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In the absence of targeted treatment options, neoadjuvant chemotherapy (NACT) is applied widely for triple-negative breast cancer (TNBC). Response to NACT is an important parameter predictive of oncological outcomes (progression-free and overall survival). An approach to the evaluation of predictive markers enabling therapy individualization is the identification of tumor driver genetic mutations. This study was conducted to investigate the role of SEC62, harbored at 3q26 and identified as a driver of breast cancer pathogenesis, in TNBC. We analyzed SEC62 expression in The Cancer Genome Atlas database, and immunohistologically investigated SEC62 expression in pre- and post-NACT tissue samples from 64 patients with TNBC treated at the Department of Gynecology and Obstetrics/Saarland University Hospital/Homburg between January 2010 and December 2018 and compared the effect of SEC62 on tumor cell migration and proliferation in functional assays. SEC62 expression dynamics correlated positively with the response to NACT (p ≤ 0.01) and oncological outcomes (p ≤ 0.01). SEC62 expression stimulated tumor cell migration (p ≤ 0.01). The study findings indicate that SEC62 is overexpressed in TNBC and serves as a predictive marker for the response to NACT, a prognostic marker for oncological outcomes, and a migration-stimulating oncogene in TNBC.

Disturbances of retinal perfusion are involved in the onset and maintenance of several ocular diseases, including diabetic retinopathy, glaucoma, and retinal vascular occlusion. Hence, knowledge on ocular vascular anatomy and function is highly relevant for basic research studies and for clinical judgment and treatment. The retinal vasculature is composed of the superficial, intermediate, and deep vascular layer. Detection of changes in blood flow and vascular diameter especially in smaller vessels is essential to understand and to analyze vascular diseases. Several methods to evaluate blood flow regulation in the retina have been described so far, but no gold standard has been established. For highly reliable assessment of retinal blood flow, exact determination of vessel diameter is necessary. Several measurement methods have already been reported in humans. But for further analysis of retinal vascular diseases, studies in laboratory animals, including genetically modified mice, are important. As for mice, the small vessel size is challenging requiring devices with high optic resolution. In this review, we recapitulate different methods for retinal blood flow and vessel diameter measurement. Moreover, studies in humans and in experimental animals are described.

Purpose To evaluate the standard of care, in particular the use of topical or subconjunctival interferon-α2b, in treating ocular surface squamous neoplasia or melanocytic tumours in tertiary eye centres in Germany. Methods A survey containing 14 questions was sent to 43 tertiary eye centres in Germany. The questions addressed the surgical and medical management of ocular surface squamous neoplasia and melanocytic tumours (primary acquired melanosis and malignant melanoma), as well as the clinical experiences and difficulties in prescribing off-label interferon-α2b eye drops and subconjunctival injections. Results Twenty-four tertiary eye centres responded to the survey. Eighty-three percent of centres had used interferon-α2b in their clinical practice and 25% prescribed it as the first-line cytostatic agent following surgical excision of ocular surface squamous neoplasia, while 10% would do so for melanocytic tumours. Correspondingly, the majority of respondents selected mitomycin C as their first-line agent. Side effects were uncommon with topical interferon-α2b eye drops but were more frequently reported after subconjunctival interferon-α2b injections. In total, eight centres had experience with interferon-α2b injections. The most significant obstacles perceived by ophthalmologists when prescribing interferon-α2b were its high cost and the reimbursement thereof. Conclusion Off-label mitomycin C was the preferred adjuvant therapy for epithelial and melanocytic tumours, with interferon-α2b being the standard second-line option. Interferon-α2b has predominantly been used to treat ocular surface squamous neoplasia and, to a lesser extent, melanocytic tumours at German tertiary eye centres. Following its market withdrawal, supply shortages of interferon-α2b are likely to have a profound impact on patient care and their quality of life.

