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Biomedical subjects

F Brivio

Publications and source records attributed to F Brivio.

At least 55 records · Page 3Linked to original sources
PubMed1985

[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↗
PubMedDate not supplied

Efficacy of the concomitant administration of the pineal hormone melatonin in cancer immunotherapy with low-dose IL-2 in patients with advanced solid tumors who had progressed on IL-2 alone.

Our preliminary studies in humans have shown that the pineal neurohormone melatonin (MLT) may enhance the antitumor activity of IL-2, by confirming the existence of a neuroendocrine control on cytokine effects. On this basis, a study was started to evaluate the influence of a concomitant administration of MLT and low-dose IL-2 in cancer patients, who had progressed during a previous immunotherapy with IL-2 alone. The study included 14 patients with advanced solid tumors (lung 6; kidney 4; stomach 2; liver 1; melanoma 1). IL-2 was given at a daily dose of 3 million IU s.c. for 6 days/week for 4 weeks. MLT was given orally at a daily dose of 40 mg every day, starting 7 days prior to IL-2. Objective tumor regression, consisting of a partial remission (PR), was achieved in 3/14 (21%) patients (lung 1; kidney 1; liver 1). Six other patients had a stable disease (SD), while the remaining 5 cases progressed. PR and SD were associated either with a significantly longer survival at 1 year, or with a significantly higher increase in lymphocyte and eosinophil mean number with respect to the patients with disease progression. This preliminary study suggests that advanced solid neoplasms resistant to IL-2 may become responsive to IL-2 therapy by a concomitant administration of the pineal hormone MLT, which could act by enhancing IL-2 antitumor immune effect and/or by increasing the susceptibility of cancer cells to the cytolysis mediated by IL-2-induced cytotoxic lymphocytes.

Aged↗
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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↗
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A biological study on the efficacy of low-dose subcutaneous interleukin-2 plus melatonin in the treatment of cancer-related thrombocytopenia.

The production of cytokines involved in platelet generation, including interleukin (IL)-3, IL-6 and IL-11, is stimulated by IL-2. However, the platelet number has been shown to decrease on IL-2 cancer therapy, and this side effect depends on the enhanced peripheral platelet destruction following the activation of the macrophage system by IL-2 itself. Our previous studies showed that IL-2-induced macrophage activation may be counteracted by the pineal hormone melatonin (MLT). On this basis, a pilot study with IL-2 plus MLT was performed to evaluate its influence on the platelet number in cancer patients with persistent thrombocytopenia. The study included 20 advanced solid tumor patients, who received IL-2 at 3 million IU/day s.c. for 6 days/week for 4 weeks in association with MLT (40 mg/day orally). A normalization of the platelet number was achieved in 14/20 (70%) patients. This pilot study shows that the therapy with low-dose IL-2 plus MLT, in addition to its previously described antitumor activity, may also be effective in the treatment of cancer-related thrombocytopenia.

Adult↗
PubMedDate not supplied

Prediction of recurrence in operable breast cancer by postoperative changes in prolactin secretion.

It has been demonstrated that breast surgery may induce prolactin (PRL) increase. Because of the potential stimulatory role of PRL on breast cancer cells, its postoperative increase may influence the prognosis of breast cancer patients. This study was performed to evaluate the influence of surgery-induced hyperprolactinemia on recurrence rate in operable breast cancer. The study included 250 consecutive breast cancer patients, clinical stage T1-3 N0-2M0, who were observed for a median follow-up of 72 months. Surgery-induced hyperprolactinemia occurred in 108/250 patients (43%). Irrespectively of node involvement, hormonal receptor, type of surgery and adjuvant therapies, the relapse rate was significantly higher in patients who had no surgery-induced hyperprolactinemia than in those with postoperative PRL increase (64/142 vs. 23/108; p < 0.001). This difference was also significant in relation to node status (N0:22/63 vs. 5/56, p < 0.001; N+:42/79 vs. 18/52, p < 0.05). The present study shows that a surgery-induced rise of PRL, despite its potential stimulation of cancer cell growth, is paradoxically associated with a longer disease-free survival in operable breast carcinoma in both patients with or without axillary node involvement. Moreover, this study suggests that the prognosis of node-negative patients who did not show postoperative hyperprolactinemia tends to be similar to that of patients with node involvement and surgery-induced PRL enhancement. Therefore, the lack of surgery-induced hyperprolactinemia would have to be grouped together with the unfavorable prognostic factors of breast cancer.

