants who met inclusion criteria. Primary cancers were breast (6 participants), upper gastrointestinal (2 participants), and thyroid (1 participant). A positive study was identified in 2/9 (22.2%) participants. One individual was a female with breast cancer who had no preceding extracranial metastases, and the other individual was a male with duodenal adenocarcinoma whose only prior metastatic disease was distant lymphadenopathy, not active at brain metastasis diagnosis. No participants have developed lung metastases as of their most recent imaging. Conclusions: In this prospective pilot study, we found no increased prevalence of PFO in patients who develop brain metastases without preceding lung involvement compared to estimates for the general population. Though a larger study is needed, the development of brain metastases in these patients may reflect tumors’ biological factors directing metastasis organotropism, rather than a structural pathway.

Brain metastases in patients diagnosed with a solid primary cancer during childhood: experience from a single referral cancer center

2014 ◽  
Vol 14 (4) ◽  
pp. 372-385 ◽  
Author(s):  
Dima Suki ◽  
Rami Khoury Abdulla ◽  
Minming Ding ◽  
Soumen Khatua ◽  
Raymond Sawaya
Keyword(s):  
Brain Metastasis ◽  
Brain Metastases ◽  
Primary Tumor ◽  
Lung Metastases ◽  
Cancer Center ◽  
Leptomeningeal Disease ◽  
Tumor Type ◽  
Primary Cancer ◽  
Extracranial Metastases ◽  
The Brain

Object Metastasis to the brain is frequent in adult cancer patients but rare among children. Advances in primary tumor treatment and the associated prolonged survival are said to have increased the frequency of brain metastasis in children. The authors present a series of cases of brain metastases in children diagnosed with a solid primary cancer, evaluate brain metastasis trends, and describe tumor type, patterns of occurrence, and prognosis. Methods Patients with brain metastases whose primary cancer was diagnosed during childhood were identified in the 1990–2012 Tumor Registry at The University of Texas M.D. Anderson Cancer Center. A review of their hospital records provided demographic data, history, and clinical data, including primary cancer sites, number and location of brain metastases, sites of extracranial metastases, treatments, and outcomes. Results Fifty-four pediatric patients (1.4%) had a brain metastasis from a solid primary tumor. Sarcomas were the most common (54%), followed by melanoma (15%). The patients' median ages at diagnosis of the primary cancer and the brain metastasis were 11.37 years and 15.03 years, respectively. The primary cancer was localized at diagnosis in 48% of patients and disseminated regionally in only 14%. The primary tumor and brain metastasis presented synchronously in 15% of patients, and other extracranial metastases were present when the primary cancer was diagnosed. The remaining patients were diagnosed with brain metastasis after initiation of primary cancer treatment, with a median presentation interval of 17 months after primary cancer diagnosis (range 2–77 months). At the time of diagnosis, the brain metastasis was the first site of systemic metastasis in only 4 (8%) of the 51 patients for whom data were available. Up to 70% of patients had lung metastases when brain metastases were found. Symptoms led to the brain metastasis diagnosis in 65% of cases. Brain metastases were single in 60% of cases and multiple in 35%; 6% had only leptomeningeal disease. The median Kaplan-Meier estimates of survival after diagnoses of primary cancer and brain metastasis were 29 months (95% CI 24–34 months) and 9 months (95% CI 6–11 months), respectively. Untreated patients survived for a median of 0.9 months after brain metastasis diagnosis (95% CI 0.3–1.5 months). Those receiving treatment survived for a median of 8 months after initiation of therapy (95% CI 6–11 months). Conclusions The results of this study challenge the current notion of an increased incidence of brain metastases among children with a solid primary cancer. The earlier diagnosis of the primary cancer, prior to its dissemination to distant sites (especially the brain), and initiation of presumably more effective treatments may support such an observation. However, although the actual number of cases may not be increasing, the prognosis after the diagnosis of a brain metastasis remains poor regardless of the management strategy.

scholarly journals Prevotella brain abscess in a healthy patient with a patent foramen ovale: Case report

