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This retrospective study aimed to clarify the occurrence and types of otologic injuries in children and adolescents with skull fractures. Files of all patients under 18 years of age who had been diagnosed with skull fractures at a tertiary trauma centre were included. The primary outcome variable was the presence of any otologic symptom or finding. Secondary outcome variables were clinically detected and radiologically detected otologic injuries. The primary predictor variable was a temporal bone fracture. Other study variables were sex, age, mechanism of injury, traumatic brain injury, and mortality. A total of 97 patients were identified for the study. Otologic symptoms and findings were frequent (33.9%). The most common clinical findings were bleeding from the external auditory canal (18.6%) and hemotympanum (13.4%). The prevailing radiological finding was blood and/or cerebrospinal fluid in the middle ear (30.9%). Patients with fractures of temporal bone had a 29-fold risk for otologic symptoms or findings (RR 28.9, 95% CI 4.1–202.9, p < 0.001) relative to those who did not have a temporal bone fracture. Severe otologic complications, such as permanent hearing loss (6.2%), cerebrospinal fluid leak (5.2%), or facial nerve palsy (1%), were infrequent. Within the limitations of the study it seems that there is the necessity of otoscopy in all pediatric patients with blunt head trauma. In case of positive otologic findings, the patient should undergo imaging and ENT consultation. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown an increased prevalence of candidiasis in patients receiving radiotherapy for head and neck cancer. However, little is known of the effect the different cancer treatment modalities have on the oral Candida status.Objective and Hypothesis: The objective of this study was to investigate the change in salivary Candida status of oral squamous cell carcinoma (OSCC) patients undergoing cancer treatment. The hypothesis was that cancer treatments change the oral microbial environment favouring an increase in the prevalence of more pathogenic non-albicans Candida (NAC).Methods: We collected paraffin-stimulated saliva from 44 OSCC patients before surgery and after a minimum of 19 months of follow-up. Chromagar, Bichro-Dupli-test and API ID 32 C were used for identification of different Candida species and results were analysed statistically.Results: At both timepoints, 75% of samples were Candida positive with C. albicans being the most common yeast. NAC strains were present in 16% of the pre-operative samples and 14% of the follow-up samples. The NAC species found were C. dubliniensis, C. krusei, C. guilliermondii (preoperatively only) and C. glabrata (at follow-up only). In 73% of the cases, the salivary Candida status remained unchanged. There was an 18% increase in the prevalence of candidiasis. However, the different treatment modalities did not statistically significantly affect the Candida status of the patients.Conclusion: The intraindividual prevalence of salivary Candida among OSCC patients seems to be stable and different treatment modalities have little to no effect on the salivary Candida status. [ABSTRACT FROM AUTHOR]

Nonsurgical primary treatment of early and advanced laryngeal squamous cell carcinoma, employing radiotherapy with or without chemotherapy, is considered a standard of care in many centers throughout the world. When patients have persistent or recurrent disease after non-surgical treatment, salvage surgery is frequently the only remaining potentially curative treatment. Depending on the extent of the residual/recurrent disease, different surgical salvage options are at the surgeon's disposal. In selected cases with limited local disease, salvage transoral laser microsurgery, transoral robotic surgery and open partial laryngectomies can be employed to achieve cure while preserving laryngeal function. For more advanced cases total laryngectomy is necessary. Identifying situations with unacceptable results from surgical salvage may guide future therapies. [ABSTRACT FROM AUTHOR]

Concomitant chemoradiotherapy (CRT) is extensively used as primary organ preservation treatment for selected advanced laryngeal squamous cell carcinomas (LSCC). The oncologic outcomes of such regimens are comparable to those of total laryngectomy followed by adjuvant radiotherapy. However, the management of loco-regional recurrences after CRT remains a challenge, with salvage total laryngectomy being the only curative option. Furthermore, the decision whether to perform an elective neck dissection (END) in patients with rN0 necks, and the extent of the neck dissection in patients with rN + necks is still, a matter of debate. For rN0 patients, meta-analyses have reported occult metastasis rates ranging from 0 to 31 %, but no survival advantage for END. In addition, meta-analyses also showed a higher incidence of complications in patients who received an END. Therefore, END is not routinely recommended in addition to salvage laryngectomy. Although some evidence suggests a potential role of END for supraglottic and locally advanced cases, the decision to perform END should weigh benefits against potential complications. In rN + patients, several studies suggested that selective neck dissection (SND) is oncologically safe for patients with specific conditions: when lymph node metastases are not fixed and are absent at level IV or V. Super-selective neck dissection (SSND) may be an option when nodes are confined to one level. In conclusion, current evidence suggests that in rN0 necks routine END is not necessary and that in rN + necks with limited nodal recurrences SND or a SSND could be sufficient. [ABSTRACT FROM AUTHOR]

Abstract Aim We herein describe the establishment of the Helsinki Vascularized Composite Allotransplantation (VCA) program and its execution in the first two face transplant cases. Methods & patients The Helsinki VCA program initially required the fulfillment of legal, hospital, financial, and ethical requirements. Thereafter, the assembling of a multidisciplinary team commenced. A team of Plastic, maxillofacial and ENT surgeons comprise the facial VCA team. The protocol involves collaboration with the Solid Organ Transplant (SOT) team, transplant immunology, immunosuppression, microbiology, psychiatric evaluation, well-defined VCA indications and informed consent. Between 2011 and 2017 two patients were selected for transplantation. Both patients had a severe composite facial deformity involving the maxilla and mandible following earlier ballistic injury. Results Patient 1 was a 35 year-old male who underwent successful near total face transplantation in February 2016 and at 30 months he has a good aesthetic outcome with symmetrical restoration of the central face and good sensory and symmetrical motor functional outcomes. Patient 2 was a 58 year-old male who underwent full face transplantation in March 2018 and at 5 months he has recovered without major problems. Conclusion A successful facial VCA program requires a well-prepared research protocol, experts from multiple specialties and careful patient selection. The establishment of the Helsinki VCA program required long and thorough planning and resulted in the first two Nordic face transplantation cases. This protocol now forms the platform (as a proof of concept) for other types of vascularized composite allotransplantations. [ABSTRACT FROM AUTHOR]

