An Unknown Foreign laryngeal Object: an exotic complication of skull base osteoradionecrosis.

BACKGROUND: Osteoradionecrosis (ORN) of the skull base is a rare complication after head and neck radiation with a broad variety of subsequent complications. METHODS: A 68-year-old woman with a complex oncological history (right-sided sphenoid meningioma; left-sided neck metastasis of a Cancer of Unknown Primary-CUP) was admitted with a right-sided epi-/ oropharyngeal mass and severe pain exacerbations for further evaluation. CT scan revealed an advanced ORN of the skull base with subsequent abruption of the ventral part of the clivus. This dislocated part of the clivus wedged in the oropharynx for 48 h and then moved towards the larynx, resulting in dyspnea and almost complete airway obstruction. RESULTS: Due to the dangerous airway situation, an urgent exploration and removal of the dislocated clivus was necessary. After a potential cervical spine instability was ruled out, the patient's airway was initially secured with an awake tracheotomy and the clivus was removed transorally. The tracheostomy tube was removed during the ongoing inpatient stay, and the patient was discharged with significant pain relief. CONCLUSIONS: The present case illustrates an orphan complication of skull base ORN resulting in a major airway emergency situation.

The role of elective neck dissection in T1 and T2 nasal cavity squamous cell carcinomas.

PURPOSE: To evaluate the role of elective neck dissection (END) on oncological outcome in early-stage nasal cavity squamous cell carcinomas (SCCs). METHODS: In total, 87 patients with T1 (n = 59; 67.8%) and T2 (n = 28; 32.2%) SCCs were evaluated regarding performance of END, regional recurrences (RR) and its impact on cancer-specific survival (CSS). We further created a risk score based on T-classification, tumor subsite and grading to identify patients whom may benefit from END and calculated the corresponding numbers needed to treat (NNT) to prevent RR. RESULTS: Nine (10.3%) patients experienced RR of whom 3 (5.1%) were T1 and 6 (21.4%) T2 tumors (p = 0.042). All RR originated from moderately or poorly differentiated (G2-G3) SCCs of the nasal septum or vestibule. END was done in 15 (17.2%) patients and none of those experienced RR (p = 0.121). Onset of RR represented the worst prognostic factor for CSS (HR 23.3; p = 0.007) with a 5y-CSS of 44.4% vs. 97.3% (p < 0.001). RR occurred in none of the patients with no or low risk scores compared to 31.6% (6/19) in patients with high-risk scores (p = 0.006). Accordingly, three high-risk patients would need to undergo END (NNT 2.63) to prevent RR compared to a NNT of 8 for the whole cohort. CONCLUSIONS: Although rare, occurrence of RR significantly deteriorates outcome in early stage nasal cavity SCCs, which could be effectively reduced by performance of END. The importance of END is currently underestimated and our proposed risk score helps identifying those patients who will benefit from END.

A new nomogram to predict oncological outcome in laryngeal and hypopharyngeal carcinoma patients after laryngopharyngectomy.

BACKGROUND: To create nomograms for better prediction of the oncological outcome in advanced laryngeal (LxCAs) or hypopharyngeal (HpxCAs) cancer after laryngopharyngectomy. MATERIALS: 239 patients who underwent total laryngectomy or laryngopharyngectomy due to LxCA (52.7%) or HpxCA (47.3%) were included in this study. Based on clinical risk factors (tumor site, lymph node involvement, salvage setting), we created nomograms for prediction of disease-specific survival (DSS) and disease-free survival (DFS). RESULTS: HpxCAs showed a higher rate of lymph node involvement (p < 0.001), a 2.47-fold higher risk of a 2nd head and neck cancer (p = 0.009) and significantly worse loco-regional control rates (p = 0.003) compared to LxCAs. Positive neck nodes and salvage procedures were associated with significantly worse outcome. Nomograms demonstrated that hypopharyngeal tumors with positive neck nodes in salvage situations had the worst oncological outcome with a 5-year DSS of 15-20%. CONCLUSIONS: The oncological outcome is worse in hypopharyngeal carcinomas and could be easily quantified by our nomograms that are based on tumor site, lymph node involvement and salvage situation.

