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Biomedical subjects

M Gasparini

Publications and source records attributed to M Gasparini.

At least 19 recordsLinked to original sources
PubMed1992

Phenotypic and functional analysis of lymphocytes infiltrating paediatric tumours, with a characterization of the tumour phenotype.

Tumour-infiltrating lymphocytes (TIL) of paediatric tumours obtained from 37 lesions of different histotype (12 osteosarcomas, 5 Wilms' tumours, 7 soft-tissue sarcomas, 5 neuroblastomas and 8 miscellaneous) were studied to establish their potential for therapy. Fresh isolated TIL were cultured for the first 2 weeks with low doses of interleukin-2 (IL-2) (20 Cetus U/ml) to select for "tumour-specific" lymphocytes potentially present in the neoplastic lesion, followed by culture with high doses of IL-2 (1000 Cetus U/ml) to achieve TIL expansion. TIL were grown with more than 10-fold expansion in only 9 cases (mean expansion: 58-fold, range 13.5-346). In 17 cases no viable cells were obtained. After 30 days of culture with IL-2 the proliferative ability of TIL declined sharply in the majority of cases and TIL became refractory to any further stimulus, including addition of IL-4, tumour necrosis factor alpha (TNF alpha) or interferon gamma, and activation with OKT3 in solid phase. In 20 out of 37 cases TIL were available for phenotypic and functional analysis. TIL after long-term culture were predominantly CD3+ but 2 cases of osteosarcoma showed a predominance of CD3+TcR gamma/delta cells. The CD4/CD8 ratio was more than 1 in 10 cases, without correlation with tumour histology, site of lesion or TIL growth. The number of CD16+ and CD25+ lymphocytes decreased progressively during culture, the latter concomitantly with a reduction of TIL growth rate. The lytic pattern of TIL against allogenic and autologous tumour (Auto-Tu) cells was variable, but specific lysis of Auto-Tu was seen in only one case (Wilms' tumour) after culture with TNF alpha and irradiated Auto-Tu cells. The immunohistochemical analysis of tumour lesions revealed a limited lymphocyte infiltrate, a low expression of histocompatibility leukocyte antigens (HLA) class I and of the adhesion molecules ICAM1, LFA3, and a significant production of transforming growth factor beta (TGF beta). These data indicate that TIL obtained from paediatric patients are difficult to expand at levels required for immunotherapy and lack a significant number of tumour-specific T lymphocytes. A low expression of immunomodulatory molecules on tumour cells or the production of suppressive factors may prevent activation and expansion of TIL in paediatric tumours.

Antigens, CD↗
PubMed1992

Hypofractionated accelerated radiotherapy in osteogenic sarcoma.

A method of hypofractionated accelerated radiotherapy (3 weekly fractions of 6 Gy over 2 weeks to a total tumor dose of 36 Gy) was used as single modality in 14 patients with osteogenic sarcoma for palliative treatment of the primary tumor site (six cases) or skeletal metastases (15 sites). A durable response, radiologically assessed, was obtained in 17 of the 21 (81%) irradiated sites. When this irradiation modality was combined with chemotherapy, to treat patients presenting with synchronous metastases (eight cases) or refusing amputation (five cases), a radiologically assessed response was observed in 12 of 13 (92%). In no case did a local recurrence occur before surgery or death because of progressive disease elsewhere. Of the seven patients who later had to undergo ablative surgery, a 100% and 95% tumor necrosis was observed in 6 and 1, respectively. Because of intralesional resection of primary osteogenic sarcoma after preoperative chemotherapy, seven additional patients were irradiated. None recurred at the level of the primary site. Although effective in inducing remission of osteogenic sarcoma, this irradiation method produced severe damages to normal tissues in a high proportion of patients.

Adolescent↗
PubMed1992

Renal artery embolism: clinical features and therapeutic options.