Purpose: This study examined the prevalence of Candida species in the saliva of oral squamous cell carcinoma patients and its effect on the mortality rate.Materials and Methods: One hundred patients with oral cavity squamous cell carcinoma undergoing protocol treatment at Helsinki University Hospital were recruited into the study from March 2011 through 2014. For comparison, 75 age-matched controls with no current or previously treated oral cancer were recruited. Paraffin-stimulated whole saliva samples were collected and cultivated on CHROMagar Candida medium (CHROMagar, Paris, France) to establish possible Candida growth. The API ID 32C yeast identification kit (bioMérieux, Lyon, France) and Bichro-Dubli Fumouze latex agglutination test (Fumouze Diagnostics, Levallois-Perret, France) were used for further identification of different Candida species. Patients' medical records were studied for information on their health habits and general health status, as well as tumor-related data. The patients' status regarding being alive and cancer free was checked at a follow-up point in December 2017. Descriptive statistics and cross tabulation were carried out, and the P value was set at .05.Results: Candida species were detected in 74% of the oral cancer patients' samples, with C. albicans being the most common species (84%). Other species identified were C. dubliniensis (8%), C. tropicalis (4%), C. glabrata (3%), C. parapsilosis (3%), C. sake (3%), C. krusei (1%), and C. guilliermondii (1%). After the follow-up period, 63% of the patients were alive and 86% of them were cancer free. Harboring Candida species in the saliva was not associated with any increase in the mortality rate.Conclusions: C. albicans was common in the oral cavity of the oral squamous cell carcinoma patients. However, in this patient population, we did not observe a statistically significant effect of the yeast on the mortality rate. [ABSTRACT FROM AUTHOR]

• Optimal treatment for T2-3 laryngeal squamous cell carcinoma (LSCC) is undecided. • Bayesian network (BN) model is used for estimation of treatment outcome from observational data. • BN gives a possibility to control for multiple variables with complex dependences. • A novel method of disjunctive confounder criterions is adapted. • Locoregional control was better in T2-3 LSCC patients who underwent surgery. [ABSTRACT FROM AUTHOR]

Objective Frontobasilar fracture types and the outcome of patients after management with the subcranial approach technique were evaluated. Material and methods A retrospective analysis of 48 patients (45 males, mean age 38,5 years; range 16–82 years) who had a subcranial approach for frontal base fracture correction between April 1996 and April 2011 at a tertiary care academic hospital in Turku, Finland. Results Sixteen (33%) patients had fractures including all frontobasilar fracture types (Type I-IV) i.e. fractures that involved frontal sinuses, orbital roofs, ethmoidal region, cribriform plate and sphenoidal region. Twenty-seven (56%) patients were considered to have had brain damage at presentation. Forty percent of patients were suffering from synchronous trauma. Peroperatively, 31 (65%) patients had exposure or defect of the dura due to bone dehiscence but only two patients suffered from cerebrospinal fluid (CSF) fistula following surgery. CSF fistulae were covered by pericranium in most of the cases (68%). There was no postoperative meningitis. Thirty-eight percent of the patients needed further operation with a subcranial craniotomy following primary reconstruction. At the last follow-up visit 35% were suffering from permanent neurological problems following brain injury. Conclusions Subcranial approach seemed successful in the management of all frontobasilar fractures in this series with reasonably low complication rate. Therefore, we would recommend it as the technique of choice in multiple and even in the most complicated frontal base fractures. [ABSTRACT FROM AUTHOR]

Backgrounds Second branchial cleft anomalies predispose to recurrent infections, and surgical resection is recommended as the treatment of choice. There is no clear consensus regarding the timing or surgical technique in the operative treatment of these anomalies. Our aim was to compare the effect of age and operative techniques to patient characteristics and treatment outcome. Methods A retrospective study of pediatric patients treated for second branchial sinuses or fistulae during 1998-2012 at two departments in our academic tertiary care referral center. Comparison of patient characteristics, preoperative investigations, surgical techniques and postoperative sequelae. Results Our data is based on 68 patients, the largest series in the literature. One-fourth (24%) of patients had any infectious symptoms prior to operative treatment. Patient demographics, preoperative investigations, use of methylene blue, or tonsillectomy had no effect on the surgical outcome. There were no re-operations due to residual disease. Three complications were observed postoperatively. Conclusions Our patient series of second branchial cleft sinuses/fistulae is the largest so far and enables analyses of patient characteristics and surgical outcomes more reliably than previously. Preoperative symptoms are infrequent and mild. There was no difference in clinical outcome between the observed departments. Performing ipsilateral tonsillectomy gave no outcome benefits. The operation may be delayed to an age of approximately three years when anesthesiological risks are and possible harms are best avoided. Considering postoperative pain and risk of postoperative hemorrhage a routine tonsillectomy should not be included to the operative treatment of second branchial cleft fistulae. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The aim of this study was to develop and test the utility of a novel systematic protocol to analyze CT images of patients with trauma in the anterior cranial base and upper midface. Material and Methods: The radiological data and primary reports of 27 consecutive patients with a frontal skull base fracture treated in two tertiary care hospitals from 2007 to 2011 were scrutinized. A novel algorithm for systematic image reviewing was used to assess the CT images and the findings were compared with the primary radiological reports. Results: The systematic review detected a substantial number of fractures and defects in anatomical structures that had not been systematically reported in the primary, on-call reports. Anterior skull base fracture was not initially reported in 32% of the patients; however, the algorithm detected this in 93% of them. The corresponding rates for fracture through cribriform plate were 28% and 72% and for fracture through the sella or hypophyseal area 22% and 78%. There were two fractures of the clivus and these were initially missed. Conclusions: Despite the failure to identify these fractures radiologically in the primary setting, all patients were still considered to have received appropriate treatment, but, the use of an image-reviewing algorithm will enhance the specificity of CT in the diagnosis of frontobasilar fractures. [Copyright &y& Elsevier]

