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Extramedullary malignant tumor refers to a malignant tumor of bone marrow origin arising outside the bone marrow. The most common ones on the head and neck region are plasmacytoma and myeloid sarcoma. Of these two, plasmacytoma is more common, though it still is rare consisting only 0.4% of all hematological malignancies. It is slowly growing, typically located submucosally and it is associated to multiple myeloma. Myeloid Sarcoma (MS) consists of immature myeloid cells and it is often associated with acute myeloid leukemia (AML). Rapid growth is typical for myeloid sarcoma. A diagnosis of MS is based on immunohistochemistry and differential diagnostics can be challenging. Treatment of MS is always systemic and surgery is used only for decompression. Case report: 34y male fire fighter was sent to ORL consultation due to right nostril obstruction. He had allogenic bone marrow transplantation for AML five years earlier and the disease had been in remission. A solid prominence was palpable on the right maxillary bone. CT and a sublabial biobsy were performed. After several immunohistochemical analyses the tumor was defined as MS and the patient received induction chemotherapy. Now patient has had a consolidation course, but new bone marrow transplantation has not been done due to severe infection problems. Conclusion: biopsy should not be hesitated when treating patients with atypical swelling symptoms especially if the patient has a history of hematologic disease. It is also important to remember that the treatment of head and neck tumor is not always surgical. [Copyright &y& Elsevier]

Increased extracellular matrix (ECM) and matrix stiffness promote solid tumor progression. However, mechanotransduction in cancers arising in mechanically active tissues remains underexplored. Here, we report upregulation of multiple ECM components accompanied by tissue stiffening in vocal fold cancer (VFC). We compare non-cancerous (NC) and patient-derived VFC cells - from early (mobile, T1) to advanced-stage (immobile, T3) cancers - revealing an association between VFC progression and cell-surface receptor heterogeneity, reduced laminin-binding integrin cell-cell junction localization and a flocking mode of collective cell motility. Mimicking physiological movement of healthy vocal fold tissue (stretching/vibration), decreases oncogenic nuclear β-catenin and YAP levels in VFC. Multiplex immunohistochemistry of VFC tumors uncovered a correlation between ECM content, nuclear YAP and patient survival, concordant with VFC sensitivity to YAP-TEAD inhibitors in vitro. Our findings present evidence that VFC is a mechanically sensitive malignancy and restoration of tumor mechanophenotype or YAP/TAZ targeting, represents a tractable anti-oncogenic therapeutic avenue for VFC., Competing Interests: Competing interests The authors declare no competing interests.

Background: Differences in the functioning of the immune system and the anatomical proportions of the neck between children and adults lead to different manifestations of deep neck infections. Magnetic resonance imaging (MRI) may serve as an alternative to computed tomography (CT) as the primary imaging modality., Objective: To study characteristic MRI findings and the diagnostic accuracy of MRI in pediatric deep neck infections., Materials and Methods: We retrospectively studied a cohort of pediatric patients who underwent a neck 3-tesla MRI study over a five-year period. Inclusion criteria were: 1) emergency MRI findings indicating an infection, 2) infection as the final clinical diagnosis, 3) diagnostic image quality verified by the radiologist reading the study and 4) age under 18 years. Patient record data, including surgery reports, were compared with the MRI findings., Results: Data of 45 children were included and analysed. Compared to adults, children had a higher incidence of retropharyngeal infection and lymphadenitis, and a lower incidence of peritonsillar/parapharyngeal infection. MRI showed evidence of an abscess in 34 children. Of these 34 patients, 24 underwent surgery, which confirmed an abscess in 21 but no abscess in three patients. In addition, three patients underwent surgery without MRI evidence of abscess, and an abscess was found in one of these cases. The measures of diagnostic accuracy among the children were sensitivity 0.96, specificity 0.77, positive predictive value 0.89, negative predictive value 0.91 and accuracy 0.89. Compared with adults, children had lower C-reactive protein, but a similar proportion of them had an abscess, and abscess size and rate of surgery were similar., Conclusion: Despite the differences in the infection foci, emergency MRI in children had equal diagnostic accuracy to that in adults., (© 2022. The Author(s).)

