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Chronic subdural hematoma (CSDH) development involves inflammatory, angiogenetic, and fibrinolytic mechanisms, several components of which are now unraveled through intensive research. The urokinase plasminogen activator receptor (uPAR) is part of the plasminogen activator system and possesses inflammatory, angiogenetic, and fibrinolytic capabilities. As a first, this study aims to identify uPAR in the hematoma fluid, hematoma membrane, dura mater, and systemic blood from patients with CSDH and, if present, to investigate if the uPAR level at the time of surgery may be a predictor for later developing recurrent CSDH. uPAR expression in the hematoma membrane and dura mater was analyzed using immunohistochemistry and presented as the H-score of the positive immunostaining. The uPAR levels in the hematoma fluid and systemic blood were determined using a multiplex antibody bead kit (Luminex). Samples were collected at the time of the first CSDH surgery, and in the case of recurrent CSDH within 90 days, the samples were again collected at reoperation. A comparison of uPAR expression between the hematoma membrane and dura mater, as well as uPAR levels in systemic blood and hematoma fluid, was performed using the Wilcoxon rank sum test. We included 112 patients, 26 of whom had recurrent CSDH. The median hematoma uPAR level was 22,125 (14,845–33,237) and significantly higher than the median systemic blood level of 789 pg/L (465–2,088) (p < 0.001). Similarly, the uPAR level of the hematoma membrane was 14.3 (7.54–44.8) and significantly higher than the dural uPAR level of 0.81 (0.3–1.98) (p < 0.001). For the first time, we identified uPAR in the subdural fluid, hematoma membrane, dura mater, and systemic blood from patients with CSDH. The high expression of uPAR in the subdural fluid and hematoma membrane indicates that the mechanisms of CSDH are predominantly in the subdural fluid collection and surrounding hematoma membrane.

The detection of lymph node metastases is a major challenge in oral and oropharyngeal squamous cell carcinoma (OSCC and OPSCC). 68Ga-NOTA-AE105 is a novel positron emission tomography (PET) radioligand with high affinity to urokinase-type plasminogen activator receptor (uPAR), a receptor expressed on the surfaces of tumor cells. The aim of this study was to investigate the diagnostic value of uPAR-PET/CT (computerized tomography) in detecting regional metastatic disease in patients with OSCC and OPSCC compared to the current imaging work-up. In this phase II trial, patients with OSCC and OPSCC referred for surgical treatment were prospectively enrolled. Before surgery, 68Ga-NOTA-AE105 uPAR-PET/CT was conducted, and SUVmax values were obtained from the primary tumor and the suspected lymph nodes. Histology results from lymph nodes were used as the standard of truth of metastatic disease. The diagnostic values of 68Ga-uPAR-PET/CT were compared to conventional routine preoperative imaging results (CT and/or MRI). The uPAR expression in resected primary tumors and metastases was determined by immunohistochemistry and quantified digitally (H-score). A total of 61 patients underwent uPAR-PET/CT. Of the 25 patients with histologically verified lymph node metastases, uPAR-PET/CT correctly identified regional metastatic disease in 14 patients, with a median lymph node metastasis size of 14 mm (range 3–27 mm). A significant correlation was found between SUVmax and the product of the H-score and tumor depth (r = 0.67; p = 0.003). The sensitivity and specificity of uPAR-PET/CT in detecting regional metastatic disease were 56% and 100%, respectively. When added to CT/MRI, uPAR-PET was able to upstage 2/11 (18%) of patients with occult metastases and increase the sensitivity to 64%. The sensitivity and specificity of 68Ga-NOTA-AE105 uPAR-PET/CT were equivalent to those of CT/MRI. The significant correlation between SUVmax and uPAR ex

Purpose: The purpose of this single-blinded, 2-centre, randomized controlled trial was to test if near-infrared (NIR) autofluorescence image guidance for parathyroid gland (PG) detection during total thyroidectomy can reduce the incidence of hypoparathyroidism in both malignant and benign cases. Method: Patients admitted for primary or completion total thyroidectomy were randomized to either the NIR intervention group or the standard care NONIR (no near infrared) group. The primary endpoint was the rate of hypoparathyroidism at the 3-month follow-up, defined as hypocalcemia and inappropriately low parathyroid hormone levels and/or continuous treatment with active vitamin D. The secondary endpoint was the PG identification rate. Results: A total of 147 patients were included of whom 73 were allocated to NIR. Primary or completion thyroidectomy was conducted in 84 and 63 cases, respectively. A total of 130 completed 3 months follow-up. Postoperative hypoparathyroidism in the NIR group at 12 h, 1 month and 3 months was, respectively, 31.8, 14.1, 6.5% compared with 35.9, 18.9, 11.8% in the NONIR group (all p > 0.46). In the NIR group, the identification rate of PGs was 69.5% (146 of 210 PGs), and 9% (19 of 210 PGs) were identified only due to additional use of NIR. For 15 out of 69 patients (21.7%) additionally PGs was found. Conclusion: Hypoparathyroidism was nominally less frequent in the NIR group, although not statistically significant. Further studies are needed to confirm if NIR may be a supportive PG identification tool to minimize the number of PG which would have been otherwise missed, especially during more complicated thyroid procedures. Trial registry: ClinicalTrials.gov: NCT04193332. Registration date: 16.08.2019.