Background: Additive manufacturing (AM) is being increasingly used for producing medical models. The accuracy of these models varies between different materials, AM technologies and machine runs. Purpose: To determine the accuracy of selective laser sintering (SLS), three-dimensional printing (3DP) and PolyJet technologies in the production of medical models. Material: 3D skull models: “original”, “moderate” and “worse”. SLS, 3DP and PolyJet models, and a coordinate measuring machine (CMM). Methods: Measuring balls designed for measurements were attached to each 3D model. Skull models were manufactured using SLS, 3DP and PolyJet. The midpoints of the balls were determined using CMM. The distances between these points were calculated and compared with the 3D model. Results: The dimensional error for the PolyJet was 0.18 ± 0.12% (first measurement) and 0.18 ± 0.13% (second measurement), for SLS 0.79 ± 0.26% (first model) and 0.80 ± 0.32% (second model), and for 3DP 0.67 ± 0.43% (original model, first measurement) and 0.69 ± 0.44% (original model, second measurement), 0.38 ± 0.22% (moderate model) and 0.55 ± 0.37% (worse model). Repeatability of the measurement method was 0.12% for the PolyJet and 0.08% for the 3DP. Conclusion: A novel measuring technique was developed and its repeatability was found to be good. The accuracy of the PolyJet was higher when compared with SLS or 3DP. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Otoplasty is the most common aesthetic surgical procedure performed in children. The goals for auricular surgery and the proportions of an aesthetically pleasing ear appear to be based on the aesthetic opinions of individual surgeons rather than on evidence-based data. Our study aimed to determine whether identifying an aesthetically pleasing auricle is possible. Methods: We used digital photographs of 29 auricles, a standardized camera setup, a panel of 20 plastic surgeons, and a visual analogue scale (VAS). We then analyzed the scores assigned by the panel for mean, median, standard deviation, analysis of variance, Tukey–Kramer Multiple Comparison Test, and Top 5 rankings. Results: Ranking by the panel was statistically significant (p <0.000001). Conclusions: It is possible to statistically rank the aesthetics of auricles, although it is difficult to identify the structural details that made an auricle aesthetically pleasing. [Copyright &y& Elsevier]

Abstract: A poly(dl-lactic-co-glycolic acid) (PLGA) sandwiched adipose derived stem cell (ADSC)/fibrin tubular construct, fabricated using a step-by-step mold/extraction method, was characterized in this work. The ADSCs were also induced into smooth-muscle-like cells using growth factors such as hepatocyte growth factor (HGF), platelet-derived growth factor BB (PDGF-BB), transforming growth factor β1 (TGFβ1), and basic fibroblast growth factor (b-FGF). Compared with the non-induced cells, the proliferation ability of induced cells was much smaller. The PLGA sandwiched cell/hydrogel construct was shown to be useful for controlling the cellular microenvironment and cellular behaviors such as growth, migration, proliferation and differentiation. This strategy seems promising in tissue engineering and organ manufacturing. [Copyright &y& Elsevier]

Laryngeal trauma is rare and can occur as an isolated injury or as part of multitrauma. On the basis of airway patency, it is decided whether the patient needs rapid surgical intervention or whether the patient would profit from preoperative imaging done with multidetector row multislice thin section computed tomography with multiplanar reconstruction in the soft-tissue and bone window setting. Grading the fracture pattern from minor isolated to multiple dislocated fracture lines helps to plan individual treatment options and to prevent long-term voice complications. [Copyright &y& Elsevier]

Background: The distal part of the internal carotid artery (ICA) close to the skull base can be reached surgically with different approaches. Exposure using the standard lateral incision is eventually limited by bony structures which preclude the wide-angled operative field necessary for en bloc resection of tumors or primary vascular pathology that abuts the parapharyngeal space. In these unusual cases, use of a combined midline mandibulotomy and neck incision provides necessary operative exposure. Aim: We report our experience using combined midline mandibulotomy and neck incision for exposure of high carotid lesions. We also discuss different surgical and endovascular approaches in light of the literature. Patients and Methods: Five patients were operated on for high ICA lesions: 2 for malignant head and neck tumors, 1 for an extended paraganglioma, and 2 for large symptomatic ICA aneurysms. All ICAs were reconstructed with an autologous vein interposition graft and the distal anastomoses were performed within the most distal 3 cm of the ICA adjacent to the orifice of bony carotid canal. Results: All operations were technically successful with no operative mortality or strokes. One aneurysm patient and the paraganglioma patient had minimal long-term sequelae from this procedure. One patient with an extended lingual epidermoid carcinoma was recurrence free at 3.6 years. One aneurysm patient died due to aspiration pneumonia 30 days postoperatively and another patient had early recurrent tumor growth and died due to that after 15 months. Four patients (80%) suffered a major cranial nerve injury in the operation mainly due to the extensive nature of the disease process. Conclusion: Exposure of the distal carotid artery using midline mandibulotomy is rarely required. However, this technique represents an excellent option for cases of malignancies arising from the oral cavity which abut the carotid artery and instances in which primary carotid pathology extends medially alongside the parapharyngeal space. Performance of these cases should be accomplished by a multidisciplinary surgical team comprised of head and neck and vascular specialists. High rates of cranial nerve deficits should be anticipated. [Copyright &y& Elsevier]

