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.

Significance of endolymphatic sac surgery with and/or without simultaneous cochlea implant surgery in respect of vertigo control and speech perception in patients with Menière's disease.

PURPOSE: The focus on treating patients with Menière's Disease (MD) lies on the reduction of vertigo attacks and the preservation of sensory function. Endolympathic hydrops is considered as an epiphenomenon in MD, which can potentially be altered by endolymphatic sac surgery (ESS). Purpose of the study was to investigate the influences on vertigo control through manipulation of the perilymphatic system with or without ESS. METHODS: Retrospective data analysis of 86 consecutive patients with MD according to current diagnostic criteria after endolymphatic sac surgery alone (ESSalone; n = 45), cochlear implantation (CI) alone (CIalone; n = 12), and ESS with CI (ESS + CI; n = 29), treated at a tertiary referral center. MAIN OUTCOME MEASURES: vertigo control, speech perception pre- and postoperatively. RESULTS: Gender, side, and preoperative treatment were similar in all groups. Age was younger in the ESSalone-group with 56.2 ± 13.0 years (CIalone = 64.2 ± 11.4 years; ESS + CI = 63.1 ± 9.7 years). Definitive MD was present in all the CIalone, in 79.3% of the ESS + CI and in 59.6% of the ESSalone-patients. Likewise, vertigo control rate was 100% in the CIalone, 89.7% in the ESS + CI and 66.0% in the ESSalone-group. CONCLUSIONS: Vertigo control was improved in all three groups, however, superior in groups treated with CI, potentially contributed by the manipulation of both the endo- and perilymphatic systems. A more systematic characterization of the patients with larger case numbers and documentation of follow up data would be needed to evaluate a clinical effect more properly.

Randomized, placebo-controlled study on efficacy, safety and tolerability of drug-induced defibrinogenation for sudden sensorineural hearing loss: the lessons learned.

PURPOSE: Disturbance of cochlear microcirculation is discussed as final common pathway of various inner ear diseases. Hyperfibrinogenemia causing increased plasma viscosity is a possible factor for a critical reduction of cochlear blood flow that might lead to sudden sensorineural hearing loss (SSHL). The aim was to determine the efficacy and safety of drug-induced defibrinogenation by ancrod for SSHL. METHODS: Double-blind, randomized, placebo-controlled, multicenter, parallel group, phase II (proof-of-concept) study (planned enrollment: 99 patients). Patients received an infusion of ancrod or placebo (day 1) followed by subcutaneous administrations (day 2, 4, 6). Primary outcome was the change in pure tone audiogram air conduction average until day 8. RESULTS: The study was terminated early due to slow recruiting (31 enrolled patients: 22 ancrod, 9 placebo). A significant improvement of hearing loss was registered in both groups (ancrod: - 14.3 dB ± 20.4 dB, - 39.9% ± 50.4%; placebo: - 22.3 dB ± 13.7 dB, - 59.1% ± 38.0%). A statistically significant group-difference was not detected (p = 0.374). Placebo response of 33.3% complete and 85.7% at least partial recovery was observed. Plasma fibrinogen levels were reduced significantly by ancrod (baseline: 325.2 mg/dL, day 2: 107.2 mg/dL). Ancrod was tolerated well, no adverse drug reaction was of severe intensity, no serious adverse events occurred. CONCLUSION: Ancrod reduced fibrinogen levels that support its mechanism of action. The safety profile can be rated positively. Since the planned number of patients could not be enrolled, no efficacy conclusion can be drawn. The high rate of placebo response challenges clinical trials for SSHL and needs to be considered in future investigations. Trial registrations This study was registered in the EU Clinical Trials Register, EudraCT-No. 2012-000066-37 at 2012-07-02.

Parameters for estimating the feasibility of implantation of a semi-implantable bone conduction device (SIBCD) in children and adolescents.

