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Background Tumor growth encompasses multiple immunologic processes leading to impaired immunity. Regarding cancer surgery, the perioperative period is characterized by an additional immunosuppression that may contribute to poor outcomes. In this exploratory study, we assessed plasma parameters, characterizing the perioperative immunity with a particular focus on their prognostic value. Patients and methods 31 patients undergoing pancreatoduodenectomy were enrolled (adenocarcinoma of the pancreatic head and its periampullary region: n=24, benign pancreatic diseases n=7). Abundance and function of circulating immune cells and the plasma protein expression were analyzed in blood samples taken pre- and postoperatively using flow cytometry, ELISA and Proximity Extension Assay. Results Prior to surgery, an increased population of Tregs, a lower frequency of intermediate monocytes, a decreased portion of activated T-cells and a reduced response of T-cells to stimulation in vitro were associated with cancer. On the first postoperative day, both groups showed similar dynamics. The preoperative alterations did not persist six weeks postoperatively. Moreover, several preoperative parameters correlated with the postoperative survival. Conclusion Our data suggest systemic immunologic changes in adenocarcinoma patients, which are reversible six weeks after tumor resection. Additionally, the preoperative immune status affects the postoperative survival. In summary, our results implicate prognostic and therapeutic potential, justifying further trials on the perioperative tumor immunity to maximize the benefit of surgical tumor therapy.

Background Minimally invasive surgery is a field of rapid development. Evidence from randomized controlled trials in visceral surgery however still falls short of attesting unequivocal superiority to laparoscopic procedures over conventional open approaches with regard to postoperative outcome. The aim of this study was to explore the perioperative immune status of patients undergoing hybrid minimally invasive or conventional open pancreatoduodenectomy in a prospective cohort study. Material and methods Subtyping, quantification and functional analysis of circulating immune cells and determination of cytokine-levels in blood samples from patients receiving either hybrid minimally invasive (laPD) or conventional open pancreatoduodenectomy (oPD) was performed. Samples were taken from 29 patients (laPD: n = 14, oPD: n = 15) prior, during and up to six weeks after surgery. Cells were analyzed by flow cytometry, cytokines/chemokines were measured by proximity extension and enzyme-linked immunoassays. Results Open surgery induced higher levels of circulating inflammatory CD14++CD16+ intermediate monocytes. In contrast, hybrid minimally invasive resection was accompanied by increased numbers of circulating regulatory CD4+CD25+CD127low T-cells and by a reduced response of peripheral blood CD3+CD4+ T-cell populations to superantigen stimulation. Yet, rates of postoperative morbidity and infectious complications were similar. Conclusions In summary, the results of this exploratory study may suggest a more balanced postoperative inflammatory response and a better-preserved immune regulation after hybrid minimally invasive pancreatoduodenectomy when compared to open surgery. Whether these results may translate to or be harnessed for improved patient outcome needs to be determined by future studies including larger cohorts and fully laparoscopic or robotic procedures.

Introduction: Testicular cancer (TC) is the most common malignancy among young men. Public awareness of the disease and testicular (self-)examination (TSE) is low. This study aims to evaluate the awareness of German medical students on TC. Methods: A 25-item questionnaire on TC was handed out during a medical student’s football tournament in Germany. Data collection was anonymous. Results: Questionnaires were answered by 573 (56%) female and 452 (44%) male medical students. Most students had gaps in their knowledge about TC: 483 (48%) students knew, the most common age at which TC occurs, and 413 (41%) knew its cure rate. Having dealt with TC during their studies was significantly associated with a better knowledge about TC (p = 0.001). These students also had a higher rate of TSE among male students (66% vs. 52%, p = 0.002). This also applies to examining the partner’s testicles by female students (25% vs. 13%, p < 0.001). Conclusion: Even in a positively selected collective like medical students, the knowledge about TC is low. Better knowledge might improve the chance of detecting the disease early. Therefore, our joint project of urologists, patients, and supporters called Prevention and Advocacy of Testicular Education e.V. (PATE) works on rising public TC awareness in Germany.

Background Mutations in DNA damage repair genes, in particular genes involved in homology-directed repair, define a subgroup of men with prostate cancer with a more unfavorable prognosis but a therapeutic vulnerability to PARP inhibition. In current practice, mutational testing of prostate cancer patients is commonly done late i.e., when the tumor is castration resistant. In addition, most sequencing panels do not include TP53, one of the most crucial tumor suppressor genes in human cancer. In this proof-of-concept study, we sought to extend the clinical use of these molecular markers by exploring the early prognostic impact of mutations in TP53 and DNA damage repair genes in men with primary, nonmetastatic prostate cancer undergoing radical prostatectomy (RPX). Methods Tumor specimens from a cohort of 68 RPX patients with intermediate (n = 11, 16.2%) or high-risk (n = 57, 83.8%) disease were analyzed by targeted next generation sequencing using a 37 DNA damage repair and checkpoint gene panel including TP53. Sequencing results were correlated to clinicopathologic variables as well as PSA persistence or time to PSA failure. In addition, the distribution of TP53 and DNA damage repair gene mutations was analyzed in three large publicly available datasets (TCGA, MSKCC and SU2C). Results Of 68 primary prostate cancers analyzed, 23 (33.8%) were found to harbor a mutation in either TP53 (n = 12, 17.6%) or a DNA damage repair gene (n = 11, 16.2%). The vast majority of these mutations (22 of 23, 95.7%) were detected in primary tumors from patients with high-risk features. These mutations were mutually exclusive in our cohort and additional data mining suggests an enrichment of DNA damage repair gene mutations in TP53 wild-type tumors. Mutations in either TP53 or a DNA damage repair gene were associated with a significantly worse prognosis after RPX. Importantly, the presence of TP53/DNA damage repair gene mutations was an independent risk factor for PSA failure or PSA persistence in multivariate Cox regression models. Conclusion TP53 or DNA damage repair gene mutations are frequently detected in primary prostate cancer with high-risk features and define a subgroup of patients with an increased risk for PSA failure or persistence after RPX. The significant adverse impact of these alterations on patient prognosis may be exploited to identify men with prostate cancer who may benefit from a more intensified treatment.