Tsutomu Nishida

Development of a tracheal stapling device

OBJECTIVE Recent years have witnessed a multitude of technical advances regarding gastrointestinal and vascular anastomosis. However, difficulties still hamper tracheal and bronchial anastomosis. We have therefore developed a novel set of instruments and performed end-to-end anastomosis of the transected canine cervical trachea to establish the operative procedures. METHODS A novel set of instruments was developed for tracheal anastomosis including two pairs of forceps for grasping the free tracheal ends, a metal connecting device, and clamping forceps for staple insertion. Briefly, the operative procedure involves fixation of forceps circumferentially to hold the cut trachea. End-to-end anastomosis is completed by joining the forceps with a clamp and stapling the tracheal ends everted outward. End-to-end anastomosis of the cervical trachea was performed on 23 dogs. Animals were monitored on a daily basis, and bronchofiberscopy was performed periodically. Deaths from all causes were evaluated by immediate necropsy. Sixteen dogs were sequentially sacrificed at 1, 2, 3 and at 6 months after surgery. RESULTS In our dog model, stenosis at the anastomosis of the cervical trachea was found as a complication in 8 of 23 cases. Tracheal rupture occurred in a further 3 cases, slight granulation in another 4, and the remaining 8 showed no complication. Histological findings of anastomotic healing were similar to those reported for hand suture.

The relationship between the expression of thymidylate synthase, dihydropyrimidine dehydrogenase, orotate phosphoribosyltransferase, excision repair cross‑complementation group 1 and class III β‑tubulin, and the therapeutic effect of S‑1 or carboplatin plus paclitaxel in non‑small‑cell lung cancer

Previous studies have reported that the expressions of specific proteins may predict the efficacy of chemotherapy agents for non-small cell lung cancer (NSCLC) patients. The present study evaluated the expression of proteins hypothesized to be associated with the effect of chemotherapeutic agents in 38 NSCLC patients with pathological stage II and IIIA. The subjects received carboplatin plus paclitaxel (CP) or S-1 as adjuvant chemotherapy following complete resection. The protein expressions evaluated were those of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phsphoribosyltransferase (OPRT), which were suspected to be associated with the effect of S-1 agents, excision repair cross-complementation group 1 (ERCC1), which was suspected to be associated with the effect of platinum-based agents, and class III β-tubulin (TUBB3), which was suspected to be associated with the effect of taxane-based agents. The positive rate of TS was 55.3% (n=21/38), DPD was 57.9% (n=22/38), OPRT was 42.1% (n=16/38), ERCC1 was 47.4% (n=18/38) and TUBB3 was 44.7% (n=17/38). Among the patients who received S-1 adjuvant chemotherapy, TS-negative cases demonstrated a significantly better disease-free survival than positive cases. Thus, TS protein expression may have been a factor that predicted the effect of S-1 agent as adjuvant chemotherapy.

S-1 vs. paclitaxel plus carboplatin as adjuvant chemotherapy for completely resected stage II/IIIA non‑small‑cell lung cancer

The majority of patients with completely resected stage II or IIIA non-small-cell lung cancer (NSCLC) require adjuvant chemotherapy to improve survival following surgery. In the present trial, the 2-year disease-free survival (DFS), and the feasibility and safety of S-1 as an adjuvant chemotherapy for advanced lung cancer were evaluated. A total of 40 patients with completely resected stage II or IIIA NSCLC were enrolled and randomized to receive postoperative chemotherapy with either up to 4 cycles of paclitaxel plus carboplatin (arm A) or with up to 1 year of S-1 (arm B). The primary endpoint was 2-year DFS. The secondary endpoints were feasibility and toxicity. A total of 40 patients were enrolled, but 3 were excluded in accordance with the exclusion criteria. The remaining 37 patients were analyzed. The 2-year DFS rate was 54.2% in arm A and 84.2% in arm B. Overall, 15/18 (83.3%) patients completed 4 cycles of paclitaxel plus carboplatin and 13/19 (68.4%) completed 1-year of S-1adjuvant chemotherapy. Of the 18 (16.7%) patients in arm A, 3 experienced grade 3 or 4 adverse events, while none in arm B experienced such events. Therefore, S-1 chemotherapy for patients with completely resected stage II or IIIA NSCLC was a feasible and safe regimen, and it may therefore be considered as a potential adjuvant chemotherapy option for advanced NSCLC.