Analyzing the Time From Discovery to Definitive Surgical Therapy for Lung Cancer Based on Referral Patterns.

OBJECTIVE: Surgery for early stage non-small cell lung cancer can be curative. A delay from diagnosis to surgery can lead to increased mortality. Our objective was to determine if referring patients to specialists before a thoracic surgeon caused a delay in definitive treatment. MATERIALS AND METHODS: A retrospective review was conducted of patients who had surgery for non-small cell lung cancer by a single surgeon at our institution from 2013 to 2016. Patients were divided into 2 groups: those who saw a specialist before a thoracic surgeon and patients who were referred directly to a surgeon once the pulmonary nodule was identified on computed tomography (CT). The time from initial CT to resection was compared. Secondary analysis compared private insurance versus Medicare/Medicaid. Percentage of patients upstaged was compared. RESULTS: There was no significant difference between groups when comparing time from CT to surgery (79.88 vs. 79.90 d; P=0.58). There was a significant decrease in time from CT to surgery for patients with private insurance compared with Medicare/Medicaid patients (66.05 vs. 86.99 d; P=0.03) and fewer private insurance patients were upstaged (22.9% vs. 31.8%; P=0.32). More patients who saw a different specialist first were upstaged compared with patients sent directly to thoracic surgery (32.6% vs. 22.2%; P=0.22). CONCLUSIONS: When comparing time from CT detection of a lung nodule to surgery, no significant difference was found between patients sent to nonthoracic specialists first and those referred directly to a thoracic surgeon. There was a significant decrease in time from CT to surgery for patients with private insurance compared with Medicare/Medicaid.

Analysis of Minimally Invasive Esophagectomy at a Single Veterans Affairs Medical Center.

BACKGROUND: To date, there are no published studies focusing on the benefits of minimally invasive esophagectomy (MIE) versus open esophagectomy at a Veterans Affairs Medical Center (VAMC). Our primary outcome was the incidence of esophageal malignancy in the veteran population and the postoperative morbidity following traditional and MIE for malignancy. DESIGN: Retrospective analysis of the incidence of esophageal malignancy at a Veteran Integrated Service Network (VISN) 5 VAMC reported to the VAMC Esophageal Tumor Registry between 2003 and 2016 and outcomes of the veterans who received esophagectomy for malignancy. Patients were followed for 5 years following diagnosis of esophageal malignancy. RESULTS: The Washington DC VAMC Tumor Registry recorded over 130 individuals with a new diagnosis of esophageal cancer between 2003 and 2016; 18 patients underwent an open transhiatal or Ivor Lewis esophagectomy and nine underwent an Ivor Lewis MIE. Surgical candidates had an average stage less than two (T1-3, N0-1, M0) and nonsurgical candidates had an average stage greater than three. Age, body mass index, smoking status, or renal function at time of surgery was similar between the two surgical groups. Patients who underwent an MIE had less blood loss (222 cc versus 822 cc, P < .001), fewer transfusions (11% versus 56%, P = .027), and more nodes harvested (10.33 versus 2.72, P < .001) with no change in leak rate (11% versus 17%, P = .703) or postoperative mortality (0% versus 6%, P = .490) compared to traditional esophagectomy. CONCLUSIONS: This report supports the migration toward MIE for malignancy and reemphasizes that veterans present with advanced disease.

Thoracoscopic Resection of Multiple Müllerian Cysts.

Müllerian cysts in the mediastinum were first described by Hattori in 2005 [1]. We report the first known case of multiple müllerian cysts in the thorax in a 35-year-old woman with cough and an abnormal chest roentgenogram. Multiple bilateral cysts were resected thoracoscopically. Histologic examination showed benign ciliated tubal epithelium that stained positive with immunohistochemical stains for estrogen receptor (ER), cancer antigen 125 (CA-125), Wilms' tumor protein 1 (WT-1), and paired box gene 8 (PAX8), confirming müllerian origin. We also review the embryogenesis and pathologic characteristics of müllerian cysts and the rare occurrence of their migration to the thorax.

Biochemical properties of tissue-engineered cartilage.

