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Background: Adenoid cystic carcinoma (ACC) is a rare type of cancer commonly occurring in salivary glands. It is characterized by slow but infiltrative growth, nerve infiltration and overall poor prognosis, with late recurrence and distant metastasis. The treatment of ACC is still limited to surgery and/or (adjuvant) radiotherapy. Till now no promising systemic therapy option exists. However, various studies deliver promising results after treatment with anti-angiogenetic agents, such as anti-EGFR-antibody Cetuximab or Tyrosinkinase inhibitor Lenvatinib. Methods: By using of immunohistological methods we analyzed and compared the macrophage and lymphocyte populations, vascularization, and PD-L1-status in 12 ACC of the salivary glands. Results: All cases showed a significant elevation of macrophages with M2 polarization and a higher vascularization in ACC compared to normal salivary gland tissue. The CD4/CD8 quotient was heterogenous. ACC does not show relevant PD-L1 expression. Conclusions: The predominant M2 polarization of macrophages in ACC could be responsible for elevated vascularization, as already been proved in other cancer types, that M2 macrophages promote angiogenesis. [ABSTRACT FROM AUTHOR]

Purpose: Several theories have been proposed regarding the origin of lateral neck cysts (LNC). Besides complete surgical resection ipsilateral tonsillectomy and dissection of a tract or its remnants is sometimes recommended. In this retrospective trial we wanted to evaluate if patients, who received LNC resection only, develop complications or recurrence to justify this surgical strategy. Methods: Patients who received LNC resection between 2004 and 2017 at the Ear Nose and Throat Department of a university hospital were included. Data was collected from the clinic database and through a structured telephone interview. Results: A total of 126 patients met the inclusion criteria. In this collective, the diagnosis of a lateral neck cyst was confirmed histologically. Mean age at time of operation was 38 years (± 14.6). The median follow-up time was 7 years (range 3–18). None of the participants experienced recurrent unilateral pharyngitis or tonsillitis during follow-up. Furthermore, there was no case of postoperative peritonsillar, neck phlegmon or neck abscess. No patient reported recurrence of LNC. Conclusions: Sole complete resection of LNCs is sufficient to avoid postoperative infections and recurrences. Therefore, ipsilateral tonsillectomy and tract dissection is not necessary in routine cases of LNC surgery. [ABSTRACT FROM AUTHOR]

Background: We aimed to evaluate multiparametric ultrasound, to achieve a better understanding of the baseline characteristics of suspected cervical lymph node metastases in head and neck cancer before induction chemotherapy or chemoradiation. Methods: From February 2020 to April 2021, our complete ultrasound examination protocol was carried out on clinically evident malignant lymph nodes of histologically proven HNSCC in the pre-therapeutic setting. Results: A total of 13 patients were eligible for analysis. Using elastography, irregular clear hardening in areas in the center of the lymph node could be detected in all cases. Elastographic Q-analysis showed a significantly softer cortex compared to the center and surrounding tissue. The time–intensity curve analysis showed high values for the area under the curve and a short time-to-peak (fast wash-in) in all cases compared to the surrounding tissue. A parametric evaluation of contrast enhanced the ultrasound in the early arterial phase and showed an irregular enhancement from the margin in almost all investigated lymph nodes. These results show that the implementation of comprehensive, multiparametric ultrasound is suitable for classifying suspected lymph node metastasis more precisely than conventional ultrasound alone in the pre-therapeutic setting of HNSCC. Thus, these parameters may be used for improvements in the re-staging after chemoradiation or neoadjuvant therapy monitoring, respectively. [ABSTRACT FROM AUTHOR]

The establishment of novel biomarkers in liquid biopsies of cancer patients has come more into focus in prognostic and diagnostic research efforts. Due to their prognostic relevance disseminated tumor cells or circulating tumor cells are the subject of intensive research and are discussed as early diagnostic indicators for treatment failure and the formation of micrometastases. A potential association of this early-systemic tumor component with poor prognosis of cancer patients could be already demonstrated for various entities including breast, colon, lung, melanoma, ovarian and prostate cancers. Thus, the detection of circulating tumor cells seems to be also applicable for minimal-invasive monitoring of therapy progress in head and neck cancer patients. A major problem of the use in clinical routine is that circulating tumor cells could not be detected by modern imaging techniques. To overcome these limitations highly sensitive detection methods and techniques for their molecular characterization are urgently needed allowing mechanistic understanding and targeting of circulating tumor cells. Especially the medical application of nanotechnology (nanomedical methods) has made valuable contributions to the field. Here, we want to provide a comprehensive overview on (nanomedical) detection methods for circulating tumor cells and discuss their merits, pitfalls and future perspectives especially for head and neck solid squamous cell carcinoma (HNSCC) patients. [ABSTRACT FROM AUTHOR]

