The role of elective neck dissection in T1 and T2 nasal cavity squamous cell carcinomas.

PURPOSE: To evaluate the role of elective neck dissection (END) on oncological outcome in early-stage nasal cavity squamous cell carcinomas (SCCs). METHODS: In total, 87 patients with T1 (n = 59; 67.8%) and T2 (n = 28; 32.2%) SCCs were evaluated regarding performance of END, regional recurrences (RR) and its impact on cancer-specific survival (CSS). We further created a risk score based on T-classification, tumor subsite and grading to identify patients whom may benefit from END and calculated the corresponding numbers needed to treat (NNT) to prevent RR. RESULTS: Nine (10.3%) patients experienced RR of whom 3 (5.1%) were T1 and 6 (21.4%) T2 tumors (p = 0.042). All RR originated from moderately or poorly differentiated (G2-G3) SCCs of the nasal septum or vestibule. END was done in 15 (17.2%) patients and none of those experienced RR (p = 0.121). Onset of RR represented the worst prognostic factor for CSS (HR 23.3; p = 0.007) with a 5y-CSS of 44.4% vs. 97.3% (p < 0.001). RR occurred in none of the patients with no or low risk scores compared to 31.6% (6/19) in patients with high-risk scores (p = 0.006). Accordingly, three high-risk patients would need to undergo END (NNT 2.63) to prevent RR compared to a NNT of 8 for the whole cohort. CONCLUSIONS: Although rare, occurrence of RR significantly deteriorates outcome in early stage nasal cavity SCCs, which could be effectively reduced by performance of END. The importance of END is currently underestimated and our proposed risk score helps identifying those patients who will benefit from END.

[Role of Robotic Surgery in ENT]. / Bedeutung der transoralen robotischen Chirurgie in der HNO.

Since the beginning of the 21st century, surgical robots have been used in the ENT-environment. They primarily support surgeons in minimal invasive transoral operations, especially in multidisciplinary treatment concepts of head and neck tumors, but also in snoring surgery the robot provides a complement to the established transoral laser surgery. In the meantime there is a large number of data that deals with the importance of oncological results, function maintenance, economics and future perspectives.Operation areas of the current robot devices are still limited in the ENT-environment. As the number of cases are small, efforts are being made to connect centres on a national and international level. Thus, uniform training standards, targeted knowledge and data exchange as well as further development of systems would be managed better. The creation of small and agile ENT-specific equipment could expand the possibilities as a next step for the future and finally lead to a wide scale of ENT-surgical applications.

Serial Percent Free Prostate Specific Antigen in Combination with Prostate Specific Antigen for Population Based Early Detection of Prostate Cancer.

PURPOSE: We characterized the diagnostic properties of serial percent free prostate specific antigen in relation to prostate specific antigen in a multiethnic, multiracial cohort of healthy men. MATERIALS AND METHODS: A total of 6,982 percent free prostate specific antigen and prostate specific antigen measurements were obtained from participants in a greater than 12-year Texas screening study comprising 1,625 men who never underwent biopsy, 497 who underwent 1 or more biopsies negative for prostate cancer and 61 diagnosed with prostate cancer. We evaluated the ROC AUC of percent free prostate specific antigen and the proportion of patients with fluctuating values across multiple visits determined according to 2 thresholds (less than 15% vs 25%). The proportion of cancer cases in which percent free prostate specific antigen indicated a positive test before prostate specific antigen greater than 4 ng/ml did and the number of negative biopsies that would have been spared by negative percent free prostate specific antigen test results were calculated. RESULTS: Percent free prostate specific antigen fluctuated around its threshold of less than 25% (less than 15%) in 38.3% (78.1%), 42.2% (20.9%), and 11.4% (25.7%) of patients never biopsied, and with negative and positive biopsies, respectively. At the same thresholds, percent free prostate specific antigen tested positive earlier than prostate specific antigen in 71.4% and 34.2% of cancer cases, respectively. Among men with multiple negative biopsies and PSA greater than 4 ng/ml, percent free PSA would have tested negative in 31.6% and 65.8%, respectively. CONCLUSIONS: Percent free prostate specific antigen should accompany prostate specific antigen testing to potentially spare unnecessary biopsies or detect cancer earlier. When near the threshold, both tests should be repeated due to commonly observed fluctuation.

