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Article ; Online: Feasibility and Intermediate Results of Transcarotid Revascularization with a Prosthetic Conduit.

Cui, Christina L / Reardon, Emily S / Loanzon, Roberto S / Williams, Zachary F / Cox, Mitchell W / Southerland, Kevin W

2024 Volume 103, Page(s) 74–80

Abstract: Background: Transcarotid artery revascularization (TCAR) is a hybrid technique with excellent initial outcomes. The technical success and safety of TCAR is heavily dependent on an anatomically suitable common carotid artery (CCA). Many patients do not ... ...

Abstract	Background: Transcarotid artery revascularization (TCAR) is a hybrid technique with excellent initial outcomes. The technical success and safety of TCAR is heavily dependent on an anatomically suitable common carotid artery (CCA). Many patients do not meet anatomic criteria and therefore are not eligible for this therapy. We sought to extend the eligibility of TCAR to patients with unfavorable CCA anatomy via the adoption of a prosthetic arterial conduit. Methods: A single-center retrospective study of patients with critical carotid artery stenosis who underwent TCAR via a prosthetic conduit between June 2019 and October 2021 was performed. All patients in the study were considered high-risk for carotid endarterectomy based on anatomic features, such as restenosis post-carotid endarterectomy and neck radiation. Unfavorable CCA anatomy was defined as a clavicle to carotid bifurcation distance <5 cm, a CCA diameter <6 mm, and/or significant atherosclerotic disease at the intended arterial access site. The primary outcome of interest was technical success. Secondary outcomes included perioperative complications, intermediate and long-term patency, intermediate and long-term stroke and/or mortality and in-hospital length of stay. Follow-up ranged from 1 to 29 months. Results: Eight patients underwent 10 TCAR procedures via a prosthetic conduit. A total of 2 procedures (20%) were performed on female patients and 8 procedures (75%) were performed on male patients. The mean age was 65 years old (standard deviation 11 years). Technical success was 100%. The 30-day ipsilateral stroke rate was 0%. The 30-day patency was 90%. There was no re-exploration for hemorrhage and 30 day mortality was 0%. Conclusions: TCAR is an excellent option for carotid artery revascularization. Unfavorable CCA anatomy has limited its applicability. TCAR via a prosthetic conduit has the potential to expand eligibility for this promising therapy.
Language	English
Publishing date	2024-02-22
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1027366-9
ISSN	1615-5947 ; 0890-5096
ISSN (online)	1615-5947
ISSN	0890-5096
DOI	10.1016/j.avsg.2023.12.075
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Article: Boerhaave's syndrome presenting as a mid-esophageal perforation associated with a right-sided pleural effusion.

Reardon, Emily S / Martin, Linda W

Journal of surgical case reports

2015 Volume 2015, Issue 11

Abstract: There are few published case reports of Boerhaave's syndrome presenting as a mid-esophageal perforation associated with a right-sided pleural effusion. We present an unusual case of spontaneous perforation of the mid-esophagus and discuss the surgical ... ...

Abstract	There are few published case reports of Boerhaave's syndrome presenting as a mid-esophageal perforation associated with a right-sided pleural effusion. We present an unusual case of spontaneous perforation of the mid-esophagus and discuss the surgical management and outcome. Our case underscores the importance of a meticulous diagnostic and therapeutic approach to the management of an often elusive and difficult disease process.
Language	English
Publishing date	2015-11-24
Publishing country	England
Document type	Case Reports
ISSN	2042-8812
ISSN	2042-8812
DOI	10.1093/jscr/rjv142
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Article ; Online: Extended resections of non-small cell lung cancers invading the aorta, pulmonary artery, left atrium, or esophagus: can they be justified?

Reardon, Emily S / Schrump, David S

Thoracic surgery clinics

2014 Volume 24, Issue 4, Page(s) 457–464

Abstract: T4 tumors that invade the heart, great vessels, or esophagus comprise a heterogenous group of locally invasive lung cancers. Prognosis depends on nodal status; this relationship has been consistently demonstrated in many of the small series of extended ... ...