Renal artery embolism is an infrequent but important cause of renal loss. However, due to its rarity and nonspecific presentation diagnosis is often delayed and occasionally missed. Furthermore, proper therapeutic intervention is not well established and aggressive surgical management is often ill-advised. We review the literature and present 3 cases seen recently at our institution. Selective intra-arterial infusion of thrombolytic agents appears to be the most favorable treatment. The duration of occlusion does not necessarily correlate with the return of renal function, and the degree of collateral renal blood flow can be important.

Adult↗
PubMed1992

Primary childhood osteosarcoma: the role of salvage surgery.

The overall results of salvage surgery for lung metastases were evaluated on 174 consecutive patients with primary osteosarcoma below the age of 20, resected in Milan between 1970 and 1988. Seventy-two children treated in the years 1970-1981 were compared with 102 children treated in the years 1982-1988. In the latter period, adjuvant chemotherapy was replaced by neo-adjuvant programs and salvage surgery was applied systematically to all patients with resectable lung metastases through median sternotomy. During the last period, the overall 5 year survival improved significantly from 35% to 58% (P less than 0.001), while the disease free survival rose from 38% to 45% (median 15 vs. 33 months, P = 0.3). The proportion of patients with completely resected lung metastases rose from 17% (7/42) to 55% (27/49), without operative mortality, and the overall survival from detection of lung metastases (including unresected cases) improved from 0 to 28% at 5 years (P less than 0.001). The survival benefit was observed only in the group of children with resected metastases. These data indicate that systematic bilateral pulmonary resection, combined with neoadjuvant chemotherapy, has contributed to improve the final cure rate of childhood osteosarcoma.

Adolescent↗
PubMed1992

Transoesophageal electrophysiological evaluation of paediatric patients with Wolff-Parkinson-White syndrome.

Forty-one consecutive children with the Wolff-Parkinson-White (1-15 years: mean 8 years), 22 symptomatic [including 20 with supraventricular tachycardia (SVT) and one with ventricular fibrillation (VF) episode--Group A) and 19 asymptomatic (Group B)], underwent transoesophageal electrophysiological examination. The mean anterograde effective refractory period of the anomalous connection (AERPAC) was 249 +/- 34 ms with no significant difference between the two groups. However, values of less than 220 ms were more frequently observed in Group A than in Group B (23% vs 11% Pns). The effective atrial refractory period was significantly shorter in Group A (183 +/- 34 ms) than in Group B (220 +/- 24 ms) (P less than 0.02). The refractory period of the AV node was 205 +/- 41 ms in Group A and 244 +/- 63 ms in Group B. Orthodromic SVT was induced exclusively in 75% of Group A patients. Atrial fibrillation (AF) was induced in a total of 46% of patients (45% of Group A, 47% of Group B) and was considered easily induced in 37%. The minimum RR interval between pre-excited beats was significantly shorter in Group A (221 +/- 23 ms) than in Group B (321 +/- 143 ms) (P less than 0.04). Four of the patients in whom AF was easily inducible had an RR interval less than 250 ms; three were symptomatic (one with VF). While the AERPAC is generally short in children, and atrial vulnerability generally slight, 9% of children with a short AERPAC had high atrial vulnerability, thus placing them at risk for life-threatening arrhythmias.

Adolescent↗
PubMed1992

[Complications and sequelae of cardiac electrostimulation in children. Our experience with 47 children].

