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In conclusion, our data suggest a promising activity of second- or third-line PD-1- plus CTLA-4-blockade in patients with anti-PD-L1-refractory MCC.

In this small retrospective study, we observed a high response rate and durable responses to subsequent combined immunotherapy with IPI/NIVO in avelumab-refractory metastatic MCC patients. In conclusion, our data suggest a promising activity of second- or third-line PD-1- plus CTLA-4-blockade in patients with anti-PD-L1-refractory MCC.

In colon cancer, the location and density of tumor-infiltrating lymphocytes (TILs) can classify patients into low and high-risk groups for prognostication. While a commercially available 'Immunoscore

' exists, the incurred expenses and copyrights may prevent universal use. The aim of this study was to develop a robust and objective quantification method of TILs in colon cancer.

A consecutive, unselected series of specimens from patients with colon cancer were available for immunohistochemistry and assessment of TILs by automated digital pathology. CD3 + and CD8 + cells at the invasive margin and in tumor center were assessed on consecutive sections using automated digital pathology and image analysis software (Visiopharm

). An algorithm template for whole slide assessment, generated cell counts per square millimeters (cells/mm

), from which the immune score was calculated using distribution volumes. Furthermore, immune score was compared with clinical and histopathological characteristics to confirm its relevance.

Based on the quantified TILs numbers by digital image analyses, patients were classified into low (n = 83, 69.7%), intermediate (n = 14, 11.8%) and high (n = 22, 18.5%) immune score groups. High immune score was associated with stage I-II tumors (p = 0.017) and a higher prevalence of microsatellite instable (MSI) tumors (p = 0.030). MSI tumors had a significantly higher numbers of CD3 + TILs in the invasive margin and CD8 + TILs in both tumor center and invasive margin, compared to microsatellite stable (MSS) tumors.

A digital template to quantify an easy-to-use immune score corresponds with clinicopathological features and MSI in colon cancer.

A digital template to quantify an easy-to-use immune score corresponds with clinicopathological features and MSI in colon cancer.Curaxins are small molecules that bind genomic DNA and interfere with DNA-histone interactions leading to the loss of histones and decondensation of chromatin. We named this phenomenon 'chromatin damage'. Curaxins demonstrated anti-cancer activity in multiple pre-clinical tumor models. Here, we present data which reveals, for the first time, a role for the immune system in the anti-cancer effects of curaxins. Using the lead curaxin, CBL0137, we observed elevated expression of several group of genes in CBL0137-treated tumor cells including interferon sensitive genes, MHC molecules, some embryo-specific antigens suggesting that CBL0137 increases tumor cell immunogenicity and improves recognition of tumor cells by the immune system. In support of this, we found that the anti-tumor activity of CBL0137 was reduced in immune deficient SCID mice when compared to immune competent mice. Anti-tumor activity of CBL0137 was abrogated in CD8+ T cell depleted mice but only partially lost when natural killer or CD4+ T cells were depleted. Further support for a key role for the immune system in the anti-tumor activity of CBL0137 is evidenced by an increased antigen-specific effector CD8+ T cell and NK cell response, and an increased ratio of effector T cells to Tregs in the tumor and spleen. CBL0137 also elevated the number of CXCR3-expressing CTLs in the tumor and the level of interferon-γ-inducible protein 10 (IP-10) in serum, suggesting IP-10/CXCR3 controls CBL0137-elicited recruitment of effector CTLs to tumors. Our collective data underscores a previously unrecognized role for both innate and adaptive immunity in the anti-tumor activity of curaxins.The standardization of procedural flow and medical documentation increasingly allows further possibilities. The best-known example of process standardization is the centralized treatment of complex clinical pictures, while patient-reported outcome measurements (PROMs) enable standardized documentation. Using the example of prostate cancer, existing literature on the topic of quality optimization in medicine is discussed. The following key points are addressed (1) Increasing use of standardized PROMs for outcome documentation. (2) The transfer of complex clinical pictures to dedicated specialized centers has been shown to increase the quality of patient care as long as standardized PROMs are used. (3) Healthcare policymakers benefit from the use of PROMs and increasingly pursue a "value-based healthcare" approach.

Radical cystectomy is associated with considerable morbidity and mortality. Based on the solid evidence in colorectal surgery, fast-track/ERAS® (Enhanced Recovery After Surgery) protocols have been developed to improve the perioperative management of patients undergoing radical cystectomy.

To review the literature and guidelines and evaluate the evidence regarding the different components of ERAS® protocols.

Systemic literature search and evaluation of relevant guidelines.

The majority of ERAS® recommendations for radical cystectomy are based on extrapolations of abdominal surgery studies. click here Four randomized, controlled trials and one ERAS® guideline were published for radical cystectomy. ERAS® seems to shorten length of stay without increasing the complication rate. Key elements are no bowel preparation, no nasogastric tube, optimized fluid substitution, multimodal pain management, early mobilization, and oral diet.

Implementation of ERAS® requires multidisciplinary collaboration. Individualization of an ERAS® program, identification of the most important components and adaption to the specific needs of radical cystectomy patients are future goals.

Implementation of ERAS® requires multidisciplinary collaboration. Individualization of an ERAS® program, identification of the most important components and adaption to the specific needs of radical cystectomy patients are future goals.