The objective of this study is to analyze the outcome of treatment for solitary fibrous tumors (SFTs) in the head and neck area. SFTs present as slow-growing masses, often with local compressive symptoms that are difficult to distinguish from other soft-tissue tumors. SFTs are commonly treated using local excision without adjuvant therapy. To date, only heterogeneous small series have been published, documenting the treatment results and outcome with these tumors. Retrospective study of patients with histopathologically confirmed SFT treated at two tertiary referral hospitals between 2004 and 2014. Eight men and four women with histologically confirmed SFT were identified in the records. Their age range was 37-82 years (mean 57.8 years). The mean follow-up period for eight patients was 6.75 years (range 1-24 years). Four patients were lost to follow-up. Sublocalizations were neck ( n = 3), orbit ( n = 2), paranasal sinus ( n = 2), cheek ( n = 2), hard palate ( n = 1), parotid gland ( n = 1), and tongue ( n = 1). The first-line treatment for all of the tumors identified was surgical excision. In four cases, the surgical margins were narrow or unclear due to piecemeal resection in the paranasal sinus and orbit ( n = 3) or a tumor location deep in the parapharyngeal space ( n = 1). Recurrences developed in two of these cases (in the orbit and parapharyngeal space), and the other two patients were lost to follow-up. Radiotherapy and chemotherapy were not administered as first-line treatments. Overall, the local recurrence rate ( n = 2/8) was 25 %. The disease-specific survival rate was 100 %. These results are consistent with the literature data and show that safe surgical excision, without opening of the tumor capsule, reduces the risk of local recurrence and leads to a favorable outcome. Tumors in the head and neck often represent a surgical challenge, and wide surgical margins are rarely possible due to the complex three-dimensional anatomic compartments in the region. Head and neck surgeons should therefore be aware that there is an increased risk of recurrence in these patients; tightly scheduled follow-up visits are mandatory for at least 10 years, if not longer. Radiotherapy only appears to be an option in patients with unresectable tumors or when wide surgical excision would cause severe functional morbidity. [ABSTRACT FROM AUTHOR]

Metastatic cervical lymph nodes are a frequent finding in head and neck squamous cell carcinoma (HNSCC). If a non-surgical approach is primarily chosen, a therapy response evaluation of the primary tumor and the affected lymph nodes is necessary in the follow-up. Supplementary contrast-enhanced ultrasound (CEUS) can be used to precisely visualize the microcirculation of the target lesion in the neck, whereby malignant and benign findings differ in their uptake behavior. The same applies to many other solid tumors. For various tumor entities, it has already been shown that therapy monitoring is possible through regular contrast-enhanced sonography of the primary tumor or the affected lymph nodes. Thus, in some cases, maybe in the future, a change in therapy strategy can be achieved at an early stage in the case of non-response or, in the case of therapy success, a de-escalation of subsequent (surgical) measures can be achieved. In this paper, a systematic review of the available studies and a discussion of the potential of therapy monitoring by means of CEUS in HNSCC are presented. [ABSTRACT FROM AUTHOR]

The lymph node ratio (LNR) combines two types of information-about the extent of neck dissection and about the extent of the pathological examination of the specimen-and thus represents an interesting variable for risk assessment in patients with head and neck cancer. This retrospective study with data from January 1, 1980, to December 31, 2010, evaluates the utility of the LNR as a potential prognostic predictor in patients with laryngeal squamous cell carcinoma (LSCC). A total of 202 consecutive patients with regionally metastasized LSCC who underwent primary surgery with or without adjuvant treatment were included. The mean follow-up period was 4.4 years. The LNR was calculated as the ratio of positive nodes to the total number of nodes removed during neck dissection. Multivariate analysis was carried out. Peak values as averaged clusters of individual LNRs were registered at three points (LNR 0.05, 0.07, and 0.09). LNR 0.09 was a significant prognostic parameter in the Cox regression model ( P = 0.007). Patients with an LNR > 0.09 had a hazard ratio of 2.065 for a disease-specific survival event in comparison with LNR < 0.09. The most accurate LNR for LSCC is expected to be located in the range of 0.08-0.1. The LNR seems to be of limited value for the decision-making process in the treatment of patients with LSCC, in comparison with other locations. Prospective trials will be required in order to allow evidence-based recommendations for treatment decisions based on the LNR. [ABSTRACT FROM AUTHOR]

To evaluate the utility of lymph node ratio (LNR) as a potential prognostic predictor and to test whether LNR may be useful as a potential selection criterion for adjuvant treatment in patients with oropharyngeal squamous cell carcinoma (OPSSC). This retrospective study included 384 patients with regionally metastasized OPSCC who underwent primary surgery with or without adjuvant therapy from 1980 to 2010. LNR was calculated as the ratio of positive lymph nodes to the total number of lymph nodes removed during neck dissection. Statistical analysis using a Cox regression model was carried out. The 5-year disease-specific survival (DSS) was 73 %. An individual LNR peak at 0.1 was closest to the median of 0.0909, and both were set as cut-off values. Patients in the group greater than median had a hazard ratio (HR) of 2.472 for a DSS event; this was close to an HR of 2.513 for LNR >0.1. In multivariate analysis, LNR showed a markedly stronger HR with regard to survival in comparison with the grouped pN classification. The covariate treatment modality did not meet the assumption of the Cox regression, and it was therefore not possible to comment reasonably on the issue of whether LNR could be a potential selection criterion for adjuvant treatment. Lymph node ratio is in itself a valuable additional prognostic factor for risk stratification. According to the current results, the most valuable LNR for OPSSC is expected to be located in the range from 0.09 to 0.1. Further investigations in large prospective trials will be required to allow evidence-based recommendations for treatment decisions based on the LNR. [ABSTRACT FROM AUTHOR]

