Nonmetastatic Ewing family tumors: high-dose chemotherapy with stem cell rescue in poor responder patients. Results of the Italian Sarcoma Group/Scandinavian Sarcoma Group III protocol.

BACKGROUND: High-dose chemotherapy (HDT) was added to conventional chemotherapy in Ewing sarcoma family tumor (EFT) patients, poor responders (PRs) to induction chemotherapy in order to improve their survival. PATIENTS AND METHODS: Patients aged ≤40 years with nonmetastatic Ewing sarcoma (ES) received vincristine (V), doxorubicin (A), cyclofosfamide (C), actinomycin (Ac), ifosfamide (I) and etoposide (E) (VACAc-IE regimen) as induction chemotherapy. As maintenance treatment, good responders (GR) received nine cycles of VACAc-IE regimen. PRs received three cycles of VAC-IE, mobilizing cycle with CE and HDT with Busulfan and Melphalan with stem cell support. RESULTS: Three hundred patients [median age 15 years (3-40 years)] entered the study. One patient refused local treatment, 242 (81%) underwent surgery [with radiotherapy (RT) in 80] and 57 (19%) RT alone. No toxic deaths were recorded. Overall GR were 146 (49%). Twenty-eight PR did not receive HDT. At a median follow-up of 64 months (21-116 months), 5-year overall and event-free survival (EFS) were 75% and 69%, respectively. Five-year EFS was 75% for GR, 72% for PR treated with HDT and 33% for PR who did not receive HDT. CONCLUSIONS: High-dose therapy added to the VACA-IE regimen in PR patients is feasible and effective. Selected groups of patients with ES can benefit from HDT.

Free amino acids in walnut kernels and young seedlings.

We investigated the composition of free amino acids in walnut (Juglans regia L.) seeds (embryo and cotyledons). We also examined xylem transport of free amino acids in young seedlings grown in the absence of external nutrients. A relatively high concentration of free alanine was found in seed tissue, whereas a relatively high concentration of citrulline was detected in young seedlings. Citrulline was the main free amino acid transported in the xylem to stem and leaves. The negligible presence of citrulline, a non-protein amino acid, in the kernel and its presence in high concentrations in all of the tissues of young seedlings, including cotyledons, embryonic axis, taproot and stem, suggest that citrulline is synthesized during walnut germination. We conclude that citrulline plays an important role in nitrogen translocation during walnut germination.

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.

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.

Surgical treatment of distant metastases in renal cell carcinoma.

Twenty-six patients with metastatic renal cell carcinoma have been submitted to metastatectomy between 1975 and 1986. The actuarial 5-year survival of the 23 patients resected for cure is 31%. The medium disease-free survival was 11 months for the 11 synchronous metastases and 26 months for the 12 metachronous metastases. Three patients with disseminated disease had palliative surgery: 2 for pathologic fractures and one for tracheal compression. All improved after surgery, and survived 7, 16 and 27 months. It is confirmed that surgical resection of solitary or single organ site distant metastases from renal cell carcinoma is justified.

Diaphyseal and metaphyseal hemiresection with autograft reconstruction in the treatment of lowgrade tumors of the long bones.

The authors discuss seven cases of parosteal tumors treated conservatively by diaphyseal and metaphyseal hemiresection with cortical autograft reconstruction. This treatment yielded excellent clinical and functional results without having to resort to resection and arthrodesis or prosthetic replacement. The slow growth and low malignancy of these tumors make the use of this technique possible even at the risk of local recurrence, which, if discovered early, can still be treated by further conservative procedures.

Membrane-associated binding sites for indoleacetic acid in the rice coleoptile.

As described previously, the sensitivity of rice (Oryza sativa L.) coleoptiles to auxin is modulated by oxygen. Under anoxia, coleoptile elongation is insensitive to exogenously applied indole-3-acetic acid (IAA), whereas its sensitivity increases in air in the presence of the exogenous stimulus. Here we report the presence of two independent classes of membrane-bound IAA-binding sites in air-grown coleoptiles. Their binding activity is strictly correlated with the system's sensitivity to IAA. We designate them as site A (high affinity) and site B (low affinity). Site A shows a relatively fast response to anoxia, and is highly specific for auxins. Regulation of site-A binding activity through ATP, whose availability decreases under anoxia, is postulated. A role as auxin carrier is suggested for site B.

Resection of the proximal humerus and I.O.R. modular prosthesis in the treatment of metastatic lesions.

The authors report a series of 20 patients affected with metastatic lesions of the proximal humerus (19 cases) or scapula (one case) treated by intra-or extra-articular resection of the humerus and successive reconstruction with an I.O.R. type shoulder modular prosthesis. This method is indicated for the treatment of patients with extensive destruction of the epiphysis and cortical bone and limited invasion of the surrounding soft tissues. Prosthetic implant does not contraindicate the use of postoperative radiotherapy, and the cement used to anchor the endomedullary shaft contributes to the sterilization of any metastatic microfoces present by means of an intense esothermic polymerization reaction. The results obtained were satisfactory, with regression of pain and good functional recovery of the limb. There were no postoperative complications.