With the COVID-19 pandemic, the role of infectious disease spreading in public places has been brought into focus more than ever. Places that are of particular interest regarding the spread of infectious diseases are international airport terminals, not only for the protection of staff and ground crew members but also to help minimize the risk of the spread of infectious entities such as COVID-19 around the globe. Computational modelling and simulation can help in understanding and predicting the spreading of infectious diseases in any such scenario. In this paper, we propose a model, which combines a simulation of high geometric detail regarding virus spreading with an account of the temporal progress of infection dynamics. We, thus, introduce an agent-based social force model for tracking the spread of infectious diseases by modelling aerosol traces and concentration of virus load in the air. We complement this agent-based model to have consistency over a period of several days. We then apply this model to investigate simulations in a realistic airport setting with multiple virus variants of varying contagiousness. According to our experiments, a virus variant has to be at least twelve times more contagious than the respective control to result in a level of infection of more than 30%. Combinations of agent-based models with temporal components can be valuable tools in an attempt to assess the risk of infection attributable to a particular virus and its variants.

Background Chromosome 3q26 amplifications have been shown to represent a frequent alteration in various cancer entities including breast cancer. SEC62 - a 3q26 encoded gene - was identified as a potential onco- and tumor-driver gene for the pathogenesis of breast cancer. Sec62 seems to induce an increased stress tolerance, enhanced cell migration and proliferation in SEC62 overexpressing cells. Patients with SEC62 overexpressing breast cancer have been shown to have a higher rate of lymph node metastasis and poorer overall prognosis. Hence, we aspired to further evaluate the function of lymphatic SEC62 expression and its predictive role on the response to neoadjuvant chemotherapy. Objectives We aimed to assess the role of lymph node SEC62 expression as a predictive biomarker for response to neoadjuvant chemotherapy, besides we sought to evaluate potential differences in SEC62 expression levels in metastatic lymph node core biopsies and final pathology specimen according to breast cancer subtype. Material & Methods All nodal positive patients treated for primary breast cancer with neoadjuvant chemotherapy at the Department of Gynaecology and Obstetricts, Saarland University Hospital, Homburg, Germany between 01/2009 and 12/2019 were enrolled in this retrospective study. We analyzed SEC62 expression in tissue samples by immunohistochemistry (IHC). Sec62 immunoreactivity was evaluated using the immunoreactive score (IRS) according to Remmele and Stegner (0-12). For the assessment of the Sec62 protein content of the tumor cells, we rated Sec62 “low” for a score of 0-8, and “high” for 9-12 as described in previous publications. IHC was performed on initial lymph node core biopsy (CB) tissue (pre-treatment) or sentinel node biopsy specimen and on definite pathology specimen (PS) obtained during axillary dissection after completion of neoadjuvant chemotherapy.SEC62 expressions in both samples were compared and correlated with response to neoadjuvant chemotherapy, evaluated pathologically using the semi-quantitative response to neoadjuvant chemotherapy scoring system by Sinn et al. ranging from 0 (no effect) to 4 (no tumor detectable). Results 103 patients were assessed for eligibility. 15 cases were excluded, due to incomplete clinical information or insufficient slide quality, leaving 88 patients for final analysis. Median patient age was 55 (32-78) years and median response to neoadjuvant chemotherapy score of 2 (0-4). 11 (12.5%) patients had luminal A, 31 (35.2%) luminal B, 21 (23.9%) Her2/neu positive and 25 (28.4%) triple negative breast cancer. Median SEC62 expression in lymph node core biopsies was significantly higher compared to expression in final specimen (p Citation Format: Julia Zimmermann, Anna Jung, Merle Doerk, Mariz Kasoha, Barbara Linxweiler, Maximilian Linxweiler, Mathias Wagner, Rainer Bohle, Marc Radosa, Erich Solomayer, Julia C Radosa. Role of lymphatic SEC62 expression in prediction of treatment response in patients undergoing neoadjuvant chemotherapy for primary breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-06-06.