Purpose: The prognosis of glottic T1a laryngeal squamous cell carcinoma (LSCC) is excellent with both transoral laser surgery (TLS) and radiation therapy (RT). Our aim was to compare TLS and RT treatment results in a randomized study., Methods and Materials: Of 56 male patients with glottic T1a LSCC, 31 were randomized for TLS and 25 for RT. Survival and larynx preservation data were collected from medical records., Results: Five-year overall survival (OS) was 87%, disease-specific survival (DSS) was 97%, and recurrence-free survival (RFS) was 81% in patients treated with TLS. Five-year OS was 92%, DSS was 100%, and RFS was 88% in patients treated with RT. The primary treatment method was not associated with OS, RFS, or DSS in a log-rank test. The larynx preservation rate was similar in both groups (TLS, 97%; RT, 92%; P = .575)., Conclusions: In a prospective randomized setting oncological outcomes of both treatment modalities (TLS or RT) for T1a LSCC were similar., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Cisplatin is combined with radiotherapy for advanced head and neck squamous cell carcinoma (HNSCC). While providing a beneficial effect on survival, it also causes side effects and thus is an important target when considering treatment de-escalation. Currently, there are no biomarkers to predict its patient-selective therapeutic utility. In this study, we examined the role of the stem cell factor OCT4 as a potential biomarker to help clinicians stratify HNSCC patients between radiotherapy and chemoradiotherapy., Materials and Methods: OCT4 immunohistochemical staining of a population-validated tissue microarray (PV-TMA) (n = 166) representative of a standard HNSCC patients was carried out, and 5-year survival was analyzed. The results were validated using ex vivo drug sensitivity analysis of HNSCC tumor samples, and further cross-validated in independent oropharyngeal (n = 118), nasopharyngeal (n = 170), and vulvar carcinoma (n = 95) clinical datasets. In vitro, genetically modified, patient-derived HNSCC cells were used., Results: OCT4 expression in HNSCC tumors was associated with radioresistance. However, combination therapy with cisplatin was found to overcome thisradioresistance in OCT4-expressing HNSCC tumors. The results were validated by using several independent patient cohorts. Furthermore, CRISPRa-based OCT4 overexpression in the HNSCC cell line resulted in apoptosis resistance, and cisplatin was found to downregulate OCT4 protein expression in vitro. Ex vivo drug sensitivity analysis of HNSCC tumors confirmed the association between OCT4 expression and cisplatin sensitivity., Conclusion: This study introduces OCT4 immunohistochemistry as a simple and cost-effective diagnostic approach for clinical practice to identify HNSCC patients benefitting from radiosensitization by cisplatin using either full or reduced dosing., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We recently reported N 4 -substituted 3-methylcytidine-5'-α,β-methylenediphosphates as CD73 inhibitors, potentially useful in cancer immunotherapy. We now expand the structure-activity relationship of pyrimidine nucleotides as human CD73 inhibitors. 4-Chloro (MRS4598 16 ; K i = 0.673 nM) and 4-iodo (MRS4620 18 ; K i = 0.436 nM) substitution of the N 4 -benzyloxy group decreased K i by ∼20-fold. Primary alkylamine derivatives coupled through a p -amido group with a varying methylene chain length ( 24 and 25 ) were functionalized congeners, for subsequent conjugation to carrier or reporter moieties. X-ray structures of hCD73 with two inhibitors indicated a ribose ring conformational adaptation, and the benzyloxyimino group ( E configuration) binds to the same region (between the C-terminal and N-terminal domains) as N 4 -benzyl groups in adenine inhibitors. Molecular dynamics identified stabilizing interactions and predicted conformational diversity. Thus, by N 4 -benzyloxy substitution, we have greatly enhanced the inhibitory potency and added functionality enabling molecular probes. Their potential as anticancer drugs was confirmed by blocking CD73 activity in tumor tissues in situ.