Early and late heat shock proteins in wheats and other cereal species.

Coleoptiles and roots of 3-day-old seedlings from five cereal species (Triticum aestivum L., T. durum Desf., Hordeum vulgare L., Secale cereale L., and Triticale) respond to heat shock at 40 degrees C by synthesizing a new set of 13 strong bands (as revealed by one-dimensional sodium dodecyl sulfate gel electrophoresis) as well as some 20 degrees C proteins. Heat shock proteins (HSPs) belong to three different size groups: high molecular mass HSPs in the 103 to 70 kilodalton range, intermediate molecular mass HSPs in the 62 to 32 kilodalton range, and low molecular mass HSPs about 17 to 16 kilodalton in size. At the beginning of the heat shock coleoptiles show a reduced ability to synthesize intermediate molecular mass HSPs but after 4 hours at 40 degrees C they exhibit fully developed HSP patterns identical to that found in roots. Synthesis of early HSPs declines after 7 hours of treatment followed by the appearance of a new set of 12 protein bands (late HSPs) in the ranges 99 to 83, 69 to 35, and 15 to 14 kilodaltons. After 12 hours at 40 degrees C, three other late HSPs of 89, 45, and 38 kilodalton are induced. The induction of late HSPs after 7 hours at 40 degrees C appears to be associated with an enhancement of radioactive methionine incorporation into proteins.

Benign epiphyseal chondroblastoma adjacent to the femoral intercondylar fossa.

The authors present three cases of epiphyseal chondroblastoma localised adjacent to the femoral intercondylar fossa which proved to be relatively common in a recent review of the case material of the G. Pini Institute of Milan (3 out of 22 cases). They were able to deduce various features of value in diagnosis and treatment which enable a single stage operation to be planned. This consisted of curettage with or without spongy bone transplants, and can be carried out even when the articular cartilage has been breached. The long term results in all three cases were satisfactory.

Aneurysmal bone cyst of the patella.

Aneurysmal bone cysts of the patella are extremely rare. Only 4 cases have been reported in the literature. The authors add a fifth case which came under their observation.

[Place of radiology in giant cell tumors of the bone]. / Ruolo della radiologia nel tumore a cellule giganti (TCG) dello scheletro.

The authors present 60 cases of histologically confirmed giant cell tumor classified by a radiological grading as quiet, active and aggressive form. On the basis of our acquired experience and mainly from the follow-up films, all the pertinent radiological findings are analysed either for a more correct therapeutic guidance or for an adequate post-operative follow-up (favourable evolution, definitive recovery, local relapse, malignant degeneration).

The treatment of simple bone cysts by topical infiltrations of methylprednisolone acetate: technique and results.

The authors report their experience in the percutaneous treatment of simple bone cysts by intra-cystic local infiltrations of methylprednisolone acetate. In particular, the method adopted, the evolution of the radiologic picture and the results achieved are described. Sixty patients were successfully treated without complications or surgery.

[Painful sacral rachischisis: considerations on the etiopathogenesis and treatment]. / Schisi sacrale dolorosa: considerazioni su etiopatogenesi e trattamento.

The Authors present 13 cases of patients with a painful spina bifida operated between 1965 and 1974. This exiguous number of patients shows that the surgical indication is placed only after a symptoms's severe valuation and the inefficacy of bloodless therapy. The 3 poor results were due to the coexistence of other diseases. The pain is caused by skeletal insufficiency. It would suitable to carry out a close research as Computerized Axial Tomographic Scanning and to join an intervention of arthodesis intersomatic when there are another malformations.

The treatment of infected pseudarthrosis.

Modern tendencies in the treatment of infected pseudarthrosis are discussed and compared with the methods of the recent past. Seventy four cases are analysed in detail. Fifty three were in the tibia, twenty six of which were treated by a standard modern technique consisting of osteomuscular decortication, excision of infected tissues and necrotic bone, external fixation and if necessary the addition of autoplastic cancellous grafts. The main purpose of this study was to analyse these results and assess the validity of this method.

Total protein release from barley aleurone layers as a bioassay for gibberellins.

The effect of gibberellic acid on the secretion of proteins from barley (Hordeum vulgare L.) aleurone layers has been investigated for its suitability as a gibberellin bioassay. Concentrations from 10(-4) µg/ml to 100 µg/ml of GA3 resulted in the release of proportionally increasing amounts of total protein. The release of proteins is not affected by indoleacetic acid and kinetin. This method has been applied and compared with the α-amylase assay for the estimation of gibberellin in extracts of tomato fruits and maize seedlings.