Abstract	T4 tumors that invade the heart, great vessels, or esophagus comprise a heterogenous group of locally invasive lung cancers. Prognosis depends on nodal status; this relationship has been consistently demonstrated in many of the small series of extended resection. Current National Comprehensive Cancer Network guidelines do not recommend surgery for T4 extension with N2-3 disease (stage IIIB). However, biopsy-proven T4 N0-1 (stage IIIA) may be operable. Localized tumors with invasion of the aorta, pulmonary artery, left atrium, or esophagus represent a small subset of T4 disease. Acquiring sufficient randomized data to provide statistical proof of a survival advantage for patients undergoing extended resections for these neoplasms will likely never be possible.Therefore, we are left to critically analyze current documented experience to make clinical decisions on a case-by-case basis.It is clear that the operative morbidity and mortality of extended resections for locally advanced T4 tumors have significantly improved over time,yet the risks are still high. The indications for such procedures and the anticipated outcomes should be clearly weighed in terms of potential perioperative complications and expertise of the surgical team. Patients with T4 N0-1 have the best prognosis and with complete resection may have the potential for cure. The use of induction therapy and surgery for advanced T4 tumors may improve survival. Current data suggest that for tumors that invade the aorta, pulmonary artery,left atrium, or esophagus, resection should be considered in relation to multidisciplinary care.For properly selected patients receiving treatment at high volume, experienced centers, extended resections may be warranted.
MeSH term(s)	Aorta, Thoracic/pathology ; Carcinoma, Non-Small-Cell Lung/pathology ; Carcinoma, Non-Small-Cell Lung/surgery ; Esophagus/pathology ; Heart Atria/pathology ; Humans ; Lung Neoplasms/pathology ; Lung Neoplasms/surgery ; Neoplasm Invasiveness ; Neoplasm Staging ; Pneumonectomy/methods ; Pulmonary Artery/pathology
Language	English
Publishing date	2014-09-11
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2149218-9
ISSN	1558-5069 ; 1547-4127
ISSN (online)	1558-5069
ISSN	1547-4127
DOI	10.1016/j.thorsurg.2014.07.012
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Article ; Online: Editorial commentary: Esophageal complications: what are the real results?

Taylor Ripley, R / Reardon, Emily S

Seminars in thoracic and cardiovascular surgery

2014 Volume 26, Issue 4, Page(s) 295–296

MeSH term(s)	Esophageal Neoplasms/surgery ; Esophagectomy/adverse effects ; Female ; Humans ; Lung/physiopathology ; Male ; Respiration Disorders/epidemiology
Language	English
Publishing date	2014
Publishing country	United States
Document type	Comment ; Editorial
ZDB-ID	1038278-1
ISSN	1532-9488 ; 1043-0679
ISSN (online)	1532-9488
ISSN	1043-0679
DOI	10.1053/j.semtcvs.2015.03.002
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Article: Pulmonary mucosa-associated lymphoma in a patient with von Hippel-Lindau disease.

Straughan, David M / Kerkar, Sid / Azoury, Saїd C / Reardon, Emily S / Schrump, David S

Journal of surgical case reports

2015 Volume 2015, Issue 7

Abstract: A 61-year-old female with a past medical history significant for von Hippel-Lindau (VHL) syndrome presented with multiple bilateral pulmonary lesions found on surveillance computed tomography scan. Positron emission tomography demonstrated avidity in a ... ...

Abstract	A 61-year-old female with a past medical history significant for von Hippel-Lindau (VHL) syndrome presented with multiple bilateral pulmonary lesions found on surveillance computed tomography scan. Positron emission tomography demonstrated avidity in a lesion in the right upper lobe. After an equivocal biopsy, a lobectomy via a thoracoscopic approach was performed as this lesion was concerning for a primary lung cancer. Pathology revealed a diagnosis of pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma. To our knowledge, this is the first reported case of a pulmonary MALT lymphoma in a patient with VHL.
Language	English
Publishing date	2015-07-14
Publishing country	England
Document type	Case Reports
ISSN	2042-8812
ISSN	2042-8812
DOI	10.1093/jscr/rjv080
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Article: Unknown primary nasopharyngeal melanoma presenting as severe recurrent epistaxis and hearing loss following treatment and remission of metastatic disease: A case report and literature review.

Azoury, Saïd C / Crompton, Joseph G / Straughan, David M / Klemen, Nicholas D / Reardon, Emily S / Beresnev, Tatiana H / Hughes, Marybeth S

International journal of surgery case reports

2015 Volume 10, Page(s) 232–235

Abstract: Introduction: Primary nasopharyngeal melanoma is an exceedingly rare pathology with unclear etiology and oftentimes obscure clinical presentation. Despite improved diagnostic capabilities, these lesions are often diagnosed at an advanced stage and ... ...

