Association between venous thromboembolism rates and different prophylactic anticoagulation regimens in patients undergoing free flap reconstruction of the head and neck region.

BACKGROUND: Venous Thromboembolism (VTE) is a serious complication after free tissue transfer to the head and neck (H&N). However, an optimal antithrombotic prophylaxis protocol is not defined in the literature. Enoxaparin 30 mg twice daily (BID) and heparin 5000 IU three times daily (TID) are among the most commonly used regimens for chemoprophylaxis. However, no studies compare these two agents in the H&N population. METHODS: A cohort study of patients who underwent free tissue transfer to H&N from 2012 to 2021 and received either enoxaparin 30 mg BID or Heparin 5000 IU TID postoperatively. Postoperative VTE and hematoma events were recorded within 30 days of index surgery. The cohort was divided into two groups based on chemoprophylaxis. VTE and hematoma rates were compared between the groups. RESULTS: Out of 895 patients, 737 met the inclusion criteria. The mean age and Caprini score were 60.6 [SD 12.5] years and 6.5 [SD 1.7], respectively. 234 [31.88%] were female. VTE and hematoma rates among all patients were 4.47% and 5.56%, respectively. The mean Caprini score between the enoxaparin (n = 664) and heparin (n = 73) groups was not statistically significant (6.5 ± 1.7 vs.6.3 ± 1.3, p = 0.457). The VTE rate in the enoxaparin group was significantly lower than in the heparin group (3.9% vs. 9.6%; OR: 2.602, 95% CI: 1.087-6.225). Hematoma rates were similar between the two groups (5.5% vs. 5.6%; OR: 0.982, 95% CI: 0.339-2.838). CONCLUSIONS: Enoxaparin 30 mg BID was associated with a lower VTE rate while maintaining a similar hematoma rate compared to heparin 5000 units TID. This association may support the use of enoxaparin over heparin for VTE chemoprophylaxis in H&N reconstruction.

Dermatological assessment of thick-skinned patients before rhinoplasty-what may surgeons ask for?

Rhinoplasty is considered a very challenging surgery since minimal changes of this central area of the face may significantly impact a person's appearance and self-awareness. This is even more challenging in thick-skinned patients because results are less predictable, and changes to the osseocartilaginous framework (OCF) may not be sufficiently visible due to the blanket effect of the thick skin. Furthermore, pre-existing skin conditions may exacerbate following surgery. Therefore, managing patients with extremely thick skin or patients who suffer from pre-existing dermatological conditions such as rosacea or acne requires a synergy of surgeons and dermatologists to achieve optimal results. In this article, we review the most significant pre- and post-surgical regimens that surgeons and dermatologists should apply in selected patients to achieve optimal results after rhinoplasty.

Assessment of BMI and Venous Thromboembolism Rates in Patients on Standard Chemoprophylaxis Regimens After Undergoing Free Tissue Transfer to the Head and Neck.

Importance: Venous thromboembolism (VTE) is a severe complication after free tissue transfer to the head and neck (H&N). Enoxaparin 30 mg twice daily (BID) is a common regimen for chemoprophylaxis. However, differences in enoxaparin metabolism based on body weight may influence its efficacy and safety profile. Objective: To assess the association between BMI and postoperative VTE and hematoma rates in patients treated with prophylactic enoxaparin 30 mg BID. Design, Setting, and Participants: This was a retrospective review of a prospectively collected cohort from 2012 to 2022. Postoperative VTE, hematoma, and free flap pedicle thrombosis were recorded within 30 days of index surgery. The setting was a tertiary academic referral center. Participants included patients undergoing H&N reconstruction with free flaps that received fixed-dose subcutaneous enoxaparin 30 mg BID postoperatively. Statistical analysis was conducted from April to May 2022. Main Outcomes and Measures: Outcomes include incidence of VTE, hematoma, and flap pedicle thrombosis events within 30 days of the surgery. Univariate and multivariable regression models were used to evaluate associations between BMI and other patient factors with these outcomes. Results: Among the 765 patients included, 262 (34.24%) were female; mean (SD) age was 60.85 (12.64) years; and mean (SD) BMI was 26.36 (6.29). The rates of VTE and hematoma in the cohort were 3.92% (30 patients) and 5.09% (39 patients), respectively. After adjusting for patient factors, BMI was the only factor associated with VTE (OR, 1.07; 95% CI, 1.015-1.129). Obesity (BMI >30) was associated with increased odds of VTE (OR, 2.782; 95% CI, 1.197-6.564). Hematoma was not associated with BMI (OR, 0.988; 95% CI, 0.937-1.041). Caprini score of at least 9 was not associated with VTE (OR, 1.259; 95% CI, 0.428-3.701). Conclusions and Relevance: This cohort study found that obesity was associated with an increased risk of VTE in patients after microvascular H&N reconstruction and while on standard postoperative chemoprophylaxis regimens. This association may suggest insufficient VTE prophylaxis in this group and a potential indication for weight-based dosing.

