Subjective Discomfort during Botulinumtoxin Injections Dependent on Injection Site and Needle Size: A Comparison Between 30G, 33G and 34G Needles.

BACKGROUND: Botulinumtoxin application in the face is amongst the most common aesthetic procedures in the head and neck region. It also has numerous medical uses. One of the main reasons for patients to refrain from it is the subjective discomfort that is experienced during injections. OBJECTIVES: The study at hand aimed to determine whether needles with 33G and 34G offer an advantage in terms of individual pain perception during botulinumtoxin injections. METHODS: We conducted a prospective study where patients were asked to grade subjective discomfort on a visual analogue scale for each region (forehead, glabella, temple) that was treated directly after treatment and 15 minutes after. Patients were treated with 30G, 33G or 34G needles, respectively. RESULTS: Ninety-nine patients that underwent treatment of 189 regions were included in the study. Patients were evenly distributed amongst the different needle sizes and regions. Subjective discomfort was greatest in all regions for 30G needles (3.9 ± 1.6 forehead, 4.3 ± 1.7 glabella and 4.0 ± 1.6 temple) followed by 33G (2.7 ± 1.5 forehead, 2.7 ± 1.9 glabella and 2.2 ± 1.2 temple) and 34G (1.7 ± 1.2 forehead, 1.6 ± 1.4 glabella and 1.6 ± 1.4 temple). All differences between needle size were statistically significant (p < 0.05) CONCLUSION: 33G and 34G needles seem to offer smaller discomfort during BTX treatments of the head and neck, with 34G being superior to 33G. 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.

MicroRNA-182-5p and microRNA-205-5p as potential biomarkers for prognostic stratification of p16-positive oropharyngeal squamous cell carcinoma.

BACKGROUND: MicroRNAs constitute promising biomarkers. OBJECTIVE: The aim was to investigate diagnostic and prognostic implications of miR-182-5p and miR-205-5p in p16-positive and p16-negative oropharyngeal squamous cell carcinomas (OPSCCs). METHODS: Expression of miR-182-5p, miR-205-5p were determined via quantitative real-time-PCR in fresh frozen tissues of 26 p16-positive, 19 p16-negative OPSCCs and 18 HPV-negative oropharyngeal controls. Associations between miRNA-expression, clinicopathological characteristics and prognosis were analyzed. RESULTS: Higher miR-182-5p expression was associated with significant inferior disease-specific survival for p16-positive OPSCCs (HR = 1.98E+09, 95% CI 0-Inf; P= 0.028) and a similar trend was observed for p16-negative OPSCCs (HR = 1.56E+09, 95% CI 0-Inf; P= 0.051). Higher miR-205-5p expression was associated with an inferior progression-free survival (HR = 4.62, 95% CI 0.98-21.83; P= 0.034) and local control rate (HR = 2.18E+09, 95% CI 0-Inf; P= 0.048) for p16-positive OPSCCs. CONCLUSIONS: Results indicate that miR-182-5p and miR-205-5p can further stratify patients with p16-positive OPSCC into prognostic groups.

Nasal Septal Perforation Closure by "Sandwich Grafts": Technique, Initial Results.

Nasal septal perforation closure represents a considerable surgical challenge. Many techniques rely on the implantation of foreign materials that pose a persisting threat of infection. The authors have identified a reliable technique closing septal perforations by an autologous "sandwich graft." It is layered around a piece of auricular cartilage, covered with temporal fascia, thus emulating the physiological layers of the nasal septum. Finally, the prepared graft is then sewn into the perforation in an underlay technique and kept in place by septal splints for 4 weeks. The technique is easily feasible and strives to reconstruct the nasal as physiological as possible. The data obtained from a case series of 11 patients highlights the efficacy of the technique.

Lipedema in a male patient: report of a rare case - management and review of the literature.

