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Biomedical subjects

M Santinami

Publications and source records attributed to M Santinami.

At least 37 records · Page 2Linked to original sources
PubMed1995

Excision of primary melanoma should allow primary closure of the wound.

There is no doubt about the fact that surgery is mandatory for primary melanoma. The problem in the recent past has been how wide and deep the excision of primary melanoma has to be. Results published from the World Health Organization (WHO) Melanoma Program have clearly demonstrated that a procedure involving up to 2-mm thickness and 1-cm margins is safe. Further trials dealing with melanoma thicker than 2 mm are being carried out, and preliminary results confirm that even in this case narrow excision is the correct procedure. At present we may assume that for stage I melanoma the excision of the primary tumor should in the majority of cases allow primary closure of the wound.

Humans↗
PubMed1995

Isolation perfusion in extracorporeal circulation with interleukin-2 and lymphokine-activated killer cells in the treatment of in-transit metastases from limb cutaneous melanoma.

BACKGROUND: Therapies of advanced melanoma patients with interleukin-2 (IL-2) and cytotoxic lymphocytes have produced interesting results, but a larger diffusion of these treatments is limited by the severe side effects due to IL-2 systemic infusion. A strictly regional administration of IL-2 and cells by an isolation perfusion (IP) in extracorporeal circulation (ECC) for the treatment of regional melanoma metastases could improve tolerability and efficacy of this specific modality of immunotherapy. METHODS: Ten patients were submitted to adoptive immunotherapy with IL-2 and lymphokine-activated killer (LAK) cells by IP in ECC. The schedule of treatment included the first course of a 5-day systemic administration of IL-2 (Proleukin, EuroCetus 9-12 x 10(6) IU/m2/day continuous infusion); autologous LAK cells were obtained via leukapheresis and after in vitro activation were given (range 8-28 x 10(9)) along with IL-2 (120-2,400 IU/ml of perfusion priming) to the affected limb by IP; IL-2 (9-12 x 10(6) IU/m2/day) was also administered by systemic continuous infusion for 5 days starting on the day after IP. RESULTS: All patients concluded the treatment without any major local or systemic toxicities. Clinical responses included one complete and six partial remissions; three patients had stable disease. All patients are alive. Follow-up after IP ranged from 12 to 35 months (median: 22). The analysis of circulating lymphocytes revealed the rapid disappearance of LAK cells, suggesting their extravasation and/or endothelial adhesion in perfused tissues. CONCLUSIONS: IP with IL-2 and LAK cells is a new approach for the treatment of in-transit metastases due to cutaneous melanoma. The treatment appears to be feasible and reliable. Further biological and immunological studies should permit amelioration of the present modality of treatment.

Adult↗
PubMed1994

Treatment of primary or relapsing limb cancer by isolation perfusion with high-dose alpha-tumor necrosis factor, gamma-interferon, and melphalan.

BACKGROUND: Utilization of alpha-tumor necrosis factor (alpha-TNF) in clinical practice is limited by severe general side effects. Very promising results with low toxicity were reported with administration of alpha-TNF by isolation perfusion in extracorporeal circulation. METHODS: From December 1991 to November 1992, 14 patients underwent perfusion with alpha-TNF (2-4 mg, total dose), gamma-interferon (1.5 x 10(6) IU), and melphalan (10 mg/l/perfused limb). Twelve patients presented in-transit metastases of the limbs, one patient, a clear cell sarcoma of the hand, and one patient, a wide spindle cell carcinoma of the thigh. Perfusion lasted 90 minutes and was conducted in mild hyperthermia (38-40.5 degrees C, muscle temperature). RESULTS: Nine complete regressions and four stable diseases were recorded. In one case, a reliable evaluation of response was not possible for diffused tissue necrosis. Five patients relapsed or progressed locally from 3 to 4 months after surgery, five presented distant localizations from 2 to 7 months after surgery, and one died of disease 6 months after perfusion. Twelve patients are alive, seven without evidence of disease. A septic-like shock syndrome was observed in all patients and required administration of dopamine, dobutamine, or noradrenaline. One patient died 30 days after perfusion from a multiorgan-failure syndrome, likely due to alpha-TNF. The follow-up time ranges from 4 to 15 months (median, 6). CONCLUSIONS: The preliminary, impressive results reported in other series were not completely confirmed in this study adopting the same treatment scheme. Further clinical experience and biologic data are needed to state the real efficacy of the approach and to reduce the severe general toxicity consistently associated with this type of treatment.