Quality of life outcome in revision rhinoplasty in regards to number of revision surgeries and cartilage donor site.

OBJECTIVES: Rhinoplasty with or without combined septoplasty is one of the most frequently performed procedures in facial plastic surgery. Patient satisfaction and improvement in quality of life (QoL) is the primary goal. This prospective study was conducted to analyse Qol outcome in revision rhinoplasty in regards to number of revision surgeries and cartilage donor site using patient-reported outcome measures (PROMs). METHODS: Preoperative and at least 12-months postoperative scores on the Nasal Obstruction Symptome Evaluation (NOSE) questionnaire (range 0-100, lower scores indicate better outcome) and the Rhinoplasty Outcomes Evaluation (ROE) questionnaire (range 0-100, higher scores indicates better outcome) were obtained. Additionally, data on age, gender and number of previous rhinoplasties were assessed. All revision rhinoplasties were performed by one surgeon (author, F.R.) between 2014 and 2017. RESULTS: Sixty-four patients (11 (17.2%) male, 53 (82.8%) female) prospectively enrolled in this study. In 41 (64.1%) cases septal cartilage and in 23 (35.9%) patients ear cartilage was the donor site in revision surgery. Patients with more than one previous surgery (n=18) started with a lower preoperative ROE score (28.2 ± 12.8) compared to patients who had received only one previous surgery. The difference however was not significant (p=0.06). This subgroup still showed significant postoperative improvement (ROE-postop 61.9 ± 24.2; p<0.05). Both cohorts (septal cartilage and ear cartilage) improved significantly in regards to their ROE and NOSE scores after surgery and therefore showed improved health-related QoL. We could not detect any differences in health-related QoL postoperatively in regards to cartilage donor site in revision surgery. CONCLUSION: Revision rhinoplasty improves health-related QoL. There are no differences in ROE- or NOSE-scores postoperatively in regards to graft material (ear- versus septal cartilage). Both subgroups show significantly higher scores postoperatively.

Subdorsal Z-flap: a modification of the Cottle technique in dorsal preservation rhinoplasty.

PURPOSE OF REVIEW: To present the novel technique of subdorsal Z-flap in dorsal preservation rhinoplasty and give an overview on current available dorsal preservation techniques in the literature. RECENT FINDINGS: The subdorsal Z-flap combines the advantages of the high and low septal strip techniques in dorsal preservation rhinoplasty and ensures well tolerated treatment of the dorsal hump and structural stability. SUMMARY: The technique and concept of Dorsal Preservation Rhinoplasty (DPR) has been used for more than a century but only recently gained significant popularity along with specific technical refinements. The advantage of DPR lies in the preservation of the delicate triangular cartilaginous unity of the septal and upper lateral cartilages with its functional and esthetic implications in contrast to all resecting techniques. A variety of modifications of DPR have been published in recent years, each with advantages and disadvantages. The issue of hump recurrence remains a major concern in DPR. We describe the 'subdorsal Z-flap' and related techniques of DPR in detail, present two clinical case studies and discuss alternative technical modifications. The 'subdorsal Z -flap' combines the advantages of the high septal strip procedure with the advantages of the traditional 'low septal strip' or Cottle technique. By starting the incision at a high level, final septal height can be adjusted precisely. By creating a triangular shape with a vertical cut below the K-Area, which is usually the highest point of the hump, significant leverage can be applied from below the hump and the septal overlap may be sutured securely for a stable correction. In combination with Piezo osteotomy and full open approach, great precision and predictability can be achieved. In a recent publication, we presented more than 100 consecutive cases of subdorsal Z-flap DPR with good functional and esthetic outcomes. The subdorsal Z-flap modification is a combination of two popular DPR techniques, fusing their advantages while minimizing risk profile. A slightly higher degree of technical difficulty and necessary tissue dissection provides the benefits of better predictability and reduction of adverse outcomes.