The interaction between noise and inhaled styrene on the structure and function of the auditory organ of the male Wistar rat was studied. The animals were exposed either to 600 ppm, 300 ppm or 100 ppm styrene (12 h/day, 5 days/week, for 4 weeks) alone or in combination with a simultaneous 100–105 dB industrial noise stimulant. Auditory sensitivity was tested by auditory brainstem audiometry at 1.0, 2.0, 4.0 and 8.0 kHz frequencies. Inner ear changes were studied by light microscopy. Exposure to 600 ppm styrene alone caused a 3 dB hearing loss only at the highest test frequency (8 kHz). Quantitative morphological analysis of cochlear hair cells (cytocochleograms) showed a severe outer hair cell (OHC) loss particularly in the third OHC row of the upper basal and lower middle coil. Exposure to noise alone caused only a mild hearing loss (2–9 dB), and only an occasional loss of OHCs (<1% missing). Exposure to the combination of noise and 600 ppm styrene caused a moderate flat hearing loss of 23–27 dB. The cytocochleograms showed a more severe damage of the OHCs than after exposure to 600 ppm styrene alone. The inner hair cells were found to be destroyed in some animals in the upper basal turn only after the combination exposure. Only in combination with noise exposure, the lower styrene concentrations (100 and 300 ppm) induced a hearing loss which was equivalent to that seen after exposure to noise alone. We conclude that: (1) There is an ototoxic interaction between styrene and noise. (2) Synergism is manifested only if styrene is applied in concentrations above the critical level (between 300 and 600 ppm in this study). [Copyright &y& Elsevier]

Knowledge on the role of matrix metalloproteinases (MMPs) in adenoid cystic carcinoma (ACC) is limited. MMPs are capable of degrading almost all extracellular and pericellular components to promote invasion and metastasis. This study aimed to evaluate the immunohistochemical expression of MMP-7, -8, -9, -15, and -25 in ACC and to relate the results with clinicopathological factors and survival. The study included 68 patients with minor salivary gland ACC treated at the Helsinki University Hospital (Helsinki, Finland) in 1974–2012. Samples from 52 patients were available, consisting of 44 primary tumours and eight recurrent tumours. We scored immunostaining of MMP-7, -8, -9, -15, and -25 and analysed the immunoscore against clinical and pathological parameters using statistical correlation test. MMP-9 immunoexpression in pseudocysts of ACC and in peritumoural inflammatory cells associated with better survival and fewer treatment failures. High tumoural MMP-7 and -25 associated with better survival. High tumoural MMP-15 associated with poorer survival and high tumoural MMP-9 with advanced stage and regional recurrences. Tumour cells did not show MMP-8 immunopositivity. These results suggest that MMP-9 may contribute to ACC carcinogenesis in different roles. MMP-7, -8, and -9 can stimulate signalling pathways that may promote tissue modulation and metastatic potential. MMP-15 and -25 may reflect prognosis. [ABSTRACT FROM AUTHOR]

Background: The prediction of overall survival in tongue cancer is important for planning of personalized care and patient counselling.Objectives: This study compares the performance of a nomogram with a machine learning model to predict overall survival in tongue cancer. The nomogram and machine learning model were built using a large data set from the Surveillance, Epidemiology, and End Results (SEER) program database. The comparison is necessary to provide the clinicians with a comprehensive, practical, and most accurate assistive system to predict overall survival of this patient population.Methods: The data set used included the records of 7596 tongue cancer patients. The considered machine learning algorithms were logistic regression, support vector machine, Bayes point machine, boosted decision tree, decision forest, and decision jungle. These algorithms were mainly evaluated in terms of the areas under the receiver-operating characteristic (ROC) curve (AUC) and accuracy values. The performance of the algorithm that produced the best result was compared with a nomogram to predict overall survival in tongue cancer patients.Results: The boosted decision-tree algorithm outperformed other algorithms. When compared with a nomogram using external validation data, the boosted decision tree produced an accuracy of 88.7% while the nomogram showed an accuracy of 60.4%. In addition, it was found that age of patient, T stage, radiotherapy, and the surgical resection were the most prominent features with significant influence on the machine learning model's performance to predict overall survival.Conclusion: The machine learning model provides more personalized and reliable prognostic information of tongue cancer than the nomogram. However, the level of transparency offered by the nomogram in estimating patients' outcomes seems more confident and strengthened the principle of shared decision making between the patient and clinician. Therefore, a combination of a nomogram - machine learning (NomoML) predictive model may help to improve care, provides information to patients, and facilitates the clinicians in making tongue cancer management-related decisions. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is a common malignancy of the head and neck region. OSCC has a relatively low survival rate and the incidence of the disease is increasing in some geographic areas. Staging and grading of OSCC are established prerequisites for management, as they influence risk stratification and are the first step toward personalized treatment. The current AJCC/UICC TNM staging (8th edition, 2017) of OSCC has included significant modifications through the incorporation of depth of invasion in the T stage and extracapsular spread/extranodal extension in the N stage. Further modifications for AJCC 8 have been suggested. On the other hand, the World Health Organization (WHO) classification (4th edition, 2017) still endorses a simple, differentiation-based histopathologic grading system of OSCC (despite its low prognostic value) and ignores factors such as tumor growth pattern and dissociation, stromal reactions (desmoplasia, local immune response), and tumor-stroma ratio. The various controversies and possible developments of the current staging and grading criteria of OSCC are briefly discussed in this update together with possible applications of artificial intelligence in the context of screening and risk stratification. [ABSTRACT FROM AUTHOR]

Parathyroid cancer (PC) is a rare malignant tumor which comprises 0.5-5% of patients with primary hyperparathyroidism (PHPT). Most of these cancers are sporadic, although it may also occur as a feature of various genetic syndromes including hyperparathyroidism-jaw tumor syndrome (HPT-JT) and multiple endocrine neoplasia (MEN) types 1 and 2A. Although PC is characterized by high levels of serum ionized calcium (Ca) and parathyroid hormone (PTH), the challenge to the clinician is to distinguish PC from the far more common entities of parathyroid adenoma (PA) or hyperplasia, as there are no specific clinical, biochemical, or radiological characteristic of PC. Complete surgical resection is the only known curative treatment for PC with the surgical approach during initial surgery strongly influencing the outcome. In order to avoid local recurrence, the lesion must be removed en-bloc with clear margins. PC has high recurrence rates of up to 50% but with favorable long-term survival rates (10-year overall survival of 60-70%) due to its slow-growing nature. Most patients die not from tumor burden directly but from uncontrolled severe hypercalcemia. In this article we have updated the information on PC by reviewing the literature over the past 10 years and summarizing the findings of the largest series published in this period. [ABSTRACT FROM AUTHOR]

