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Limb salvage surgery and adjuvant radiotherapy for soft tissue sarcomas of the forearm and hand.

Twenty-five consecutive patients with soft tissue sarcoma of the forearm and hand were assessed for limb-salvage surgery and were entered into a prospective study evaluating oncologic details and functional outcome. Seventeen patients had received incomplete primary excision elsewhere and presented with local recurrence or residual disease. Three had pulmonary metastases at the time of presentation. Twenty-three patients were candidates for limb-salvage surgery and 20 received adjuvant radiotherapy. The mean follow-up period was 37 months. There was local recurrence in three patients who had initially received marginal excision of the primary sarcoma, and three patients died of systemic disease. Limb function was assessed prospectively using both patient-based and clinician-based functional scoring systems and revealed good to excellent results in all but three patients. Eighty-eight percent of those who survived and did not require amputation were able to return to occupational and activities of daily living with no or minimal functional limitation. This study demonstrates that limb-salvage surgery, with adjuvant radiotherapy when necessary, is an effective alternative to amputation in the majority of patients with sarcoma of the forearm and hand. Radiation toxicity is rarely a problem.

Activities of Daily Living↗

DNA content as a predictor of clinical outcome in soft tissue sarcoma patients.

The prognostic relevance of cellular DNA content has been shown for a variety of human malignancies. However, only a few studies concerning soft tissue sarcomas have been published. Biopsies of 81 patients with soft tissue sarcomas, referred for primary or secondary surgery, were analysed by flow cytometry to determine cellular DNA content of tumours. Most patients (60/81) already had one or more local recurrences at the time of first presentation at Essen University. The median age of the patients was 45 years (range 14-79). 44 (54%) patients had euploid and 37 (46%) had aneuploid tumours. Age, sex, and tumour localisation (trunk versus extremity) were equally distributed between euploid and aneuploid sarcoma patients. The median follow-up was 69 months (range 9-312). The median survival time for euploid and aneuploid tumours was 84 and 30 months, respectively (P < 0.0005). In the univariate analysis, ploidy, S-phase percentage, localisation and tumour grading were significant predictors of survival, whereas in the multivariate analysis, only DNA content and tumour localisation were independent prognostic variables for survival.

Adolescent↗

Resection of soft tissue sarcoma of the lower limb after evaluation of vascular invasion with intraoperative intravascular ultrasonography.

BACKGROUND: This study investigated the value of intravascular ultrasonography (IVUS) in the intraoperative assessment of vascular invasion of soft tissue sarcoma. METHODS: In a 4-year interval, of 337 patients with soft tissue sarcoma, 20 patients with tumours of the lower limb in close relation to the neurovascular bundle underwent intraoperative IVUS (20 MHz). Intraoperative findings were correlated with preoperative imaging, histopathological appearance of the resection specimen and patient outcome. RESULTS: Intraoperative IVUS was technically successful in all 20 patients. It correctly predicted vascular involvement (true positive) in ten of 11 patients who required resection of major vessels. There was one false-negative and one false-positive result. With magnetic resonance imaging, there were ten true-positive and three false-positive scans, and one false-negative diagnosis. IVUS improved the assessment of vascular involvement in four of the 20 patients. Histopathological examination confirmed complete resection (R0) in 18 patients. Mean survival was 37 months, and no local recurrence was observed in these patients. CONCLUSION: Vascular infiltration by soft tissue sarcoma can be visualized accurately by IVUS. This may improve intraoperative decisions about vessel resection.

Adult↗

Intravenous infusion of fosphenytoin produces prolonged pain relief: a case report.

The objective of this case report is to emphasize the analgesic effect of antiepileptic drugs in those with neuropathic pain, confirm that fosphenytoin possesses these analgesic properties, and to highlight that intravenous administration of fosphenytoin for 24 hours can produce good quality pain relief that lasts for many weeks. A 37-year-old woman with a neuroma (caused by surgical intervention for an endometrial sarcoma) producing neuropathic pain unresponsive to opiates was successfully treated with intravenous infusion of 1,500 phenytoin equivalent units fosphenytoin for 24 hours. The pain relief after this and subsequent infusions persisted for between 3 and 14 weeks and was associated with a reduced opiate requirement and an increase in activities of daily living. Fosphenytoin infusion can give good quality pain relief in the patient with neuropathic pain.

Journal Article↗

The N-ras oncogene assigned to the short arm of human chromosome 1.