Surgical and Nonsurgical Management of the Nasal Skin-Soft Tissue Envelope.

Management of the skin-soft tissue envelope (SSTE) in rhinoplasty is challenging and critical for the overall outcome. The preoperative identification of patients with thick or thin skin and with preexisting skin conditions may contribute significantly to the postsurgical result. Most publications and textbooks focus on the management of the osseocartilaginous framework, but the SSTE management is often not addressed in detail. However, nonsurgical treatments, such as skin preconditioning, topical steroid-injections, oral isotretinoin, and topical vitamin A derivatives, may provide strong benefits. In this article, we reviewed the literature to present a comprehensive review on the available surgical and nonsurgical approaches pre-, intra-, and postoperatively dealing with SSTE in rhinoplasty.

Optimization of the Soft Tissue Envelope of the Nose in Rhinoplasty Utilizing Fat Transfer Combined with Platelet-Rich Fibrin.

A thin or damaged skin soft tissue envelope may cause concerns in primary and secondary rhinoplasty. During postoperative healing, unpredictable scarring and contraction may occur and lead to significant aesthetic and trophic sequelae. Besides a meticulous surgical technique, there are no reliable techniques to prevent long-term skin damage and shrinkage. Fat transfer with addition of platelet-rich fibrin (PRF) harbors the possibility of local soft tissue regeneration and skin rejuvenation through growth factors and mesenchymal stem cells. It may also facilitate the creation of a thin fat layer on the dorsum to prevent shrink-wrap forces and conceal small irregularities. The goal is to provide evidence for the feasibility, durability, and beneficial effect of diced macrofat transfer bonded with PRF on the nasal dorsum. We present the technique of fat transfer conjugated with PRF as a nasal dorsal graft. Clinical endpoints were the prevention of trophic disturbances and atrophy at a 1-year postoperative follow-up. We present the skin mobility test as a clinical indicator of a healthy soft tissue envelope. The presented case series consists of 107 rhinoplasties. Fat was harvested in the umbilical or costal region. PRF was created by centrifugation of autologous whole blood samples. Macrofat was diced, cleaned, and bonded with PRF. The compound transplants were transferred to the nasal dorsum. There were no perioperative complications or wound-healing issues. Mean follow-up was 14 months. Clinical inspection showed good skin quality and no signs of shrinkage, marked scarring, or color changes with positive skin mobility test in all patients. Survival of fat was confirmed by ultrasonography and magnetic resonance imaging. Diced macrofat transfer in conjunction with PRF to the nasal dorsum is a feasible and safe method. A beneficial effect on the soft tissue envelope is demonstrated as well as the prevention of shrink-wrap forces.

Symptom Control of Patients With Chronic Rhinosinusitis With Nasal Polyps Under Maintenance Therapy With Daily Acetylsalicylic Acid.

INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAID)-exacerbated respiratory disease (NERD) is defined by intolerance to cyclooxygenase 1 inhibitors, chronic rhinosinusitis with recurrent nasal polyps, and/or intrinsic bronchial asthma. Long-term administration of acetylsalicylic acid (ASA) after desensitization has been used to mitigate these sequelae, but the optimal dose and balancing symptom relief and side effects remain unsettled. METHODS: Retrospective data analysis of 85 patients with NERD receiving maintenance therapy of 300 mg ASA was followed by questionnaires (our own, not validated and the Sino-Nasal Outcome Test-20). We received responses from 55 patients and examined 30 of them clinically. RESULTS: Patients with no ASA-associated side effects were 56.4% (56 of 85 patients) of the cohort. In this study, 60% (33 of 55 patients) continued prophylaxis of 300 mg ASA daily for an average of 34.7 months. Elective surgery was the most frequent cause of discontinuation of ASA (21.8%; 12 of 55 patients). Rhinomanometry values were significantly improved with ASA (P < .05; Wilcoxon), but there was no significant reduction in nasal polyposis or improvement in olfaction at the time of follow-up examination. CONCLUSIONS: Minor clinical improvements were identified. Side effects were well tolerated by most patients, and no serious sequelae occurred. The indications for long-term ASA therapy in NERD patients remain unsettled.

