[Antineoplastic activity of complex compounds of platinum(IV)].
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Between 1979 and 1986, 37 patients with sarcoma of the distal femur underwent limb salvage using a custom prosthetic knee replacement. Thirteen (35%) had early complications. Fourteen (38%) had late complications, which consisted of 6 aseptic femoral loosenings, 1 aseptic tibial loosening, 2 tibial fractures, 2 contractures, 1 femoral fracture, 1 prosthetic fracture, and 1 septic loosening. By 1988, nine patients died. Thirteen prostheses failed in 12 patients, resulting in 9 revisions, 2 above-knee amputations, and 2 Van Nes rotationplasties. The 2- and 5-year prosthetic survival rates were 82% and 57%, respectively. Twenty-two of the 26 survivors (85%) had successful limb salvage. Preventable factors were implicated in the loosening of six femoral components and in one femoral fracture. The mean Hospital for Special Surgery Knee Score was 69 (range: 62 to 86).
In our series of 37 patients with Kaposi's sarcoma, a larger than expected incidence of Americans of Italian and Jewish lineage was found, with 51% of Italian and 38% of Jewish background. Although a predominance of these two groups has been clearly shown previously, this may be the highest percentage of any series. In addition, 12, or 32%, of the patients were found to have concurrent diabetes mellitus. This association has been observed previously, but is not generally appreciated.
Yondelis (ET-743) is a novel anticancer agent isolated from the marine ascidian Ecteinascidia turbinata. ET-743 possesses potent antitumour activity and a novel mechanism of action at the level of gene transcription. We conducted two sequential phase I dose escalation and pharmacokinetic studies of ET-743 given as a 1- or a 3-h intravenous (i.v.) infusion. Seventy-two adults with metastatic or advanced solid tumours received ET-743 in escalating doses between 50 and 1100 microg/m(2), initially as a 1-h infusion, and later at doses between 1000 and 1800 microg/m(2) as a 3-h infusion every 3 weeks. The maximum tolerated dose (MTD) of ET-743 was 1100 microg/m(2) for the 1-h infusion schedule and 1800 microg/m(2) when given as a 3-h infusion. Dose-limiting toxicities (DLTs) were fatigue, neutropenia and thrombocytopenia. Transient non-cumulatives grade 3-4 increase in transaminases (not considered DLT) and grades 3-4 nausea and vomiting were frequently observed. Other toxicities (maximum grade 3) included anaemia, increased lactate dehydrogenase (LDH), bilirubin and alkaline phosphatase serum levels, and phlebitis; there were no toxic deaths. One pCR (melanoma), CR (uterine leiomyosarcoma), one PR (colon stromal sarcoma) and a MR (37% tumour shrinkage, gastric stromal sarcoma) were observed. A further 9 patients with colorectal, mesothelioma, bile duct carcinoma and bladder cancer had SD which lasted for six or more treatment cycles. ET-743 pharmacokinetics were linear with the 3-h infusion schedule. The haematological and hepatic toxicities of ET-743 were dose-dependent and not cumulative. Based on the current trial, the recommended dose of ET-743 for phase II studies is 1650 microg/m(2) given as a 3-h infusion.
