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The molecular pathogenesis of salivary gland acinic cell carcinoma (AciCC) is poorly understood. The secretory Ca-binding phosphoprotein (SCPP) gene cluster at 4q13 encodes structurally related phosphoproteins of which some are specifically expressed at high levels in the salivary glands and constitute major components of saliva. Here we report on recurrent rearrangements [t(4;9)(q13;q31)] in AciCC that translocate active enhancer regions from the SCPP gene cluster to the region upstream of Nuclear Receptor Subfamily 4 Group A Member 3 (NR4A3) at 9q31. We show that NR4A3 is specifically upregulated in AciCCs, and that active chromatin regions and gene expression signatures in AciCCs are highly correlated with the NR4A3 transcription factor binding motif. Overexpression of NR4A3 in mouse salivary gland cells increases expression of known NR4A3 target genes and has a stimulatory functional effect on cell proliferation. We conclude that NR4A3 is upregulated through enhancer hijacking and has important oncogenic functions in AciCC. Acinic cell carcinoma (AciCC) is a rare salivary gland carcinoma that is poorly understood. Here the authors perform genomic, transcriptomic and epigenomic profiling of AciCC and find highly recurrent and specific rearrangements [t(4;9)(q13;q31)], which lead to enhancer hijacking that activates oncogenic transcription factor NR4A3.

Hearing loss is one of the most common disorders worldwide. It affects communicative abilities in all age groups. However, it is well known that elderly people suffer more frequently from hearing loss. Two different model approaches were employed: A generalised linear model and a random forest regression model were used to quantify the relationship between pure-tone hearing loss, age, and speech perception. Both models were applied to a large clinical data set of 19,801 ears, covering all degrees of hearing loss. They allow the estimation of age-related decline in speech recognition for different types of audiograms. Our results show that speech scores depend on the specific type of hearing loss and life decade. We found age effects for all degrees of hearing loss. A deterioration in speech recognition of up to 25 percentage points across the whole life span was observed for constant pure-tone thresholds. The largest decrease was 10 percentage points per life decade. This age-related decline in speech recognition cannot be explained by elevated hearing thresholds as measured by pure-tone audiometry.

Background Extramedullary plasmacytoma (EMP) is a solitary tumor consisting of neoplastic plasma cells, with very little to no bone marrow involvement. EMPs are usually located in the head and neck region, but can also occur along the digestive tract, in lungs, or extremities. Methods Following our publication on EMP, which appeared in 1999 (Cancer 85:2305–14), we conducted a literature search for EMP‐related reports published between 1999 and 2021. The documented cases, as well as 14 of our own patients from the ENT Clinic Erlangen, were extensively analyzed. Results Between 1998 and 2021, 1134 patients with EMP were reported, for whom information about the tumor localization was available. Among those, 62.4% had EMP in the head and neck area and 37.6% in other body regions. Data on therapy were reported in 897 patients, including 34.3% who received radiation, 28.1% surgery, 22.6% a combination of surgery and radiation, and 15.9% another therapy. In 76.9% patients no recurrence or transformation to multiple myeloma (MM) was reported, 12.8% showed local recurrence and 10.2% developed MM. Radiotherapy alone was associated with a tendency for increased occurrence of MM. In patients with EMP of head and neck area, combination therapy (surgery and radiation) resulted in a 5‐year overall survival rate of 98.3%, surgery alone of 92.4%, and radiotherapy of 92.7%. Conclusions Collectively, our analyses indicate that surgical resection alone can achieve long‐term tumor control in patients with EMP, if the tumor can be removed within safe limits without causing serious functional impairment. However, if this is not certain, either radiation or a combination of surgery and radiation therapy is suggested as an effective means of local tumor control. This paper provides an overview of the extramedullary plasmacytoma cases reported between 1999 and 2021. The global patients’ cohort and the current therapy options are compared to our previous report from 1999.

Head and neck cancer is a common disease and is associated with a poor prognosis. A promising approach to improving patient outcomes is personalized treatment, which uses information from a variety of modalities. However, only little progress has been made due to the lack of large public datasets. We present a multimodal dataset, HANCOCK, that comprises monocentric, real-world data of 763 head and neck cancer patients. Our dataset contains demographical, pathological, and blood data as well as surgery reports and histologic images, that can be explored in a low-dimensional representation. We can show that combining these modalities using machine learning is superior to a single modality and the integration of imaging data using foundation models helps in endpoint prediction. We believe that HANCOCK will not only open new insights into head and neck cancer pathology but also serve as a major source for researching multimodal machine-learning methodologies in precision oncology. Head and neck cancer patients could greatly benefit from personalised treatment, but a lack of large public datasets hampers this potential. Here, the authors present HANCOCK, a multimodal dataset that integrates demographical, clinical, and histopathological data for 763 head and neck cancer patients that empowers machine learning models for clinical outcome prediction.

