Aesthetics of the Nasal Dorsum: Proportions, Light, and Shadow.

Due to its central location, the nose plays a prominent role in facial aesthetics. As tastes have shifted and techniques have advanced, the accepted "ideal" appearance and proportions of the nose have evolved over time. By assessing the aesthetics of the nasal dorsum through the use of lines and angles, one can more precisely elucidate a goal for the patient's postoperative nasal shape, which should, in turn, guide the surgeon to execute specific operative maneuvers needed to achieve that contour. In assessing the aesthetics of the nasal dorsum, practitioners calculate and observe aspects such as the paired dorsal aesthetic lines, the nasofrontal angle, and the nasofacial angle. There is also additional consideration given to nasal tip position as this must fit harmoniously with the shape of the dorsum. In contrast to the established aesthetic lines and angles, using nasal geometric polygons for the aesthetic evaluation and development of operative goals in rhinoplasty has recently been described in the literature. Constructed ideals, in the form of proportions, lines, and angles, should be used with caution, as there are many factors to consider in the aesthetic analysis of the nasal dorsum, including ethnic differences, and subjective and changing views of beauty.

Complications in periorbital surgery.

Comprehensive rejuvenation of the periorbital region commonly involves management of the brow, as well as the upper and lower eyelids. Browlifting, upper and lower blepharoplasty, fat transfer, and neuromodulators are frequently utilized with excellent results. However, surgery in this region can be fraught with potential complications ranging from a poor cosmetic outcome to orbital hematoma and vision loss. Although avoidance of complications is preferred, it is incumbent on the surgeon to have a detailed understanding of the pathophysiology, prevention, and management of these complications. The authors examine the more common complications of periorbital surgery.

Repair of Gauged Earlobes: Case Series and Review of Two Techniques According to Size.

BACKGROUND: Earlobe stretching is a common body modification typically performed in individuals under 30 years old. Individuals may later desire restoration of a natural earlobe contour. There is a paucity of literature regarding technique and outcomes for repair of the gauged earlobe defect. AIMS AND OBJECTIVES: The primary aim of this study was to provide a strategy to assess stretched earlobe defects and choose between the repair techniques of de-epithelialization and closure or excision and rotation. The secondary aim of this study was to evaluate complication rates of the two techniques. MATERIALS AND METHODS: Retrospective review of all patients who underwent repair of stretched (gauged) earlobes at a single institution from 2012 to 2019. Patient demographics, maximum earlobe size, motivation for seeking repair, surgical technique, and complication rate were recorded. RESULTS: Fifty-three patients underwent stretched earlobe repair. The average age was 25.9 years old; 60.0% of the patients were male. Defects repaired with de-epithelialization and closure had been stretched to an average of 12.4 (SD = 3.2) mm compared to 29.3 (SD = 10.9) mm for excision and rotation. The minor complication rate was 12.5% with de-epithelialization and 10.8% for excision and rotation. Motivations for seeking repair included a desire to look more professional for work (34.0%), personal preference (30.0%), and joining the military (23.0%). CONCLUSION: Smaller earlobe defects (<15 mm) with nonptotic lobules can be repaired with de-epithelialization and primary closure, whereas larger earlobes (>15.0 mm) with ptotic lobules require excision and rotation. Stretched earlobe repair is a well-tolerated procedure, although a significant number of patients will require minor revisions.

Evaluation of promoter hypermethylation detection in body fluids as a screening/diagnosis tool for head and neck squamous cell carcinoma.