Objectives: Due to its superior soft-tissue contrast and ability to delineate abscesses, MRI has high diagnostic accuracy in neck infections. Whether MRI findings can predict the clinical course in these patients is unknown. The purpose of this study was to determine the clinical and prognostic significance of various MRI findings in emergency patients with acute neck infections., Materials and Methods: We retrospectively reviewed the 3-T MRI findings of 371 patients with acute neck infections from a 5-year period in a single tertiary emergency radiology department. We correlated various MRI findings, including retropharyngeal (RPE) and mediastinal edema (ME) and abscess diameter, to clinical findings and outcomes, such as the need for intensive care unit (ICU) treatment and length of hospital stay (LOS)., Results: A total of 201 out of 371 patients (54%) with neck infections showed evidence of RPE, and 81 out of 314 patients (26%) had ME. Both RPE (OR = 9.5, p < 0.001) and ME (OR = 5.3, p < 0.001) were more prevalent among the patients who required ICU treatment than among those who did not. In a multivariate analysis, C-reactive protein (CRP) levels, RPE, and maximal abscess diameter were independent predictors of the need for ICU treatment, and CRP, ME, and maximal abscess diameter were independent predictors of LOS., Conclusion: In patients with an acute neck infection that requires emergency imaging, RPE, ME, and abscess diameter, as shown by MRI, are significant predictors of a more severe illness., Key Points: • Two hundred one out of 371 patients (54%) with neck infection showed evidence of retropharyngeal edema (RPE), and 81 out of 314 patients (26%) had mediastinal edema (ME). • Maximal abscess diameter, RPE, and C-reactive protein (CRP) were independent predictors of the need for intensive care unit (ICU) treatment, and maximal abscess diameter, ME, and CRP were independent predictors of length of hospital stay. • Prognostic significance of MRI findings was evident also while controlling for CRP values., (© 2021. The Author(s).)

Objectives: To analyze the long-term side effects of radiation therapy (RT) for head and neck cancer (HNC)., Methods: Retrospective chart analysis of all 688 HNC patients treated during 2010-2015 at Turku University Hospital, Finland. All patients who survived for more than a year after RT/chemoRT were included ( n  = 233). Intensity modulated RT (IMRT) with standard fractionation was applied in each case., Results: One hundred and six patients (45%) reported persisting dysphagia, for which neck RT increased risk. Definitive neck RT to high-risk volume did not increase late toxicity risks compared to elective neck RT. Radiation-induced hypothyroidism (29%, n  = 67) was more common among younger patients and females. Osteoradionecrosis (12%, n  = 29) was more common in the oral cavity cancer group (20.7%, n  = 92) compared to all other subsites., Conclusions: Late toxicities of RT for HNC are common. Age, gender, tumor subsite, and neck RT affect susceptibility to long-term side effects., Level of Evidence: 4., Competing Interests: The authors have no conflict of interests to disclose., (© 2021 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

The objective was to investigate work satisfaction among recently graduated otorhinolaryngologist - head and neck surgeons - (ENT surgeons). An electronic questionnaire was sent to all ENT surgeons graduated in Finland during a ten-year period. Answers about work satisfaction were analyzed in detail with regards to age, gender, university of specialist training, experience, place of work and further education.Altogether 125/129 (96.9%) responded. The majority (87.8%) of the respondents enjoyed their current main occupation. The older age group (≥40 vs <40 years) was more satisfied (93.7% vs. 81.7%; p=0.042). Consultation opportunities and workplace atmosphere were reported as good by 85.6% and 90.4% of the respondents, respectively. Training opportunities were considered good by 82.4%, albeit by only 60% of the private physicians (p=0.047). Private sector practitioners were also less satisfied with the versatility of their work (p<0.001). Work at a university hospital was considered more strenuous (p<0.001). Over half (54.8%) felt insecure about continuation of their employment status. Most of the recently graduated Finnish ENT surgeons are satisfied with their current occupation, consultation opportunities and workplace atmosphere. However, work at university hospitals in particular was considered often strenuous and over half of the respondents felt insecure about the continuity of their employment.

Purpose: We assessed the treatment outcome and the benefits of routine follow-up visits in T1 glottic laryngeal squamous cell carcinoma (LSCC)., Methods: Medical records of patients diagnosed with stage T1 glottic LSCC (N = 303) in five Finnish university hospitals between 2003 and 2015 were reviewed. Moreover, data from the Finnish Cancer Registry and the Population Register Center were collected., Results: Of all 38 recurrences, 26 (68%) were detected during a routine follow-up visit, and over half (21 of 38, 55%) presented without new symptoms. Primary treatment method (surgery vs. radiotherapy) was not connected with 5-year disease-specific survival (DSS) or laryngeal preservation rate., Conclusion: The majority of recurrences were detected on a routine follow-up visit, and local recurrences often presented without new symptoms. Routine post-treatment follow-up of T1 glottic LSCC seems beneficial., Trial Registration: Trial registration number and date of registration HUS/356/2017 11.12.2017., (© 2021. The Author(s).)