INTRODUCTION: Breast adenomyoepithelioma is a very uncommon tumor, which is generally considered to be benign, however malignant transformation has been reported. PRESENTATION OF CASE: We report two cases of two women with breast adenomyoepithelioma. CONCLUSION: Diagnosis of adenomyoepithelioma is challenging because tumor may mimic other breast diseases. It has neither specific clinical signs nor radiological features, and the diagnosis is based on histopathological examination of the lesion. The treatment of choice is surgery. The type of surgery depends on the tumor factors and breast size. In malignant cases treatment such as radiotherapy, chemotherapy, immunotherapy may be used as well. It is very important to give an adequate treatment, otherwise the risk of tumor recurrence, growth or even metastatic spread, when tumor has malignant potential, increases.

INTRODUCTION. Thyroid nodules are very common and constitute an increasing clinical challenge since improved imaging capabilities and utilisation have led to a higher number of incidental findings. Ultrasoundguided fine-needle aspiration biopsy (FNAB) is the standard diagnostic tool in the work-up of thyroid nodules suspected of malignancy. Non-diagnostic results remain common and require repeated FNAB, leading to increased costs and delayed treatment of thyroid diseases, including treatment of thyroid cancer. If cytological diagnoses cannot be achieved, surgery may be warranted, which may potentially lead to overtreatment. Optimisation of the FNAB procedure is therefore essential. Spinal needles with a stylet have been found to lead to fewer non-diagnostic results, but studies on the subject are few.METHODS. This is a multicentre, two-arm, randomised clinical trial. Adults with thyroid nodules suspected of malignancy will be included consecutively. A total of 350 patients will be assigned randomly 1:1 to have a FNAB with either a spinal (25G) or a conventional (25G) needle. The primary outcome is the rate of diagnostic cytological samples according to the Bethesda system. Secondary outcomes are patient-experienced pain, complication rate and sensitivity and specificity.CONCLUSIONS. This trial will explore whether FNAB from thyroid nodules employing spinal needles compared with conventional fine needles improves diagnostic results, thereby providing evidence-based recommendations for a future choice of the FNAB needle. Secondary outcomes are patient-experienced pain, complication rate and sensitivity and specificity.

The clinical introduction of molecular imaging for the management of oropharyngeal squamous cell carcinoma (OPSCC) relies on the identification of relevant cancer-specific biomarkers. The application of three membrane-bound receptors, namely urokinase-type plasminogen activator receptor (uPAR), tissue factor (TF) and EGFR have been previously explored for targeted imaging and therapeutic strategies in a broad range of solid cancers. The present study aimed to investigate the expression patterns of uPAR, EGFR and TF by immunohistochemistry (IHC) to evaluate their potential for targeted imaging and prognostic value in OPSCC. In a retrospective cohort of 93 patients with primary OPSCC, who were balanced into the 45 human papillomavirus (HPV)-positive and 48 HPV-negative groups, the IHC-determined expression profiles of uPAR, TF and EGFR in large biopsy or tumor resection specimens were analyzed. Using the follow-up data, overall survival (OS) and recurrence-free survival were measured. Specifically, associations between survival outcome, biomarker expression and clinicopathological factors were examined using Cox proportional hazards model and log-rank test following Kaplan-Meier statistics. After comparing the expression pattern of biomarkers within the tumor compartment with that in the adjacent normal tissues, uPAR and TF exhibited a highly tumor-specific expression pattern, whereas EGFR showed a homogeneous expression within the tumor compartment as well as a consistent expression in the normal mucosal epithelium and salivary gland tissues. The positive expression rate of uPAR, TF and EGFR in the tumors was 98.9, 76.3 and 98.9%, respectively. No statistically significant association between biomarker expression and survival outcome could be detected. Higher uPAR expression levels had a trend towards reduced OS according to results from univariate analysis (P=0.07; hazard ratio=2.01; 95% CI=0.92-4.37). Taken together, these results suggest that uPAR, TF and EGFR

Silicone implants have been used for breast augmentations, both cosmetically and in reconstructive surgery since the 1960s. Rupture of breast implants and silicone migration is a well-known complication. In this case report and literature review, we present a case of a 53-year-old woman with bilateral cosmetic silicone gel breast implant in 1986, and a replacement with saline gel in 2005. The patient had no breast complaints and observed no change in breast volume during this period. In 2020, silicone was randomly identified in a right-sided cervical lymph node in an attempt to remove suspicious lymphadenopathy. The source of the silicone is still doubted; that is, it is not known if the silicone originated from the saline implant or the silicone gel implant. In our literature review, we find that distant migration of silicone and lymphadenopathy have occurred for silicone breast implants although very rare for saline gel breast implants.