PURPOSE: To evaluate aberrant promoter hypermethylation of candidate tumor suppressor genes as a means to detect epigenetic alterations specific to solid tumors, including head and neck squamous cell carcinoma (HNSCC). EXPERIMENTAL DESIGN: Using promoter regions identified via a candidate gene and discovery approach, we evaluated the ability of an expanded panel of CpG-rich promoters known to be differentially hypermethylated in HNSCC in detection of promoter hypermethylation in serum and salivary rinses associated with HNSCC. We did preliminary evaluation via quantitative methylation-specific PCR (Q-MSP) using a panel of 21 genes in a limited cohort of patients with HNSCC and normal controls. Using sensitivity and specificity for individual markers as criteria, we selected panels of eight and six genes, respectively, for use in salivary rinse and serum detection and tested these in an expanded cohort including up to 211 patients with HNSCC and 527 normal controls. RESULTS: Marker panels in salivary rinses showed improved detection when compared with single markers, including a panel with 35% sensitivity and 90% specificity and a panel with 85% sensitivity and 30% specificity. A similar pattern was noted in serum panels, including a panel with 84.5% specificity with 50.0% sensitivity and a panel with sensitivity of 81.0% with specificity of 43.5%. We also noted that serum and salivary rinse compartments showed a differential pattern of methylation in normal subjects that influenced the utility of individual markers. CONCLUSIONS: Q-MSP detection of HNSCC in serum and salivary rinses using multiple targets offers improved performance when compared with single markers. Compartment-specific methylation in normal subjects affects the utility of Q-MSP detection strategies.

Nasal obstruction symptom evaluation (NOSE) score outcomes after septorhinoplasty.

OBJECTIVES/HYPOTHESIS: The time interval at which Nasal Obstruction Symptom Evaluation (NOSE) scores stabilize after functional septorhinoplasty has not been determined. Our goal was to characterize longitudinal trends of patient-reported outcomes of nasal obstruction using the NOSE survey instrument following functional septorhinoplasty. STUDY DESIGN: Prospective longitudinal cohort study. METHODS: Adult patients (≥18 years) with nasal obstruction who underwent functional septorhinoplasty by three different surgeons at a single academic, tertiary referral center were identified. NOSE scores were obtained preoperatively and prospectively during three postoperative intervals defined as early (1-3 months), middle (4-6 months), and late (≥10 months.) Longitudinal analysis included repeated measures analysis of variance and adjustments for multiple comparisons. RESULTS: A total of 49 patients met inclusion criteria. For the total cohort, mean NOSE scores significantly improved between preoperative and early postoperative evaluations (71.4, standard deviation [SD] ± 17.0 vs. 24.2, SD ± 19.5; P < .001) but did not significantly change between early and middle (20.6, SD ± 19.1; P = .543) or middle and late (23.1, SD ± 24.9; P > .999) time intervals. CONCLUSIONS: Patients with nasal obstruction who undergo functional septorhinoplasty can be expected to have significant improvement in self -reported nasal obstruction as early as 1 to 3 months postoperatively with a continued, durable, long-standing benefit lasting at least 10 months after surgery. Future studies can consider the 3-month time frame as a proxy for 1 year outcomes to help reduce survey burden. LEVEL OF EVIDENCE: 2c Laryngoscope, 129:841-846, 2019.

Positive correlation of tissue inhibitor of metalloproteinase-3 and death-associated protein kinase hypermethylation in head and neck squamous cell carcinoma.

OBJECTIVES/HYPOTHESIS: Promoter hypermethylation of tumor suppressor genes is common in head and neck cancer as well as other primary cancers resulting in epigenetic gene silencing. Tissue inhibitor of metalloproteinase-3 (TIMP-3) has been shown to have promoter hypermethylation in several solid tumors, but has not been identified in head and neck squamous cell carcinoma (HNSCC). Our objective was to determine if TIMP-3 promoter was hypermethylated in HNSCC, if there was any correlation with death associated protein kinase (DAPK), a tumor suppressor whose promoter has been hypermethylated at high levels in HNSCC, and if any clinical factors influence hypermethylation of either of these genes. STUDY DESIGN: Prospective study. METHODS: Tumor samples from 124 patients with HNSCC were evaluated for promoter hypermethylation for TIMP-3 and DAPK using quantitative methylation specific polymerase chain reaction (qMSP). We compared both TIMP-3 and DAPK hypermethylation in HNSCC with each other as well as with other clinical variables. RESULTS: We found that TIMP-3 was hypermethylated in approximately 71.8% of the tumor samples and DAPK was hypermethylated in 74.2%. The presence of TIMP-3 and DAPK promoter hypermethylation was significantly higher than in control specimens. More importantly, TIMP-3 and DAPK hypermethylations in these samples were highly correlated with a concordance of 78% (P < .001). DAPK was also correlated with current alcohol consumption (P < .028), but neither TIMP-3 nor DAPK hypermethylation was significantly correlated with other clinical variables or with survival. CONCLUSION: TIMP-3 promoter hypermethylation is elevated in HNSCC and is highly correlated with DAPK hypermethylation, implying a functional relationship between these genes.