Background and Objectives: Sentinel node biopsy (SNB) is a safe and effective way to examine an N0 neck in early-stage oral cavity cancer (OCC). In this study, we evaluated the variables of SNB detection, surgery, and outcome., Material and Methods: Ninety-two patients with N0 OCC examined with SNB were included. Number and brightness of nodes detected on preoperative imaging and during surgery were analyzed and compared with histological findings. Patients with recurrent disease were evaluated separately and the effect of smoking and alcohol consumption was analyzed., Results: Eighteen patients had at least malignant cells in the sentinel lymph node (SLN); 18 patients had recurrent disease and nine patients died from the cancer. The negative predictive value of SNB was 95%. Six patients did not have metastases in the node with the strongest signal, but metastases were found in an SLN with a weaker signal. Smoking and alcohol consumption did not affect disease-specific or overall survival., Conclusion and Significance: SNB has been confirmed to be safe and effective in early stage N0 OCC. However, it is important to carefully harvest up to four hottest SLNs that emit a signal. Treatment of patients with only isolated tumor cells (ITC) in the SLN appears to be necessary.

Purpose: Pediatric deep neck space infection (DNI) is a relatively rare but potentially life-threatening condition and requires prompt and accurate management. This study retrospectively reviews our experience in a tertiary referral hospital from 2004 to 2019., Methods: Systematic data collection from medical records using ICD10 codes between 2004 and 2019., Inclusion Criteria: age ≤16 years, DNI requiring hospitalization and/or surgery. EXCLUSION: peritonsillar abscess without complications., Results: We identified 42 patients, 21 boys and 21 girls, with a median age of 4.9 years. Most of the patients had severe symptoms, the most common of which were neck swelling (n = 39; 92.9%), neck pain (n = 39; 92.9%) and fever (n = 32; 76.2%). Twenty-two (52.4%) had torticollis, and the mean duration of symptoms before hospitalization was 4.95 days. Diagnosis was confirmed by MRI (n = 24), contrast-enhanced CT (n = 11) or ultrasonography (n = 6), except in one case. Twenty-three (54.8%) required an open neck incision, ten (23.8%) patients had intraoral surgery and nine were treated conservatively. Twelve (28.6%) patients were admitted to the pediatric ICU. Median hospitalization duration was six days. The infection most commonly had tonsillopharyngeal etiology (n = 18) and a retropharyngeal location (n = 17). Staphylococcus Aureus (n = 7) and Streptococcus pyogenes (n = 7) were the most frequent pathogens. We compared the early surgical intervention group (<2 days of intravenous antibiotics; n = 18; 42.9%) to the late surgery group (n = 15; 35.7%) and the conservatively treated groups (n = 9; 21.4%). The overall length of stay (LOS) was lower in the shorter preoperative medication group (mean 4.4 vs. 7.2; p = 0.009). The size of the abscess did not differ between the groups (mean 28 mm; 30 mm; 21 mm; p = 0.075) and the neck incision rate was similar in the operated groups., Conclusion: Early surgical intervention is associated with decreased LOS among severe pediatric DNI patients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Locoregional recurrence remains a major cause of failure in head and neck squamous cell carcinoma (HNSCC). Human papilloma virus (HPV)-associated HNSCCs generally have a good prognosis but may recur even after standard photon radiotherapy (RT). Another incentive in observing patterns of recurrence is increased use of highly conformal techniques such as proton therapy. We therefore studied geographic distribution of recurrent tumors in relation to the high-risk treatment volume in a cohort of patients with HNSCC receiving combined modality therapy., Methods: Medical records of 508 patients diagnosed with HNSCC in 2010-2015 were reviewed. We identified a subgroup that had local and/or regional recurrence at hybrid positron emission tomography (PET)/computed tomography (CT) and/or magnetic resonance imaging (MRI). We adapted p16 as a surrogate marker for HPV-positivity and only patients with known p16 status were eligible for a detailed analysis where recurrent tumor was copied on the planning CT and the dose received by the recurrent tumor volume was determined using dose-volume histograms., Results: Twenty-five patients who had received either cisplatin (n = 23) or cetuximab-enhanced (n = 2) RT were identified. 31 locoregional recurrent tumors were detected among 18 p16 negative and 7 p16 positive patients. Of recurrent tumors 14 (45%) were classified as in-field, 5 (16%) as marginal miss, and 12 (39%) as true miss. p16 positive patients had 4 in-field, 2 marginal, and 1 true miss. By contrast, p16 negative patients had 10 in-field, 3 marginal, and 11 true miss recurrences., Conclusions: Both p16 positive and negative HNSCC recur in high-risk treatment volume despite the common view of high radiosensitivity of the former. Biomarkers predicting radioresistance should be characterized in p16 positive tumors before widely embarking on de-escalated CRT protocols. Another concern is how to decrease the number of true or marginal misses in p16 negative cases despite multimodality imaging-based target delineation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Importance: Incorporation of patient perspectives, or patient-reported outcomes, in functional outcome measures has been gaining prominence in the literature on reconstructive surgery., Objective: To create and validate an instrument for measuring the main functional areas of concern for patients with head and neck cancer., Design, Setting, and Participants: This 4-phase mixed-methods qualitative study was conducted from July 1, 2013, to June 30, 2016, in a quaternary head and neck oncology center in Edmonton, Alberta, Canada. Patients were recruited from 3 Head and Neck Research Network sites: University of Alberta (Edmonton, Canada), Mount Sinai Health Network (New York, New York), and University of Turku Hospital (Turku, Finland). The inclusion criteria included 18 years of age or older, diagnosis of squamous cell carcinoma involving the subsites of the head and neck (ie, oral cavity, oropharynx, hypopharynx, and larynx), and at least 1 year since treatment completion. Those patients who were undergoing additional active treatment or with evidence of disease recurrence were excluded. Data were analyzed from July 1, 2013, to June 30, 2016., Main Outcomes and Measures: The primary outcome measures were the clinical correlation of the Edmonton-33 instrument scores with swallowing, speech, dry mouth, and chewing assessment outcomes., Results: In total, 10 patients with head and neck cancer (mean age, 59.6 years; 6 men [60%]) were included in phase 1 of the study, 5 patients (mean age, 55.2 years) were included in phase 2, 10 patients were included in phase 3, and 25 patients with head and neck cancer (mean age, 62.6 years; 14 men [56%]) participated in the phase 4 validation. The Edmonton-33 instrument scores correlated strongly with the swallowing scores of the MD Anderson Dysphagia Inventory (r = 0.77; 95% CI, 0.49-1.0), the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck 35 (EORTC QLQ-H&N35) (r = -0.73; 95% CI, -1.0 to -0.44), and the modified barium swallow test (r = -0.60; 95% CI, -0.94 to -0.25). The instrument scores were also strongly correlated with the Speech Handicap Index scores (r = -0.64; 95% CI, -0.97 to -0.31), word intelligibility scores (r = 0.61; 95% CI, 0.27-0.95), and sentence intelligibility scores (r = 0.55; 95% CI, 0.19-0.91). A moderate to strong correlation was observed between the Edmonton-33 instrument and the EORTC QLQ-H&N35 scores in the dry mouth (r = -0.54; 95% CI, -0.91 to -0.18) and chewing (r = -0.45; 95% CI, -0.84 to -0.06) domains. The factor loading values for the domains of swallowing, speech, dry mouth, and chewing were all greater than 0.3. The mean factor loading values for the items related to swallowing were 0.71 (95% CI, 0.62-0.80) and for the items related to speech were 0.76 (95% CI, 0.72-0.80). The mean factor loading values for the items related to dry mouth were 0.71 (95% CI, 0.59-0.83) and for those related to chewing were 0.77 (95% CI, 0.69-0.85)., Conclusions and Relevance: The Edmonton-33 appears to be a validated instrument that will allow patients with head and neck cancer to assess and report their own functional outcomes. It could serve as a single comprehensive measure for functional outcomes.

