Objective/Hypothesis Laryngopharyngeal reflux (LPR) is thought to be a significant risk factor for laryngeal squamous cell carcinoma (SCC), but causality has never been proven. It is accepted that chronic reflux into the esophagus can induce metaplastic changes in esophageal mucosa with subsequent increased risk of esophageal adenocarcinoma, but no similar associations have been established for LPR and laryngopharyngeal SCC. The objective of this study was to test the hypothesis that reflux of pepsin into the laryngopharynx can promote carcinogenesis. Study Design Translational research study Methods Normal human laryngeal primary epithelial cell cultures and hypopharyngeal FaDu SCC cells were exposed to human pepsin and analyzed by Human Cancer PathwayFinder and miRNA Superarrays, flow cytometry and Western blot to determine the effect of pepsin on carcinogenesis. Laryngeal biopsy specimens, taken from cancer patients and normal control subjects, were analyzed for the presence of pepsin by Western blot. Results Microarray analysis demonstrated that pepsin significantly altered the expression of 27 genes implicated in carcinogenesis and also affected the expression of 22 microRNAs known to be altered in human head and neck cancers. Pepsin increased proliferation in both FaDu SCC cells and cultured normal laryngeal epithelial primary cells by increasing S phase distribution on flow cytometry analysis in a time and dose dependent manner. Furthermore, pepsin was detected in 60% (3/5) human laryngeal cancer biopsies, absent in all (0/5) normal control specimens. Conclusion These data support a role for refluxed pepsin in the promotion of epithelial proliferation and carcinogenesis of the larynx and pharynx.

Reconstructive surgery for complex craniofacial defects challenges even the most experienced surgeons. Preoperative reconstructive planning requires consideration of both functional and aesthetic properties of the mandible, orbit, and midface. Technological innovations allow for computer-assisted preoperative planning, computer-aided manufacturing of patient-specific implants (PSIs), and computer-assisted intraoperative navigation. Although many case reports discuss computer-assisted preoperative planning and creation of custom implants, a general overview of computer-assisted innovations is not readily available. This article reviews innovations in computer-assisted reconstructive surgery including anatomic considerations when using PSIs, technologies available for preoperative planning, work flow and process of obtaining a PSI, and implant materials available for PSIs. A case example follows illustrating the use of this technology in the reconstruction of an orbital-frontal-temporal defect with a PSI. Computer-assisted reconstruction of complex craniofacial defects provides the reconstructive surgeon with innovative options for challenging reconstructive cases. As technology advances, applications of computer-assisted reconstruction will continue to expand.

Objective Despite widespread use of proton pump inhibitors (PPIs), the incidence of esophageal adenocarcinoma (EAC) continues to rise. PPIs reduce reflux acidity, but only transiently inactivate gastric enzymes. Nonacid reflux, specifically nonacid pepsin, contributes to carcinogenesis in the larynx. Given the carcinogenic potential of pepsin and inefficacy of PPIs to prevent EAC, the presence and effect of pepsin in the esophagus should be investigated. Methods Normal and Barrett’s biopsies from eight Barrett’s esophagus patients were collected for pepsin analysis via Western blot and RT-PCR. Human esophageal cells cultured from healthy patients were treated with pepsin (0.01-1mg/ml; 1-20hours), acid (pH4) +/− pepsin (5minutes); real-time RT-PCR, ELISA and cell migration were assayed. Results Pepsin was detected in all eight Barrett’s, and four of eight adjacent normal specimens. Pepsinogen mRNA was observed in two Barrett’s, but not in normal adjacent samples. Pepsin induced PTSG2 (COX-2) and IL1β expression and cell migration in vitro. Conclusions Pepsin is synthesized by metaplastic, Barrett’s esophageal mucosa. Nonacid pepsin increases metrics of tumorigenicity in esophageal epithelial cells in vitro. These findings implicate refluxed and locally synthesized pepsin in development and progression of EAC and, in part, explain the inefficacy of PPIs in prevention of EAC.

Pepsin in sinus lavages from patients with CRS is consistent with previous studies. This study reveals the damaging effect of pepsin on mitochondria in nasal epithelial cells in vitro. Cytokines previously associated with CRS were elevated following pepsin treatment of HNEpC cells in vitro. These results demonstrate mechanisms by which pepsin may potentiate CRS.

Objectives Although oropharyngeal neoplasia can often lead to dysphagia, salivary gland tumors rarely grow within the tongue base. We present the case of a 75-year-old man with adenoid cystic carcinoma of the base of the tongue causing profound dysphagia and weight loss, and provide a current literature review and update on the management of these rare tumors. Methods We present a case report and a literature review. Results Physical examination performed at the initial visit revealed a firm right base-of-tongue mass with no palpable lymphadenopathy. Flexible fiberoptic laryngoscopy confirmed a large submucosal mass at the right base of the tongue that obscured the right vallecula. Histopathologic analysis of the operative biopsy specimens revealed the classic features of adenoid cystic carcinoma. Treatment included radical pharyngotomy with wide local excision and primary closure, followed by postoperative radiation treatment. Conclusions We demonstrate the clinical examination findings and histopathologic characteristics of this disease, and review the literature for clinical treatment recommendations for this rare cause of dysphagia.