The pedicled levator labii superioris alaeque nasi flap: A durable single-stage option for reconstruction of full-thickness nasal defects.

IMPORTANCE: Repair of full-thickness nasal defects can often be associated with multi-stage operations that can result in significant physical and psychological morbidity for patients. We present a single-stage option for reconstruction of these defects. OBJECTIVE: Demonstrate the utility of the pedicled levator labii superioris alaeque nasi flap and consistency of its vascular pedicle. DESIGN: Anatomical study using fresh cadavers. SETTING: Academic medical center. MAIN OUTCOME AND MEASURES: Evaluation of vascular anatomy of pedicled flap and measurements of distances with relationship to facial anatomic landmarks. RESULTS: With few noted anatomic variations, the vascular pedicle of the pedicled levator labii superioris alaeque nasi flap arises from the superior labial artery and is reliably located within 1 cm lateral and inferior of the nasal sill. CONCLUSIONS AND RELEVANCE: As a robust single-stage option, the pedicled levator labii superioris alaeque nasi flap can serve as a powerful option in the arsenal of the reconstructive surgeon. The technique for harvest is simple with attention to a few anatomic variations as described herein, and excellent results can be obtained with proper application.

Stem cells enhance reperfusion following ischemia: Validation using laser speckle imaging in predicting tissue repair.

OBJECTIVES: The lack of real-time assessment of vascular perfusion changes remains a major weakness in assessing the efficacy of bone marrow stromal cells (BMSC) therapeutic ischemia reperfusion (I/R) injury. This study provides for the first time the real-time in vivo perfusion monitoring in I/R mice with BMSC therapy. STUDY DESIGN: Animal model. METHODS: Surgically created cutaneous flaps perfused by the inferior epigastric vessels were subjected to 3.5 hours of ischemia/reperfusion. Wound healing and vascular perfusion were assessed by Image-J and laser speckle contrast analysis (LSCA) in three groups (sham, I/R, and I/R + BMSC). BMSC tracking was quantified in an additional two groups (with/without I/R) using intravital fluorescent microscopy. The histopathology of skin flaps was examined by hematoxylin and eosin stain. Infiltrated macrophages were analyzed by confocal immunofluorescent microscopy. RESULTS: Postischemic tissues treated with BMSC demonstrated significantly greater survival than I/R control. On days 3 to 7 postreperfusion, both proximal and distal areas in BMSC-treated flaps demonstrated greater levels of perfusion than untreated I/R flaps (P < 0.05). Intravital fluorescent microscopy revealed that numbers of labeled BMSC were significantly increased in the distal area compared to the proximal area in both with and without ischemic mice. Histological examination showed lower necrosis and infiltrated inflammatory cells in I/R + BMSC-treated mice versus I/R controls. CONCLUSION: BMSC accumulated in I/R flaps and exerted beneficial effects including: 1) improving vascular perfusion and 2) attenuating inflammatory cell infiltration. LSCA facilitates monitoring of the real-time restitution of perfusion during flap wound healing in experimental animals and could also similarly applied in clinical investigations. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:E198-E205, 2018.

Dynamics of early stem cell recruitment in skin flaps subjected to ischemia reperfusion injury.

OBJECTIVE: Bone marrow-derived stromal cell (BMSCs) therapy improves survival of skin flaps subject to ischemia/reperfusion (I/R) injury. However, very little is known about the trafficking and distribution of BMSCs in post-ischemic skin tissue following intravenous administration. The aim of this study was to assess the behavior of BMSCs in post-ischemic skin flaps and to compare the magnitude and kinetics of accumulation of BMSCs and leukocytes following I/R. METHODS: Cutaneous flaps perfused by the inferior epigastric vessels were created in C57Bl6 mice. The flaps were subjected to 3.5h of ischemia followed by reperfusion. Wound healing and vascular perfusion were assessed in 3 groups of mice (sham, I/R, and I/R+BMSCs treatment) on days 3, 5, 7 and 14 post-reperfusion. The kinetics and magnitude of BMSCs and leukocyte recruitment were quantified in additional 2 groups (Sham and I/R) after I/R using intravital fluorescence microscopy at 2 and 4h after the intravenous injection of fluorescently labeled BMSCs. RESULTS: Wound healing after I/R was significantly enhanced in skin flaps of mice treated with BMSCs, compared to controls. The rolling velocity of BMSCs was higher compared to leukocytes both in control mice (32.4±3.7µm/s vs 24.0±2.2µm/s, p<0.05) and in I/R mice (34.6±3.8µm/s vs 20.2±2.3µm/s, p<0.005). However, the rolling velocity of both cell populations was not altered by I/R. The firm adhesion and transendothelial migration of BMSCs did not differ from the values detected for leukocytes for both control and I/R mice. CONCLUSIONS: The magnitude and kinetics of BMSCs recruitment in skin flaps subjected to I/R are not significantly different from the responses noted for leukocytes, suggesting that similar mechanisms may be involved in the recruitment of both cell populations following I/R.