Temporal fluctuations of post-tonsillectomy haemorrhage.

PURPOSE: Although haemorrhage is a common and in some cases life-threatening complication after tonsillectomy, surprisingly little is known about the temporal fluctuations of the onset of bleeding. The purpose of this study was to assess circadian and seasonal rhythms of post-tonsillectomy haemorrhage (PTH) and potential ramifications to educate patients and health care staff. METHODS: This retrospective study carried out at a tertiary referral hospital included paediatric and adult patients requiring emergency surgery due to severe PTH between 1993 and 2019. Medical records were reviewed and patient demographics, details regarding the initial procedure, postoperative day of haemorrhage, and start time of emergency surgery were extracted. Descriptive statistics, Kruskal-Wallis test, Mann-Whitney U test, and Chi-square goodness of fit tests were used to detect potential differences. RESULTS: A total of 300 patients with severe PTH and subsequent emergency surgery were identified. The median postoperative duration until PTH was 6 (range: < 1-19) days. 64.7% (n = 194) of all emergency surgeries had to be performed during evening and night hours (6 pm-6 am) (p < 0.0001). Compared to diurnal incidents, the risk of a nocturnal PTH event increased, the longer ago the initial surgery was (p < 0.0001). No seasonal variations were identified. Age, sex, and details of the initial procedure had no significant influence on the start time according to the surgical protocol. CONCLUSION: The discovered temporal fluctuations of PTH are of relevance for patient awareness and preoperative education. Due to possible life-threatening complications, management of severe PTH requires specific resources and trained medical staff on call.

Peaks in online inquiries into pharyngitis-related symptoms correspond with annual incidence rates.

OBJECTIVE: To assess whether web-based public inquiries into pharyngitis-related search terms follow annual incidence peaks of acute pharyngitis in various countries from both hemispheres. METHODS: Google Trends (GT) was utilized for systematic acquisition of pharyngitis-related search terms (sore throat, cough, fever, cold). Six countries from both hemispheres including four English (United Kingdom, United States, Canada, and Australia) and two non-English speaking countries (Austria and Germany) were selected for further analysis. Time series data on relative search interest for pharyngitis-related search terms, covering a timeframe between 2004 and 2019 were extracted. Following reliability analysis using the intra-class correlation coefficient, the cosinor time series analysis was utilized to determine annual peaks in public-inquiries. RESULTS: The extracted datasets of GT proved to be highly reliable with correlation coefficients ranging from 0.83 to 1.0. Graphical visualization showed annual seasonal peaks for pharyngitis-related search terms in all included countries. The cosinor time series analysis revealed these peaks to be statistically significant during winter months (all p < 0.001). CONCLUSION: Our study revealed seasonal variations for pharyngitis-related terms which corresponded to winter incidence peaks of acute pharyngitis. These results highlight the need for easily accessible information on diagnosis, therapy, and red-flag symptoms for this common disease. Accurately informed patients might contribute to a reduction of unnecessary clinic visits and potentially cutback the futile antibiotic overuse.

A new nomogram to predict the need for tracheostomy in burned patients.

PURPOSE: To evaluate the impact of tracheostomy on complications, dysphagia and outcome in second and third degree burned patients. METHODS: Inpatient mortality, dysphagia, severity of burn injury (ABSI, TBSA) and complications in tracheotomized burn patients were compared to (I) non-tracheotomized burn patients and (II) matched tracheotomized non-burn patients. RESULTS: 134 (30.9%) out of 433 patients who underwent tracheostomy, had a significantly higher percentage of inhalation injury (26.1% vs. 7.0%; p < 0.001), higher ABSI (8.9 ± 2.1 vs. 6.0 ± 2.7; p < 0.001) and TBSA score (41.4 ± 19.7% vs. 18.6 ± 18.8%; p < 0.001) compared to 299 non-tracheotomized burn patients. However, complications occurred equally in tracheotomized burn patients and matched controls and tracheostomy was neither linked to dysphagia nor to inpatient mortality at multivariate analysis. In particular, dysphagia occurred in 6.2% of cases and was significantly linked to length of ICU stay (OR 6.2; p = 0.021), preexisting neurocognitive impairments (OR 5.2; p = 0.001) and patients' age (OR 3.4; p = 0.046). A nomogram was calculated based on age, TBSA and inhalation injury predicting the need for a tracheostomy in severely burned patients. CONCLUSION: Using the new nomogram we were able to predict with significantly higher accuracy the need for tracheostomy in severely burned patients. Moreover, tracheostomy is safe and is not associated with higher incidenc of complications, dysphagia or worse outcome.

