Concomitant minimally invasive surgery for tricuspid valve papillary fibroelastoma and right lung cancer in an elderly patient: a case report and review of the literature.

BACKGROUND: It is very common for patients with newly diagnosed lung masses to have heart disease. However, papillary fibroelastomas (PFEs) of the tricuspid valve (TV) combined with lung cancer are rarely reported. It is thus unclear whether a two-stage surgery or concomitant surgery is optimal. CASE PRESENTATION: We report the case of a 73-year-old Chinese male who was diagnosed with PFEs on the TV by transthoracic echocardiography (TTE) examination while being evaluated to undergo video-assisted thoracic surgery (VATS) for a right lower lung nodule. We resected both the PFEs and the lung nodule via right minithoracotomy. The surgery was uneventful, and histopathology reports confirmed PFEs of the TV and moderately to poorly differentiated squamous cell carcinoma. The patient recovered uneventfully, and there was no sign of tumor recurrence during 15 months of follow-up. CONCLUSIONS: We suggest that after careful evaluation, concomitant minimally invasive radical resection of primary lung cancer after cardiac PFE removal is an acceptable and safe treatment strategy and should be performed as soon as possible.

Not Your Typical Tonsil: Metastatic Merkel Cell Carcinoma or Primary Disease?

Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine tumor that almost always presents as a cutaneous lesion in the sun-exposed areas on the bodies of elderly white males. Metastasis to lymph nodes in the presence or absence of a known primary site and occurrence of these tumors in non-sun-exposed sites have also been described; however, an incidence of recurrent disease arising in the palatine tonsil in the absence of any detectable primary lesion has never been reported in the literature. In this report, we discuss a case of a 72-year-old female who was found to have a single axillary lymph node, which was resected and proved to be positive forMCC of unknown primary (MCCUP). Since there was no evidence of additional disease, the patient elected not to pursue adjuvant therapies. Six and a half months later, she presented with a complaint of dysphagia and a right-sided exophytic tonsillar mass. Tonsillectomy revealed MCC with no detectable primary cutaneous lesion. She received adjuvant therapy with avelumab and demonstrated a complete response after one year of bi-weekly treatments. Seven months following cessation of adjuvant treatments, surveillance positron emission tomography (PET) revealed enlarged retroperitoneal, pretracheal, periaortic, and left axillary lymph nodes concerning for recurrence. She elected to forgo additional biopsies and restarted avelumab the following month. She continues to be followed up on a monthly basis.

Prophylactic Flexible Bronchoscopy Immediately following Open Airway Reconstruction in Children.

OBJECTIVES: Prophylactic flexible bronchoscopy immediately following open airway reconstruction allows for directed clearance of the distal airways, potentially reducing the rate of certain postoperative respiratory complications. In this investigation, we sought to determine if prophylactic flexible bronchoscopy at the conclusion of pediatric open airway reconstruction has any benefit over blind flexible suctioning of the trachea. METHODS: A retrospective, single-center study at an urban tertiary care hospital was completed. From January 2010 to April 2013, patients underwent open airway reconstruction, immediately followed by blind flexible suctioning of the trachea for distal airway clearance. From May 2013 through December 2016, sequential patients underwent prophylactic flexible bronchoscopy immediately following airway reconstruction. RESULTS: A total of 29 patients (age: 3.6 months-6.2 years) met inclusion criteria. Sixteen sequential patients underwent simple blind flexible suctioning and 13 sequential patients underwent directed, prophylactic flexible bronchoscopy. Demographics and comorbidities between the groups were equivalent other than slightly older age in the prophylactic bronchoscopy group. All clinical outcomes analyzed were equivalent other than faster time to room air (P < .002) and a decrease in the number of chest physical therapy sessions (P < .02) in a subset of patients who did not undergo prophylactic bronchoscopy. CONCLUSION: This investigation suggests that the use of prophylactic flexible bronchoscopy immediately following open airway reconstruction may not be superior to blind flexible suctioning of the trachea in limiting postoperative pulmonary complications. Further studies of greater power are needed to better elucidate any small differences that may exist between these two interventions.

Breast Cancer Metastases to the Paranasal Sinuses Mimicking Inflammatory Sinus Disease.

