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Introduction Age and lymph node ratio have been attributed as independent predictors for survival and recurrence in carcinoma of unknown primary (CUP).

Introduction Parapharyngeal space tumors with complex anatomy and diverse histology have remained a challenging phenomenon for treating physicians. Objectives We have conducted a comprehensive web search on the PubMed, Web of Science, EMBASE, Cochrane Library, Biomedical Literature Database (CBM), and Clinicaltrials.gov databases to determine the factors that are associated with postoperative complications in parapharyngeal space tumors. Data Synthesis Two researchers reviewed all identified articles independently with a third reviewer for adjudication. Patient demographics and other clinicopathological characteristics were explored. The systematic review has identified 631 benign parapharyngeal space tumors with neurogenic and salivary tissue histology in 13 studies, with a mean age of 42.9 ± 7.76 years old and a median follow-up of 40.98 ± 19.1 months. Salivary gland (50.8%) and neurogenic (49.1%) tumors were the most common histological entities. Tumor size, location, histology, deep parotid lobe involvement, and proximity to great vessels or to the skull base were the deciding factors in selecting the surgical approach. The factors considered to select the surgical approach do not seem to have a correlation with the outcome in terms of neurological sequalae (p = 0.106). Tumors with neurogenic histology have significantly increased chances of developing neurological complication (OR 6.07; p = 0.001). Conclusion Neurologic complications are significantly associated with neurogenic benign tumors rather than surgical approach.

Dog-bite injuries are regularly treated in emergency departments. Every bite wound is unique, and thus requires a customized treatment plan. Here, we report the case of a 27-year-old woman who was transferred to the main hospital of Vienna due to a facial dog-bite injury. Primary closure of the wound was possible. The patient received amoxicillin–clavulanate as antimicrobial therapy, and was vaccinated against tetanus, polio, pertussis and diphtheria due to her unknown immunization status. At 183 days after the attack, the aesthetic outcome and nasal ventilation were satisfactory. Based on the reconstructive ladder for wound closure, more severe injuries may require skin or composite grafts, distant or local flaps and microsurgical procedures. Anti-infective therapy against tetanus, rabies and other bacteria also represents a central pillar of dog-bite injury treatment. This case report adds to the knowledge about dog-bite injuries and the required individual multidisciplinary treatment approach.

Shima Mehrabian,1 Larissa Schwarzkopf,2 Stefanie Auer,3 Iva Holmerova,4 Milica G Kramberger,5 Marina Boban,6 Elka Stefanova,7 Catalina Tudose,8 Natalia Bachinskaya,9 Tibor Kovács,10 Petr Koranda,11 Todor Kunchev,1 Latchezar Traykov,1 Janine Diehl-Schmid,12 Katrina Milecka,12 Alexander Kurz12On behalf of the Danubian Network for Dementia Education Care (DANDEC) Consortium1UH “Alexandrovska”, Department of Neurology, Medical University Sofia, Sofia, Bulgaria; 2Helmholtz-Centre Munich, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Munich, Germany; 3Department for Clinical Neurosciences and Preventive Medicine, Danube University Krems, Krems, Austria; 4CELLO Faculty of Humanities, Charles University, Prague, the Czech Republic; 5University of Ljubljana, Department of Neurology, Ljubljana, Slovenia; 6University of Zagreb, Department of Cognitive Neurology, Zagreb, Croatia; 7School of Medicine, University of Belgrade, Neurology Clinic, Belgrade, Serbia; 8University of Medicine and Pharmacy Carol Davila, Department of Clinical Neurosciences, Bucharest, Romania; 9Acacdemy of Medical Sciences Kiev, Department of clinical physiology and pathology of the central nervous system, Kiev, the Ukraine; 10Department of Neurology, Semmelweis University, Budapest, Hungary; 11MEDIWARE corp., Prague, the Czech Republic; 12Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Munich, GermanyCorrespondence: Alexander KurzCentre for Cognitive Disorders at the Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar; Technische Universität München, Ismaninger Strasse 22 Munich 81675, GermanyTel +49 894 140 4285Email a.kurz@tum.deBackground: Dementia is a particularly severe societal challenge in several countries of the Danube Region due to higher-than-average increment in population longevity, disproportionate increase of the old-age dependency ratio, and selective outward migration of health care professionals. A survey was conducted among dementia experts to obtain a deeper understanding of the dementia care structures and services in this geographical area, and to identify the educational needs of health care professionals, and the availability of assistive technology.Subjects and methods: A standardized questionnaire was sent out to 15 leading dementia experts/clinicians in 10 Danube Region countries inquiring about professional groups involved in dementia care, availability and reimbursement of services, inclusion of dementia in professional education and training, acceptability of Internet-based education, and availability of assistive technology. The authors are the survey respondents.Results: The majority of individuals with dementia receive care in the community rather than in institutions. The roles of medical specialties are disparate. General practitioners usually identify dementia symptoms while specialists contribute most to clinical diagnosis and treatment. Health care professionals, particularly those who work closely with patients and carers, have limited access to dementia-specific education and training. The greatest need for dementia-specific education is seen for general practitioners and nurses. An Internet-based education and skill-building program is considered to be equivalent to traditional face-to-face but offer advantages in terms of convenience of access. Assistive technology is available in countries of the Danube Region but is significantly underused.Conclusion: Dementia care in the Danube Region can be improved by an educational and skill-building program for health care professionals who work in the frontline of dementia care. Such a program should also attempt to enhance interdisciplinary and intersectorial collaboration, to intensify the interaction between primary care and specialists, and to promote the implementation of assistive technology.Keywords: dementia, Danube Region, expert survey, dementia care structures, education, assistive technology