Differences in men and women suffering from CRSwNP and AERD in quality of life.

PURPOSE: While the overall impact of chronic rhinosinusitis (CRS) on patients' health is diverse, many affected individuals have a substantially impaired quality of life (QoL). The aim of this study was to evaluate the impact of sex-associated differences specifically in the subgroups of CRS with nasal polyps (CRSwNP) and aspirin-exacerbated respiratory disease (AERD) by assessing QoL parameters in women and men separately. METHODS: In a retrospective single-center study, 59 patients with CRSwNP (39 males and 20 females) and 46 patients with AERD (18 males and 28 females) were included. Patient-reported outcome measures (PROM) evaluating QoL via the Sino-Nasal Outcome Test-20 German Adapted Version (SNOT-20 GAV) as well as the total polyp score (TPS) were analysed. RESULTS: There was no significant difference in TPS (p = 0.5550) and total SNOT-20 GAV scores (p = 0.0726) between male or female patients with CRSwNP or AERD. Furthermore, no significant sex differences were found within disease groups regarding the subcategories of the SNOT-20 GAV items. CONCLUSION: Thus, quality of life is severely impaired in patients suffering from various forms of CRS regardless of their sex.

The vascularized fascia lata free flap: an anatomical study and clinical considerations.

PURPOSE: Fascia lata (FL) is often used as fascial component of the anterolateral thigh (ALT) flap in head and neck reconstruction. No distinct data exist on whether the FL has its own reliable vascular supply and whether the fascia alone can be harvested as a fascia lata free flap. METHODS: We dissected 25 thighs of 15 cadavers. The lateral circumflex femoral artery (LCFA) was identified, and the size of stained fascia and skin were measured after injection of methylene blue into the descending branch (DB). Finally, topography of fascial vessels was determined. RESULTS: Staining of fascia and skin paddle was found in all 25 cases. Ascending skin perforators of the DB of the LCFA gave off branches for supply of the FL enabling harvest of a fascia lata free flap. Septo- or musculocutaneous perforators pierced FL and entered skin within the proximal 38.6-60% of the thigh. The mean length and width of stained FL was 15.8 ± 4.1 cm and 8.7 ± 2.0 cm, respectively, and size of stained FL ranged from 40.0 to 336.0 cm2. In 20 cases (80%), skin paddles were 2.4 times larger on average compared to corresponding FL. CONCLUSION: We could demonstrate that the FL receives its own vascular supply from perforators of the DB originating from the LCFA. Hence, harvest of a fascia lata free flap is possible, reliable, and the size of the fascia is suitable for reconstruction of small and large defects of the head and neck.

Bacterial colonization of Montgomery salivary bypass tubes after hypopharyngeal reconstruction in head and neck cancer patients.

BACKGROUND: Hypopharyngeal reconstruction after salvage pharyngolaryngectomy results in high postoperative morbidity. The use of salivary bypass tubes can reduce pharyngocutaneous fistula (PCF) formation. The influence of bacterial colonization has not been described in literature. METHODS: Bacterial swipes from 26 consecutive patients reconstructed after laryngopharyngectomy in combination with Montgomery salivary bypass tubes (MSBT) were analyzed in regards to PCF formation. RESULTS: PCF occurred in 2 untreated primary and in 9 salvage laryngopharyngectomies, respectively. Bacterial colonization showed high rates of gram-negative pathogens and drug resistance to standard Ampicillin treatment. Type of bacteria was not associated with fistula formation. Antibiotic resistance was found in 6 out 11 patients (54%) with PCF. CONCLUSIONS: We identified high rates of antibiotic-resistant Gram-negative pathogens on MSBT. Although not statistically significant, PCF were found more frequently in drug-resistant patients. Bacterial colonization of hypopharyngeal reconstructions should therefore be taken into account for perioperative prophylaxis.