INTRODUCTION: Breast cancer is one of the most common cancers in women. Metastatic disease is a leading cause of morbidity and mortality. It frequently metastasizes to bone, lungs, regional lymph nodes, liver and brain. Metastasis to the orbit and paranasal sinuses is uncommon. Patients presenting with sinus pain, nasal congestion, or visual disturbance can be misdiagnosed with an infectious process. METHODS: The authors describe 2 patients with metastatic breast cancer to the paranasal sinuses presenting with signs and symptoms of sinusitis and orbit pathology unresponsive to antibiotics. The authors discuss diagnostic strategy and perform a literature review. Both patients had biopsy-proven metastatic breast adenocarcinoma lesions, and subsequently underwent various treatment options. RESULTS: A literature review reveals that metastatic breast adenocarcinoma lesions to the paranasal sinuses are a rare entity that commonly denotes a very poor prognosis. These lesions can significantly affect one's quality of life, and can cause blurry vision, diplopia, proptosis, sinus pressure and pain, nasal congestion, mandibular misalignment or difficulty with mastication. However, early diagnosis and treatment of these lesions can lead to prolonged survival and improved quality of life. If the lesion is surgically resectable, endoscopic sinus surgery is generally considered to be the optimal treatment. However, radiotherapy, chemotherapy, and immunotherapy can potentially play a role in controlling the symptomatology. CONCLUSION: Metastatic lesions to the paranasal sinuses are a rare entity that should be considered in the appropriate clinical setting in order to expedite the proper treatment modality for improved morbidity and mortality.

Squamous cell carcinoma presenting with trigeminal anesthesia: An uncommon presentation of head & neck cancer with unknown primary.

BACKGROUND: The differential diagnosis of facial anesthesia is vast. This may be secondary to trauma, neoplasm, both intracranial and extracranial, infection, and neurologic disease. When evaluating a patient with isolated facial anesthesia, the head and neck surgeon often thinks of adenoid cystic carcinoma, which has a propensity for perineural invasion and spread. When one thinks of head and neck squamous cell carcinoma with or without unknown primary, the typical presentation involves dysphagia, odynophagia, weight loss, hoarseness, or more commonly, a neck mass. Squamous cell carcinoma presenting as facial anesthesia and perineural spread, with no primary site is quite rare. METHODS: Case presentations and review of the literature. CONCLUSIONS: Trigeminal anesthesia is an uncommon presentation of head and neck squamous cell carcinoma with unknown primary. We present two interesting cases of invasive squamous cell carcinoma of the trigeminal nerve, with no primary site identified. We will also review the literature of head and neck malignancies with perineural spread and the management techniques for the two different cases presented.

Metastatic breast carcinoma of the jugular foramen: a rare case of Villaret syndrome.

BACKGROUND: The differential diagnosis of skull base masses is diverse and includes benign and malignant neoplasms, vascular anomalies, congenital lesions, as well as infectious and inflammatory processes. Metastatic masses of the skull base are a rare manifestation of systemic malignancies. Breast cancer is the most common cause of skull base metastases. Villaret syndrome refers to cranial nerves IX, X, XI, and XII and sympathetic chain neuropathies. It is a clinical subtype of jugular foramen syndromes. METHODS AND RESULTS: A 62-year-old woman with a history of breast carcinoma presented with hoarseness dating to shortly after her mastectomy years earlier. CT angiography showed enhancing tissue just outside the right jugular foramen, and biopsy confirmed metastatic adenocarcinoma consistent with breast cancer. CONCLUSION: Villaret syndrome caused by breast cancer metastases has not been previously described. We present a case of Villaret syndrome caused by metastasis of invasive breast adenocarcinoma and a review of the literature of metastases of breast cancer to the skull base.

Quantitative assessment of myocardial perfusion using time-density curve analysis after elective percutaneous coronary intervention.

UNLABELLED: The aim of this study was to assess myocardial blush (MB) using a novel software algorithm that quantifies time-density curves (TDC) after percutaneous coronary intervention (PCI). METHODS: Thirty-two patients referred for elective PCI were enrolled. TDC curves were generated and mean maximal myocardial contrast density (Dmax) was calculated from 5 regions of interest in the PCI territory. Dmax was normalized to contrast injected in the proximal coronary artery (DI). RESULTS: Mean DI significantly increased after PCI in all subjects. Dmax correlated directly with subjective grading of Thrombolysis in Myocardial Infarction (TIMI) myocardial blush (R=0.47; P<.01). In 7 subjects referred for PCI of a chronic total occlusion (CTO), mean DI remained increased after PCI. Mean DI was lower in CTO versus non-CTO subjects; however, fold-improvement was higher after PCI of CTO lesions. CONCLUSION: Quantifying MB using TDC analysis is feasible and correlates with subjective MB grading. The clinical utility of MB quantitation after PCI requires further study.

Oral squamous cell carcinoma in post-transplant patients.

