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Biomedical subjects

F Brivio

Publications and source records attributed to F Brivio.

At least 19 recordsLinked to original sources

Prevention of interleukin-2-induced thrombocytopenia during the immunotherapy of cancer by a concomitant administration of the pineal hormone melatonin.

Thrombocytopenia is a frequent haematologic complication of IL-2 immunotherapy of cancer. Preliminary results suggest a role of melatonin in the regulation of platelet production, so a study was started to evaluate the influence of the pineal hormone on IL-2-induced thrombocytopenia. Of 25 lung cancer patients, 10 were treated with melatonin alone, 7 received IL-2 alone and 8 patients were concomitantly treated with IL-2 and melatonin. Thrombocytopenia occurred in 3/7 patients treated with IL-2 alone, and in none of those treated with IL-2 plus melatonin; this difference was statistically significant. Platelet number increased during IL-2 plus melatonin, even though not significantly; on the contrary, platelet number decreased during IL-2 alone. Platelet number observed in patients treated with IL-2 plus melatonin was significantly higher than in those who received IL-2 alone. Finally, melatonin alone did not substantially influence platelet number. These results show that melatonin may abolish IL-2-induced thrombocytopenia. This might be due to an inhibitory effect of melatonin on macrophage-mediated platelet destruction, with a following increase in platelet number due to an enhanced IL-3 production in response to IL-2.

Adult

Serum levels of insulin-like growth factor-I in operable breast cancer in relation to the main prognostic variables and their perioperative changes in relation to those of prolactin.

AIMS AND BACKGROUND: In addition to estrogens, prolactin (PRL) and IGF-I have also appeared to stimulate breast cancer growth. The present study was performed to evaluate IGF-I blood levels in operable breast cancer in relation to PRL values and the main prognostic variables. METHODS: The study included 40 patients, clinical stage T1-3NO-2MO. Venous blood samples were collected before and 7 days after surgery. PRL and IGF-I were measured by radioimmunoassay. The control group consisted of 50 healthy women. RESULTS: Mean serum levels of IGF-I were significantly higher in patients than in controls, without any apparent relation to the main prognostic variables, including estrogen receptor and node status. Surgery-induced hyperprolactinemia occurred in 22/40 patients. IGF-I mean concentrations observed in the postoperative period in patients with surgery-induced hyperprolactinemia were significantly lower than those seen in patients showing no postoperative PRL rise. CONCLUSIONS: The study showed that operable breast cancer may be associated with abnormally high levels of tumor growth factor IGF-I, and that surgery was followed by an IGF-I decline only in patients who showed surgery-induced hyperprolactinemia. Our previous studies have shown that postoperative hyperprolactinemia is a favorable prognostic factors for operable breast cancer. The present study, by showing that a postoperative PRL rise is associated with a fall in IGF-I, would suggest that surgery-induced hyperprolactinemia may determine a lower tumor relapse rate by determining a diminished secretion of breast tumor growth factor IGF-I.

Adult

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.

Adult

Neuroimmunotherapy with subcutaneous low-dose interleukin-2 and the pineal hormone melatonin as a second-line treatment in metastatic colorectal carcinoma.

On the basis of our previous preliminary data which showed that the pineal hormone melatonin (MLT) may potentiate IL-2 activity and reduce the dose of IL-2 required to determine an effective host antitumor response, we performed a clinical study with low-dose IL-2 given once/day subcutaneously (3 million IU/day for 6 days/week for 4 weeks) in association with MLT (50 mg/day orally at 8.00 p.m. every day) as a second-line therapy in metastatic colorectal cancer patients pretreated with 5-fluorouracil. Evaluable patients were 13/14, and most of them showed disseminated liver metastases. No objective tumor regression was seen. A stabilization of disease was achieved in 4/13 patients (median duration 5+ months), and the other 9 patients progressed. Mean number of lymphocytes and eosinophils significantly increased during the treatment. Moreover, the mean increase in lymphocyte number was significantly higher in patients with stable disease than in those with progressive disease, whereas there was no difference as regards eosinophils. Serum levels of neopterin and tumor necrosis factor (TNF) significantly increased during therapy, and TNF increase was correlated to the side effects rather than to the control of cancer development. This study shows that neuroimmunotherapy with low-dose interleukin-2 and MLT, even though capable of determining an evident expansion of immune cells involved in host antitumor response, does not seem to be effective in terms of tumor regression in metastatic colon cancer patients pretreated with 5-fluorouracil.

