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Sprague-Dawley rats were administered low doses of metronidazole similar to those used in humans, and then subjected to a long-term follow-up. Metronidazole caused a significant rise in mammary tumors in the female rats (p < 0.001) after a mean latency period of 100.5 weeks.

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 < 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.

The clinical features and the treatment results of 15 patients with solitary plasmacytoma of the spine observed in a 28-year period (1950–1977) are reported. The signs at presentation were back pain in 4 cases and spinal cord compression in 11 cases. Three of these patients had paraplegia. Radiologically, the alteration encountered was an osteolytic lesion in all cases. The local treatment was radiotherapy in 11 cases and surgery plus radiotherapy in 4 cases. In 3 patients systemic chemotherapy was also employed. Seven patients are alive without signs of disease 3 to 9 years (mean 6 years) after diagnosis. Eight patients developed multiple myeloma in a period ranging from 1 to 8 years (mean 3.5 years). The relationship between multiple myeloma and solitary plasmacytoma of the spine, as well as the best treatment for the latter, are discussed.

The pretreatment serum lactic acid dehydrogenase (LDH) level of 246 patients with Ewing's sarcoma of bone (47 metastatic and 199 localized at presentation) was examined to evaluate the use of LDH as a tumor marker. The percentage of patients with increased serum LDH levels was significantly higher in the metastatic group than in the group of patients with localized disease (83 %vs 41 %; p < 0.01). In the latter group the relapse rate after treatment with combined therapy was significantly higher in patients with an elevated serum LDH at admission than in those with normal serum levels (68.2 % vs 39.3 %; p < 0.01). After local treatment, in 73 out of 82 patients with an elevated serum LDH at admission the enzyme level normalized whereas in 9 it fell but never reached a normal value. The rate of relapse in these two groups was respectively 64 % and 100 %.The value of serum LDH at the time of recurrence, determined in 62 patients, was elevated in 50 (80.7 %). These data demonstrate that in Ewing's sarcoma of bone pretreatment serum LDH levels have a definitive value in establishing the prognosis and could also be used in evaluating the response to therapy. A persistent elevated value of serum LDH, or an increasing value after a transient normalization, is usually followed by relapse.

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 %).

Of 255 cases of Ewing's sarcoma recorded at the Bone Tumor Center of the Rizzoli Orthopaedic Institute, 78 patients (irradiated and with a follow-up of longer than 3 years) were considered « at risk » for the development of a second radio-induced sarcoma (RIS). Three of the 78 patients developed an RIS in the irradiated field. Theoretical and statistical analyses were carried out considering different modalities of local treatment. Statistically, the only significant factor was related to the irradiation dose. Surgical resection seems to prevent RIS.

Thirty consecutive cases of localized primary non-Hodgkin's lymphoma of bone (PNHLB) were treated in a 10-year period at the Istituto Ortopedico Rizzoli with localized radiation (4 cases) and localized radiation and adjuvant chemotherapy (26 cases). The doses of radiation varied from 3000-4500 rad. A variety of staging procedures evolving with new diagnostic techniques over the 10 years were performed. Adjuvant chemotherapy comprised two different regimens of vincristine, adriamycin and cyclophosphamide. Twenty-four of the 26 patients (92 %) have been free of disease with a median follow-up of 75.5 months (18-144 months). Two patients developed meningeal involvement and one patient, treated with radiation therapy only, developed a local recurrence. The results are compared to the management of 68 Ewing's sarcoma patients treated during the same period. Here, higher doses of localized radiation therapy (approximately 5000 rad) and similar adjuvant chemotherapy were administered. The survival was 32 % (22/68) with a higher incidence of local recurrence (21 %). These data indicate that PNHLB should be considered a separate entity from Ewing's sarcoma and can be treated successfully with lower doses of radiation to the primary tumor and adjuvant chemotherapy. The observations are also compared to a variety of other biological characteristics of Ewing's sarcoma. Since only two patients developed meningeal relapse, our experience does not permit a firm recommendation for routine prophylactic treatment of the central nervous system in PNHLB.

Fifty-five cases of osteosarcoma of the extremities were treated between 1972 and 1976 with combination surgery and polychemotherapy (vincristine, adriamycin and methotrexate at medium doses) for 18 months. Their follow-up presently ranges between 30 and 80 months (x̄ = 48 months). Twenty-six patients remained free from disease signs, 2 showed local recurrence but no metastases, and 27 exhibited metastases (4 of these also had local recurrences). In 12 patients, the metastases appeared after the end of chemotherapy. Both metastases and local recurrences were more frequent in those patients submitted to segmental bone resection (7/8) than in those treated by more radical surgery (22/47). Comparison with a historical group (94 osteosarcoma patients treated with surgery alone at our Institute between 1960 and 1971) revealed that, during the follow-up period considered, the percentage of patients free from disease signs was higher in the group that also received chemotherapy. In addition, in this group metastatic appearance was delayed (x̄ = 15 months) as compared to historical controls (x̄ = 8 months). On the other hand, after the same kind of surgery, the rate of local recurrences and the time of their appearance was practically the same in both groups.

Metronidazole, which is widely used in the treatment of «Trichomonas vaginalis», «Entamoeba histolytica» and «Giardia lamblia» infections, was administered to BALB/c mice by stomach tube in an aqueous solution at a dose rate of 2 mg/day for 100 days (total 200 mg) to test its carcinogenicity. The treatment induced a significant increase in lung tumors in male mice (p < 0.001) and provoked the appearance of lymphomas in females (p < 0.001). Although there is insufficient evidence to pass judgement on the potential carcinogenicity of metronidazole in man, the results of this and other investigations reported in the literature have demonstrated that metronidazole develops carcinogenic activity in rats and mice.

From June 1983 to December 1985, thirty-eight paients with localized Ewing's sarcoma of the extremities were treated with a protocol that consisted of an initial nine week period of polychemotherapy (vincristine, adriamycin and cyclophosphamide) followed by local therapy and additional chemotherapy (vincristine, adriamycin, cyclophosphamide and dactino-mycln) for one year. As local treatment all patients were offered surgery; thirty-two accepted and six refused. These six patients were locally treated with radiotherapy alone (50 Gy). In the remaining patients an amputation was performed in one case and a resection in thirty-one. In resected patients when a wide margin was achieved (24 cases) no further local treatment was performed; when it was marginal (5 cases) or intralesional (2 cases) radiotherapy at lower doses (40 Gy) followed. At mean follow-up of thirty-seven months the percentage of continuously disease-free patients was 50 % for those treated with radiotherapy, 76 % with surgery, and 85 % with surgery and radiotherapy. Eight patients developed metastatic disease and two patients had local recurrence and metastases. The local recurrences were seen in one patient locally treated with surgery and in one locally treated with radiotherapy. Nine major local complications were observed: three in patients treated with radiotherapy, five in patients treated with surgery, and one in a patient treated with surgery and radiotherapy. These results indicate that after induction chemotherapy conservative surgery is possible in almost all cases of Ewing's sarcoma of the extremities and that such treatment is better than radiotherapy alone as local therapy.