OBJECTIVE: Patients on immunosuppressant therapy after transplantation have an increased risk of developing cutaneous squamous cell carcinomas. The risk of developing solid tumors of the upper aerodigestive tract in this population has been less defined. We present five patients that subsequently developed oral squamous cell carcinoma after transplantation. STUDY DESIGN: Retrospective chart review and literature review. RESULTS: Three bone marrow and two heart transplant patients were subsequently diagnosed with oral (oral cavity or oropharynx) carcinoma. The timing of diagnosis of oral cancer after transplant ranged from 18 months to 17 years post-transplantation. CONCLUSIONS: Patients with a history of transplantation should be routinely assessed for the potential development of oral neoplastic lesions. Oral squamous cell carcinoma in transplant patients can be more aggressive and clinically mistaken for chronic graft versus host disease. It is therefore reasonable to consider early biopsy in these patients to guide the need for intervention.

Management of a postradiation esophageal web in the setting of a coexisting Zenker's diverticulum.

We present a case of postradiation obstructive esophageal web, seen in the setting of a coexisting Zenker's diverticulum, that was treated with combined anterograde and retrograde esophagoscopy puncture and dilation. We also review the relevant literature. Obstructing esophageal webs and stenoses are well-documented complications seen in patients with head and neck cancer treated with radiation therapy. For thin webs, combined anterograde and retrograde esophagoscopy along with puncture and dilation can be a relatively safe treatment option for selected patients. The presence of a coexisting Zenker's diverticulum may predispose the patient to the development of postradiation esophageal complications and make subsequent assessment more difficult to perform.

Distinct effects of unfractionated heparin versus bivalirudin on circulating angiogenic peptides.

BACKGROUND: Human studies of therapeutic angiogenesis, stem-cell, and progenitor-cell therapy have failed to demonstrate consistent clinical benefit. Recent studies have shown that heparin increases circulating levels of anti-angiogenic peptides. Given the widely prevalent use of heparin in percutaneous and surgical procedures including those performed as part of studies examining the benefit of therapeutic angiogenesis and cell-based therapy, we compared the effects of unfractionated heparin (UFH) on angiogenic peptides with those of bivalirudin, a relatively newer anticoagulant whose effects on angiogenic peptides have not been studied. METHODOLOGY/PRINCIPAL FINDINGS: We measured soluble fms-like tyrosine kinase-1 (sFLT1), placental growth factor (PlGF), vascular endothelial growth factor (VEGF), and soluble Endoglin (sEng) serum levels by enzyme linked immunosorbent assays (ELISA) in 16 patients undergoing elective percutaneous coronary intervention. Compared to baseline values, sFLT1 and PlGF levels increased by 2629±313% and 253±54%, respectively, within 30 minutes of UFH therapy (p<0.01 for both; n = 8). VEGF levels decreased by 93.2±5% in patients treated with UFH (p<0.01 versus baseline). No change in sEng levels were observed after UFH therapy. No changes in sFLT1, PlGF, VEGF, or sEng levels were observed in any patients receiving bivalirudin (n = 8). To further explore the direct effect of anticoagulation on circulating angiogenic peptides, adult, male wild-type mice received venous injections of clinically dosed UFH or bivalirudin. Compared to saline controls, sFLT1 and PlGF levels increased by >500% (p<0.01, for both) and VEGF levels increased by 221±101% (p<0.05) 30 minutes after UFH treatment. Bivalirudin had no effect on peptide levels. To study the cellular origin of peptides after anticoagulant therapy, human coronary endothelial cells were treated with UFH and demonstrated increased sFLT1 and PlGF levels (ANOVA p<0.01 for both) with reduced VEGF levels (ANOVA p<0.05). Bivalirudin had no effect on peptide levels in vitro. CONCLUSIONS/SIGNIFICANCE: Circulating levels of sFLT1, PlGF, and VEGF are significantly altered by UFH, while bivalirudin therapy has no effect. These findings may have significant implications for clinical studies of therapeutic angiogenesis, stem-cell and progenitor-cell therapy.

Effects of a percutaneous mechanical circulatory support device for medically refractory right ventricular failure.

