Paul Weinberger

Deaconess Clinic · Otolaryngology

The North American Airway Collaborative (NoAAC) previously published a 3‐year multi‐institutional prospective cohort study showing variation in treatment effectiveness between 3 primary surgical techniques for idiopathic subglottic stenosis (iSGS). In this report, we update these findings to include 5 years of data evaluating treatment effectivenes...

Objectives: Serial intralesional steroid injection (SILSI) has been increasingly used to treat idiopathic subglottic stenosis (iSGS). Prior studies have shown effectiveness, but not in all patients. This multi-institutional study evaluates the effect of SILSI on time to recurrent operation, peak expiratory flow (PEF), and dyspnea. Methods: Post-...

Anaplastic thyroid cancer is among the most aggressive of human cancers, and currently there are few effective treatments for most patients. YM155, first identified as a survivin inhibitor, was highlighted in a high-throughput screen performed by the National Cancer Institute, killing anaplastic thyroid cancer cells in vitro and in vivo. However, t...

Introduction: Anaplastic thyroid cancer (ATC) is among the most aggressive of all human cancers with a median survival of 4.3 months. Currently, there is no effective treatment for most ATC patients - surgery, radiation, and chemotherapy all fail to significantly prolong ATC patient survival. YM155, first identified as a survivin inhibitor, was hig...

Objective Develop a prototype steroid eluting stent suitable for endoscopic treatment of subglottic stenosis. Methods Rectangular-shaped spoke design stents thermally molded into horseshoe-shaped stents were developed using AutoCAD program, and printed on a Lulzbot 3D printer with polycaprolactone (PCL). Kenalog saturated AEROSIL 200 was embedded...

Objectives To examine whether social determinants of health (SDH) factors are associated with time to diagnosis, treatment selection, and time to recurrent surgical intervention in idiopathic subglottic stenosis (iSGS) patients. Methods Adult patients with diagnosed iSGS were recruited prospectively (2015-2017) via clinical providers as part of th...

Anaplastic thyroid cancer (ATC) is one of the most lethal malignancies with a median survival time of about 4 months. Currently, there is no effective treatment, and the development of new therapies is an important and urgent issue for ATC patients. YM155 is a small molecule that was identified as the top candidate in a high-throughput screen of sm...

Physiological and pathological roles for R-loop structures continue to be discovered, and studies suggest that R-loops could contribute to human disease. R-loops are nucleic acid structures characterized by a DNA:RNA hybrid and displaced single-stranded DNA that occur in connection with transcription. R-loops form naturally and have been shown to b...

Introduction: Anaplastic thyroid cancer (ATC) is a rapidly fatal disease with a median survival of less than 6 months. Although rare, ATC is responsible for a disproportionate number of thyroid cancer deaths and is highly resistant to common cancer therapies. YM155 is a small molecule drug identified in a screen by the National Cancer Institute tha...

Objectives Pneumatic compression garment therapy (PCGT) has been established as treatment for postradiotherapy lymphedema, and its use in head and neck patients is becoming more common. Although effects on interstitial edema of the cervical soft tissues have been studied, effects on internal laryngopharyngeal edema, as well as associated symptoms o...

Importance Surgical treatment comparisons in rare diseases are difficult secondary to the geographic distribution of patients. Fortunately, emerging technologies offer promise to reduce these barriers for research. Objective To prospectively compare the outcomes of the 3 most common surgical approaches for idiopathic subglottic stenosis (iSGS), a...

Objectives: p16INK4A (p16) is the most widely used clinical biomarker for Human Papillomavirus (HPV) in head and neck squamous cell cancer (HNSCC). HPV is a favourable prognostic marker in HNSCC and is used for patient stratification. While p16 is a relatively accurate marker for HPV within the oropharynx, recent reports suggest it may be unsuitab...

Objectives/hypothesis: The most promising stem cell-derived tracheal transplantation approach is dependent upon the use of decellularized tracheal grafts. It has been assumed that a sterilization step, such as gamma radiation, would damage the delicate extracellular matrix of the graft, thus rendering it less viable for cellular repopulation, alth...

Background: Anaplastic thyroid carcinoma (ATC) accounts for only 3% of thyroid cancers, yet strikingly, it accounts for almost 40% of thyroid cancer deaths. Currently, no effective therapies exist. In an effort to identify ATC-specific therapeutic targets, we analyzed global gene expression data from multiple studies to identify ATC-specific dysre...

YM155 (sepantronium bromide) has been evaluated in clinical trials as a survivin suppressant, but despite positive signals from early work, later studies were negative. Clarification of the mechanism of action of YM155 is important for its further development. YM155 affects cells in a cell cycle-specific manner. When cells are in G1, YM155 prevente...