Abstract	Introduction: Primary nasopharyngeal melanoma is an exceedingly rare pathology with unclear etiology and oftentimes obscure clinical presentation. Despite improved diagnostic capabilities, these lesions are often diagnosed at an advanced stage and associated prognosis is poor, partly due to high rates of recurrences and metastasis. Presentation of case: A 74-year-old woman was diagnosed with metastatic melanoma to the liver, of unknown primary. Just prior to the time of diagnosis, she experienced several episodes of severe epistaxis which she managed conservatively. Her symptoms eventually subsided without further medical evaluation. The patient was initially treated with interleukin-2 (IL-2) for her advanced disease, but her cancer progressed. She was then enrolled in a protocol for percutaneous hepatic perfusion (PHP) with melphalan and had complete radiographic resolution of disease, yet her nosebleeds recurred and persisted despite conservative measures. Six years after her initial diagnosis, a nasopharyngoscopy demonstrated a pigmented lesion in the posterior nasopharynx. Surgical resection was performed (pathology consistent with mucosal melanoma) followed by radiation therapy. She has since had complete resolution of bleeding and shows no evidence of cancer. Discussion: To our knowledge, this is the first report of a diagnosis of primary nasopharyngeal melanoma 6-years following complete remission of metastatic disease. Surgery remains the primary treatment for disease and symptom control in this setting. Conclusion: Timely diagnosis of nasopharyngeal melanomas remains challenging. Thorough clinical evaluations should be performed in such patients, and attention should be paid to recurrent and persistent symptoms, such as epistaxis and hearing loss. This may allow for earlier detection of primary disease.
Language	English
Publishing date	2015-04-01
Publishing country	Netherlands
Document type	Journal Article
ISSN	2210-2612
ISSN	2210-2612
DOI	10.1016/j.ijscr.2015.03.053
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Article ; Online: Pulmonary Metastases Exhibit Epigenetic Clonality: Implications for Precision Cancer Therapy.

Reardon, Emily S / Hong, Julie A / Straughan, David M / Azoury, Saïd C / Zhang, Mary / Schrump, David S

The Annals of thoracic surgery

2015 Volume 100, Issue 5, Page(s) 1839–48; discussion 1848

Abstract: Background: Development of effective cancer therapies may be limited by intratumoral heterogeneity, which facilitates outgrowth and organ-specific dissemination of treatment resistant clones. At present, limited information is available regarding ... ...

Abstract	Background: Development of effective cancer therapies may be limited by intratumoral heterogeneity, which facilitates outgrowth and organ-specific dissemination of treatment resistant clones. At present, limited information is available regarding epigenetic landscapes of pulmonary metastases. This study was undertaken to characterize epigenetic signatures of pulmonary metastases and to identify potential therapeutic targets. Methods: RNA and DNA were extracted from 65 pulmonary metastases resected from 12 patients (5 with sarcoma, 7 with adrenocortical carcinoma). Quantitative reverse transcription polymerase chain reaction techniques were used to evaluate expression levels of cancer-testis (CT) genes (NY-ESO-1, MAGE-A3, MAGE-A9, MAGE-A12, GAGE1, CT-45, SSX-1, and SSX-2), tumor suppressor (TS) genes (p16 and RASSF1A), and genes encoding epigenetic modifiers (DNMT1, DNMT3A, DNMT3B, EZH2, EED, and SUZ12), aberrantly expressed in human malignant diseases. Pyrosequencing techniques were used to quantitate DNA methylation levels in LINE1, NBL2, and D4Z4 repetitive sequences and promoter methylation status of differentially regulated genes. Results of these analyses were compared with a standardized panel of normal lung tissues. Results: Pulmonary metastases exhibited histologically related and patient-specific global DNA demethylation. Significant interpatient heterogeneity of gene expression was observed even among patients with similar tumor histologic features. Epigenetic signatures appeared consistent among metastases from the same patient, irrespective of the time of resection (synchronous/metachronous) or the anatomic location. EZH2, EED, and SUZ12 (core components of Polycomb repressive complex-2 [PRC-2]) were upregulated in the majority of metastases. Conclusions: Pulmonary metastases exhibit patient-specific epigenetic clonality, which may be exploited for precision therapies targeting aberrant CT or TS gene expression. PRC-2 may be a shared target for epigenetic therapy of pulmonary metastases.
MeSH term(s)	Adolescent ; Adult ; Aged ; Epigenesis, Genetic ; Female ; Humans ; Lung Neoplasms/genetics ; Lung Neoplasms/secondary ; Lung Neoplasms/therapy ; Male ; Middle Aged ; Precision Medicine ; Young Adult
Language	English
Publishing date	2015-11
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	211007-6
ISSN	1552-6259 ; 0003-4975
ISSN (online)	1552-6259
ISSN	0003-4975
DOI	10.1016/j.athoracsur.2015.05.089
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Article ; Online: UHRF1 Is a Novel Druggable Epigenetic Target in Malignant Pleural Mesothelioma.

