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Biomedical subjects

M Avella

Publications and source records attributed to M Avella.

At least 73 records · Page 4Linked to original sources

Metastatic patterns in osteosarcoma.

The clinical courses of 193 patients with high-grade, non-metastatic osteosarcoma were reviewed to ascertain the evolution of the natural history of the disease. All patients had the primary lesion in the extremities and were treated at the Rizzoli Orthopaedic Institute between 1976 and 1982 with surgery alone (30 cases) or surgery plus adjuvant chemotherapy (163 cases). All patients were regularly followed at our Institute. One hundred and fourteen patients, of which 27 were treated with surgery alone and 87 treated with adjuvant chemotherapy, developed overt metastatic disease. No differences were found concerning the sites of the first relapse which, for approximately 90% of cases, were lungs in both groups. However, in the group of patients treated with adjuvant chemotherapy the development of overt metastatic disease, as compared to non-adjuvant patients, was delayed with time (13 vs 8 months) and the number of metastatic nodules in the lung at first relapse was reduced. This alteration in metastatic pattern due to adjuvant chemotherapy is important because it allows surgical resection of pulmonary metastases in a larger number of patients (51% vs 29%).

Adult↗

The effectiveness of chemotherapy in localized malignant fibrous histiocytoma (MFH) of bone: the Rizzoli Institute experience with 66 patients treated with surgery alone or surgery + adjuvant or neoadjuvant chemotherapy.

Between January, 1974 and July, 1985 66 patients with non-metastatic malignant fibrous histiocytoma (MFH) of bone in the estremities were surgically treated with amputation (34 cases) or resection (32 cases) according to the extension of the tumor. With the exception of 3 patients, who had severe medical contraindications to the chemotherapeutic drugs, all the patients were offered, in addition to the surgery, adjuvant chemotherapy (patients treated before 1983) or neoadjuvant chemotherapy (patients treated after 1983). 33 patients accepted, while 30 wanted to be treated with surgery alone. At median follow-up of 7 years (3-14) 25 patients remained continuously disease-free and 41 relapsed (27 with metastatic disease, 1 with local recurrence and 13 with both metastases and local recurrence). The percentage of patients who remained continuously disease-free was 12.1% (4:33) in the group of patients treated with surgery alone and 63.5% (21:33) in the group treated with surgery plus adjuvant or neoadjuvant chemotherapy. Although the two groups of patients were not completely superimposable (the patients treated with surgery alone were older and more often the MFH arose in pre-existing bone lesions) these results seem to suggest the usefulness of adjuvant and neoadjuvant chemotherapy for this tumor.

Adolescent↗

Adjuvant chemotherapy with six drugs (adriamycin, methotrexate, cisplatinum, bleomycin, cyclophosphamide and dactinomycin) for non-metastatic high grade osteosarcoma of the extremities. Results of 32 patients and comparison to 127 patients concomitantly treated with the same drugs in a neoadjuvant form.

Between March, 1983 and June, 1986, 32 patients with localized high grade osteosarcoma of the extremities who refused chemotherapy before surgery (neoadjuvant chemotherapy), were immediately operated on and treated with a protocol of adjuvant chemotherapy. This was performed with adriamycin, methotrexate, cisplatinum, bleomycin, cyclophosphamide and dactinomycin. At a median follow-up of 40 months (12-57), 20 patients (63%) remained continuously disease-free. These results appear to be better than the results achieved in our institution in 108 patients treated between 1980 and 1982 with an adjuvant chemotherapy protocol in which only adriamycin and methotrexate were employed. They also seem comparable to the results obtained in 127 contemporary patients treated with neoadjuvant chemotherapy in which the same drugs were used (methotrexate i.v., cisplatinum i.a. preoperatively; adriamycin- methotrexate- cisplatinum or adriamycin -bleomycin -cyclophosphamide-dactinomycin postoperatively, depending on the degree of necrosis achieved by preoperative treatment). These data seem to indicate that the improved survival with neoadjuvant chemotherapy compared to a previous group of patients treated with adjuvant chemotherapy may be related to the improved effectiveness of the agents used rather than the sequence of treatment.

Antineoplastic Combined Chemotherapy Protocols↗

Neoadjuvant chemotherapy for osteosarcoma of the extremities. Good response of the primary tumor after preoperative chemotherapy with high-dose methotrexate followed by cisplatinum and adriamycin. Preliminary results.