A total of 37 adult patients with locally advanced or metastatic soft-tissue sarcoma (STS) entered a pilot study of combination chemotherapy based on the CYVADIC (cyclophosphamide, vincristine, doxorubicin, and dacarbazine) regimen, in which cyclophosphamide was replaced by ifosfamide and mesna (1 g/m2 ifosfamide given daily on days 1-5 as 2-h infusions, 1.5 mg/m2 vincristine given on day 1 as a bolus injection, 50 mg/m2 doxorubicin given on day 1 as a 5-min infusion, and 250 mg/m2 dacarbazine given daily on days 1-5 as 30-min infusions). The overall response rate in 24 patients who were evaluable for response was 46% [95% confidence interval (CI), 25%-67%] and that in subjects who had not undergone prior chemotherapy was 50% (CI, 27%-73%). In all, 4 patients achieved a complete response (17%; CI, 5%-37%) and 2 remain in remission; 3 additional subjects were surgically rendered disease-free after they had shown a partial response. Overall, 31 patients were evaluable for toxicity. Toxicity was mainly hematological; in 3 patients the nadir WBC was less than 0.5 x 10(9)/l, and in 2 cases the nadir platelet count was less than 50 x 10(9)/l. During neutropenia, infections requiring intravenous antibiotics occurred in 8 patients (26%) and in 14 of 190 cycles (7.5%); 1 of these was fatal. We conclude that this new regimen offers promise for the treatment of advanced STS, producing acceptable toxicity.
Abercrombie 's confronted explant technique was used to study the role of tumor surface antigens in malignant invasion. Plasma membranes were isolated from mouse sarcoma cells ( FS9 ) and a mouse cell line (L929) of the same H-2 haplotype. FS9 cells are highly invasive when confronted with chicken heart fibroblasts, whereas the L929 cells are not [ Abercrombie , M. (1979) Nature (London) 281, 259-262]. The FS9 plasma membranes contained significantly higher concentrations of a 37,000-dalton glycoprotein. When antiserum directed against FS9 plasma membranes was preabsorbed with L929 cells, the antibodies remaining reacted predominantly with the 37,000-dalton antigen. Fab fragment prepared from the preabsorbed antiserum inhibited the invasion of chicken heart fibroblasts by FS9 cells. Fab prepared from a monoclonal antibody directed against the 37,000-dalton antigen also inhibited invasivity , whereas monoclonal antibodies reacting with two other FS9 cell surface antigens did not. The results imply a relationship between the increased concentration of the 37,000-dalton glycoprotein on the surface of the FS9 cells and their invasivity .
This is a fifteen years' retrospective analysis of 37 kaposi's sarcoma cases diagnosed in the Department of Pathology, Addis Ababa University Medical Faculty between 1981-1994 G.C.. There were 12 female (32%) and 25 male (66%) patients. The median age was 35 years. There was a marked increase in 1994 when 14 cases (38%) were diagnosed. The most frequent site of the lesion is the lower extremeties followed by lymph nodes. The predominant histologic findings were spindle cell proliferation, vascular proliferation, extravasation and slit spaces. The authors believe that the finding of this study may serve as a base-line data for future studies.
Sequential gallium scans were performed in 37 patients with newly diagnosed osteogenic sarcoma. High gallium uptake was found more often in males in the 10 to 19 age group and in femoral lesions. High uptake was also seen in patients who had predominantly osteoblastic or mixed changes on radiographs and in those who had a soft tissue mass. Following chemotherapy, significant decrease of tumor to nontumor ratio occurred in the patients who responded to treatment as shown by a Grade III or IV response on histologic examinations at the time of en bloc resection. It is concluded that semiquantitative gallium scintigraphy is useful in monitoring therapeutic response in patients with osteogenic sarcoma.