Transnasal Endoscopic Eustachian Tube Surgery.

The purpose of this article is to give a contemporary review of transnasal endoscopic surgery for Eustachian tube disorders. The authors' perspective of the relevant anatomy, pathophysiology, and evaluation of Eustachian tube disorders as related to surgical intervention also is provided.

Interobserver agreement of confocal laser endomicroscopy for detection of head and neck neoplasia.

OBJECTIVES/HYPOTHESIS: We have described the feasibility of using the probe-based confocal laser endomicroscopy (pCLE) in differentiating benign from malignant lesions of the head and neck. Therefore, we wanted to determine the interobserver agreement of pCLE offline images of noncancerous, precancerous, and cancerous lesions of the head and neck. STUDY DESIGN: Single tertiary referral center. METHODS: In the feasibility study, image criteria for nondysplasia, dysplasia, and cancer were defined. The pCLE was performed before lesions were biopsied. Fifty offline images and 10 videos of good quality were selected. Seven surgeons and one pathologist were asked to review and categorize the images into the three categories above. The overall accuracy of 29 offline pCLE images and six videos were compared with histopathology. Interobserver agreement and accuracy kappa (κ) scores were measured with 95% confidence intervals (CI). RESULTS: There were six nondysplasia, seven dysplasia, and 11 squamous cell carcinoma (SCCA) cases, each with multiple images. There was substantial agreement between the eight reviewers on the pCLE images and videos (κ = 0.66; 95% CI 0.51-0.82 and κ = 0.71; 95% CI 0.42-0.97, respectively). The overall agreement with the final histopathology was also substantial for both the images and video sequences (κ = 0.70; 95% CI 0.50-0.88 and κ = 0.73; 95% CI 0.39-1.00, respectively). CONCLUSION: The ability to differentiate normal mucosa, dysplasia, and invasive SCCA using pCLE with high accuracy and reliability was demonstrated. This technology has the potential to decrease sampling error of lesions in the head and neck. This is the first study to test the reliability of this technology in mucosal lesions of the head and neck. LEVEL OF EVIDENCE: NA. Laryngoscope, 126:632-637, 2016.

Enhanced Systemic Bioavailability of Curcumin Through Transmucosal Administration of a Novel Microgranular Formulation.

BACKGROUND/AIM: Curcumin is a promising nutraceutical for chemoprevention of head and neck squamous cell carcinoma (HNSCC). Capsular formulations of curcumin demonstrate low systemic bioavailability. We aimed to determine if curcumin levels were higher in healthy volunteers and cancer patients with microgranular curcumin that allows for transmucosal absorption and identify a consistent biomarker. PATIENTS AND METHODS: Eight healthy volunteers and 15 HNSCC patients completed the trials. Serum levels of curcumin were measured by HPLC. Biological activity of curcumin was assessed with Multiplex Immunoassay and immunohistochemistry. RESULTS: We achieved higher serum levels of curcumin compared to trials using capsular formulation. In cancer patients a significant decrease in expression of fibroblast growth factor-2 (FGF-2) in post-biopsy samples and decreased serum levels of FGF-2, granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin-17 (IL-17) (p<0.05) was observed. CONCLUSION: Transmucosal administration of microgranular curcumin leads to enhanced curcumin bioavailability that is associated with significant biological effects.