Adult↗
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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.

Adult↗
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Circulating immature and mature dendritic cells in relation to lymphocyte subsets in patients with gastrointestinal tract cancer.

Cancer-related deficiency in circulating dendritic cells (DC), whose important anticancer role is well established, has been proven to be associated with lymphocytopenia. This study was performed to evaluate which lymphocyte subset is most markedly related to the failure of the DC system. The study included 30 patients with gastrointestinal tract cancer, 10 of whom had distant organ metastases. Immature and mature DCs were measured by FACS and monoclonal antibodies against CD123 and CD11c antigens, respectively. Low levels of immature and mature DCs were observed in 63% and 43% of patients, respectively. Patients with low levels of circulating mature DCs had significantly lower values of T lymphocytes, T helper lymphocytes and NK cells than those with normal mature DC levels. In contrast, no significant difference was seen between patients with normal or abnormally low values of immature DCs. Conversely, patients with a decreased number of T lymphocytes, T helper lymphocytes and NK cells showed significantly lower values of circulating mature DCs than those with lymphocyte subsets within the normal range, whereas no difference was seen in immature DC amounts. This study suggests that only mature DC deficiency may be associated with important lymphocyte subset alterations in cancer patients, whereas deficiency in immature DCs does not seem to be related to other immune cell disorders.

Antigens, CD↗
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Changes in circulating dendritic cells and IL-12 in relation to the angiogenic factor VEGF during IL-2 immunotherapy of metastatic renal cell cancer.

Angiogenesis and immunosuppression are the main biological mechanisms responsible for cancer progression. Moreover, recent observations suggesting a negative influence of angiogenesis on anticancer immunity have shown that some angiogenic factors, such as VEGF, may induce immunosuppression. In addition, the evidence of abnormally high blood levels of VEGF has been proven to be associated with resistance to IL-2 immunotherapy. The present study was performed to establish a possible relation ship between the efficacy of IL-2 cancer immunotherapy and changes in circulating levels of VEGF, IL-12, mature and immature dendritic cells (DC). The study included 25 metastatic renal cell cancer patients who underwent subcutaneous low-dose IL-2 immunotherapy (6 MIU/day for 6 days/week for 4 weeks). Immature and mature DCs were identified as CD123+ and CD11c+ cells, respectively. The clinical response consisted of partial response (PR) in five, stable disease (SD) in 11 and progressive disease (PD) in the remaining nine patients. The mean IL-12 levels observed during IL-2 immunotherapy were significantly higher in patients with PR or SD than in those with PD, whereas the mean VEGF concentrations were significantly higher in patients who had PD than in those with PR or SD. Finally, a significant increase in the mean number of circulating mature DCs occurred only in patients with PR or SD, whereas no significant change was seen in patients with PD. By contrast, no significant change was observed in the mean number of immature DCs. This study shows that the efficacy of IL-2 immunotherapy is associated with a significant increase in circulating mature DCs and IL-12, without any concomitant increase in VEGF concentrations. Further studies will be required to better define the relationship between activation of anticancer immunity and control of angiogenesis-related mechanisms.

Adult↗
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Changes in circulating VEGF levels in relation to clinical response during chemotherapy for metastatic cancer.

Abnormally high blood levels of vascular endothelial growth factor (VEGF) appear to be associated with a poor prognosis in advanced cancer, probably as a consequence of its angiogenic and immunosuppressive effects. The prognostic significance of changes in VEGF secretion during cancer chemotherapy is still unknown. This study aimed to investigate the relation between VEGF variations and therapeutic results during chemotherapy in advanced malignancies. The study included 90 metastatic cancer patients, 59 with non-small cell lung cancer and 31 with colorectal carcinoma. Chemotherapy consisted of cisplatin plus etoposide for NSCLC and camptothecin for colorectal cancer. Abnormally high (> 2 SD with respect to values in healthy controls) pretreatment VEGF levels were found in 38/90 (42%) patients. The percentage of non-progressive disease in response to chemotherapy was significantly higher in patients with normal levels of VEGF prior to therapy than in those with elevated pretreatment values of VEGF (10/32 vs 4/27; p < 0.05). Moreover, the percentage of VEGF level normalization during chemotherapy was significantly higher in patients with objective tumor response or stable disease than in progressing patients (10/18 vs 0/20; p < 0.001). Finally, among patients with tumor response or disease stabilization, the one-year survival rate was significantly higher in patients with chemotherapy-induced normalization of VEGF than in those with persistently high VEGF blood levels (9/10 vs 3/8; p < 0.05). These results suggest that changes in VEGF levels during chemotherapy may represent a useful biomarker to predict the effect of chemotherapy in terms of tumor response and survival in patients with metastatic solid neoplasms.