BackgroundThe aim of this study was to evaluate whether surgeons´ experience and perioperative single-shot antibiotic prophylaxis affect outcome of patients undergoing stapes surgery.Patients and methodsWe retrospectively evaluated audiological outcomes and postoperative complications of 538 consecutive patients who underwent stapes surgery at a single tertiary referral center between 1990 and 2017. Effects of different clinical variables, including single-shot antibiotic prophylaxis and surgeons' experience on outcome were assessed.Results538 patients underwent 667 stapedotomies and postoperative complication rate was 7.5% (n = 50). Air conduction and air-bone gap closure improved significantly after surgery (14.2 ± 14.8 dB, p = 0.001; 14.5 ± 12.8 dB, p = 0.001). Multivariate analysis revealed that 6 years or less of surgical experience was independently associated with a higher incidence of persisting or recurrent conductive hearing loss (p = 0.033, OR 5.13) but perioperative application of antibiotics had no significant effect on outcome.ConclusionFirst, clinical outcome regarding persisting or recurrent conductive hearing loss caused by incus necrosis and prosthesis luxation is linked to surgical performance. This underlines the need for a meticulous training and supervision of less experienced surgeons performing stapes surgery. Second, our results do not support the need for perioperative antibiotic prophylaxis in stapes surgery. Potential standard limitations of retrospective cohort studies (selection bias, confusion bias etc.) could play a role in interpreting our results. However, the probability for these limitations is minimized due to the large patient sample.

Background. The purpose of this study was to analyze the value of different diagnostic methods in detecting the primary site and the impact of primary tumors on the clinical outcome of carcinoma of unknown primary (CUP). Methods. In this multicenter, retrospective study, 124 patients with true CUP (n = 94) and CUP turned to primary carcinoma (n = 30) were included. Patients with evidence of primary site during the clinical examination were excluded a priori. The diagnostic procedure was comprised of imaging and invasive methods (fine-needle-aspiration, tonsillectomy and panendoscopy). All patients were treated with curative intent. Results. Despite extensive diagnostic workup, the primary site remained unknown in 75.8%. Invasive diagnostic methods showed higher primary detection rates than imaging modalities (15.1% vs. 7.8%). Tonsillectomy and panendoscopy revealed the primary tumor in 14.9% and 15.2% of patients, whereas the detection rates of CT, MRI and FDG-PET-CT were 10.1%, 4.8% and 6.5%, respectively. The occurrence of primary tumors led to a significantly deteriorating 5-year overall survival (p = 0.002) and emerged as survival prognosticator (HR = 2.764, p = 0.003). Conclusion. Clinical examination in combination with tonsillectomy and panendoscopy was superior to imaging alone in detecting the primary tumor. When the CUP of patients turned to a primary tumor, clinical outcome was significantly worse than in CUP patients.

The aim of this study was to determine the prevalence of MCPyV in Merkel cell carcinoma (MCC) primaries versus lymph node metastasis and to evaluate possible prognostic factors.Samples of MCC primaries and lymph node metastases were stained immunohistochemically for the MCPyV large T-antigen and expression was compared to patients´ clinical outcome.41 MCC patients were included. 33 (61%) out of 54 specimens were MCPyV-positive in the immunohistochemistry. 15 (47%) out of 32 primary tumors were positive compared to 18 (82%) out of 22 lymph node metastases. Eleven patients with positive polyomavirus expression died from the carcinoma compared to 4 patients without virus expression. Cox regression analysis showed worse disease-free survival in patients with MCPyV compared to virus-negative lymph nodes (p = 0.002).To our knowledge this is the first study to describe a negative prognostic effect of the MCPyV expression in lymph node metastasis in MCC patients.