Conclusion: In pT2 floor of mouth cancer (FOMC), a standardized neck dissection (ND) should be carried out, due to the high risk of occult metastases. In cases of pT1 carcinomas with a clinically negative neck using high imaging standards and expertise a tight 'wait and watch' strategy can be used. Objective: To report on the oncologic results with primary surgical treatment of pT1/pT2 FOMC and to examine the benefit of elective ND in cN0. Methods: This was a retrospective study design including 216 patients who were treated between 1980 and 2010 for pT1/2 FOMC. The 5-year disease-specific survival (DSS), local and (loco)regional control based on the T and N classification and depth of infiltration were investigated. Results: DSS was 79.5% and (loco)regional control was 89.8%. DSS in patients staged pN0 was significantly higher, at 84.6%, than in those staged pN+, at 60%. ND was performed in 165 patients, and adjuvant therapy was administered in 124 patients. Ninety patients (41.7%) were staged cN0, and 53.3% of them underwent elective ND. The risk of occult metastases was 4.8% in pT1 and 28.6% in pT2. A depth of infiltration of ≥ 5 mm showed a markedly higher relative frequency of occult neck metastases and pN+ status. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the medium- to long-term functional and oncologic results when the myocutaneous platysma flap (MPF) was used for defect reconstruction of the oral cavity and the pharynx in selected patients. The MPF was used in 70 patients for closure of small to medium-sized defects. 37.1 % of the tumors were in the oral cavity, 24.3 % in the oropharynx and 38.6 % in the hypopharynx. Histopathological risk factors, adjuvant therapy, recurrence rates, and survival rates were assessed. Rehabilitation of swallowing and airways function was analyzed. UICC staging was I in 18.6 %, II in 15.7 %, III in 18.6 %, and IV in 47.1 %. Histopathological risk factors were noted in 51.4 and 84.3 % patients received adjuvant treatment. Recurrences were observed in 27.2 %. The 5-year recurrence-free survival rate was 63.1 %, and the disease-specific survival rate was 66.7 %. Permanent tracheostomy closure was achieved in 74.4 %, and complete recovery of swallowing in 57.4 %. Analysis of the functional and oncologic data after defect closure with the MPF showed acceptable results. The MPF should be included in the range of surgical methods for closure of small to medium-sized defects in the head and neck region in selected patients. [ABSTRACT FROM AUTHOR]

This study evaluated the myocutaneous platysma flap (MPF) as an alternative to free flaps for closing defects after head and neck tumor resection in selected cases. MPFs were used to close small to medium-sized full-thickness oral and pharyngeal defects after surgery for tumors staged cT1-3 (oral cavity 37.1%, oropharynx 24.3%, hypopharynx 38.6%) in 70 patients. Flap-related complications developed in 27% of cases (partial necrosis 7%, total necrosis 3%, salivary fistula 11.4%, bleeding/hematoma 5.7%) and donor-site complications in 10%. Defect closure was adequate in 97%; 62.5% of the patients required intraoperative tracheotomies (closed again in 72.5%). Postoperative swallowing was not significantly disturbed in 72% of the patients. The MPF allows closure of small to medium-sized defects in the head and neck region in selected patients, with acceptable aesthetic and functional outcomes. The success rate (>90%) is comparable with surgical alternatives associated with considerably greater surgical effort and risk. [ABSTRACT FROM AUTHOR]

Background: It has previously been shown that the viability of swine uteri can be maintained within the physiological range in an open perfusion model for up to 8 hours. The aim of this study was to assess mediumto long-term perfusion of swine uteri using a modified Krebs-Ringer bicarbonate buffer solution (KRBB) in the established open perfusion model. Methods: In an experimental study at an infertility institute, 30 swine uteri were perfused: group 1: n = 11, KRBB; group 2: n = 8, modified KRBB with drainage of perfusate supernatant; group 3: n = 11, modified KRBB with drainage of perfusate every 2 h and substitution with fresh medium. Modified and conventional KRBB were compared with regard to survival and contraction parameters: intrauterine pressure (IUP), area under the curve (AUC), and frequency of contractions (F). Results: Modified KRBB showed significantly higher IUP, AUC, and F values than perfusion with conventional KRBB. In group 3, the organ survival time of up to 17 h, with a 98% rate of effective contraction time, differed significantly from group 1 (P < 0.001). Conclusions: Using modified KRBB in combination with perfusate substitution improves the open model for perfusion of swine uteri with regard to survival time and quality of contraction parameters. This model can be used for medium- to long-term perfusion of swine uteri, allowing further metabolic ex vivo studies in a cost-effective way and with little logistic effort. [ABSTRACT FROM AUTHOR]

This report describes a rare case of histopathologically confirmed glomus faciale tumor. The role of imaging in the differential diagnosis is discussed and therapeutic options are evaluated, along with a review of the previous literature on glomus faciale tumors. A 39-year-old male patient presented with total peripheral facial nerve paralysis. He underwent radical tumor resection and facial nerve grafting for a histopathologically confirmed paraganglioma of the facial nerve. He is now tumor-free after a 4-year follow-up period, and the functional outcome after primary nerve grafting is satisfactory. Facial nerve paragangliomas are a rare cause of facial nerve paralysis. Early imaging using computed tomography and magnetic resonance imaging is essential to clarify the differential diagnosis and assess the location and extent of the tumor. Precise pathological diagnosis requires additional targeted immunohistochemical examinations. The treatment of choice in patients with preoperative facial nerve paralysis is radical tumor resection with nerve reconstruction. [ABSTRACT FROM AUTHOR]