Permanent cardiac pacing is now easily feasible in children and even in small infants, but the long-term results of this procedure are not well known. We analyzed our experience to determine the morbidity of pacing in children. Over the past 10 years, 47 pediatric patients (pts) required pacemaker implantation in our institution. The mean age was 8.3 +/- 4 years (1 day-17 years) and mean body weight was 23 +/- 14 Kg (2.2-60 Kg). 25 pts had heart disease. 40 children had an A-V block (congenital in 22 cases, post-operative in 17 pts, and secondary to a systemic disease in 1 case); 7 pts had a sick sinus syndrome, primitive in 4 and postoperative in 3 cases. The first pacemaker implantation was epicardial in 17 and transvenous in 30 pts. The pacing was single-chamber in 45 pts (VVI 32, VVIr 7, AAI 5, AAIr 1) and dual-chamber in 2 pts (DDD 1, VDD 1). Two newborns, both with a congenital A-V block and severe heart failure, died in the first hours after epicardial pacing. Two other children, both with congenital heart disease, died during follow-up, but the death was not pacemaker-related. Finally, two children were lost to follow-up. The mean follow-up of the 41 remaining pts was 5.2 +/- 3.5 years (4 months-10 years). Twelve children (29%) required 19 implant revisions and the causes were: lead fracture (26%), rising stimulation threshold (26%), growth problems (21%), erosion and/or pocket infection (21%). Revisions were more common in epicardial (52%) than in endocardial (22%) implantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Palliative percutaneous and endoscopic urinary diversion for malignant ureteral obstruction.

We performed a retrospective analysis of 22 patients with malignant ureteral obstruction who underwent palliative urinary diversion by retrograde ureteral stenting or nephrostomy tube placement. The average duration of survival after diversion was 526 days and was unrelated to tumor type, patient's age or sex, renal function, or indications for diversion. As a group, patients without previous hormonal or chemotherapy survived longer. Morbidity related to the urinary diversion was low. The majority of patients (77%) were discharged from the hospital, and this group spent 86 percent of their survival time at home. We conclude that modern palliative urinary diversion can be performed with low morbidity and can result in long-term survival and improved quality of life. Predictions or assumptions concerning survival of individual patients should be made with caution.

Adult↗
PubMed1991

Radioimmunoscintigraphy of ovarian cancer with the MOv18 monoclonal antibody.

The monoclonal antibody (Mab) 131I-MOv18 was administered to 30 patients with ovarian carcinoma intravenously (n = 20) and intraperitoneally (n = 10). After intraperitoneal administration, higher tumour uptake (mean values 1.3% vs. 0.8%) and a better tumour/background ratio (mean values 2.8 vs. 1.9) than after intravenous injection were obtained. Moreover, after intraperitoneal administration the uptake in non-affected organs, such as liver and spleen, was lower. However, occasionally the favourable results of the intraperitoneal route were cancelled by persistent pelvic non-specific accumulations of 131I-MOv18. The possibility to change the biodistribution pattern in the latter cases with peritoneal washing was evaluated. 3 patients were submitted to this procedure and an improvement in the radiotracer biodistribution was obtained in 1 case. With regard to tumour detection, the average sensitivity (73%) showed a significant difference from the sensitivities for abdominal (61%) and pelvic lesions (90%). No false positive results were noted.

Adult↗
PubMed1991

Immunoscintigraphy of colorectal carcinoma with an anti-CEA monoclonal antibody: a critical review.

An anti-CEA monoclonal antibody (FO23C5), belonging to the IgG1a class, was used to perform several preclinical and clinical studies on radioimmunoscintigraphy (RIS) in patients with colorectal carcinoma. Preliminary screening on different tissues showed high specificity of this antibody for gastric and colorectal carcinomas. A pilot study on 51 patients with 64 localizations of colorectal carcinoma was realized, followed by a multicenter validation study in which, among 509 patients bearing CEA secreting tumors, 254 patients had primary or relapsed colorectal tumors. High sensitivity and specificity values were obtained by these studies and many "unsuspected" localizations were recorded. In order to better define the clinical utility of this approach, a prospective trial was run on 59 patients previously submitted to surgery for colorectal carcinoma and with suspected local relapses. A comparative evaluation of RIS, CT scan, US and MRI was performed. RIS and MRI have the highest value of accuracy (86%) followed by CT scan (68%) and US (54%). No adverse reactions were noticed in any of the patients examined.

Antibodies, Monoclonal↗
PubMed1991

The contribution of salvage surgery to the management of childhood osteosarcoma.