Forty-nine patients with localized osteosarcoma of the extremities were treated with a new protocol of neoadjuvant chemotherapy. Preoperatively the patients received high-dose methotrexate intravenously, followed after a week by cisplatinum intra-arterially for a continuous infusion over a 72-hour period, plus adriamycin intravenously infused over an 8-hour period. In all cases the clinical and radiographic response was good and in 44 cases (89.7%) it was possible to perform conservative surgery. The histologic examination of the surgical specimen resulted in necrosis being "good" (greater than or equal to 90% of necrosis) in 41 patients (83.6%). This percentage of "good necrosis" was significantly higher than the percentage previously obtained in our Center as well as in others for preoperative treatment of this tumor. Up to now, patients with localized osteosarcoma of the extremities who showed a good histologic response to the preoperative chemotherapy have had a very good prognosis (82% of patients are continuously disease-free). These results suggest that this new regimen represents a substantial improvement in the treatment of this disease.

Adolescent↗

The effects of methotrexate (MTX) on bone. A densitometric study conducted on 59 patients with MTX administered at different doses.

The bone density of two groups of patients with osteosarcoma treated with high and low doses of MTX is compared with that of a group of healthy subjects of the same age. Bone density was measured in the radius at the mid point and at the trabecular distal point. In the patients treated with low doses there were differences in bone density as compared with the controls. In those treated with high doses the bone mineral content values were significantly lower than those for the controls (p greater than 0.01) at the trabecular distal point but not at the mid point. The significant reduction in BMC in patients treated with high doses indicated that the osteopaenic effect is dose-dependent. The decrease in density only at the site at which trabecular bone is prevalent shows that MTX acts mainly at the level of this type of bone in accordance with the proven greater sensitivity of trabecular bone to the action of other osteopaenic agents.

Adolescent↗

Neoadjuvant chemotherapy in the treatment of osteosarcoma of the extremities: preliminary results in 131 cases treated preoperatively with methotrexate and cisdiamminoplatinum.

The results of 131 cases of classic non-metastatic osteosarcoma of the extremities treated with preoperative chemotherapy, surgery and postoperative chemotherapy are reported. Preoperatively, the patients were given Methotrexate (MTX) intravenously (high and average doses) and Cisplatinum (CDP) intraarterially. For postoperative chemotherapy, the drugs and treatment protocols were based on the degree of necrosis observed (good, fair, poor). Conservative surgery was performed in 73% of the cases and amputation in 27%. At an average 30 month follow-up (9-48 months) 59.5% of the patients had remained disease-free, 37.5% had developed metastases, and 3% had developed local recurrence. The percentage of disease-free patients was higher for those treated with high doses of MTX (68% vs. 51%) and for those in whom preoperative chemotherapy had induced good necrosis (75% vs. 44%). Neither the age or sex of the patients, nor the site of the tumor or type of surgery performed influenced prognosis.

Antineoplastic Combined Chemotherapy Protocols↗

[Usefulness of stratigraphy and computerized tomography in the initial staging of osteosarcoma of the extremities. Retrospective study of 217 cases].

The value of stratigraphy and pulmonary CT in the initial work-up of osteosarcoma of the extremities is assessed with reference to 217 patients encountered in the Bone Tumour Centre of Rizzoli Orthopaedic Institute in May 1983-May 1986. Stratigraphy revealed lung metastases not identified by standard radiography in 4 patients (1.8%), while CT revealed metastases not identified by either standard X-rays or stratigraphy in a further 6 cases (2.7%). It is concluded that the increase in the percentage of cures (about 30%) reported in the last 10 years in osteosarcoma cases given adjuvant chemotherapy cannot be explained by any difference in initial selection due to the use of these techniques that were not adopted in the historical series.

Bone Neoplasms↗

Prognostic value of serum alkaline phosphatase in osteosarcoma.

In 163 patients with osteosarcoma of the extremities treated with adjuvant chemotherapy, serum alkaline phosphatase (SAP) levels were evaluated before treatment and successively closely monitored in an attempt to determine whether serum levels of this enzyme had clinical value in predicting the course of the disease. Of 121 patients with elevated preoperative SAP levels, 78 (64%) recurred. Of 42 patients with normal preoperative SAP levels, only 8 (19%) recurred (P less than 0.00001). Of the 140 patients locally treated with amputation, SAP returned to normal values in 77 patients; 46 of these (59%) relapsed. Of the 21 patients whose SAP remained elevated after amputation, all but 2 relapsed (90%). Among 119 patients with normal postoperative values of SAP, at the time of relapse SAP resulted elevated in 22 of 41 patients (53%). These data confirm that in osteosarcoma, preoperative SAP levels have a definite value in establishing the prognosis and that posttreatment follow-up examination should include SAP determination, since persistent elevated or increasing values herald the appearance of a recurrence.