The human N-ras oncogene, isolated from the HL-60 promyelocytic leukemia cell line, is distantly related to viral oncogenes of Kirsten and Harvey sarcoma viruses. We have determined its chromosomal location by Southern blot analysis of DNAs from 37 human x rodent hybrid cell lines derived from 8 different human donors, some of whom carried balanced rearrangements of chromosome 1. The results indicate that the N-ras oncogene (RASN) is localized on the proximal part of the short arm of human chromosome 1, in region p3200 leads to cen.

Animals↗

Ribosomal RNA on the surfaces of nonleukemic mouse ascites tumor cells.

RNAs on the cell surfaces of two nonleukemic and two leukemic strains of mouse ascites tumor cells were studied by fractionating the RNAs released from the cell surface by gentle pronase treatment after sucrose density gradient centrifugation, by indirect membrane immunofluorescence that used anti-RNA antibody and by cell electrophoresis. RNA was extracted from the cell supernatants of Ehrlich ascites tumor and sarcoma 180 cells (nonleukemic) that had been treated or not treated with pronase (1 microgram/ml, 37 degrees C, 20 min) followed by sucrose density gradient centrifugation. It was clearly demonstrated that the amounts of ribosomal RNA (18S and 28S) released after pronase treatment were approximately 80% greater than that of nonpronase-treated cells. Ehrlich ascites tumor cells that had been treated with actinomycin D (100 micrograms/kg body weight of mouse, 16 h) in vivo released an amount of ribosomal RNA after pronase treatment only 20% greater than the value for untreated cells. Actinomycin D treatment greatly reduced both the cell surface negative charge and the cell surface immunofluorescence when rabbit anti-RNA antibody was used. Under the same experimental conditions with actinomycin D, only ribosomal RNA synthesis showed preferential inhibition, not the syntheses of poly A-containing messenger RNA, 4S or other small-size RNAs. In contrast, L1210 and C1498 cells (leukemic) showed no change in the amounts of ribosomal RNA released after pronase treatment. L1210 cells also showed no change in the surface negative charge after being treated with actinomycin D.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[The volume of the surgical treatment and follow-up of patients with malignant ovarian tumors in the first stages].

From 1987 till 1997 110 patients with stage-I ovarian malignant tumors were treated and follow-up at the Department of Gynaecological Oncology, National Oncological Center. Papillifery-adenocarcinoma were in 40 cases, serous carcinoma were in 26 cases, mucinous carcinoma were in 15 cases, malignant granulosa cell tumor were in 14 cases, endometrioid carcinoma were in 6 cases, dysgerminoma were in 6 cases, Teilum's tumour were in 2 cases, and 1 case of ovary sarcoma were detected. Radical operated on the first operation were 69 patients (62.8%), and in 37 cases (33.6%) second operation for radicality were performed. In 4 cases only adnexectomy were done. In all cases post operative adjuvant chemotherapy were used. The patients were follow-up by tumour markers, sonography and CT. Follow-up period is from 5 months till 11 years. Alive were 80 patients (73%), and 30 patients (27%) were died. The patients with stage Ic and those nonradical operated in the first operation have worst prognosis then patients with stage Ia and stage Ib. The patients with ovarian tumours must be operated only in the hospitals with possibility of urgent hystological diagnosis for better prognosis in the cases of stage-I malignant ovarian tumours.

Bulgaria↗

Kaposi's sarcoma-associated herpesvirus-like DNA sequences (KSHV/HHV-8) in oral AIDS-Kaposi's sarcoma: a PCR and clinicopathologic study.