Adult↗
PubMed1994

Treatment of in-transit metastases from cutaneous melanoma by isolation perfusion with tumour necrosis factor-alpha (TNF-alpha), melphalan and interferon-gamma (IFN-gamma). Dose-finding experience at the National Cancer Institute of Milan.

From December 1991 to July 1993, 22 consecutive patients with grade IIIA-IIIAB melanoma underwent isolation perfusion with TNF-alpha (0.5-4 mg), melphalan (10 mg/l perfused limb) and, in the first 12 cases, IFN-gamma (1.5 x 10(6) U). The first series of 12 patients received a total dosage TNF-alpha of 2-4 mg, and the second series of 10 cases received an escalating dosage of TNF-alpha (1.5-1.0-0.5 mg) and no IFN-gamma before or during surgery. The perfusion lasted 90 min and was conducted in mild hyperthermia (39-39.5 degree C muscle temperature). The results of the first series included seven patients in complete remission, four with stable disease and one case not evaluable for local toxicity. Fifty per cent of cases developed a regional relapse from 3 to 4 months after surgery. Presently with a median follow up of 10 months, five patients of this group have no evidence of disease, four are alive with disease, two died from melanoma and one died of complications likely due to treatment (multi-organ failure syndrome). In the second series, the immediate responses included seven patients in complete remission and three in partial remission; with a median follow up of 3 months, two patients developed a regional relapse, respectively, 3 and 5 months after surgery. So far our experience of perfusion with TNF-alpha has not reproduced the data reported by other investigators. Further clinical and biological findings and a longer follow-up period are needed to draw any conclusion, and a decreasing TNF-alpha dose should be carefully evaluated.

Adult↗
PubMed1994

Hyperthermic antiblastic perfusion in the treatment of stage IIIA-IIIAB melanoma patients. Comparison of two experiences.

Many reports have been published concerning the efficacy of hyperthermic antiblastic perfusion (HAP) for the treatment of recurrent limb melanoma. In terms of tumour response, loco-regional control and survival, the results vary greatly even in patients with the same disease stage treated with the same technique. The aim of the present report was therefore to compare the experiences of two institutes, the Regina Elena National Cancer Institute of Rome and the National Tumour Institute of Milan, in treating a total of 327 patients with stage IIIA and IIIAB melanoma with HAP. The study also examined whether, and to what extent some prognostic factors influence the course of the disease. The tumour temperature proved to be the most important parameter for obtaining a complete tumour response which, in turn, positively affected survival. A direct relationship was found between the rates of complete tumour response and the clinical status of the patients. The complete response rates obtained in patients with no evidence of disease were 62.5% at the Rome institute and 70.1% at the Milan institute as opposed to 23.6% and 39%, respectively, in patients who died of the disease.

Adolescent↗
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↗
PubMed1990

Combined treatment of osteosarcoma of the limbs at an advanced stage, including hyperthermic-antiblastic perfusion.

Between August 1983 and September 1986 18 patients affected with osteosarcoma of the limbs in which the extent of the neoplasm would normally have required amputation were treated by two cycles of intra-arterial infusion of CDDP, associated with methotrexate at high doses administered i.v., followed by a hyperthermic-antiblastic perfusion confined to the affected limb with CDDP at high doses. At the end, the patients were administered two more cycles of methotrexate at high doses and CDDP intravenously. The immediate response, evaluated in radiological, clinical and histological terms, was such that in 11 patients it was possible to obtain satisfactory results with conservative treatment alone. None of the patients developed local recurrence.

Adolescent↗
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

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↗
PubMed1989

Antitumor activity of hyperthermia alone or in combination with cisplatin and melphalan in primary cultures of human malignant melanoma.