Adult↗
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Efficacy of cancer chemotherapy in relation to the pretreatment number of lymphocytes in patients with metastatic solid tumors.

The evidence of lymphocytopenia has been demonstrated to predict a poor prognosis in terms of survival in advanced cancer patients. This finding is not surprising because of the fundamental role of lymphocytes in mediating tumor cell destruction. Despite the importance of lymphocytes in the pathogenesis of cancer, there are only few data about the profile and the function of lymphocytes during the various antitumor therapies, and in particular the relation between lymphocyte pretreatment number and response to chemotherapy remains to be established. The present study was performed to evaluate whether the evidence of lymphocytopenia before the onset of treatment may influence the efficacy of chemotherapy in metastatic cancer patients affected by the most frequent tumor types. The study included 183 patients (lung cancer: 89; colorectal cancer: 63; breast cancer: 31), 95 of whom had been previously treated with chemotherapy. The chemotherapeutic regimens consisted of oxaliplatin plus 5-fluorouracil and folates in untreated colorectal cancer, weekly irinotecan in pretreated colorectal cancer, cisplatin plus gemcitabine or etoposide in untreated lung cancer, weekly vinorelbine in pretreated lung cancer, and taxotere in breast cancer patients who had been previously treated with anthracyclines. Lymphocyte count was considered to be abnormally low for values below 1500/mm3. Lymphocytopenia was found in 79/183 (43%) patients, without any significant differences in relation to tumor histology. A complete response (CR) was achieved in 6/104 patients with a normal lymphocyte count and in none of the 79 lymphocytopenic patients. A partial response (PR) was obtained in 39 patients with a normal lymphocyte count and in only eight patients with a low lymphocyte count prior to therapy. Therefore, irrespective of the type of chemotherapy, the objective tumor response rate (CR + PR) in lymphocytopenic patients was significantly lower than in patients with normal pretreatment lymphocyte counts (8/79 vs 45/104; p < 0.001). This study shows that the evidence of lymphocytopenia prior to chemotherapy is associated with a lower efficacy of treatment in terms of objective tumor regression rates in patients with metastatic solid tumors, and suggests that the action of chemotherapy may depend at least in part on an interaction with the antitumor immunity. Pretreatment lymphocyte count may represent a new, simple biological marker to be taken into consideration by oncologists in the chemotherapeutic treatment of metastatic cancer.

Adult↗
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The favorable prognostic significance of surgery-induced hyperprolactinemia in node-positive breast cancer patients: ten-year disease-free survival results.

It has been shown that each manipulation of the mammary region, including breast surgery, may stimulate prolactin secretion. However, it has also been observed that in more than 50% of breast cancer patients surgical removal of the tumor is not followed by enhanced prolactin secretion. This might be indicative of an altered psychoneuroendocrine control of the mammary gland, which could lead to the onset of more biologically aggressive breast cancer. In fact, surgery-induced hyperprolactinemia has been proven to be associated with a better prognosis in terms of survival in node-negative breast cancer patients. The present study was performed to investigate the impact of postoperative hyperprolactinemia on the disease-free survival (DFS) of breast cancer patients with axillary node involvement. The study included 100 consecutive node-positive breast cancer patients who were followed for at least 10 years. Surgery-induced hyperprolactinemia occurred in 45/100 (45%) patients without any significant correlation with the main prognostic variables including number of involved nodes and ER status. The two groups of patients received the same adjuvant therapies. After a median follow-up of 151 months, the recurrence rate in patients with surgery-induced hyperprolactinemia was significantly lower than in patients with no postoperative hyperprolactinemia (23/45 vs 43/55, p<0.01). Moreover, DFS was significantly longer in hyperprolactinemic patients than in patients who had no enhanced secretion of prolactin postoperatively. In agreement with the results described previously in node-negative breast cancer, our study demonstrates the favorable prognostic significance of surgery-induced hyperprolactinemia in terms of DFS duration also in breast cancer patients with axillary node involvement, independent of the other well-known prognostic variables, thereby confirming that the psychoneuroendocrine status of cancer patients may influence the prognosis of their disease.