Simple Summary: As the incidence of thyroid lesions in Europe is rising, more and more people affected by thyroid pathologies seek treatment in a clinic. Every suspicious thyroid nodule needs to be confirmed as benign or malignant in order to be treated correctly. Unnecessary invasive diagnostics and thyroid surgery should be avoided. The aim of this retrospective study was to improve the distinction between benign and malignant nodules by using new high-performance multiparametric ultrasound examination techniques. By analyzing 122 thyroid nodules we created a score-based system combining B-mode, shear-wave elastography and contrast-enhanced ultrasound malignancy criteria. This system allows for a quite accurate detection of thyroid carcinomas with a sensitivity of 95% and specificity of 75.49%. Shear-wave elastography and contrast-enhanced ultrasound can detect unique malignancy features, which cannot be found in B-mode. Therefore, these criteria would present a relevant addition to the B-mode TI-RADS classification. Background: The aim was to improve preoperative diagnostics of solid non-cystic thyroid lesions by using new high-performance multiparametric ultrasound examination techniques. Methods: Multiparametric ultrasound consists of B-mode, shear-wave elastography and contrast enhanced ultrasound (CEUS) including Time-Intensity-Curve (TIC) analysis. A bolus of 1–2.4 mL Sulfur Hexafluorid microbubbles was injected for CEUS. Postoperative histopathology was the diagnostic gold standard. Results: 116 patients were included in this study. 102 benign thyroid nodules were diagnosed as well as 20 carcinomas. Suspicious B-mode findings like microcalcifications, a blurry edge and no homogeneous sonomorphological structure were detected in 60, 75 and 80% of all carcinomas but only in 13.7, 36.3 and 46.1% of all benign lesions. The average shear-wave elastography measurements of malignant lesions (4.6 m/s or 69.8 kPa centrally and 4.2 m/s or 60.1 kPa marginally) exceed the values of benign nodules. Suspicious CEUS findings like a not-homogeneous wash-in and a wash-out were detected almost twice as often in carcinomas. Conclusion: Multiparametric ultrasound offers new possibilities for the preoperative distinction between benign and malignant thyroid nodules. A score based system of B-mode, shear-wave and CEUS malignancy criteria shows promising results in the detection of thyroid carcinomas. It reaches a sensitivity of 95% and specificity of 75.49%. [ABSTRACT FROM AUTHOR]

Simple Summary: PD-L1 expression determines patients' eligibility for immunotherapy. Current sampling does not consider the heterogeneity of PD-L1 expression in head and neck squamous cell carcinoma (HNSCC) within the primary tumor. Moreover, potential differences are not considered when comparing primary tumors and their associated metastases or local recurrences, hereby excluding potential responders to immunotherapy. Here, we investigated the inter-sample heterogeneity of PD-L1 expression by analyzing multiple samples from individual patients. Multisection staining revealed clinically relevant CPS changes, which would have potentially affected treatment decisions in 28.7% (intra-tumoral), 44.4% (tumor vs. metastases), and 61.5% (initial tumor vs. local recurrence) of patients, respectively, compared with single-region staining. Increased CPS in primary tumors and lymph node metastases were associated with improved 5-year overall survival. Our results suggest that multiple tumor sections should be evaluated in HNSCC patients when assessing PD-L1 expression prior to potential immunotherapy, particularly if the initial result was negative. For practical reasons, in many studies PD-L1 expression is measured by combined positive score (CPS) from a single tumor sample. This does not reflect the heterogeneity of PD-L1 expression in head and neck squamous cell carcinoma (HNSCC). We investigated the extent and relevance of PD-L1 expression heterogeneity in HNSCC analyzing primary tumors and recurrences (LRs), as well as metastases. Tumor tissue from 200 HNSCC patients was immunohistochemically stained for PD-L1 and analyzed using image-analysis software QuPath v3.4 with multiple specimens per patient. CPS was ≥20 in 25.6% of primary tumors. Intra-tumoral heterogeneity led to a therapeutically relevant underestimation of PD-L1 expression in 28.7% of patients, when only one specimen per patient was analyzed. Inter-tumoral differences in PD-L1 expression between primary tumors and lymph node metastasis (LNM) or LR occurred in 44.4% and 61.5% (CPS) and in 40.6% and 50% of cases (TPS). Overall survival was increased in patients with CPS ≥ 1 vs. CPS < 1 in primary tumors and LNM (hazard ratio: 0.46 and 0.35; p < 0.005); CPS in LR was not prognostic. Our analysis shows clinically relevant intra- and inter-sample heterogeneity of PD-L1 expression in HNSCC. To account for heterogeneity and improve patient selection for immunotherapy, multiple sample analyses should be performed, particularly in patients with CPS/TPS < 1. [ABSTRACT FROM AUTHOR]

Background: Handheld ultrasound (HHUS) devices have chiefly been deployed in emergency medicine, where they are considered a valid tool. The data situation is less clear in the case of internal questions in abdominal sonography. In our study, we investigate whether HHUS devices from different manufacturers differ in their B-scan quality, and whether any differences are relevant for the significance of an internal ultrasound examination. Method: The study incorporated eight HHUS devices from different manufacturers. Ultrasound videos of seven defined sonographic questions were recorded with all of the devices. The analogue recording of the same findings with a conventional high-end ultrasound (HEUS) device served as an evaluation criterion. Then, the corresponding findings were played side by side and evaluated by fourteen ultrasound experts using a point scale (5 points = very good; 1 point = insufficient). Results: The HHUS devices achieved relatively good results in terms of both the B-scan quality assessment and the ability to answer the clinical question, regardless of the manufacturer. One of the tested HHUS devices even achieved a significantly (p < 0.05) higher average points score in both the evaluation of B-scan quality and in the evaluation of clinical significance than the other devices. Regardless of the manufacturer, the HHUS devices performed best when determining the status/inferior vena cava volume and in the representation of ascites/free fluid. Conclusion: In various clinical abdominal sonography questions, HHUS systems can reliably reproduce findings, and are—while bearing their limitations in mind—an acceptable alternative to conventional HEUS systems. Irrespective of this, the present study demonstrated relevant differences in the B-scan quality of HHUS devices from different manufacturers. [ABSTRACT FROM AUTHOR]