Triggering receptor expressed on myeloid cells 2 (TREM2) is suggested to hamper antitumor immune response in multiple cancers. However, the role of TREM2 in oral squamous cell carcinoma (OSCC) and its expression in tumor-associated macrophages (TAMs) are unknown. In this study, TREM2 expression was analyzed in the primary tumors and corresponding lymph-node metastases of OSCC patients via immunohistochemistry on tissue microarrays. Human peripheral blood mononuclear cells (PBMCs) and single-cell suspensions of tumor and healthy adjacent tissues were analyzed for the presence of TREM2+ macrophages and TAMs using flow cytometry. The serum levels of soluble TREM2 (sTREM2) were quantified using an enzyme-linked immunosorbent assay. High TREM2 expression was associated with advanced UICC stages (Spearman’s rank correlation (SRC), p = 0.04) and significantly reduced survival rates in primary tumors (multivariate Cox regression, progression-free survival: hazard ratio (HR) of 2.548, 95% confidence interval (CI) of 1.089–5.964, p = 0.028; overall survival: HR of 2.17, 95% CI of 1.021–4.613, p = 0.044). TREM2 expression was significantly increased in the PBMCs of OSCC patients in UICC stage IV compared with healthy controls (ANOVA, p < 0.05). The serum levels of sTREM2 were higher in advanced UICC stages, but they narrowly missed significance (SRC, p = 0.059). We demonstrated that TREM2 was multi-factorially associated with advanced stages and inferior prognosis in OSCC patients and that it could serve as a prognostic biomarker in OSCC patients. Targeting TREM2 has the potential to reshape the local and systemic immune landscape for the potential enhancement of patients’ prognosis.

Purpose Strategies for Indolamine-2,3-dioxygenase 1 (IDO1) inhibition in cancer immunotherapy once produced encouraging results, but failed in clinical trials. Recent evidence indicates that immune cells in the tumour microenvironment, especially macrophages, contribute to immune dysregulation and therefore might play a critical role in drug resistance. Methods In this study, we investigated the significance of IDO1 expressing immune cells in primary tumours and corresponding lymph node metastases (LNMs) in oral squamous cell carcinoma (OSCC) by immunohistochemistry. The link between IDO1 and macrophages was investigated by flow cytometry in tumour tissue, healthy adjacent tissue and peripheral blood mononuclear cells (PBMCs). IDO1 activity (measured as Kynurenine/Tryptophan ratio) was assessed by ELISAs. Results High IDO1 expression in tumour-infiltrating immune cells was significantly correlated with advanced stages [Spearman’s rank correlation (SRC), p = 0.027] and reduced progression-free survival (multivariate Cox regression, p = 0.034). IDO1 was significantly higher expressed in PBMCs of patients in advanced stages than in healthy controls (ANOVA, p + macrophages were more abundant in intratumoural areas than peritumoural (t test, p p t test, p Conclusion All in all, IDO1 expressing immune cells, especially macrophages, are more abundant in advanced stages of OSCC and are associated with reduced progression-free survival. Further investigations are needed to explore their role in local and systemic immune response. The IDO1 activity might be a suitable biomarker of metastasis in OSCC patients.

Introduction Head and neck squamous cell carcinomas (HNSCCs) are cancers with generally poor prognosis. Outcomes have not improved in decades, with more than half of the patients presenting with lymph node metastases at the time of diagnosis. A unique subtype of HNSCC, cancer of unknown primary of the head and neck (HNCUP) is associated with a poor outcome. Increased expression of the D2-40 gene (podoplanin) has been described for several human malignancies and has been associated with increased metastatic potential of cancer cells. Methods In order to examine the role of podoplanin in lymph node metastasis of HNSCC generally and HNCUP specifically, we evaluated the prognostic impact of podoplanin expression in HNSCC- (n = 68) and HNCUP-associated lymph node metastases (n = 30). The expression of podoplanin was analyzed by immunohistochemical staining of lymph node tissue samples and correlated with clinical and histopathological data. Results We found a non-significant tendency towards a higher podoplanin expression in HNCUP compared to HNSCC lymph node metastases and a significant correlation between a high podoplanin expression and advanced node-stage classification. Podoplanin expression had no significant impact on overall survival for both groups and did not correlate with human papillomavirus tumor status. Conclusion Taken together, our results suggest that upregulation of podoplanin may be associated with a stimulation of lymphatic metastasis in head and neck cancer.