Lymph node ratio as a prognostic marker in advanced laryngeal and hypopharyngeal carcinoma after primary total laryngopharyngectomy.

BACKGROUND: We evaluated the prognostic value of lymph node ratio (LNR) in patients with advanced laryngeal and hypopharyngeal squamous cell carcinoma. STUDY DESIGN: Retrospective chart review. METHODS: Between 1994 and 2018, 79 patients underwent total laryngopharyngectomy and adjuvant therapy. LNR was determined and statistically compared to patients' overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), locoregional and distant failure. RESULTS: The 5-year OS, DSS and DFS rates were 45.6%, 73.4% and 56.9%, respectively. 24.1% and 25.3% developed loco- regional failure or distant metastatic disease, respectively. Univariate analyses showed that high LNR (cut-off >0.07) was significantly associated with distant and locoregional failure. On multivariate analysis, LNR remained an independent predictor for OS (P = .004), DSS (P = .009) and DFS (P = .044). CONCLUSION: Increased LNR in patients with advanced laryngeal or hypopharyngeal carcinoma is significantly linked to shortened OS, DSS, DFS and higher locoregional and distant metastatic disease.

Quantitative proteome analysis of Merkel cell carcinoma cell lines using SILAC.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumour of the skin with growing incidence. To better understand the biology of this malignant disease, immortalized cell lines are used in research for in vitro experiments. However, a comprehensive quantitative proteome analysis of these cell lines has not been performed so far. METHODS: Stable isotope labelling by amino acids in cell culture (SILAC) was applied to six MCC cell lines (BroLi, MKL-1, MKL-2, PeTa, WaGa, and MCC13). Following tryptic digest of labelled proteins, peptides were analysed by mass spectrometry. Proteome patterns of MCC cell lines were compared to the proteome profile of an immortalized keratinocyte cell line (HaCaT). RESULTS: In total, 142 proteins were upregulated and 43 proteins were downregulated. Altered proteins included mitoferrin-1, histone H2A type 1-H, protein-arginine deiminase type-6, heterogeneous nuclear ribonucleoproteins A2/B1, protein SLX4IP and clathrin light chain B. Furthermore, several proteins of the histone family and their variants were highly abundant in MCC cell lines. CONCLUSIONS: The results of this study present a new protein map of MCC and provide deeper insights in the biology of MCC. Data are available via ProteomeXchange with identifier PXD008181.

Use of the myocutaneous serratus anterior free flap for reconstruction after salvage glossectomy.

PURPOSE: To describe the use of a myocutaneous serratus anterior free flap (SAFF) for tongue reconstruction after salvage subtotal (STG) and total glossectomy (TG). METHODS: In this prospective case series, seven patients underwent salvage STG or TG and reconstruction with a myocutaneous SAFF between 10/2015 and 02/2017. Functional and oncologic outcomes were prospectively evaluated. Donor side morbidity was determined using the Disabilities of the Arm, Shoulder and Hand (DASH) score. RESULTS: SAFF with mean skin paddles of 6.7 cm × 8.7 cm was used in five STG and two TG patients, respectively. There was a 100% flap survival and a mean DASH score of 10.8 reflected normal arm and shoulder function after surgery. One year after salvage surgery, 1 (14.3%) and 4 (57.1%) patients were tracheostomy and gastrostomy tube dependent. Gastrostomy tube dependence was significantly worse in patients with tumors of the base of tongue compared to other tumor sites (p = 0.030) and in patients who underwent transcervical compared to transoral tumor resection (p = 0.008). Local recurrence rate was 57.1% with a disease-free survival of 17.6 months. CONCLUSION: The myocutaneous SAFF represents a safe and reliable flap for tongue reconstruction after salvage glossectomy with satisfying functional outcomes and low donor side morbidity.

Preoperative plasma fibrinogen as a predictive factor for post-tonsillectomy haemorrhage.