RATIONALE: Tumor biopsy cannot detect heterogeneity and an association between heterogeneity in functional imaging and molecular biology will have an impact on both diagnostics and treatment possibilities.PURPOSE: Multiparametric imaging can provide 3D information on functional aspects of a tumor and may be suitable for predicting intratumor heterogeneity. Here, we investigate the correlation between intratumor heterogeneity assessed with multiparametric imaging and multiple-biopsy immunohistochemistry.METHODS: In this prospective study, patients with primary or recurrent head and neck squamous cell carcinoma (HNSCC) underwent PET/MRI scanning prior to surgery. Tumors were removed en bloc and six core biopsies were used for immunohistochemical (IHC) staining with a predefined list of biomarkers: p40, p53, EGFR, Ki-67, GLUT1, VEGF, Bcl-2, CAIX, PD-L1. Intratumor heterogeneity of each IHC biomarker was quantified by calculating the coefficient of variation (CV) in tumor proportion score among the six core biopsies within each tumor lesion. The heterogeneity in the imaging biomarkers was assessed by calculating CV in 18F-fluorodeoxyglucose (FDG)-uptake, diffusion and perfusion. Concordance of the two variance measures was quantified using Spearman's rank correlation RESULTS: Twenty-eight patients with a total of 33 lesions were included. There was considerable heterogeneity in most of the IHC biomarkers especially in GLUT1, PD-L1, Ki-67, CAIX and p53, however we only observed a correlation between the heterogeneity in GLUT1 and p53 and between Ki-67 and EGFR. Heterogeneity in FDG uptake and diffusion correlated with heterogeneity in cell density.CONCLUSION: Considerable heterogeneity of IHC biomarkers was found, however, only few and weak correlations between the studied IHC markers were observed. The studied functional imaging biomarkers showed weak associations with heterogeneity in some of the IHC biomarkers. Thus, biological heterogeneity is

Background: Comorbidity is presumed to impact survival of head and neck squamous cell cancer (HNSCC) patients. However, the prevalence and prognostic impact of comorbidity in these patients is not yet well established. The aim of this study is to outline the comorbidity burden of HNSCC patients and investigate the relation to overall survival and cancer-specific mortality.Methods: The comorbidity burden of patients registered with HNSCC in the Danish Cancer Registry between 1980 and 2014 was evaluated based on the Charlson Comorbidity Index (CCI). Patients' risks of comorbid conditions compared to age- and gender-matched controls were estimated by odds ratios (OR). The impact of comorbidity on overall survival and cancer-specific mortality was evaluated by Cox regression and Kaplan-Meier survival analysis.Results: A total of 25,388 HNSCC patients were included (72.5% male; mean age 63.2 years at diagnosis; median follow-up 3.0 years). CCI at diagnosis was significantly higher in patients compared to controls (p < 0.001). The most common comorbid conditions among the patients were additional non-metastatic malignancy (10.9%) and cerebrovascular disease (7.7%). Compared to controls, patients had higher odds of metastatic malignancy (OR: 4.65; 95% CI: 4.21-5.15; p < 0.001), mild liver disease (OR: 6.95; 95% CI: 6.42-7.53; p < 0.001), and moderate-severe liver disease (OR: 7.28; 95% CI: 6.14-8.65; p < 0.001). The multivariate Cox analysis revealed increasing hazard ratios with increasing CCI and in coherence the Kaplan-Meier curves showed poorer overall survival and increased cancer-specific mortality in patients with higher CCI.Conclusion: HNSCC patients' comorbidity burden was significantly greater compared to the general population and increased comorbidity was correlated with increased cancer-related mortality.

BACKGROUND: The purpose of this study is to test if functional multiparametric imaging with 18F-FDG-PET/MRI correlates spatially with immunohistochemical biomarker status within a lesion of head and neck squamous cell carcinoma (HNSCC), and also whether a biopsy with the highest FDG uptake was more likely to have the highest PD-L1 expression or the highest percentage of vital tumour cells (VTC) compared with a random biopsy.METHODS: Thirty-one patients with HNSCC were scanned on an integrated PET/MRI scanner with FDG prior to surgery in this prospective study. Imaging was quantified with SUV, ADC and Ktrans. A 3D-morphometric MRI scan of the specimen was used to co-register the patient and the specimen scans. All specimens were sectioned in consecutive slices, and slices from six different locations were selected randomly from each tumour. Core biopsies were performed to construct TMA blocks for IHC staining with the ten predefined biomarkers. The spatial correlation was assessed with a partial correlation analysis.RESULTS: Twenty-eight patients with a total of 33 lesions were eligible for further analysis. There were significant correlations between the three imaging biomarkers and some of the IHC biomarkers. Moreover, a biopsy taken from the most FDG-avid part of the tumour did not have a statistically significantly higher probability of higher PD-L1 expression or VTC, compared with a random biopsy.CONCLUSION: We found statistically significant correlations between functional imaging parameters and key molecular cancer markers.