BACKGROUND: It was the purpose of this study to test the monoclonal theory in ovarian carcinosarcoma. METHODS: Twenty-six women with a diagnosis of ovarian carcinosarcoma were subjected to a clinicopathologic analysis. Biopsies from metastatic lesions obtained at primary surgery and surgery for recurrent disease were reviewed. Special attention was paid to the composition of metastatic lesions and to florid desmoplastic reaction as a potential pitfall for the detection of sarcomatous areas. RESULTS: Biopsies derived from metastatic disease at primary surgery (n = 107) consisted of carcinoma cells only (n = 71, 66%), >50% carcinoma cells (n = 21, 20%), >50% sarcoma cells (n = 13, 12%), or sarcoma cells only (n = 2, 2%). The microscopic analysis demonstrated a preponderance of epithelial cells in the primary setting and suggested the epithelial component to drive the tumor, a finding consistent with the monoclonal theory. Biopsies derived from surgery for recurrent disease (n = 8) consisted of carcinoma cells only (0%), >50% carcinoma cells (n = 1, 13%), >50% sarcoma cells (n = 4, 50%), or sarcoma cells only (37%). Since sarcomatous cells dominated the tumorigenic cell population in the recurrent setting, this analysis revealed a change of the composition of metastatic lesions in time when compared to the data in the primary setting. This change was supported by the observation of a threefold higher incidence of sarcoma-dominated metastatic lesions at interval debulking when compared to primary debulking (24 vs 8%, respectively). The potential of a phenotypic change during ovarian cancer progression was further highlighted by the detection of two cases of carcinosarcoma that presented as a recurrence of epithelial ovarian carcinoma. CONCLUSION: Our results are consistent with the monoclonal theory of ovarian carcinosarcoma histogenesis, but suggest that there is a tendency toward a sarcomatous differentiation during disease progression. These data are important to understand the tumor biology and might have implications for a tailored treatment of ovarian carcinosarcoma.
We report a case of phlegmonous gastritis associated with Kaposi sarcoma in a 37-year-old, human immunodeficiency virus (HIV)-positive man who presented with an acute abdomen. Computed tomographic scan revealed free fluid in the abdominal cavity and a thickened gastric wall. A partial gastrectomy was performed. The resected portion of stomach had a hemorrhagic, necrotic thickened wall and showed extensive, acute suppurative inflammation, especially in the submucosa, with focal transmural involvement. Beneath an area of healing ulceration, a focus of Kaposi sarcoma was present. Group A beta-hemolytic streptococcus was grown from peritoneal fluid, and treatment with numerous antibiotics was initiated. After a difficult postoperative course that responded to 8 weeks of antibiotic therapy, the patient was medically stable and discharged from the hospital on antiretroviral therapy for HIV. Phlegmonous gastritis is a rare and rapidly progressive bacterial infection of the gastric wall. Kaposi sarcoma is one of the most common malignancies in HIV-positive patients, and gastric involvement is relatively common in those patients with systemic Kaposi sarcoma. To our knowledge, this is the first reported case of phlegmonous gastritis associated with Kaposi sarcoma, and it represents a rare survival following surgical and antibiotic therapy.
This is the first report on a primary choroidal alveolar soft part sarcoma in a 37-year-old male, who died 1 1/2 years following enucleation secondary to multiple metastases. Histology and differential diagnosis of this tumour are discussed. Histogenetically, because of the localization in the choroid, as far as the origin of these tumour cells is concerned, they supposedly stem from cell systems of the neuroectoderm. Since from these cell systems the malignant melanoma of the choroid arises too, a close relationship of these tumours is concluded.
The role of irradiation in the management of synovial sarcoma (SS) in pediatric patients is evaluated. The review covers all children seen at St. Jude Children's Research Hospital between May 1969 and December 1992 with the diagnosis of soft tissue sarcoma, of the 37 patients with the subtype SS, 16 received irradiation for the management of primary site disease. There were four IRS Group I, six Group II, four Group III, and two Group IV patients receiving irradiation. Tumor grade included seven Grade II, and nine Grade III lesions. TMN staging identified eight T1 and eight T2 lesions. Follow-up has ranged from 14 to 117 months (med = 33 months). All IRS Group I patients had documented local control. Five of six IRS Group II and 4/4 Group III patients have had documented local control at last follow-up. IRS Group IV patients had either local control tumor stabilization (n=1) or evidence of tumor regression (n=1) at autopsy. Complications following irradiation include wound dehiscence (n=1), surgery to revise a painful scar (n=1) extremity length discrepancy (n=2), and femoral head avascular necrosis (n=1). At last follow-up, 10 of 14 patients receiving curative intent irradiation remain alive. This review indicates questionable benefit to the addition of irradiation for patients with adequate surgical resection and having "good" tumor characteristics (Grade I, II; IRS Group I, TMN T1A,T1B. For lesions that have had incomplete resection or partial response to chemotherapy, there is evidence that irradiation may provide durable local control. The role of irradiation in those patients with IRS Group IV disease is at present confined to palliative roles until the time when more effective chemotherapy will mandate the decision to treat primary disease for curative measures.