Purpose: This study reviews our experience with deep neck space infections (DNIs) requiring surgical intervention, including cervical necrotizing fasciitis. The aim of the study was to identify predisposing and aggravating factors of the disease and recognize the possible factors that can lead to life-threatening complications and slow down the healing process., Methods: We compare the results to previous data from 1985 to 2005 to find possible alterations and changing trends. The characteristics of four lethal cases are described. This retrospective analysis includes patient data from 2004 to 2015 in tertiary referral hospital and in total, 277 patients were found., Results: Surgical drainage through a neck opening ± intraoral incision was made in 215 (77.6%) patients, an intraoral incision was only made in 62 patients (22.4%). ICU care was needed in 66 (23.8%) cases. Odontogenic etiology (44.8%) was the most common origin. The most common comorbidity was a psychiatric disorder and/or dementia and occurred in 55 (19.9%) patients. Patients with underlying illnesses were more likely to be admitted to the ICU (p = 0.020), required a longer ICU stay (p = 0.004) and repeated surgery (p = 0.009). Gas formation seemed to be predictive of a more severe course of infection. Early extraction of the odontogenic foci was related to a lower length of stay (LOS) (p = 0.039)., Conclusion: The annual numbers have risen from 14 to 24 cases per year when compared to previous data. DNIs remain a cause of lethal complications; the mortality was 1.4% and overall complications occurred in 61 (22.0%) patients.