Recently, a new human herpesvirus (KSHV/HHV-8) has been identified in classic, transplant, endemic, and AIDS Kaposi's sarcoma that may be involved in the pathogenesis of Kaposi's sarcoma. The purpose of this study was to evaluate oral AIDS-Kaposi's sarcoma for detection of KSHV/HHV-8 DNA. DNA extracted from 54 oral AIDS-Kaposi's sarcoma lesions (47 initial, 7 postvinblastine treated), 5 non-Kaposi's sarcoma HIV-positive lesions, and 3 non-Kaposi's sarcoma HIV-negative lesions was evaluated by polymerase chain reaction (KS330(233bp)amplicon) for KSHV/HHV-8. The AIDS-Kaposi's sarcoma study population consisted of 52 patients (51:1, men:woman; 92% men having sex with men, 8% heterosexual; mean age, 38 years; mean, CD4 59/mm3) Opportunistic infections occurred in 88% (candidiasis, 65%; Pneumocystis carinii pneumonia, 31%; nonoral Kaposi's sarcoma, 25%; mycobacterium avium-intracellulare (MAI), 16%; cytomegalovirus, 14%; herpes simplex virus, 14%). Sexually transmitted diseases occurred in 73% (gonorrhea, 37%; syphilis, 23%; condyloma, 22%; HSV, 16%). Most frequent lesion sites were palate (74%) and gingiva (17%). Most common lesion types were purple nodular (48%) and macular (42%). Histopathologic subtypes were nodular (71%), plaque (27%), and patch (2%). Polymerase chain reaction analysis detected KSHV/HHV-8 DNA in 53 of 54 AIDS-Kaposi's sarcoma lesions (47 of 47 initial, 6 of 7 postvinblastine treatment). KSHV/HHV-8 DNA was not detected in non-Kaposi's sarcoma lesions in HIV-positive or HIV-negative persons. KSHV/HHV-8 DNA sequence is present in a high proportion of oral AIDS-Kaposi's sarcoma lesions. Whether KSHV/HHV-8 is an etiologic agent or a cofactor in the development of this vascular neoplasm is uncertain and remains to be proven. Polymerase chain reaction analysis for KSHV/HHV-8 DNA sequence detection may be helpful in identifying Kaposi's sarcoma in early vascular proliferations, when the characteristic histopathologic features are not present.

AIDS-Related Opportunistic Infections↗

DNA content prognostic in soft tissue sarcoma. 102 patients followed for 1-10 years.

In a prospective study of 102 patients with soft tissue sarcoma, the prognostic importance of DNA content and clinicopathologic features was analyzed. Based on DNA flow cytometry, 37 lesions were diploid (normal DNA content) and 65 were nondiploid (abnormal DNA content). The 5-year metastasis-free survival rate of the whole series was 0.59. The survival rate was 0.77 for patients with diploid tumors and 0.48 for those with nondiploid tumors (P = 0.01). Multivariate analysis identified two independent metastatic risk factors: increasing tumor size and nondiploidy. Unexpectedly, high malignancy grade (III-IV) was not found to be an independent risk factor for metastasis. The risk of metastasis was strongly related to the number of risk factors present. Thus, the 5-year survival for the 76 patients with no or one risk factor was 0.69, as compared with 0.30 for the 26 patients with two risk factors (P less than 0.0001). Our study shows that metastatic disease in soft tissue sarcoma is closely related to nondiploidy. A prognostication model based on DNA content and tumor size was found to discriminate between patients with a good and a poor prognosis after surgical treatment. The model can be used to identify patients who should be excluded from trials with adjuvant chemotherapy.

Adult↗

Rapid induction of uterine tumors with p53 point mutations in heterozygous p53-deficient CBA mice given a single intraperitoneal administration of N-ethyl-N-nitrosourea.

To investigate the sensitivity of heterozygous p53-deficient CBA mice to carcinogens, 20 female mice [p53(+/-)] and 20 wild-type littermates [p53(+/+)] were given an intraperitoneal injection of 120 mg/kg body wt of N-ethyl-N-nitrosourea (ENU) and were maintained without any other treatment for a further 26 weeks. Histopathology showed that uterine tumors (endometrial polyps and stromal sarcomas) and lung adenomas were induced in both p53(+/-) and p53(+/+) mice. The incidence of uterine tumors and lung adenomas (94% and 81%, respectively) in p53(+/-) mice was significantly greater than that in p53 (+/+) mice (37% and 42%, respectively). Malignant lymphomas were only induced in p53(+/-) mice, at an incidence of 31%. Concerning uterine tumors and preneoplastic lesions, there were endometrial stromal sarcomas and atypical hyperplasias of the endometrial gland in 90% and 63%, respectively, of p53(+/-) mice, with significantly greater incidences than in p53(+/+) mice. Gene analysis revealed GCG-->GTG point mutations in codon 135 of exon 5 of the p53 allele in all of the uterine endometrial stromal sarcomas examined. Our results suggest that female p53(+/-) CBA mice are very susceptible to uterine carcinogenesis, providing a useful model for ENU-induced uterine tumors.

Animals↗

Conformational change coupling the dimerization and activation of KSHV protease.