Between January 1970 and December 1988, 174 consecutive patients under the age of 20 years with curatively resected primary osteosarcoma were treated at our institute; 72 in the years of 1970 to 1981 and 102 in the years 1982 to 1988. In the latter period, adjuvant chemotherapy was replaced by neoadjuvant programs, and new criteria were adopted for the management of lung metastases, consisting in early bilateral surgical staging and lung resection through median sternotomy for all patients with purely intrathoracic relapse. Follow-up was updated in December 1989. During the last period, the overall 5-year survival improved significantly from 35% to 58% (P less than .001). The disease-free survival rose from 38% to 45% at 5 years, with median values of 15 months versus 33 months, while the frequency of isolated lung metastases dropped from 58% to the actuarial 48%. The proportion of patients who underwent complete resections of their pulmonary metastases rose from 17% (seven of 42) to 55% (27 of 49), without operative mortality. Due to such a high proportion of patients eligible for salvage surgery, the overall survival from detection of lung metastases improved from 0% to 28% at 5 years (P less than .001). Contralateral occult metastases were resected in three of 15 subjects with monolateral clinical lesions, and five patients underwent subsequent lung resections. These data indicate that systematic bilateral pulmonary resection plays an important role in improving the final cure rate of childhood osteosarcoma, beyond the benefit resulting from neoadjuvant chemotherapy.

Adolescent↗
PubMed1990

Median sternotomy and multiple lung resections for metastatic sarcomas.

In the attempt to apply salvage surgery to the majority of patients with pulmonary tumour relapse, we have adopted a new treatment plan consisting of early bilateral lung exploration and resection through median sternotomy in all cases of sarcoma with resectable lung metastases, including synchronous or previously resected ones. The present paper summarizes the early results achieved with this technique in 56 consecutive patients treated between 1985 and 1988. Perioperative mortality was zero, and morbidity negligible. Occult contralateral metastases were resected in about one third of subjects with monolateral clinical lesions. Overall actuarial survival from first pulmonary resection is 51% at 2 years and 35% at 3 years. A slightly more favourable trend is evident for solitary lesions but the difference is not statistically significant. No difference in survival is observed in relation to the initial disease-free interval or to the histological type. The majority of relapses occurred within 6 months of sternotomy (23/35) and were confined to the lungs (21/35). Ten of these 21 patients with pulmonary relapse have undergone further resection and 5 of them are alive, with a median survival of 28 months. Present results are encouraging as far as resectability and early recurrence rate are concerned. Median sternotomy appears a most valuable therapeutic approach to pulmonary metastases from sarcomas, being safe and effective in local control of disease, and compatible with further surgical management of pulmonary recurrences.

Adolescent↗
PubMed1990

Results of salvage surgery for metastatic sarcomas.

Between January 1970 and December 1988, 105 consecutive patients underwent complete resection for lung metastases from sarcoma, 33 of them in the years from 1970 to 1983 and 72 between 1984 and 1988. In the latter period, new criteria consisting of early bilateral surgical staging and lung resection through median sternotomy were adopted for the management of lung metastases, in all patients with purely intrathoracic relapse. There was no operative mortality, follow-up was updated in August 1989, and actuarial survivals were calculated by the logrank method at 36 months from the time of first lung resection. During the second period, the overall actuarial survival at three years improved significantly (24% vs. 50%, P less than 0.02), notwithstanding the higher incidence of patients with unfavourable prognostic factors. The three-year survival was also significantly better in the subset of patients with a disease-free interval less than or equal to 12 mos. and/or multiple pathological lesions (9% vs. 45%, P less than 0.05). Contralateral occult metastases were resected in 10 of 29 subjects who underwent sternotomy for monolateral clinical lesions. Of 26 patients with further intrapulmonary recurrence, 16 (62%) were amenable to re-operation and eventual surgical rescue. These data suggest that median sternotomy and early management of occult contralateral disease may contribute to an improvement in the long-term survival of patients with metastatic sarcomas. On the other hand, it is possible that the effectiveness of salvage surgery is related to the higher activity and wider application of adjuvant and salvage chemotherapy.