Adult↗
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The pineal gland and breast cancer: serum levels of melatonin in patients with mammary tumors and their relation to clinical characteristics.

Several studies have suggested that the pineal gland hormone melatonin may influence the growth of breast cancer. The importance of melatonin blood concentrations in the clinical history of human breast cancer, however, has still to be defined. To further investigate this problem, we used a RIA method to assay serum levels of the pineal hormone in 74 untreated breast cancer patients, clinical stage T1-3 NO-2 MO, and in 46 age-matched healthy women as controls. Mean serum melatonin levels were significantly higher in patients than in controls. Melatonin concentrations were highest in breast cancer patients with the best prognosis (i.e. estrogen receptor-positive/node-negative cases). Mean levels of melatonin were significantly higher in estrogen receptor-positive patients than in the negative ones. They were also higher in node-negative than in node-positive cases, and in progesterone receptor-positive patients than negative ones, but none of these differences was statistically significant. No difference was observed in relation to menopausal status and to tumor histotype. These results suggest that melatonin plays a role in the hormone-dependency of human breast cancer.

Adult↗
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Lack of changes in soluble interleukin-2 receptor serum levels during chemotherapy-induced lymphocyte damage.

The biological significance of soluble IL-2 receptors (sIL-2R) is still unknown; in particular, it is not yet clear whether their increase in the blood may reflect activation of immune cells, or whether it is related to an immune dysfunction. To investigate this problem, we evaluated serum levels of sIL-2R before and after administration of a highly lymphocytolitic chemotherapy (FEC: fluorouracil, epirubicin, cyclophosphamide) in a group of 6 patients with advanced breast cancer. SIL-2R were analyzed in relation to lymphocyte number. Absolute mean number of lymphocytes was significantly lower after than before chemotherapy. On the contrary, no significant difference was seen in sIL-2R mean levels, and no significant correlation was observed between changes in sIL-2R and in lymphocyte number following chemotherapy. These results would exclude that sIL-2R may simply be due to a passive release following lymphocytic damage.

Adult↗
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Pre-operative IL-2 immunoprophylaxis of cancer recurrence: long-term clinical results of a phase II study in radically operable colorectal cancer.

This study evaluates retrospectively the outcome of 20 colorectal cancer patients radically operated (M/F 13/7; primary/recurrent 15/5; Dukes B=11; C=6; D=3) who received pre-operative IL-2 (18,000, 000 IU/daily s.c. for 3 days) and the outcome of 40 colorectal cancer (primary/recurrent 40/0) patients age, sex and stage-matched radically operated, as control group. After a median follow-up of 72 months, in the IL-2 pre-operative group we observed 6/20 recurrences (30%) vs. 19/40 (47.5%) in controls. Mean and median disease-free period in patients who relapsed were respectively 21 months and 20.5 months (range 6-36) in IL-2 group vs. 14.1 and 12 months in the control group (range 3-34). After a 5-year follow-up, 4/20 (20%) IL-2 treated patients were dead vs. 19/40 control patients (47.5%) (log-rank chi2=3.7, p=0.05). Pre-operative IL-2 administration is safe, active in preventing post-operative lymphocytopenia and seems to improve the clinical outcome in radically operated colorectal cancer patients.

Adult↗
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Which immunological parameters are clinically essential to monitor IL-2 cancer immunotherapy?

The evaluation of the immunobiological changes occuring during IL-2 cancer immunotherapy is not only important to correlate them with the clinical response or to understand the immune mechanism involved in tumor growth control, but also to predict the efficacy of treatment itself. As far as the immune status of patients prior to therapy is concerned, the evidence of the activation of the inflammatory response correlates with resistance to IL-2. Therefore, the evidence of abnormally high pretreatment values of inflammatory response markers, including ESR, CRP, neopterin and SIL-2R, may predict a lack of IL-2 efficacy. In contrast, changes in inflammatory parameters during IL-2 administration have no prognostic significance. The evidence of elevated pretreatment levels of the immunosuppressive cytokine IL-10 has also an unfavourable prognostic significance. At the other side, the evidence of a marked increase in hemopoietic cells involved in tumor cell destruction, such as lymphocytes and eosinophils, as well as in blood levels of antitumor cytokines, such as IL-12, correlates with efficacy of IL-2 cancer immunotherapy. A better definition of the prognostic significance of immunoinflammatory markers will allow us to manipulate and improve host biological response during cancer immunotherapy with IL-2.

Blood Sedimentation↗