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.

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.

Influence of blood transfusions on surgery-induced immune changes in colorectal carcinoma.

Perioperative blood transfusions have been shown to enhance recurrence rates in patients with operable solid tumors, perhaps by inducing immunosuppression through unknown mechanisms. Since the surgical treatment per se has been proven to induce immune alterations, the present study was carried out to evaluate the immune effect of blood transfusions on surgery-induced immune variations. The study included 27 patients with resectable colorectal carcinoma, 18 of whom received no transfusion, while the other 9 received blood transfusions in the perioperative period. Total lymphocytes, total T lymphocytes (CD3) and soluble IL-2 receptor serum levels (SIL-2R) were measured on venous blood samples collected from each patient either before or 7 days after surgery. Both in non transfused and in transfused patients, SIL-2R mean levels were significantly higher after than before surgery. Their increase was associated with a significant decrease in both lymphocytes and CD3 cells in non-transfused patients, while in the transfused ones lymphocytes and CD3 cells did not show significant changes with surgery. This study shows that blood transfusions modify the relation between changes in SIL-2R and those in lymphocyte number induced by major surgery. It remains to be understood which relation exist between these immune effects and the promoting action of blood transfusion on relapse frequency in cancer.

Effects of a preoperative course of interleukin-2 on surgical and immunobiological variables in patients with colorectal cancer: a phase 2 study.

OBJECTIVE: A phase 2 study to evaluate the effects of a short preoperative course of interleukin-2 (IL-2) on the postoperative course of patients with cancer. DESIGN: Open study. SETTING: San Gerardo Hospital, Monza, Italy. SUBJECTS: 16 Consecutive patients with locally advanced colorectal cancer, with or without metastases. INTERVENTION: IL-2 in a dose of 9 x 10(6) IU/m2 twice daily for three days; patients were operated on within 36 hours of the cessation of IL-2 treatment. MAIN OUTCOME MEASURES: Morbidity, mortality, and changes in numbers of lymphocytes, T lymphocytes, natural killer (NK) cells, and CD25 (cluster of determination) positive cells. RESULTS: There was no morbidity or mortality--in particular, there were no infections even in the patients who were at highest risk. The mean numbers of lymphocytes, T lymphocytes, NK cells, and CD25 positive cells increased significantly during the postoperative period. All patients showed evidence of infiltration of lymphocytes or eosinophils (or both) into the tumour tissue. CONCLUSIONS: The results suggest that a three day course of IL-2 preoperatively is well tolerated, stimulates would repair, neutralizes the lymphocytopenia induced by major operation, and induces immune cells to infiltrate the tumour. Randomised studies are needed to confirm these results.

Effects of a preoperative therapy with interleukin-2 on surgery-induced lymphocytopenia in cancer patients.

It is known that major surgery may determine immunosuppression. This side effect might have a prognostic significance particularly in cancer patients, in whom the decrease in host defenses during the postoperative period could promote the proliferation of possible micrometastases. Since antitumor immune response is an IL-2-dependent phenomenon, a study was started to evaluate the effects of a preoperative injection of IL-2 on surgery-induced immune changes in cancer patients. The study included 12 colon cancer patients, treated subcutaneously with IL-2 at a dose of 9 x 10(6) IU/m2 twice daily for 3 consecutive days before surgery. Patients underwent surgery within 36 h from IL-2 interruption. The results were compared to those found in a control group of 18 colon cancer patients. Mean number of lymphocytes, T lymphocytes and NK cells significantly decreased after surgery in control patients; on the contrary, no postoperative decrease in immune cells was seen in IL-2 group. No anesthesiologic or surgical complication was seen in patients pretreated with IL-2 before surgery. This preliminary study would suggest that a preoperative therapy with IL-2 is an effective and well tolerated medical approach to neutralize surgery-induced immunosuppression in cancer patients.

[Choice of technique in "difficult" inguinal hernias. Personal experience]. / Zur Wahl der Technik bei der Beseitigung der "schwierigen" Leistenhernien. Unsere Erfahrung.

The authors refer on their positive results in the treatment of so-called difficult inguinal hernias (relapsing or multiple hernias) with the use of prosthetic prolene mesh according to Stoppa's procedure (partly modified) through a preperitoneal approach after a Pfannenstiel's incision. On the other hand recurrent hernias in risky patients as well as gross hernias are treated by Rives' method which consists in a prolene mesh placement through the inguinal approach.

[Anastomosis in emergency large intestine resections in the therapy of obstructing colonic cancer]. / Die Anastomose bei notfallmässigen Dickdarmresektionen in der Therapie des obturierenden Kolonkarzinoms.

A comparative inquiry has been performed on 57 cases of colonic resections for colon carcinoma carried out in emergency with intestinal anastomoses which have been performed according to Gambee's technique (single layer little introflecting suture), Nockemann's technique (a continuous suture in dexon comprising mucosal and submucosal layers and a separate no introflecting stitch suture of the serosal and mucosal layers in teflene) and 'Auf Stoss'-technique (single layered end-on, no introflecting, no mucosal comprising). We have noticed leakages in 20% of the cases performed with the first method, 13% with the second and 12% with the third method. Here below shown the reasons, why the second and the third method are to be considered the best ones and the indications relevant to their usage. Also are discussed: intraoperative irrigation of the colon according to Dudley and the own technique, short term chemotherapeutic prophylaxis, transanastomotic drain, fibrin glue on colon anastomosis.

[Two-time traumatic rupture of the gallbladder]. / Rottura traumatica in due tempi della colecisti.

Two cases of traumatic perforation of the gallbladder following open and closed injury to the abdomen respectively are described. Their common feature was a long, oligosymptomatic free interval. A brief account is given of the aetiopathogenetic, clinical and therapeutic problems raised by cases of this kind.

[Perforations of the small intestine]. / Perforazioni del tenue

Six cases of perforation of the small intestine, one secondary to anaphylactoid purpura and five spontaneous, are reported. Ingestion of an iced drink acted as a trigger in two cases. A vascular genesis is put forward to explain the aetiopathogenesis of two cases and it is noted that perforation of this type is present in the final ileal ansa, at the mesenterial margin. In three cases, histology revealed the presence of double refraction crystal. These came from vegetal residues and are probably capable of penetrating from the lumen into the mucosa causing a foreign body reaction, abscess and subsequent perforation. In these cases, perforation occurred in an ansa located further away than the last ileal ansa (about 3 m) and on the mesenterial margin. Intestinal resection and subsequent end-to-end, single layer anastomosis were performed in all cases.