Adolescent↗
PubMed1990

Questionable role of CNS radioprophylaxis in the therapeutic management of childhood rhabdomyosarcoma with meningeal extension.

A series of 15 consecutive children with head and neck nonorbital rhabdomyosarcoma (RMSA) with meningeal extension were prospectively treated with chemotherapy consisting of Adriamycin (doxorubicin; Adria Laboratory, Columbus, OH) (ADM), vincristine (VCR), cyclophosphamide (CPM), and dactinomycin (DACT) followed by radiotherapy (60 Gy) to the primary tumor volume, along with intrathecal methotrexate (IT MTX). Thirteen of 15 responded to preradiation chemotherapy. Four of 13 relapsed. Relapse occurred at the level of the primary tumor in three of four. The 3-year progression-free survival (PFS) was 59%, similar to that achieved in a previous series treated with a comparable therapeutic approach that also included whole-brain radiotherapy as a prophylaxis of possible occult meningeal seeding. It is concluded that CNS prophylaxis with radiotherapy is questionable in the management of childhood RMSA with meningeal extension.

Adolescent↗
PubMed1990

[Cardiovascular involvement and relative risk factors in systemic sclerosis. Personal contribution].

In systemic sclerosis (SS), cardiovascular commitment was recorded in an autopsy series, in widely different percentages, from 12 to 81%. On the other hand, clinical diagnosis of cardiopathy is made in far fewer cases. In addition, the coexistence of renal and/or pulmonary commitment makes difficult separation between primary and secondary heart damage. In 22 patients (2 m, 20 f) aged between 34 and 75 (average 55 +/- 11) with SS, a study has been made of the a) prevalence of cardiovascular commitment; b) the significance of the classic risk factors; c) the erythrocyte filtration time or TF (index of microangiopathic damage). Metabolic stability, fibrinogen, haematocrit and TF (Reid et al. method) were assessed in each patient. Nine patients (40.9%) presented ischaemic cardiopathy (myocardial infarction in three and effort angina in six), one (4.5%) presented hypertensive cardiopathy. Conduction disturbances were observed in five patients (22.7%). Whereas a statistically significant increase in TF was observed in cardiopaths, no differences in plasma levels of glucose, cholesterol or fibrinogen were observed. The incidence of smoking and the familial factor were also insignificant.

Adult↗
PubMed1989

Prognostic significance of the extent of myocardial injury in acute myocardial infarction treated by streptokinase (the GISSI trial).

To evaluate the different contributions of infarct site and infarct extent in determining the in-hospital outcome and efficacy of thrombolytic therapy, 8,731 patients with a first Q-wave acute myocardial infarction (AMI) enrolled in the GISSI trial were studied. On the basis of the standard 12-lead electrocardiogram, the sample was classified in 2 ways: classic electrocardiographic site pattern (anterior, inferior, lateral and multiple location), and number of standard electrocardiographic leads with ischemic ST elevation (small, modest, large and extensive infarct in 2 to 9 leads). In-hospital mortality was evaluated according to infarct site, infarct extent and fibrinolytic treatment. The mortality rate was differently distributed in the various infarct sites. Streptokinase significantly reduced mortality only in anterior (13.8 vs 18.7%) and multiple site infarcts (8.1 vs 12.5%). According to the infarct extent observed, there is a progressive increase in the mortality rate--from 6.5% in small infarcts to 9.6% in modest, 14.3% in large and 21.7% in extensive. No significant benefit was obtained by streptokinase in small infarcts; in contrast, a significant decrease in mortality was achieved in modest (7.7 vs 11.4%), large (12.8 vs 16.6%) and extensive infarcts (19.5 vs 23.9%). Thus, the extent of myocardial injury seems to be more relevant than the site in determining in-hospital mortality and efficacy of thrombolytic therapy.

Electrocardiography↗