Emergency critical care: closing the gap between onset of critical illness and intensive care unit admission.

Critical illness is an exquisitely time-sensitive condition and follows a disease continuum, which always starts before admission to the intensive care unit (ICU), in the majority of cases even before hospital admission. Reflecting the common practice in many healthcare systems that critical care is mainly provided in the confined areas of an ICU, any delay in ICU admission of critically ill patients is associated with increased morbidity and mortality. However, if appropriate critical care interventions are provided before ICU admission, this association is not observed. Emergency critical care refers to critical care provided outside of the ICU. It encompasses the delivery of critical care interventions to and monitoring of patients at the place and time closest to the onset of critical illness as well as during transfer to the ICU. Thus, emergency critical care covers the most time-sensitive phase of critical illness and constitutes one missing link in the chain of survival of the critically ill patient. Emergency critical care is delivered whenever and wherever critical illness occurs such as in the pre-hospital setting, before and during inter-hospital transfers of critically ill patients, in the emergency department, in the operating theatres, and on hospital wards. By closing the management gap between onset of critical illness and ICU admission, emergency critical care improves patient safety and can avoid early deaths, reverse mild-to-moderate critical illness, avoid ICU admission, attenuate the severity of organ dysfunction, shorten ICU length of stay, and reduce short- and long-term mortality of critically ill patients. Future research is needed to identify effective models to implement emergency critical care systems in different healthcare systems.

['Against Nature'-On the social psychological dimension of the alliance between conspiracy beliefs and spirituality in COVID-19 protests. A case study]. / "Wider die Natur" ­ Zur sozialpsychologischen Dimension des Bündnisses von Verschwörungsdenken und Spiritualität in den Corona-Protesten. Eine Fallanalyse.

In the light of increasingly loud and highly visible public protests against protective measures and policies against COVID-19, the concept of conspirituality has recently gained a lot of attention. It is used to theoretically grasp the ideological glue of the heterogeneous milieu of protesters. The aim of this article is twofold. First, we show how, in conspirituality, elements of conspiracy beliefs are intertwined with esoteric-spiritual ideas. Going back to occultic milieus, these worldviews are then diffused and slowly popularized. Second, using depth-hermeneutic analyses of a biographical interview with a protest participant, we show that fragments of ideology are ingested in an idiosyncratic manner and interlaced with existing subjective interpretive patterns. This will further reveal the fundamental insecurities caused by the pandemic itself and by the political attempts to deal with its effects. Against this background, we conclude that conspirituality serves as a pattern of 'crooked cure', mitigating inner conflicts (co-)produced by society. This is achieved by protectively ascribing unbearable affects, ambivalences, and anxieties, but also unfulfilled desires of harmony, security, and comfort either to nature or to malignant conspirators.

Diffraction-limited hyperspectral mid-infrared micro-ellipsometry.

The recent introduction of quantum cascade lasers (QCL) in infrared spectroscopic ellipsometry led to decisive improvements in measurement times and signal-to-noise ratios of this powerful analytical method. In this contribution, we present another significant enhancement leading to the first, to the best of our knowledge, diffraction-limited micro-ellisometry setup in the mid-infrared spectral range with a spatial resolution better than 13.3 µm. The fast spectral tunability of the QCL combined with phase-modulated polarization enabled simultaneous acquisition of broadband (900 cm-1-1204 cm-1) high-resolution (1 cm-1) hyperspectral Ψ, Δ-cubes in a scanning approach in reasonable time scales. The spatial resolution of the QCL micro-ellipsometer was experimentally characterized by the knife-edge method and measurements of a resolution test target. Furthermore, the hyperspectral ellipsometric investigation of a polymer multilayer cross section and the portrait window of a 200-euro bank note demonstrate the capabilities of diffraction-limited QCL micro-ellipsometry.

Targeting TGF beta receptor 1 in head and neck squamous cell carcinoma.

