Surgical Management of the Internal Nasal Valve: A Review of Surgical Approaches.

BACKGROUND: Nasal valve collapse is relatively common with a lifetime prevalence of up to 13%. Etiologies include prior rhinoplasty, other surgical procedures, facial paralysis, congenital defects, trauma, and aging. Internal nasal valve collapse leads to impairment of nasal breathing, which significantly disturbs quality of life. Many approaches to increase the cross-sectional area of the internal nasal valve have been described. RESULTS: The main categories reviewed in this article are cartilage grafting, implants, and suture suspension techniques. Cartilage grafting techniques include alar batten graft, butterfly graft, spreader graft, autospreader graft, and alar composite graft. The implant technique includes the titanium butterfly implant. The suspension techniques included are the transconjunctival approach, Mitek bone anchor, flaring suture, lateral pull-up, and piriform rim suspension. Surgeons must carefully consider functionality, cosmesis, and technical difficulty when selecting an approach. DISCUSSION: We review indications, general approach, benefits, and considerations for a number of available techniques to help surgeons decide what approach might be best suited to the individual patient. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Biomechanical Analysis of Patellar Tendon Repair With Knotless Suture Anchor Tape Versus Transosseous Suture.

BACKGROUND: Patellar tendon ruptures have routinely been repaired with transosseous suture tunnels. The use of knotless suture anchors for repair has been suggested as an alternative. PURPOSE: To compare the load to failure and gap formation of patellar tendon repair at the inferior pole of the patella with knotless suture anchor tape versus transosseous sutures. A secondary objective was to investigate whether either technique shows an association between bone density and load to failure. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 20 human tibias with attached patellar and quadriceps tendons were sharply incised at the bone-tendon junction at the inferior pole of the patella. A total of 10 tendons were repaired using 2 knotless suture anchors in the inferior pole of the patella and a single suture tape with 2 core sutures. The other 10 tendons were repaired using No. 2 suture passed through 3 transosseous tunnels. A distracting force was then applied through the suture in the quadriceps tendon. Gap distance through load cycling at the repair site and maximum load at repair failure were then measured. Bone density was measured using computed tomography scanning. RESULTS: No difference was found in the mean load to failure of knotless patellar tendon repair versus transosseous suture repair (367.6 ± 112.2 vs 433.9 ± 99 N, respectively; P = .12). After 250 cycles, the mean repair site gap distance was 0.85 ± 0.45 mm for the knotless patellar tendon repair versus 2.94 ± 2.03 mm for the transosseous suture repair (P = .03). A small correlation, although not statistically significant, was found between bone density and load to failure for the knotless tape repair (R 2 = 0.228; P = .66). No correlation was found between bone density and load to failure for the transosseous repair (R 2 = 0.086; P = .83). CONCLUSION: Suture tape repair with knotless anchors for repair of patellar tendon rupture has comparable load to failure with less gap formation than transosseous suture repair. There is a small correlation between bone density and failure load for knotless anchor repair, which may benefit from further investigation. CLINICAL RELEVANCE: Using knotless suture anchors for patellar tendon rupture repair would allow for a smaller incision, less dissection, and likely shorter operating time.

Facial nerve transfer for facial reanimation with parotidoplasty approach.

BACKGROUND: Facial paralysis has a profound impact on quality of life in affected individuals, primarily through loss of verbal and nonverbal communication. Common facial nerve reanimation techniques include coaptation to the masseteric or hypoglossal nerve. Most techniques require nerve grafts to achieve a tension-free neurorrhaphy. Our report aims to show a surgical adaption to current facial reanimation procedures using a partial parotidoplasty approach in order to avoid challenges caused by interpositional nerve grafts through primary neurorrhaphy. PATIENTS AND METHODS: The modified surgical approach was performed on four patients, aged 30-67. Length of paralysis ranged from 6 to 13 months. Cause of paralysis included one patient with Bell's palsy in one patient, prior surgery in two patients, and traumatic fracture in the remaining patient. A modified Blair approach is used to expose the parotid capsule. The facial nerve is dissected proximally toward the stylomastoid foramen and distally toward the masseter. The parotid gland substance is sectioned overlying each branch of the facial nerve using ultrasonic dissection or hemostatic scalpel, allowing mobilization of the proximal segment and upper and lower divisions of the facial nerve. The superficial lobe of the parotid is preserved in most cases. The House-Brackmann (H-B) functional scale was used to assess facial nerve function pre- and post-operatively. RESULTS: All patients showed H-B score V or greater prior to reanimation. Follow-up was conducted at 3-, 6-, and 12-months in all patients with resultant improvement of H-B scores of I in three patients and II in the remaining patient. Only one complication was noted, with one patient developing a right postauricular hematoma that was adequately managed without sequelae. All remaining patients experienced an uncomplicated post-operative course. CONCLUSION: Our modified approach to facial nerve reanimation works well with a planned parotidoplasty allowing for successful reanimation outcomes without the need for interpositional grafting. This technique may be considered in masseteric and hemi-hypoglossal nerve transfers for the reinnervation of facial muscles.