Adult

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.

Adult

Effect of antitumor surgery on soluble interleukin-2 receptor serum levels.

Surgically induced immunosuppression may play a role in cancer, because of the possible existence of micrometastases at the time of surgical removal of tumors. Antitumor immune reactions are mediated by interleukin-2 (IL-2). IL-2 acts on a specific IL-2 cell surface receptor; moreover, a soluble form of IL-2 receptor (sIL-2R) can be released in the blood. This study was carried out to evaluate the effect of surgery on sIL-2R serum levels in patients with operable solid tumors. A total of 48 patients with cancer and 11 controls who underwent major surgery for non-neoplastic disease were evaluated before and 7 days after surgery. Serum mean levels of sIL-2R were significantly higher after than before surgery in both the cancer and control groups. No correlation was seen between surgery-induced changes in sIL-2R and in T lymphocyte subsets. Because of its capacity of binding to IL-2, the increased blood concentrations of sIL-2R could reduce the IL-2 availability and negatively affect antitumor immune reactions.

Breast Neoplasms

Increase in soluble interleukin-2 receptor and neopterin serum levels during immunotherapy of cancer with interleukin-2.

Both immunostimulatory and immunosuppressive events would occur during the immunotherapies of cancer, including interleukin 2 (IL-2) therapy. The marked increase in soluble IL-2 receptor (SIL-2R) levels during IL-2 therapy could represent a potentially negative biological effect, because of the receptor's capacity to bind IL-2 and compete for it with IL-2 cell surface receptor. Since it has been observed that macrophages stimulate in vitro the release of SIL-2R, a study was started to evaluate in vivo the role of macrophages in IL-2-induced SIL-2R rise by measuring neopterin, which is a marker of macrophage activity. The study included 9 advanced renal cancer patients, treated subcutaneously with IL-2 at 1.8 x 10(6) IU/m2 twice daily for 5 days/week for 6 weeks. Both SIL-2R and neopterin serum mean levels significantly increased during IL-2 treatment, and the highest concentrations were reached on the second week of therapy. SIL-2R rise was significantly correlated to that of neopterin. This study, by showing a positive correlation between SIL-2R and neopterin rise, would suggest a macrophage involvement in the stimulation of SIL-2R release during IL-2 immunotherapy of cancer.

Adenocarcinoma

Decrease in cholesterol levels during the immunotherapy of cancer with interleukin-2.

IL-2, in addition to its immunomodulating and antitumour properties, induces important systemic actions, including cardiovascular, neuroendocrine and metabolic effects. The present study was carried out to evaluate IL-2 effects on cholesterol metabolism. The study included 14 advanced cancer patients (renal carcinoma: ten; colon carcinoma: four), who received IL-2 subcutaneously at a dose of 1.8 x 10(6) IU ml-2 twice daily for 5 days/week for 6 weeks. Venous blood samples were collected 7 days before, on days 0, 3, 7, 14, 21, 42 of IL-2 therapy, and on days 14 and 28 of the rest-period. IL-2 induced a rapid and evident decrease in cholesterol levels, with a normalisation of its concentrations within 7 days in 10/10 hypercholesterolemic patients. The lowest mean levels of cholesterol were reached within the first 2 weeks; after that they still slowly increased. LDL-/HDL-cholesterol ratio was significantly reduced by IL-2 therapy. Cholesterol fall was associated with a marked increase in conjugated biliary acid levels. Finally, triglyceride values increased during IL-2 therapy, but not in a significant manner. These results, by showing that IL-2 exerts an evident and very rapid cholesterol-lowering activity, would represent a further demonstration of the physiological importance of cytokines in the control of cholesterol metabolism.