BACKGROUND: Medically refractory right ventricular failure (MR-RVF) is associated with high in-hospital mortality and is managed with surgical assist devices, atrial septostomy, or extracorporeal membrane oxygenation. This study explored the hemodynamic effect associated with a percutaneous RV support device (pRVSD) for MR-RVF. METHODS: Between 2008 and 2010, 9 patients with MR-RVF, defined as cardiogenic shock despite maximal medical therapy, were treated with a pRVSD. Medical records were reviewed for demographics, hemodynamic and laboratory data, and details of pRVSD implantation. RESULTS: MR-RVF was due to severe sepsis in 1 patient (11.1%), post-cardiotomy syndrome in 2 (22.2%), and acute inferior wall myocardial infarction (IWMI) in 6 (66.7%). Five patients underwent right internal jugular-to-femoral cannulation, and 4 required bifemoral cannulation. No intra-procedural deaths or major vascular complications requiring surgical or peripheral intervention occurred. Time from admission to pRVSD implantation was 2.9 ± 3.3 days, with an average of 6516 ± 698 rotations/min, providing flow at 3.3 ± 0.4 liters/min. Mean duration of pRVSD activation was 3.1 ± 1.8 days. Compared with pre-procedural values, mean arterial pressure (57 ± 7 vs 75 ± 19 mm Hg, p < 0.05), right atrial pressure (22 ± 3 vs 15 ± 6 mm Hg, p < 0.05), cardiac index (1.5 ± 0.4 vs 2.3 ± 0.5 liters/min/m(2), p < 0.05), mixed venous oxygen saturation (40 ± 14 vs 58 ± 4 percent, p < 0.05), and RV stroke work (3.4 ± 3.9 vs 9.7 ± 6.8 g · m/beat, p < 0.05) improved significantly within 24 hours of pRVSD implantation. In-hospital mortality was 44% (n = 4). Time from admission to pRVSD placement was lower in patients who survived to hospital discharge (0.9 ± 0.8 days) vs non-survivors (4.8 ± 3.5 days; p = 0.04). All survivors presented with IWMI. CONCLUSION: Use of a pRVSD for MR-RVF is feasible and associated with improved hemodynamics. Algorithms promoting earlier pRVSD use in MR-RVF warrant further investigation.

Elevated soluble fms-like tyrosine kinase-1 levels in acute coronary occlusion.

OBJECTIVE: Early recognition of an acute coronary occlusion (ACO) improves clinical outcomes. Soluble fms-like tyrosine kinase-1 (sFLT1) is an endothelium-derived protein induced by hypoxia. We tested whether sFLT1 levels are elevated in ACO. METHODS AND RESULTS: Serum sFLT1 levels were measured by enzyme-linked immunosorbent assay in patients with ST-segment elevations and angiographically confirmed ACO, unstable angina/non ST-segment elevation myocardial infarction, and 2 control groups. To further explore sFLT1 release, a mouse model of ACO and in vitro human coronary artery endothelial cell injury were used. sFLT1 levels were increased in ACO compared with unstable angina/non-ST-elevation myocardial infarction, catheterized controls, or healthy volunteers (200.7±15.5 versus 70.7±44.0 versus 10.2±4.0 versus 11.7±1.7 pg/mL respectively, P<0.001 versus ACO). At presentation, all ACO patients had elevated sFLT1 levels (>15 pg/mL, 99th percentile in controls), whereas 57% had levels of the MB isoform of creatine kinase levels >10 ng/mL (P<0.01) and 85% had ultrasensitive troponin I levels >0.05 ng/mL (P<0.05). Within 60 minutes after symptom onset, sFLT1 was more sensitive than the MB isoform of creatine kinase or ultrasensitive troponin I for ACO (100% versus 20% versus 20% respectively; P≤0.01 for each). Within 60 minutes of ACO in mice, sFLT1 levels were elevated. Hypoxia and thrombin increased sFLT1 levels within 15 minutes in human coronary artery endothelial cells. CONCLUSIONS: sFLT1 levels may be an early indicator of endothelial hypoxia in ACO.

Directed evolution of a magnetic resonance imaging contrast agent for noninvasive imaging of dopamine.

The development of molecular probes that allow in vivo imaging of neural signaling processes with high temporal and spatial resolution remains challenging. Here we applied directed evolution techniques to create magnetic resonance imaging (MRI) contrast agents sensitive to the neurotransmitter dopamine. The sensors were derived from the heme domain of the bacterial cytochrome P450-BM3 (BM3h). Ligand binding to a site near BM3h's paramagnetic heme iron led to a drop in MRI signal enhancement and a shift in optical absorbance. Using an absorbance-based screen, we evolved the specificity of BM3h away from its natural ligand and toward dopamine, producing sensors with dissociation constants for dopamine of 3.3-8.9 microM. These molecules were used to image depolarization-triggered neurotransmitter release from PC12 cells and in the brains of live animals. Our results demonstrate the feasibility of molecular-level functional MRI using neural activity-dependent sensors, and our protein engineering approach can be generalized to create probes for other targets.