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer

2020 Volume 16, Issue 1, Page(s) 89–103

Abstract: Introduction: Ubiquitin-like with plant homeodomain and ring finger domains 1 (UHRF1) encodes a master regulator of DNA methylation that has emerged as an epigenetic driver in human cancers. To date, no studies have evaluated UHRF1 expression in ... ...

Abstract	Introduction: Ubiquitin-like with plant homeodomain and ring finger domains 1 (UHRF1) encodes a master regulator of DNA methylation that has emerged as an epigenetic driver in human cancers. To date, no studies have evaluated UHRF1 expression in malignant pleural mesothelioma (MPM). This study was undertaken to explore the therapeutic potential of targeting UHRF1 in MPM. Methods: Microarray, real-time quantitative reverse transcription-polymerase chain reaction, immunoblot, and immunohistochemistry techniques were used to evaluate UHRF1 expression in normal mesothelial cells (NMCs) cultured with or without asbestos, MPM lines, normal pleura, and primary MPM specimens. The impact of UHRF1 expression on MPM patient survival was evaluated using two independent databases. RNA-sequencing, proliferation, invasion, and colony formation assays, and murine xenograft experiments were performed to evaluate gene expression and growth of MPM cells after biochemical or pharmacologic inhibition of UHRF1 expression. Results: UHRF1 expression was significantly higher in MPM lines and specimens relative to NMC and normal pleura. Asbestos induced UHRF1 expression in NMC. The overexpression of UHRF1 was associated with decreased overall survival in patients with MPM. UHRF1 knockdown reversed genomewide DNA hypomethylation, and inhibited proliferation, invasion, and clonogenicity of MPM cells, and growth of MPM xenografts. These effects were phenocopied by the repurposed chemotherapeutic agent, mithramycin. Biochemical or pharmacologic up-regulation of p53 significantly reduced UHRF1 expression in MPM cells. RNA-sequencing experiments exhibited the pleiotropic effects of UHRF1 down-regulation and identified novel, clinically relevant biomarkers of UHRF1 expression in MPM. Conclusions: UHRF1 is an epigenetic driver in MPM. These findings support the efforts to target UHRF1 expression or activity for mesothelioma therapy.
MeSH term(s)	Animals ; CCAAT-Enhancer-Binding Proteins/genetics ; Cell Line, Tumor ; Cell Proliferation ; Epigenesis, Genetic ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/genetics ; Mesothelioma/drug therapy ; Mesothelioma/genetics ; Mesothelioma, Malignant ; Mice ; Pleural Neoplasms/drug therapy ; Pleural Neoplasms/genetics ; Ubiquitin-Protein Ligases
Chemical Substances	CCAAT-Enhancer-Binding Proteins ; UHRF1 protein, human (EC 2.3.2.27) ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Uhrf1 protein, mouse (EC 2.3.2.27)
Language	English
Publishing date	2020-09-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2432037-7
ISSN	1556-1380 ; 1556-0864
ISSN (online)	1556-1380
ISSN	1556-0864
DOI	10.1016/j.jtho.2020.08.024
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Article ; Online: Induction of Thioredoxin-Interacting Protein by a Histone Deacetylase Inhibitor, Entinostat, Is Associated with DNA Damage and Apoptosis in Esophageal Adenocarcinoma.

Molecular cancer therapeutics

2018 Volume 17, Issue 9, Page(s) 2013–2023

Abstract: In 2017, an estimated 17,000 individuals were diagnosed with esophageal adenocarcinoma (EAC), and less than 20% will survive 5 years. Positron emission tomography avidity is indicative of high glucose utilization and is nearly universal in EAC. TXNIP ... ...