Facial skin rejuvenation in the Asian patient.

Asian skin exhibits increased dermal thickness, collagen, and melanin content when compared with Caucasian skin. As a result of these features, the stigmata of aging skin in Asians is characterized more by pigmentation changes rather than fine, facial wrinkles, and it has an increased tendency toward pigmentary dyschromia after treatment. All facial skin rejuvenation techniques may not be applicable toward this selected population. This article highlights the various skin rejuvenation techniques that balance safety and efficacy and are most suitable toward treating the aging Asian face.

Osteocutaneous radial forearm free flap in nonmandible head and neck reconstruction.

BACKGROUND: The osteocutaneous radial forearm free flap (RFFF) is a versatile flap primarily used to reconstruct composite defects involving the mandible. The purpose of this study was to describe our experience with this flap for nonmandible reconstruction. METHODS: All patients undergoing nonmandible osseous reconstruction with free-tissue transfer were reviewed. Patients with osteocutaneous RFFF reconstructions were evaluated. The retrospective review of all osteocutaneous RFFFs was performed from 1998 to 2014. RESULTS: One hundred forty-two nonmandible osseous reconstructions were performed. Twenty-five patients underwent nonmandible osteocutaneous RFFF reconstruction. Eleven patients failed previous nonmicrovascular reconstruction. Reconstruction was for defects of the: palatomaxillary complex (n = 15), orbitomaxillary complex (n = 4), nasomaxillary complex (n = 4), larynx (n = 1), and clavicle (n = 1). There were no flap compromises. Postoperative complications included: 2 partial intraoral dehiscences; 1 recipient-site infection; and 1 seroma. Eight reconstructions required secondary procedures to improve functional and/or cosmetic outcomes. CONCLUSION: The osteocutaneous RFFF is a robust flap that can be used to reconstruct composite defects involving bone and soft-tissue beyond the mandible.

Head and neck cancer cell lines exhibit differential mitochondrial repair deficiency in response to 4NQO.

Constituents of tobacco can cause DNA adduct formation and are implicated in head and neck squamous cell cancer (HNSC) development. We investigated the capacity of HNSC cell lines to repair mitochondrial DNA (mtDNA) damage induced by a DNA adduct-forming agent. HNSC cell lines underwent 4-nitroquinoline 1-oxide (4NQO) exposure with subsequent rescue with normal media. Real-time quantitative PCR for nuclear DNA (nDNA) and mtDNA was performed. mtDNA to nDNA ratios were calculated and standardized to mock-treated cells to assess mtDNA repair ability. Two of three tested cancer cell lines exposed to 4NQO exhibited consistent decreases in mtDNA/nDNA ratios throughout the different repair timepoints. At 24 h mtDNA/nDNA ratios of JHU-O19 and JHU-O22 decreased to 63% and 60% of controls, respectively. Conversely, a control keratinocyte cell line exhibited overall increases in mtDNA/nDNA ratios compared to baseline suggesting intact DNA repair mechanisms. By using a DNA adduct formation and repair model featuring 4NQO and HNSC cell lines, we have implicated faulty mtDNA repair as having a potential role in HNSC.

Mitochondrial DNA quantity increases with histopathologic grade in premalignant and malignant head and neck lesions.