Objective: Lipedema is a relatively common yet debilitating and often misdiagnosed lipodystrophy that mainly affects females. Very little is known about the etiology and pathophysiology of the disease. However, due to its high preference for female patients, hormonal factors may contribute to the pathogenesis. Case: A 62-year-old male patient presented to the authors with painful swelling of the thighs. The patient had been treated elsewhere for lymphedema with subsequent disease progression. Lipedema stage IV was confirmed by clinical examination and ultrasound. The patient underwent three sessions of tumescence liposuction which was well tolerated. Later on, the patient reported great improvement in terms of complaints as well as disfigurement. Conclusion: The etiology and pathophysiology of lipedema remain unclear. However, the case at hand shows that lipedema may, albeit rare, also present in male patients. Moreover, we show that liposuction is efficient and safe in treating lipedema even in atypical cases.

Human microRNA-182-5p and kinectin 1: Potential biomarkers for prognosis in oral squamous cell carcinoma.

BACKGROUND: The prognostic impact of hsa-miRNA-182-5p in oral cancer remains unexplored. Therefore, the aim of this study was to investigate the prognostic value of hsa-miRNA-182-5p and its predicted target kinectin 1 (KTN1) in oral squamous cell carcinoma (OSCC). METHOD: Expression level of hsa-miRNA-182-5p was analyzed in tumor tissue (n = 36) and healthy oral mucosal tissue (n = 17) using quantitative real-time polymerase chain reaction. Protein level of the predicted target KTN1 was detected via immunohistochemistry. Results were validated in a cohort of The Cancer Genome Atlas (TCGA). RESULTS: After dividing the data into a subgroup with high and low hsa-miRNA-182-5p expression level, a significant better overall (p = 0.016), recurrence-free (p = 0.009), and progression-free survival (p = 0.004) was observed in an upregulation of hsa-miRNA-182-5p. Staining intensity of KTN1 showed a reciprocal impact on the prognosis. Validation in a TCGA cohort confirmed these results. CONCLUSION: Our results indicate hsa-miRNA-182-5p and KTN1 as potential biomarkers for OSCC.

Cancer Stem Cell Markers in Squamous Cell Carcinomas of the Salivary Glands.

BACKGROUND: Cancer stem cells (CSC) are cells that exhibit stem cell properties and are pivotal in tumor biology. CSC markers have been described for many tumorous entities. However, to this date, there is no data on CSC markers in respect to squamous cell carcinomas (SCC) of the salivary glands. METHODS: Histologic samples from patients with salivary gland SCCs were stained for CSC markers (ALDH-1/BMI-1/SOX-2/CD-44/vimentin) and divided into high and low expression subgroups. These were then correlated with tumor and patient characteristics as well as overall survival (OS), disease-specific survival, recurrence-free survival and local control rates (LCR) after 3 and 5 years. RESULTS: Overall, 31 samples were included. CD-44 and ALDH-1 expression were associated with tumor origin (metastatic/primary disease, p = 0.048 and p = 0.011, respectively). Strong BMI-1 expression was associated with poorer OS (62.9 vs. 27.3%, p = 0.029), strong SOX-2 expression was associated with poorer LCR (62.5 vs. 21.9%, p = 0.007). CONCLUSION: CD-44 and ALDH-1 may be useful in differentiating between primary SCCs and metastatic disease. BMI-1 and SOX-2 are correlated with poorer prognosis.

Etiology, Management, and Outcome of Pediatric Epistaxis.

OBJECTIVE: Epistaxis in children is one of the most common causes for seeking professional medical help. Patients may be treated by several disciplines with various approaches to pediatric epistaxis. We reviewed cases of pediatric epistaxis from an otorhinolaryngologist's point of view. METHODS: A retrospective chart review was performed on all patients younger than 18 years presenting with epistaxis to the Department of Otorhinolaryngology at the University of Bonn, Germany. RESULTS: Sixty episodes of epistaxis in 58 patients were included in the study. Mean age was 10.1 ± 4.5 years. In terms of risk factors, 3 patients had a hemorrhagic diathesis, 3 had taken medication that interfered with hemostasis, and 8 had a history of previous trauma, most of which was digital manipulation. Twenty-six patients did not need invasive therapy. Twenty-six patients received cauterization to control the bleeding, and 4 patients needed surgery. The necessity for surgery was mainly noncooperation. CONCLUSIONS: Epistaxis in children is seldom serious. However, hemorrhagic diathesis needs to be kept in mind as a potential cause of epistaxis. In most cases, careful instruction of the patients and the relatives concerning nasal mucosal care is sufficient. If cauterization is necessary, silver nitrate coagulation should be preferred over electrocoagulation.