2021 ◽  
Vol 12 ◽  
pp. 548
Author(s):  
Yu Akimoto ◽  
Kiyoyuki Yanaka ◽  
Kuniyuki Onuma ◽  
Kazuhiro Nakamura ◽  
Eiichi Ishikawa
Keyword(s):  
Brain Abscess ◽  
Patent Foramen Ovale ◽  
Foramen Ovale ◽  
Brain Infection ◽  
Source Of Infection ◽  
Venous Shunt ◽  
Life Threatening ◽  
Brain Abscesses ◽  
The Right ◽  
The Brain

Background: Brain abscesses are relatively rare life-threatening infectious lesions often concomitant with a direct spillover of inflammation in the head or neck, hematogenous infections, and immunocompromised conditions. They rarely occur in adults without such predisposing factors. Prevotella is a well-known dental pathogen that very rarely causes brain abscesses. Case Description: We report such an abscess in a 51-year-old man who was innately healthy and had no oral lesions. A comprehensive computed tomography examination of the chest, abdomen, and pelvis, was inconclusive but a transesophageal echocardiogram bubble study revealed a mild patent foramen ovale (PFO) that matched Grade 1 criteria. We deduced that the right-left shunt due to the PFO could have contributed to the brain infection and treated the patient successfully via surgical abscess aspiration and antibiotics. Conclusion: In case of a brain abscess occurring in healthy adults, it is essential to investigate the source of infection and the existence of an arterio-venous shunt, such as PFO.

Real-world hypothesis-generating cohort of pancreatic cancer patients with brain metastases.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16720-e16720
Author(s):  
Derek Cridebring ◽  
David Hadley ◽  
Timothy S Scott ◽  
Alex B Vilner ◽  
Tammy M Heckman ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Lung Metastases ◽  
The United States ◽  
The Body ◽  
Secondary Malignancy ◽  
Information Management Systems ◽  
Age Of Diagnosis ◽  
The Brain

e16720 Background: Pancreatic cancer (PC) is the third most lethal form of cancer in the United States, and is most often diagnosed having already metastasized, making its 5-year survival rate one of the lowest. Metastatic PC (mPC) is most common at sites such as liver, lymph nodes, and lung while, in contrast, brain metastases from PC are rare. Brain metastases present a major challenge for future oncological research, as they are difficult to treat. If PC patients most likely to develop brain metastases can be identified earlier, there is an opportunity for rapid therapeutic intervention. There is limited research and understanding of the relationship between pancreatic cancer and brain metastases. Methods: We performed a retrospective, non-interventional study using deidentified data. Inteliquet’s data was aggregated from its consortium of 175 US healthcare locations, which includes a variety of source systems at each site. These sources include electronic medical record systems, laboratory information management systems, and other sources. A subset of the adult mPC data originally treated at HonorHealth was identified as an exploratory cohort. Results: 833 patient records were identified with drug treated mPC, 33 (4%) of which had metastasized to the brain. The PC dataset had a median diagnosis age of 65 and was 46% female. The site of the primary tumor within the pancreas was acquired from ICD10 code: 35% were in the head, 14% in the tail, 15% in the body, 5% in overlapping sites, 6% in other parts and 26% where location was unspecified. Metastatic locations came from secondary malignancy ICD10 codes: 63% had liver and 25% had lung metastases, which aligns with prior studies. For patients with brain metastases, the gender distribution was 42% female, while the distribution of primary PC site was: 33% head, 9% tail, 6% body, 6% in overlapping locations, 12% in other parts and 33% with unspecified location. The median age of diagnosis in the brain metastasis group was 67 years. Conclusions: This is the largest study of PC patients with brain metastases that we could find. 33 patients out of 833 had brain metastases compared to a recent review which had 25 cases. Our data suggests that specification of the primary pancreatic site is more difficult, aside from the head of the pancreas. Analyses are underway to explore correlations between other clinical factors and brain metastases, and to calculate the time in between the initial pancreatic cancer diagnosis and detection of the brain metastasis. This hypothesis-generating cohort will be tested in patient data from the rest of the consortium.