Pectoralis Major Muscle Free Flap: Anatomical Studies on Pedicle Length and Vessel Diameter.

Large and deep defects resulting from lateral skull base surgery represent a challenge to the head and neck surgeon. Different microvascular free flaps have specific advantages and disadvantages. While the pedicled pectoralis major flap is considered a "work horse," it comes with a rather short pedicle. The aim of this study was to analyze the vascular anatomy of the pectoralis major flap and assess its suitability for microvascular transfer. Anatomical studies have been performed on 6 Thiel-fixed cadavers allowing a harvest of 12 flaps by the same surgeon. Measurements of the pedicle's length and vessel diameters have been taken with a ruler and caliper. The mean pedicle length and mean diameters (Ø) of the thoracoacromial artery and concomitant vein were found to be 9.8 cm, Ø 4.2 mm, and Ø 4.9 mm, respectively. These results suggest the potential utility of a free pectoralis major flap with microvascular anastomosis.

Mucosal melanoma of the cranio-facial region: Surgical challenges and therapeutic options.

OBJECTIVE: Although current therapeutic options for cutaneous melanoma (CM) are constantly improving survival, mucosal melanoma (MM) remains a rare tumor disease with a poor clinical outcome. While radical surgery is the gold standard, clear margin resections in the head and neck area are particularly critical due to high density of vulnerable structures. Adjuvant therapeutic options increases local control and data on the effect of systemic agents is sparse. The aim of this study was to elucidate surgical challenges in the craniofacial area and to evaluate the effect of local and systemic therapy in Head and Neck Mucosal Melanoma (HNMM). METHODS: In total, 21 patients with nasal mucosal malignant melanoma were included in this study over the course of 20 years in two German tertiary referral centers. Patient characteristics and conducted therapy as well as clinical outcomes were analyzed retrospectively. RESULTS: By performing survival analysis for multimodal therapies, we observed a superiority effect of interferon therapy compared to surgery with radiation and surgery alone in the first therapeutic approach. However, patients treated with surgery alone in a recurrent setting showed the best outcome. CONCLUSION: Both, Interferon and radiation as adjuvant therapies, demonstrated survival benefits in initial treatment compared to surgery alone. Analysis after recurrence, however, revealed salvage surgery as a reliable and powerful tool to prolong post-recurrence survival without exposing palliative patients to the risk of severe adverse events from systemic therapies.

Systematic Review of Quality-of-Life Measurement After Aesthetic Rhinoplasty.

INTRODUCTION: The assessment of outcomes in aesthetic rhinoplasty is highly relevant because patient satisfaction and improved health-related quality of life (QoL) are the predominant factors in determining success. The patient-reported outcome measures (PROMs) employed in rhinoplasty research studies are remarkably diverse, thus yielding difficulties with data analysis. The aim of this article is to provide a comprehensive review of the literature to reveal the relevance of the QoL assessment for rhinosurgeons. METHODS: A systematic literature search with the terms "Rhinoplasty" and "Quality of Life" was conducted using PubMed/MEDLINE, Google Scholar and Cochrane databases. Primarily, all publications related to QoL following aesthetic rhinoplasty between 2002 and 2017 were identified. As a secondary selection, we focused on articles with a prospective study design, a significant cohort size (at least 50 patients) and a follow-up period of at least 6 months after aesthetic rhinoplasty. RESULTS: A total of 62 PROM studies assessing QoL following aesthetic rhinoplasties were obtained. We ascertained an increasing publication rate of QoL articles over the last 15 years. Only 17 studies satisfied comprehensive inclusion criteria of a high qualitative study selection. The Rhinoplasty Outcome Evaluation was the most frequently used QoL questionnaire of the secondary selection (70.6%). The total number of 16 various questionnaires exhibit high heterogeneity. CONCLUSION: Our data strengthen the increasing importance of the assessment of QoL after rhinoplasty. Despite a lack of reliable publications with considerable heterogeneity and large variability in outcomes, functional-aesthetic rhinoplasty leads to a significant improvement of patient's health-related QoL. LEVEL OF EVIDENCE II: 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 .