PURPOSE: Mitochondria are highly susceptible to oxidative damage. Although mitochondrial function decreases with oxidative damage, overall mitochondrial DNA (mtDNA) content increases to compensate for general mitochondrial dysfunction. We performed quantitative polymerase chain reaction for genes specific to mitochondrial and nuclear genomes to investigate relative mitochondrial abundance in a spectrum of dysplastic head and neck lesions. EXPERIMENTAL DESIGN: DNA from mild, moderate, and severe dysplasias, as well as invasive tumors and normal mucosal cells, was extracted. Using quantitative polymerase chain reaction, mitochondrial to nuclear DNA ratios were determined by quantification of cytochrome c oxidase subunit 1 (CoxI) and beta-actin genes. RESULTS: Mean CoxI/beta-actin DNA ratios for mild, moderate, and severe premalignant lesions were 0.0529, 0.0607, and 0.1021, respectively. The mean ratio for the normal mucosal cells contained in saliva was 0.0537, whereas the mean ratio for tumors was 0.1667. As a whole, our experimental model demonstrated significance (P = 0.0358). Comparisons between individual categories showed borderline significance when compared with the normal group, with P values of 0.0673, 0.0747, and 0.0824 for moderate and severe dysplasia and invasive tumor, respectively. CONCLUSIONS: Head and neck squamous cell carcinomas arise through premalignant intermediates and may be merely morphologic manifestations of accumulated genetic alterations. In keeping with this molecular tumor progression model, our study shows that mtDNA increases according to histopathologic grade, a phenomenon that may be a feedback mechanism that compensates for a generalized decline in respiratory chain function. Therefore, high mtDNA content may be another marker of genetic alteration, a measure of relative DNA injury, and a surrogate measure of histopathologic grade.

Increased Expression of CD169 on Blood Monocytes and Its Regulation by Virus and CD8 T Cells in Macaque Models of HIV Infection and AIDS.

Increased expression of CD169 on monocytes has been reported in HIV-1-infected humans. Using rhesus macaque models of HIV infection, we sought to investigate whether simian immunodeficiency virus (SIV) infection upregulates CD169 expression on monocytes/macrophages. We also sought to determine whether CD8 T cells and plasma viral load directly impact the expression of CD169 on monocytes during SIV infection. We longitudinally assessed monocyte expression of CD169 during the course of SIV infection by flow cytometry, and examined the expression of CD169 on macrophages by immunohistochemistry in the spleen and lymph nodes of uninfected and infected macaques. CD169 expression on monocytes was substantially upregulated as early as 4 days during the hyperacute phase and peaked by 5-15 days after infection. After a transient decrease following the peak, its expression continued to increase during progression to AIDS. Monocyte CD169 expression was directly associated with plasma viral loads. To determine the contribution of CD8(+) T lymphocytes and virus to the control of monocyte CD169 expression, we used experimental CD8(+) lymphocyte depletion and antiretroviral therapy (ART) in SIV-infected macaques. Rapid depletion of CD8 T cells during acute infection of rhesus macaques induced an abrupt increase in CD169 expression. Importantly, levels of CD169 expression plummeted following initiation of ART and rebounded upon cessation of therapy. Taken together, our data reveal independent roles for virus and CD8(+) T lymphocytes in controlling monocyte CD169 expression, which may be an important link in further investigating the host response to viral infection.

Habitual risk factors for head and neck cancer.

UNLABELLED: Chronic tobacco smoking and alcohol consumption are well-established risk factors for the development of squamous cell carcinoma (SCC) of the head and neck. There are, however, a variety of other habitual and culturally based activities that are less commonly seen in the Western world and that are also risks factors for the development of this type of cancer. In this era of globalization, many of these habits have now crossed borders and appear in various areas throughout the world. This article reviews habitual and social risk factors for cancer of the head and neck, excluding smoking and alcohol consumption. These factors include chewing tobacco and snuff, areca nut in its various forms, Khat leaves, and the drinking of Mate. EBM RATING: D.

Updates in forehead flap reconstruction of facial defects.

PURPOSE OF REVIEW: The versatile and reliable paramedian forehead flap is the workhorse interpolated flap for nasal reconstruction and its use has been expanded to reconstruct other areas of the face. The goal of this article is to review the recent research describing the modern concepts and techniques in forehead flap reconstruction of facial defects. RECENT FINDINGS: A variety of forehead flap concepts, techniques, and applications have been described in the recent literature in both nasal and facial reconstruction. Recent concepts include the phenomenon of vascular delay as well as more detailed study of the perfusion of the forehead flap at its various stages. Novel techniques include various approaches in staged reconstruction, adoption of the forehead flap for reconstruction of internal lining defects, and flap thinning. SUMMARY: Although basic principles of the forehead flap have remained unchanged over the years, specific techniques and applications continue to be refined. The forehead flap continues to be a mainstay in the armamentarium of facial plastic and reconstructive surgeons.