PURPOSE: In children and adolescents, preoperative planning for a semi-implantable bone conduction device (SIBCD) is crucial. The geometric changes of the new version of a common SIBCD should enable a higher rate of successful implantation due to its flatter actuator. Thus, this radioanatomic study compared the rate of successful implantation of both device versions at the traditional mastoidal localization and two alternative sites, retrosigmoidal, and parietal, and investigated parameters helping to estimate the feasibility. METHODS: A retrospective analysis of 136 CT scans of 0 to 20-year-old patients, evaluation of demographic parameters, radioanatomy, and assessment of head diameter was conducted. The feasibility was investigated for certain age groups at three implantation sites. Prediction of feasible implantation by means of different parameters was calculated. RESULTS: A significant higher implantation rate was observed with the new device for all three sites and age groups. The age group of 6-8 years (n = 19) had most striking differences with a 58.1% rate of successful implantation with the new device without spacer (80% with spacer) at the mastoidal localization, whereas none with the old implant. Head diameter was identified as the most predictive parameter regarding all implantation sites (mastoidal: p = 0.030; retrosigmoidal: p = 0.006; parietal: p < 0.0001), age for the mastoidal (p < 0.0001) and retrosigmoidal (p < 0.0001), and gender for the parietal site (p = 0.001). CONCLUSION: The geometric changes of the actuator lead to a higher rate of successful implantation in all age-groups and all three localizations with reducing the requirement for spacers. Parameters age and head diameter might aid in estimating the rate of successful implantation in young patients and may be a novel tool to assist in the decision-making process for a SIBCD.

Vestibular and audiometric results after endolymphatic mastoid shunt surgery in patients with Menière's disease.

PURPOSE: Treatment of Menière's Disease (MD) comprises an array of both non-destructive and destructive treatment options. In patients who are therapy-refractory to non-destructive medical treatment, endolymphatic mastoid shunt surgery (EMSS) is both recommended and debated controversially. The aim of this study was to investigate safety in terms of hearing, vestibular function, complication rate, and efficacy with regards to vertigo control of EMSS in patients with MD according to the current diagnostic criteria of 2015. METHODS: Retrospective analysis of 47 consecutive patients with definite or probable MD with description of demographic parameters, pre- and postoperative MD treatment, pre- and postoperative audiometric (pure tone audiometry) and vestibular (caloric testing) results. The parameters were compared between patients with and without postoperative vertigo control. RESULTS: 31/47 patients (66.0%) had improved vertigo control postoperatively. Postoperative hearing and vestibular preservation were predominantly stable. No significant differences between patients with improved vertigo control and patients with no change or worse vertigo episodes were found. In the treatment refractory group, 4 patients required a revision EMSS and 6 a destructive MD treatment (5 gentamicin intratympanically, 1 labyrinthectomy). No peri- or postsurgical complications were reported. CONCLUSIONS: EMSS was found to be beneficial in two thirds of the patients with definite or probable Morbus Menière and a safe procedure regarding hearing and vestibular preservation with no postoperative complications. Therefore, EMSS should be considered before inducing destructive treatment options, such as intratympanic gentamicin application or labyrinthectomy.

Subgroups in the treatment of nasal polyposis with dupilumab: A retrospective study.

Dupilumab has been shown to be safe and effective in treating chronic rhinosinusitis with polyposis (CRSwNP). There is to this date no published data whether subgroups like patients with aspirin exacerbated respiratory disease (AERD), increased histologic eosinophilia or elevated blood eosinophil or IgE-levels benefit greater from dupilumab therapy. Moreover, there is no data comparing the efficacy of functional endoscopic sinus surgery (FESS) with dupilumab therapy. We conducted a retrospective chart review of all patients that were treated at a tertiary referral center for CRswNP with dupilumab. We also contacted the patients with a questionnaire to evaluate the efficacy of previous surgeries and dupilumab therapy by visual analogue scale (VAS) and the glasgow benefit inventory (GBI) as well as report on side effects. Overall, 75 patients were included in the study at hand that reported back 138 times. While dupilumab treatment was efficient, we found no systematic evidence of greater efficacy of dupilumab in patients with AERD, histologic eosinophilia or increased blood eosinophil or IgE-levels. All patients showed a considerable decrease in subjective burden of disease, objective smell tests and endoscopic findings. From the patients point of view, dupilumab therapy showed greater efficacy both in the VAS and the GBI overall and all subcategories but "social support." Dupilumab is efficient in treating CRSwNP; this effect is independent from disease characteristics like AERD, histologic eosinophilia, serum IgE-levels or eosinophil counts. There seems to be a group of patients that benefit greater from dupilumab therapy compared to FESS.