Adenocarcinoma

Pineal gland and tumor cell kinetics: serum levels of melatonin in relation to Ki-67 labeling rate in breast cancer.

Recent observations showed that host may regulate either endocrinologically or immunologically tumor growth and differentiation, perhaps by modulating oncogene expression. Within the endocrine system, the pineal hormone, melatonin, seems to play an important antineoplastic role. To investigate its secretion in relation to tumor growth, we have evaluated the daily serum levels of melatonin in a group of 25 untreated breast cancer patients with a locally limited disease. Tumor cell proliferation was established by measuring Ki-67 labeling rate. As controls, 46 healthy women were considered. Breast cancer patients showed significantly higher mean values of melatonin than controls. Moreover, patients with negative Ki-67 labeling rate had significantly higher levels of the pineal hormone than those with a positive Ki-67 rate. Since tumors with high growth fraction present a worse prognosis, this study would suggest that the relief of an increased melatonin secretion represents a favorable prognostic sign, because of its association with less proliferating breast cancers.

Adult

[Choice of technique in "difficult" inguinal hernias. Personal experience].

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.

Hernia, Inguinal

A proposal for intraoperative washout of colon for the endoscopic diagnosis of the lower gastrointestinal tract haemorrhage.

The authors refer about a proposal for an intraoperative wash-out of colon in order to improve the endoscopic diagnosis of the bleeding's precise site in case of lower gastrointestinal tract haemorrhage. The colonic wash-out is obtained by the transanal insertion of a Baker type silicone tube this is guided by the surgeon up to the caecum followed by the insertion of the colonoscope. This method turned out useful in one case of haemorrhagic shock.

Colon

[Anastomosis in emergency large intestine resections in the therapy of obstructing colonic cancer].

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.

Anti-Bacterial Agents

A randomized study of low-dose subcutaneous interleukin-2 plus melatonin versus supportive care alone in metastatic colorectal cancer patients progressing under 5-fluorouracil and folates.

Chemotherapy with 5-fluorouracil (5-FU) and folates represents the first-line standard therapy for metastatic colorectal cancer, whereas at present there is no conventional second-time treatment. Because of its importance in generating an effective anticancer immune response, interleukin-2 (IL-2) could constitute a new promising therapy of advanced colon cancer. Generally, IL-2 may determine tumor regressions in colon cancer only when it is given at high toxic doses. Our preliminary studies have shown that the pineal hormone melatonin may amplify IL-2 activity, which becomes active also at low doses in several tumor histotypes. On the basis, we have performed a clinical trial to evaluate the impact of low-dose IL-2 plus melatonin on the survival time in metastatic colon cancer, which progressed in response to 5-FU plus folates. The study included 50 metastatic colorectal cancer patients, who did not respond or progressed after initial response to first-line chemotherapy with 5-FU and folates. Patients were randomized to receive supportive care alone or low-dose subcutaneous IL-2 (3 million IU/day for 6 days/week for 4 weeks) plus melatonin (40 mg/day orally). No spontaneous tumor regression occurred in patients receiving supportive care alone. A partial response was achieved in 3/25 patients treated with immunotherapy. Percent survival at 1 year was significantly higher in patients treated with immunotherapy than in those treated with supportive care alone (9/25 vs. 3/25, p < 0.05). This study suggests that low-dose subcutaneous IL-2 plus melatonin may be effective as a second-line therapy to induce tumor regression and to prolong percent survival at 1 year in metastatic colorectal cancer patients progressing under 5-FU and folates.

Adult