Aims: Reporting of head and neck ultrasound (HNU) has been outlined to be a major obstacle during ultrasound training due to a lack of standardized structure, content and terminology. Consequently, overall report quality differs significantly between various examiners posing a severe risk factor for information loss and miscommunication. Therefore, the present study's purpose is to compare the overall quality of free text reports (FTR) and structured reports (SR) of HNU at various stages of training in order to determine the optimal educational level to implement SR.Material and Methods: Typical pathologies in HNU were reported upon using SR and FTR by medical students, junior residents and senior residents. The reports were assessed for overall quality, time efficiency and readability. Additionally, user satisfaction was determined using a questionnaire.Results: SRs exhibited a significantly superior report quality (93.1% vs. 45.6%, p<0.001) at all training levels. Overall time efficiency was significantly better for SRs, especially at the stages of medical school and early residency (89.4 s vs. 160.2 s., p<0.001). Using structured reporting also increased user satisfaction significantly (VAS 8.6 vs. 3.9, p<0.001).Conclusions: Implementing structured reporting of HNU results in a superior report quality at all training stages. Greatest benefits for time efficiency are achieved by implementation during medical school. Therefore, structured reporting of HNU should be implemented early on in the training of HNU. [ABSTRACT FROM AUTHOR]

Background: ultrasound diagnostics have a broad spectrum of applications, including among diseases of the musculoskeletal system. Accordingly, it is important for the users to have a well-founded and up-to-date education in this dynamic examination method. The right balance between online and in-class teaching still needs to be explored in this context. Certifying institutions are currently testing digitally transformed teaching concepts to provide more evidence. Methods: this study compared two musculoskeletal ultrasound blended learning models. Model A was more traditional, with a focus on in-person teaching, while Model B was more digitally oriented with compulsory webinar. Both used e-learning for preparation. Participants completed evaluations using a seven-point Likert scale, later converted to a 0–1 scale. Digital teaching media (e-learning) were used for preparation in both courses. Results: the analysis included n = 41 evaluations for Model A and n = 30 for Model B. Model B received a better overall assessment (median: 0.73 vs. 0.69, p = 0.05). Model B also excelled in "course preparation" (p = 0.02), "webinar quality" (p = 0.04), and "course concept" (p = 0.04). The "gain of competence" (p = 0.82), "learning materials" (p = 0.30), and "tutor quality" (p = 0.28) showed no significant differences. Conclusion: participants favorably assessed blended learning in ultrasound teaching. Certifying institutions should consider accrediting models that combine digital methods (e.g., internet lectures/webinars) and materials (e.g., e-learning) with hands-on ultrasound training. Further research is needed to validate these subjective findings for a stronger evidential basis. [ABSTRACT FROM AUTHOR]

In the head and neck area, a large proportion of clinically relevant fistulas occur in childhood. The present case describes the use of contrast enhanced ultrasound with intraductal administration of the contrast medium for preoperative visualization of the fistula duct in the case of a second brachial cleft fistula. This provided the surgeon with important additional information, such as the detailed course of the fistula and its relation to the large vessels of the neck. The method can help to improve surgical planning, reduce radiation exposure and to avoid imaging under general anesthesia, especially in children. [ABSTRACT FROM AUTHOR]

Background: Evaluating the tumor microenvironment and its influence on clinical management and therapy response is becoming increasingly important. However, only a few studies deal with the spatial distribution of immune cells within the tumor. This study aimed to describe the topology of immune cells in the microenvironment of oral squamous cell carcinoma (OSCC) sectioned by tumor invasion front and tumor center and to test their prognostic relevance regarding patient survival. Methods: A total of 55 OSCC patient specimens were collected retrospectively. The cancer tissue was immunohistochemically stained using an automated tissue stainer Ventana Benchmark Ultra (Roche) and analyzed using discrete expression marker profiles on immune cells. We investigated CD4+ lymphocytes, CD8+ lymphocytes, CD68+ macrophages, CD163+ macrophages, and M1 macrophages regarding their spatial distribution. Results: The statistical analysis revealed that the quantity and distribution of CD4+ (p = 0.007), CD8+ (p < 0.001), CD68+ (p < 0.001), CD163+ cells (p = 0.004), and M1 (p < 0.001) macrophages were significantly higher at the invasion front compared to the tumor center in all observed cases. However, high and low immune cell counts in the tumor center and invasion front were not associated with overall survival. Conclusion: Our results show two distinct immune microenvironments of the tumor center compared to the invasion front. Future studies are needed to explore how these results can be leveraged to improve patient therapy and outcome. [ABSTRACT FROM AUTHOR]

In Germany, progress assessments in head and neck ultrasonography training have been carried out mainly theoretically and lack standardisation. Thus, quality assurance and comparisons between certified courses from various course providers are difficult. This study aimed to develop and integrate a direct observation of procedural skills (DOPS) in head and neck ultrasound education and explore the perceptions of both participants and examiners. Five DOPS tests oriented towards assessing basic skills were developed for certified head and neck ultrasound courses on national standards. DOPS tests were completed by 76 participants from basic and advanced ultrasound courses (n = 168 documented DOPS tests) and evaluated using a 7-point Likert scale. Ten examiners performed and evaluated the DOPS after detailed training. The variables of "general aspects" (6.0 Scale Points (SP) vs. 5.9 SP; p = 0.71), "test atmosphere" (6.3 SP vs. 6.4 SP; p = 0.92), and "test task setting" (6.2 SP vs. 5.9 SP; p = 0.12) were positively evaluated by all participants and examiners. There were no significant differences between a basic and advanced course in relation to the overall results of DOPS tests (p = 0.81). Regardless of the courses, there were significant differences in the total number of points achieved between individual DOPS tests. DOPS tests are accepted by participants and examiners as an assessment tool in head and neck ultrasound education. In view of the trend toward "competence-based" teaching, this type of test format should be applied and validated in the future. [ABSTRACT FROM AUTHOR]