Up to one in four patients with nasopharyngeal carcinoma present with non-metastatic stage IV disease (i.e. T4 or N3). Distinct failure patterns exist, despite the routine adoption of contemporary treatment modalities such as intensity modulated radiotherapy and systemic chemotherapy. Concurrent chemoradiotherapy (CCRT) followed by adjuvant chemotherapy or induction chemotherapy followed by CCRT are commonly employed in this setting, with the latter emerging as the preferred option. Additionally, emerging radiation technologies like proton therapy has become available offering new opportunities for prevention of radiation-induced side effects. This article reviews not only the current treatment strategies, but also discusses novel ways to tackle this challenging disease with respect to the patterns of failure. [ABSTRACT FROM AUTHOR]

As a consequence of the current excellent loco-regional control rates attained using the generally accepted treatment paradigms involving intensity-modulated radiotherapy for nasopharyngeal carcinoma (NPC), only 10-20% of patients will suffer from local and/or nodal recurrence after primary treatment. Early detection of recurrence is important as localized recurrent disease is still potentially salvageable, but this treatment often incurs a high risk of major toxicities. Due to the possibility of radio-resistance of tumors which persist or recur despite adequate prior irradiation and the limited tolerance of adjacent normal tissues to sustain further additional treatment, the management of local failures remains one of the greatest challenges in this disease. Both surgical approaches for radical resection and specialized re-irradiation modalities have been explored. Unfortunately, available data are based on retrospective studies, and the majority of them are based on a small number of patients or relatively short follow-up. In this article, we will review the different salvage treatment options and associated prognostic factors for each of them. We will also propose a treatment algorithm based on the latest available evidence and discuss the future directions of treatment for locally recurrent NPC. [ABSTRACT FROM AUTHOR]

Objectives: No prognostic or predictive biomarkers for oral squamous cell carcinoma (OSCC) exist. We aimed to discover novel proteins, altered in OSCC, to be further investigated as potential biomarkers, and to improve understanding about pathways involved in OSCC.Materials and Methods: Proteomic signatures of seven paired healthy and OSCC tissue samples were identified using ultra-definition quantitative mass spectrometry, then analysed and compared using Anova, principal component analysis, hierarchical clustering and OPLS-DA modelling. A selection of significant proteins that were also altered in the serum from a previous study (PMID: 28632724) were validated immunohistochemically on an independent cohort (n = 66) to confirm immunopositivity and location within tumour tissue. Ingenuity Pathways Analysis was employed to identify altered pathways.Results: Of 829 proteins quantified, 257 were significant and 72 were able to classify healthy vs OSCC using OPLS-DA modelling. We identified 19 proteins not previously known to be upregulated in OSCC, including prosaposin and alpha-taxilin. KIAA1217 and NDRG1 were upregulated in stage IVa compared with stage I tumours. Altered pathways included calcium signalling, cellular movement, haematological system development and function, and immune cell trafficking, and involved NF-kB and MAPK networks.Conclusions: We found a set of proteins reliably separating OSCC tumour from healthy tissue, and multiple proteins differing between stage I and stage IVa OSCC. These potential biomarkers can be studied and validated in larger cohorts. [ABSTRACT FROM AUTHOR]

Purpose/Objectives: Artificial intelligence (AI) and its subfields such as machine learning (ML) and deep learning (DL) have been reported to show high performance, particularly in the diagnosis and prognosis of various cancers 1–3. Despite the promising results obtained from these studies, advancements in technology have increased the availability of medical images in different formats such as computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and ultrasound images 1,2. Interestingly, these image formats are more than pictures, they are in fact, data 4. As a result, several approaches such as radiomics have been recently used to extract information that is not visible to the human eye during routine examination from these images 5. Hence, radiomics is an emerging field in radiology that provides a non-invasive approach for extracting quantitative features from medical cancer images such as CT, PET, MRI, or a combination of these image formats 5. Traditionally, the extracted features are processed using statistical approaches. However, due to the large amount of extracted features, statistical approaches can no longer effectively handle these features 6,7. Therefore, in recent years, several studies exploring the potential of AI or its subfields such as ML and DL in handling the extracted features to produce a predictive model have shown promising results that are capable of revolutionizing HNC management 8. However, in actual everyday clinical practice, the use of AI-based radiomics models remains limited 5. This is due to several implementation challenges 5. Objectives: This study provides a systematic review of the challenges, concerns, and limitations of AI-based models in head and neck cancer (HNC) oncology. Furthermore, we suggest possible solutions to these challenges. We searched OvidMedline, PubMed, Scopus, and Web of Science databases for articles that examine the challenges of AI-based models in HNC oncology. The quality of included studies and their risk of biases were evaluated using the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) and Prediction Model Risk of Bias Assessment Tool (PROBAST). A total of 11 studies examined the challenges of these models in HNC oncology. These challenges have been summarized into 5 themes. These include data, science of machine learning, model generalizability, model maintenance and performance improvements, and ethical and regulatory concerns. The data concerns include data management, data imbalance and heterogeneity, privacy, and confidentiality. The concerns relating to the science of machine learning include model and result interpretability, explainability, and model performance. The model's generalizability encompasses internal and external independent geographic validation of the models. Some of the ethical and regulatory concerns were as follows: model-clinician disagreement (contradictory diagnostic or prognostic opinion between the model and clinician), workflow and user-design challenges, patient's liberty to decide the type of treatment to follow may be violated, patient–clinician relationship may change, standardized reporting guidelines of AI model development, and outdated regulatory and legal frameworks. Stakeholders such as the governments, medical institutions, hospital management, clinicians, physicians, regulatory agencies, technological companies, politicians, ethicists, philosophers, legal experts, patient representatives, data scientists, and machine learning experts need to be deeply involved in the development of internationally standardized and structured reporting guidelines for the AI-based model to be beneficial in daily clinical practice. The envisioned guidelines should define solutions to data issues by defining a robust data economy framework. Model interpretability and explainability can be handled using explainability techniques by providing both local and global interpretations of the predictions made by the model. Independent external geographic validation of the model should be a standard procedure. A federated learning paradigm can enhance continuous model improvement and generalizability. The guidelines should also include a defined ethical and regulatory framework for the development and reporting of AI-based radiomics models. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The process of fabricating physical medical skull models requires many steps, each of which is a potential source of geometric error. The aim of this study was to demonstrate inaccuracies and differences caused by DICOM to STL conversion in additively manufactured medical skull models. Material and methods: Three different institutes were requested to perform an automatic reconstruction from an identical DICOM data set of a patients undergoing tumour surgery into an STL file format using their software of preference. The acquired digitized STL data sets were assessed and compared and subsequently used to fabricate physical medical skull models. The three fabricated skull models were then scanned, and differences in the model geometries were assessed using established CAD inspection software methods. Results: A large variation was noted in size and anatomical geometries of the three physical skull models fabricated from an identical (or “a single”) DICOM data set. Conclusions: A medical skull model of the same individual can vary markedly depending on the DICOM to STL conversion software and the technical parameters used. Clinicians should be aware of this inaccuracy in certain applications. [Copyright &y& Elsevier]