OBJECTIVES: The transforming growth factor-Beta (TGF-ß) pathway may be involved in the radioresistance of head and neck squamous cell carcinoma (HNSCC). This study analyzed TGF-ß receptor 1 (TGFBR1) expression in HNSCC patients and evaluated the antineoplastic and radiosensitizing effects of vactosertib, a novel TGFBR1 inhibitor, in vitro. MATERIALS AND METHODS: TGFBR1 expression was examined in HNSCC patients at the mRNA level in silico and the protein level by immunohistochemistry, including surgical specimens of primary tumors, matched lymph node metastasis, and recurrent disease. Furthermore, a novel small molecule TGFBR1 inhibitor was evaluated in HNSCC cell lines. Finally, an indirect coculture model using patient-derived cancer-associated fibroblasts was applied to mimic the tumor microenvironment. RESULTS: Patients with high TGFBR1 mRNA levels showed significantly worse overall survival in silico (OS, p = 0.024). At the protein level, an association between TGFBR1+ tumor and OS was observed for the subgroup with TGFBR1-stroma (p = 0.001). Those results prevailed in multivariable analysis. Inhibition of TGFBR1 showed antineoplastic effects in vitro. In combination with radiation, vactosertib showed synergistic effects. CONCLUSION: Our results indicate a high risk of death in tumorTGFBR1+ |stromaTGFBR1- expressing patients. In vitro data suggest a potential radiosensitizing effect of TGFBR1 inhibition by vactosertib.

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.

Evaluation of the Prognostic Capacity of a Novel Survival Marker in Patients with Sinonasal Squamous Cell Carcinoma.

Sinonasal squamous cell carcinoma (SNSCC) is a malignant tumor associated with poor survival, and easily obtainable prognostic markers are of high interest. Therefore, we aimed to assess the prognostic value of a novel survival index (SI) combining prognostic values of clinical (T and N classifications and invasion across Ohngren's line), inflammatory (neutrophil-to-lymphocyte ratio), and nutritional (albumin and body-mass index) markers. All patients with primarily treated SNSCC between 2002 and 2020 (n = 51) were included. Each of the six SI components was stratified into a low- (0) and high-risk (1) categories. Subsequently, the cohort was stratified into low- (SI of 0-2) and high-risk SI groups (SI of 3-6). Overall survival (OS) and disease-free survival (DFS) were compared between patients with low- and high-risk SI. The log-rank test was used to test for statistical significance. Overall, the mortality rate was 41.2% (n = 21), and the recurrence rate was 43.1% (n = 22). We observed significantly better OS in patients with low-risk SI (n = 24/51, 47.1%, mean OS: 7.9 years, 95% confidence interval (CI): 6.3-9.6 years) than in high-risk SI (n = 27/51, 52.9%, mean OS: 3.4 years, 95% CI: 2.2-4.5 years; p = 0.013). Moreover, we also showed that patients with low-risk SI had a longer DFS than patients with high-risk SI (mean DFS: 6.4, 95% CI: 4.8-8.0 vs. mean DFS: 2.4 years, 95% CI 1.3-3.5, p = 0.012). The SI combines the prognostic capacity of well-established clinical, radiologic, inflammatory, and nutritional prognosticators and showed prognostic potential in our cohort of SNSCC patients.

Deficiency of B vitamins leads to cholesterol-independent atherogenic transformation of the aorta.

Atherosclerosis, the leading cause of cardiovascular disease responsible for the majority of deaths worldwide, cannot be sufficiently explained by established risk factors, including hypercholesterolemia. Elevated plasma homocysteine is an independent risk factor for atherosclerosis and is strongly linked to cardiovascular mortality. However, the role of homocysteine in atherosclerosis is still insufficiently understood. Previous research in this area has been also hampered by the lack of reproducible in vivo models of atherosclerosis that resemble the human situation. Here, we have developed and applied an automated system for vessel wall injury that leads to more homogenous damage and more pronounced atherosclerotic plaque development, even at low balloon pressure. Our automated system helped to glean vital details of cholesterol-independent changes in the aortic wall of balloon-injured rabbits. We show that deficiency of B vitamins, which are required for homocysteine degradation, leads to atherogenic transformation of the aorta resulting in accumulation of macrophages and lipids, impairment of its biomechanical properties and disorganization of aortic collagen/elastin in the absence of hypercholesterolemia. A combination of B vitamin deficiency and hypercholesterolemia leads to thickening of the aorta, decreased aortic water diffusion, increased LDL-cholesterol and impaired vascular reactivity compared to any single condition. Our findings suggest that deficiency of B vitamins leads to atherogenic transformation of the aorta even in the absence of hypercholesterolemia and aggravates atherosclerosis development in its presence.

