We describe here the preliminary results of the systemic administration of autologous lymphokine-activated killer (LAK) cells and the recombinant-derived lymphokine interleukin-2 to patients with advanced cancer. This regimen was based on animal models in which the systemic administration of LAK cells plus interleukin-2 mediated the regression of established pulmonary and hepatic metastases from a variety of murine tumors in several strains of mice. We treated 25 patients with metastatic cancer in whom standard therapy had failed. Patients received both 1.8 to 18.4 X 10(10) autologous LAK cells, generated from lymphocytes obtained through multiple leukaphereses, and up to 90 doses of interleukin-2. Objective regression of cancer (more than 50 per cent of volume) was observed in 11 of the 25 patients: complete tumor regression occurred in one patient with metastatic melanoma and has been sustained for up to 10 months after therapy, and partial responses occurred in nine patients with pulmonary or hepatic metastases from melanoma, colon cancer, or renal-cell cancer and in one patient with a primary unresectable lung adenocarcinoma. Severe fluid retention was the major side effect of therapy, although all side effects resolved after interleukin-2 administration was stopped. Further development of this approach and additional patient follow-up are required before conclusions about its therapeutic value can be drawn.

Interleukin-2 (IL-2) is a 15,000 dalton glycoprotein produced naturally by human T-cells during an immune response. IL-2 has been demonstrated to have substantial activity alone or in combination with the adoptive transfer of lymphokine-activated killer cells in murine tumor models. IL-2 derived from both natural (Jurkat human T-cell tumor) and recombinant (Escherichia coli) sources has been studied in Phase I protocols designed to evaluate toxicity in patients with a variety of solid tumors and to ascertain improvement in clinical parameters and immunologic status. A total of 16 patients (7 with acquired immune deficiency syndrome [AIDS] and 9 with non-AIDS malignancies) were treated with Jurkat derived IL-2. The total maximum dose (1.3 X 10(5) U/kg) was limited only by supply of this reagent. A total of 25 patients have been treated with recombinant IL-2 (RIL-2) alone. Dose-limiting toxicity manifested by marked malaise and weight gain was achieved with doses of RIL-2 of 10(6) U/kg as a single bolus or 3000 U/kg/hr. IL-2 could be administered intraperitoneally with similar toxicity. Minimal renal or hepatic toxicity was demonstrated. Hematologic toxicity was limited to mild anemia (25/25), thrombocytopenia (10/25), and marked reversible eosinophilia (15/25). Pronounced weight gain greater than 2 kg (16/25) occurred in most patients, primarily those who received cumulative doses of greater than 1-3 X 10(5) U/kg of IL-2. The weight gain amounted to as much as 10% to 20% of the pretreatment weight over 3 weeks of treatment and limited our ability to give higher doses. Two partial responses (greater than 50% decrease in cross sectional diameters) were seen in two patients with melanoma metastatic to the lung.

Summary Prophylactic mastectomy (PM) offers 90% or greater reduction in risk of breast cancer to women at increased hereditary risk. Nonetheless, acceptance in North America has been low (0–36%). Most women report reduced cancer worry post-operatively, but up to 25–50% of women electing surgery also report psychological distress and/or difficulty adapting following PM. Psychological consultation to aid decision-making and improve post-surgical coping isn’t routinely offered. This retrospective, cross-sectional study explored, quantitatively and qualitatively, interest in and acceptability of psychological consultation for issues related to PM among 108 women who had undergone or were considering surgery. Of the 71 women who had undergone PM, more than half felt pre-surgical psychological consultation was advisable and nearly 2/3 felt post-surgical psychological consultation would be helpful. All 37 women (100%) currently considering PM believed psychological consultation would aid decision-making and preparation for surgery. Narratives from the interviews illustrate the nature and intensity of the need for psychological support and describe preferences for the role of the psychologist. Suggestions are offered for the integration of psychological services for women deciding about or adapting to PM.