HPV positive patients suffering from head and neck cancer benefit from intensified radiotherapy when applied as a primary as well as an adjuvant treatment strategy. However, HPV negative patients treated with surgery and adjuvant radiotherapy lack validated prognostic biomarkers. It is therefore important to define prognostic biomarkers in this particular patient population. Especially, ´high-risk groups´ need to be defined in order to adapt treatment protocols. Since dysregulation of the sonic hedgehog pathway plays an important role in carcinogenesis, we aimed to assess whether members of the sonic hedgehog-signaling pathway may act as prognostic factors in patients with HPV negative head and neck squamous cell carcinoma.In this prospective study, pretreatment tumor biopsies of patients with head and neck squamous cell carcinoma were taken during panendoscopy (2005 to 2008). All patients were treated with surgery and postoperative radiotherapy. After assessment of HPV and p16 status, protein expression profiles of the Sonic hedgehog-signaling pathway were determined by immunohistochemistry and tissue microarray analyses in 36 HPV negative tumor biopsies. Expression profiles of Sonic hedgehog, Indian hedgehog, Patched, Smoothened, Gli-1, Gli-2 and Gli-3 were correlated with patients´ clinical data, local-control rate, disease-free as well as overall survival. Data from The Cancer Genome Atlas databank were used for external validation of our results.Gli-1 (p = 0.04) and Gli-2 (p = 0.02) overexpression was significantly linked to improved overall survival of HPV negative patients. Gli-2 (p = 0.04) overexpression correlated significantly with prolonged disease-free survival. Cox-multivariate analysis showed that overexpression of Gli-2 correlated independently (HR 0.40, 95% CI 0.16-0.95, p = 0.03) with increased overall survival.Gli-1 and Gli-2 overexpression represents a substantial prognostic factor for overall and disease-free survival in patients with locally advanced HPV negative head and neck cancer undergoing surgery and postoperative radiotherapy.

We aimed to determine the prognostic significance of pretreatment plasma fibrinigen in patients with oral and oropharyngeal squamous cell carcinoma (OOSCC).A cohort of 183 patients with locally advanced OOSCC receiving preoperative chemoradiotherapy was retrospectively examined. Using ROC curve analysis, a pretreatment plasma fibrinogen cutoff value of 447mg/dL was determined. The primary endpoints were overall survival and recurrence-free survival. A secondary endpoint was to determine whether pretreatment plasma fibrinogen could predict treatment response to neoadjuvant chemoradiotherapy. Cox regression models and Kaplan-Meier curves were used for survival analyses.Seventy-one patients had an elevated pretreatment plasma fibrinogen (fibrinogen >447mg/dL). Patients with high fibrinogen showed significantly higher pathologic stages after neoadjuvant treatment than those with low fibrinogen (p = 0.037). In univariate analysis, elevated fibrinogen was associated with poor overall survival (p = 0.005) and recurrence-free survival (p = 0.008) Multivariate analysis revealed that elevated fibrinogen remained an independent risk factor for death (hazard ratio 1.78, 95% CI 1.09-2.90, p = 0.021) and relapse (hazard ratio 1.78, 95% CI 1.11-2.86, p = 0.016).Elevated pretreatment plasma fibrinogen is associated with lack of response to neoadjuvant chemoradiotherapy and reduced OS and RFS in patients with OOSCC. Thus, plasma fibrinogen may emerge as a novel prognostic indicator and a potential therapeutic target in OOSCC.

Since the first description of the Merkel cell carcinoma by Cyril Toker in 1972, the number of studies has significantly increased over the last 4 decades. In this review, we will illustrate the historical background of the Merkel cell carcinoma beginning with the 19th century, the first description of the Merkel cell to the finding of the CK20 as a highly specific diagnostic marker and finally to the recently detected Merkel cell polyomavirus (MCPyV). Moreover, we will highlight the beginning of adjuvant therapeutic regimens with radiotherapy and chemotherapy and discuss the diagnostic work-up including imaging and histology of patients with Merkel cell carcinoma. Another very rapidly growing and interesting field of research is the development of patients' specific and tailored targeted therapy, in particular in patients with distant metastatic disease.