Zerumbone acts as a radiosensitizer in head and neck squamous cell carcinoma.

INTRODUCTION: Zerumbone is a phytochemical compound of the ginger plant Zingiber zerumbet with cytotoxic effects in various cancer cell lines. To date, zerumbone has shown an antiproliferative effect in oral squamous cell carcinoma cells lines. However, the effect of combination with radiation or cisplatin in head and neck squamous cell carcinoma (HNSCC) is unclear. The aim of this study was to investigate the effect of zerumbone alone, and in combination with irradiation and cisplatin on HNSCC cell lines. METHODS: The three HNSCC cell lines SCC25, Cal27 and FaDu were treated with zerumbone, radiation and/or cisplatin. Cell viability and clonogenic assays were performed. The interaction between zerumbone and radiation or cisplatin was evaluated using the combination index. Apoptosis was measured by flow cytometry and cell migration was assessed using a wound healing assay. RESULTS: Treatment with zerumbone resulted in a dose dependent induction of cytotoxicity and apoptosis in all three cell lines. The combination with cisplatin revealed a synergistic to additive effect in Cal27. The clonogenic assay showed a significant radiosensitizing effect in all three cell lines. The wound healing assay showed a reduction of cell migration in Cal27. CONCLUSION: The natural compound zerumbone shows a cytotoxic and proapoptotic effect on HNSCC cell lines. Furthermore, zerumbone enhances the radiation effect in all three cell lines and thus may be a suitable candidate for combination therapy in HNSCC.

A New Classification System to Predict Functional Outcome after Laryngectomy and Laryngopharyngectomy.

(1) Objective: To evaluate long-term functional outcome in patients who underwent primary or salvage total laryngectomy (TL), TL with partial (TLPP), or total pharyngectomy (TLTP), and to establish a new scoring system to predict complication rate and long-term functional outcome; (2) Material and Methods: Between 1993 and 2019, 258 patients underwent TL (n = 85), TLPP (n = 101), or TLTP (n = 72). Based on the extent of tumor resection, all patients were stratified to (i) localization I: TL; II: TLPP; III: TLTP and (ii) surgical treatment (A: primary resection; B: salvage surgery). Type and rate of complication and functional outcome, including oral nutrition, G-tube dependence, pharyngeal stenosis, and voice rehabilitation were evaluated in 163 patients with a follow-up ≥ 12 months and absence of recurrent disease; (3) Results: We found 61 IA, 24 IB, 63 IIA, 38 IIB, 37 IIIA, and 35 IIIA patients. Complications and subsequently revision surgeries occurred most frequently in IIIB cases but rarely in IA patients (57.1% vs. 18%; p = 0.001 and 51.4% vs. 14.8%; p = 0.002), respectively. Pharyngocutaneous fistula (PCF) was the most common complication (33%), although it did not significantly differ among cohorts (p = 0.345). Pharyngeal stenosis was found in 27% of cases, with the highest incidence in IIIA (45.5%) and IIIB (72.7%) patients (p < 0.001). Most (91.1%) IA patients achieved complete oral nutrition compared to only 41.7% in class IIIB patients (p < 0.001). Absence of PCF (odds ratio (OR) 3.29; p = 0.003), presence of complications (OR 3.47; p = 0.004), and no need for pharyngeal reconstruction (OR 4.44; p = 0.042) represented independent favorable factors for oral nutrition. Verbal communication was achieved in 69.3% of patients and was accomplished by the insertion of voice prosthesis in 37.4%. Acquisition of esophageal speech was reached in 31.9% of cases. Based on these data, we stratified patients regarding the extent of surgery and previous treatment into subgroups reflecting risk profiles and expectable functional outcome; (4) Conclusions: The extent of resection accompanied by the need for reconstruction and salvage surgery both carry a higher risk of complications and subsequently worse functional outcome. Both factors are reflected in our classification system that can be helpful to better predict patients' functional outcome.

