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Biomedical subjects

F Belli

Publications and source records attributed to F Belli.

At least 73 records · Page 4Linked to original sources
PubMed1994

Prevalence of sexual dysfunction in male cancer patients treated with rectal excision and coloanal anastomosis.

Impotency due to parasympathetic nerve injury is one of the most feared consequences of rectal cancer surgery. Sexual relationships make a significant contribution to the quality of life for almost everybody. Rectal excision and coloanal anastomosis (CAA) is a new surgical procedure for low rectal tumor with little data regarding the prevalence of sexual impairment as yet. We have examined the sexual life of 21 male patients who have undergone CAA by means a self-administered questionnaire. Only two patients reported reactive impotency. On the other hand 17 out of 21 patients had no ejaculation after undergoing surgery. According to our data it appears that CAA results in surgery a low degree of sexual impairment (impotency). Both sexual dysfunction and quality of life investigations should be integrated with oncological results when reporting data about colorectal surgery.

Adult↗
PubMed1993

Adoptive immunotherapy of advanced melanoma patients with interleukin-2 (IL-2) and tumor-infiltrating lymphocytes selected in vitro with low doses of IL-2.

Freshly isolated tumor-infiltrating lymphocytes (TIL) from stage IV melanoma patients were cultured for 2 weeks with low doses of interleukin-2 (IL-2; 120 IU/ml), to select potentially for tumor-specific lymphocytes present in the neoplastic lesion, followed by high doses (6000 IU/ml) to achieve lymphocyte expansion. TIL were serially analyzed for their expansion, phenotype and cytotoxic activity against autologous and allogenic tumor cells. A preferential lysis of autologous melanoma cells was obtained in long-term cultures of 7/13 cases (54%), while the remaining ones showed a major-histocompatibility-complex-unrestricted, lymphokine-activated-killer(LAK)-like activity at the time of in vivo injection. Sixteen patients with metastatic melanoma were infused with TIL (mean number: 6.8 x 10(9), range: 0.35 x 10(9)-20 x 10(9)) and IL-2 (mean dose: 130 x 10(6) IU, range: 28.8 x 10(6)-231 x 10(6) IU); 1 complete and 3 partial responses were observed in 12 evaluable patients (response rate 33%). In all responding patients, injected TIL showed an in vitro preferential lysis of autologous tumor cells, while in no cases were TIL with LAK-like activity associated with a clinical response. The mean autologous tumor cytotoxic activity of TIL at the time of in vivo injection was significantly higher in responding patients in comparison to nonresponding ones, suggesting that a marked and preferential cytolysis of autologous tumor cells is associated with the therapeutic efficacy of TIL.

Adult↗
PubMed1993

Neuropsychological and neurophysiological assessment of the central effects of interleukin-2 administration.

Neuropsychiatric disturbances may occur following interleukin-2 (IL2) administration. We studied the effects of IL2 infusion on cerebral functions in 7 patients with neuropsychological tests and event-related evoked potentials (P300). We observed a failure in the cognitive performances, an increase in latency, and a decrease in amplitude of P300. These effects followed IL2 administration and were reversible.

Adult↗
PubMed1993

The case for minimal margins and delayed regional node dissection for high-risk cutaneous melanoma.

Some aspects of the surgical treatment of cutaneous melanoma are still currently debated. There is presently a general agreement in favor of a less wide excision of primary lesions. Specifically, data coming from a randomized study of the World Health Organization (WHO) Melanoma Programme indicates that the width of resection has no impact on either disease-free and overall survival of 612 stage I entered patients. Opportunity of an elective (ELND) or delayed (DLND) lymph node dissection remains much more controversial. Complications, including lymphedema, associated with this type of surgery, and no evidence of regional lymph node disease in at least 70% of clinical stage I patients submitted to node dissection, argue for avoiding ELND. Some studies show a positive value for ELND, but they are flawed by biased entry of patients into the ELND group, and conclusions are not derived from randomized studies. Two prospective trials show that ELND does not improve the prognosis of patients with stage I cutaneous melanoma. The results of the WHO study of 553 cases will be evaluable at 20 years. So far, on the basis of many biologic, clinical, and statistical findings, there is no evidence, in our opinion, of a substantial benefit related to ELND.