Studies on pathophysiology and the therapeutic potential of extracellular ATP and other purines represent an important and rapidly evolving field. The integral response of the cell is determined by multiple factors, including the release of endogenous ATP, co-expression of different types of nucleotide- and adenosine-selective receptors, as well as the specific makeup of ectoenzymes governing the duration and magnitude of purinergic signaling. Current findings support the presence of an extensive network of purine-converting ectoenzymes that are co-expressed to a variable extent among the mammalian tissues and share similarities in substrate specificity. Here, we describe a histochemical approach for simultaneous detection of ecto-nucleotidase and tissue-nonspecific alkaline phosphatase (TNAP) activities in the same tissue slice. Further employment of this technique for staining human palatine tonsil cryosections revealed selective distribution of the key ectoenzymes within certain tonsillar structures, including germinal centers and connective tissues (ecto-5'-nucleotidase/CD73), as well as interfollicular area (TNAP and NTPDase1/CD39).

Lymphatic vessels form a critical component in the regulation of human health and disease. While their functional significance is increasingly being recognized, the comprehensive heterogeneity of lymphatics remains uncharacterized. Here, we report the profiling of 33,000 lymphatic endothelial cells (LECs) in human lymph nodes (LNs) by single-cell RNA sequencing. Unbiased clustering revealed six major types of human LECs. LECs lining the subcapsular sinus (SCS) of LNs abundantly expressed neutrophil chemoattractants, whereas LECs lining the medullary sinus (MS) expressed a C-type lectin CD209. Binding of a carbohydrate Lewis X (CD15) to CD209 mediated neutrophil binding to the MS. The neutrophil-selective homing by MS LECs may retain neutrophils in the LN medulla and allow lymph-borne pathogens to clear, preventing their spread through LNs in humans. Our study provides a comprehensive characterization of LEC heterogeneity and unveils a previously undefined role for medullary LECs in human immunity., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Nasopharyngeal carcinoma (NPC) is a malignant disease with an enigmatic etiology. NPC associates with Epstein-Barr virus (EBV) and human papillomaviruses (HPVs), while immunological factors also play a role in carcinogenesis. Toll-like receptors (TLRs) are pattern recognition receptors that participate in the immunological defence against pathogens, but their functions are also linked to cancer., Methods: In our whole population-based study, we retrieved 150 Finnish NPC cases and studied their tumour samples for TLR1, TLR2, TLR4, TLR5, TLR7, and TLR9 expressions by immunohistochemistry, and for the presence of EBV and high-risk HPVs with EBV RNA and HPV E6/E7 mRNA in situ hybridizations. In addition, we analyzed the TLR expression patterns according to age, tumour histology, EBV/HPV status, and outcome., Results: We found that all TLRs studied were highly expressed in NPC. Viral status of the tumours varied, and 62% of them were EBV-positive, 14% HPV-positive, and 24% virus-negative. The tumours with strong TLR2 nucl or TLR5 expression were mostly virus-negative or HPV-positive keratinizing squamous cell carcinomas, and the patients with these tumours were significantly older than those with mild or negative TLR2 nucl /TLR5 expression. In Kaplan-Meier analysis, the patients with strong TLR5 expression had worse survival compared to the patients with negative or mild TLR5 expression, but the results were linked to other patient and tumour characteristics. In multivariable-adjusted Cox regression analysis, the patients with positive TLR7 tumour expression had better overall survival than those with no TLR7 expression. The 5-year overall survival rates according to TLR7 expression were 66% (mild), 52% (moderate or strong), and 22% (negative)., Conclusions: TLRs are highly expressed in non-endemic NPC. Intensity of TLR2 and TLR5 expressions correlate with viral status, and TLR7 seems to be an independent prognostic factor of non-endemic NPC.