To improve management of head and neck squamous cell carcinoma patients, we need to increase our understanding of carcinogenesis, to identify biomarkers, and drug targets. This study aimed to identify novel biomarkers by providing transcriptomics profiles of matched primary tumors, lymph node metastasis, and non-malignant tissue of 20 HNSCC patients as well as by bioinformatic analyses of a TCGA HNSCC cohort, comprising 554 patients. We provide cancer cell signaling networks differentially expressed in tumors versus metastases, such as mesenchymal–epithelial transition, and structural integrity networks. As a proof of principle study, we exploited the data sets and performed functional analyses of a novel cytokeratin, cytokeratin24 (cKRT24), which had not been described as biomarker for tumors before. Survival analysis revealed that low cKRT24 expression correlated with poor overall survival in HNSCC. Experimentally, downregulation of cKRT24 in primary tumors, metastases, and HNSCC cell lines was verified on mRNA and protein level. Cloning and ectopic overexpression of cKRT24 not only affected viability and growth of HNSSC cell lines, but also inhibited tumor growth in murine xenograft studies. We conclude that cKRT24 functions as a tumor suppressor in HNSCC, and may serve as an additional prognostic biomarker and novel target to support current HNSCC treatments. [ABSTRACT FROM AUTHOR]

The objective of the present study is to report on the clinical course and management of thyroglossal duct cysts. Retrospective review of all patients who underwent surgery for thyroglossal duct cysts between 2000 and 2013 at a tertiary referral center was carried out. The operations were performed using a modification of the Sistrunk operation: transcervical cystectomy, partial dissection of the hyoid bone, and dissection of all tracts identified during surgery. A total of 352 patients (176 men, 176 women) underwent surgery for a cyst ( n = 282) or discharging sinus ( n = 70). The mean age for the incidence of cysts was 26 years. Four of the patients (1.4 %) had a papillary thyroid carcinoma in the epithelium of the cyst. The follow-up period ranged from 7 months to 10 years. The overall recurrence rate was 4.5 %. Resection is often regarded as an elective surgical procedure in patients with thyroglossal duct cysts, but surgery should always be considered. Papillary thyroid carcinoma in the epithelium of the cyst is a rare but possible differential diagnosis. Dissection of all tracts found is recommended and partial dissection of the hyoid bone is mandatory. Dissection of the foramen cecum is not imperative. The recurrence rates with this approach are comparable to more extensive methods such as those described by Sistrunk. [ABSTRACT FROM AUTHOR]

Treatment of metastasized or recurrent oral (OSCC) and oropharyngeal (OPSCC) squamous cell carcinoma remains challenging. Targeted antibody-based therapy inter alia for PD-1 / PD-L1 axis shows promising results, but whether PD-L1 expression varies between the subentities remains unclear. The expression pattern of PD-L1 (EPR19759 antibody, Abcam, Berlin, Germany) and p16 (CINtech® Histology Kit, Ventana, Oro Valley, USA) was determined immunohistochemically and analyzed by HALO™ Image Analysis Software (Indica Lab, Albuquerque, USA). For PD-L1, combined positivity score (CPS), tumor proportion score (TPS) and histoscore, were assessed and results correlated with epidemiological data. In total, 161 patients (OSCC: n = 78, OPSCC: n = 83) were included. A mean of 43.6% (±34.0%) of the specimen showed increased PD-L1 expression that did not differ quantitatively between subentities (TPS: p = 0.159, CPS: p = 0.078), but qualitatively (histoscore: p = 0.003). In the mean follow-up period (45.6 months), contrary to age (p = 0.006) and advanced T-Status (p = 0.018), PD-L1 expression did not correlate with overall (OS, p = 0.191) and recurrence free survival (RFS: p = 0.193) in both subentities. No correlation of p16 and PD-L1 expression was found (p = 0.844). PD-L1 is differentially expressed between OSCC and OPSCC, however without influence on OS. Furthermore, p16 status was not related to PD-L1 expression. This may have implications for future (immune) therapeutical approaches for oral cancer. [ABSTRACT FROM AUTHOR]

Objectives. The aim of this study was to assess the efficacy of primary surgical treatment in the management of locally limited oral tongue carcinoma. Methods. A retrospective evaluation was carried out for all patients treated with primary surgery for pT1-pT2 oral tongue carcinomas at a tertiary referral center between 1980 and 2005. All cases were assessed for disease-specific survival and local control rates in relation to T classification, N classification, infiltration depth of the primary tumor, and decision making on neck management and adjuvant therapy. The cases were additionally evaluated for the incidence of major complications and tracheotomies. Results. 263 cases were assessed. The 5-year disease-specific survival rate was 75.2%. Positive neck disease was shown to be a significant negative prognostic factor. The occult metastasis rate was 20.2%. Conclusions. Primary surgical treatment is a very effective modality against T1-T2 oral tongue carcinoma, and a low rate of complications can be anticipated. [ABSTRACT FROM AUTHOR]

Objective. To compare long-term quality of life outcomes after treating early stage oropharyngeal carcinoma either with surgery, surgery combined with radiotherapy, or surgery combined with chemoradiotherapy. Methods. Questionnaire based method: 111 eligible patients agreed to fill out a quality of life questionnaire. Results. Of the 32 scales contained in the EORTC's combined QLQ-C30 and HN35, 11 scales show significantly better results for the surgery-only treatment group when compared to either surgery combined with radiotherapy or surgery combined with any type of adjuvant therapy. These eleven scales are role function (P = 0.019/0.008), social function (P = 0.01/0.034), nausea (P = 0.017/0.025), pain (P = 0.014/0.023), financial problems (P = 0.030/0.012), speech (P = 0.02/0.015), social eating (P = 0.003/<0.001), mouth opening (P = 0.033/0.016), sticky saliva (P = 0.001/<0.001), swallowing (P < 0.001/<0.001), and dry mouth (P < 0.001/0.001). Conclusion. Treatment of early stage oropharyngeal carcinoma with surgery alone has definite advantages over treatments including any formof adjuvant therapy when considering quality of life. Advantages manifest themselves especially in functional aspects of the head and neck realm; however general health aspects as well as psychosocial aspects show improvements as well. This study does not show any indication of QOL-related drawbacks of surgery-only treatment approaches. [ABSTRACT FROM AUTHOR]