The Next Generation of Clinical Decision Making Tools: Development of a Real-Time Prediction Tool for Outcome of Prostate Biopsy in Response to a Continuously Evolving Prostate Cancer Landscape.

PURPOSE: We evaluate whether annual updating of the PCPT Risk Calculator would improve institutional validation compared to static use of the PCPT Risk Calculator alone. MATERIALS AND METHODS: Data from 5 international cohorts including SABOR, Cleveland Clinic, ProtecT, Tyrol and Durham VA, comprising 18,400 biopsies, were used to evaluate an institution specific annual recalibration of the PCPT Risk Calculator. Using all prior years as a training set and the current year as the test set, annual recalibrations of the PCPT Risk Calculator were compared to static use of the PCPT Risk Calculator in terms of AUC and the Hosmer-Lemeshow goodness of fit statistic. RESULTS: For predicting high grade disease the median AUC (higher is better) of the recalibrated PCPT Risk Calculator (static PCPT Risk Calculator) across all test years for the 5 cohorts was 67.3 (67.5), 65.0 (60.4), 73.4 (73.4), 73.9 (74.1) and 69.6 (67.2), respectively, and median Hosmer-Lemeshow goodness of fit statistics indicated better fit for recalibration compared to the static PCPT Risk Calculator for Cleveland Clinic, ProtecT and the Durham VA but not for SABOR and Tyrol. For predicting overall cancer median AUC was 63.5 (62.7), 61.0 (57.3), 62.1 (62.5), 66.9 (67.3) and 68.5 (65.5), respectively, and median Hosmer-Lemeshow goodness of fit statistics indicated a better fit for recalibration in all cohorts except for Tyrol. CONCLUSIONS: A simple method has been provided to tailor the PCPT Risk Calculator to individual hospitals to optimize its accuracy for the patient population at hand.

Improving patient prostate cancer risk assessment: Moving from static, globally-applied to dynamic, practice-specific risk calculators.

Clinical risk calculators are now widely available but have generally been implemented in a static and one-size-fits-all fashion. The objective of this study was to challenge these notions and show via a case study concerning risk-based screening for prostate cancer how calculators can be dynamically and locally tailored to improve on-site patient accuracy. Yearly data from five international prostate biopsy cohorts (3 in the US, 1 in Austria, 1 in England) were used to compare 6 methods for annual risk prediction: static use of the online US-developed Prostate Cancer Prevention Trial Risk Calculator (PCPTRC); recalibration of the PCPTRC; revision of the PCPTRC; building a new model each year using logistic regression, Bayesian prior-to-posterior updating, or random forests. All methods performed similarly with respect to discrimination, except for random forests, which were worse. All methods except for random forests greatly improved calibration over the static PCPTRC in all cohorts except for Austria, where the PCPTRC had the best calibration followed closely by recalibration. The case study shows that a simple annual recalibration of a general online risk tool for prostate cancer can improve its accuracy with respect to the local patient practice at hand.

Pelargonium Extract EPs 7630 in the Treatment of Human Corona Virus-Associated Acute Respiratory Tract Infections - A Secondary Subgroup-Analysis of an Open-Label, Uncontrolled Clinical Trial.

Background: Experience in treating human coronavirus (HCoV) infections might help to identify effective compounds against novel coronaviruses. We therefore performed a secondary subgroup-analysis of data from an open-label, uncontrolled clinical trial published in 2015 investigating the proanthocyanidin-rich Pelargonium sidoides extract EPs 7630 in patients with the common cold. Methods: 120 patients with common cold and at least 2 out of 10 common cold symptoms received one film-coated 20 mg tablet EPs 7630 thrice daily for 10 days in an uncontrolled, interventional multicentre trial (ISRCTN65790556). At baseline, viral nucleic acids were detected by polymerase chain reaction. Common cold-associated symptoms and treatment satisfaction were evaluated after 5 days and at treatment end. Based on the data of patients with proof of viral nucleic acids, we compared the course of the disease in patients with or without HCoV infection. Results: In 61 patients, viral nucleic acids were detected. Of these, 23 (37.7%) were tested positive for at least one HCoV (HCoV subset) and 38 (62.3%) for other viruses only (non-HCoV subset). Patients of both subsets showed a significant improvement of common cold symptoms already after 5 days of treatment, although the observed change tended to be more pronounced in the HCoV subset. At treatment end, more than 80% of patients of both groups were completely recovered or majorly improved. In both subsets, less than 22% of patients took concomitant paracetamol for antipyresis. The mean number of patients' days off work or school/college was similar (0.9 ± 2.6 days in HCoV subset vs 1.3 ± 2.8 days in non-HCoV subset). In both groups, most patients were satisfied or very satisfied with EPs 7630 treatment. Conclusion: EPs 7630 treatment outcomes of common cold patients with confirmed HCoV infection were as favourable as in patients with other viral infections. As this trial was conducted before the pandemic, there is currently no evidence from clinical trials for the efficacy of EPs 7630 in patients with SARS-CoV-2 infection. Dedicated non-clinical studies and clinical trials are required to elucidate the potential of EPs 7630 in the early treatment of HCoV infections.