Objectives: Cervical cancer is the second most common cancer of women worldwide. In this prospective study, we attempted to identify a set of serum biomarkers, which could identify patients who have invasive cervical cancer and possibly help monitor disease status (recurrence, remission). Methods: Luminex bead array was used to measure serum protei...

Tiny bubbles or glass microspheres/microcapsules are used in our society today in many ways. The microspheres can be solid or hollow and represent particles that are generally in the range of 0.1-100 μm. Solid and hollow microspheres have significantly different densities, properties, and capabilities and are commercially available. Special morphol...

Infection or damage to the trachea, a thin walled and cartilage reinforced conduit that connects the pharynx and larynx to the lungs, leads to serious respiratory medical conditions which can often prove fatal. Current clinical strategies for complex tracheal reconstruction are of limited availability and efficacy, but tissue engineering and regene...

Background: Transgelin is an actin-binding protein that promotes motility in normal cells. Although the role of transgelin in cancer is controversial, a number of studies have shown that elevated levels correlate with aggressive tumor behavior, advanced stage, and poor prognosis. Here we sought to determine the role of transgelin more directly by...

Objectives/hypothesis: Clinically, inflammatory polyps are found in the middle turbinate (MT) in patients with chronic rhinosinusitis (CRS) but not in the inferior turbinate (IT). The purpose of this study was to investigate differences in protein expression between IT and MT tissue in patients with CRS. Study design: Prospective cohort. Method...

Background Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papi...

Hypothesis: An inexpensive temporal bone model for use in a temporal bone dissection laboratory setting can be made using a commercially available, consumer-grade 3D printer. Background: Several models for a simulated temporal bone have been described but use commercial-grade printers and materials to produce these models. The goal of this project...

Balloon dilation is generally considered first-line treatment for airway stenosis. Some dilation systems utilize a compliant balloon that can conform around rigid structures. Others use a noncompliant balloon that does not conform, allowing for dilation of more rigid stenoses. We hypothesized that subglottic dilation with a noncompliant balloon inc...

Please find the full text at: http://www.jultrasoundmed.org/content/34/8/1.6.short

Cancer biologists and other healthcare researchers face an increasing challenge in addressing the molecular complexity of disease. Biomarker measurement tools and techniques now contribute to both basic science and translational research. In particular, liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM) for multiplexed me...

The Cancer Genome Atlas profiled 279 head and neck squamous cell carcinomas (HNSCCs) to provide a comprehensive landscape of somatic genomic alterations. Here we show that human-papillomavirus-associated tumours are dominated by helical domain mutations of the oncogene PIK3CA, novel alterations involving loss of TRAF3, and amplification of the cell...

Objectives/HypothesisSuture closure and fibrin glue placement have been advocated as alternatives to healing by secondary intention. The aim of this study was to examine the tensile strength of these microflap closure techniques.Study DesignBasic research.Methods Three pairs of excised bovine true vocal folds underwent microflap creation and closur...

Objectives/HypothesisTo determine structural biomechanical changes in tracheal scaffolds resulting from cellular reduction and storage at −80oC.Study DesignLaboratory-based study.Methods Forty-four rabbit tracheal segments were separated into four treatment groups: untreated (group A, control), cellular-reduced (group B), storage at −80oC followed...

High charge and energy (HZE) particles are a main hazard of the space radiation environment. Uncertainty regarding their health effects is a limiting factor in the design of human exploration-class space missions, that is, missions beyond low earth orbit. Previous work has shown that HZE exposure increases cancer risk and elicits other aging-like p...

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Here, we describe the genomic landscape of 496 PTCs. We observed a low frequency of somatic alterations (relative to other carcinomas) and extended the set of known PTC driver alterations to include EIF1AX, PPM1D, and CHEK2 and diverse gene fusions. These discoveries reduc...

Purpose Whereas selection of endotracheal tube (ETT) size in pediatric patients benefits from predictive nomograms, adult ETT sizing is relatively arbitrary. We sought to determine associations between cervical tracheal cross-sectional area (CTCSA) and clinical variables. Methods One hundred thirty-two consecutive patients undergoing noncontrasted...

Objectives/HypothesisSurgical advancements rely heavily on validated animal models. The New Zealand White (NZW) rabbit is a widely used model for airway research, including regenerative medicine applications. Currently, the biomechanical properties of the normal rabbit trachea are not known. Our objective was to define these properties to assist in...

To improve understanding of aspects of end-of-life care which may not be intuitive to the otolaryngology community. A comprehensive review of the literature was performed by searching Medline, Embase, and Google Scholar databases. Primary manuscripts' bibliographies were reviewed to identify any non-indexed references. Prospective consultation by m...