Introduction Tonsillectomy and adenoidectomy are common procedures. Most surgeries in children and young adults are recommended due to recurring infections or obstructive constraints. However, occult malignant findings are reported in the literature. The clinical guidelines still refrain from recommending routine histopathologic analyses when discussing these procedures. Objective The present study aims to define the value of a routine histopathologic analysis after tonsillectomy, adenoidectomy and tonsillotomy. Methods We conducted a prospective survey including all German ear, nose and throat (ENT) departments, asking physicians about their current clinical practice and opinion. Furthermore, we reviewed all patients attending our department for tonsillectomy/adenoidectomy/tonsillotomy or a combination of these procedures between 2011 and 2016. In addition to this, a cost analysis was conducted to assess the financial burden of a routine histopathologic analysis. Results Most German ENT departments perform a routine histopathologic analysis after tonsillectomy/adenoidectomy/tonsillotomy. Despite this, only a minority deemed this approach necessary. Our retrospective review of the histopathologic analysis after tonsillectomy/adenoidectomy/tonsillotomy in our department rendered a cohort size of 2,157 patients. Within this group, there were no occult malignant findings. We found a yearly burden of 2,509,401€ for routine histopathologic analyses in patients under the age of 15 years in Germany in 2016. Conclusion We found a divergence between the physicians opinions and their current clinical practice concerning the question of whether to conduct routine histopathologic analyses. Even though there was no occult malignant finding in our cohort, unsuspected malignant findings are reported in the literature. Therefore, we call for a discussion on clinical practice guidelines. [ABSTRACT FROM AUTHOR]

Purpose: Free text reports (FTR) of head and neck ultrasound studies are currently deployed in most departments. Because of a lack of composition and language, these reports vary greatly in terms of quality and reliability. This may impair the learning process during residency. The purpose of the study was to analyze the longitudinal effects of using structured reports (SR) of head and neck ultrasound studies during residency. Methods: Attending residents (n = 24) of a tripartite course on head and neck ultrasound, accredited by the German Society for Ultrasound in Medicine (DEGUM), were randomly allocated to pictures of common diseases. Both SRs and FTRs were compiled. All reports were analyzed concerning completeness, acquired time and legibility. Overall user contentment was evaluated by a questionnaire. Results: SRs achieved significantly higher ratings regarding completeness (95.6% vs. 26.4%, p < 0.001), description of pathologies (72.2% vs. 58.9%, p < 0.001) and legibility (100% vs. 52.4%, p < 0.001) with a very high inter-rater reliability (Fleiss' kappa 0.9). Reports were finalized significantly faster (99.1 s vs. 115.0 s, p < 0.001) and user contentment was significantly better when using SRs (8.3 vs. 6.3, p < 0.001). In particular, only SRs showed a longitudinally increasing time efficiency (− 20.1 s, p = 0.036) while maintaining consistent completeness ratings. Conclusions: The use of SRs of head and neck ultrasound studies results in an increased longitudinal time-efficiency while upholding the report quality at the same time. This may indicate an additive learning effect of structured reporting. Superior outcomes in terms of comprehensiveness, legibility and time-efficiency can be observed immediately after implementation. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV)-related head and neck squamous cell carcinoma represents an important subgroup of head and neck cancer, but HPV occurs also in the less common neuroendocrine carcinomas (NEC). The PD-1/PD-L1 pathway appears to be activated in pulmonary NEC and correlates with a higher mutation burden, but the potential of NEC to respond to checkpoint inhibitors is unknown to a large extent.Objectives: To determine the HPV status of NEC of the head and neck region and to investigate the expression of PD-1 and its ligands PD-L1 and PD-L2.Methods: Surgical tumor samples from 2006 to 2017 were analyzed. HPV status was determined by p16 immunohistochemistry (IHC) and multiplex PCR. IHC using the Cologne Score was performed for PD-1, PD-L1, and PD-L2.Results: Seven NEC tumor samples were analyzed, three of them showed HPV type 18. Expression of PD-1 and PD-L1 differed widely and showed no correlation to HPV status. IHC showed an overexpression of PD-L2 in most of the patients.Conclusions and Significance: A multicentric analysis of NEC is needed to further evaluate the role of HPV as well as immunocheckpoints with regard to inflammatory immune response in genesis and clinical course of this rare tumor entity. Biomarkers for selection of novel treatment regimens, including immunotherapeutic approaches, are warranted. [ABSTRACT FROM AUTHOR]