PRKCA Overexpression Is Frequent in Young Oral Tongue Squamous Cell Carcinoma Patients and Is Associated with Poor Prognosis.

Oral tongue squamous cell carcinomas (OTSCCs) have an increasing incidence in young patients, and many have an aggressive course of disease. The objective of this study was to identify candidate prognostic protein markers associated with early-onset OTSCC. We performed an exploratory screening for differential protein expression in younger (≤45 years) versus older (>45 years) OTSCC patients in The Cancer Genome Atlas (TCGA) cohort (n = 97). Expression of candidate markers was then validated in an independent Austrian OTSCC patient group (n = 34) by immunohistochemistry. Kaplan-Meier survival estimates were computed, and genomic and mRNA enrichment in silico analyses were performed. Overexpression of protein kinase C alpha (PRKCA) was significantly more frequent among young patients of both the TCGA (p = 0.0001) and the Austrian cohort (p = 0.02), associated with a negative anamnesis for alcohol consumption (p = 0.009) and tobacco smoking (p = 0.02) and poorer overall survival (univariate p = 0.02, multivariate p< 0.01). Within the young subgroup, both overall and disease-free survival were significantly decreased in patients with PRKCA overexpression (both p < 0.001). TCGA mRNA enrichment analysis revealed 332 mRNAs with significant differential expression in PRKCA-upregulated versus PRKCA-downregulated OTSCC (all FDR ≤ 0.01). Our findings suggest that PRKCA overexpression may be a hallmark of a novel molecular subtype of early-onset alcohol- and tobacco-negative high-risk OTSCC. Further analysis of the molecular PRKCA interactome may decipher the underlying mechanisms of carcinogenesis and clinicopathological behavior of PRKCA-overexpressing OTSCC.

An analysis of distant metastasis cases from HPV-associated oropharyngeal squamous cell carcinoma.

Although mostly associated with good survival outcomes, some patients with HPV-positive oropharyngeal squamous cell carcinoma develop distant metastasis and face dire prognosis. The aim of this study was to analyze distant metastatic patients in regards to survival, clinical staging, therapy approach and p16/HPV status. This retrospective single-centre study assessed patients with HPV-associated oropharyngeal cancer with distant metastasis treated in a tertiary referral center from 2005 to 2019. Overall- (OS) and survival after diagnosis of distant metastasis (OMS), clinical staging and different therapy approaches were assessed. Moreover, the overall mortality was assessed, as well as the association of different therapy approaches and p16/HPV status with the survival outcome. Out of 211 patients with HPV-associated oropharyngeal cancer that were treated in the study period, 15 developed distant metastases (7.1%). Median OS and OMS of the total group were 11 months (range 0.1-32 months) and 3 months (range 0.1-21 months), respectively. The overall mortality rate was 53.3% (n = 8). Significantly better outcome was present in patients treated with primary chemoradiotherapy (median OS 17 months vs. not reached, p = .03, median OMS 8 months vs not reached, p = .05). The OMS was significantly better in patients treated with chemotherapy initially after diagnosis (mean OMS 21 months vs 4 months; P = .001). Surgical resection after initial diagnosis was associated with a significantly shorter OMS (median OMS 3 vs. 21 months, p = .005). Interestingly, postoperative adjuvant therapy was delayed in all of these cases due to surgical site complications. Systemic treatment after initial diagnosis may be beneficial in clinical outcome of HPV associated distant metastases. Furthermore, surgical site complications should be treated with immediate care in order to avoid delay of adjuvant therapy. Further studies are warranted for validation of our results.

Outcome in Patients with Partial and Full-Thickness Cheek Defects following Free Flap Reconstruction-A Multicentric Analysis of 47 Cases.