Background: Isolated regional recurrences following head-neck squamous-cell carcinomas (HNSCC) are often accessible for curatively intended salvage treatment. Factors prognostic for outcome were investigated in a large cohort of HNSCC patients. Methods: In total, 1811 patients receiving curatively intended radiotherapy from 2007 to 2017 were reviewed and isolated cervical nodal recurrences were identified. Factors associated with survival and second recurrence were investigated using univariate and multivariate analyses. Results: Isolated regional recurrence was seen in 95/1811 (5.2%) patients. Eighty of 95 patients (84%) received salvage surgery. Two-year survival after isolated regional recurrence was 40%. Overall survival (OS) and time to second recurrence were associated with resection status of the salvage surgery and presence of extranodal spread (ENS), while p16-positive oropharyngeal squamous-cell carcinoma (OPSCC) was associated with better OS. Conclusion: Long-term survival after regional recurrence in HNSCC is possible. p16-positive OPSCC, complete salvage surgery, and lack of ENS are associated with better outcome.

Introduction: Lymph node yield (LNY) in neck dissection has been identified as a prognostic factor in oral cavity cancer. The purpose of this study was to investigate the impact of additional use of optical imaging on LNY in therapeutic ND in oral cancer. Methods: Consecutive patients with oral squamous cell carcinoma with clinical neck metastasis planned for primary tumor resection were randomized to conventional neck dissection or near-infrared fluorescence (NIRF)-guided neck dissection, respectively. In the intervention group, patients were injected with ICG-Nanocoll prior to surgery. Intraoperatively, an optical hand-held camera system was used for lymph node identification. Also, NIRF imaging of the neck specimen was performed, and optical signals were pinned with needle markings to guide the pathological examination. The endpoint of the study was LNY per neck side in levels Ib-III. Results: 31 patients were included with 18 neck sides in the control group and 18 neck sides in the intervention group for evaluation. During NIRF-guided ND, individual lymph nodes could be identified by a bright fluorescent signal and individual tumor-related drainage patterns could be observed in the neck. The LNY in the intervention group was significantly higher compared to the control group (p = 0.032) with a mean of 24 LN (range: 12–33 LN in levels Ib-III compared to 18 LN (range: 10–36 LN) in the control group, respectively. Conclusions: NIRF-guided ND significantly improved the nodal yield compared to the control group. Intraoperative real-time optical imaging enabled direct visualization of tumor-related drainage patterns within the neck lymphatics.

Jakob Schmidt Jensen,1 Kathrine Kronberg Jakobsen,1 Christian Mirian,1 Julie Thor Christensen,1 Katrine Schneider,1 Arvin Nahavandipour,1 Vibe Lindeblad Wingstrand,1 Irene Wessel,1 Jesper Filtenborg Tvedskov,1 Thomas Frisch,1 Anders Christensen,1 Lena Specht,2 Elo Andersen,3 Giedrius Lelkaitis,4 Christian Grønhøj,1 Christian von Buchwald11Department of Otorhinolaryngology, Head and Neck Surgery, and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen 2100, Denmark; 2Department of Oncology, Rigshospitalet, University of Copenhagen, Copenhagen 2100, Denmark; 3Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev 2730, Denmark; 4Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen 2100, DenmarkCorrespondence: Christian von BuchwaldDepartment of Otorhinolaryngology, Head and Neck Surgery, and Audiology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, Copenhagen 2100, DenmarkTel +45 3 545 2370Email Christian.von.buchwald@regionh.dkObjective: The aim was to establish a large comprehensive database of patients with oral cavity squamous cell carcinoma (OSCC) to enable surveillance and research of the disease.Methods: All patients diagnosed and/or treated for OSCC at Rigshospitalet, University of Copenhagen, Denmark in the period 2000–2014 were included. Rigshospitalet is a tertiary treatment center and covers the Eastern Denmark region, comprising nearly half of the approximately 5.8 million inhabitants of Denmark. Data on numerous variables regarding general information of the patients at diagnosis, their primary cancer, recurrence, treatment, prior cancers, and secondary cancers were collected from the Danish Pathology Register and by evaluation of medical charts.Results: One thousand three hundred and ninety-nine OSCC patients were included in the database (62% males). The median age at diagnosis was 63 years (range: 23–99 years). The most common anatomical locatio