Introduction: Implementation of pediatric telemedicine has been emphasized. We examined whether parents could perform smartphone otoscopy for the diagnosis of otitis media. Materials and Methods: We included children (6-35 months) attending day care with at least one episode of acute otitis media (AOM) within 90 days of the study entry. The timing for a teaching intervention was randomized. In the immediate teaching group, parents were taught smartphone otoscopy and cerumen was removed at the first visit. The delayed teaching group received the teaching intervention after 1 week's independent use. During the 60 study days, parents performed home examinations. The main outcome, the diagnostic quality of the tympanic membrane videos to determine healthy ear, otitis media with effusion (OME) and AOM diagnoses was measured with a structured video analysis independently by three physicians. Parents' experience was measured with a questionnaire. Results: AOM could be detected or excluded in 87% (609/699) of the videos during acute symptoms. After the teaching intervention, healthy ear, OME, or AOM could be diagnosed in 40% (521/1,293) of the videos. During the first week's intervention, one of the three diagnoses was attained in 33% (50/153) and in 12% (22/179) of the videos in the immediate and delayed teaching group, respectively ( p  < 0.001). The performance of the smartphone otoscopy examination was easy in 85% (35/41) of families. Discussion: After been taught, parents are able to perform smartphone otoscopy for the remote detection or exclusion of AOM. Conclusions: Future studies should assess the clinical usefulness of parent-performed smartphone otoscopy.

Background: Nasopharyngeal carcinoma (NPC) is related to Epstein-Barr virus (EBV) in endemic areas; however, the role of viruses in nonendemic countries is unclear. Our nationwide study investigated the prevalence and prognostic significance of EBV and human papillomaviruses (HPVs) in Finnish NPC tumors., Methods: We analyzed samples from 150 patients diagnosed between 1990 and 2009. Viral status was determined using EBV and HPV RNA in situ hybridizations, and p16 immunohistochemistry. Patient and treatment characteristics were obtained from patient records., Results: In our white patient cohort, 93 of 150 (62%) patients were EBV-positive and 21/150 (14%) patients were HPV-positive with no coinfections. Thirty-six (24%) tumors were negative for both viruses. The 5-year disease-specific survival for patients with EBV-positive, HPV-positive, and EBV/HPV-negative tumors was 69%, 63%, and 39%, respectively. In multivariable-adjusted analysis, overall survival was better among patients with EBV-positive (P = .005) and HPV-positive (P = .03) tumors compared to patients with EBV/HPV-negative tumors., Conclusions: In our low-incidence population, EBV and HPV are important prognostic factors for NPC., (© 2018 The Authors. Head & Neck published by Wiley Periodicals, Inc.)

Background: The purpose of this retrospective study was to present our assessment of modifiable perioperative factors for major cardiac and cerebrovascular events (MACCE)., Methods: This study included an unselected cohort of patients with head and neck cancer (n = 456) treated in Turku University Hospital between 1999 and 2008., Results: Perioperative and postoperative univariate predictors of MACCE at 30-day follow-up were: total amount of fluids (during 24 hours) over 4000 mL, any red blood cell (RBC) infusion, treatment in the intensive care unit (ICU), tracheostomy, and microvascular reconstruction surgery. Median time from operation to MACCE was 3 days. Patients receiving >4000 mL of fluids had MACCE more often compared with those receiving <4000 mL (10.8% vs 2.4%; p < .001, respectively). Moreover, every RBC unit transfused or every liter of fluid administered over 4000 mL/24h increased the risk of MACCE 18% per unit/liter, respectively., Conclusion: Patients with head and neck cancer receiving excessive intravenous fluid administration perioperatively and postoperatively are at high risk for cardiac complications, especially heart failure. © 2016 Wiley Periodicals, Inc. Head Neck 39: 37-41, 2017., (© 2016 Wiley Periodicals, Inc.)

Purpose of Review: There is no general agreement on which diagnostic procedures are required and optimal in searching for primary tumors among patients with cervical metastasis of unknown primary (CUP). Because of the rising incidence of human papillomavirus (HPV)-associated oropharyngeal carcinoma, it is reasonable to assume that the number of small oropharyngeal tumors with neck metastasis will increase. The purpose of this review is to highlight the diagnostic approaches more useful in detecting such lesions., Recent Findings: After the introduction of the narrow band imaging technique, positron emission tomography-computed tomography, and transoral diagnostic procedures, the accuracy in discovering the primary lesion is up to 80-90%. By far, most primaries arise in the oropharynx, especially among patients with p16/HPV-positive CUP., Summary: The oropharynx is the most likely primary site in patients with CUP, especially in p16/HPV-positive cases. By utilizing recent techniques, a high diagnostic accuracy in detecting the primary tumor is achievable; this may offer better survival rates with cost-effective efforts. We recommend some approaches for the diagnostic protocol used in searching for primary tumors in patients with CUP.