Population Based Average Parotid Gland Volume and Prevalence of Incidental Tumors in T1-MRI.

Representative epidemiologic data on the average volume of the parotid gland in a large population-based MRI survey is non-existent. Within the Study of Health in Pomerania (SHIP), we examined the parotid gland in 1725 non-contrast MRI-scans in T1 weighted sequence of axial layers. Thus, a reliable standard operating procedure (Intraclass Correlation Coefficient > 0.8) could be established. In this study, we found an average, single sided parotid gland volume of 27.82 cm3 (95% confidence interval (CI) 27.15 to 28.50) in male and 21.60 cm3 (95% CI 21.16 to 22.05) in female subjects. We observed positive associations for age, body mass index (BMI), as well as male sex with parotid gland size in a multivariate model. The prevalence of incidental tumors within the parotid gland regardless of dignity was 3.94% in the Northeast German population, slightly higher than assumed. Further epidemiologic investigations regarding primary salivary gland diseases are necessary.

Factors influencing outcomes in selective neck dissection in 661 patients with head and neck squamous cell carcinoma.

BACKGROUND: Selective neck dissection (SND) is the surgical treatment of choice in squamous cell carcinoma of the head and neck (HNSCC) with suspected or manifest metastases in the cervical lymph nodes. For SND to be successful, treated lymph node levels should be selected according to anatomic considerations and the extent of the disease. Aim of this study was to identify neck dissection levels that had an impact on individual prognosis. METHODS: We conducted a retrospective review of SND as part of primary treatment of HNSCC. Overall survival (OS) and regional control rates (RCR) were calculated for all patients treated at one academic tertiary referral center. RESULTS: 661 patients with HNSCC were included, 644 underwent ipsilateral and 319 contralateral SND. Average follow-up was 78.9 ± 106.4 months. 67 (10.1%) patients eventually developed nodal recurrence. Tumor sites were oral cavity (135), oropharynx (179), hypopharynx (118) and larynx (229). Tumor categories pT1-pT4a, and all clinical and pathological nodal categories were included. Multivariate analysis indicated improved OS rates for patients undergoing SND in ipsilateral levels I and V as well as level III contralaterally. Analysis for tumor origin showed that SND in ipsilateral level I showed significantly improved OS in HNSCC of the oral cavity. CONCLUSION: The dissection of ipsilateral level I in oral cavity cancer was of particular relevance in our exploratory, retrospective analysis. To clarify the relevance for the determination of the extent of SND, this should be investigated prospectively in a more homogenous patient cohort.

Functional results with active middle ear implant or semi-implantable bone conduction device in patients with comparable hearing loss.

OBJECTIVE: In patients with conductive (CHL) or mixed hearing loss (MHL), hearing rehabilitation with an implantable hearing system, active middle ear implant (AMEI) or a semi-implantable bone-conduction device (SIBCD), is an option when conventional hearing aids are insufficient, or patients are unable to wear them. DESIGN: Retrospective analysis of 20 consecutive patients (24 implants) with a comparison of demographic characteristics and audiometric results (air-bone gap = ABG, effective hearing gain = EHG, functional hearing gain = FHG, Freiburg Monosyllabic Test in quiet, Oldenburg Sentence Test in noise = OLSA). STUDY SAMPLE: Patients, eligible for both devices, who received either AMEI or SIBCD due to CHL or MHL. RESULTS: Analysis showed no significant differences in post-operative functional hearing results between the group of AMEI vs. SIBCD (ABG-reduction: 31.6 ± 12.4 dB HL vs. 28.0 ± 11.8 dB HL; p = 0.702; EHG: -1.6 ± 7.7 dB HL vs. -1.2 ± 4.2 dB HL; p = 0.090; FHG: 33.4 ± 12.6 dB HL vs. 26.1 ± 11.7 dB HL; p = 0.192; Freiburg: 83.0 ± 15.6% vs. 83.6 ± 14.2%; Freiburg-improvement: 57.7 ± 26.8% vs. 68.2 ± 19.7%; p = 0.294; OLSA: -2.7 ± 3.0 SNR vs. -1.4 ± 3.6 SNR; OLSA-improvement: 2.6 ± 2.1 dB vs. 3.7 ± 2.8 dB; p = 0.323). Four patients had the AMEI explanted due to insufficient functioning and later received a SIBCD. CONCLUSIONS: Due to more challenging anatomical conditions, a surgical technique for the AMEI is more complex. However, functional results are comparable to the SIBCD. Therefore, proper patient counselling and cautious choice of the device are mandated before surgery.

