ABSTRACT
As off-pump coronary artery bypass grafting becomes the method of choice for cardio-thoracic surgeons, it has become apparent that the facilitation of coronary artery anastomosis on a beating heart needs to be addressed by improved instrumentation. We propose an intraluminal anastomosis device used in conjunction with a biologic-glue to eliminate suturing and serve as a scaffold for constructing stable anastomoses. The device will continue to serve as an eluting stent postoperatively. The simple technique of using the device and the adhesive will require 5 minutes or less for anastomosis. Moreover, we introduce a novel parallel port vacuum stabilizer foot equipped with a uniform lateral tension inducing turnbuckle mechanism to be used with off-pump stabilization systems. A proposed in vitro protocol details using saphenous vein segments and coronary arteries to test the patency of multiple end-to-side grafts. A pressure transducer will be attached to the graft to monitor flow characteristics. An in vivo protocol details construction of anastomoses during off-pump coronary artery bypass grafting in pigs using the anastomosis device, the turnbuckle vacuum foot, and the biologic-glue. Anastomosis patency will be evaluated intraoperatively and one month postoperatively. Furthermore, the graft site will be examined via flow measurement, angiography, and histological analysis.
ABSTRACT
Irinotecan (CPT11) has established activity in the treatment of advanced colorectal cancer without cross-resistance with established 5-fluorouracil/folinic acid-based therapy. This phase II study was conducted to establish the efficacy and tolerance of combination treatment with irinotecan and 5-fluorouracil as salvage treatment for this disease. Open phase II trial of CPT11 180 mg/m2 on day 1, leucovorin 200 mg/m2 on days 1 and 2, and 5-fluorouracil 400 mg/m2 loading dose followed by 600 mg/m2 infusion on days 1 and 2. Treatment was continued until progression or limiting toxicity. Responders could proceed to surgical resection of residual disease. Thirty-nine patients from 2 institutions received a total of 287 cycles of therapy (median 7 cycles/patient). Eight patients achieved an objective response (7 for liver metastasis and 1 for lung metastasis), and an additional 12 obtained stabilization of disease or minor responses (MR); of these patients, 8 with liver metastasis (7 partial response and 1 MR) underwent hepatic resection of metastases and all them obtained a complete response. The median duration of response was 14 months, and the median survival was 11 months. Hematologic toxicity (neutropenia) was the most common serious side effect (29% of patients in 2% of cycles), but significant fever developed in only 4 patients. Grade III diarrhea was experienced in at least 1 cycle by 10% of patients. The results of this schedule compare favorably with previously reported experience of a phase I study designed to establish the dose of CPT11. Efficacy in this poor prognosis group of patients is very encouraging, and the schedule is well tolerated by even previously treated patients.