The effects of heat and the interaction between hyperthermia and alkylating agents, such as cisplatin (CDDP) and melphalan (L-PAM) in human malignant melanoma biopsies have been investigated by a short-term assay based upon the inhibition of 3H-thymidine incorporation. Cell suspensions from 50 cutaneous and lymph nodal metastases were heated at 40.5 degrees C or at 42 degrees C for 1 h. There were significant antiproliferative effects due to heat in 10% of the tumors exposed to 40.5 degrees C and 34% to 42 degrees C. Thermal resistance was evident in 73% (at 40.5 degrees C) and 54% (at 43 degrees C) of tumors, and there was significant enhancement of cell growth in 17% and 12% of tumors. The combined effects of hyperthermia and drugs were studied on 36 tumors. Cell suspensions were exposed to different concentrations of CDDP or L-PAM for 1 h at 40.5 degrees C and 42 degrees C. Synergy between heat and CDDP was observed in 7% of cases treated with the lowest drug dose and 38% of cases treated with the highest (40.5 degrees C), with only a slight increase in the frequency of synergy at 42 degrees C. Synergy between heat and L-PAM was also observed in 12% to 44% of tumors at 42 degrees C as a function of drug concentration.

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↗
PubMed1987

Hyperthermic antiblastic perfusion with DTIC in stage IIIA-IIIAB melanoma of the extremities.

The aim of this paper is to evaluate the effectiveness of DTIC when employed at a local level in hyperthermic antiblastic perfusion (HAP) for stage IIIA-IIIAB melanoma patients. Twenty-seven consecutive patients have been treated at the National Cancer Institute of Milan from October 1983 to June 1985. All the patients were submitted to HAP at 40 degrees for 60' with DTIC at the dosage of 2.5 g/m2 [corrected] for lower extremities and 1.5 g/m2 [corrected] for upper extremities. We observed a complete local response in three patients and a partial local response 50% in seven patients, 10 patients has a response less than 50% and 4 patients did not show any response. After surgical removal of the residual tumor when possible, 14 patients are alive without detectable disease while 11 are alive with disease and two dead for progression. No serious complications were observed. These data indicate that DTIC seems able to obtain in HAP, results superimposable to L-PAM without any significant toxicity.

Adult↗
PubMed1986

Regional non-nodal metastases of cutaneous melanoma.

The authors studied the prognosis of patients with so called local recurrences, satellites and in-transit metastases from cutaneous melanoma on the basis of 291 patients. These are the 19.3% of the 1503 patients with stage I and II melanoma originally submitted to surgical treatment at the National Cancer Institute of Milano (Italy). The majority of patients were males (M/F = 0.7): 102 had local recurrence, 99 in-transit metastases, 24 satellites and 66 both local and in-transit metastases. Regional non-nodal metastases were not related with the site of origin, and inadequate treatment of primary. These metastases were more frequently observed in patients who were submitted to regional node dissection no matter whether in discontinuity or in continuity with primary tumor. The frequency of regional non-nodal metastases was found to increase with increasing thickness of primary melanoma or, in stage II patients, with the number of involved nodes. Local and in-transit metastases were related with prognostic criteria in the same way. The overall survival was very close between in-transit and local metastases. Similar survival rates were observed comparing regional non-nodes and disseminated cutaneous and subcutaneous metastases. The authors conclude that the distinction between local recurrences, satellites and in-transit metastases is artificial and that these metastatic events are not prognostically dissimilar from metastases in distant skin areas.

Adolescent↗
PubMed1985

Hyperthermic antiblastic perfusion in the treatment of cancer of the extremities.

From February 1982 to December 1983, 42 patients affected by neoplasms of the limbs were treated at the Istituto Nazionale Tumori of Milan by hyperthermic antiblastic perfusion in extracorporeal circulation at the temperature of 40-41 degrees C for 1 h. Thirty-two were affected by melanoma, 4 by osteogenic sarcoma, 2 by squamous-cell carcinoma, 1 by liposarcoma, 1 by hemangiopericytoma, 1 by clear-cell sarcoma and 1 by Kaposis's sarcoma. As regards the immediate response, a complete plus partial remission rate of 88% without any major complication was obtained. The follow-up period is too short for any considerations about overall survival. However, because of these good clinical results we consider this method able to locally control the evolution of neoplasms of the extremities, allowing in many cases a limb salvage.

Adolescent↗