Abstract	In 2017, an estimated 17,000 individuals were diagnosed with esophageal adenocarcinoma (EAC), and less than 20% will survive 5 years. Positron emission tomography avidity is indicative of high glucose utilization and is nearly universal in EAC. TXNIP blocks glucose uptake and exhibits proapoptotic functions. Higher expression in EAC has been associated with improved disease-specific survival, lack of lymph node involvement, reduced perineural invasion, and increased tumor differentiation. We hypothesized that TXNIP may act as a tumor suppressor that sensitizes EAC cells to standard chemotherapeutics. EAC cell lines and a Barrett epithelial cell line were used. qRT-PCR, immunoblot, and immunofluorescence techniques evaluated gene expression. TXNIP was stably overexpressed or knocked down using lentiviral RNA transduction techniques. Murine xenograft methods examined growth following overexpression of TXNIP. Apoptosis and DNA damage were measured by annexin V and γH2AX assays. Activation of the intrinsic apoptosis was quantitated with green fluorescence protein-caspase 3 reporter assay. In cultured cells and an esophageal tissue array, TXNIP expression was higher in Barrett epithelia and normal tissue compared with EAC. Constitutive overexpression of TXNIP decreased proliferation, clonogenicity, and tumor xenograft growth. TXNIP overexpression increased, whereas knockdown abrogated, DNA damage and apoptosis following cisplatin treatment. An HDAC inhibitor, entinostat (currently in clinical trials), upregulated TXNIP and synergistically increased cisplatin-mediated DNA damage and apoptosis. TXNIP is a tumor suppressor that is downregulated in EACC. Its reexpression dramatically sensitizes these cells to cisplatin. Our findings support phase I/II evaluation of "priming" strategies to enhance the efficacy of conventional chemotherapeutics in EAC.
MeSH term(s)	Adenocarcinoma/drug therapy ; Adenocarcinoma/genetics ; Adenocarcinoma/metabolism ; Animals ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Apoptosis/drug effects ; Apoptosis/genetics ; Benzamides/pharmacology ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Cell Line, Tumor ; Cisplatin/administration & dosage ; DNA Damage ; Esophageal Neoplasms/drug therapy ; Esophageal Neoplasms/genetics ; Esophageal Neoplasms/metabolism ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Histone Deacetylase Inhibitors/pharmacology ; Humans ; Mice, Nude ; Pyridines/pharmacology ; Transcriptional Activation/drug effects ; Xenograft Model Antitumor Assays
Chemical Substances	Benzamides ; Carrier Proteins ; Histone Deacetylase Inhibitors ; Pyridines ; TXNIP protein, human ; entinostat (1ZNY4FKK9H) ; Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2018-06-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	2063563-1
ISSN	1538-8514 ; 1535-7163
ISSN (online)	1538-8514
ISSN	1535-7163
DOI	10.1158/1535-7163.MCT-17-1240
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Article ; Online: ASXL3 Is a Novel Pluripotency Factor in Human Respiratory Epithelial Cells and a Potential Therapeutic Target in Small Cell Lung Cancer.

Cancer research

2017 Volume 77, Issue 22, Page(s) 6267–6281

Abstract: In this study, we generated induced pluripotent stem cells (iPSC) from normal human small airway epithelial cells (SAEC) to investigate epigenetic mechanisms of stemness and pluripotency in lung cancers. We documented key hallmarks of reprogramming in ... ...

Abstract	In this study, we generated induced pluripotent stem cells (iPSC) from normal human small airway epithelial cells (SAEC) to investigate epigenetic mechanisms of stemness and pluripotency in lung cancers. We documented key hallmarks of reprogramming in lung iPSCs (Lu-iPSC) that coincided with modulation of more than 15,000 genes relative to parental SAECs. Of particular novelty, we identified the PRC2-associated protein, ASXL3, which was markedly upregulated in Lu-iPSCs and small cell lung cancer (SCLC) lines and clinical specimens.
MeSH term(s)	Animals ; Cell Line, Tumor ; Cells, Cultured ; Cellular Reprogramming ; Epigenesis, Genetic ; Epithelial Cells/metabolism ; Gene Expression Profiling/methods ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Induced Pluripotent Stem Cells/transplantation ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism ; Lung Neoplasms/pathology ; Mice, Inbred NOD ; Mice, Knockout ; Mice, SCID ; Respiratory Mucosa/cytology ; Small Cell Lung Carcinoma/genetics ; Small Cell Lung Carcinoma/metabolism ; Small Cell Lung Carcinoma/pathology ; Teratoma/genetics ; Teratoma/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transplantation, Heterologous
Chemical Substances	ASXL3 protein, human ; Transcription Factors
Language	English
Publishing date	2017-09-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-17-0570
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