Patent Foramen Ovale, the Role of Antiplatelet Therapy Alone or Anticoagulant Therapy Alone Versus Device Closure for Cryptogenic Stroke: A Review of the Literature and Current Recommendations

2020 ◽  
Vol 18 (2) ◽  
pp. 135-150
Author(s):  
Harsha S. Nagarajarao ◽  
Chandra P. Ojha ◽  
Archana Kedar ◽  
Debabrata Mukherjee
Keyword(s):  
Patent Foramen Ovale ◽  
Cryptogenic Stroke ◽  
Narrow Channel ◽  
Paradoxical Embolism ◽  
Current Evidence ◽  
Foramen Ovale ◽  
The Right ◽  
The Relationship ◽  
Current Guidelines

: Cryptogenic stroke and its relation to the Patent Foramen Ovale (PFO) is a long-debated topic. Recent clinical trials have unequivocally established the relationship between cryptogenic strokes and paradoxical embolism across the PFO. This slit-like communication exists in everyone before birth, but most often closes shortly after birth. PFO may persist as a narrow channel of communication between the right and left atria in approximately 25-27% of adults. : In this review, we examine the clinical relevance of the PFO with analysis of the latest trials evaluating catheter-based closure of PFO’s for cryptogenic stroke. We also review the current evidence examining the use of antiplatelet medications versus anticoagulants for stroke prevention in those patients with PFO who do not qualify for closure per current guidelines.

scholarly journals BSCI-11. STROMAL PLATELET DERIVED GROWTH FACTOR RECEPTOR-β (PDGFRβ) PROMOTES BREAST CANCER BRAIN METASTASIS

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i3-i3
Author(s):  
Katie Thies ◽  
Anisha Hammer ◽  
Blake Hildreth ◽  
Luke Russell ◽  
Steven Sizemore ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Tumor Cells ◽  
Mammary Tumor ◽  
Growth Factor Receptor ◽  
Platelet Derived Growth Factor ◽  
Mammary Tumor Cells ◽  
The Brain

Abstract Stromal platelet-derived growth factor receptor-beta (PDGFRβ) has emerged as an actionable mediator of breast tumor-stromal communication. As a receptor tyrosine kinase, PDGFRβ is activated by its ligand, PDGFB, which is released by neighboring tumor epithelium and endothelium. However, how PDGF signaling mediates breast cancer (BC) initiation, progression, and metastasis remains unclear. To evaluate PDGFRβ in this disease, we developed a mouse model of stromal-specific PDGFRβ activation using the Fsp-cre transgene previously published by our group. Mesenchymal-specific activation of PDGFRβ promotes preferential experimental brain metastasis of PDGFB-expressing mammary tumor cells when injected intravenously and accelerates intracranial tumor growth of these cells. Mammary tumor cells expressing low levels of PDGFB do not exhibit a similar increase in brain metastases in PDGFRβ mutant mice. To our knowledge, this is the first example where genetic manipulation of the stroma leads to an increased incidence of BCBM. Our pre-clinical data suggests that primary breast tumors that express high PDGFB could preferentially metastasize to the brain. To test this in patients, we analyzed PDGFB protein expression in a tissue microarray comprised of HER2-positive and triple negative BC primary tumors. While high PDGFB did not correlate with site-independent metastatic recurrence, it was prognostic of brain metastasis, mirroring our mouse data. Our findings suggest that high primary tumor PDGFB expression defines a subset of BC patients predisposed to brain metastases. These patients may benefit from therapeutic intervention of PDGFRβ signaling. To test this pre-clinically, we treated mice harboring intracranial tumors with the PDGFR-specific inhibitor, crenolanib. Excitingly, crenolanib treatment significantly inhibited the brain tumor burden in these mice. Combined, our findings (1) advocate that primary tumor expression of PDGFB is a novel prognostic biomarker for the development of BCBM and (2) support clinical trial evaluation of PDGFR inhibitors for the prevention and treatment of BCBM.