Cancer stem cell markers in adenocarcinoma of the salivary glands - reliable prognostic markers?

PURPOSE: Adenocarcinoma of the salivary glands is of low incidence and a broad range of histopathological subtypes. Cancer stem cell markers (CSC) might serve as novel prognostic parameters. To date, only a few studies examined the expression of CSC in adenocarcinoma of the salivary glands with diverging results. To further investigate the reliability in terms of prognostic value, a histopathological analysis of CSCs on a cohort of patients with adenocarcinomas of the major salivary glands was performed. METHODS: Tumor samples of 40 consecutive patients with adenocarcinoma of the major salivary gland treated with curative intend at one tertiary center were stained with the CSCs ALDH1, BMI-1, CD44, Nanog, and SOX2. Expression of these markers was correlated with clinicopathological parameters and survival estimates. RESULTS: Correlation of high expression of ALDH1 with higher grading (p < 0.001) and high expression of CD44 with the localization of the neoplasm (p = 0.05), larger tumor size (p = 0.006), positive pN-category (p = 0.023), and advanced UICC stage (p = 0.002) was found. Furthermore, high expression of SOX2 correlated with a negative perineural invasion (p = 0.02). No significant correlation of any investigated marker with survival estimates was observed. CONCLUSION: In conclusion, our study did not find a significant correlation of the investigated CSCs with survival estimates in adenocarcinoma of the major salivary glands. Recapitulating the results of our study in conjunction with data in the literature, the CSCs ALDH1, BMI-1, CD44, Nanog, and SOX2 do not seem to serve as reliable prognostic parameters in the treatment of adenocarcinoma of the salivary glands.

Role of cancer stem cell markers ALDH1, BCL11B, BMI-1, and CD44 in the prognosis of advanced HNSCC.

PURPOSE: Cancer stem cells (CSCs) are held accountable for the progress of head and neck squamous cell carcinoma (HNSCC). In the presented study, the authors evaluated the prognostic value of CSC markers in two particular HNSCC cohorts. METHODS: This two cohort study consisted of 85 patients with advanced stage HNSCC, treated with primary radio(chemo)therapy (pRCT), and 95 patients with HNSCC, treated with surgery and partially adjuvant radio(chemo)therapy. Overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) were assessed. Samples were assessed for the expression of different molecular stem cell markers (ALDH1, BCL11B, BMI­1, and CD44). RESULTS: In the pRCT cohort, none of the baseline patient and tumor features exhibited a statistically significant relation with survival in either the cohort or the human papillomavirus (HPV)-stratified subcohorts. High expression of BMI­1 significantly decreased OS and DFS, while high expression of CD44 decreased all modes of survival. Multivariate analysis showed significant prognostic influence for all tested CSC markers, with high BMI­1 and CD44 decreasing survival (BMI-1: OS, DFS, DSS; CD44: OS, DFS) and high ALDH1 and BCL11B showing a beneficial effect on survival (ALDH1: OS, DFS; BCL11B: OS, DSS). In the surgical cohort, classical prognosticators such as HPV status, R1 resection, and nodal status in HPV-negative HNSCC played a significant role, but the tested CSC markers showed no significant effect on prognosis. CONCLUSION: Although validation in independent cohorts is still needed, testing for CSC markers in patients with advanced or late stage HNSCC might be beneficial, especially if many comorbidities exist or disease is irresectable. The findings might guide the development and earlier use of targeted therapies in the future.

Prognostic impact of additional HPV diagnostics in 102 patients with p16-stratified advanced oropharyngeal squamous cell carcinoma.

PURPOSE: p16 overexpression was considered as surrogate marker to identify human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCCs). METHODS: 102 patients with advanced stage OPSCCs treated primarily by transoral lasermicrosurgery were included. Prognostic associations of p16- and HPV-status were analyzed separately and combined. RESULTS: In contrast to p16, the HPV-status resulted in no significant survival discrepancies (5-year overall survival (OS) HPV-positive 64.9%, HPV-negative 78.7%). Combining both markers, p16-positive (p16-positive/HPV-positive, p16-positive/HPV-negative) and p16-negative/HPV-negative groups demonstrated comparable high survival (OS 78.1% vs. 85.6% vs. 73.6%). Lowest survival was observed for patients with p16-negative/HPV-positive OPSCCs (OS 40.8%). Never smoking patients with p16-positive OPSCCs demonstrated the highest survival, whereas within former/current smokers with p16-positive and p16-negative disease it was comparable low (OS 90.0% vs. 63.0% vs. 57.4%). CONCLUSIONS: p16- and HPV-status should not be considered as equivalent markers for a better prognosis. Furthermore, they should not generally predominate patient associated factors like smoking.