Introduction: Radial forearm flap donor side defects can be treated by vacuum therapy and conventional wound dressing. The aim of this study was to compare different wound management considering wound healing, including risk factors and cost effectiveness. Materials and methods: Retrospective study including patients treated with radial flaps in the Department of Head and Neck Surgery in Erlangen from January 2005 to August 2013. Wound healing was assessed regarding complications considering several risk factors and comorbidities. Data were analyzed comparing conventional dressing and vacuum therapy, including a calculation of costs. Results: The study included 138 patients (n=55 conventional dressing; n=83 vacuum dressing). The incidence of wound complications in the vacuum group was 50.6 and 32.7% in the conventional dressing group (p=.058). The presence of risk factors and comorbidities did not have significant impact on the occurrence of complications. Costs for vacuum therapy turned out to be at least five times higher. Conclusion: In view of the current state of research, these results show that using vacuum dressings has no significant benefit in the wound management of forearm donor side defect covered with fullthickness skin grafts. If the costs and economical aspects are also considered, conventional wound dressing may be preferred. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the clinical relevance and prognostic value of preoperative and postoperative oesophagography in patients with Zenker's diverticulum. The medical records of 155 patients who underwent surgical treatment (with an endoscopic or transcervical approach) for Zenker's diverticulum between 1992 and 2010 in a tertiary referral centre were retrospectively evaluated. The size of the diverticula on oesophagography, recognizable muscular septum, and protection of the diverticulum were assessed relative to the surgical procedures performed. The incidence of diverticular remnants on postoperative oesophagography was also assessed relative to the surgical procedure. It was investigated whether the detection of a residual pharyngeal pouch and filling of it with contrast medium were related to the patients' immediate postoperative symptoms and the development of symptomatic recurrence. Larger diverticula (Brombart III-IV) were manageable significantly more often with endoscopic procedures ( P = 0.007). Residual diverticulum and filling with contrast medium were strongly associated with prolonged dysphagia immediately postoperatively ( P = 0.005 and P = 0.009, respectively). However, these parameters failed to correlate significantly with a symptomatic recurrence. Preoperative oesophagography proved to be extremely important for surgical planning, with the surgeon's personal preference seeming to be the driving indicator in many cases. Postoperative oesophagography is only useful for excluding postoperative complications in the immediate postoperative phase and did not have a prognostic value as to a recurrence of the disease. [ABSTRACT FROM AUTHOR]

Background: detailed information about circulating tumor cells (CTCs) as an indicator of therapy response and cancer metastasis is crucial not only for basic research but also for diagnostics and therapeutic approaches. Here, we showcase a newly developed IsoMAG IMS system with an optimized protocol for fully automated immunomagnetic enrichment of CTCs, also revealing rare CTC subpopulations. Methods: using different squamous cell carcinoma cell lines, we developed an isolation protocol exploiting highly efficient EpCAM-targeting magnetic beads for automated CTC enrichment by the IsoMAG IMS system. By FACS analysis, we analyzed white blood contamination usually preventing further downstream analysis of enriched cells. Results: 1 µm magnetic beads with tosyl-activated hydrophobic surface properties were found to be optimal for automated CTC enrichment. More than 86.5% and 95% of spiked cancer cells were recovered from both cell culture media or human blood employing our developed protocol. In addition, contamination with white blood cells was minimized to about 1200 cells starting from 7.5 mL blood. Finally, we showed that the system is applicable for HNSCC patient samples and characterized isolated CTCs by immunostaining using a panel of tumor markers. Conclusion: Herein, we demonstrate that the IsoMAG system allows the detection and isolation of CTCs from HNSCC patient blood for disease monitoring in a fully-automated process with a significant leukocyte count reduction. Future developments seek to integrate the IsoMAG IMS system into an automated microfluidic-based isolation workflow to further facilitate single CTC detection also in clinical routine. [ABSTRACT FROM AUTHOR]

Simple Summary: Growth factor expression is a negative prognostic factor in head and neck squamous cell carcinoma (HNSCC). Targeted therapy has a limited effect on the treatment of advanced stages due to evolving resistance mechanisms. The aim of this study was to assess the distribution of growth factor receptors in oropharyngeal squamous cell cancer (OPSCC) and evaluate their role in the context of the human papillomavirus status, prognosis and possible relevance for targeted therapy. Tissue microarrays of 78 primary OPSCC, 35 related lymph node metastasis, 6 distant metastasis and 9 recurrent tumors were manufactured to evaluate the expression of human epidermal growth factor receptor (EGFR/erbB/Her)1–4 and c-Met by immunohistochemistry. EGFR and c-Met are relevant negative prognostic factors especially in noxae-induced OPSCC. Thus, dual targeting of EGFR and c-Met could be a promising prospective target in OPSCC treatment. Frequent coexpression of assessed receptors represents a possible intrinsic resistance mechanism in targeted therapy. This study aimed to assess the distribution of growth factor receptors in oropharyngeal squamous cell cancer (OPSCC) and evaluate their role in the context of human papillomavirus (HPV) status, prognosis and potential relevance for targeted therapy. The protein expression of human epidermal growth factor receptor (Her)1–4 and c-Met were retrospectively assessed using semiquantitative immunohistochemistry on tissue microarrays and analyzed for correlations as well as differences in the clinicopathological criteria. Her1–4 and c-met were overexpressed compared to normal mucosa in 46%, 4%, 17%, 27% and 23%, respectively. Interestingly, most receptors were coexpressed. Her1 and c-Met were inversely correlated with p16 (p = 0.04; p = 0.02). Her2 and c-Met were associated with high tobacco consumption (p = 0.016; p = 0.04). High EGFR, Her3, Her4 and c-Met expression were associated with worse overall and disease-free survival (p ≤ 0.05). Furthermore, EGFR and c-Met expression showed raised hazard ratios of 2.53 (p = 0.02; 95% CI 1.24–5.18) and 2.45 (p = 0.02; 95% CI 1.13–5.35), respectively. Her4 was expressed less in distant metastases than in corresponding primary tumors and was correlated to a higher T category. EGFR and c-Met are relevant negative prognostic factors in OPSCC, independent of known clinicopathological parameters. We suggest dual targeting of EGFR and c-Met as a promising strategy for OPSCC treatment. [ABSTRACT FROM AUTHOR]