Nomogram Identifies Age as the Most Important Predictor of Overall Survival in Oral Cavity Squamous Cell Cancer After Primary Surgery.

Our goal was to determine the most important predictors and construct a nomogram for overall survival (OS) in oral cavity squamous cell cancer (OCSCC) treated with primary surgery followed by observation, adjuvant radiation or chemoradiation. Multivariable analysis was performed using Cox Proportional Hazard model of 9258 OCSCC patients from Surveillance, Epidemiology and End Results Program (SEER) database treated with surgery from 2003 to 2009. Potential predictors of OS were age, gender, race, tobacco use, oral cancer sub-sites, pathologic tumor stage and grade, pathologic nodal stage, extra-capsular invasion, clinical levels IV and V involvement, and adjuvant treatment selection. Weighted propensity scores for treatment were used to balance observed baseline characteristics between three treatment groups in order to reduce bias. Following primary surgery, patients underwent observation (56%), radiation alone (31%) or chemoradiation (13%). All tested predictors were statistically significant and included in our final nomogram. Most important predictor of OS was age, followed by pathologic tumor stage. SEER based-survival nomogram for OCSCC patients differs from published models derived from patients treated in a single or few academic treatment centers. An unexpected finding of patient age being the best OS predictor suggests that this factor may be more critical for the outcome than previously anticipated.

Computational analysis of swallowing mechanics after surgery for obstructive sleep apnea.

Multilevel upper airway surgery for obstructive sleep apnea (OSA) has been shown to cause clinically significant dysphagia in some patients. We describe the cases of 2 adults with OSA who developed persistent dysphagia after multilevel upper airway surgery. Patient-specific computational analysis of swallowing mechanics (CASM) revealed absent pharyngeal shortening and aberrant tongue base retraction in both patients. These findings are consistent with the OSA surgical goal of enlarging the hypopharyngeal airway but likely contributed to our patients' dysphagia. Patient-specific CASM allows for sensitive identification of swallowing mechanical dysfunction that might otherwise be overlooked, and it may be utilized in future head and neck surgery patients to analyze swallowing dysfunction associated with treatment.

Landmarks for endoscopic approach to the parapharyngeal internal carotid artery: a radiographic and cadaveric study.

OBJECTIVES/HYPOTHESIS: To define transnasal endoscopic surgical landmarks for the parapharyngeal segment of the internal carotid artery (ppICA) using radiographic analysis and cadaveric dissection. STUDY DESIGN: Cadaveric and radiographic study. METHODS: One hundred seventy-nine computed tomography angiography studies of the head and neck were analyzed using Osirix third-party software (Pixmeo, Geneva, Switzerland). Dissection of a cadaveric specimen was used as a correlate to radiographic findings. The posterior aspect of the lateral pterygoid process and posterior border of the mandibular ramus were used as bony landmarks for the ppICA. RESULTS: At the level of the nasal floor, the distance from the ppICA to the posterolateral pterygoid process and to the posterior mandibular ramus was 2.36 cm and 1.94 cm, respectively, in males, and 2.37 cm and 1.99 cm, respectively, in females. At the level of the skull base, the distance from the ppICA to the posterolateral pterygoid process and to the posterior mandible was 2.33 cm and 1.49 cm, respectively, in males, and 2.20 cm and 1.57 cm, respectively, in females. Cadaver dissection demonstrated the utility of identifying these landmarks. CONCLUSIONS: The posterior border of the mandibular ramus and the posterolateral aspect of the pterygoid process may serve as consistent bony landmarks for identification of the ppICA.

Analysis of the petrous portion of the internal carotid artery: landmarks for an endoscopic endonasal approach.