The type of tumor-infiltrating macrophages may be decisive in tumor immunity, lymphangiogenesis and in the clinical outcome of cancer. Here, we elucidated the prognostic significance of lymphatic vessels, different types of macrophages and the balance between different macrophage types in colorectal cancer. We analyzed the impact of density, type and location of macrophages on the clinical behavior of 159 primary colorectal carcinomas using CD68 as a pan-macrophage marker and CLEVER-1/Stabilin-1 as a marker for regulatory/suppressive macrophages. Podoplanin was used as a pan-lymphatic vessel marker. A high number of CLEVER-1/Stabilin-1(+) peritumoral macrophages positively correlated with survival (p = 0.04). However, in more advanced disease (Stage IV), the patients with a high number of peritumoral or intratumoral CLEVER-1/Stabilin-1(+) macrophages had a shorter disease-specific survival (p = 0.05, and p = 0.008, respectively). Moreover, a low number of suppressive intratumoral CLEVER-1/Stabilin-1(+) macrophages among high numbers of CD68(+) macrophages correlated with a low number of distant recurrences (p = 0.01) and to fewer disease relapses exclusively in the liver as well (p = 0.006). A high number of intratumoral lymphatics correlated with poor survival (p = 0.03). The results of this work suggest that the type of macrophages, number of lymphatic vessels and their location contribute to the clinical behavior of colorectal cancer in a disease stage-specific manner., (Copyright © 2011 UICC.)

When treating head and neck cancer of an advanced stage, additional therapy modalities are often combined with surgery. This sets new challenges for the reconstructive surgery, especially after segmental mandibulectomy. There is continuous discussion considering the optimal timing of the surgery with relation to other treatment methods such as radiation therapy and chemotherapy. In this work, we have analyzed a series of 10 patients treated with segmental mandibulectomy and preoperative irradiation or chemoradiation in our institute between 1999 and 2006. Surgery was scheduled within 5 weeks from the radiation therapy. 9 out of 10 reconstruction flaps were vital at the last follow-up. In general the outcome of these patients was consistent with the results published earlier by other institutes using postoperative irradiation or chemoradiation. We conclude that preoperative irradiation does not have negative impact on microvascular reconstruction with free bone flap and this procedure offers an equal option for the treatment of these patients.

The prognosis of cancer patients is highly dependent on the time of diagnosis. Early, stage 1 disease is often curable whereas late stage diseases are usually beyond curable treatments. Therefore, new diagnostic tools for malignancies of the upper aerodigestive tract are developed all the time and narrow band imaging (NBI) is one of these new options for early diagnostics. In this paper, we describe the implementation of NBI technique in our institution. During the first 6 weeks we used NBI to examine 73 patients with different types of pharyngeal or laryngeal problems. Most of the patients (77%) were on follow-up visits after earlier malignant disease. In our series we had 11 NBI-positive patients and the histological diagnosis was carcinoma or dysplasia among 10 of these. Among the NBI negative patients we found four carcinomas. It is notable that NBI affected the decision of a biopsy procedure in three patients, with final diagnosis of dysplasia or carcinoma. In conclusion, we find NBI useful in the diagnostics of malignancies of the upper aerodigestive tract. This is a useful tool in improving the accuracy of the diagnostics. However, it still takes an experienced clinician and a learning curve can be expected.

Although approximately 50% of cancers give rise to metastases via the lymphatic system, the mechanisms mediating this process have remained unknown. In this study, we have investigated the role of two lymphatic endothelial molecules, the mannose receptor (MR) and common lymphatic endothelial and vascular endothelial receptor (CLEVER)-1 in adhesion of malignant cells to the lymphatic endothelium, and analyzed their expression in two clinical series consisting of squamous cell cancers of the head and neck (n = 17) and breast cancers (n = 72). Affinity of the tested head and neck cancer cell lines to the lymphatic endothelium varied greatly, but adhesion of all cell lines was dependent on both the MR and CLEVER-1. Almost all cancer specimens contained peritumoral vessels that expressed CLEVER-1 and MR, and also the intratumoral lymph vessels often expressed them in both tumor types. However, only intratumoral expression of these molecules seems to be essential for metastatic spread to the regional lymph nodes. Only 8 (22%) of the 36 axillary node-negative breast carcinomas expressed the MR on the intratumoral lymph vessels as compared with 16 (50%) of the 32 node-positive carcinomas (P = 0.017), and all eight head and neck carcinoma patients with regional lymph node metastases at diagnosis had tumors that expressed CLEVER-1 on the intratumoral lymph vessels. These data suggest a role for both the MR and CLEVER-1 in directing the traffic of cancer cells within the lymphatic system.