The objective of this study was to evaluate whether the extent of tumor resection and free flap reconstruction influences functional outcome and complications in patients with solid malignancies of the cheek. Therefore, we retrospectively assessed recipient site complications and functional outcomes in 47 patients with solid malignancies of the cheek who underwent either partial (n = 30; 63.8%) or full-thickness (n = 17; 36.2%) cheek resection with free flap reconstruction. Complications occurred in 12 (70.6%) patients after full thickness resections with creation of through-and-through defects compared to 14 (70.6%) patients with partial defects (p = 0.138). Among those 26 patients (55.3%), major recipient site complications, like development of salivary fistula or free flap loss, were observed in 10 (21.3%) and 2 (4.3%) cases, respectively, while minor complications, like wound dehiscence and local infections, were found in 14 (29.8%) and 9 (19.1%) patients. Complications were noticed particularly after reconstruction of suborbital defects (69.2%; p = 0.268), of which occurrence of salivary fistulae was the most common (46.2%; p = 0.035). Similarly, functional outcomes including oral incompetence, ectropion, and trismus were not affected by the extent of resection (p = 0.766). However, oral incompetence was higher in patients with tumors originating from the oral cavity (p = 0.020) and after the performance of mandibulectomy (p = 0.003). Overall, there was no difference in functional outcome or recipient site morbidity between tumor resections resulting in full-thickness and partial defects.

Intraparotid and cervical lymph nodes metastasis in primary parotid gland carcinoma-impact on clinical outcome.

OBJECTIVE: The aim of this study was to investigate the prognostic value of evaluation of intraparotid and cervical lymph node metastases in primary parotid cancer. STUDY DESIGN: A retrospective medical chart review and histopathologic evaluation of all patients surgically treated for primary parotid cancer during the period 1993 to 2010 was performed. The presence and ratio of intraparotid and cervical lymph node metastases were assessed and determined as primary predictor variables. Overall survival (OS) and disease-free survival (DFS) were defined as primary outcome variables. RESULTS: In total, 50 patients were included. The presence of pathologic cervical lymph nodes (P = .005) and a high cervical lymph node ratio (LNR) (P = .0001) had a significant association with worse OS. Worse DFS was found in patients with a high cervical LNR (P = .001) and intraparotid lymph node metastases (P = .029). In high-grade carcinoma, a high LNR showed worse DFS (P = .05). A high cervical LNR (P = .012) and resection margin status (P = .002) were identified as independent prognostic markers for OS and the presence of intraparotid lymph nodes for DSS (P = .05). CONCLUSIONS: Evaluation of patterns of lymph node metastases provides additional prognostic value in patients with primary parotid gland cancer.

Impact of pretherapeutic neutrophil-to-lymphocyte ratio, serum albumin, body-mass index, and advanced lung cancer inflammation index on clinical outcome in sinonasal squamous cell carcinoma.

BACKGROUND: Squamous cell carcinoma of the nasal cavity and paranasal sinuses is a rare and aggressive cancer entity with poor survival rates. Data on this group of head and neck tumors are scarce. Inflammation and cachexia-based markers and their impact on clinical outcome have been studied in several cancer groups. The aim of this study was to evaluate their prognostic potential in sinonasal squamous cell carcinoma. PATIENTS AND METHODS: This retrospective analysis included all patients treated for sinonasal squamous cell carcinoma at a tertiary referral center between 2002 and 2015. Patients were divided into groups with low and high pretherapeutic values based on the values of serum albumin (ALB, median 41.6 g/l), neutrophil-to-lymphocyte ratio (NLR, median 3.5), body-mass index (BMI, median 24.7), or advanced lung cancer inflammation index (ALI, median 29.5). Main outcome measures were overall survival (OS) and disease-free survival (DFS). Statistical analysis included calculation of survival differences using log-rank tests, hazard ratios (HR), and respective 95% confidence intervals (CI). RESULTS: 41 patients were included. Low ALB values did not influence OS (median OS not reached in both groups; p = 0.59, HR = 0.75, CI = 0.3-2.1) or DFS (median DFS 0.9 years vs 2.2 years; p = 0.6, HR = 0.8, CI = 0.4-1.8). High NLR was significantly associated with worse OS rates (median OS not reached vs 1.7 years, p = 0.02, HR = 3.4, CI = 1.0-108) but with no influence on DFS (median DFS 3.1 years vs 0.8 years; p = 0.15, HR = 1.8, CI = 0.8-4.2). Similar results were observed for patients with low ALI (median OS 1.7 years vs not reached; p = 0.03, HR = 0.3, CI = 0.1-0.9 and median DFS 0.8 years vs 2.2 years; p = 0.58, HR = 0.8, CI = 0.3-1.8). BMI was the strongest prognosticator in our study. Low pretherapeutic BMI was linked to significantly worse OS (median OS 1.4 years vs not reached; p = 0.003, HR = 0.2, CI = 0.0-0.6) and DFS (median DFS 0.8 years vs not reached; p = 0.02, HR = 0.4, CI = 0.2-0.8). In multivariate analysis BMI was revealed as an independent marker for OS (p = 0.015). No marker reached the level of significance in regard to DFS in multivariate analysis. CONCLUSION: Pretherapeutic BMI had a superior prognostic value in patients with sinonasal squamous cell carcinoma in comparison with other tested variables. BMI may be a simple tool for estimating clinical outcome in SNSCC. However, larger studies are necessary to validate our results.