Background: Ultrasound is established as a diagnostic tool in salivary glands for obstructive diseases such as sialolithiasis and tumors. Concerning inflammatory diseases and in non-sialolithiasis-caused obstruction, much fewer data are available. In recent years, technical development has allowed a better assessment of the gland parenchyma, and knowledge about intraductal pathologies has increased considerably, which has provided new insights and a new interpretation of ultrasound findings. Objectives: To provide a comprehensive review of the literature that includes our own experiences and to point out the state of the art in ultrasound in the diagnostics of inflammatory and obstructive salivary gland diseases, taking adequate techniques and recent technical developments into consideration. Data sources and study eligibility criteria: A systematic literature search was performed in Pubmed using various specific key words. Results: According to the literature results, including our own experiences, ultrasound is of value in up to >90% of cases presenting with inflammatory and/or obstructive diseases. Technical developments (e.g., elastography) and the application of modified ultrasound techniques (e.g., transoral ultrasound) have contributed to these results. Today, ultrasound is considered a first-line diagnostic tool in these diseases. However, in some inflammatory diseases, the final diagnosis can be made only after inclusion of the anamnesis, clinical symptoms, serologic blood tests, or histopathologic investigation. Conclusions: Ultrasound can be considered as a first-line diagnostic tool in obstructive and inflammatory salivary gland diseases. In obstructive diseases, it may be sufficient for diagnostics in >90% of cases. In inflammatory diseases, ultrasound is at least an excellent screening method and can be used to establish the diagnosis in cases of an early suspicion. In all diseases ultrasound can contribute to better management and can be used for monitoring during follow-up.

Background Over the last decades numerous initiatives have been set up that aim at translating the best available medical knowledge and treatment into clinical practice. The inherent complexity of the programs and discrepancies in the terminology used make it difficult to appreciate each of them distinctly and compare their specific strengths and weaknesses. To allow comparison and stimulate dialogue between different programs, we in this paper provide an overview of the German Cancer Society certification program for multidisciplinary cancer centers that was established in 2003. Main body In the early 2000s the German Cancer Society assessed the available information on quality of cancer care in Germany and concluded that there was a definite need for a comprehensive, transparent and evidence-based system of quality assessment and control. This prompted the development and implementation of a voluntary cancer center certification program that was promoted by scientific societies, health-care providers, and patient advocacy groups and based on guidelines of the highest quality level (S3). The certification system structures the entire process of care from prevention to screening and multidisciplinary treatment of cancer and places multidisciplinary teams at the heart of this program. Within each network of providers, the quality of care is documented using tumor-specific quality indicators. The system started with breast cancer centers in 2003 and colorectal cancer centers in 2006. In 2017, certification systems are established for the majority of cancers. Here we describe the rationale behind the certification program, its history, the development of the certification requirements, the process of data collection, and the certification process as an example for the successful implementation of a voluntary but powerful system to ensure and improve quality of cancer care. Conclusion Since 2003, over 1 million patients had their primary tumors treated in a certified center. There are now over 1200 sites for different tumor entities in four countries that have been certified in accordance with the program and transparently report their results from multidisciplinary treatment for a substantial proportion of cancers. This led to a fundamental change in the structure of cancer care in Germany and neighboring countries within one decade.

Purpose Although neural networks have shown remarkable performance in medical image analysis, their translation into clinical practice remains difficult due to their lack of interpretability. An emerging field that addresses this problem is Explainable AI. Methods Here, we aimed to investigate the ability of Convolutional Neural Networks (CNNs) to classify head and neck cancer histopathology. To this end, we manually annotated 101 histopathological slides of locally advanced head and neck squamous cell carcinoma. We trained a CNN to classify tumor and non-tumor tissue, and another CNN to semantically segment four classes - tumor, non-tumor, non-specified tissue, and background. We applied Explainable AI techniques, namely Grad-CAM and HR-CAM, to both networks and explored important features that contributed to their decisions. Results The classification network achieved an accuracy of 89.9% on previously unseen data. Our segmentation network achieved a class-averaged Intersection over Union score of 0.690, and 0.782 for tumor tissue in particular. Explainable AI methods demonstrated that both networks rely on features agreeing with the pathologist’s expert opinion. Conclusion Our work suggests that CNNs can predict head and neck cancer with high accuracy. Especially if accompanied by visual explanations, CNNs seem promising for assisting pathologists in the assessment of cancer sections.