Clinical Consensus Statement: Septoplasty with or without Inferior Turbinate Reduction.

OBJECTIVE: To develop a clinical consensus statement on septoplasty with or without inferior turbinate reduction. METHODS: An expert panel of otolaryngologists with no relevant conflicts of interest was assembled to represent general otolaryngology and relevant subspecialty societies. A working definition of septoplasty with or without inferior turbinate reduction and the scope of pertinent otolaryngologic practice were first established. Patients 18 years and older were defined as the targeted population of interest. A modified Delphi method was then used to distill expert opinion into clinical statements that met a standardized definition of consensus. RESULTS: The group defined nasal septoplasty as a surgical procedure designed to correct a deviated nasal septum for the purpose of improving nasal function, form, or both. After 2 iterative Delphi method surveys, 20 statements met the standardized definition of consensus, while 13 statements did not. The clinical statements were grouped into 8 categories for presentation and discussion: (1) definition and diagnosis, (2) imaging studies, (3) medical management prior to septoplasty, (4) perioperative management, (5) surgical considerations, (6) adjuvant procedures, (7) postoperative care, and (8) outcomes. CONCLUSION: This clinical consensus statement was developed by and for otolaryngologists and is intended to promote appropriate and, when possible, evidence-based care for patients undergoing septoplasty with or without inferior turbinate reduction. A complete definition of septoplasty with or without inferior turbinate reduction was first developed, and additional statements were subsequently produced and evaluated addressing diagnosis, medical management prior to septoplasty, and surgical considerations, as well as the appropriate role of perioperative, postoperative, and adjuvant procedures, in addition to outcomes. Additionally, a series of clinical statements were developed, such as "Computed tomography scan may not accurately demonstrate the degree of septal deviation," "Septoplasty can assist delivery of intranasal medications to the nasal cavity," "Endoscopy can be used to improve visualization of posterior-based septal deviation during septoplasty," and "Quilting sutures can obviate the need for nasal packing after septoplasty." It is anticipated that the application of these principles will result in decreased variations in the care of septoplasty patients and an increase in the quality of care.

Long-term Functional Outcomes of Total Glossectomy With or Without Total Laryngectomy.

IMPORTANCE: The optimal reconstruction of total glossectomy defects with or without total laryngectomy is controversial. Various pedicled and free tissue flaps have been advocated, but long-term data on functional outcomes are not available to date. OBJECTIVES: To compare various total glossectomy defect reconstructive techniques used by multiple institutions and to identify factors that may lead to improved long-term speech and swallowing function. DESIGN, SETTING, AND PARTICIPANTS: A multi-institutional, retrospective review of electronic medical records of patients undergoing total glossectomy at 8 participating institutions between June 1, 2001, and June 30, 2011, who had a minimal survival of 2 years. INTERVENTION: Total glossectomy with or without total laryngectomy. MAIN OUTCOMES AND MEASURES: Demographic and surgical factors were compiled and correlated with speech and swallowing outcomes. RESULTS: At the time of the last follow-up, 45% (25 of 55) of patients did not have a gastrostomy tube, and 76% (42 of 55) retained the ability to verbally communicate. Overall, 75% (41 of 55) of patients were tolerating at least minimal nutritional oral intake. Feeding tube dependence was not associated with laryngeal preservation or the reconstructive techniques used, including flap suspension, flap innervation, or type of flap used. Laryngeal preservation was associated with favorable speech outcomes, such as the retained ability to verbally communicate in 97% of those not undergoing total laryngectomy (35 of 36 patients) vs 44% (7 of 16) in those undergoing total laryngectomy (P < .001), as well as those not undergoing total laryngectomy achieving some or all intelligible speech in 85% (29 of 34 patients) compared with 31% (4 of 13) undergoing total laryngectomy achieving the same intelligibility (P < .001). CONCLUSIONS AND RELEVANCE: In patients with total glossectomy, feeding tube dependence was not associated with laryngeal preservation or the reconstructive technique, including flap innervation and type of flap used. Laryngeal preservation was associated with favorable speech outcomes such as the retained ability to verbally communicate and higher levels of speech intelligibility.