Adolescent↗

[Therapy of non-metastatic Ewing's sarcoma (pelvis excluded). Results obtained in 48 cases combining local therapy (radiation and/or surgical) and adjuvant chemotherapy with vincristine, adriamycin, dactinomycin and cyclophosphamide].

Combined therapy was used on a consecutive series of 48 patients with extrapelvic Ewing's sarcoma at the Rizzoli Orthopaedic Institute. The adjuvant chemotherapy protocol (VCR, ADM, D-ACT, EDX) was identical in all patients whereas local treatment consisted of amputation, resection and radiation treatment or radiation alone. At a mean follow-up of 58 months (39-78) 30 patients (60%) were free of the disease. This is a significantly higher percentage than that obtained in the same period with adjuvant chemotherapy using only 3 drugs (VCR, ADM, EDX). As far as the type of local treatment is concerned, the percentage of local recurrences and metastases was lower when the primary lesion was treated with surgery or surgery combined with radiotherapy, rather than radiation treatment alone. These suggest that if associated with radiation treatment and chemotherapy, surgery can play an important role that should be considered in the treatment of extrapelvic Ewing's sarcoma.

Antineoplastic Combined Chemotherapy Protocols↗

Estimation of sodium uptake through the gill of the rainbow trout Salmo gairdneri.

Sodium exchanges through the gill epithelia were estimated in the rainbow trout, Salmo gairdneri, using the perfused head technique. The head tissues accumulate radioactivity. In addition there exists an extrabranchial entry of sodium, which is 20 times smaller than the branchial one. The study of the evolution of venous and arterial sodium specific activities as a function of time is necessary before flux measurements are achieved. Contrary to previous studies, an uptake at the primary lamella level is demonstrated. Uptake of sodium through the secondary lamellae can be measured rapidly while at least 30 min are needed for measurement of uptake through the primary lamellae. Chloride cells of the primary lamellae contribute to about 20% of the total sodium uptake.

Animals↗

The internal redox balance of the cells influences the metabolism of lipids of dietary origin by J774 macrophages: implications for foam cell formation.

The effects of chylomicron remnants on lipid accumulation in J774 macrophages, and the incorporation of radioactivity from remnant lipids radiolabelled with [3H]oleate into cellular lipids was investigated. After 24 h of incubation with chylomicron remnants, there was considerable accumulation of lipid within the cells as assessed by staining with oil red O, indicating that the particles induce the formation of foam cells. Fatty acids released from the radiolabelled remnant lipids after uptake were found to be incorporated into cellular triacylglycerol (52%), phospholipid (37%) and cholesteryl ester (8%), but at higher remnant concentrations, the proportion used for triacylglycerol formation increased (up to 73%). When the macrophages were shifted into a pro-oxidising or pro-reducing state by incubation (24 h) with CuSO4 (2.5 microM) or N-acetylcysteine (5 mM), respectively, the incorporation of [3H]oleate from remnant lipid into cellular triacylglycerol and phospholipid was increased by 20-30% in the more oxidised as compared with the more reduced cells. These findings indicate that exposure of J774 macrophages to chylomicron remnants leads to the accumulation of lipid within the cells, and that this process is enhanced by pro-oxidising conditions. We conclude, therefore, that both lipids of dietary origin and the redox balance within macrophages may have a significant role in the induction of foam cell formation.

Acetylcysteine↗

[Ewing's sarcoma of the bone. Anatomoclinical study of 424 cases].

