Centralized and Interdisciplinary Therapy Management in the Treatment of Sarcomas.

Sarcoma treatment requires a high level of expertise due to its rarity and heterogeneity. Sarcoma patients should, therefore, be referred to an expert centre as early as possible to ensure optimal treatment. Numerous studies have been carried out to provide evidence for this strategy. In compliance with the 2020 PRISMA guidelines, a systematic search was conducted in PubMed, EMBASE, Ovid Medline, ClinicalTrials.gov and Cochrane Library databases. The subject of these studies was the centralised treatment of adult sarcoma patients at expert centres and the use of interdisciplinary tumour boards. Uncertainty in therapy, delays in referral to expert centres, and limited access to therapeutic modalities continue to be a challenge in sarcoma therapy. At expert centres, diagnostic procedures were more frequently and adequately performed, and treatment was associated with an improvement in outcomes in the majority of studies: patients benefited from longer survival, lower local recurrence rates and a better postoperative outcome. The implementation of an interdisciplinary tumour board was associated with discrepant results. In a greater number of studies, it was associated with a lower local relapse rate, better overall survival and surgical outcome. In two studies, however, a shorter overall survival was observed. The establishment of expert centres and the consistent use of interdisciplinary tumour boards are important structures for ensuring multidisciplinary therapy approaches. There is growing evidence that this holds great potential for optimising sarcoma therapy.

Role of extracellular matrix structural components and tissue mechanics in the development of postoperative pancreatic fistula.

Radical resection remains the only curative treatment option in pancreatic cancer. Postoperative pancreatic fistulas (POPF) occur in up to 30% of patients leading to prolonged hospital-stay, increased cost of care and morbidity and mortality. Mechanical properties of the pancreas are associated with POPF. The aim of this study is to analyze the role of extracellular matrix (ECM) and tissue mechanics in the risk of POPF. Biopsies of 41 patients receiving a partial pancreas-resection are analyzed. Clinical data, ECM components and mechanical properties are correlated with POPF. Preoperative cholestasis is correlated with reduced risk of POPF, which comes along with a dilatation of the pancreatic duct and significantly higher content of collagen I. Patients developing POPF exhibited a degenerated tissue integrity, with significantly lower content of fibronectin and a trend for lower collagen I, III, IV and hyaluronic acid. This correlated with a soft tactile sensation of the surgeon during the intervention. However, this was not reflected with tissue mechanics evaluated by ex vivo uniaxial compression testing, where a significantly higher elastic modulus and no effect on the stress relaxation time were found. In conclusion, patients with cholestasis seem to have a lower risk for POPF, and an increase in collagen I. A degenerated matrix with lower content of structural ECM components correlates with increased risk of POPF. However, ex vivo uniaxial compression testing failed to clearly explain the link of ECM properties and POPF.

Characterization of Pancreatic and Biliary Cancer Stem Cells in Patient-derived Tissue.

BACKGROUND/AIM: Pancreatic ductal adenocarcinoma (PDAC) and extrahepatic cholangio-carcinoma (eCC) represent two cancer entities with devastating prognoses. Despite recent progress in research and treatment, therapy remains challenging. Cancer stem cells (CSCs) have been shown to play an important role in metastasis and chemoresistance. Therefore, CSCs may play a promising role as a potential therapeutic target. MATERIALS AND METHODS: A total of 31 patients (23 PDAC, 8 eCC) were included in the study. CSCs were analyzed in a single-cell suspension of tumor samples via fluorescence-activated cell scanning (FACS) with a functional Hoechst 33342 staining as well as a cell surface marker staining of the CSC-panel (CD24, CD44 and EpCAM) and markers to identify fibroblasts, leukocytes and components of the notch signaling pathway. Furthermore, the potential presence of CSCs among primary cancer-associated fibroblasts (CAFs) was assessed using the same FACS-panel. RESULTS: We showed that CSCs are present in patient-derived dissociated tumor tissue. The functional and surface marker profile of CSC-detection did in fact correlate. The amount of CSCs was significantly correlated with tumor characteristics such as a higher UICC stadium and nodal invasion. CSCs were not restricted to the epithelial cell fraction in tumor tissues, which has been verified in independent analysis of primary cell cultures of CAFs. CONCLUSION: Our study confirms the in vivo presence of CSCs in PDAC and eCC, stating a clinical significance thereof and thus their plausibility as therapeutic targets. In addition, stem-like cells also seem to constitute a part of the CAFs.