Disease-Free Survival↗
PubMed1993

Total rectal resection, colo-endoanal anastomosis and colic reservoir for cancer of the lower third of the rectum.

The treatment of low rectal cancer is still a widely debated topic in surgical oncology. From March 1990 to August 1991, 18 patients with tumors sited in the lower third of the rectum underwent a total rectal resection extended to the ano-rectal junction. As restorative procedure, a colic J-shaped pouch and a handsewn pouch-endoanal anastomosis was adopted. All the lesions were less than 8 cm from the anal verge; in 94.5% the distal tumor margin was located within 6.5 cm of the cutaneous edge. Histological clearance of the rectum cut edge was documented in all cases. Only one patient (Dukes C) relapsed four months later at the para-anastomotic level. No mortality or major complications related to surgical procedure were found. In 13 patients perfect continence was achieved and in 12 cases less than two bowel movements a day were recorded. No one complained of severe sexual dysfunction. All patients are still alive. The follow up ranged from 6 to 22 months (median: 12). This experience together with data obtained from last years' literature indicate that a conservative surgical procedure, as total rectal resection and colo-anal anastomosis, can be considered a feasible and radical option for treatment of low rectal cancer.

Adult↗
PubMed1992

Treatment of recurrent in transit metastases from cutaneous melanoma by isolation perfusion in extracorporeal circulation with interleukin-2 and lymphokine activated killer cells. A pilot study.

Chemoresistant melanoma cells are known to be susceptible in vitro to lymphokine activated killer (LAK) cells. To obtain a high LAK/tumour cell ratio in vivo and avoid systemic toxicity due to interleukin-2 (IL-2), we used IL-2 plus LAK cells in the treatment of in transit melanoma metastases of the limbs by isolation perfusion (IP). In vivo immunological modifications induced by this immunotherapeutic approach were also analysed. Six patients previously treated with IP in extracorporeal circulation with tumour cytotoxic drugs and presently relapsing or not responding, were submitted to locoregional adoptive therapy consisting of 5 days systemic administration of IL-2 (Proleukin, EuroCetus) (9-12 x 10(6) IU/m2/day c.i.). Autologous LAK cells were derived from leukapheresis and subsequent in vitro stimulation with IL-2; LAK cells were then given along with IL-2 (120-2400 IU/ml of perfusion priming) to the affected limb by IP. In addition, 7-16 x 10(9) LAK cells were administered by systemic infusion the day after together with IL-2 (9-12 x 10(6) IU/m2/day) by c.i. for 5 days. All patients concluded the treatment without major toxicity. The analysis of circulating lymphocytes obtained from extracorporeal circuit at different times revealed rapid disappearance of LAK cells, suggesting their extravasation and/or endothelial adhesion in perfused tissues. Clinical responses included four partial and one complete response; another patient had stable disease. All patients are presently alive. Follow-up after IP ranges from 8 to 22 months.

Adult↗
PubMed1992

Recombinant human erythropoietin in patients with ovarian carcinoma and anaemia secondary to cisplatin and carboplatin chemotherapy: preliminary results.

Preliminary results from the first 21 patients of a group of 30 with International Federation of Gynaecology and Obstetrics (FIGO) stage II-IV epithelial ovarian carcinoma and anaemia are reported. Patients entered this open-label, comparative-group, out-patient study and were randomized to receive conventional support alone (control patients) or recombinant human erythropoietin (r-HuEPO) in addition to conventional support for 6 months. The aim of the study was to determine the effects of r-HuEPO on the anaemia induced by platinum-based chemotherapy. Patients randomized to r-HuEPO therapy received 300 U/kg subcutaneously 3 times weekly in addition to conventional chemotherapy. All patients underwent regular haematological monitoring. One patient developed a deep venous thrombosis after 17 doses of r-HuEPO; it was thought that this event may have been related to therapy and the patient was withdrawn from the study. Three other withdrawals occurred after 11, 15 and 40 doses of r-HuEPO because of progressive anaemia, metoclopramide-induced skin rash and change of chemotherapy, respectively. In the 21 patients analysed to date, there was a notable reduction in blood transfusion requirements during the 6 months of chemotherapy and an improvement in mean serial haemoglobin concentrations in patients on r-HuEPO compared with the control group. In conclusion, r-HuEPO has the potential for reducing haematological toxicity in patients with ovarian carcinoma receiving platinum-based chemotherapy. Also, r-HuEPO may allow modest dosage increments in chemotherapy or the addition of abdominopelvic radiotherapy.