Objectives/HypothesisThere is a paucity of experience in the published literature documenting complications of powered surgical instruments in laryngologic surgery. Our objective was to ascertain the nature of these complications from expert opinion and review of the literature, and to recommend strategies to decrease major complications.Study Desi...

The primary objective is to design a reporter assay to measure molecular release kinetics from a new porous-wall hollow glass microsphere biomaterial with great potential in regenerative medicine and drug delivery. Second, future avenues for research will be discussed specifically in regards to potential clinical uses in Laryngology. N/A - basic sc...

Urothelial carcinoma of the bladder is a common malignancy that causes approximately 150,000 deaths per year worldwide. So far, no molecularly targeted agents have been approved for treatment of the disease. As part of The Cancer Genome Atlas project, we report here an integrated analysis of 131 urothelial carcinomas to provide a comprehensive land...

The purpose of our study was to evaluate whether swallowing maneuvers designed to impact pharyngeal physiology would also impact esophageal physiology. Healthy volunteers underwent high-resolution manometry while performing three randomized swallowing maneuvers with and without a 5-ml bolus: normal swallowing, Mendelsohn maneuver, and effortful swa...

Objectives There is no formal body of literature focusing on complications in laryngologic and airway surgery performed with microdebriders. Attendees can expect to: 1) Describe potential complications that may occur with microdebrider use during laryngologic and airway surgery. 2) Recognize which clinical situations are better suited to the use of...

Program Description This miniseminar will highlight advances in clinical case management of patients with dyspnea associated with upper airway tract abnormalities. Both endoscopic and open management of the difficult airway will be discussed. A perspective on advances and options for office based management will be offered. A perspective on indicat...

We studied a case series to evaluate the effect of topical bethanechol chloride on esophageal function in individuals with ineffective esophageal motility. Five subjects with ineffective esophageal motility underwent high resolution esophageal manometry. Ten 5 mL liquid swallows were performed to establish a baseline. Five milligrams of topical bet...

Purpose: While selection of endotracheal tube (ETT) size in pediatric patients has established predictive nomograms, in adults ETT sizing is relatively arbitrary. We sought to determine associations between cervical tracheal cross-sectional area (TCSA) and clinical demographic variables. Methods: Inclusion criteria were consecutive patients undergo...

Prenatal ultrasound exams have become increasingly frequent. Although no serious adverse effects are known, the public health implications would be enormous should adverse effects on auditory development be shown. This study looks to establish a possible correlation between hearing loss and increased prenatal ultrasound exposure. Retrospective coho...

A preponderance of literature supports the safety of office-based flexible endoscopic procedures of the upper aerodigestive tract; however, until recently there were no data regarding hemodynamic stability during these procedures. A recent study showed intraprocedure changes in patients' hemodynamic parameters, raising the concern that perhaps pati...

Objective: To investigate the presence of Helicobacter pylori (H pylori), a key pathogen in chronic gastritis and recognized as a major cause of gastric cancer, in cancer samples and adjacent normal tissues of the head and neck region. Method: Twenty-eight fresh-frozen HNSCC samples and 11 biopsies from normal tissue were obtained from fully inform...

A 73-year-old man presented for an updated hearing evaluation along with complaints of a white, flaky discharge from his left ear. He reported a long-standing history of hearing loss. He had been unable to wear a hearing aid on the left side for the previous 2 to 3 years because of chronic irritation. Physical examination of his left ear revealed s...

Reconstruction of long-segment tracheal stenosis remains problematic. Ex vivo transplantation of stem cell-derived tracheas has been established in humans using external tissue bioreactors. These bioreactors, however, are not widely accessible. Thus, we are developing a rotational flap-based "internal bioreactor" to allow in vivo stem cell engraftm...

Tracheal resection anastomoses are often under tension and can be technically challenging. New suture materials such as V-loc (barbed, knotless wound closure device) may offer advantages over conventional methods. The objective of this study is to determine if a running V-loc suture is of comparable tensile strength to conventional closure. Laborat...

Up to 50% of oral squamous cell carcinomas (OSCCs) recur following surgical resections with conventional "histologically-negative" margins. Three members of the SIBLING family of proteins: dentin sialophophoprotein (DSPP); bone sialoprotein (BSP); and osteopontin OPN are upregulated in OSCCs. In this study, we aimed to correlate the expression of D...

To determine the prevalence of helmet use in children involved in all-terrain vehicles (ATV) accidents. Retrospective chart review. Tertiary Academic Medical Center. Retrospective review was performed using the trauma registry of an academic tertiary medical center identifying ATV injured patients under 13 years of age between 2003-2008. Data regar...