The clinic-epidemiologic and prognostic features of 424 cases of Ewing sarcoma observed at "Rizzoli" Institute between 1972-1990 are reported. The incidence of the tumor was higher in the second decade of life with slight predominance in the male sex. The primary lesion was especially localized in the extremity and the ratio lower/upper extremity was 5/1. We did not find, in contrast with other Authors, differences in height or in incidence of congenital malformations when compared to controls. The pain was the first common symptom at debut (90%) followed by swelling (50%) and fever (40%). Diagnosis was made 5.5 months after the first symptom and the delay was due to wrong diagnosis at debut in 3/4 of the patients. Laboratory tests showed anemia in about half of the patients and increased value of ESR (60%) and LDH (40%). Seventy-one of the patients were metastatic at presentation, none of these patients were still living after three years. At a median follow-up of 9 years 43% of the patients with localized disease, treated with adjuvant and neo-adjuvant chemotherapy remained continuously disease free, 53% developed metastatic disease and/or local recurrences and 2% had a second malignancy. In 24% of the patients metastases and/or local recurrences appeared three years after the beginning of treatment. Better prognosis was observed in female patients, without fever at diagnosis, with tumor localized at extremities and with normal value of hemoglobin, ERS and LDH. Regarding the type of treatment, better results were obtained by surgery of the primary tumor and by chemotherapy with four drugs (vincristine, cyclophosphamide, adriamycin dactinomycin) in comparison to radiotherapy of the primary tumor and chemotherapy with three drugs (vincristine, cyclophosphamide, adriamycin).

Adolescent↗

The prognostic value of serum alkaline phosphatase in osteosarcoma of the limbs.

The values for serum alkaline phosphatase were evaluated in 340 patients affected with osteosarcoma of the limbs. The percentage of patients with high values for the enzyme at the onset of disease was significantly higher in the 69 cases who presented with metastases at the time of diagnosis, as compared to the 271 cases in which the neoplasm still appeared to be localized (81% vs 62%: p less than 0.001). In this last group of patients, treated with neoadjuvant chemotherapy, an evident relationship between values for alkaline phosphatase and prognosis was demonstrated. The percentage of patients who developed metastases was in fact 22% in the group with normal serum values for the enzyme at the onset of the disease and 40% for the patients with high values of the same (P less than 0.001). These data confirm the prognostic value for serum alkaline phosphatase in osteosarcoma, which should be taken into consideration when planning chemotherapy and in classifying patients for randomized therapeutic studies.

Adolescent↗

Neoadjuvant chemotherapy for the treatment of osteosarcoma of the limbs. Preliminary results in 100 patients treated preoperatively with high doses of methotrexate i.v. followed by cisplatin (i.a.) and adriamycin.

One-hundred patients affected with non-metastatic osteosarcoma of the limbs were treated according to a new adjuvant chemotherapy protocol. Preoperative treatment consisted in high doses of methotrexate (i.v.), followed after one week by cisplatin continuous intra-arterial infusion for 72 hours and adriamycin in intravenous infusion for 8 hours. There was good clinical and radiographic response in all of the cases, and conservative treatment was used in 86 cases (86%). A postsurgery histological examination of the segment showed "good" necrosis (greater than 90%) in 75 patients (75%). The incidence of "good" necroses obtained with this protocol was significantly higher as compared to that observed previously at our Center when a preoperative chemotherapy scheme was used, which involved methotrexate and cisplatin alone. Up until now, patients with a good histological response to preoperative chemotherapy have always had an excellent prognosis. Thus, it is our belief that the 23% increase in good histological responses observed must correspond to an increase in the percentage of healing. The preliminary results (83% of patients with no signs of disease) seem to encourage our hypothesis.

Adolescent↗

The role of surgery in the treatment of localized Ewing's sarcoma.

This study includes 193 patients affected with localized Ewing's sarcoma and treated at the Rizzoli Orthopaedic Institute between April 1972 and May 1988. It is the purpose of this study to evaluate the efficacy of surgical treatment with regard to the prognosis of patients affected with E.S. and to define its indications as well as its limits as compared with radiotherapy. Ninety patients were treated surgically: 13 underwent amputation (localization of the disease in the leg and foot), 4 underwent debulking, 48 had resection of the tumor without any reconstruction (expendable bones), while for 25 other patients resection of the tumor required alloplastic or allograft replacement. In cases of E.S. localized in the pelvis and spine, surgery did not obtain improvement in prognosis. In the other sites, the percentage of disease-free patients increased from 57% to 72% in cases where surgery +/- radiotherapy was used instead of radiotherapy alone, while the percentage of local recurrences decreased from 18% to 5.5%, respectively. As for functional results, the highest incidence of excellent to good scores was obtained with surgery associated with radiotherapy (69%). The incidence of complications was only slightly different for the two groups.

Amputation, Surgical↗

Osteosarcoma associated with Paget's disease: a description of a rare case.

Osteosarcoma associated with Paget's disease is very malignant and has an extremely severe prognosis. This is also related to the usually advanced age of the patient and to the consequent impossibility of carrying out suitable chemotherapy. The case presented here is exceptional because of the young age of the patient, which allowed us to use a neoadjuvant chemotherapy protocol.

Adult↗