PurposeFor locoregionally recurrent head and neck squamous cell carcinoma (HNSCC), appropriate therapeutic decisions remain unclear. We examined the treatment outcomes of a national cohort to determine suitable treatments for and prognostic factors in patients with locoregionally recurrent HNSCCs at different stages and sites.Patients and methodsWe analyzed data of >20-year-old patients with HNSCC at American Joint Committee on Cancer clinical stages I–IV without metastasis from Taiwan National Health Insurance and cancer registry databases. The index date was the date of recurrent HNSCC diagnosis. Recurrent HNSCC was defined as the annotation of locoregional recurrence with tissue proof in cancer registry databases. The enrolled patients were categorized into three groups: Group 1 comprised those undergoing chemotherapy (CT) alone; Group 2 comprised those receiving reirradiation (re-RT) alone (total radiation dose ≥ 60 Gy through intensity modulation radiation therapy [IMRT]); Group 3 comprised those receiving concurrent chemoradiotherapy (CCRT) alone (irradiation total dose ≥60 Gy through IMRT); and Group 4 comprised those receiving salvage surgery with or without RT or CT.ResultsWe enrolled 4,839 and 28,664 HNSCC patients with and without locoregional recurrence, respectively (median follow-up, 3.25 years). Locoregional recurrence rate and incidence were 14.44% and 40.73 per 1,000 person-years, respectively. Age ≥ 65 years, Charlson comorbidity index (CCI) score > 6, advanced clinical stage at first diagnosis, and recurrence-free interval < 1 year were significant independent prognostic risk factors for overall survival as per univariate and multivariate Cox regression analyses. After adjusting for age, sex, CCI scores, clinical stage at first diagnosis, and recurrence-free interval, adjusted hazard ratios (aHRs; 95% confidence intervals [CIs]) for overall mortality in recurrent clinical stages I and II were 0.63 (0.45–0.89, p = 0.009), 0.65 (0.52–0.83, p < 0.001), and 0.32 (0.26–0.40, p < 0.001) in Groups 2, 3, and 4, respectively, whereas they were 1.23 (0.99–1.52, p = 0.062), 0.69 (0.60–0.79, p < 0.001), and 0.39 (0.34–0.44, p < 0.001) for Groups 2, 3, and 4, respectively, for overall mortality in recurrent clinical stage III and IV.ConclusionsAge, CCI score, clinical stage at first diagnosis, and recurrence-free interval are significant independent prognostic factors for overall survival of recurrent HNSCC patients. Regardless of recurrence stage or site, salvage surgery is the recommended first recurrent HNSCC treatment choice. Re-RT alone and CCRT are more suitable for inoperable recurrent early-stage oral and nonoral cavity recurrent HNSCCs, respectively.
Objective. Osteoarthritis is characterized by an imbalance in cartilage homeostasis, which could potentially be corrected by mesenchymal stem cell (MSC)-based therapies. However, in vivo implantation of undifferentiated MSCs has led to unexpected results. This study was undertaken to establish a model for preconditioning of MSCs toward chondrogenesis as a more effective clinical tool for cartilage regeneration.Methods. A coculture preconditioning system was used to improve the chondrogenic potential of human MSCs and to study the detailed stages of chondrogenesis of MSCs, using a human MSC line, Kp-hMSC, in commitment cocultures with a human chondrocyte line, hPi (labeled with green fluorescent protein [GFP]). In addition, committed MSCs were seeded into a collagen scaffold and analyzed for their neocartilage-forming ability.Results. Coculture of hPi-GFP chondrocytes with Kp-hMSCs induced chondrogenesis, as indicated by the increased expression of chondrogenic genes and accumulation of chondrogenic matrix, but with no effect on osteogenic markers. The chondrogenic process of committed MSCs was initiated with highly activated chondrogenic adhesion molecules and stimulated cartilage developmental growth factors, including members of the transforming growth factor  superfamily and their downstream regulators, the Smads, as well as endothelial growth factor, fibroblast growth factor, insulin-like growth factor, and vascular endothelial growth factor. Furthermore, committed Kp-hMSCs acquired neocartilageforming potential within the collagen scaffold. Osteoarthritis (OA), one of the most common musculoskeletal diseases, has been ascribed to an imbalance in cartilage homeostasis in the aging process (1,2). Hyaline cartilage has little capacity for self-repair. As a result, continuous mechanical stress can lead to the degradation of articular cartilage, culminating in a vicious cycle of destructive processes (3). Many therapeutic interventions directed at the restoration of the reparative capacity of chondrocytes have been explored (3-5). One of the emerging approaches is cell-based therapy, in which expanded chondrocytes are used for cartilage repair. However, the outcome of this approach has been disappointing, due to the difficulties in maintaining chondrocytic phenotypes and the decrease in proliferative capacity of autologous chondrocytes with increasing age (1,6,7). Conclusion. These findings help define the molecular markers of chondrogenesis and more accuratelyCell therapy based on autologous mesenchymal stem cells (MSCs), which have a vast proliferative ca-
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