Background: Immunological and rheological properties are important factors of the surfactant protein (SP) family, whose impact on tumorigenesis is not yet known, although some SPs have been identified as tumor marker candidates for various malignancies. This study describes the detection of the two surfactant family proteins SP-G and PLUNC in healthy glottis, the presence of SP-G in glottic cancer, and the in vitro tissue regeneration potential of SP-G and PLUNC on epithelial cells. Methods: The expression and distribution of SP-G and PLUNC were investigated immunohistochemically in squamous cell carcinomas of the vocal folds. The expression of both proteins was analyzed by Western blot in micro-dissected healthy vocal fold mucosa from body donors. The hypopharyngeal squamous carcinoma cell line (FaDu) was used as an in vitro model for wound healing experiments with Electric cell–substrate impedance sensing (ECIS). Results: The results show the presence of SP-G and PLUNC in epithelial cells of the healthy vocal folds and the submucosal glands of the vestibular folds. SP-G was detected in squamous cell carcinomas of the vocal folds. SP-G and PLUNC show accelerated wound healing of FaDu cells in vitro. Conclusions: SP-G and PLUNC were first detected in the vocal fold of the human larynx. SP-G shows a distinct presence in glottic carcinoma, whose relevance needs to be determined in future studies. SP-G and PLUNC exhibit a positive influence on the repair mechanisms of epithelial lesions of the glottis. The data presented form the basis for follow-up studies focusing on the impact of SP-G in glottic cancer development and the potentially meaningful clinical effect of SP-G and PLUNC on tissue repair of the human vocal fold.

BackgroundTo determine safety and efficacy of single cycle induction treatment with cisplatin/docetaxel and durvalumab/tremelimumab in stage III-IVB head and neck cancer.MethodsPatients received a single cycle of cisplatin 30 mg/m² on days 1–3 and docetaxel 75 mg/m² on day 1 combined with durvalumab 1500 mg fix dose on day 5 and tremelimumab 75 mg fix dose on day 5. Patients with pathologic complete response (pCR) in the rebiopsy after induction treatment or at least 20% increase of intratumoral CD8+ cell density in the rebiopsy compared with baseline entered radioimmunotherapy with concomitant durvalumab/tremelimumab. The objective of this interim analysis was to analyze safety and efficacy of the chemoimmunotherapy-induction treatment before radioimmunotherapy.ResultsA total of 57 patients were enrolled, 56 were treated. Median pretreatment intratumoral CD8+ cell density was 342 cells/mm². After induction treatment, 27 patients (48%) had a pCR in the rebiopsy and further 25 patients (45%) had a relevant increase of intratumoral CD8+ cells (median increase by a factor of 3.0). Adverse event (AE) grade 3–4 appeared in 38 patients (68%) and mainly consisted of leukopenia (43%) and infections (29%). Six patients (11%) developed grade 3–4 immune-related AE. Univariate analysis computed p16 positivity, programmed death ligand 1 immune cell area and intratumoral CD8+ cell density as predictors of pCR. On multivariable analysis, intratumoral CD8+ cell density predicted pCR independently (OR 1.0012 per cell/mm², 95% CI 1.0001 to 1.0022, p=0.016). In peripheral blood CD8+ cells, the coexpression of programmed death protein 1 significantly increased especially in patients with pCR.ConclusionsSingle cycle induction treatment with cisplatin/docetaxel and durvalumab/tremelimumab is feasible and achieves a high biopsy-proven pCR rate.

Background There is a large lack of evidence for optimal treatment in oligometastatic head and neck cancer and it is especially unclear which patients benefit from radical local treatment of all tumour sites. Methods 40 patients with newly diagnosed oligometastatic head and neck cancer received radical local treatment of all tumour sites from 14.02.2008 to 24.08.2018. Primary endpoint was overall survival. Time to occurrence of new distant metastases and local control were evaluated as secondary endpoints as well as prognostic factors in univariate und multivariate Cox’s regression analysis. To investigate the impact of total tumour volume on survival, all tumour sites were segmented on baseline imaging. Results Radical local treatment included radiotherapy in 90% of patients, surgery in 25% and radiofrequency ablation in 3%. Median overall survival from first diagnosis of oligometastatic disease was 23.0 months, 2-year survival was 48%, 3-year survival was 37%, 4-year survival was 24% and 5-year survival was 16%. Median time to occurrence of new distant metastases was 11.6 months with freedom from new metastases showing a tail pattern after 3 years of follow-up (22% at 3, 4- and 5-years post-treatment). In multivariate analysis, better ECOG status, absence of bone and brain metastases and lower total tumour volume were significantly associated with improved survival, whereas the number of metastases and involved organ sites was not. Conclusions Radical local treatment in oligometastatic head and neck cancer shows promising outcomes and needs to be further pursued. Patients with good performance status, absence of brain and bone metastases and low total tumour volume were identified as optimal candidates for radical local treatment in oligometastatic head and neck cancer and should be considered for selection in future prospective trials.