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.

Management of chronic rhinosinusitis with nasal polyps in Samter triad by low-dose ASA desensitization or dupilumab.

ABSTRACT: Samter triad is a chronic condition where patients suffer from intolerance to aspirin, recurring nasal polyposis and bronchial asthma. Causative treatment is often hard. Potential approaches are the daily intake of acetylsalicylic acid (ASA), shunting arachidonic acid into the lipoxygenase pathway, and a subsequent habituation to this constant inflammatory stimulus. Alternatively, the paramount interleukins 4 and 13 may be antagonized by the monoclonal antibody dupilumab. Hence, we evaluated the daily intake of 100 mg ASA and systemic dupilumab (300 mg s.c. every 2 weeks) therapy in refractory patients for its efficacy and compliance.We conducted a retrospective chart review for the efficacy and compliance of both continuous ASA desensitization and systemic dupilumab therapy for refractory patients.Thirty-one patients were included in this retrospective chart review, mean follow-up was 20.4 ±â€Š15.7 months. All patients underwent ASA desensitization. Twenty-one patients had eventually discontinued therapy after 5.8 ±â€Š4.5 months; 11 for its side effects, 12 for its inefficacy. Twenty patients developed sinunasal complaints soon thereafter. Ten patients were still undergoing desensitization (mean duration 15.3 ±â€Š15.7 months). These patients had a higher prevalence of concomitant anti-asthmatic medication. Seventeen refractory patients underwent systemic dupilumab therapy. After 6.4 ±â€Š2.7 months of treatment, sinunasal outcome test (68.1 ±â€Š13.9 vs 20.1 ±â€Š13.9) and visual analogue scales of overall complaints (8.7 ±â€Š0.9 vs 2.2 ±â€Š1.5) as well as endoscopic findings and olfactory function (brief smell identification test; 3.5 ±â€Š2.6 vs 8.6 ±â€Š2.4) all improved significantly.A considerable number of patients with Samter triad discontinued ASA desensitization, equally for ineffectiveness or side effects. If desensitization is to be effective, special care needs to be taken in respect to concomitant anti-asthmatic medication. Dupilumab is highly effective and safe in treating refractory patients.

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.

The course of subjective and objective chemosensory dysfunction in hospitalized patients with COVID-19: a 6-month follow-up.

PURPOSE: It has been established that the infection with SARS-CoV-2 may cause an impairment of chemosensory function. However, there is little data on the long-term effects of SARS-CoV-2 infection on chemosensory function. METHODS: Twenty three SARS-CoV-2-positive patients diagnosed in spring 2020 with subjective hyposmia (out of 57 positive patients, 40.3%) were compared to SARS-CoV-2-positive patients without hyposmia (n = 19) and SARS-CoV-2-negative patients (n = 14). Chemosensory function was assessed by the Brief Smell Identification Test (BSIT), Taste Strips (TS), Visual Analogue Scales (VAS), and the SNOT-22. The initial cohort with hyposmia were also examined at 8 weeks and 6 months after initial examination. RESULTS: There were no differences between the SARS-CoV-2-positive cohort without hyposmia and negative controls in terms of BSIT (8.5 ± 2.6 vs. 10.2 ± 1.8), TS (3.4 ± 0.6 vs. 3.9 ± 0.3) or VAS (2.1 ± 1.3 vs. 1.1 ± 0.5); yet the SNOT-22 was significantly elevated (27.7 ± 11.2 vs. 16.4 ± 10.8). The SARS-CoV-2-positive group with hyposmia performed significantly poorer in BSIT (4.0 ± 1.7 vs. 8.5 ± 2.6/10.2 ± 1.8), TS (2.6 ± 1.3 vs. 3.4 ± 0.6/3.9 ± 0.3), and VAS (7.9 ± 2.2 vs. 2.1 ± 1.3/1.1 ± 0.5) compared to both control groups. At week 8 and month 6 control, six and five patients, respectively, still suffered from subjectively and objectively impaired chemosensory function. The other patients had recovered in both respects. CONCLUSION: SARS-CoV-2 patients with subjectively impaired chemosensory function regularly perform poorly in objective measurements. About 70% of patients suffering from olfactory dysfunction in SARS-CoV-2 quickly recover-the rest still suffers from considerable impairment 6 months after infection.