Low SOX2 expression marks a distinct subset of adenoid cystic carcinoma of the head and neck and is associated with an advanced tumor stage.

INTRODUCTION: The transcription factor SOX2 has been identified as a lineage survival oncogene in squamous cell carcinoma and copy number gain is a common event in several human malignancies including head and neck cancer. However, the regulation and function of SOX2 during carcinogenesis as well as its prognostic value appears to be highly context dependent. As an example, high SOX2 expression in lung squamous cell carcinoma (SCC) is related to a favorable prognosis, while it is associated with poor outcome in lung adenocarcinoma. More recently, higher SOX2 levels and improved survival was also reported for head and neck SCC (HNSCC), and silencing of SOX2 expression in HNSCC cell lines revealed a mesenchymal-like phenotype with prominent vimentin expression. So far, SOX2 expression and its clinical relevance for other head and neck cancers, such as adenoid cystic carcinoma (HNACC) have not been sufficiently investigated. MATERIAL AND METHODS: SOX2, vimentin and E-cadherin expression was assessed by immunohistochemical staining on serial sections from formalin fixed and paraffin embedded tissue samples of a patient cohort (n = 45) with primary ACC and correlated with patient and tumor characteristics as well as survival. RESULTS: High SOX2 expression was found in 14 (31%) primary tumor specimens and was significantly correlated with a N0 lymph node status (p = 0.04), while low SOX2 expression was correlated with a solid growth pattern (p = 0.031). Of the 45 patients, 27 tumor samples resembled an EMT-like phenotype, as assessed by high vimentin and low E-cadherin levels. However, in HNACC SOX2 levels were neither correlated with vimentin nor with E-cadherin expression, further supporting a context dependent regulation and function of SOX2 in distinct tumor entities. CONCLUSION: The absence of SOX2 was predominantly found in solid HNACC, which are characterized by a more aggressive phenotype in ACC. However, the underlying molecular mechanisms of SOX2 regulation and function in distinct HNACC subgroups remain to be fully elucidated.

Adenoid cystic carcinoma of the head and neck area: Oncologic treatment and plastic-reconstructive options.

Adenoid cystic carcinoma of the head and neck area is a rare malignant tumor with acceptable short-term but mediocre long-term prognosis. Radical tumor excision with clear resection margins, and sometimes resection of the facial nerve due to perineural growth, remains the fundamental therapy. We present 3 distinct clinical cases and discuss the current therapeutic options with special focus on plastic-reconstructive techniques. For reconstruction, the full armament of local and free flaps, as well as prosthetics, may be necessary. Adjuvant radiotherapy increases local control in advanced stages or close resection margins. However, systemic treatment options are limited. Further multicenter clinical trials are necessary due to the rare occurrence of the tumor.

[Virtual Planning of Prosthetic Treatment of the Orbit]. / Virtuelle Planung bei der epithetischen Orbitaversorgung.

Optimal positioning of bone-anchored implants in the treatment of patients with orbital prosthesis is challenging. The definition of implant axis as well as the positioning of the implants is important to prevent failures in prosthetic rehabilitation in these patients. We performed virtual planning of enossal implants at a base of a standard fan beam CT scan using the software CoDiagnostiX™ (DentalWings, Montréal, Canada). By 3D-printing a surgical guide for drilling and implant insertion was manufactured (Med-610™, Stratasys, Rehovot, Israel). An orbital exenteration was performed in a patient after shrinkage of the eyelids 20 years after enucleation and radiation of the orbit due to rhabdomyosarcoma. 4 Vistafix-3 implants (Cochlear™, Cochlea, Centennial, USA) were primarily inserted after resection with the help of the 3D-surgical guide. Prosthetic rehabilitation could be achieved as preplanned to a predictable result. The individual prosthesis of the orbit showed good functional and esthetic outcome. The virtual 3D-planning of endosseous implants for prosthetic orbital and periorbital reconstruction is easy to use and facilitates optimal placement of implants especially in posttherapeutically altered anatomic situations.

Checkpoint inhibition for advanced mucosal melanoma.