Pluripotent Stem Cell-Derived Mesenchymal Stem Cells Show Comparable Functionality to Their Autologous Origin.

A multimodal therapeutic approach involving radiotherapy is required when treating head and neck squamous cell carcinoma. However, radiotherapy is restricted due to its high risk for damages to the surrounding healthy tissue of the treated area. Tissue regeneration and wound healing is promoted by the survival and regenerative capacities of tissue-resident or invading stem cells. Mesenchymal stem cells (MSCs) exhibit a promising therapeutic potential in the field of cell-based tissue engineering and regenerative medicine due to their immunomodulatory properties and differentiation capacity. However, the generation of MSCs for therapeutic applications is still a major challenge. We aimed to produce highly homogeneous induced pluripotent stem cell-derived mesenchymal stem cells (iP-MSCs) in an autologous manner from initially isolated human mucosa mesenchymal stem cells (mMSCs) of the upper respiratory tract. Therefore, mMSCs were reprogrammed into induced pluripotent stem cells (iPSCs) by non-integrative chromosomal technologies and differentiated into corresponding iP-MSCs. We demonstrated that mMSCs and iP-MSCs show similar cell characteristics in terms of morphology, clonogenic potential, differentiation, and surface phenotype. Moreover, iP-MSCs demonstrated related immunosuppressive capacity as mMSCs including the secretion of cytokines, and T cell inhibition. Therefore, generating iP-MSCs in an autologous manner may be a novel personalized treatment option in regenerative medicine.

Neurosarcoidosis As a Rare Differential Diagnosis for Single Or Multiple Lesions of the Nervous System.

Objective: Sarcoidosis is a multisystemic granulomatous disease of unknown cause which affects the lung or bilateral hilar lymphadenopathy in over 90% of the cases. Neurosarcoidosis (NS) is rare and accounts for approximately 5 - 15% of the cases. Involvement of all parts of the central and peripheral nervous system is possible with various clinical symptoms, e. g. seizures, hydrocephalus, optic/facial nerve palsy or hearing loss.Methods: We screened the neuropathological data bases and the medical records of two neurosurgical university hospitals for cases of NS. All these cases had been verified by surgical biopsy. We retrospectively evaluated the patient's records with special regard to the histopathology reports and specific clinical symptoms.Results: We identified 9 cases of NS between 1994 and 2014 (3 female, 6 male patients). The average age at the time of diagnosis of NS was 41,4 years. Various clinical symptoms like hydrocephalus (n = 3), seizures (n = 1), meningitis (n = 1), optical nerve involvment with vision disorder (n = 1), myelitis with paraplegia (n = 1), mastoiditis with hearing loss (n = 1), back pain syndrome (n = 2) were present. 7 patients were treated with corticosteroids, 1 patient with cyclophosphamide and 1 with a combination of corticosteroids and methotrexate.Conclusion: NS is a rare but potentially life-threatening disease. It is difficult to distinguish sarcoidosis from other granulomatous diseases, infectious diseases like tuberculosis, multiple sclerosis or neoplasm. For a definite diagnosis, a neurosurgical biopsy with histological evidence of noncaseating epithelioid cell granulomas is required, followed by multidisciplinary treatment.

Clinical features of sarcoidosis patients presenting with head and neck manifestations - a two-center retrospective study and proposal of a diagnostic algorithm for the otorhinolaryngologist.