Objectives/HypothesisTechniques available for reconstruction of the cricotracheal region in adults are currently suboptimal. We sought to 1) understand the anatomic basis for the thyroid ala perichondrial flap, 2) describe the technique of harvesting and intraluminal placement, and 3) learn the limitations of defects for which it can be used. Study...

Objective: Although multiple theories in the past have linked hearing loss to dysphonia, clear evidence of an association is lacking. It is well known that both hearing loss and dysphonia contribute to decreased quality of life. The objective of this study is to elucidate the association of hearing loss with dysphonia. Method: Patients presenting w...

Intraoperative parathyroid hormone (IOPTH) monitoring has emerged as a useful adjunct in parathyroidectomy. Originally performed within the operating room, removal of the Nichols assay from the market forced many surgeons to rely on testing done in central laboratories, reducing convenience and prolonging operative times. The authors hypothesized t...

To determine whether there is an association between the presence of asthma and a clinically aggressive disease course in patients with recurrent respiratory papillomatosis (RRP). Retrospective multi-institutional cohort study (level III evidence). Two academic medical centers in the southeastern United States. Adult patients with RRP treated at th...

Objective: Up to 50% of oral squamous cell carcinomas (OSCCs) recur following surgical resections with conventional "histologically-negative" margins. Three members of the SIBLING family of proteins: dentin sialophophoprotein (DSPP); bone sialoprotein (BSP); and osteopontin OPN are upregulated in OSCC. This study aimed to correlate the expression o...

The intraoperative parathyroid hormone (IOPTH) assay is an important tool that facilitates targeted parathyroidectomy and may increase surgical cure rates. We sought to evaluate the utility of a point-of-care assay to distinguish parathyroid adenomas from nonparathyroid tissues, which can sometimes pose a challenge during parathyroidectomy and is c...

As with many epithelial cancers, presence of nodal metastases in patients with Head and Neck Squamous Cell Carcinoma (HNSCC) predicts early recurrence and poor survival. Determination of occult metastases in the clinically N-zero (cN0) patient remains problematic and therefore prophylactic neck dissections are routinely performed for high risk cN0...

Mortality for black males with head and neck squamous cell carcinoma (HNSCC) is twice that of white males or females. Human papillomavirus (HPV)-active HNSCC, defined by the concurrent presence of high-risk type HPV DNA and host cell p16(INK4a) expression, is associated with decreased mortality. We hypothesized that prevalence of this HPV-active di...

We sought to determine the role of human papillomavirus (HPV) E6 and E7 oncogenes in nuclear beta-catenin accumulation, a hallmark of activated canonical Wnt signaling pathway. We used HPV16-positive oropharyngeal cancer cell lines 147T and 090, HPV-negative cell line 040T, and cervical cell lines SiHa (bearing integrated HPV16) and HeLa (bearing i...

HPV-positive oropharyngeal squamous cell carcinomas (OSCC) represent a distinct disease entity from traditional OSCC. We hypothesized that for HPV DNA-positive cases, p16 expression status differentiates the biologically relevant ones. We determined HPV16DNA viral load in a cohort of 79 oropharyngeal squamous cell cancers by real-time polymerase c...

The objective of this study was to obtain more accurate quantitation of HSPB1 expression in HNSCC using a novel quantitative protein expression analysis system based on multispectral imaging. The study was a retrospective laboratory study of HNSCC patients treated at tertiary care academic medical center. Archival tissue samples from forty seven pa...

HSPB1 functions to prevent stress-induced cellular damage and has is elevated in multiple cancer types. The significance of HSPB1 in HNSCC remains controversial. We sought to perform a meta-analysis of HSPB1 expression to clarify previous findings. Meta-analysis of all published studies of HSPB1 in HNSCC patients using IHC techniques. A literature...

Identify proteins that are differentially expressed between head and neck squamous cell cancer (HNSCC) and patient-matched normal adjacent tissue, and validate findings in a separate patient cohort. Cross-sectional study of surgical specimens. Tertiary care academic medical center. Laser capture microdissection and two-dimensional difference gel el...

The purpose of this study was to determine if oropharyngeal squamous cell carcinoma (OSCC) classified into three groups based on human papillomavirus (HPV) 16 DNA presence and p16 expression display different protein expression patterns. Cross-sectional study. A laboratory-based study of patients with OSCC treated at a tertiary care academic medica...

A 54-year-old woman who had previously been treated for intermittent dizziness of an indeterminate nature presented with a 1-week history of left-sided otalgia that radiated to the deep neck structures on the left side. She was otherwise in good health, with no recent history of trauma to the neck or head. Her pain was described as a deep retroauri...