BACKGROUND: Whereas anti-PD-1 therapy has demonstrated a significant and durable response against advanced cutaneous melanoma, conventional chemotherapies have shown only minor benefit against advanced mucosal melanoma. OBJECTIVES: To investigate the efficacy of anti-PD-1 therapy in a small cohort of patients with mucosal melanoma of the head and neck. MATERIALS & METHODS: We analysed five patients with mucosal melanoma of the head and neck who received nivolumab or pembrolizumab, at an advanced stage. Expression of PD-L1 and PD-1 in all tumour samples was evaluated immunohistochemically. RESULTS: All patients received at least two cycles of nivolumab or pembrolizumab. The most severe adverse events were categorised as CTCAE (common terminology criteria for adverse events) Grade 2. All patients showed progressive disease after restaging at three and six months, and no partial or complete response was observed. Immunohistochemical staining demonstrated PD-L1 expression in less than 5% of tumour cells. CONCLUSION: Systemic therapy with either nivolumab or pembrolizumab showed no clinical response, however, tumour progression was identified in all patients using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 and immune-related response criteria (irRC) to evaluate tumour response.

Three different turbinoplasty techniques combined with septoplasty: Prospective randomized trial.

OBJECTIVES/HYPOTHESIS: Septal deviation and hypertrophic inferior turbinates are a frequent cause of nasal breathing disorders. The goal of this study was to prove the effectiveness and safety of three current turbinoplasty techniques. STUDY DESIGN: This is a prospective, three-arm, single-blinded, single-center, randomized controlled trial. METHODS: Sixty patients were randomly assigned to either anterior turbinoplasty (ATP) (n = 20), radiofrequency ablation (RFA) (n = 19; Celon Pro Breath), or novel submucous radial diode laser ablation (DLA) (n = 21; ELVeS Radial PainLess, wavelength = 1,470 nm), each in combination with standard septoplasty. Acoustic rhinometry, rhinomanometry, subjective nose questionnaire, and saccharin test served as outcome parameters for preoperative and 3-month, 1-year, and 2-year postoperative examinations. RESULTS: After 3 months 47/60 patients were evaluated, 28/60 patients were evaluated after 1 year, and 26/60 patients were evaluated in the 2-year follow-up visit. An improvement of nasal breathing was observed in all three groups in all follow-up visits. The increase of endonasal volume 2 (volume between the nasal valve and body of the inferior turbinate) was statistically significant in the ATP and RFA group after 3 months and 2 years, and in the RFA group also after 1 year. The DLA group failed to reach significance level in all follow-up visits. Subjective evaluation of nasal breathing improved in all three groups. CONCLUSIONS: In this trial, three different current techniques of turbinate surgery in combination with standard septoplasty were effective for the improvement of nasal breathing. The ATP and RFA techniques were more effective in the long term than DLA. LEVEL OF EVIDENCE: 1b. Laryngoscope, 2016 127:303-308, 2017.

Hybrid procedure for total laryngectomy with a flexible robot-assisted surgical system.

INTRODUCTION: Total laryngectomy is a standard procedure in head-and-neck surgery for the treatment of cancer patients. Recent clinical experiences have indicated a clinical benefit for patients undergoing transoral robot-assisted total laryngectomy (TORS-TL) with commercially available systems. Here, a new hybrid procedure for total laryngectomy is presented. METHODS: TORS-TL was performed in human cadavers (n = 3) using a transoral-transcervical hybrid procedure. The transoral approach was performed with a robotic flexible robot-assisted surgical system (Flex®) and compatible flexible instruments. Transoral access and visualization of anatomical landmarks were studied in detail. RESULTS: Total laryngectomy is feasible with a combined transoral-transcervical approach using the flexible robot-assisted surgical system. Transoral visualization of all anatomical structures is sufficient. The flexible design of the robot is advantageous for transoral surgery of the laryngeal structures. CONCLUSION: Transoral robot assisted surgery has the potential to reduce morbidity, hospital time and fistula rates in a selected group of patients. Initial clinical studies and further development of supplemental tools are in progress. Copyright © 2016 John Wiley & Sons, Ltd.

Expression of Kallikrein-Related Peptidase 6 in Primary Mucosal Malignant Melanoma of the Head and Neck.