The paper deals with the experience gained in carrying out rehabilitative surgery in 33 infant patients (37 operations) with bone sarcoma within 12 months to 12 years after combined treatment of primary tumor. Twenty-two operations using procedures of compression-distraction osteosynthesis were performed in 18 patients for post-surgery development of bone deformities and shorter limbs. shortening. Advantages of compression-distraction procedures are discussed since their application allows to make incisions and remove bone in areas outside the zone of radiation injury and permanent monitoring of exposed soft tissue condition. Twenty-two infants survived 5 years after orthopedic treatment. Four children died from metastases into the lungs 1-4 years after orthopedic rehabilitation.
Cell surface antigens of transformed cells are the traditional targets for antibody-guided detection and therapy of solid neoplasms. Alternative targets may be found in the tumor stroma, which contains newly formed blood vessels, reactive fibroblasts, and extracellular matrix proteins. The F19 cell surface glycoprotein of reactive fibroblasts is a prototypic stromal antigen since it is found in the stroma of > 90% of common epithelial cancers but is absent or expressed at low levels in normal tissues and benign epithelial tumors. In the present study, we define an additional tumor stromal antigen, FB5, that is selectively expressed in vascular endothelial cells of malignant tumors. Immunohistochemical analysis of 128 tumors identified FB5 in endothelial cells in 67% of the samples (including 41 of 61 sarcomas, 26 of 37 carcinomas, and 18 of 25 neuroectodermal tumors) whereas normal blood vessels and other adult tissues tested lacked FB5 expression. In vitro studies showed that FB5 is a M(r) 165,000 cell surface glycoprotein, comprised of a M(r) 95,000 core polypeptide and highly sialyated O-linked oligosaccharides but few if any N-linked sugars, and that the FB5 gene is located on chromosome 11q13-qter. The restricted tissue distribution of the FB5 protein, which we refer to as endosialin, suggests strategies for tumor imaging and therapy that are aimed primarily at the tumor vasculature.
Chick embryo fibroblasts and chorioallantoic membranes of chick embryos infected with oncogenic or nononcogenic viruses were analyzed for polyamines. Nononcogenic viruses (influenze, Newcastle disease, or vaccinia virus) had no effect on the polyamine content of chorioallantoic membranes. Transformation of chorioallantoic membranes by a wild-type or temperature-sensitive mutant strain of Rous sarcoma virus under permissive conditions (37 degrees) caused a 2- to 4-fold increase in cellular spermidine and putrescine content. Only putrescine accumulated in chick embryo fibroblasts transformed by Rous sarcoma virus at 37 degrees. At the nonpermissive temperature (42 degrees), the temperature-sensitive mutant, unlike the wild-type strain, did not alter cellular morphology or polyamine content.
Because of new therapeutic trends of multi-modality and the importance of late effects, we have updated our series of radiation induced bone sarcomas seen at Memorial Sloan-Kettering Cancer Center over the past four decades. A total of 37 cases of bone sarcoma arising from normal bone in the irradiated field was analyzed. The median for latent period from irradiation to diagnosis of bone sarcoma was 11 years with a minimum latent period of four years. The median radiation dose for the bone sarcoma was 6000 rad in 6 weeks with a minimum total radiation dose of 3000 rad in 3 weeks. We have found nine patients who developed bone sarcomas in the radiation field after successful treatment of Hodgkin's disease. Criteria for radiation induced bone sarcomas and the magnitude of the risk of bone sarcomas are briefly discussed.