Ephemeral seeds: microembolization of tumor cells during surgery.

One of the most effective therapies for in transit melanoma metastases is hyperthermic isolated limb perfusion. Since its introduction in 1957 by Edward Krementz and his colleagues in the Department of Surgery at Tulane University, hyperthermic isolated limb perfusion has been used extensively for management of in transit melanoma metastases. Of note, the original goal of research performed by this group was to develop a method to treat primary or metastatic cancers in the liver.1 The technology and understanding of extracorporal circulation in the 1950s were limited, and the mortality rate of isolated liver perfusion in animal experiments was unacceptably high. Thus, they focused their efforts on treatment of patients who would otherwise undergo amputation for their extensive in transit melanoma metastases. Hyperthermic isolated limb perfusion for melanoma has since undergone several refinements, and active investigation in the field continues. An ongoing, prospective randomized trial is currently being conducted to determine if the addition of tumor necrosis factor to the melphalan perfusion circuit enhances the effect of this treatment against melanoma without simultaneously increasing systemic or regional toxicity. Alternative methods for regional therapy of melanoma have been proposed, including ischemic isolated limb infusion in which a catheter is placed in the artery, followed by temporary tourniquet occlusion of both arterial inflow and venous outflow.2 Another byproduct of Dr. Krementz’s initial work has been the clinical investigation of hyperthermic isolated liver perfusion for treatment of liver tumors. Richard Alexander and his group in the Surgery Branch at the National Cancer Institute have been instrumental in the development of hyperthermic isolated perfusion for management of hepatic malignancies. The rationale for intensive regional therapy is that some patients with regional metastases do not have clinically relevant distant metastases, or that alternatively, the regional metastases will become symptomatic or life threatening before the time at which distant metastases manifest themselves. Indeed, one third of patients that underwent amputation for advanced regional melanoma experienced long-term survival in retrospective reports from the Memorial Sloan-Kettering Cancer Center.2 Similarly, a large proportion of patients with liver metastases from colon carcinoma will have the disease confined to the liver. Issues relevant to the application of intensive regional therapies include: (1) whether a better understanding of the presence of occult distant metastases would influence the decision whether or not to offer regional therapy; (2) whether detection of occult circulating tumor cells correlates with the presence of distant metastases; and (3) whether regional therapies such as isolated organ perfusion themselves lead to dissemination of circulating tumor cells that may give rise to distant metastases. In an article published in this issue of the Annals of Surgical Oncology, Dr. Wu3 and other researchers in Dr. Alexander’s laboratory have addressed the third issue by using polymerase chain reaction (PCR) amplification to detect evidence of circulating tumor cells in patients undergoing isolated organ perfusion for treatment of either melanoma or colon carcinoma. They have concluded that isolated organ perfusion does not result in systemic microembolization of tumor cells. On one hand, the single round PCR assay used by the investigators is quite sensitive, as it is capable of detection of as few as 10 tumor cells in 1 ml of whole blood. On the other hand, this particular assay is incapable of detecting any fewer than 10,000 shed tumor cells in a 1 liter perfusion circuit! Use of nested PCR primers and two rounds of PCR Received September 20, 1999; accepted September 20, 1999. From the Division of Surgical Oncology, Massachusetts General Hospital, Boston, Massachusetts. Address correspondence to: Kenneth K. Tanabe, MD, Division of Surgical Oncology, Cox 626, Massachusetts General Hospital, Boston, MA 02114; Fax: 617-724-3895. Annals of Surgical Oncology, 6(7):631–632 Published by Lippincott Williams & Wilkins © 1999 The Society of Surgical Oncology, Inc.