OBJECTIVES: To assess whether preoperative plasma fibrinogen is able to predict severe post-tonsillectomy haemorrhage. STUDY DESIGN: Retrospective chart review. METHODS: We included 456 patients who underwent tonsillectomy between 2008 and 2013. Preoperative plasma fibrinogen levels (PFL) were assessed in patients who developed severe bleeding requiring surgical revision under general anesthesia compared to those with uneventful postoperative courses. RESULTS: 414 (90.8%) had no severe post-tonsillectomy haemorrhage. In contrast, 42 (9.2%) patients needed surgical hemostasis. PFL were significantly higher (P = .023) in patients with a severe bleeding. Univariate Cox-regression analysis revealed that elevated preoperative fibrinogen represents a significant worse (P = .003; HR 2.66; 95% CI 1.38-5.10) prognostic factor for postoperative bleeding. Even at multivariable analysis, increased PFLs were a significantly worse prognostic factor for post-tonsillectomy haemorrhage (P = .016; HR 15.4; 95% CI 0.01-0.6). High preoperative PFL was associated with significantly higher risk for post-tonsillectomy haemorrhage within the first 31 days after surgery (65% vs 90%; P = .002). Moreover, accurate negative predictive value (NPV) of 95.1% pointed out that PFL could be used as a reliable preoperative screening marker. CONCLUSIONS: Elevated PFL represents an independent worse prognostic factor for severe bleeding after tonsillectomy and could be helpful to identify patients at higher risk for PTH.

Design of skin islands for a myocutaneous serratus anterior free flap-An anatomical study and clinical implication for pharyngeal reconstruction after laryngopharyngectomy.

OBJECTIVES: The main purpose of this study was to evaluate flap size and flap design of skin islands in myocutaneous serratus anterior free flaps (SAFFs) in fresh cadavers and to further investigate whether myocutaneous SAFFs are suitable flaps for pharyngeal reconstruction after laryngopharyngectomy. METHODS: Dissection and injection of methylene blue were performed in 20 hemithoraces of 13 fresh cadavers to evaluate flap size and location of skin islands. Based on these pre-clinical data, we performed pharyngeal reconstruction with myocutaneous SAFF in five patients after laryngopharyngectomy. RESULTS: Perfused skin paddles were found in all specimens with a mean size of perfused skin islands of 85.6 ± 49.8 cm2 . Lengths and widths of skin islands ranged from 10-21 cm and 6-20.5 cm respectively. Flap size did not significantly differ between males and females (P = 0.998), left compared to right hemithoraces (P = 0.468) and between paired specimens (P = 0.915). All skin islands were found within the upper 29.3%-51.7% of hemithorax (calculated from axilla to costal arch), and between latissimus dorsi muscle posteriorly and anterior axillary line anteriorly. Accordingly, myocutaneous SAFFs were used for pharyngeal reconstruction after laryngopharyngectomy in five patients with advanced hypopharyngeal carcinomas. Three patients had uneventful courses, while one patient developed immediate intraoperative flap loss and another patient developed partial necrosis of SAFF on postoperative day 7. CONCLUSION: Skin islands of SAFF have reliable blood supply, which allow harvest of large myocutaneous SAFFs that can be used also for pharyngeal reconstruction after laryngopharyngectomy.

Dysregulation of ß-catenin, WISP1 and TCF21 predicts disease-specific survival and primary response against radio(chemo)therapy in patients with locally advanced squamous cell carcinomas of the head and neck.

OBJECTIVE: The objective of this study was to determine the prognostic and predictive impact of ß-catenin, TCF21 and WISP1 expression in patients with squamous cell carcinomas of the head and neck who underwent primary radiotherapy or concomitant chemoradiotherapy. STUDY DESIGN: Prospective cohort study. SETTING: University hospital. PARTICIPANTS: Protein expression profiles of ß-catenin, TCF21, WISP1 and p16 were determined by immunohistochemical analyses in tissue samples of 59 untreated patients. Expression was correlated with different outcome parameters. MAIN OUTCOME MEASURES: Impact of TNM classification, grading, sex, age, gender, type of therapy, response to therapy and p16 status on disease-specific (DSS) and disease-free survival (DFS). RESULTS: Patients with high expression of TCF21 were associated with significantly worse disease-specific survival (P = 0.005). In a multivariable analysis, TCF21 was a significant determinant of disease-specific survival. (HR 3.01; P = 0.036). Conversely, low expression of ß-catenin (P = 0.025) and WISP1 (P = 0.037) revealed a better response to radiotherapy. CONCLUSION: Since data show that TCF21 is a prognostic factor for disease-specific survival and WISP1 and ß-catenin are predictive factors for clinical outcome after definitive radiotherapy, further studies are warranted to prove these preliminary but very promising findings.

