Efficacy and Tolerability of Weekly Paclitaxel in Combination with High-dose Toremifene Citrate in Patients with Metastatic Breast Cancer

Toremifene citrate is expected to prevent drug resistance in cancer patients by inhibiting p-glycoprotein activity. The safety and efficacy of combination therapy with high-dose toremifene citrate and paclitaxel were investigated. Between December 2003 and June 2004, 15 women with a mean age of 53 years old with metastatic breast cancer were enrolled. The administration schedule was 80mg/m2 of paclitaxel given on Days 1, 8, and 15, and 120mg/day of toremifene citrate orally administered starting on Day 18. On Days 32 and 39, paclitaxel was concurrently administered again. Toxicities, response rate, and time to treatment failure were assessed. All patients had been treated with endocrine or chemotherapy. Grade 3 leukopenia occurred in 2 patients on the administration of paclitaxel alone, and grade 3 febrile neutropenia occurred in 1 patient given the combination therapy. There was no grade 3 or greater non-hematological toxicity. There was no complete response and 1 partial response, producing a response rate of 6.7%. Median time to treatment failure was 2.7 months. Combination therapy of paclitaxel and toremifene was safe and well tolerated with minimal toxicity. Further clinical trials targeting patients with functional p-glycoprotein are warranted.</p

Peculiar mechanisms of graft recovery through anti-inflammatory responses after rat lung transplantation from donation after cardiac death

Background: Although lung transplantation from donation after cardiac death (DCD), especially uncontrolled DCD, is limited by warm ischemic periods, the molecular mechanism of warm ischemia-reperfusion-injury (IRI) has not been well elucidated. The purpose of this study was to clarify the particular longitudinal mechanisms of molecular factors involved in warm IRI. Methods: Cold ischemic-time (CIT)-group lungs were retrieved and subjected to 3-h of cold preservation, whereas warm ischemic-time (WIT)-group lungs were retrieved after 3-h of warm ischemia. Orthotopic rat lung transplantation was performed and the grafts were reperfused for 1 or 4-h. The graft functions, gene expression, and activation of inflammatory molecules in the grafts were analyzed. Exhaled-carbon-monoxide-concentration (ExCO-C) was measured during reperfusion. Results: Only the WIT-group showed obvious primary graft dysfunction at 1-h reperfusion, but the graft function was recovered during 4-h reperfusion. Most of pro-inflammatory cytokines and stress-induced molecules showed different expression and activation patterns between CIT and WIT groups. In the WIT-group, the expressions of anti-inflammatory molecules, IL-10 and HO-1, were significantly increased at 1-h reperfusion compared to the CIT-group, and these high levels were maintained through 4-h reperfusion. Furthermore, ExCO-C levels in the WIT-group increased immediately after reperfusion compared to the CIT-group. Conclusions: This study indicates that warm IRI may involve a different mechanism than cold IRI and anti-inflammatory pathways may play important roles in the graft recovery after lung transplantation from uncontrolled DCD

'The parachute method': A novel technique for laparoscopic tumour handling

Aims and Objectives: Although laparoscopic surgery for submucosal tumours (SMTs) may require multiple support threads, the traction direction of a single thread is only one option and cannot be freely changed. To solve this problem, we introduced a novel innovative technique for tumour handling, named 'the parachute method'. Subjects and Methods: Prior to suturing, the surrounding vessel was treated when the tumour was located near the lesser or greater curvature. A monofilament thread was ligated in the serous muscle layer along the peritumoural markings with approximately five stitches in a row, with moderate deflection. Next, the other monofilament thread was passed through the deflection and ligated; this resembled a parachute shape that could be pulled in any direction over the entire circumference with uniform tension. Results: We performed this procedure in three patients with extramural growth-type gastrointestinal stromal tumours of approximately 2–3 cm. The median suturing time was 10 minutes. Laparoscopic local resection of the stomach was safely performed, and the patients were discharged without any complications. Conclusion: In this study, we demonstrate a novel, simple, inexpensive, useful and reasonable technique for handling SMTs, named 'the parachute method'. We believe that this technique will have additional applications in cooperative surgery with endoscopy