Patients with metastatic melanoma undergoing therapy with cyclophosphamide (CPM), tumor-infiltrating lymphocytes (TIL), and interleukin-2 (IL-2) were studied for the ability of their 111In-labeled TIL or peripheral blood lymphocytes (PBL) to localize in sites of tumor using gamma camera imaging and biopsies. Nineteen infusions of radiolabeled TIL were given to 18 patients, while five patients received radiolabeled autologous PBL during TIL therapy. Clear tumor localization was seen on 13 of 18 nuclear scan series performed on 111In-TIL recipients, while tumor was imaged in only one of four scan sequences on patients given 111In-PBL. Nineteen paired biopsies of tumor and normal skin were completed on 10 patients receiving 111In-TIL, while eight biopsies were done on three PBL patients receiving 111In-PBL. The mean percentage of total injectate activity localizing per gram of tumor tissue was 0.0049% in the TIL group and 0.0010% in the PBL group (P2 = .0004). The mean of the tumor to normal skin ratios of the 111In-TIL group was three times that for 111In-PBL (P2 = .0072). One patient was studied by nuclear scanning on three consecutive treatment courses of CPM, TIL, and IL-2. He initially demonstrated clear tumor localization by 111In-TIL at several sites, then faint localization with 111In-PBL at a single site, and subsequently positive tumor imaging on repeat 111In-TIL infusion at multiple sites. These results confirm and expand our initial data demonstrating that human TIL transferred with CPM pretreatment and followed by IL-2 preferentially localize to tumor sites and indicate that this localization is greater for TIL than PBL.
OVER THE PAST 20 years, many reports have documented that surgical resection of isolated hepatic metastases from colorectal carcinoma can result in a 25% to 30% 5-year survival benefit.'-13 Relative contraindications for hepatic resection include the presence of positive hepatic nodes, extrahepatic metastases, or four or more liver metastases.12 As this therapy has gained acceptance, the question of appropriate therapy for recurrent hepatic metastases has become relevant. We present our experience with hepatic resection along with an overview of the few anecdotal case reports to be found in the literature. RESULTSBetween 1970 and 1987,106 patients had undergone resection of colorectal liver metastases at the National Cancer Institute (84 patients) or Emory University School of Medicine (22 patients). Among these patients, 9 had a second hepatic resection of recurrent liver metastases (7 at NCI, 2 at Emory). Median follow-up for 11/56/14278these patients was 21 months (range, 9 to 67) from the time of the second liver resection.A summary of these nine cases is compiled in Table I. The median patient age at follow-up was 57 years (range, 44 to 70 years). There were six men and three women. At the first hepatic resection, eight patients had wedge resections and one patient had a right trisegmentectomy for removal of metastatic lesions. Wedge resections were classified as operations that entailed the removal of less than a major lobe. Seven patients had solitary metastases, while patients 3 and 5 had bilobar metastases. Patients 3 through 9 had documented negative resection margins; the status of resection margins for patients 1 and 2 is unknown. In six of nine patients, hepatic resections were performed at the time of primary tumor excisions. The remaining three patients had resection of metachronous liver tumors, which were all diagnosed by elevations in carcinoembryonic antigen levels. Patient 2 received adjuvant systemic fluorouracil chemotherapy after the first hepatic resection.The median interval from the time of the first hepatic resection to the diagnosis of the hepatic recurrence was 21 months (range, 1 to 39 months). Recurrent disease was initially diagnosed on the basis of elevations in carcinoembryonic antigen levels in six patients and computed tomography (CT) scans in the other three patients. Preoperative evaluation to exclude extrahe- 230
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