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.

Lipopolysaccharide decreases cochlear blood flow dose dependently in a guinea pig animal model via TNF signaling.

OBJECTIVE: To evaluate the effect of Lipopolysaccharide (LPS), a bacterial endotoxin on cochlear microcirculation, and its mode of action. METHODS: Twenty-five Dunkin-Hartley guinea pigs were divided into five groups of five animals each. After surgical preparation, cochlear microcirculation was quantified by in vivo fluorescence microscopy. Placebo or LPS (1 mg, 10 µg, and 100 ng) was applied topically, and microcirculation was measured before and twice after application. A fifth group was pretreated with etanercept, a tumor necrosis factor (TNF) antagonist, and afterward the lowest LPS concentrations that yielded significant results (10 µg) were applied. RESULTS: In the groups that had been treated with 1 mg and 10 µg LPS, a significant drop in cochlear microcirculation was observed after 30 (.791 ± .089 Arbitrary Units (AU), compared to baseline, and .888 ± .071AU) and 60 (.756 ± .101 AU and .817 ± .124 AU, respectively) minutes. The groups that had been treated with 100 ng LPS and that had been pretreated with etanercept showed no significant change in cochlear blood flow compared to placebo. CONCLUSION: Lipopolysaccharide shows a dose-dependent effect on cochlear microcirculation; this effect can already be observed after 30 min. Pretreatment with etanercept can abrogate this effect, indicating that TNF mediates the effect of LPS on cochlear microcirculation.

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.

Safety and Efficacy of Blue Light Laser Treatment in Hereditary Hemorrhagic Telangiectasia.

BACKGROUND AND OBJECTIVES: Hereditary hemorrhagic telangiectasia (HHT) is a hereditary condition that is associated with arteriovenous malformations. A common site for these malformations is the nasal mucosa, which is associated with severe epistaxis and debilitation for affected patients. We evaluated the efficacy and safety of blue light laser technology in treating these endonasal manifestations in a retrospective chart analysis. Additionally, we compared blue light laser technology to bipolar coagulation in an animal model. STUDY DESIGN/MATERIALS AND METHODS: We performed a retrospective chart analysis of all patients that were diagnosed with HHT and received endonasal blue light laser treatment between 10/2017 and 04/2019. In addition, we performed bipolar or blue light laser coagulation of all macroscopically visible vessels on thyroid gland lobes (n = 4) from Dunkin-Hartley Guinea Pigs. Hematoxylin-eosin (HE) staining was then used to visualize depth and area of coagulation surrounding these vessels. RESULTS: One hundred and fifty-one treatments in 23 patients were analyzed. Under regular blue light laser treatment, quality of life (QOL), indicated on a visual analog scale from 1 to 10, gradually increased significantly from 5.6 ± 0.5 (before the first treatment) to 7.5 ± 0.9 (after the second treatment). Following this, QOL remained steady throughout additional treatments. Adverse effects were not recorded. HE staining showed that coagulation depth (162 ± 56 vs. 586 ± 192 µm) and area (74 ± 35 vs. 1015 ± 449 µm2 ) were significantly lower after laser treatment. CONCLUSION: Blue light laser therapy is safe and efficient in treating HHT. Damage to the surrounding tissue is significantly lower compared with bipolar coagulation. © 2020 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC.

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.