Vaccinations in early life are not associated with development of islet autoimmunity in type 1 diabetes high-risk children: Results from prospective cohort data.

AIMS/HYPOTHESIS: Vaccinations in early childhood potentially stimulate the immune system and may thus be relevant for the pathogenesis of autoimmune diseases such as type 1 diabetes (T1D). We determined the association of vaccination burden with T1D-associated islet autoimmunity in children with high familial risk followed prospectively from birth. METHODS: A total of 20,570 certified vaccination records from 1918 children were correlated with time to onset of T1D-associated islet autoimmunity using Cox regression, considering multiple time periods up until age two years and vaccination types, and adjusting for HLA genotype, sex, delivery mode, season of birth, preterm delivery and maternal T1D status. Additionally, prospective claims data of 295,420 subjects were used to validate associations for the tick-borne encephalitis (TBE) vaccination. RESULTS: Most vaccinations were not associated with a significantly increased hazard ratio (HR) for islet autoimmunity (e.g. HR [95% confidence interval]: 1.08 [0.96-1.21] per additional vaccination against measles, mumps and rubella at age 0-24months). TBE vaccinations within the first two years of life were nominally associated with a significantly increased autoimmunity risk (HR: 1.44 [1.06-1.96] per additional vaccination at age 0-24months), but this could not be confirmed with respect to outcome T1D in the validation cohort (HR: 1.02 [0.90-1.16]). CONCLUSIONS: We found no evidence that early vaccinations increase the risk of T1D-associated islet autoimmunity development. The potential association with early TBE vaccinations could not be confirmed in an independent cohort and appears to be a false positive finding.

Perioperative transfusion of leukocyte depleted blood products in gastric cancer patients negatively influences oncologic outcome: A retrospective propensity score weighted analysis on 610 curatively resected gastric cancer patients.

The influence of perioperative transfusion (PT) on outcome following surgery for gastric cancer (GC) remains controversial, with randomized trials lacking and observational series confounded by patient risk factors. This analysis determines the association between reception of leukocyte-depleted blood products and post-operative survival for GC.Data from 610 patients who underwent curative surgery for GC in a German tertiary care clinic from 2001 to 2013 were included. Kaplan-Meier survival curves and Cox proportional hazards regression were applied to determine the association of PT and clinical and patient risk factors for overall and relapse-free survival. Propensity score analysis was performed to adjust for observational biases in reception of PT.Higher Union International Contre le Cancer/American Joint Committee on Cancer (UICC/AJCC)-stages (P <0.001), postoperative complications and severity according to the Clavien-Dindo (CD) classification (P <0.001), PT (P = 0.02), higher age (P <0.001), and neoadjuvant chemotherapy (P <0.001) were related to increased mortality rates. Higher UICC-stages (P <0.001), neoadjuvant chemotherapy (P <0.001), and type of surgery (P = 0.02) were independently associated with increased relapse rates. Patients were more likely to receive PT with higher age (P = 0.05), surgical extension to adjacent organs/structures (P = 0.002), tumor location (P = 0.003), and female gender (P = 0.03). In the adjusted propensity score weighted analysis, PT remained associated with an increased risk of death (hazard ratio (HR): 1.31, 95% CI: 1.01-1.69, P = 0.04).Because of the association of PT with negative influence on patient survival following resection for GC, risks from application of blood products should be weighed against the potential benefits.