OBJECTIVE: Microtia is treated with rib cartilage sculpting and staged procedures; though aesthetically pleasing, these constructs lack native ear flexibility. Tissue-engineered (TE) elastic cartilage may bridge this gap; however, TE cartilage implants lead to hypertrophic changes with calcification and loss of flexibility. Retaining flexibility in TE cartilage must focus on increased elastin, maintained collagen II, decreased collagen X, with prevention of calcification. This study compares biochemical properties of human cartilage to TE cartilage from umbilical cord mesenchymal stem cells (UCMSCs). Our goal is to establish a baseline for clinically useful TE cartilage. METHODS: Discarded cartilage from conchal bowl, microtic ears, preauricular tags, rib, and TE cartilage were evaluated for collagen I, II, X, calcium, glycosaminoglycans, elastin, and fibrillin I and III. Human UCMSCs were chondroinduced on 2D surfaces and 3D D,L-lactide-co-glycolic acid (PLGA) fibers. RESULTS: Cartilage samples demonstrated similar staining for collagens I, II, and X, elastin, and fibrillin I and III, but differed from rib. TE pellets and PLGA-supported cartilage were similar to auricular samples in elastin and fibrillin I staining. TE samples were exclusively stained for fibrillin III. Only microtic samples demonstrated calcium staining. CONCLUSIONS: TE cartilage expressed similar levels of elastin, fibrillin I, and collagens I and X when compared to native cartilage. Microtic cartilage demonstrated elevated calcium, suggesting this abnormal tissue may not be a viable cell source for TE cartilage. TE cartilage appears to recapitulate the embryonic development of fibrillin III, which is not expressed in adult tissue, possibly providing a strategy to control TE elastic cartilage phenotype.

Effects of connective tissue growth factor on the regulation of elastogenesis in human umbilical cord-derived mesenchymal stem cells.

BACKGROUND: A key to clinical microtia reconstruction is construct flexibility. The most significant current limitation to engineered elastic cartilage is maintaining an elastic phenotype, which is principally dependent on elastin production (although other parameters, including maintenance of a ratio above 1 for collagens II to I, minimizing collagen X content, and presence of adequate matrix fibrillin for elastin binding, all play supporting roles). Connective tissue growth factor (CTGF), a compound secreted by chondrocytes, has been shown to promote an elastic phenotype in mature rabbit chondrocytes; however, CTGF effect on undifferentiated mesenchymal stem cells (MSCs) has not been characterized. The principal aim of this study is to analyze CTGF effect on elastin production in umbilical cord (UC)-derived MSCs and to determine optimal timing of treatment to maximize elastin production. METHODS: Human UCMSCs (hUCMSCs) were isolated from Wharton jelly using an explant technique, grown to passage 3, seeded onto nanofiber scaffolds, and chondroinduced for 21 days. Nanofiber scaffolds were electrospun using solubilized poly L-lactide/D-lactide/glycolide (PLGA). Chondrogenic media was supplemented with 25 µg/mL CTGF starting at day 0 or 7. Messenger RNA (mRNA) for Collagen I, II, X, fibrillin, and elastin was quantified by RT-PCR; glycosaminoglycan (GAG) matrix deposition was assessed and normalized by cellular DNA content. Elastin protein was assessed by Western blot analysis. All experiments were performed in triplicate with MSCs from 4 distinct cords. Multiway analysis of variance with Newman-Keuls post test was used to determine statistical significance. RESULTS: Connective tissue growth factor treatment results in increased GAG/DNA ratio; the differentiation index was maintained above 1 in all conditions, with increased collage II noted at days 7 and 14 in CTGF conditions; no difference in collagen X or fibrillin mRNA was noted. Increased elastin mRNA and protein were noted at day 14 in conditions treated with CTGF at day 7 after differentiation. CONCLUSIONS: Connective tissue growth factor leads to maximal elastin increase in UCMSCs after 7 days of chondroinduction and not in undifferentiated MSCs. With appropriately timed treatment, CTGF may be a useful adjunct in maintaining an elastic cartilage phenotype in engineered cartilage from human UCMSCs.