OBJECTIVES/HYPOTHESIS: While there are many benefits to the endoscopic endonasal approach to the infratemporal fossa, involvement of the petrous portion of the internal carotid artery (ICA) poses a unique challenge. The endoscopic endonasal approach requires establishing the relationship of the petrous ICA to anatomical landmarks to guide the surgeon. This study evaluates the relationship of petrous ICA to specific anatomic landmarks, both radiographically and through cadaveric dissections. STUDY DESIGN: Cadaveric and radiographic study. METHODS: An endoscopic endonasal approach was used to access the petrous carotid and infratemporal fossa. Dissections exposed the petrous portion of the carotid artery and identified the foramen rotundum, ovale, and spinosum. Both anatomical and radiographic representations of these landmarks were then evaluated and compared relative to the petrous carotid. RESULTS: The endoscopic endonasal approach to the infratemporal fossa with exposure of the petrous ICA afforded complete visualization of the entire segment of this portion of the ICA with limited anatomical obstruction. The foramen rotundum, ovale, and spinosum were successfully identified and dissected with preservation of their neuro/vascular contents. Computed tomography analysis calculated a mean distance to the petrous ICA of 16.34 mm from the foramen rotundum, 4.88 mm from the ovale, and 5.11 mm from the spinosum in males. For females, the values were 16.40 mm from the rotundum and 4.36 mm each from the ovale and spinosum. CONCLUSION: An endonasal endoscopic approach to the infratemporal fossa with exposure of the petrous ICA is feasible. The anatomical landmarks can serve as both radiographic and surgical landmarks in this approach.

Trans-oral robotic submandibular gland removal.

Submandibular gland excision is traditionally performed via a trans-cervical approach. While generally regarded as a relatively simple surgical procedure, several complications are possible, including injury to the marginal mandibular branch of the facial nerve, lingual nerve, hypoglossal nerve, facial artery and a visible unsightly neck scar or keloid. The trans-oral route has the ability to eliminate a cervical scar and decrease risk of injury to several structures. Coincident with the development of the trans-oral approach, robotic surgery has been gaining popularity in the operative management of early oral cavity, tonsil, and tongue base malignancies. A 51-year-old female presented to our institution with a 15-year history of recurrent left submandibular gland sialoadenitis. She previously underwent a rhytidectomy with cervicoplasty and was interested in a trans-oral approach to avoid a neck incision. Here we present a novel application of the da Vinci Surgical Robot for trans-oral removal of the submandibular gland.

Evaluating the adult patient with a neck mass.

The objective of this article is to provide the internist with general considerations when confronted with an adult patient presenting with a neck mass. A thorough gathering of historical information and a complete physical examination are crucial in developing a differential diagnosis for these patients. Specifically, the location of the mass, its time of onset, and duration are important because of the high likelihood of neoplastic processes in patients older than 40 years. The young adult patient has an increased incidence of inflammatory, congenital, and traumatic processes as causes of their neck mass, but again, neoplasms are not out of the realm of possibility. Judicious use of imaging studies, namely computed tomography scanning with contrast, is a valuable adjunct to the physical examination. Other than infectious etiology, referral to an otolaryngologist is frequently warranted to obtain a definitive diagnosis for the development of an appropriate treatment plan, which is predominantly surgical.

A subpopulation of CD133(+) cancer stem-like cells characterized in human oral squamous cell carcinoma confer resistance to chemotherapy.

The potential role of cancer stem-like cells (CSCs) in chemoresistance of human oral squamous cell carcinoma (OSCC) was examined. A small subpopulation (1-2%) of CD133(+) CSCs was identified in OSCC cell lines and tissues. These CD133(+) CSCs possess higher clonogenicity, invasiveness, and increased in vivo tumorigenicity as compared to CD133(-) counterparts. Meanwhile, CD133(+) CSCs were substantially resistant to standard chemotherapy, wherein both in vitro and in vivo treatment with paclitaxel resulted in a marked enrichment for CD133(+) CSCs. Our data suggest that CD133(+) cells represent a small subpopulation of CSCs that may contribute to chemoresistance in human OSCC.

Tumor-like stem cells derived from human keloid are governed by the inflammatory niche driven by IL-17/IL-6 axis.