Background: Previous work in type I pollen allergies has focused on aberrant immunoresponses. Objective: Our systems-level analyses explore the role of epithelium in early pathogenesis of type I allergic reactions. Methods: We began top-down analyses of differences in human nasal epithelial cells and biopsy specimens obtained from patients with birch allergy and healthy control subjects in the resting state and after intranasal in vivo birch pollen challenges. Immunohistochemistry, immunotransmission electron microscopy, mass spectrometry, transcriptomics, and integration of data to a pathway were conducted. Results: Bet v 1 allergen bound to epithelium immediately after in vivo birch pollen challenge during winter only in allergic individuals. It also travelled through epithelium with caveolae to mast cells. Sixteen unique proteins were found to bind to the Bet v 1 column only in lysates from allergic epithelial cells; 6 of these were caveolar and 6 were cytoskeletal proteins. The nasal epithelial transcriptome analysis from allergic and healthy subjects differed during the winter season, and these subjects also responded differentially to birch pollen challenge. Within this pollen-induced response, the gene ontology categories of cytoskeleton and actin cytoskeleton were decreased in allergic patients, whereas the actin-binding category was enriched in healthy subjects. Integration of microscopic, mass spectrometric, and transcriptomic data to a common protein-protein binding network showed how these were connected to each other. Conclusion: We propose a hypothesis of caveolae-dependent uptake and transport of birch pollen allergen in the epithelium of allergic patients only. Application of discovery-driven methodologies can provide new hypotheses worth further analysis of complex multifactorial diseases, such as type I allergy. [Copyright &y& Elsevier]

Summary: Chemoradiotherapy (CRT) of head and neck squamous cell carcinoma (HNSCC) is often accompanied by severe mucosal reactions. We have recently shown that the single nucleotide polymorphism (SNP) rs1982073 of the TGFβ1 gene (TGFB1) is associated with the survival of HNSCC patients who have undergone CRT. In order to evaluate possible mechanisms mediating this, we investigated if the TGFB1 polymorphism was associated with the severity of mucositis induced by CRT. Peripheral blood DNA of 34 HNSCC patients who had undergone CRT was genotyped for the SNP rs1982073 of the TGFB1. Mucositis was graded according to acute toxicity criteria of radiation therapy oncology group (RTOG). The mean follow-up time was 48months (range, 4–115months). We did not find a significant association between the TGFB1 polymorphism and the degree of acute mucositis (OD=2.65; 95% CI 0.50–13.89; p =0.25). The degree of acute mucositis was not connected to disease-free survival (p =0.35). However, the TGFB1 polymorphism was associated with survival irrespective of the degree of mucositis (HR=3.23; 95% CI 1.19–8.77; p =0.02). [Copyright &y& Elsevier]

Summary: Articulatory proficiency of /r/ and /s/ sounds, voice quality and resonance, speech intelligibility, and intraoral sensation were examined prospectively before operation, and at four time points during a 1-year follow-up after microvascular transfer. Forty-one patients with a large oral or oropharyngeal carcinoma undergoing tumor resection and free-flap reconstruction usually combined with radiotherapy participated in the study. Articulation, voice, and resonance were investigated both live and from recorded speech samples by two trained linguistic examiners. The patients completed a self-rating of their speech intelligibility and were assessed for anterior intraoral surface sensation by means of 2-point moving discrimination. Misarticulations of /r/ and /s/ increased significantly after the therapy. Voice quality and resonance remained essentially normal. Speech intelligibility deteriorated significantly. Intraoral sensation decreased postoperatively but was not related to speech outcome. Sensate flaps did not prove to be superior in relation to speech tasks. A multidisciplinary approach is advocated in assessment of speech outcome after cancer surgery. Speech therapy is strongly recommended, even in the absence of a gross articulatory handicap. [Copyright &y& Elsevier]