Twenty patients with extremity soft tissue tumors were prospectively evaluated with magnetic resonance imaging (MRI) and computed tomography (CT) scans with subsequent anatomic correlation of surgical findings. MRI and CT had a similar percentage of accuracy in assessing tumor relationship with major neurovascular (80% and 70%, respectively) and skeletal (80% and 75%, respectively) structures. MRI was significantly better than CT in displaying contrast between tumor and muscle when using the T2 weighted spin echo (SE) (p2 less than 0.002) and inversion recovery (IR) (p2 less than 0.005) pulse sequences. MRI and CT were comparable in demonstrating contrast between tumor and fat. The contrast between tumor and vessel was better displayed by MRI compared with CT when using the T1 weighted SE (p2 less than 0.001) and T2 weighted SE (p2 less than 0.001) pulse sequences. T1 and T2 values were measured on fresh tumor and normal tissue samples and were used to predict relative contrast on different MRI pulse sequences using isosignal contour plots. MRI appears to offer several advantages over CT in the evaluation of extremity soft tissue tumors.

Using our head and neck service database, we reviewed 3,200 surgical procedures performed at our institution over a 7-year period. We identified 54 patients whose surgery was complicated postoperatively by wound bleeding. The procedure most often complicated by wound bleeding was parotidectomy, 1.7% (14 of 510 patients), followed by thyroidectomy, 1.6% (8 of 504 patients), neck dissection combined with other procedures, 1.3% (12 of 885 patients), and neck dissection alone, 1.1% (6 of 534 patients). Bleeding developed in flap donor sites in 2 of 227 patients and followed miscellaneous procedures in 12 others. Thirty-one patients were treated by reexploration in the operating room, 13 had limited exploration on the ward and 10 were observed with no intervention. There was no difference in wound healing between the three treatment groups. However, mean hospital stay was shortest for patients who had wound exploration in the operating room, 6.2 days, for exploration on the ward, 10.8 days, and 18.9 for those that were observed. Drains had no effect on wound healing or mean hospital stay.

From 1961 to 1991, a total of 1,452 esophagectomies were performed for esophageal cancer at Memorial Sloan-Kettering Cancer Center. Of these patients, 40 (2.7%) developed complications requiring a second operation during the same hospitalization. The majority of the carcinomas were located in the midesophagus or the gastroesophageal junction. The pathologic diagnosis was squamous cell carcinoma in two-thirds of the patients. Few comorbid factors could be identified. Twenty-nine patients (72%) had a standard Ivor-Lewis resection, 5 (12%) had a transhiatal resection, 5 (12%) had a transabdominal approach, and 1 (3%) had a cervical approach only. Complications requiring reoperation were the following: respiratory failure in 13 patients, anastomotic leak in 6, bowel obstruction in 5, major bleeding in 4, wound dehiscence in 4, tracheo-esophageal fistula in 3, feeding tube malposition in 2, empyema in 1, chyle leak in 1, a positive margin in 1. Twelve of these same patients had a persistent or second complication and required a third operation. Among the 40 patients in this study, the mortality was 40%.

Purified recombinant human interleukin 2 (RIL 2) derived from E. coli containing the inserted gene encoding for IL 2 was administered to 20 patients with a variety of malignancies. Toxicity was dose related and included fever, chills, malaise, arthralgias, myalgias, and unexpectedly, weight gain related to marked fluid retention. All patients receiving more than 10(5) U/kg total cumulative dose developed evidence of fluid retention, and all patients requiring discontinuance of RIL 2 (11/20) received total doses of between 2.54 X 10(5) U/kg to 15.4 X 10(5) U/kg. The limiting dose with this preparation was 3000 U/kg/hr by continuous administration or 10(6) U/kg by bolus administration. IL 2 was rapidly cleared from the plasma, with a half life of 6.9 min, and a later delayed clearance was consistent with a two-compartment model, with slower release from the extravascular space back into the plasma compartment. A marked change in lymphoid cells in the periphery was noted with an early depletion of all lymphoid cells, followed by an expansion of such cells with continuous IL 2 administration. A twofold to 16-fold expansion of total lymphoid cells in the peripheral blood could be demonstrated. TAC+ cells representing up to 25% of the circulating peripheral blood mononuclear cells could be demonstrated with 3 wk of continuous RIL 2 administration. Interferon-gamma levels increased in patients treated with IL 2. Precursors of lymphokine-activated killer cells generated under standard conditions were depleted within 2 to 3 min after IL 2 administration, but repopulated the peripheral blood after 7 to 10 days of continuous IL 2 administration. No tumor regression was seen in any of the cancer patients treated with IL 2 alone.

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