Postoperative management in laryngeal cancer with subglottic extension and histologically negative nodes: which patients need adjuvant radiotherapy?

We conducted a study of 19 patients who had laryngeal cancer with subglottic extension (LCSE) and pathologically negative lymph nodes (pN0) following total laryngectomy and neck dissection (TLND). These patients had undergone surgery during a 17-year period from 1986 through 2002. Of this group, 9 did not receive postoperative radiotherapy (non-RT group) and 10 did (RT group). Adjuvant irradiation had been administered to those with additional histopathologic risk factors for recurrence. We found that recurrence rates in the neck were 44% in the non-RT group and 11% in the RT group (1 of 9 evaluable patients), and the corresponding 5-year disease-free survival rates were 51 and 89%. While both of these differences were clinically significant, neither was statistically significant (p = 0.29 and p = 0.14, respectively). The presence of LCSE was not known prior to or during TLND in 4 non-RT patients and in 7 RT patients; their corresponding neck recurrence rates were 50 and 0%. Two of 8 patients (25%) whose ipsilateral lobe of the thyroid gland was not removed experienced a stomal recurrence. We conclude that three factors can be used to identify patients with pN0 LCSE who may be candidates for adjuvant postoperative radiotherapy: (1) a failure to remove the ipsilateral thyroid gland lobe during TLND, (2) a failure to examine the level VI lymph node for metastatic disease status, and (3) unfavorable histopathologic findings.

Confocal Laser Endomicroscopy in the Detection of Head and Neck Precancerous Lesions.

OBJECTIVE: This study aimed to determine the feasibility of using probe-based confocal laser endomicroscopy (pCLE) in the diagnostic differentiation of non-neoplastic lesions from precancerous and cancerous lesions of head and neck patients. STUDY DESIGN: Diagnostic test evaluation. SETTING: Louisiana State University Health Shreveport. SUBJECTS AND METHODS: Intravenous injection of fluorescein was given to patients with precancerous and cancerous head and neck lesions (n = 21) followed by the use of a 1.8-mm GastroFlex probe in the oral cavity with subsequent biopsies of selected areas. Probe-based confocal laser endomicroscopy images were compared to histologic evaluation of visualized sites using sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). RESULTS: The dorsal surface of the tongue was not well visualized. The remaining nonkeratinized subsites, including the buccal mucosa, floor of mouth, and ventral tongue, were well visualized. Diagnoses based on pCLE images correlated well with the gold standard diagnoses based on tissue histology. The overall sensitivity for diagnosis of dysplasia versus nondysplasia was 80.0% (95% confidence interval [CI], 62.0-98.0), specificity and PPV were 100%, and the NPV was 80.0% (95% CI, 60.0-100.0). The overall specificity, sensitivity, PPV, and NPV for pCLE diagnosis of carcinoma versus nondysplasia were 100%. The overall sensitivity for diagnosis of carcinoma versus dysplasia was 85.7% (95% CI, 73.0-99.0), specificity and PPV were 100%, and the NPV was 80.0% (95% CI, 60.0-100.0). CONCLUSION: The pCLE is a promising method for differentiating between nondysplastic, precancerous, and cancerous lesions of the head and neck.

Improved wound healing of postischemic cutaneous flaps with the use of bone marrow-derived stem cells.

OBJECTIVES/HYPOTHESIS: To determine if the intravascular delivery of mesenchymal stem cells improves wound healing and blood perfusion to postischemic cutaneous flap tissues. STUDY DESIGN: Randomized controlled study. METHODS: A murine model of a cutaneous flap was created based on the inferior epigastric vessels. Mice (n = 14) underwent 3.5 hours of ischemia followed by reperfusion. Bone marrow stromal cells (BMSCs) 1 × 10(6) were injected intravenously. Wound healing was then assessed measuring percent flap necrosis, flap perfusion, and tensile strength of the flap after a period of 14 days. Localization of BMSCs was determined with radiolabeled and fluorescent labeled BMSCs. RESULTS: Postischemic cutaneous flap tissues treated with BMSCs demonstrated significantly less necrosis than control flaps (P <0.01). Beginning on postoperative day 5, BMSC-treated flaps demonstrated greater blood perfusion than untreated flaps (P <0.01). Tensile strength of BMSC-treated cutaneous flaps was significantly higher (P <0.01), with a mean strength of 283.4 ± 28.4 N/m than control flaps with a mean of 122.4 ± 23.5 N/m. Radiolabeled BMSCs localized to postischemic flaps compared to untreated tissues (P = 0.001). Fluorescent microscopy revealed incorporation of BMSCs into endothelial and epithelial tissues of postischemic flaps. CONCLUSIONS: This study demonstrates that the intravascular delivery of BMSCs increases wound healing and promotes flap survival following ischemia-reperfusion injury of cutaneous tissue flaps.