Risk factors for acute unplanned tracheostomy during panendoscopy in HNSCC patients.

BACKGROUND: Despite of careful pre-operative risk evaluation some patients require an acute unplanned tracheostomy during panendoscopy. METHODS: Risk factors of patients requiring an unplanned tracheostomy during panendoscopy (n = 32) were compared to a control group with panendoscopy without tracheostomy (n = 180). RESULTS: 2131 panendoscopies for Head and Neck squamous cell carcinoma were performed at our Department between 2000 and 2014. Unplanned tracheostomies were necessary in 1.6% of all panendoscopies. Patients with laryngeal cancer (p = 0.001) or abnormal activated partial thromboplastin time (aPTT) (p = 0.03) had a statistically significant higher risk of unplanned tracheostomy. Regression analysis showed that patients with advanced laryngeal cancer had an almost 6 times higher risk for tracheostomy than patients with early stage oropharyngeal cancer. CONCLUSIONS: We identified abnormal aPTT and laryngeal carcinoma as significant predictors for unplanned tracheostomy during panendoscopy. The results of our study could improve preoperative risk evaluation in HNSCC patients.

Effect of postoperative radiotherapy in pT1pN1cM0 and pT2p/cN0cM0 oropharyngeal squamous cell carcinoma.

OBJECTIVES/HYPOTHESIS: Consulting of patients with oropharyngeal carcinoma, classified as pT1pN1cM0 and pT2p/cN0cM0, about postoperative radiotherapy is a precarious task as data are lacking. The aim of this study was to evaluate the effects of postoperative radiotherapy for patients with intermediate-stage oropharyngeal carcinoma. STUDY DESIGN: Multicentric retrospective study. METHODS: This analysis was conducted at seven Austrian institutions and included data of patients treated between 2000 and 2012. A total of 81 patients with oropharyngeal squamous cell carcinoma were included, of whom 33 patients received postoperative radiotherapy. p16 status determined by immunohistochemistry was available in 68 patients. RESULTS: Median follow-up was 47.9 months. Postoperative radiotherapy showed no benefits in regard to overall survival (P = .701). In contrast, disease-free survival was significantly shortened in all patients without postoperative radiotherapy (P = .001). When dividing the cohort in dependence of p16, p16-positive patients did not benefit from postoperative radiotherapy regarding overall and disease-free survival (P = .934 and P = .102), whereas p16-negative patients showed improved disease-free survival after postoperative radiotherapy (P = .007). Multivariate analysis showed that outcome of postoperative radiotherapy is dependent on p16 status. CONCLUSIONS: In terms of disease-free survival, patients with p16-negative tumors may benefit from postoperative radiotherapy, whereas survival of p16-positive patients is good regardless of additional treatment. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1075-1082, 2018.

Bone resection for facial cutaneous malignancies.

BACKGROUND AND OBJECTIVES: The aim of this study is to analyze the clinical outcomes of patients who underwent bone resection for cutaneous malignancy of the face and scalp. METHODS: We retrospectively collected patient data from 62 patients who underwent bone resection for craniofacial cutaneous malignancy of the face and scalp over the last 10 years. We investigated risk factors for disease progression and assessed the utility of pre-operative imaging to predict bone, dura, and brain infiltration. RESULTS: Out of all factors analyzed, brain invasion, surgical margin involvement, and dural margin involvement were found to significantly reduce survival. CT and MRI correctly predicted bone infiltration in 88% and 89% of cases. MRI correctly predicted dura invasion in 89% but grossly underestimated the amount of dural invasion in 23% of reports. CONCLUSIONS: Our data indicate that the resection of bone is a reasonable surgical option in the treatment of patients with advanced cutaneous malignancies of the face and scalp. Brain invasion and positive margins reduced the probability of survival.