Background and Aims: We aimed to investigate the clinical characteristics of patients presenting with sarcoidosis of the head and neck as the initial manifestation and to provide recommendations for the diagnostic work-up for the practicing otorhinolaryngologist.Material and Methods: We performed a retrospective cohort study at two university medical centers in Germany. Patients with a histopathologically confirmed diagnosis of sarcoidosis treated in the otorhinolaryngology departments were analyzed.Results: We identified 62 patients (2003-2016). In total, 85.4% (n = 53) of patients received the initial diagnosis of sarcoidosis during their ENT treatment. Sarcoidosis was detected in the lymph nodes in 42.3% (n = 30) of the patients; 57.7% had extra-lymphatic manifestations. Fifteen patients (24.2%) showed pulmonary involvement. 30.6% (n = 19) were treated with oral glucocorticoids (GC) alone, three patients with GC and methotrexate, one patient initially received a combination of GC and azathioprine, one patient rejected the recommended treatment.Conclusions: Sarcoidosis should be considered as a differential diagnosis in patients presenting with head and neck symptoms. The most frequent presenting symptoms were cervical lymphadenopathy and affection of the paranasal sinuses. Therefore, otorhinolaryngologists should be aware of sarcoidosis and help guide referral strategies as they may be the first physicians treating these patients.

Benefit of postoperative radiotherapy for early tumors with single ipsilateral lymph node metastasis.

OBJECTIVES/HYPOTHESIS: Indication for postoperative radiotherapy in patients with locally circumscribed tumors (pT1-pT2) and a single ipsilateral lymph node metastasis (pN1) is debatable. The aim of this study was to evaluate the oncological long-term outcome of patients with pT1-pT2 pN1 squamous cell carcinoma (SCC) of the oral cavity, the oropharynx, and the hypopharynx without extracapsular spread (ECS) after a margin-negative surgical resection, who either received or did not receive postoperative (chemo)radiotherapy. STUDY DESIGN: Retrospective case series. METHODS: The oncological outcome of patients with pT1-pT2 pN1 SCC without ECS was evaluated retrospectively. All patients underwent primary tumor resection that included transoral laser microsurgery and neck dissection at an academic tertiary referral center. RESULTS: Of 65 identified patients treated between 1986 and 2015 (18 oral cavity, 30 oropharynx, 17 hypopharynx), 21 (32%) received postoperative radiotherapy, and 44 (68%) were treated by surgery alone. The group of patients receiving postoperative treatment showed a significantly superior 5-year disease-specific (94.4% vs. 73.2%, P = .029) and recurrence-free survival (85.2% vs. 43.2%, P = .002), as well as a higher local control rate (90.2% vs. 64.9%, P = .042). The overall survival was 71.4% vs. 62.6% (P = .53). The mean follow-up was 80.7 months. CONCLUSIONS: Patients with locally circumscribed carcinomas and a single ipsilateral ECS-negative lymph node metastasis seem to benefit from postoperative radiotherapy. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:E530-E538, 2020.

Long-Term Stability and Functional Outcome of an Active Middle Ear Implant Regarding Different Coupling Sites.

OBJECTIVES: Indication and implantation of active middle ear implants (AMEI) are well established. Choice of the coupling site depends from the individual anatomical situation. Long-term stability of different coupling sites in terms of functional outcome and complications are rare and were investigated in this study. DESIGN: Retrospective analysis of 41 consecutive patients (45 ears) with coupling of the AMEI at the incus, stapes, and round window. Analysis of preoperative, postoperative, and long-term results of pure-tone average, speech discrimination in quiet at 65 dB (German language Freiburg Monosyllabic Test) and noise (German language Oldenburger Sentence Test), rate of revision surgeries as well as explantations and the novel parameter patient years (py). RESULTS: Mean of follow-up was 3.0 ±â€Š1.7 years resulting in a total of 135.6 py. Bone conduction was stable in all patients pre- to postoperatively as well as preoperatively to the long-term. Round window patients had the broadest air-bone gap (31.4 ±â€Š19.4 dB HL) benefitting the most from the AMEI (functional gain = 39.0 ±â€Š12.8 dB HL). Regarding speech discrimination, incus patients performed the best both in quiet (77.7 ±â€Š22.8%) and noise (3.4 ±â€Š2.9 dB SNR). In terms of revision surgery and explantations, round window patients exhibited the highest rates (20%). CONCLUSIONS: Regarding all coupling sites, satisfying long-term stability results and comparable complication rates were reported with best performance of coupling to the incus. Implementation of patient years might be a novel parameter for the comparison of revisions and explantations.

