Jason T. Rich

TRANSORAL LASER MICROSURGERY AS PRIMARY TREATMENT FOR ADVANCED-STAGE OROPHARYNGEAL CANCER: A UNITED STATES MULTICENTER STUDY

Nonsurgical modalities are sometimes advocated as the standard of care for advanced oropharyngeal tumors. Oncologic and functional results have been modest. The aim of our study was to evaluate outcomes of a minimally invasive approach, using transoral laser microsurgery (TLM) as the primary treatment for advanced oropharyngeal carcinoma.

A PRACTICAL GUIDE TO UNDERSTANDING KAPLAN-MEIER CURVES

In 1958, Edward L. Kaplan and Paul Meier collaborated to publish a seminal paper on how to deal with incomplete observations. Subsequently, the Kaplan-Meier curves and estimates of survival data have become a familiar way of dealing with differing survival times (times-to-event), especially when not all the subjects continue in the study. “Survival” times need not relate to actual survival with death being the event; the “event” may be any event of interest. Kaplan-Meier analyses are also used in nonmedical disciplines. The purpose of this article is to explain how Kaplan-Meier curves are generated and analyzed. Throughout this article, we will discuss Kaplan-Meier estimates in the context of “survival” before the event of interest. Two small groups of hypothetical data are used as examples in order for the reader to clearly see how the process works. These examples also illustrate the crucially important point that comparative analysis depends upon the whole curve and not upon isolated points.

Transoral laser microsurgery (TLM) +/- adjuvant therapy for advanced stage oropharyngeal cancer: outcomes and prognostic factors.

Document survival, prognostic variables, and functional outcomes of patients with AJCC stage III or IV oropharyngeal cancer, treated with transoral laser microsurgery (TLM) ± adjuvant therapy.

Transoral laser microsurgery: A new approach for unknown primaries of the head and neck

To evaluate the efficacy of transoral laser microsurgery (TLM) used at examination under anesthesia (EUA) for detection and management of an unidentified primary site and to determine survival with both TLM EUA and traditional rigid pharyngolaryngoscopy EUA, with directed biopsies.

Swallowing function after transoral laser microsurgery (TLM) ± adjuvant therapy for advanced-stage oropharyngeal cancer †‡§¶

To perform a longitudinal description of swallowing function following transoral laser microsurgery (TLM) ± adjuvant therapy for advanced‐stage oropharyngeal cancer (OPC) and identify prognostic factors associated with swallowing performance.

Management of human papillomavirus–related unknown primaries of the head and neck with a transoral surgical approach

Amidst a rising incidence of p16‐positive (p16+) oropharyngeal cancer, a significant number of cases present as regionally metastatic disease with an “unknown” primary. Preliminary data support transoral surgery as an effective method of primary detection/treatment.

Effects of botulinum toxin-induced paralysis on postnatal development of the supraspinatus muscle.

The mechanical environment plays an important role in musculoskeletal tissue development. The present study characterized changes in supraspinatus muscle due to removal of mechanical cues during postnatal development. An intramuscular injection of botulinum toxin type A (BTX) was used to induce and maintain paralysis in the left shoulders of mice since birth while the right shoulders received saline and served as contralateral controls. A separate group of animals was allowed to develop normally without any injections. Muscles were examined postnatally at various time points. The maximum isometric tetanic force generated by the muscle was significantly reduced in the BTX group compared to saline and normal groups. The paralyzed muscles were smaller and showed significant muscle atrophy and fat accumulation on histologic evaluation. Myogenic genes myogenin, myoD1, myf5, myf6, and fast type II myosin heavy chain (MHC) isoform were significantly upregulated while slow type I MHC isoform was significantly downregulated in the BTX group. Adipogenic genes C/EBPα, PPARγ2, leptin, and lipoprotein lipase were significantly upregulated in the BTX group. Results indicate that reduced muscle loading secondary to BTX‐induced paralysis leads to fat accumulation and muscle degeneration in the developing muscle. Understanding the molecular and compositional changes in developing supraspinatus muscles may be useful for identifying and addressing the pathological changes that occur in shoulder injuries such as neonatal brachial plexus palsy.

Upregulation of Runx2 and Osterix during in vitro chondrogenesis of human adipose-derived stromal cells

The aim of this study was to create a gene expression profile to better define the phenotype of human adipose-derived stromal cells (HADSCs) during in vitro chondrogenesis, osteogenesis and adipogenesis. A novel aspect of this work was the analysis of the same subset of genes during HADSC differentiation into all three lineages. Chondrogenic induction resulted in increased mRNA expression of Sox transcription factors, COL2A1,COL10A1, Runx2, and Osterix. This is the first report demonstrating significant upregulation in expression of osteogenesis-related transcription factors Runx2 and Osterix by TGF-beta3 induction of HADSCs during in vitro chondrogenesis. These findings suggest that the commonly-used chondrogenic induction reagents promote differentiation suggestive of hypertrophic chondrocytes and osteoblasts. We conclude that alternative strategies are required to induce efficient articular chondrocyte differentiation in order for HADSCs to be of clinical use in cartilage tissue engineering.

Current concepts in tracheal reconstruction.

Purpose of reviewMany patients require tracheal reconstruction either for tracheal stenosis/malacia or following tumor extirpation. However, such patients can be debilitated following failed conventional treatments. Recent advances in tissue engineering and vascularized composite grafts are accelerating the field of tracheal reconstruction. This article reviews new clinical concepts for tracheal reconstruction. Recent findingsNovel treatments include composite autografts, allografts, chimeric autografts and allografts, tissue-engineered grafts, prosthetic scaffolds, and the use of free-tissue vascularized carriers. SummaryNew procedures for tracheal reconstruction hold much promise for treating difficult tracheal disorders and improving the quality of life for affected patients. Many of the techniques reviewed herein are single case series and require further investigation and validation.

A practical guide to understanding systematic reviews and meta-analyses

A systematic review is a transparent and unbiased review of available information. The published systematic review must report the details of the conduct of the review as one might report the details of a primary research project. A meta-analysis is a powerful and rigorous statistical approach to synthesize data from multiple studies, preferably obtained from a systematic review, in order to enlarge the sample size from smaller studies to test the original hypothesis and/or to generate new ones. The objective of this article is to serve as an easy to read practical guide to understand systematic reviews and meta-analyses for those reading them and for those who might plan to prepare them.