Selectin blockade decreases postischemic recruitment of bone marrow stromal cells.

OBJECTIVES/HYPOTHESIS: Investigate the localization mechanisms of bone marrow stromal cells following transient ischemia-reperfusion injury in a murine flap model. STUDY DESIGN: Controlled laboratory study. METHODS: A cutaneous flap based on the inferior epigastric artery was elevated, and transient ischemia of 3.5 hours using a microvascular clamp was achieved. Fucoidan was injected intravenously 24 hours before the ischemic period. Following the period of ischemia, radiolabeled bone marrow stromal cells were injected intravenously, and radioactivity was determined postoperatively. RESULTS: Attenuation of the uptake of bone marrow stromal cells into postischemic tissue was observed in those mice treated with fucoidan as indicated by gamma counts measured in the flaps when compared with controls (P < . 001). CONCLUSIONS: Decreased uptake of radiolabeled bone marrow stromal cells into postischemic tissues pretreated with fucoidan indicates selectin-mediated bone-marrow stromal cell recruitment in a murine cutaneous flap model.

Establishment of a cutaneous flap animal model to study platelet and leukocyte dynamics after ischemia-reperfusion injury.

OBJECTIVES To study a cutaneous flap in an animal model for platelet and leukocyte dynamics after ischemia-reperfusion injury and to explain how such a model is relevant to the understanding of reconstructive flaps in a clinical setting. METHODS Cutaneous flaps based on the inferior epigastric artery were raised on C57BL/6 mice and were subjected to various periods of ischemia followed by reperfusion. We used intravital microscopy to observe and characterize platelet and leukocyte interactions within the microvasculature. RESULTS Platelet and leukocyte adherence to the microvasculature was greater after a longer reperfusion period in contrast to the adherence pattern seen after a shorter reperfusion period. Leukocyte rolling activity occurred at a greater rate after longer ischemia and shorter reperfusion periods, whereas the rate of platelet saltation occurred after shorter ischemia and longer reperfusion periods. CONCLUSIONS With the establishment of an animal model of cutaneous flaps to study cellular dynamics within the microvasculature after ischemia-reperfusion injury, further investigation into the cellular and molecular characteristics of such injury and the analysis of pharmacological interventions is warranted.

Cervical thoracic duct cyst: Importance of preoperative suspicion for appropriate management of left-sided neck mass.

Cervical thoracic duct cysts occur infrequently but are an important consideration when evaluating cystic supraclavicular masses. Only 22 cases have been reported to date. We review the clinical presentation, evaluation, and treatment of 2 cases of large thoracic duct cysts treated with surgical resection. A high suspicion of thoracic duct cyst based on location, radiographic findings, and fine-needle aspiration results is sufficient evidence for recommendation of surgical excision. However, enlarged cysts, as noted in our cases, can obliterate or attenuate the thoracic duct, making it difficult to identify intraoperatively. A high suspicion of thoracic duct cyst is important for identifying and ligating the duct to prevent complications such as chyle leak or chylothorax.

Sinonasal teratocarcinosarcoma with yolk sac elements: a neoplasm of somatic or germ cell origin?