Molecular Characterization of Lipoaspirates Used in Regenerative Head and Neck Surgery.

IMPORTANCE: Adipose-derived mesenchymal stem cells (ASCs) have been used commonly in regenerative medicine and increasingly for head and neck surgical procedures. Lipoaspiration with centrifugation is purported to be a mild method for the extraction of ASCs used for autologous transplants to restore tissue defects or induce wound healing. The content of ASCs, their paracrine potential, and cellular potential in wound healing have not been explored for this method to our knowledge. OBJECTIVE: To evaluate the characteristics of lipoaspirates used in reconstructive head and neck surgical procedures with respect to wound healing. DESIGN, SETTING, AND PARTICIPANTS: This case series study included 15 patients who received autologous fat injections in the head and neck during surgical procedures at a tertiary referral center. The study was performed from October 2017 to November 2018, and data were analyzed from October 2017 to February 2019. MAIN OUTCOMES AND MEASURES: Excessive material of lipoaspirates from subcutaneous abdominal fatty tissue was examined. Cellular composition was analyzed using immunohistochemistry (IHC) and flow cytometry, and functionality was assessed through adipose, osteous, and chondral differentiation in vitro. Supernatants were tested for paracrine ASC functions in fibroblast wound-healing assays. Enzyme-linked immunosorbent assay measurement of tumor necrosis factor (TNF), vascular endothelial growth factor (VEGF), stromal-derived factor 1α (SDF-1α), and transforming growth factor ß3 (TGF-ß3) was performed. RESULTS: Among the 15 study patients (8 [53.3%] male; mean [SD] age at the time of surgery, 63.0 [2.8] years), the stromal vascular fraction (mean [SE], 53.3% [4.2%]) represented the largest fraction within the native lipoaspirates. The cultivated cells were positive for CD73 (mean [SE], 99.90% [0.07%]), CD90 (99.40% [0.32%]), and CD105 (88.54% [2.74%]); negative for CD34 (2.70% [0.45%]) and CD45 (1.74% [0.28%]) in flow cytometry; and negative for CD14 (10.56 [2.81] per 300 IHC score) and HLA-DR (6.89 [2.97] per 300 IHC score) in IHC staining; they differentiated into osteoblasts, adipocytes, and chondrocytes. The cultivated cells showed high expression of CD44 (mean [SE], 99.78% [0.08%]) and CD273 (82.56% [5.83%]). The supernatants were negative for TNF (not detectable) and SDF-1α (not detectable) and were positive for VEGF (mean [SE], 526.74 [149.84] pg/mL for explant supernatants; 528.26 [131.79] pg/106 per day for cell culture supernatants) and TGF-ß3 (mean [SE], 22.79 [3.49] pg/mL for explant supernatants; 7.97 [3.15] pg/106 per day for cell culture supernatants). Compared with control (25% or 50% mesenchymal stem cell medium), fibroblasts treated with ASC supernatant healed the scratch-induced wound faster (mean [SE]: control, 1.000 [0.160]; explant supernatant, 1.369 [0.070]; and passage 6 supernatant, 1.492 [0.094]). CONCLUSIONS AND RELEVANCE: The cells fulfilled the international accepted criteria for mesenchymal stem cells. The lipoaspirates contained ASCs that had the potential to multidifferentiate with proliferative and immune-modulating properties. The cytokine profile of the isolated ASCs had wound healing-promoting features. Lipoaspirates may have a regenerative potential and an application in head and neck surgery. LEVEL OF EVIDENCE: NA.

MicroRNA expression patterns in oral squamous cell carcinoma: hsa-mir-99b-3p and hsa-mir-100-5p as novel prognostic markers for oral cancer.