Summary: Swallowing and intraoral sensation outcome were investigated prospectively after microvascular free-flap reconstruction. Forty-one patients with a large oral or oropharyngeal carcinoma underwent free-flap surgery usually combined with radiotherapy. The patients completed modified barium swallow, self-rating of swallowing, and 2-point moving discrimination preoperatively and at four time points during the 12-month follow-up period, and a plain chest X-ray one year after operation. Swallowing was impaired with respect to an objective and subjective measure after therapy. Rates for nonsilent and silent aspiration increased during the follow-up. Intraoral sensation deteriorated. Swallowing outcome was not related to sensation. One year after surgery, 86% of the patients ate regular masticated or soft food. Microvascular transfers offer a reasonable option for oral reconstruction. This study does not support the need for sensate flaps. Swallowing problems should be routinely sought and patients rehabilitated during a sufficiently long follow-up with videofluorography regardless of the patient’s perception of swallowing. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Background: Radiomics is a rapidly growing field used to leverage medical radiological images by non-invasively extracting quantitative features 1. These are supposed to characterize a patient's phenotype, and when combined with artificial intelligence techniques, to improve the accuracy of diagnostic models and clinical outcome prediction 2. Objectives: This review aims at examining the application areas of artificial intelligence-based radiomics (AI-based radiomics) for the management of head and neck cancer (HNC). It further explores the workflow of AI-based radiomics for personalized and precision oncology in HNC. Finally, it examines the current challenges of AI-based radiomics in daily clinical oncology and offers possible solutions to these challenges. Comprehensive electronic databases (PubMed, Medline via Ovid, Scopus, Web of Science, and Institute of Electrical and Electronics Engineers (IEEE)) were searched following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. The quality of included studies and their risk of biases were evaluated using the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) and Prediction Model Risk of Bias Assessment Tool (PROBAST). A total of 45 articles fulfilled the inclusion criteria. Our review revealed that the application of AI-based radiomics model as an ancillary tool for improved decision-making in HNC management includes radiomics-based cancer diagnosis and radiomics-based cancer prognosis. The radiomics-based cancer diagnosis includes tumor staging, tumor grading, and classification of malignant and benign tumors. Similarly, radiomics-based cancer prognosis includes prediction for treatment response, recurrence, metastasis, and survival. In addition, the challenges in the implementation of these models for clinical evaluations include data imbalance, feature engineering (extraction and selection), model generalizability, multi-modal fusion, and model interpretability. Considering the highly subjective and interobserver variability that is peculiar to the interpretation of medical images by expert clinicians, AI-based radiomics seeks to offer potentially useful quantitative information, which is not visible to the human eye or unintentionally often remains ignored during clinical imaging practice. By enabling the extraction of this type of information, AI-based radiomics has the potential to revolutionize HNC oncology, providing a platform for more personalized, higher quality, and cost-effective care for HNC patients. [ABSTRACT FROM AUTHOR]

Endonasal endoscopic surgery (EES) has been applied to the management of sinonasal (SN) tumors based on recent advances in endoscopic surgical techniques and technologies over the past three decades. EES has been mainly indicated for benign tumors and less aggressive malignant tumors. Notwithstanding this, EES has been gradually adopted for squamous cell carcinoma (SCC), which is the most common histology among SN malignancies. However, an analysis of the outcomes of EES for patients with SCC is difficult because most articles included SCC a wide range of different tumor histologies. Therefore, we herein review and clarify the current status of EES focusing on SCC from an oncological perspective. The oncologic outcomes and the ability to achieve a histologically complete resection are similar between endoscopic and open approaches in highly selected patients with SN-SCC. Surgical complications associated with EES are likely similar for SN-SCC compared to other sinonasal malignancies. The indications for a minimally invasive approach such as EES in the management of patients with SN-SCC should be stricter than those for less aggressive malignant tumors because of the aggressive nature of SCC. Also, it is important to achieve negative surgical margins with EES in patients with SCC. We believe that the indications for EES for SN-SCC are widening due to advances in diagnostic imaging, and endoscopic surgical techniques and technologies. However, while expanding the indications for EES for SN-SCC we must carefully confirm that the outcomes support this strategy. [ABSTRACT FROM AUTHOR]

The purpose of this study was to review the outcomes of the different therapies for extracranial head and neck arteriovenous malformations (AVMs). AVMs are high-flow congenital vascular anomalies. They are composed of a complex system of vessels directly connecting feeding arteries to draining veins forming a nidus. They may be potentially life-threatening due to progressive symptoms and infiltrative disease. Extracranial AVMs most commonly affect the head and neck area (47.4%) followed by the extremities (28.5%). AVMs are best characterized as being either focal or diffuse. Focal AVMs have good outcomes following adequate treatment. Diffuse lesions have multiple feeding vessel, which results in high rates of recurrence despite treatment. The management of AVMs includes conventional surgery and endovascular techniques. A combination of embolization and surgical resection has become the treatment of choice over the last years. The main goal of both forms of treatment being the complete blockage or resection of the nidus. Transcatheter embolization of vessels has evolved over the years and new embolic agents have emerged. The types of materials available for embolization are classified into mechanical devices, liquid agents and particulates. Efficacy, rate of recurrence and most common complications were evaluated. AVMs recurrence after embolization or resection is reported in up to 80% of cases. Incomplete resection and embolization can induce aggressive growth of the remaining nidus and the risk of progression is up to 50% within the first 5 years and recurrences can occur up to 10 years later. Although ethanol seems to be associated with the highest degree of cure and permanent occlusion, the overall complication rate reported was 48%. Other materials, such as cyanoacrylate, have obtained modest rates of complete remission, while the reported rates of complete regression of AVMs with Fibrin glue and Polyvinyl alcohol are above 50%. At present, there are no unified agreement on the ideal embolic agent. Therefore, a multidisciplinary approach is recommended to support decision making about the best therapeutic approach and to achieve optimal outcome. A long-term post-treatment follow-up is recommended to recognize early recurrence. [ABSTRACT FROM AUTHOR]

• Multiple neurological structures and organs are inadvertently irradiated during radiotherapy for head and neck cancer. • Radiation-associated neurological complications significantly impair patients' quality of life. • This article reviews ten distinct radiation-associated neurological complications in head and neck cancer survivors who underwent modern radiotherapy. • Current incidence data, prevention strategies, and potential management options of these complications are discussed. Radiotherapy is one of the mainstay treatment modalities for the management of non-metastatic head and neck cancer (HNC). Notable improvements in treatment outcomes have been observed in the recent decades. Modern radiotherapy techniques, such as intensity-modulated radiotherapy and charged particle therapy, have significantly improved tumor target conformity and enabled better preservation of normal structures. However, because of the intricate anatomy of the head and neck region, multiple critical neurological structures such as the brain, brainstem, spinal cord, cranial nerves, nerve plexuses, autonomic pathways, brain vasculature, and neurosensory organs, are variably irradiated during treatment, particularly when tumor targets are in close proximity. Consequently, a diverse spectrum of late neurological sequelae may manifest in HNC survivors. These neurological complications commonly result in irreversible symptoms, impair patients' quality of life, and contribute to a substantial proportion of non-cancer deaths. Although the relationship between radiation dose and toxicity has not been fully elucidated for all complications, appropriate application of dosimetric constraints during radiotherapy planning may reduce their incidence. Vigilant surveillance during the course of survivorship also enables early detection and intervention. This article endeavors to provide a comprehensive review of the various neurological complications of modern radiotherapy for HNC, summarize the current incidence data, discuss methods to minimize their risks during radiotherapy planning, and highlight potential strategies for managing these debilitating toxicities. [ABSTRACT FROM AUTHOR]

