Selective treatment and monitoring of disseminated cancer micrometastases in vivo using dual-function, activatable immunoconjugates.

Drug-resistant micrometastases that escape standard therapies often go undetected until the emergence of lethal recurrent disease. Here, we show that it is possible to treat microscopic tumors selectively using an activatable immunoconjugate. The immunoconjugate is composed of self-quenching, near-infrared chromophores loaded onto a cancer cell-targeting antibody. Chromophore phototoxicity and fluorescence are activated by lysosomal proteolysis, and light, after cancer cell internalization, enabling tumor-confined photocytotoxicity and resolution of individual micrometastases. This unique approach not only introduces a therapeutic strategy to help destroy residual drug-resistant cells but also provides a sensitive imaging method to monitor micrometastatic disease in common sites of recurrence. Using fluorescence microendoscopy to monitor immunoconjugate activation and micrometastatic disease, we demonstrate these concepts of "tumor-targeted, activatable photoimmunotherapy" in a mouse model of peritoneal carcinomatosis. By introducing targeted activation to enhance tumor selectively in complex anatomical sites, this study offers prospects for catching early recurrent micrometastases and for treating occult disease.

Surgeons' knowledge, attitude, and use of preoperative autologous blood donation.

Before a comprehensive educational program on preoperative autologous blood donation was begun, 118 surgeons from three different areas of the country were tested to assess their baseline knowledge and attitude about this practice. Test results were correlated with the percentage of eligible patients that the surgeons actually referred for preoperative donation during a period of observation. The purpose of this preliminary effort was to identify areas in the educational program that required emphasis. Overall, the surgeons' attitude toward preoperative donation was quite favorable, but their depth of knowledge varied. Misunderstandings may have led to diminished use of this service (eg, about 50% didn't realize that many patients with medical conditions or low hematocrits are permitted to donate). However, it is not clear that simply bolstering surgeons' knowledge will increase their appropriate use of preoperative donation. When all 118 surgeons were studied, their knowledge and attitude were unrelated to the percentage of eligible patients referred. However, when 44 surgeons who managed the largest number of eligible patients were analyzed separately, their use of preoperative donation was directly correlated with their knowledge and attitude. The local awareness of AIDS also significantly influenced the use of this service. It is proposed that knowledge of preoperative donation may be important for inducing surgeons to begin referring patients for this service. Once a pattern of successful participation is established, referral seems to increase with the acquisition of working knowledge.

Predeposited autologous blood for elective surgery. A national multicenter study.

To determine the extent to which autologous blood that has been donated in advance ("predeposited") is used in patients undergoing elective surgery and to assess whether predonation decreases the use of homologous blood and the demand on the blood supply, we studied 4996 patients undergoing elective surgery at 18 tertiary care hospitals. Cross-matched blood was ordered for 1287 patients (26 percent), and of these, 590 (46 percent) were considered eligible for predepositing blood. Only 5 percent (32) of the eligible patients actually predeposited blood, indicating that predonation is not widely used. Of those who predeposited, only 13 percent (4 of 32) subsequently received homologous blood, as compared with 36 percent (199 of 558) of those who did not predeposit (P less than 0.01). Among the 199 patients who did not predeposit but required transfusion, we estimate that predonation could have avoided homologous transfusion in as many as 68 percent. If all eligible patients had predeposited autologous blood, they could have supplied as much as 72 percent of their own transfused red cells. The blood for as much as 10 percent of all red-cell transfusions could have been predonated by and transfused into the patients undergoing elective surgery. Greater use of predonation would not only reduce the demand on the blood supply by decreasing the need for homologous transfusion, but would probably also reduce the risk of hepatitis and other transfusion-associated illnesses.

Underutilization of autologous blood donation among eligible elective surgical patients.

In January 1983, blood banks encouraged the use of autologous blood for transfusion in elective surgical patients due to the advent of transfusion-associated AIDS. Since autologous blood does not transmit hepatitis and other viruses and does not cause alloimmunization, it should be utilized whenever possible. To determine whether patients eligible to predeposit autologous blood before elective operation were actually doing so, we studied patients at three hospitals between January 1 and June 30, 1985. Patients considered eligible for autologous predeposit blood donation were adults with preoperative hemoglobin levels of 11 g/dl or more who underwent elective surgical procedures for which blood transfusion was anticipated. Excluded were patients undergoing cardiovascular, intracranial, or renal transplant procedures. Of eligible patients, only 11 percent (32 of 278) predeposited blood; of these, 81 percent (26 of 32) were transfused with only autologous blood. Among eligible patients who did not predeposit blood, all could have benefited from predepositing because transfusion was likely for the procedure. Of those who did not predeposit, 33 percent (83 of 246) received homologous blood and therefore would have benefited from autologous donation. We conclude that autologous donations are underutilized for medically eligible patients undergoing elective operation.