ELMO3 expression indicates a poor prognosis in head and neck squamous cell carcinoma - a short report.

PURPOSE: Previously, the engulfment and cell motility 3 (ELMO3) protein has been reported to be involved in cell migration and cytoskeletal remodeling. As of yet, nothing is known about the role of ELMO3 in head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to asses ELMO3 expression in postoperatively irradiated HNSCC patients and to evaluate a possible correlation between this expression and patient survival. METHODS: 125 postoperatively irradiated HNSCC patients were included in this study. ELMO3 expression was assessed using immunohistochemistry (IHC). The expression of ELMO3 in the respective HNSCC tumor tissues and its lymph node metastases was correlated with patient survival using Kaplan-Meier curve analyses. RESULTS: Through IHC, ELMO3 expression was detected in 71.2% of the HNSCC cases tested. We found significantly increased overall and disease-free survival rates and decreased recurrence rates in patients with no detectable ELMO3 expression. In reverse, we found that ELMO3 expression served as an independent marker for a decreased overall and disease-free survival. CONCLUSION: Our data indicate that in the surgically treated and postoperatively irradiated patients tested, ELMO3 expression serves as a predictive marker for reduced survival.

The prognostic significance of ß-catenin, cyclin D1 and PIN1 in minor salivary gland carcinoma: ß-catenin predicts overall survival.

Minor salivary gland carcinoma is a rare and heterogeneous type of cancer. Molecular prognostic and predictive markers are sparse. The aim of this study was to identify new prognostic and predictive markers in minor salivary gland carcinoma. 50 tissue samples of carcinomas of the minor salivary glands (adenoid cystic carcinoma n = 23, mucoepidermoid carcinoma n = 12, adenocarcinoma n = 10, carcinoma ex pleomorphic adenoma n = 2, salivary duct carcinoma n = 1, clear cell carcinoma n = 1, basal cell carcinoma n = 1) were immunohistochemically stained for ß-catenin, cyclin D1 and PIN1. Expression patterns were analyzed and correlated to clinical outcome of 37 patients with complete clinical data. High expression of membranous ß-catenin was linked to significantly better overall survival in patients with adenoid cystic carcinoma (log rank test, χ (2) = 13.3, p = .00397, Bonferroni corrected p = .024). PIN1 and cyclin D1 did not show any significant correlation to patients' clinical outcome. Expression of ß-catenin in adenoid cystic carcinoma of the minor salivary glands significantly correlates with better overall survival. Hence, evaluation of ß-catenin might serve as a clinical prognostic marker.

Effect of the coffee ingredient cafestol on head and neck squamous cell carcinoma cell lines.

BACKGROUND AND PURPOSE: Cafestol is a diterpene molecule found in coffee beans and has anticarcinogenic properties. The aim of the study was to examine the effects of cafestol in head and neck squamous cell carcinoma (HNSCC) cells. MATERIALS AND METHODS: Three HNSCC cell lines (SCC25, CAL27 and FaDu) were treated with increasing doses of cafestol. Then combination experiments with cisplatin and irradiation were carried out. Drug interactions and possible synergy were calculated using the combination index analysis. Clonogenic assays were performed after irradiation with 2, 4, 6 and 8 Gy, respectively, and the rate of apoptosis was measured with flow cytometry. RESULTS: Treatment of HNSCC cells with cafestol leads to a dose-dependent reduction of cell viability and to induction of apoptosis. Combination with irradiation shows a reduction of clonogenic survival compared to each treatment method alone. In two of the cell lines a significant additive effect was observed. CONCLUSION: Cafestol is a naturally occurring effective compound with growth-inhibiting properties in head and neck cancer cells. Moreover, it leads to a significant inhibition of colony formation.