Sinonasal teratocarcinosarcoma is an uncommon, aggressive, morphologically heterogenous tumor composed of cells derived from the 3 somatic layers. A histogenetic origin from a multipotential adult somatic stem cell with divergent differentiation has been favored over a germ cell origin. This assumption has been based on the lack of germ cell elements and, until recently, the absence of demonstrable amplification of 12p. We report a case that exhibited foci of yolk sac elements with papillary structures and intracytoplasmic periodic acid-Schiff-positive, diastase-resistant, α-fetoprotein-positive, hyaline globules. An expanded area of undifferentiated cells, likely precursor cells, in the basal layer of the overlying mucosal epithelium transitions into and merges with the immature epithelial, neuroepithelial, and mesenchymal components. These previously unreported histomorphological features support the hypothesis that this tumor is a teratomatous tumor arising from pluripotent embryonic stem cells in the basal layer of the sinonasal epithelium. That notion is further supported by fluorescence in situ hybridization cytogenetic analysis, which showed a distinct subpopulation of the tumor cells with an extra copy of chromosome 12p13.

A unique case of infraorbital myxoid liposarcoma.

Liposarcomas of the head and neck are rare, owing to the paucity of adipose tissue in this region. We present what we believe is a unique case of a myxoid liposarcoma in the infraorbital region, which arose in a 38-year-old man. The patient had presented with a slowly growing mass under his left eye that had been present for about 3 months. A wide local excision was performed, and the tumor was removed in its entirety. The final pathology report identified the mass as a well-differentiated myxoid liposarcoma. The patient's postoperative course was uneventful, and at the 12-month follow-up, he exhibited no evidence of disease.

Pharmacodynamic evaluation of temsirolimus in patients with newly diagnosed advanced-stage head and neck squamous cell carcinoma.

BACKGROUND: Activation of the mammalian target of rapamycin (mTOR) pathway in surgical margins of head and neck squamous cell carcinoma (HNSCC) is a predictor of recurrence and patients with minimal residual disease may benefit from adjuvant therapy with temsirolimus, an mTOR inhibitor. METHODS: The effects of 3 weekly doses of 25 mg of temsirolimus on Akt/mTOR pathway biomarkers were evaluated in tumor and peripheral blood mononuclear cells (PBMCs) of patients with HNSCC. Adverse events were assessed. RESULTS: Temsirolimus significantly decreased pS6 and p4E-BP1 in tumors, and pS6 and pAkt in PBMCs (p < .05). There was no significant upregulation of pAkt(Ser(473)) in tumor tissue. Side effects were minimal and reversible. CONCLUSION: Significant inhibition of the mTOR pathway was noted in both tumors and PBMCs of HNSCC with minimal side effects. The mTOR inhibitors can potentially be used as adjuvant therapy for patients with minimal residual disease and PBMCs are potential surrogate markers in this setting.

Radiologic findings after successful chemoradiation for nasopharyngeal cancer with skull base erosion.

Nonoperative management is generally accepted as a treatment strategy for nasopharyngeal cancer characterized by destruction of the skull base. Chemoradiotherapy is considered the standard of care in these cases. We report a case in which imaging studies documented the successful treatment of the patient's locally extensive nasopharyngeal carcinoma with this nonsurgical approach.

Extracranial infrasellar ectopic craniopharyngioma: a case report and review of the literature.

We present a case of a purely infrasellar craniopharyngioma that initially presented as a sphenoid sinus mass. Craniopharyngiomas are usually located within the sella. Purely infrasellar craniopharyngiomas have only rarely been reported in the literature. A 25-year-old woman presented with 6-month history of progressive headaches. Initial neuroimaging revealed the presence of a sphenoid sinus mass. Initially, she underwent an endoscopic biopsy of the mass by our ENT service. Pathology was consistent with craniopharyngioma and she was referred to neurosurgery for further surgical management. She then underwent an endoscopic transsphenoidal approach for complete resection of the purely extracranial, infrasellar craniopharyngioma. The Rathke pouch arises from the roof of the primitive mouth and grows toward the brain at the fourth week of gestation. Normally, it loses its attachment with the stomadeum completely by the eighth week of gestation. The craniopharyngeal canal (CPC) extends from the floor of the sella to the vomer and may rarely give rise to ectopic craniopharyngiomas. This case shows that such ectopic tumors may arise anywhere along the CPC. Endoscopic endonasal approach provides an excellent route for the resection of these tumors.