Background. The goal of this paper is to review contemporary multidisciplinary treatment with reference to Merkel cell carcinoma. Management of this rare but highly aggressive skin cancer is a complex undertaking that necessitates an understanding of its etiology, epidemiology, clinical presentation, and the coordinated work of several clinical specializations. Recent Findings. The contemporary literature employs a multidisciplinary approach to achieve the best patient's treatment. Conclusion. This paper presents an algorithm for contemporary management for the rare and aggressive Merkel cell carcinoma. Multidisciplinary approach in a tumor center provides high-quality care for patients with Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine tumor of the skin with a mortality rate of approximately 25% (Peloschek et al., 2010). Accurate assessment of nodal involvement in patients with MCC predicts significantly overall outcome (Smith et al., 2012 and Ortin-Perez et al., 2007). Due to the rarity of this highly aggressive disease, only a few imaging reports on MCC were published, and subsequently still to date no accepted imaging algorithm for MCC is available. For primary staging of MCC, general recommendations have included ultrasonography, chest X-ray CT, and MRI, but recent articles show that the use of sentinel node and FDG-PET/PET-CT is gaining more and more importance.

Background: The study aimed to evaluate the diagnostic efficacy of routine follow‐up in detecting recurrent disease in hypopharyngeal carcinoma. Methods: Data from 76 patients with a total of 620 follow‐up visits, 367 radiological studies, and 126 panendoscopies were retrospectively assessed regarding the diagnosis of recurrent disease based on the results of (I) radiological studies, (II) clinical examinations, and (III) clinical symptoms. Results: All locally relapsed patients became symptomatic, and new onset of dysphagia (p < 0.001) was the most frequent complaint. The sensitivity for detecting local recurrences was 100% for both patients' symptom assessments and clinical examinations. The highest overall accuracy was found for clinical examinations (93.4%), followed by symptom assessments (80.5%), and radiological studies (73.8%). The risk of false positive radiological reports and subsequent panendoscopies was 2.2 times higher after previous radiotherapy (32.0% vs. 14.6%; p < 0.001). Conclusion: Symptom assessments and clinical examinations are highly efficient for detection of local failures. [ABSTRACT FROM AUTHOR]

Background: Sinonasal malignancies with orbital invasion have dismal prognosis even when treated with orbital exenteration (OE). Sugawara et al. developed a surgical strategy called "extended‐OE (EOE)," showing encouraging outcomes. We hypothesized that a similar resection is achievable under endoscopic guidance through the exenterated orbit (endoscopic‐EOE). Methods: The study was conducted in three institutions: University of Vienna; Mayo Clinic; University of Insubria; 48 orbital dissections were performed. A questionnaire was developed to evaluate feasibility and safety of each step, scoring from 1 to 10, ("impossible" to "easy," and "high risk" to "low risk," respectively), most likely complication(s) were hypothesized. Results: The step‐by‐step technique is thoroughly described. The questionnaire was answered by 25 anterior skull base surgeons from six countries. Mean, median, range, and interquartile range of both feasibility and safety scores are reported. Conclusions: Endoscopic‐EOE is a challenging but feasible procedure. Clinical validation is required to assess real‐life outcomes. [ABSTRACT FROM AUTHOR]

BackgroundWe aimed to determine the prognostic significance of pretreatment plasma fibrinigen in patients with oral and oropharyngeal squamous cell carcinoma (OOSCC).MethodsA cohort of 183 patients with locally advanced OOSCC receiving preoperative chemoradiotherapy was retrospectively examined. Using ROC curve analysis, a pretreatment plasma fibrinogen cutoff value of 447mg/dL was determined. The primary endpoints were overall survival and recurrence-free survival. A secondary endpoint was to determine whether pretreatment plasma fibrinogen could predict treatment response to neoadjuvant chemoradiotherapy. Cox regression models and Kaplan-Meier curves were used for survival analyses.ResultsSeventy-one patients had an elevated pretreatment plasma fibrinogen (fibrinogen >447mg/dL). Patients with high fibrinogen showed significantly higher pathologic stages after neoadjuvant treatment than those with low fibrinogen (p = 0.037). In univariate analysis, elevated fibrinogen was associated with poor overall survival (p = 0.005) and recurrence-free survival (p = 0.008) Multivariate analysis revealed that elevated fibrinogen remained an independent risk factor for death (hazard ratio 1.78, 95% CI 1.09-2.90, p = 0.021) and relapse (hazard ratio 1.78, 95% CI 1.11-2.86, p = 0.016).ConclusionElevated pretreatment plasma fibrinogen is associated with lack of response to neoadjuvant chemoradiotherapy and reduced OS and RFS in patients with OOSCC. Thus, plasma fibrinogen may emerge as a novel prognostic indicator and a potential therapeutic target in OOSCC.