Detection of promoter hypermethylation in salivary rinses as a biomarker for head and neck squamous cell carcinoma surveillance.

PURPOSE: Hypermethylation of tumor suppressor gene promoters has been found in head and neck squamous carcinoma (HNSCC) and other solid tumors. We evaluated these alterations in pretreatment salivary rinses from HNSCC patients by using real-time quantitative methylation-specific PCR (Q-MSP). EXPERIMENTAL DESIGN: Pretreatment saliva DNA samples from HNSCC patients were evaluated for patterns of hypermethylation by using Q-MSP. Target tumor suppressor gene promoter regions were selected based on a previous study describing a screening panel for HNSCC in a high-risk population subjects. The selected genes were: DAPK, DCC, MINT-31, TIMP-3, p16, MGMT, CCNA1. RESULTS: We analyzed the panel in a cohort of 61 HNSCC patients. Thirty-three of the analyzed patients (54.1%) showed methylation of at least one of the selected genes in the saliva DNA. Pretreatment methylated saliva DNA was not significantly associated with tumor site (P = 0.209) nor clinical stage (P = 0.299). However, local disease control and overall survival were significantly lower in patients presenting hypermethylation in saliva rinses (P = 0.010 and P = 0.015, respectively). Multivariate analysis confirmed that this hypermethylation pattern remained as an independent prognostic factor for local recurrence (HR = 12.2; 95% CI = 1.8-80.6; P = 0.010) and overall survival (HR = 2.8; 95% CI = 1.2-6.5; P = 0.016). CONCLUSIONS: We were able to confirm an elevated rate of promoter hypermethylation in HNSCC saliva of patients by using a panel of gene promoters previously described as methylated specifically in HNSCC. Detection of hypermethylation in pretreatment saliva DNA seems to be predictive of local recurrence and overall survival. This finding has potential to influence treatment and surveillance of HNSCC patients.

Use of customized polyetheretherketone (PEEK) implants in the reconstruction of complex maxillofacial defects.

Extensive maxillofacial defects resulting from trauma or oncologic resection present reconstructive challenges. Various autografts and alloplastic materials in conjunction with standard soft-tissue techniques have been used in the reconstruction of these types of defects. Polyetheretherketone (PEEK) is a semicrystalline polyaromatic linear polymer exhibiting an excellent combination of strength, stiffness, durability, and environmental resistance. Recent investigations of PEEK as a biomaterial resulted in the successful treatment of cervical disk disease. We describe a series of 4 patients whose defects were reconstructed using customized PEEK implants. All had excellent postoperative aesthetic and functional results without complications such as infections or extrusions. Because PEEK implants are customizable, easily workable, inert, and nonporous, they represent an ideal alloplastic material for maxillofacial reconstruction.

Molecular pathology of head-and-neck cancer.

Each year approximately 40,000 people in the United States and 500,000 people worldwide are diagnosed with head-and-neck squamous cell carcinoma (HNSC). Although there have been significant improvements in the treatment of this disease, leading to decreased morbidity, over the past few decades the 5-year survival rate has remained largely unchanged at 50%. Genetic and epigenetic alterations as well as viral agents have been implicated in the development of head-and-neck cancer. Advances in our understanding of the molecular biology underlying these processes have spawned numerous, diverse strategies to exploit this understanding in applied pathology. Preliminary investigations have analyzed body fluids and margins for the presence of cancer cells. Specific molecular alterations have been associated with improved treatment response and prognosis. Molecular therapy has been shown to have some clinical efficacy in HNSC. Expression profiles may be generated for specific primary tumors and compared to known markers of disease. Improved molecular characterization of primary tumors, surgical margins and body fluids may allow clinicians to detect and treat earlier lesions, predict a tumor's response to treatment, tailor treatment to specific molecular alterations and ultimately improve clinical outcomes related to HNSC.