Adult↗
PubMed1990

Cytokine-mediated modulation of HLA-class II, ICAM-1, LFA-3 and tumor-associated antigen profile of melanoma cells. Comparison with anti-proliferative activity by rIL1-beta, rTNF-alpha, rIFN-gamma, rIL4 and their combinations.

Nine different human melanomas and 16 clones, isolated from 2 of them, were characterized for susceptibility to rIL1-beta-, rIL4-, rTNF-alpha- and rIFN-gamma-mediated effects on proliferation and surface expression of class-II HLA (DR and DP), ICAM-1 and LFA-3 molecules and of 3 tumor-associated antigens (recognized by MAb 763.74T, 149.53 and R24). In spite of marked inter- and intra-tumor heterogeneity for susceptibility to the effects of each cytokine, the most frequent upregulation was induced on the HLA class-II antigens by rIFN-gamma and on adhesion molecules by rIFN-gamma, rTNF-alpha and rIL1-beta, while tumor-associated antigens were often down-modulated by rIFN-gamma. Tumor heterogeneity was also evident on tumor-cell proliferation with an apparent hierarchy in the frequency and extent of inhibitory effects: rIFN-gamma greater than rTNF-alpha greater than rIL1-beta = rIL4. Combinations of 2 cytokines resulted in rare and limited changes in the antigenic profile in comparison to the effects seen with single factors, while the combination of rTNF-alpha and rIFN-gamma resulted in significant synergistic antiproliferative effects on most tumor cells and clones. Taken together, these results indicate that single cytokines can profoundly affect the antigenic profile of melanoma cells, while strong tumor-growth inhibition is often achieved by combinations of 2 cytokines acting in synergism.

Antigens, Neoplasm↗
PubMed1990

The role of parotidectomy in the treatment of nodal metastases from cutaneous melanoma of the head and neck.

Forty-six patients affected by head and neck melanoma were submitted to elective or therapeutic parotidectomy associated with laterocervical dissection from 1980 to 1983 at the National Cancer Institute of Milan. The study showed that parotidectomy is indicated in the presence of clinically palpable nodes or where primaries originate in the temporo-zygomatic area. It also demonstrated that survival is not affected by type of dissection performed and that cervical lymphadenectomy must always be associated with parotidectomy because of the high incidence of occult metastases in other nodal groups in these cases.

Adult↗
PubMed1989

Differences between in vivo and in vitro activation of cancer patient lymphocytes by recombinant interleukin 2: possible role for lymphokine-activated killer cell infusion in the in vivo-induced activation.

In this study 15 consecutive melanoma patients were treated with two courses of bolus recombinant interleukin 2 (rIL2) and rIL2 plus in vitro-generated lymphokine-activated killers (LAK), respectively. The immunological monitoring performed after 4 days of rIL2 or rIL2 plus LAK, indicate that the in vivo peripheral blood lymphocyte (PBL), activation (spontaneous proliferation, tumor cytotoxicity, number of DR+ PBL, obtained after the second cycle of rIL2 plus LAK is significantly higher than after the first cycle of rIL2 alone. During the 5-day interval between the two courses, PBL activation returns to baseline levels and no evidence for increased sensitivity of PBL to rIL2 is present. To further confirm this, two additional patients were studied, in whom rIL2 was administered by continuous i.v. infusion. In these two patients the in vitro versus in vivo PBL activation could be directly and simultaneously compared by using in vitro the same concentration of rIL2 reached and maintained in the patients' sera. The PBL activation induced in vivo by a cycle of rIL2 alone was significantly less (about 10 times) than that obtained in vitro with a comparable rIL2 concentration. Thus, the infusion of in vitro highly activated PBL could explain the increased in vivo lymphocyte activation of the second cycle of rIL2 plus LAK over the first cycle of rIL2 alone.