Sudden Onset of Diplopia and a Skeletal Muscle Antibody

2021 ◽  
pp. 160-162
Author(s):  
John R. Mills
Keyword(s):  
Computed Tomography ◽  
Myasthenia Gravis ◽  
Patent Foramen Ovale ◽  
Time Course ◽  
Vision Loss ◽  
Sudden Onset ◽  
Foramen Ovale ◽  
Clinical Disorder ◽  
History Of ◽  
The Right

A 62-year-old man with a history of migraine came to the emergency department with sudden onset of horizontal diplopia and, subsequently, bilateral ptosis. He noted feeling unsteady when walking. He reported that the diplopia worsened throughout the day. He had a history of hepatitis C infection. He had some vision loss in his left eye, which was thought to relate to a retinopathy. He disclosed that he had a history of cold feet and had notably high arches. He had a pacemaker because of syncope attributed to sick sinus syndrome. Computed tomography angiography of the head and neck were ruled negative for intracranial stenosis, occlusions, or aneurysms. Computed tomography of the head indicated a tiny lacunar infarct in the right caudate head. Magnetic resonance imaging of the brain identified a tiny, periaqueductal, enhancing abnormality in the right midbrain that was thought to be likely ischemic, but there was some concern for a demyelinating or inflammatory lesion. Cerebrospinal fluid evaluation indicated an increased protein concentration. Serologic evaluation for myasthenia gravis striational antibodies were positive at a titer of 1:240. Serum protein studies indicated the presence of polyclonal hypergammaglobulinemia. Myasthenia gravis was effectively ruled out. Given the hyperacute time course, the patient’s clinical disorder was most probably explained by an ischemic stroke that affected the oculomotor nuclei regions causing ptosis and ophthalmoparesis. On follow-up, the patient was discovered to have a patent foramen ovale. Whether the patent foramen ovale was a contributing factor to the stroke is uncertain. The recurrence rate in this setting is thought to be low relative to other causes of stroke. Ultimately it was decided to not close the patent foramen ovale and to maintain the patient on clopidogrel and adult low-dose aspirin. The onset of diplopia is typically sudden, but this occurs exclusively with vascular pathologic processes. Diplopia that appears intermittently with diurnal variation suggests the possibility of a neuromuscular junction disease such as myasthenia gravis.

scholarly journals P1317 Very late onset of platypnoea orthodeoxia syndrome as first clinical scenario of patent foramen ovale

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
S M Binno ◽  
L Moderato ◽  
G Pastorini ◽  
B Matrone ◽  
D Aschieri ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Left Atrium ◽  
Right Atrium ◽  
Patent Foramen Ovale ◽  
Standing Position ◽  
Clinical Scenario ◽  
Foramen Ovale ◽  
Multiple Focus ◽  
Pulmonary Shunting ◽  
The Right

Abstract We report a case of a 83-year-old female, who had an admission for dyspnea. Laboratory showed D-dimer 1000 ng/ml, haemoglobin 12.4 mg/dL, CPR 0.08mg/dl whereas on Arterial Blood Gas test she had hypoxia with respiratory alkalosis. In view of suspected pulmonary embolism, she underwent Thoracic Computed Tomography scan that excluded it. During the stay the patient seemed more symptomatic while in standing position(with SpO2s 89% while supine plunging to 50% while standing): ABGs were performed both standing (reservoir 15 l/min pH 7.50, pO2 37.2 mmHg, pCO2 37.1 mmHg, HCO3 28.9 mmol/l) and recumbent position (reservoir 15 l/min pH 7.47, pO2 65.5 mmHg, pCO2 35.1 mmHg, HCO3 25.6 mmol), showing a difference of 28 mmHg. Subsequently the patient underwent v/p pulmonary scintigraphy: no signs of pulmonary embolism though it revealed a multiple focus of capitation Tc-99m macro aggregated albumin in brain, thyroid and kidneys (IMG top), compatible for veno-arterial shunt. Trans-esophageal echocardiography (TOE) revealed a massive stretched patent foramen ovale (PFO) with continuous right-to-left shunting through the atria. The bubble test (IMG bottom) confirmed the presence of patency along with sudden passage of microbubbles through the foramen. Qp/Qs = 0.8, due to volume overload in the left atrium from the right atrium. The imaging along with clinical scenario confirmed the suspected diagnosis of platypnea-orthodeoxia, finding the patent foramen ovale as the anatomical cause. Platypnea-orthodeoxia syndrome is a clinical condition characterized by dyspnea. Typically blood oxygen saturation declines with standing position while it resolves with recumbent. The classification entails 3 groups: intracardiac shunting (most common presentation), pulmonary shunting, ventilation-perfusion mismatch. Presence of multiple focus of albumin macroaggregates outside the lungs in v/p scintigraphy examination is suggestive for veno-arteriuous shunt: without shunt, normally all the albumin aggregates are hampered in the lungs’ field. Images in bottom are taken in sequence from a single acquisition during the TOE, in one single cardiac beat. Here is depicted the evidence of the PFO, the influx of bubbles in the right atrium and the instantaneous and massive shunt of the bubbles across the interatrial septum, in the left atrium. Usually the diagnosis is performed within 55 years old: it is interesting how late the diagnosis occurred in this patient with such resounding clinical manifestation. Top Scintigraphy with ventilation and perfusion lung scan sequences. Next, scintigraphy with capitation of Tc-99m macro aggregated albumin in brain, thyroid and kidneys. Bottom, Transesophageal echocardiogram: images taken within the same heart beat proving right-to-left passage of bubble across the septum. Abstract P1317 Figure. Scintigraphy and Transesophageal echo

