Peri-operative SARS-CoV-2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS-CoV-2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre-operative SARS-CoV-2 infection were compared with those without previous SARS-CoV-2 infection. The primary outcome measure was 30-day postoperative mortality. Logistic regression models were used to calculate adjusted 30-day mortality rates stratified by time from diagnosis of SARS-CoV-2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre-operative SARS-CoV-2 diagnosis. Adjusted 30-day mortality in patients without SARS-CoV-2 infection was 1.5% (95%CI 1.4-1.5). In patients with a pre-operative SARS-CoV-2 diagnosis, mortality was increased in patients having surgery within 0-2 weeks, 3-4 weeks and 5-6 weeks of the diagnosis (odds ratio (95%CI) 4.1 (3.3-4.8), 3.9 (2.6-5.1) and 3.6 (2.0-5.2), respectively). Surgery performed ≥ 7 weeks after SARS-CoV-2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5 (0.9-2.1)). After a ≥ 7 week delay in undertaking surgery following SARS-CoV-2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2-8.7) vs. 2.4% (95%CI 1.4-3.4) vs. 1.3% (95%CI 0.6-2.0), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS-CoV-2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay.

Background:Lung cancer is the most life-threatening cancer type worldwide. Treatment options include surgery, radio- and chemotherapy, as well as the use of immunomodulatory antibodies. Interleukin (IL)-10 is an immunosuppressive cytokine involved in tumour immune escape.Methods:Immunohistochemistry (IHC) on human lung surgery tissue as well as human tumour cell line cultures, FACS analysis, real-time PCR and experimental lung cancer.Results:Here we discovered a positive correlation between IL-10 and IL-10 receptor (IL-10R) expression in the lung with tumour diameter in patients with lung cancer (non-small cell lung cancer), the most life-threatening cancer type worldwide. IL-10 and IL-10R were found induced in cells surrounding the lung tumour cells, and IL-10R was mainly expressed on the surface of Foxp-3+ T-regulatory lymphocytes infiltrating the tumour of these patients where its expression inversely correlated with programmed cell death 1. These findings were confirmed in translational studies. In a human lung adenocarcinoma cell line, IL-10R was found induced under metabolic restrictions present during tumour growth, whereby IL-10 inhibited PDL1 and tumour cell apoptosis.Conclusions:These new findings suggest that IL-10 counteracts IFN-γ effects on PD1/PDL1 pathway, resulting in possible resistance of the tumour to anti-PD1/PDL1 immunotherapy.

SARS-CoV-2 has been associated with an increased rate of venous thromboembolism in critically ill patients. Since surgical patients are already at higher risk of venous thromboembolism than general populations, this study aimed to determine if patients with peri-operative or prior SARS-CoV-2 were at further increased risk of venous thromboembolism. We conducted a planned sub-study and analysis from an international, multicentre, prospective cohort study of elective and emergency patients undergoing surgery during October 2020. Patients from all surgical specialties were included. The primary outcome measure was venous thromboembolism (pulmonary embolism or deep vein thrombosis) within 30 days of surgery. SARS-CoV-2 diagnosis was defined as peri-operative (7 days before to 30 days after surgery); recent (1-6 weeks before surgery); previous (≥7 weeks before surgery); or none. Information on prophylaxis regimens or pre-operative anti-coagulation for baseline comorbidities was not available. Postoperative venous thromboembolism rate was 0.5% (666/123,591) in patients without SARS-CoV-2; 2.2% (50/2317) in patients with peri-operative SARS-CoV-2; 1.6% (15/953) in patients with recent SARS-CoV-2; and 1.0% (11/1148) in patients with previous SARS-CoV-2. After adjustment for confounding factors, patients with peri-operative (adjusted odds ratio 1.5 (95%CI 1.1-2.0)) and recent SARS-CoV-2 (1.9 (95%CI 1.2-3.3)) remained at higher risk of venous thromboembolism, with a borderline finding in previous SARS-CoV-2 (1.7 (95%CI 0.9-3.0)). Overall, venous thromboembolism was independently associated with 30-day mortality ). In patients with SARS-CoV-2, mortality without venous thromboembolism was 7.4% (319/4342) and with venous thromboembolism was 40.8% (31/76). Patients undergoing surgery with peri-operative or recent SARS-CoV-2 appear to be at increased risk of postoperative venous thromboembolism compared with patients with no history of SARS-CoV-2 infection. Optimal venous thromboembolism prophylaxis and treatment are unknown in this cohort of patients, and these data should be interpreted accordingly.

Exosomes, the smallest group of extracellular vesicles, carry proteins, miRNA, mRNA, DNA, and lipids, which they efficiently deliver to recipient cells, generating a communication network. Exosomes strongly contribute to the immune suppressive tumor microenvironment of head and neck squamous cell carcinomas (HNSCC). Isolation of exosomes from HNSCC cell culture or patient’s plasma allows for analyzing their molecular cargo and functional role in immune suppression and tumor progression. Immune affinity-based separation of different exosome subsets, such as tumor-derived or T cell-derived exosomes, from patient’s plasma simultaneously informs about tumor status and immune dysfunction. In this review, we discuss the recent understanding of how exosomes behave in the HNSCC tumor microenvironment and why they are promising liquid biomarkers for diagnosis, prognosis, and therapy in HNSCC.

