Basic Research Of Tissue Engineering Trachea And Clinical Research Of Tracheal Surgery

Objective: The most essential factor of tissue engineered trachea research is the development of scaffolds.Acellular matrix scaffold is a hot topic in the field of tissue engineering scaffold materials,but the raw acellular matrix has to be modified,generally by crosslinking treatment,because of the insufficient physical and chemical properties.In this study,a new method was used to modify porcine-derived acellular dermal matrix(PADM)to lay the foundation for further study of tissue engineered trachea in the future.Methods: Full-thickness abdominal wall defects were created in 75 Sprague-Dawley(SD)rats and repaired with non-crosslinked(NC,negative control group),Glutaraldehyde(GA,positive control group)-crosslinked and Electron beam irradiation(EBI,treatment group)PADM grafts,respectively.Five rats were sacrificed at 2,4,8,12 and 24 weeks to evaluate the presence of herniation,infection,adhesions and changes in physical and chemical properties of the regenerated tissue at the defect site.Histopathology and immunohistochemistry were performed to evaluate the host tissue integration process assessed by the level of inflammatory host responses and vascularization.Results: Two SD rats with abdominal wall hernia was found in NC group.Prior to implantation,ex vivo strength tests showed that tensile strength in the crosslinkingly treated groups,namely GA or EBI,was significantly greater than that in the NC group.The degree of abdominal adhesion reached a peak at eighth weeks after implantation,but there was no significant difference among the three groups(p>0.05).In vivo integration strength tests indicated that the minimum tensile strength occurred in the fourth week,and the tensile fracture occurred at the the junction of patch and normal tissue.At 24 weeks,tensile strength in the EBI group is significantly better than thant of GA group(P < 0.05),and tensile strength in GA group is stronger than that in the NC group(P < 0.01).Inflammatory cells infiltration showed that in the first 4 weeks(p<0.01)and 8 weeks(p<0.05)CD 15+ cell infiltration of GA group was significantly higher than that of the NC group,and in second(p<0.01)and fourth weeks(P<0.05)CD 15+ cell infiltration was significantly higher in the GA group in comparison with NC group.CD68 cell staining showed that in the 12 th week,it was significantly higher in the crosslinked group than that of the non-crosslinked group(P<0.05).There was no significant difference among the three groups with respect to new blood vessel count(p>0.05),but the GA group was the lowest.Conclusions: The mechanical properties of PADM were significantly improved by cross-linking treatment,and the increased stability was achieved.GA treatment is more likely to cause inflammation in vivo.PADM crosslinked with EBI had the optimal comprehensive performance.Introduction: To discuss the best strategy for primary tracheal adenoid cystic carcinoma.Methods: This retrospective review included patients with localized primary tracheal adenoid cystic carcinoma(ACC)treated surgically at our institu tion between January 1995 and December 2014.Patients were classified according to the timing of first surgery: patients in the group A were performed surgery between January 1995 and December 2002,and patients in the group B were performed surgery between January 2003 and December 2014,group B.Results: A total of 109 tracheal ACC patients were identified.ACC patients in group A were significantly younger than those in group B at diagnosis(49.3±7.8 vs.45.7±9.4 years,p=0.042),and the resected tumor size and tracheal lengths tended to be smaller(28.2±7.6 vs.30.3±7.0 mm,p=0.161)and shorter(32.1±7.7 vs.34.4±6.7 mm,p=0.123).The use of postoperative radiotherapy in patients with R1 resection was also managed more effectively in group A compared with those in the group B(90.6% vs.65.0%,p=0.009).Overall survival(OS)for all patients with primary tracheal ACC was 88.7% at 5 years and 43.2% at 10 years.The 5-and 10-year OS rates in group A and group B were 86.4% and 90.8%,and 31.8% and 61.2%,respectively.Five-and 10-year OS rates in the group A and B were 86.4% and 90.8%,and 31.8% and 61.2%,respectively(p=0.084),and the corresponding 5-and 10-year DFS rates were 39.7% and 75.3%,and 9.9% and 21.2%,respectively(p=0.025).Survival analysis based on airway-margin status combined with the use of postoperative radiotherapy showed that 5-and 10-year OS rates in R0/0,R1/1,and R1/0 patients were 90.0%,88.4%,and 88.9%,and 75.0%,37.6%,and 15.5%,respectively.The overall comparisons among R0/0,R1/1,and R1/0 groups were significantly different(p=0.017).Pairwise comparisons showed a significant difference between group R0/0 and R1/1(p=0.036)and between group R0/0 and R1/0(p=0.004),while not between group R1/1 and R1/0(p=0.194).Similar outcomes were demonstrated for 5-and 10-year DFS rates(70.0%,67.8%,and 23.3%,and 42.0%,14.0%,and not evaluated,respectively)(p=0.001).Pairwise comparisons showed a significant difference between group R0/0 and R1/0(p=0.005)and between group R1/1 and R1/0(p=0.002),while not between group R0/0 and R1/1(p=0.137).Cox multivariate analysis of patients with resected ACC identified female sex(p=0.047),R0/0(p=0.026),and R1/1(p=0.010)as significantly favorable prognostic factors for DFS,and only R0/0(p=0.032)as the corresponding variable for OS.Conclusion: Tracheal adenoid cystic carcinoma tends to have a wide range of invasion,leading to low rate of R0 resection;R1 resection of patients with adjuvant radiotherapy can effectively improve the prognosis;surgical resection combined with postoperative radiotherapy can be used as the first choice for the treatment of patients with primary tracheal ACC.