BACKGROUND: MicroRNAs (miRNA) recently evolved as potential cancer biomarkers. Therefore, the aim of the present study was to evaluate the prognostic impact of eight miRNAs connected to oral squamous cell carcinoma (OSCC). METHOD: Expression levels of hsa-mir-21-5p, hsa-mir-29b-3p, hsa-mir-31-5p, hsa-mir-99a-5p, hsa-mir-99b-3p, hsa-mir-100-5p, hsa-mir-143-3p and hsa-mir-155-5p were analyzed in tumor tissue (n = 36) and healthy oral mucosal tissue (n = 17) and correlated with clinical variables. Results of the study cohort were validated in an OSCC cohort of The Cancer Genome Atlas. RESULTS: Increased hsa-mir-99b-3p expression level showed a tendency toward advanced tumor stages, and high levels of hsa-mir-100-5p expression were associated with extracapsular extension. While a high expression level of hsa-mir-99b-3p was associated with better survival, a high expression level of hsa-mir-100-5p was correlated with a poorer survival in the study cohort. CONCLUSION: Our results indicate that hsa-mir-99b-3p and hsa-mir-100-5p may serve as novel prognostic biomarkers in OSCC.

Reconstruction of the skull base in spontaneous rhinoliquorrhea.

Objective/Hypothesis: Spontaneous rhinoliquorrhea often occurs due to defects of the skull base. It is often misinterpreted as rhinitis and is surgically the most difficult rhinoliquorrhea entity to close. Methods: We conducted a retrospective chart analysis of patients that were diagnosed with spontaneous rhinoliquorrhea at the University Hospital Bonn between 2001 and 2017. Results: Overall, twelve patients were included in this study. On average, the time between occurrence of nasal discharge and diagnoses of rhinoliquorrhea was 123 days. In ten patients, the localization of the skull base defect could be localized by computed tomography or MRI cisternography. Ten patients underwent surgery, of which 9 remained recurrence free. One patient underwent revision surgery and from thereon was recurrence free. Conclusion: Spontaneous rhinoliquorrhea still remains a diagnostic and therapeutic challenge. Whenever persistent watery nasal discharge appears in a patient, rhinoliquorrhea must be considered. Endoscopic surgical reconstruction of the skull base is the therapeutic gold standard and should be attempted as soon as the diagnosis is secured.

Transoral laser microsurgery for treatment of oropharyngeal cancer in 368 patients.

BACKGROUND: Oncological and functional outcome of transoral laser microsurgery (TLM) for primary treatment of oropharyngeal cancer was examined using a multimodal treatment concept. METHODS: A total of 368 patients with oropharyngeal squamous cell carcinoma (pT1-4, pN0-2, M0) underwent TLM +/- neck dissection (85%), +/- (chemo)radiotherapy (57%). The majority of patients had advanced stage III and IVa disease (79%). RESULTS: Five-year Kaplan-Meier estimates for local control were 83.5% for pT1, 74.1% for pT2, 77.3% for pT3, and 76.0% for pT4a tumors. Five-year estimates of overall, disease-specific, and recurrence-free survival for stage I were 76.0%, 92.8%, and 69.1%; for stage II 71.1%, 85.7%, and 49.6%; for stage III 61.7%, 72.5%, and 58.8%; and for stage IVa 57.3%, 73.7%, and 63.9%, respectively. Postoperative (chemo)radiotherapy improved the outcome for advanced disease. p16-positive tumors had superior survival estimates. Overall, 93.5% maintained regular oral nutrition without feeding tube dependency. CONCLUSION: Primary TLM in multimodal concepts of treatment offers good oncologic outcome even for advanced-stage oropharyngeal cancer.

Radiation-induced sensitivity of tissue-resident mesenchymal stem cells in the head and neck region.

BACKGROUND: Tissue-resident mesenchymal stem cells (MSCs) possess the ability to migrate to areas of inflammation and promote the regeneration of damaged tissue. However, it remains unclear how radiation influences this capacity of MSC in the head and neck region. METHODS: Two types of MSCs of the head and neck region (mucosa [mMSC] and parotid gland [pMSC]) were isolated, cultured and exposed to single radiation dosages of 2 Gy/day up to 10 days. Effects on morphology, colony forming ability, apoptosis, chemokine receptor expression, cytokine secretion, and cell migration were analyzed. RESULTS: Although MSC preserved MSC-specific regenerative abilities and immunomodulatory properties following irradiation in our in vitro model, we found a deleterious impact on colony forming ability, especially in pMSC. CONCLUSIONS: MSC exhibited robustness and activation upon radiation for the support of tissue regeneration, but lost their potential to replicate, thus possibly leading to depletion of the local MSC-pool after irradiation.