BACKGROUND: Alterations in the stem cell niche are likely to contribute to tumorigenesis; however, the concept of niche promoted benign tumor growth remains to be explored. Here we use keloid, an exuberant fibroproliferative dermal growth unique to human skin, as a model to characterize benign tumor-like stem cells and delineate the role of their "pathological" niche in the development of the benign tumor. METHODS AND FINDINGS: Subclonal assay, flow cytometric and multipotent differentiation analyses demonstrate that keloid contains a new population of stem cells, named keloid derived precursor cells (KPCs), which exhibit clonogenicity, self-renewal, distinct embryonic and mesenchymal stem cell surface markers, and multipotent differentiation. KPCs display elevated telomerase activity and an inherently upregulated proliferation capability as compared to their peripheral normal skin counterparts. A robust elevation of IL-6 and IL-17 expression in keloid is confirmed by cytokine array, western blot and ELISA analyses. The altered biological functions are tightly regulated by the inflammatory niche mediated by an autocrine/paracrine cytokine IL-17/IL-6 axis. Utilizing KPCs transplanted subcutaneously in immunocompromised mice we generate for the first time a human keloid-like tumor model that is driven by the in vivo inflammatory niche and allows testing of the anti-tumor therapeutic effect of antibodies targeting distinct niche components, specifically IL-6 and IL-17. CONCLUSIONS/SIGNIFICANCE: These findings support our hypothesis that the altered niche in keloids, predominantly inflammatory, contributes to the acquirement of a benign tumor-like stem cell phenotype of KPCs characterized by the uncontrolled self-renewal and increased proliferation, supporting the rationale for in vivo modification of the "pathological" stem cell niche as a novel therapy for keloid and other mesenchymal benign tumors.

Nondestructive imaging of live human keloid and facial tissue using multiphoton microscopy.

OBJECTIVES: To use multiphoton microscopy to image collagen fibers and matrix structure in nonfixed human keloid tissue and normal human facial skin obtained following surgery and to compare the findings to existing knowledge of normal skin and keloid morphology to determine if this technology is a suitable adjunct for conventional histology. METHODS: Epidermis was removed to expose the fibroblast-rich dermal layer that was then imaged using a multiphoton confocal microscope (Zeiss-Meta 510; Carl Zeiss, Jena, Germany). An 800-nm tunable titanium/sapphire femtosecond laser (Mai-Tai; Newport Co Spectra-Physics, Mountain View, California) was used to excite the tissue; second harmonic generation between 397 and 408 nm and autofluorescent signals were collected. Images were obtained using a Plan-Neofluar x40 oil immersion objective lens and a Plan-Apochromat x63 oil immersion lens. RESULTS: Compared with normal skin, keloids showed disorganized collagen fibers arranged in complex swirls and bundles 20 to 30 microm in diameter. Normal tissue showed collagen fibers as distinct, straight strands less than 10 microm in diameter. Differences between normal and keloid tissue were subtle but apparent. CONCLUSIONS: The value of imaging living tissue is a significant benefit. Because keloids and hypertrophic scars result from altered collagen metabolism, the development of clinical multiphoton microscopy systems may allow examination of wound healing dynamics in vivo and potentially provides a means to monitor therapy without the need for biopsy or the risk of injury to tissue.

Overexpression of human papillomavirus type 16 oncoproteins enhances hypoxia-inducible factor 1 alpha protein accumulation and vascular endothelial growth factor expression in human cervical carcinoma cells.