The mechanism of herpesviral protease activation upon dimerization was studied using two independent spectroscopic assays augmented by directed mutagenesis. Spectroscopic changes, attributable to dimer interface conformational plasticity, were observed upon dimerization of Kaposi's sarcoma-associated herpesvirus protease (KSHV Pr). KSHV Pr's dissociation constant of 585 +/- 135 nM at 37 degrees C was measured by a concentration-dependent, 100-fold increase in specific activity to a value of 0.275 +/- 0.023 microM product min(-1) (microM enzyme)(-1). A 4 nm blue-shifted fluorescence emission spectrum and a 25% increase in ellipticity at 222 nm were detected by circular dichroism upon dimer association. This suggested enhanced hydrophobic packing within the dimer interface and/or core, as well as altered secondary structures. To better understand the structure-activity relationship between the monomer and the dimer, KSHV Pr molecules were engineered to remain monomeric via substitution of two separate residues within the dimer interface, L196 and M197. These mutants were proteolytically inactive while exhibiting the spectroscopic signature and thermal stability of wild type, dissociated monomers (T(M) = 75 degrees C). KSHV Pr conformational changes were found to be relevant in vivo, as the autoproteolytic inactivation of KSHV Pr at its dimer disruption site [Pray et al. (1999) J. Mol. Biol. 289, 197-203] was detected in viral particles from KSHV-infected cells. This characterization of structural plasticity suggests that the structure of the KSHV Pr monomer is stable and significantly different from its structure in the dimer. This structural uniqueness should be considered in the development of compounds targeting the dimer interface of KSHV Pr monomers.

Cell Line↗

Antitumor activities of conjugates of mitomycin C with estradiol benzoate and estradiol via glutaric acid in suspension dosage form.

Conjugates of mitomycin C (MMC) with estradiol bezoate and estradiol via glutaric acid (EB-glu-MMC and E-glu-MMC, respectively) were examined for their antitumor activities against P388 leukemia and sarcoma 180. EB-glu-MMC and E-glu-MMC were suspended in 10% (v/v) propylene glycol in saline and administered intraperitoneally to mice bearing P388 leukemia intraperitoneally or to mice bearing sarcoma 180 subcutaneously. The antitumor effect against P388 leukemia was greater in the order MMC>E-glu-MMC>EB-glu-MMC, and only the former two compounds significantly increased life span. On the other hand, EB-glu-MMC and E-glu-MMC showed suppression of sarcoma 180 growth at higher doses close to or better than MMC. In the mixture of 1/15 M phosphate buffer (pH 7.4, ionic strength (mu) adjusted to 0.3 with NaCl)-propylene glycol (9:1, v/v) at 37 degrees C, MMC was released much more slowly from EB-glu-MMC suspension than from E-glu-MMC suspension. With regard to chemotherapy against sarcoma 180, both conjugates were considered to supply MMC slowly but effectively at higher doses.

Animals↗

Soft tissue and visceral sarcomas in Irish patients. Interim analysis of data obtained by the Dublin Soft Tissue Tumour Panel.

The Dublin Soft Tissue Sarcoma Panel was established in 1989 with a view to achieving a unified approach to diagnosis and management of soft tissue and visceral sarcomas. This interim report presents data on 265 prospectively-evaluated patients and on a separate retrospective series of 126 patients. The patients in the prospective series were treated by 93 different surgical and medical specialists. Tumours presented in all anatomic sites and ranged in size from 0.2 to 60 cm. Leiomyosarcoma was the commonest tumour type. Eighty-nine tumours were inoperable at clinical presentation. There was a consensus panel diagnosis in over 90%, non-neoplastic reactive lesions and primitive round cell tumours being the most difficult cases diagnostically. Management, including onward referral for chemotherapy or radiation therapy, was inconsistent. The 2-year survival figures were: 43% (1989-91) and 37% (1980-88). These findings should provide a basis for the evaluation of coherent treatment strategies for Irish sarcoma patients.

Adolescent↗

Doxorubicin chemotherapy in the treatment of soft-tissue sarcoma. Combined results of two randomized trials.

In 1978, there were initiated two independent randomized, prospective trials of adjuvant doxorubicin hydrochloride (Adriamycin) following primary therapy for soft-tissue sarcoma. The virtual identity of these two protocols permits their combination for analysis. A total of 75 patients (42 men, 33 women) with soft-tissue sarcoma (stages IIB to IVA) were randomized, after receiving optimal regional therapy, to receive either doxorubicin hydrochloride (450 mg/m2) (37 patients) or observation (38 patients). Follow-up has ranged from 16 to 80 months (median, 49 months). Twenty-five patients (33%) died, and two patients receiving doxorubicin developed cardiotoxicity. No significant differences in local control, metastasis-free survival, disease-free survival, and overall survival were observed for the two treatment arms. Despite temporary prolongation of disease-free survival with doxorubicin in some subgroups, we conclude that there is no advantage to the use of adjuvant doxorubicin in the treatment of soft-tissue sarcoma.

