Rationale and experimental design for the VA Cooperative Study of Anticoagulation (Warfarin) in the Treatment of Cancer.

Anticoagulants have been demonstrated to reduce tumor growth in certain experimental animal systems. Inhibition of clot formation interferes with tumor growth and spread while enhancement of coagulation promotes tumor growth and spread. The fact that the coagulation mechanism is commonly activated in human malignancy together with preliminary reports of therapeutic efficacy of anticoagulants suggests that the coagulation mechanism may be of pathophysiologic significance also in the growth of human tumors. A VA Cooperative Study has been established to test the hypothesis that warfarin anticoagulation will modify the course of malignancy in man. The purpose of this paper is to present the rationale and experimental design for this study with emphasis on management of anticoagulant administration in cancer patients. This paper serves as the basis for forthcoming reports of toxicity and therapeutic efficacy of warfarin in human malignancy.

Limb salvage and selectivity.

In a group of properly prepared poor risk patients with advanced atherosclerosis of both the aortoiliac and femoropopliteal segments, a combined procedure, extra-anatomic bypass with an extended profundoplasty, was used for successful salvage of their ischemic--mean calf pressure=27 millimeters of mercury--limbs. Prediction of success versus failure could be determined on neither clinical nor angiographic-anatomic grounds but was possible using two simple measurements: a large aortoiliac differential pressure--deltaP--between inflow pressure obtained from a standard arm cuff and outflow pressure measured directly from the femoral artery, 89.3 millimeters of mercury versus 33.2 millimeters of mercury, p less than 0.001, and a potentially adequate outflow bed as determined by the percentage drop in outflow [(deltaPo/Po) per cent] upon papaverine injection, 36.3 versus 11.3 per cent, p less than 0.001. These values became an important part of the selection scheme developed in the approach to 24 ischemic limbs.

Screening for lower extremity deep venous thrombosis. An improved plethysmographic and Doppler approach.

Noninvasive screening of the lower extremities for deep vein thrombosis was performed bilaterally on 1,118 patients. Impedance plethysmography alone was used in 868. Venography in 135 revealed an accuracy of 88%, with a false-negative rate of 5.3% and a false-positive rate of 18.6%. A combined ultrasonic Doppler and modified impedance technic was used in 250 patients. Venography in forty revealed an accuracy of 95%, with a false-positive rate of 10% and no undetected thrombi. The combined technic, emphasizing the more accurate modality in three anatomic areas, has proven sensitive, specific, and reliable as a screening test for deep venous thrombosis.

Plastic mesh repair of incisional hernias.

During eight years polypropylene mesh was used in fifty-three patients for the repair of difficult incisional hernias. There was no operative mortality, and the mesh has been uniformly well tolerated. To date, recurrences have been observed in six patients (11.3%), a distinct improvement over the era before mesh was used. Greater attention to the details of mesh fixation may further lower the recurrence rate.

Factors related to survival following resection for gastric carcinoma: analysis of 903 cases.

This report is based on 903 patients with resections for gastric carcinoma between October 1957, and July 1969, entered in controlled trials of adjuvant therapy with Thio-TEPA and FUDR. Neither Thio-TEPA nor FUDR, as administered, prolonged survival. The extent of disease at the time of curative surgery is related to survival for the first 36 months postoperatively. Involvement of lymph nodes, resection of the esophagus, and serosal penetration are predictive of recurrence up to 36 months. There appear to be three groups of patients: 1) Cured (26%); 2) Slowly growing tumor--23% (median survival, 25 months); and 3) Rapidly growing tumor--51% (median survival, eight months). The absence of blood-vessel invasion, lymphatic invasion, lymph-node involvement, and serosal penetration characterize those patients in Group A.