Preoperative interleukin-2 subcutaneous immunotherapy may prolong the survival time in advanced colorectal cancer patients.

It has been demonstrated that surgery may induce immunosuppression. This finding could influence the clinical course of surgically treated cancer patients. Moreover, preliminary experimental studies have shown that a preoperative injection of IL-2, whose importance in generating the antitumor immune response is well known, may neutralize surgery-induced immunosuppression. At present, however, it is still unknown whether preoperative IL-2-induced immune improvement in the postoperative period may influence the prognosis of surgically treated cancer patients. The present study was performed to evaluate the prognostic impact of IL-2 presurgical therapy in advanced colorectal cancer patients. The study included 50 colorectal cancer patients, Dukes' stage D, who were randomized to be treated with or without IL-2 preoperatively (18.10(6) IU/day subcutaneously for 3 consecutive days). After surgery, all patients underwent chemotherapy with 5-FU and folates until disease progression. Postoperative mean numbers of lymphocytes, T lymphocytes, natural killer cells and activated lymphocytes were significantly higher in IL-2-treated patients than in controls. Moreover, the percent of lymphocytic and/or eosinophilic tumor infiltration was significantly higher in IL-2 group than in controls. Finally, both survival curve and the percent of survival at 1 year were significantly greater in patients pretreated with IL-2 than in controls. This clinical trial demonstrates that preoperative IL-2-induced neutralization of postoperative lymphocytopenia is associated with a prolonged survival time in advanced colorectal cancer patients.

Pre-operative interleukin-2 immunotherapy induces eosinophilic infiltration in colorectal neoplastic stroma.

Interleukin-2 (IL-2) may induce peripheral eosinophilia and this phenomenon is related with response to IL-2 immunotherapy in patients with metastatic renal cell carcinoma. In previous experiences is reported that preoperative course with IL-2 may reverse the surgery-induced immunosuppression. This study's objective is to evaluate the histological changes of inflammatory infiltration in tumour stroma, in patients pretreated with IL-2 immunotherapy. 7 patients admitted to our surgical department with resectable recurrent colorectal cancer were treated with pre-operative course of IL-2; the tissue samples were analyzed for eosinophilic and inflammatory infiltration and compared with the samples obtained in the primary operation, performed without immunotherapy. In all patients were observed an increase of eosinophilic infiltration in tumour tissue. The mean increase were 200%, with high statistical significance (p < 0.0001). IL-2 pre-operative immunotherapy is able to change the interaction between host and tumour, by modifying the histological inflammatory infiltration in colorectal cancer tissue.

Immune effects of preoperative immunotherapy with high-dose subcutaneous interleukin-2 versus neuroimmunotherapy with low-dose interleukin-2 plus the neurohormone melatonin in gastrointestinal tract tumor patients.

Surgery-induced immunosuppression could influence tumor/host interactions in surgically treated cancer patients. Previous studies have shown that high-dose IL-2 preoperative therapy may neutralize surgery-induced lymphocytopenia. Moreover, experimental studies have demonstrated that the immunomodulating neurohormone melatonin (MLT) may amplify IL-2 activity and reduce its dose required to activate the immune system. On this basis, we have compared the immune effects of presurgical therapy with high-dose IL-2 with respect to those obtained with preoperative neuroimmunotherapy consisting of low-dose IL-2 plus MLT. The study included 30 patients with gastrointestinal tract tumors, who were randomized to undergo surgery alone, or surgery plus a preoperative biotherapy with high-dose IL-2 (18 million IU/day subcutaneously for 3 days) or low-dose IL-2 (6 million IU/day subcutaneously for 5 days) plus MLT (40 mg/day orally). Patients underwent surgery within 36 hours from IL-2 interruption. Both IL-2 plus MLT were able to prevent surgery-induced lymphocytopenia. However, mean number of lymphocytes, T lymphocytes and T helper lymphocytes observed on day 1 of postoperative period was significantly higher in patients treated with IL-2 plus MLT than in those receiving IL-2 alone. Moreover, toxicity was less in patients treated with IL-2 and MLT. This biological study shows that both immunotherapy with high-dose IL-2 or neuroimmunotherapy with low-dose IL-2 plus MLT preoperatively are tolerated biotherapies, capable of neutralizing surgery-induced lymphocytopenia in cancer patients. Moreover, the study would suggest that the neuroimmunotherapy may induce a more rapid effect on postoperative immune changes with respect to IL-2 alone.

Preoperative neuroimmunotherapy with subcutaneons low-dose interleukin-2 and melatonin in patients with gastrointestinal tumors - its efficacy in preventing surgery-induced lymphocytopenia.

Our previous studies have shown that a preoperative injection of high dose IL-2 is able to abrogate surgery-induced immunosuppression in colorectal cancer patients. Moreover, our previous clinical investigations have indicated the possibility of amplifying IL-2 activity by a concomitant administration of the pineal immunomodulating hormone melatonin (MLT). On this basis, a biological study was performed to investigate the immune effects of a preoperative biotherapy consisting of low-dose IL-2 plus MLT in patients with gastrointestinal tumors. The study included 20 consecutive patients with gastrointestinal tract tumors, who underwent radical or palliative surgery. Patients were randomized to receive no preoperative treatment or a presurgical neuroimmunotherapeutic regimen consisting of low dose of IL-2 and MLT. IL-2 was injected subcutaneously at 3 million IU twice/day for 5 days in combination with MLT at 40 mg/day in the evening. Patients underwent surgery within 36 h from the last IL-2 injection. The mean number of lymphocytes, T lymphocytes and NK cells significantly decreased during the postoperative period in control patients, whereas it increased in patients pre-treated by immunotherapy. CD25-positive mean cell number increased in both groups of patients; however, postoperative mean number of CD25 expressing cells was significantly higher in patients pretreated with IL-2 and MLT than in controls. No immunotherapy-related toxicity occurred. This preliminary study would suggest that a neuroimmunotherapeutic regimen with low-dose IL-2 and MLT given preoperatively is a well tolerated therapy, which is able to prevent surgery-induced lymphocytopenia in cancer patients. This perioperative manipulation of host anticancer defenses could have a prognostic role in the clinical course of the neoplastic disease.

[Use of the computer in total parenteral nutrition. Our experience]. / Utilizzo del computer nella N.P.T. Nostra esperienza.

The Authors show their method to set up and to plan a T.P.N. for surgical patients. They emphasize how the introduction of the computer in the intensive therapy practice, not only helps the work of the medical corps and the hospital attendants, but it marks and plans again every day the components' dosages on the blood-metabolical alterations, daily checked on the patients. They are here showing their experiences since 1977, appraising in a critical way the directions and the results.