Cell Line↗
PubMed1989

A phase II study of the administration of recombinant interleukin 2 (rIL-2) plus lymphokine activated killer (LAK) cells in stage IV melanoma patients.

From January 1987 to February 1988, 15 stage IV melanoma patients were treated with two courses of bolus injection of rIL-2 plus LAK cell infusions at the National Cancer Institute of Milan. The original treatment regimen included a first course of rIL-2 administration (400 micrograms/m2 bolus injection 3 times a day [TID] for 4 days) and a second course of rIL-2 administration (800 micrograms/m2 bolus injection TID for 7 days) separated by 4 consecutive daily leukaphereses. Autologous lymphokine activated killer (LAK) cells were reinfused into each patient on three occasions during the second period of rIL-2 administration. Due to the appearance of grade III-IV neurological, hepatic and cardiopulmonary toxicity, 7 patients discontinued dosing before the end of treatment, one patient desired to be withdrawn and one patient died from rapidly progressive disease, although complications of rIL-2 administration may have contributed to her death. Only 6 patients completed the schedule without evidence of major intolerance, even though the planned dose during the second course of rIL-2 was reduced to 400 micrograms/m2. The complete duration of treatment ranged from 11 to 19 days. The total dose of rIL-2 injected ranged from 12.6 to 30.4 mg. The number of infused LAK cells ranged from 15.5 x 10(9) to 60 x 10(9)/patient. Two of the 14 evaluable patients showed a minor anti-tumor response. In 5 patients new metastases in other sites were documented from 2 to 5 months after completion of dosing. No apparent association was found between progression of the disease (or the appearance of new metastases) and the total dose of rIL-2 injected, the number of LAK cells administered or the number of days of treatment. By December 1988, all patients had died of their disease in a period ranging from 3 to 14 months from the last injection of rIL-2. The lack of significant clinical responses in this study and the high toxicity of this treatment lead us to conclude that at least as far as melanoma patients are concerned, adoptive immunotherapy with rIL-2 plus LAK cells (as described here) is not a justifiable treatment option unless new evidence presents itself.

Adult↗
PubMed1989

Management of nodal metastases from head and neck melanoma.

Ninety-three patients with nodal metastases from melanoma (stage II) located in the head and neck underwent surgery at the National Cancer Institute of Milan. Different surgical techniques were employed, ranging from radical to conservative treatment. Analysis of the data shows no significant difference from an oncological standpoint between radical and conservative surgery when a radical dissection is performed. Elective nodal dissections for malignant melanoma of the head and neck region, like those at other sites of lymphatic drainage such as the groin and axilla, did not prove beneficial. We do recommend parotidectomy in cases where the primary tumor arises in the superior area of the head. The number of nodes involved and the type of disease spread constitute the major prognostic factors, as in the case of melanomas located in other sites. Our data further indicate that the incidence of distant and local recurrence is not influenced by the type of dissection performed.

Adult↗
PubMed1989

Seven years experience with hyperthermic perfusions in extracorporeal circulation for melanoma of the extremities.

One hundred forty patients affected by high risk or locally advanced melanoma of the extremities were submitted to hyperthermic perfusion in extracorporeal circulation at the National Cancer Institute of Milan, Italy. Using adequate temperature and drug dosage, we increased survival of stage IIIA patients from 8-15% to 51% and stage IIIAB patients from 7-8% to 35%, and good local control was achieved in stage IV patients. A comparison was made with 297 patients with similar disease treated in a previous period in this institute with conventional therapies such as surgery with or without chemotherapy. In stage IIIA patients we obtained 51% overall survival at 5 years in perfused cases, whereas survival in the series with conventional treatment reached 16%. Similarly, in stage IIIAB patients we observed 34% (perfused) versus 16% (conventional treatment) survival. There are still no data available for high-risk stage I, in which perfusion is employed as an adjuvant treatment.

