Split transplantation of the trachea: A new operative procedure for extended tracheal resection

AbstractBefore tracheal transplantation can be applied clinically, several problems must be solved: immunosuppression, blood supply to grafts, and reliable long-term preservation of grafts. We have conducted experiments on tracheal transplantation to solve these problems. In the present study, we tried a new operative procedure to accomplish reliable revascularization of transplanted tracheal grafts. It has been reported that transplantation of a 10-ring length of trachea is difficult even with omentopexy. Long tracheal allografts can be transplanted with use of direct revascularization, but this technique is extremely troublesome. Thus we developed a new operative procedure, “split tracheal transplantation,” in which grafts are divided at the midportion and covered with omentum, after demonstrating that the blood supply to tracheal grafts can be reestablished around the suture lines. Two groups of dogs were used. In group A (control, n = 4), a 10-ring length of trachea was autotransplanted. The anastomotic sites and grafts were covered with omental pedicles. In group B (split tracheal transplantation, n = 10), tracheal grafts 10 rings long were autotransplanted. These grafts were divided at the midportion, a piece of omentum was inserted between the two halves, and the midportion was sutured. Grafts were observed regularly by bronchoscopy and examined histopathologically after the animals died or were killed. In some animals, microangiography of the bronchial circulation was done. In the control group, necrosis, stenosis, or malacia of the grafts was observed in three of the four animals. In the split transplantation group, all animals survived for at least 2 months, all grafts were incorporated, and none showed ischemia, stenosis, or malacia. Microscopic examination and microangiography revealed that neovascularization of the graft was promoted by omentum inserted at the midportion of the graft. Split transplantation of the trachea is an easy and reliable way to extend tracheal resection. (J Thorac Cardiovasc Surg 1996;112:-8

The clinical significance of splice variants and subcellular localisation of survivin in non-small cell lung cancers

Survivin is a member of the inhibitor of apoptosis protein family. Survivin has splice variants with different biological functions associated with tumorigenesis. We investigated 134 non-small cell lung cancers (NSCLCs) to study the clinical significance of wild-type survivin, survivin-2B, and survivin-deltaEx3. Real-time PCR analyses were performed for their gene expressions. The subcellular localisation of survivin proteins was evaluated by immunohistochemistry. The Ki-67 proliferation index and the apoptotic index were also evaluated. The survivin-deltaEx3 gene expression was significantly higher in stage II–III than in stage I (P=0.0174), and significantly correlated with the nuclear pan-survivin expression (P<0.0001). The Ki-67 index was significantly higher in wild-type survivin-positive tumours (P<0.0001), survivin-deltaEx3-positive tumours (P<0.0001), and tumours with positive expression of the nuclear pan-survivin (P=0.0047). In contrast, the apoptotic index was significantly lower only in wild-type survivin-positive tumours (P<0.0001). Thus, the wild-type survivin gene expression was associated with apoptotic inhibition and tumour proliferation. Furthermore, the survivin-deltaEx3 gene expression was strongly associated with tumour proliferation, especially in advanced stage NSCLCs. In contrast, the survivin-2B gene expression did not correlate with tumour proliferation or tumour apoptosis

Evaluations of biomarkers associated with 5-FU sensitivity for non-small-cell lung cancer patients postoperatively treated with UFT

The sensitivity to 5-fluorouracil (5-FU) has been reported to be associated with target molecule thymidylate synthase (TS), fluoropyrimidine-metabolising enzymes such as orotate phosphoribosyltransferase (OPRT), and dihydropyrimidine dehydrogenase (DPD). We performed an immunohistochemical study on the clinical significance of TS, OPRT, and DPD expression using 151 resected non-small-cell lung cancer (NSCLC) patients postoperatively treated with a combination of tegafur and uracil (UFT). Eighty-two carcinomas were TS-positive, 105 carcinomas were OPRT-positive, 68 carcinomas were DPD-positive. No correlation was observed in the HSCORE between the TS and OPRT expression (r=0.203), between the TS and DPD expression (r=0.098), or between the OPRT and DPD expression (r=0.074). Regarding the survival of NSCLC patients treated with UFT, the 5-year survival rate of patients with TS-negative tumours was significantly higher than that with TS-positive tumours (P=0.0133). The 5-year survival rate of patients with OPRT-positive stage II to III tumours was significantly higher than that with OPRT-negative stage II to III tumours (P=0.0145). In addition, the 5-year survival rate of patients with DPD-negative tumours was also significantly higher than that with DPD-positive tumours (P=0.0004). A Cox multivariate regression analysis revealed the TS status (hazard ratio 2.663; P=0.0003), OPRT status (hazard ratio 2.543; P=0.0005), and DPD status (hazard ratio 2.840; P<0.0001) to all be significant prognostic factors for the survival of resected NSCLC patients postoperatively treated with UFT