• Boron neutron capture therapy (BNCT) was effective in the treatment of locally recurred inoperable squamous cell head and neck cancer despite conventional photon radiotherapy in history. • Forty-seven (68%) of the 69 evaluable patients responded; 25 (36%) achieved complete response with BNCT. • A small tumor size and a high minimum tumor dose from BNCT were identified as factors that predict for response and survival. Head and neck squamous cell carcinoma (HNSCC) that recurs locally is a therapeutic challenge. We investigated the efficacy of boron neutron capture therapy (BNCT) in the treatment of such patients and the factors associated with treatment response and survival. Seventy-nine patients with inoperable, locally recurred HNSCC were treated with l -boronophenylalanine-mediated BNCT in Espoo, Finland, between February, 2003 and January, 2012. Prior treatments consisted of surgery and conventionally fractionated radiotherapy to a median cumulative dose of 66 Gy (interquartile range [IQR], 59–70 Gy) administered with or without concomitant chemotherapy. Tumor response was assessed using the RECISTv.1.0 criteria. Forty patients received BNCT once (on 1 day), and 39 twice. The median time between the 2 treatments was 6 weeks. Forty-seven (68%; 95% confidence interval [CI], 57–79%) of the 69 evaluable patients responded; 25 (36%) had a complete response, 22 (32%) a partial response, 17 (25%) a stable disease lasting for a median of 4.2 months, and 5 (7%) progressed. The patients treated with BNCT twice responded more often than those treated once. The median follow-up time after BNCT was 7.8 years. The 2-year locoregional progression-free survival rate was 38% and the overall survival rate 21%. A high minimum tumor dose and a small volume were independently associated with long survival in a multivariable analysis. Most patients responded to BNCT. A high minimum tumor dose from BNCT was predictive for response and survival. [ABSTRACT FROM AUTHOR]

Abstract The pattern of clinical behaviour and response to treatment of recurrent and/or metastatic head and neck squamous cell carcinoma is heterogeneous. Treatment strategies that can be employed vary from potentially curative salvage surgery and re-irradiation to palliative systemic therapies and best supportive care. The advent of new therapeutic options, in terms of more sophisticated surgical approaches and techniques, highly conformal and precise radiation techniques and immunotherapy may offer improved control of disease and longer survival. Moreover, the epidemiological changes during the last decades, including the increase of human papilloma virus-related oropharyngeal primary tumors, are also reflected in the recurrent and metastatic setting. In this complex context the identification of predictive and prognostic factors is urgently needed to tailor treatment, to increase its efficacy, and to avoid unnecessary toxicities. A better knowledge of prognosis may also help the patients and caregivers in decision making on the optimal choice of care. The purpose of our review is to highlight the current evidence and shortcomings in this field. [ABSTRACT FROM AUTHOR]

Abstract Purpose Few studies have reported large inter-observer variations in target volume selection and delineation in patients treated with radiotherapy for head and neck squamous cell carcinoma. Consensus guidelines have been published for the neck nodes (see Grégoire et al., 2003, 2014), but such recommendations are lacking for primary tumour delineation. For the latter, two main schools of thoughts are prevailing, one based on geometric expansion of the Gross Tumour Volume (GTV) as promoted by DAHANCA, and the other one based on anatomical expansion of the GTV using compartmentalization of head and neck anatomy. Method For each anatomic location within the larynx, hypopharynx, oropharynx and oral cavity, and for each T-stage, the DAHANCA proposal has been comprehensively reviewed and edited to include anatomic knowledge into the geometric Clinical Target Volume (CTV) delineation concept. A first proposal was put forward by the leading authors of this publication (VG and CG) and discussed with opinion leaders in head and neck radiation oncology from Europe, Asia, Australia/New Zealand, North America and South America to reach a worldwide consensus. Results This consensus proposes two CTVs for the primary tumour, the so called CTV-P1 and CVT-P2, corresponding to a high and lower tumour burden, and which should be associated with a high and a lower dose prescription, respectively. Conclusion Implementation of these guidelines in the daily practice of radiation oncology should contribute to reduce treatment variations from clinicians to clinicians, facilitate the conduct of multi-institutional clinical trials, and contribute to improved care of patients with head and neck carcinoma. [ABSTRACT FROM AUTHOR]

The overall assessment of tumor-infiltrating lymphocytes (TILs) evaluated using hematoxylin and eosin (HE) staining has been recently studied in oropharyngeal squamous cell carcinoma (OPSCC). We conducted a systematic review of Scopus, Ovid Medline, PubMed, Web of Science, and Cochrane Library to retrieve studies assessing TILs in HE-stained sections of OPSCC. We used fixed-effect models and random-effect models to estimate the pooled hazard ratios (HRs) and confidence intervals (CIs) for disease-free survival (DFS), overall survival (OS) and disease-specific survival (DSS). Eleven studies were identified that had analyzed the prognostic significance of TILs in OPSCC using HE-stained specimens. Our meta-analyses showed that a high infiltration of TILs was significantly associated with improved DFS (HR 0.39, 95%CI 0.24–0.65, P = 0.0003), OS (HR 0.38, 95%CI 0.29–0.50, P < 0.0001), and DSS (HR 0.32, 95%CI 0.19–0.53, P < 0.0001). Findings of our meta-analysis support a growing body of evidence indicating that assessment of TILs in OPSCC using HE-stained sections has reliable prognostic value. The clinical significance of such assessment of TILs has been reported repeatedly in many studies on OPSCC. The assessment is cost-effective, feasible, easy to transfer from lab to clinic, and therefore can be incorporated in daily practice. [ABSTRACT FROM AUTHOR]