BackgroundAttempts to relate patellar cartilage involvement to anterior knee pain (AKP) have yielded conflicting results. We determined whether the condition of the cartilage of the patella at the time of knee replacement, as assessed by the OARSI score, correlates with postsurgical AKP.Patients and methodsWe prospectively studied 100 patients undergoing knee arthroplasty. At surgery, we photographed and biopsied the articular surface of the patella, leaving the patella unresurfaced. Following determination of the microscopic grade of the patellar cartilage lesion and the stage by analyzing the intraoperative photographs, we calculated the OARSI score. We interviewed the patients 1 year after knee arthroplasty using the HSS patella score for diagnosis of AKP.Results57 of 95 patients examined had AKP. The average OARSI score of painless patients was 13 (6–20) and that of patients with AKP was 15 (6–20) (p = 0.04). Patients with OARSI scores of 13–24 had 50% higher risk of AKP (prevalence ratio = 1.5, 95% CI: 1.0–2.3) than patients with OARSI scores of 0–12.InterpretationThe depth and extent of the cartilage lesion of the knee-cap should be considered when deciding between the various options for treatment of the patella during knee replacement.

Background: Thymic epithelial tumors are rare thoracic tumors for which pathological diagnosis is challenging due to the definition of multiple subtypes, tumor heterogeneity, and variations in interobserver reproducibility. In this study, we aimed at analyzing the quality of pathological reporting in line with the consistency between initial diagnosis and final diagnosis after expert review through a collaboration between the largest thoracic oncology center in Estonia, and one expert center in France. Methods: Hospital electronic database and pathology databases from the Tallinn North Estonia Medical Centre were searched for thymic and mediastinal tumors from 2010 to 2017. Pathology specimens were referred to the Pathology Department of the Lyon University hospital. Overall, 55 tissue specimens from 49 patients were included. Results: From pathology reports, tumor size, diagnosis, and invasion had been mentioned in ≥80% of cases, while resection status and staging were assessed in only 48% and 17% of cases, respectively. The initial diagnosis was consistent with that of the review in 60% of cases. Diagnostic concordance for thymoma subtypes was low (Cohen's kappa 0.34, 95% CI: 0.16-0.52). Overall, a major change in the management of 8 (16%) patients had to be made after pathological review: 3 patients had a normal thymus according to the reference centre, while thymoma B1 or B2 had been diagnosed locally; 5 additional patients had a final diagnosis of non-thymic tumor. Conclusions: Implementing structured pathology reports may help to decrease discrepancies in the diagnosis of thymic epithelial tumors. The development of expert networks is an opportunity to improve diagnosis and patient care, particularly in regard to rare cancers.

Research on mitochondrial metabolism and respiration are rapidly developing areas, however, efficient and widely accepted methods for studying these in solid tumors are still missing. Here, we developed a new method without isotope tracing to quantitate time dependent mitochondrial citrate efflux in cell lines and human breast cancer samples. In addition, we studied ADP-activated respiration in both of the sample types using selective permeabilization and showed that metabolic activity and respiration are not equally linked. Three times lower amount of mitochondria in scarcely respiring MDA-MB-231 cells convert pyruvate and glutamate into citrate efflux at 20% higher rate than highly respiring MCF-7 mitochondria do. Surprisingly, analysis of 59 human breast cancers revealed the opposite in clinical samples as aggressive breast cancer subtypes, in comparison to less aggressive subtypes, presented with both higher mitochondrial citrate efflux and higher respiration rate. Additionally, comparison of substrate preference (pyruvate or glutamate) for both mitochondrial citrate efflux and respiration in triple negative breast cancers revealed probable causes for high glutamine dependence in this subtype and reasons why some of these tumors are able to overcome glutaminase inhibition. Our research concludes that the two widely used breast cancer cell lines fail to replicate mitochondrial function as seen in respective human samples. And finally, the easy method described here, where time dependent small molecule metabolism and ADP-activated respiration in solid human cancers are analyzed together, can increase success of translational research and ultimately benefit patients with cancer.

We separated CSCs from cell lines and lung cancer tissues by CSC marker CD133 and ALDH. Then we knock down the expression of TLR9 and then investigate biological changes of CSCs, including sphere formation, self-renewing ability, invasion, resistance to drugs, and in vivo tumor formation. Result: We found toll-like receptor (TLR9) are constitutively overexpressed on cancer stem cells (CSCs) derived from lung cancer cell lines and patients' tissue when compared with non-stem cells. Knocking down of TLR9 in lung CSCs resulted in inhibited capacity for proliferation, invasion, tumorigenesis and resistance to chemotherapeutic drugs. Furthermore, cell cycle was arrested at G2/M stages and more apoptosis existed after TLR9 expression decreased. Further analysis indicated that TLR9 maintain the stemness of cancer cells by changing expression of other stem cell markers Gli1, Notch1 and beta-catenin, drug transporters ABCB1, ABCC1 and ABCG2 and anti-apoptotic factors BCL2 and Survivin. Of which, beta-catenin, was found to be most obviously related with TLR9 expression. Moreover, TLR9 expression was positively associated with tumor differentiation and inversely associated with lung cancer patient survival in clinic. Conclusion: Based on above data, TLR9 is crucial for marker and phenotype of lung CSC. It might work as a lung cancer stem cell maintainer.

5FU-related MI, and one patient with bowel perforation. No treatment related deaths occurred. Patients older than 70 had a lower completion rate (28.5% vs. 77%, p ¼ 0.016), higher admission rate (85% vs. 61%, p ¼ 0.228) but similar grade 3/4 toxicity rate (57% vs. 61%, p ¼ 0.832) compared to younger counterparts. Compared to AIO -FLOT4 trial, our patients had higher rates of: discontinuation (33.3% vs. 6%), dose reductions (24% vs. 6%) and serious adverse events (70% vs. 41%). The commonest grade3/4 toxicity was neutropenia in both cohorts, but was less frequent in our institution (30% vs. 52%) probably due to primary GCSF prophylaxis. Grade 3/4 nausea/ vomiting was commonest in the AOI-FLOT 4 cohort (12% vs. 6%), while grade3/4 diarrhoea was more frequent in our institution (12% vs. 7%). Fatigue grade 3/4 was commonest in our cohort (12% vs. 9%). No grade 3/4 cases of neurotoxicity were reported in our cohort, compared with the AIO-FLOT4 (8%). Conclusion: Neoadjuvant FLOT for resectable GOA was less tolerable and more toxic in our cohort, with higher rate of early treatment discontinuations, dose reductions, serious adverse events. The above results demonstrate that every day clinical practice often differs from trial results and underscore the importance of reporting real world experience data, especially regarding safety issues.