Background: The impact of demographic change on the age at diagnosis in German head and neck cancer (HNC) patients is unclear. Here we present an evaluation of aging trends in HNC at a tertiary referral center. Methods: Retrospective cohort study on aging trends at the initial diagnosis of newly diagnosed patients with HNC between 2004 and 2018 at the head and neck cancer center Ulm in relation to demographic data of the catchment area. Results: The study population consisted of 2450 individuals diagnosed with HNC with a mean age of 62.84 (±11.67) years. We observed a significant increase in annual incidence rates and mean age over time. Mean age among HNC patients increased significantly more than among the population in the catchment area. Whereas the incidence rate of patients <50 years did not change, the incidence of HNC patients aged ≥70 years increased the most. The mean patient age in the main tumor sites increased significantly. Surprisingly, HPV-positive patients were not younger than HPV-negative patients, but showed a non-significant trend towards a higher mean age (63.0 vs. 60.7 years). Conclusions: Increasing incidence rates in older patients pose a challenge for health care systems. A nationwide study is needed to assess the dynamics and impact of aging on the incidence of HNC.

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Purpose Cancer patients have to overcome various barriers to obtain diagnostics and treatment at head and neck cancer centers. Travel distance to a specialized hospital may result in psychosocial and financial distress, thus interfering with diagnostics, treatment, and follow-up care. In this study, we have aimed to analyze the association of travel distance with cTNM status, UICC stage at primary diagnosis, and survival outcomes of head and neck cancer (HNC) patients. Methods We have analyzed data of 1921 consecutive HNC patients diagnosed between 2014 and 2019 at the head and neck cancer center of the Comprehensive Cancer Center Ulm (CCCU), Germany. Postal code-based travel distance calculation in kilometers, TNM status, and UICC stage were recorded at initial diagnosis. The assembly of travel distance-related groups (short, intermediate, long-distance) has been investigated. Moreover, group-related survival and recurrence analysis have been performed. ResultsIn contrast to observations from overseas, no association of travel distance and higher cTNM status or UICC stage at primary diagnosis has been observed. Furthermore, no significant differences for recurrence-free survival and overall survival by travel distance were detected. Conclusion In southern Germany, travel distance to head and neck cancer centers seems to be tolerable. Travel burden is not synonymous with travel distance alone but also involves sociodemographic, monetary, and disease-specific aspects as well as accessibility to proper infrastructure of transport and health care system.

ZusammenfassungDemografisch zeigt sich eine alternde, morbider werdende deutsche Bevölkerung. Gleichzeitig werden Urbanisierungstendenzen, medizinische Überkapazitäten und steigende, auch innovationsbedingte Versorgungskosten bei einem knappen Gesundheitsetat beobachtet. Zentralisierung, Spezialisierung und Ambulantisierung sollen Abhilfe verschaffen und können durch Modifikationen der Vergütung mitgesteuert werden. Dieser Umbruch birgt für Patient*innen und Ärzt*innen neue Herausforderungen, welche exemplarisch am Kopf-Hals-Tumor (KHT) -Zentrum des Universitätsklinikums Ulm analysiert wurden. Dabei handelt es sich um eine retrospektive, monozentrische Kohortenstudie zur Entwicklung des Patientenaufkommens, Einzugsgebiets, der Behandlungsmodalität und Demografie unter Einschluss von 2070 KHT-Patient*innen zwischen den Jahren 2011 und 2020 der HNO-Klinik. Es wurde beobachtet, dass die Anzahl (Neudiagnosen 2011: 134 vs. 2020: 204) und das Durchschnittsalter (2011: 61,5 Jahre vs. 2020: 65,8 Jahre; p<0,0001) der KHT-Patient*innen im zeitlichen Verlauf anstiegen. Außerdem nahmen die Patient*innen hierbei tendenziell größere Anfahrtswege auf sich (2011: 54,4km vs. 2020: 64,4km; p=0,05). Gleichzeitig wuchs die mittlere Anzahl an Konsultationen und Behandlungen pro Patient*in und 5-Jahres-Nachsorgeintervall (bei Erstdiagnose 2011: 7,8 vs. 2016: 10,4; p=0,0003), wobei sich der Anteil ambulanter Patientenkontakte von 2011–2020 von 58,9% auf 62,4% (p=0,09) erhöhte. Dementsprechend ist zu erwarten, dass klinische Zentren im Zuge der Spezialisierung, Ambulantisierung und Zentralisierung des Gesundheitssystems an Bedeutung bei der Versorgung von KHT-Patient*innen gewinnen. Daraus folgende Konsequenzen für die Patientenversorgung sollten bei Umstrukturierungsstrategien berücksichtigt werden.