Achim Fieß,1 Marilena Brandt,1 Eva Mildenberger,2 Michael Siegfried Urschitz,3 Felix Mathias Wagner,1 Stephanie Desiree Grabitz,1 Esther Maria Hoffmann,1 Norbert Pfeiffer,1 Alexander Konrad Schuster1 1Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; 2Division of Neonatology, Department of Pediatrics, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; 3Division of Pediatric Epidemiology, Institute for Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, GermanyCorrespondence: Achim Fieß, Department of Ophthalmology, Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, Mainz, 55131, Germany, Tel +49-6131-17-5150, Fax +49-6131-17-8495, Email Achim.fiess@gmail.comPurpose: Prenatal growth restriction is associated with impaired neurodevelopment in childhood. This study investigated the effects of being born small for gestational age (SGA) on peripapillary retinal nerve fiber layer (pRNFL) thickness in adults born at term.Methods: A retrospective cohort study was conducted with a prospective ophthalmologic examination of participants born at full-term (gestational age ≥ 37 weeks) between 1969 and 2002. All participants were examined with spectral-domain optical coherence tomography and grouped according to their birth weight in correlation to gestational age as former moderate (birth weight (BW) percentile 3rd to < 10th) and severe SGA (< 3rd percentile), normal (10th-90th percentile, AGA), and moderately (> 90th to 97th percentile) and severely (> 97th percentile) large for gestational age (LGA) adults (18 to 52 years).Results: Overall, 547 eyes of 285 individuals (age 29.9± 9.4 years, 151 females) born at term were included. Multivariable regression analyses revealed a strong association between a lower global pRNFL thickness in the severe SGA (B=− 8.99 [95%-CI: − 12.68; − 5.30] μm; p< 0.001) and in the moderate SGA groups (B=− 6.40 [95%-CI: − 10.29; − 2.50] μm; p=0.001) compared to the reference AGA group.Conclusion: Our results indicate that restricted fetal growth affects neurologic tissue development of the optic nerve head, particularly in individuals born severely SGA at term. This indicates that fetal growth restriction may exert disturbances in the development of neurologic tissue, which persists in adulthood.Keywords: birth weight, small for gestational age, large for gestational age, peripapillary retinal nerve fiber layer, optic nerve head, epidemiology

Purpose Liquid-based cytology (LBC) is routinely used in gynecology but is rarely applied in head and neck oncology though many suspicious lesions are easily accessible. While several studies have evaluated the potential use of LBC for early detection and molecular characterization of head and neck squamous cell carcinomas (HNSCCs), no study investigated its potential role in surgical management and therapy planning so far. Methods Twenty-five patients with cT1-2 squamous cell carcinomas of the oral cavity and oropharynx were prospectively enrolled in this study and were randomized to two treatment arms: in the control arm, a diagnostic panendoscopy with incisional biopsy was followed by a second operation with transoral tumor resection ± neck dissection and tracheostomy. In the intervention arm, patients underwent LBC diagnostics and in case of a positive result received one single operation with panendoscopy and incisional biopsy for confirmation of LBC result by rapid section histology followed by transoral tumor resection ± neck dissection and tracheostomy in the same session. Results Time between clinical diagnosis and definitive surgical treatment was significantly shorter in the intervention group compared with the control group (p p p = 0.062) were shorter in the intervention group. No significant differences in overall, progression-free, and disease-specific survival were observed. Conclusion Cytology-based cancer surgery is a promising therapeutic strategy that can potentially be considered for a well-defined group of early-stage HNSCC patients and help to avoid repetitive general anesthesia, shorten the diagnosis-to-treatment interval and spare operation as well as hospitalization time.

Background Leiomyosarcoma (LMS) of the inferior vena cava (IVC) is a rare malignancy that originated from the smooth muscle tissue of the vascular wall. Diagnoses, as well as, treatment of the disease are still challenging and to date, a radical surgical resection of the tumor is the only curative approach. Case report We report on the case of a 49-year old male patient who presented with suddenly experienced dyspnea. Besides bilateral pulmonary arterial embolism, a lesion close to the head of the pancreas was found using CT scan, infiltrating the infrahepatic IVC. Percutaneous ultrasound-guided biopsy revealed a low-grade LMS. Intraoperatively, a tumor of the IVC was observed without infiltration of surrounding organs or distant metastases. Consequently, the tumor was removed successfully, by en-bloc resection including prosthetic graft placement of the IVC. Histological workup revealed a completely resected (R0) moderately differentiated LMS of the IVC. Conclusion LMS of the infrahepatic IVC is an uncommon tumor, which may present with dyspnea as its first clinical sign. Patients benefit from radical tumor resection. However, due to the poor prognosis of vascular LMS, a careful follow-up is mandatory.