PURPOSE: Human papillomavirus (HPV)-16 oncoproteins, E6 and E7, are associated with enhanced tumor angiogenesis in human cervical cancers. The purpose of this study was (a) to investigate whether expression of HPV-16 E6 and E7 oncoproteins induces hypoxia-inducible factor 1 alpha (HIF-1 alpha) and vascular endothelial growth factor expression in cervical cancer cells; and (b) to assess the effect of resveratrol on 16 E6- and E7-induced HIF-1 alpha and VEGF gene expression. EXPERIMENTAL DESIGN: Human cervical cancer cell lines C-33A and HeLa were transiently cotransfected with pSG5-HPV-16 E6 or 16 E7 constructs along with HIF-1 alpha small interfering RNA (siRNA) or nonspecific siRNA. The expression of HIF-1 alpha/VEGF was measured using real-time PCR, Western blot analysis, or ELISA. The in vitro angiogenic activity induced by 16 E6- and E7-transfected cells was examined. The effect of resveratrol on oncoprotein-induced HIF-1 alpha/VEGF expression and in vitro angiogenesis was investigated. RESULTS: HPV-16 E6- and E7-transfected cervical cancer cells express increased HIF-1 alpha protein and VEGF expression. These stimulatory effects were abrogated by cotransfection with either HIF-1 alpha siRNA or treatment with resveratrol. Blocking extracellular signal-regulated kinase 1/2 (ERK 1/2) and phosphoinositide-3-kinase by PD98059 and LY294002, respectively, abolished 16 E6- and E7-induced HIF-1 alpha and VEGF expression. Functionally, we showed that HPV-16 E6- and E7-transfected cervical cancer cells stimulated in vitro capillary or tubule formation, and these angiogenic effects could be abolished either by cotransfection with HIF-1 alpha siRNA or by treatment with resveratrol. CONCLUSION: HPV-16 oncoproteins contribute to enhanced angiogenesis in cervical cancer cells via HIF-1 alpha-dependent VEGF expression. Resveratrol suppresses 16 E6- and E7-induced HIF-1 alpha-mediated angiogenic activity and, thus, is a promising chemotherapeutic agent for human cervical cancer.

Resveratrol inhibits hypoxia-induced accumulation of hypoxia-inducible factor-1alpha and VEGF expression in human tongue squamous cell carcinoma and hepatoma cells.

Hypoxia-inducible factor-1alpha (HIF-1alpha) is overexpressed in many human tumors and their metastases, and is closely associated with a more aggressive tumor phenotype. In this study, we investigated the effect of resveratrol, a natural product commonly found in grapes and various other fruits, on hypoxia-induced HIF-1alpha protein accumulation and vascular endothelial growth factor (VEGF) expression in human tongue squamous cell carcinomas and hepatoma cells. Our results showed that resveratrol significantly inhibited both basal level and hypoxia-induced HIF-1alpha protein accumulation in cancer cells, but did not affect HIF-1alpha mRNA levels. Pretreatment of cells with resveratrol significantly reduced hypoxia-induced VEGF promoter activities and VEGF expression at both mRNA and protein levels. The mechanism of resveratrol inhibition of hypoxia-induced HIF-1alpha accumulation seems to involve a gradually shortened half-life of HIF-1alpha protein caused by an enhanced protein degradation through the 26S proteasome system. In addition, resveratrol remarkably inhibited hypoxia-mediated activation of extracellular signal-regulated kinase 1/2 and Akt, leading to a marked decrease in hypoxia-induced HIF-1alpha protein accumulation and VEGF transcriptional activation. Functionally, we observed that resveratrol also significantly inhibited the hypoxia-stimulated invasiveness of cancer cells. These data suggested that HIF-1alpha/VEGF could be a promising drug target for resveratrol in the development of an effective chemopreventive and anticancer therapy in human cancers.

Human squamous cell carcinoma of the tongue and colon undergoes apoptosis upon phagocytosis of Saccharomyces cerevisiae, the baker's yeast, in vitro.

The present study was carried out to evaluate the effect of phagocytosis of killed yeast on the induction of apoptosis in two human solid tumors of the gastrointestinal (GI): the squamous cell carcinomas of the tongue (SCCA) are (SCC-4 and SCC-9) and the adenocarcinomas of the colon (ADENOCA) are (Caco-2 and DLD-1). Cancer cells were cultured with heat killed Saccharomyces cerevisiae, baker's and brewer's yeast, at ratio of yeast to cancer cells = 10:1. The percentage of tumor cells that had attached/phagocytosed yeast and oxidative burst was determined by using oxidative sensitive dye (DCFH-DA) and flow cytometry. SCC-4 and colon Caco-2 cells demonstrated initial high levels of phagocytosis that peaked (35.8-52.8%) at 2 hr. The oral SCC-9 and colon DLD-1 cells demonstrated low phagocytic activity (7-12%). Phagocytosis was not associated with oxidative burst. Upon phagocytosis of yeast, cancer cells underwent apoptosis that was maximized at 4 hr. Yeast-induced apoptosis was significant in SCC-4 (45%), as compared with SCC-9 cells (17%), and Caco-2 (76%), as compared with DLD cells (12%). Apoptosis in cancer cells was inhibited by caspase inhibitor, Z-VAD-FMK; this suggests that caspases may be involved in apoptosis of the GI cancers. This data may have clinical implications for the treatment of solid tumors.