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 fluorescenceactivated cell scanning (FACS) with a functional Hoechst 33342 staining as well as a cell surface marker staining of the 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.Pancreatic cancer consists of pancreatic ductal adenocarcinoma (PDAC) in 95% of patients and represents one of the deadliest cancer types, with a 5-year relative survival rate of 8% (1, 2). The survival rate has barely improved over the last decades, with the incidence and mortality projected to increase (3). Surgical resection remains the only curative option (4). Extrahepatic cholangiocarcinoma (eCC), comprising perihilar (Klatskin) and distal cholangiocarcinoma (dCC), shares several characteristics with PDAC, such as embryological development and many patterns of tumorigenesis, while having a slightly better prognosis (5-7). In the past, chemotherapy consisting mainly of gemcitabine in combination with nab-paclitaxel or FOLFIRINOX in PDAC as well as gemcitabine and cisplatin in eCC has been established as the standard of care in palliative patients (8, 9). New adjuvant treatment regimens have also improved survival in patients with PDAC as well as with eCC (10, 11). However, even in patients who have undergone R0 resection followed by adjuvant treatment, the long-term survival remains poor, with a 5-year survival rate of 15-20% for PDAC and 27-30% for eCC (5,12). Thus, new therapies are urgently awaited (13).Cancer stem cells (CSCs) seem to be a promising target for future therapeutic approaches. CSCs are characterized by the potential of self-renewal and multilineage differentiation and play ...
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.
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