scholarly journals Nuclear-Biased DUSP6 Expression is Associated with Cancer Spreading Including Brain Metastasis in Triple-Negative Breast Cancer

2019 ◽  
Vol 20 (12) ◽  
pp. 3080 ◽  
Author(s):  
Fan Wu ◽  
Robert D. McCuaig ◽  
Christopher R. Sutton ◽  
Abel H. Y. Tan ◽  
Yoshni Jeelall ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Cancer Progression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Lung Metastases ◽  
Her2 Positive ◽  
Pathway Gene ◽  
Dual Specificity ◽  
The Brain

DUSP6 is a dual-specificity phosphatase (DUSP) involved in breast cancer progression, recurrence, and metastasis. DUSP6 is predominantly cytoplasmic in HER2+ primary breast cancer cells, but the expression and subcellular localization of DUSPs, especially DUSP6, in HER2-positive circulating tumor cells (CTCs) is unknown. Here we used the DEPArray system to identify and isolate CTCs from metastatic triple negative breast cancer (TNBC) patients and performed single-cell NanoString analysis to quantify cancer pathway gene expression in HER2-positive and HER2-negative CTC populations. All TNBC patients contained HER2-positive CTCs. HER2-positive CTCs were associated with increased ERK1/ERK2 expression, which are direct DUSP6 targets. DUSP6 protein expression was predominantly nuclear in breast CTCs and the brain metastases but not pleura or lung metastases of TNBC patients. Therefore, nuclear DUSP6 may play a role in the association with cancer spreading in TNBC patients, including brain metastasis.

scholarly journals Molecular and cellular mechanisms underlying brain metastasis of breast cancer

2020 ◽  
Vol 39 (3) ◽  
pp. 711-720 ◽  
Author(s):  
Mari Hosonaga ◽  
Hideyuki Saya ◽  
Yoshimi Arima
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Cancer Cells ◽  
Metastatic Cancer ◽  
Breast Cancer Patients ◽  
Cellular Mechanisms ◽  
Her2 Positive ◽  
Cells Of The Microenvironment ◽  
The Brain

Abstract Metastasis of cancer cells to the brain occurs frequently in patients with certain subtypes of breast cancer. In particular, patients with HER2-positive or triple-negative breast cancer are at high risk for the development of brain metastases. Despite recent advances in the treatment of primary breast tumors, the prognosis of breast cancer patients with brain metastases remains poor. A better understanding of the molecular and cellular mechanisms underlying brain metastasis might be expected to lead to improvements in the overall survival rate for these patients. Recent studies have revealed complex interactions between metastatic cancer cells and their microenvironment in the brain. Such interactions result in the activation of various signaling pathways related to metastasis in both cancer cells and cells of the microenvironment including astrocytes and microglia. In this review, we focus on such interactions and on their role both in the metastatic process and as potential targets for therapeutic intervention.

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