Impact of anatomic origin of primary squamous cell carcinomas of the nasal cavity and ethmoidal sinus on clinical outcome.

PURPOSE: Since squamous cell carcinomas (SCCs) of the nasoethmoidal complex are rare and aggressive malignancies, the purpose of this study was to evaluate whether anatomic subsites of SCCs of the nasal cavity and ethmoid sinuses affect clinical outcome. METHODS: We retrospectively analyzed data from 47 patients with primary SCCs of the nasal cavity and ethmoid sinuses who were treated at the Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, between 1993 and 2018. The impact of anatomic subsites of nasoethmoidal SCCs was evaluated with respect to tumor and nodal classification, disease-free survival (DFS) and disease-specific survival (DSS). RESULTS: Of the 47 cases, 17 SCCs (36.2%) originated from lateral nasal wall followed by 13 (27.7%) tumors of the edge of naris to mucocutaneous junction, 11 (23.4%) SCCs of the nasal septum, 3 tumors of the nasal floor (6.4%) and 3 SCCs of the ethmoid sinuses (6.4%), respectively. SCCs of the nasal septum were associated with significantly higher rates of neck node metastasis (p = 0.007), which represented a significantly worse prognostic factor for DSS (HR 7.87; p < 0.001). Moreover, advanced tumor stage (HR 5.38; p = 0.014) and tumor origin of nasal septum (HR 4.05; p = 0.025) were also significantly worse prognostic factors for DSS. Fourteen patients (29.8%) developed recurrent disease, including eight local (17.0%), five regional (10.6%) and one distant (2.1%) recurrence. Elective neck dissection (ND) was associated with lower (0 vs. 20.0%) but not significantly different regional and distant DFS (p = 0.075). CONCLUSION: Anatomic origin of nasal SCC has significant impact on clinical outcome. SCCs of the nasal septum were associated with higher rates of positive neck nodes and worse outcome.

Dying blood mononuclear cell secretome exerts antimicrobial activity.

BACKGROUND: Several activities are attributed to antimicrobial peptides (AMPs), including bacterial killing, leucocyte recruitment and angiogenesis. Despite promises of advanced cellular therapies for treatment of diabetic foot ulcer, it is currently accepted that paracrine factors rather than cellular components are causative for the observed effects. Whether AMPs are present in the mononuclear cell (MNC) secretome (MNC-sec) of white blood cells that are beneficial in experimental wound healing is not known. MATERIALS AND METHODS: Antimicrobial activity of the secretomes of nonirradiated (MNC-sec) and γ-irradiated MNCs (MNC-sec rad) was analysed by microdilution assay. AMPs were determined by quantitative real-time PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Whether human MNC-sec rad causes AMP secretion in vivo was examined in an experimental rat model. Image flow cytometry was used to determine the type of cell death induced in MNCs after exposure to γ-radiation. RESULTS: The antimicrobial activity assay revealed a bactericidal activity of MNC-sec rad and to a lesser degree also of MNC-sec. Image flow cytometry showed that γ-irradiation of MNCs induced early apoptosis followed mainly by necroptosis. RT-PCR and ELISA revealed a high abundance of different AMPs in the secretome of MNCs. In addition, human MNC-sec elicited an increase in de novo endogenous AMP production in rats in vivo. CONCLUSION: We provide evidence that the secretome of MNCs has direct and indirect positive effects on the immune defence system, including augmentation of antibacterial properties. Our data further suggest that necroptosis could play a key role for the release of paracrine factors and the therapeutic action of MNC-sec rad.