Mucosal melanomas of the head and neck (MMHN) are aggressive tumors with poor prognosis, different opposed to cutaneous melanoma. In this study, we characterized primary mucosal malignant melanoma for the expression of Kallikrein-related peptidase 6 (KLK6), a member of the KLK family with relevance to the malignant phenotype in various cancer types including cutaneous melanoma. Paraffin-embedded MMHN of 22 patients were stained immunohistochemically for KLK6 and results were correlated with clinical and pathological data. In 77.3% (17/22) of MMHN cases, positive KLK6 staining was found. Staining pattern for tumor cells showed a predominant cytoplasmic staining. However, in six cases we also observed a prominent nuclear staining. MMHN with a high KLK6 expression showed significantly better outcome concerning local recurrence-free survival (p = 0.013) and nuclear KLK6 staining was significantly associated with the survival status (p = 0.027). Overexpression of KLK6 was detected in more than 70% of MMHN and approximately 40% of tumors showed a strong expression pattern. Correlation between clinical outcome of MMHN patients and overexpression of KLK6 has not been addressed so far. Our data demonstrate for the first time increased levels of KLK6 in MMHN and strengthen the hypothesis that there might be a context-specific regulation and function of KLK6 in mucosal melanoma.

Expression and clinical significance of MAGE and NY-ESO-1 cancer-testis antigens in adenoid cystic carcinoma of the head and neck.

BACKGROUND: Adenoid cystic carcinoma (ACC) of the head and neck is a rare but highly malignant tumor. Cancer-testis antigens (CTAs) represent an immunogenic family of cancer-specific proteins and thus represent an attractive target for immunotherapy. METHODS: Eighty-four cases of ACC were identified, the CTAs pan-Melanoma antigen (pan-MAGE; M3H67) and New York esophageal squamous cell carcinoma (NY-ESO-1; E978) were detected immunohistochemically (IHC) and correlated with clinical data. RESULTS: Expression of NY-ESO-1 was found in 48 of 84 patients (57.1%) and of pan-MAGE in 28 of 84 patients (31.2%). Median overall survival (OS) in NY-ESO-1 positive versus negative patients was 130.8 and 282.0 months (p = .223), respectively. OS in pan-MAGE positive versus negative patients was 105.3 and 190.5 months, respectively (p = .096). Patients expressing both NY-ESO-1 and pan-MAGE simultaneously had significantly reduced OS with a median of 90.5 months compared with 282.0 months in negative patients (p = .047). CONCLUSION: A significant fraction of patients with ACC show expression of the CTAs NY-ESO-1 and/or pan-MAGE with promising immunotherapeutic implications. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1008-1016, 2016.

Expression of Submaxillary Gland Androgen-regulated Protein 3A (SMR3A) in Adenoid Cystic Carcinoma of the Head and Neck.

BACKGROUND: Adenoid cystic carcinoma of the head and neck (ACC) is a rare tumor entity which originates from the salivary glands. The prognosis remains poor, as the tumor tends to exhibit perineural invasion and frequently develops distant metastases. The submaxillary gland androgen-regulated protein 3A (SMR3A) belongs to a gene family producing opiorphin homologs and is physiologically secreted by salivary glands. Expression of SMR3A has been identified as an unfavorable risk factor in survival of patients with squamous cell carcinoma in the head and neck, but its value as a prognostic biomarker for ACC has not been addressed. MATERIALS AND METHODS: Tissue sections from primary ACC (n=86) and healthy glandular tissue as reference, were stained by immunohistochemistry. SMR3A expression levels were correlated with clinical and pathological features, including overall survival. RESULTS: All patients had undergone surgery and 67 received adjuvant radiotherapy. The median disease-free survival (DFS) was 37 months and the median overall survival (OS) was 75 months. Prominent SMR3A expression in tumor cells was found in 24 of 86 patients (27,9%), and was inversely correlated with a male gender (p=0.009). There was no significant correlation between SMR3A expression and DFS, metastasis-free survival or OS. CONCLUSION: Our data demonstrate for the first time decreased levels of SMR3A in ACC compared to normal glandular tissue. These data suggest a context-dependent regulation of SMR3A expression in the pathogenesis of distinct subtypes of head and neck tumors, and support the assumption that detection of SMR3A expression serves as a surrogate for aberrant differentiation into mucosal- or glandular-like cells in ACC and head and neck squamous cell carcinoma.