Antineoplastic Agents↗
PubMed1988

HLA antigens in familial and sporadic cutaneous melanoma.

One hundred and twenty-four subjects belonging to 25 families, 51 with familial malignant melanoma (FMM), and 186 subjects belonging to 41 families, 41 with sporadic malignant melanoma, were typed for the HLA A, B, C and DR loci of the HLA system. There was the same statistically significant difference in the frequency of the haplotype A9, B35, Cw4 between each group of patients and the respective healthy relatives (p = 0.01, p = 0.01 and p = 4 x 10(-3), respectively). Moreover, the higher frequency of the haplotype A9, B35, Cw4 in the healthy members of the FMM families (42.46%) compared with the healthy members of the SMM families (23.44%) indicates that in the latter group other individuals are at risk for the disease. Furthermore, the different frequency of haplotypes B5, DR5 and B5, Cw1 suggest that differences exist between the two groups of healthy relatives. These observations confirm that the HLA region is involved in the etiology of malignant melanoma.

Gene Frequency↗
PubMed1988

In vivo activation of lymphocytes in melanoma patients receiving escalating doses of recombinant interleukin 2.

A phase-I study of the recombinant, non-mutagenized interleukin 2 (rIL2, BioleukinTM) was performed in 12 melanoma patients (Pts). From 100 to 800 micrograms/m2 of rIL2 were administered by i.v. bolus injection, TID for 4-8 days. Side-effects included fever, malaise, low serum K+ and Ca++ values, electrocardiographic abnormalities, leukopenia and thrombocytopenia. No major organ toxicity and no significant fluid retention were observed at the administered doses. Treatment induced a rapid depletion of peripheral blood lymphocytes (PBL) with a rebound (2-6 times the pre-treatment values), 24-48 hr after rIL2 discontinuation. PBL obtained between the 5th treatment day and the 2nd post-treatment day showed: (a) enhanced proliferation (II/12 Pts) with stimulation indexes of 6-52; (b) increased cytotoxicity against autologous tumor cells (2/2 Pts), allogeneic melanomas (5/7 Pts), the Daudi (5/6 Pts) and K562 cell lines (7/12 Pts); and (c) increased expression of IL2 receptors (8/12 Pts) and of DR antigens (6/12 Pts). Lymphocytes collected 1-2 days after treatment and activated in vitro with rIL2 showed a more rapid development of tumor cytotoxicity, with an earlier loss of activity. Spontaneous proliferation, autologous or allogeneic tumor cytotoxicity and expression of IL2 receptors obtained after in vivo treatment with rIL2 were significantly weaker than those induced during in vitro stimulation. No major objective responses were detected in these patients.

Antigens, Surface↗
PubMed1988

Anti-melanoma monoclonal antibody 225-28S: evaluation of toxicity in man.

To investigate possible undesirable effects due to the intravenous administration of a reagent of a xenogenic nature (monoclonal antibody 225-28S) in man, a toxicologic study was carried out on 85 patients with metastatic cutaneous melanoma. Two reagents were tested in this study: purified monoclonal antibody (MoAb) 225-28S and its F(ab')2 fragment. Purified MoAb was labelled with 131I and F(ab')2 fragment with 131I, or 123I, or 111In or 99Tc. The quantity of MoAb or F(ab')2 injected ranged from 14 to 750 micrograms, and the specific activity from 37.0 to 2116.4 MBq/mg. The total radioactivity injected varied from 25.9 to 891.7 MBq/mg. In addition to a careful clinical examination, the following tests were done to monitor possible adverse effects: blood glucose, azotemia, RBC, WBC, platelet count, serum creatinine, creatinine clearance, plasma electrolyte levels, serum proteins, albumin/globulin ratio, serum bilirubin, SGOT, SGPT, gamma GT, and CPK. These tests were done before the injection and on days 7 and 14. No patient experienced adverse general effects like fever, nausea, vomiting or allergic reactions. None of the aforementioned hematometric and biochemical tests showed significant variations compared with the initial values. It is concluded that a single injection of these reagents at the dosages tested is completely atoxic.

Adolescent↗