Clinical Trials as Topic↗

Hexose and amino acid transport by chicken embryo fibroblasts infected with temperature-sensitive mutant of Rous sarcoma virus. Comparison of transport properties of whole cells and membrane vesicles.

The effect of transformation on hexose and amino acid transport has been studied using whole cells and membrane vesicles of chicken embryo fibroblasts infected with the temperature-sensitive mutant of the Rous sarcoma virus, TS-68. In whole cells, TS-68-infected chicken embryo fibroblasts cultured at the permissive temperature (37 degrees C) had a 2-fold higher rate of 2-deoxy-D-glucose uptake than the same cells cultured at the non-permissive temperature (41 degrees C). However, both the non-transformed and transformed cells had comparable rates of alpha-aminoisobutyric acid transport. Membrane vesicles, isolated from TS-68-infected chicken embryo fibroblasts cultured at 41 degrees C or 37 degrees C, displayed carrier-mediated, intravesicular uptake of D-glucose and alpha-aminoisobutyric acid. Membrane vesicles from TS-68-infected chicken embryo fibroblasts cultured at 37 degrees C had an approx. 50% greater initial rate of stereospecific hexose uptake than the membrane vesicles from fibroblasts cultured at 41 degrees C. The two types of membrane vesicle had similar uptake rates of alpha-aminoisobutyric acid. The results of hexose and amino acid uptake by the membrane vesicles correlated well with those observed with the whole cells. Km values for stereospecific D-glucose uptake by the membrane vesicles from TS-68-infected chicken embryo fibroblasts cultured at 41 and 37 degrees C were similar, but the V value was greater for the membrane vesicles from TS-68-infected cells cultured at 37 degrees C. Cytochalasin B competitively inhibited stereospecific hexose uptake in both types of membrane vesicle. These findings suggest that the membrane vesicles retained many of the features of hexose and amino acid transport observed in whole cells, and that the increased rate of hexose transport seen in the virally-transformed chicken embryo fibroblasts was due to an increase in the number or availability of hexose carriers.

Amino Acids↗

Bone infarct-associated osteosarcoma.

Reported is a patient with an osteosarcoma arising in a medullary infarct of the humerus. Infarct-associated sarcoma (IAS) of bone is rare. In a collective review of 50 cases reported in the medical literature, only 37 were fully documented. Including our patient, 26 men and 12 women, ranging in age from 18 to 82 years (mean, 53.4 years) have been reported. Black patients appeared to be disproportionately represented, accounting for 36% of the group. In most patients, there was no known cause for the infarct, whereas in the remainder, the most common underlying condition was a prior dysbaric event or alcoholism. Approximately 75% of the patients had multiple bone infarcts. The femur was involved in 21 patients, the tibia in 14, the humerus in 2, and the radius in 1. Among 40 sarcomas in these patients, 7 (18.4%) were osteosarcomas, and 29 (72.5%) were malignant fibrous histiocytomas. The survival rate in patients with IAS is poor: 5 of the 7 patients with osteosarcoma (71%) and 20 of the 31 other patients (65%) died of tumor. Eight patients are alive and well, all for longer than 5 years.

Aged↗

Rhabdomyosarcoma of the head and neck in children.

OBJECTIVE: The purpose of this study was to determine the rhabdomyosarcoma types involving the head and neck (H&N) region in children and their immunophenotype. DESIGN: Anatomic pathology archives at Texas Children's Hospital were searched for all rhabdomyosarcoma cases over a 20-year period. One-hundred and thirty-seven cases were identified, with 50 being H&N cases. The cases were typed according to the Intergroup Rhabdomyosarcoma Study (IRS) criteria. Immunocytochemistry for myogenic and non-myogenic markers was performed on all H&N cases. Electron micrographs from cases (n=32) where ultrastructural examination had been performed at the time of original diagnosis were reviewed. RESULTS: Children with H&N rhabdomyosarcomas had a mean age of 5.3 years (median 4 years). There was a male predilection (1.7M:1.0F). Primary tumor sites were: face NOS (18%), orbit/periorbital (16%), nasal cavity/nose (14%), lymph nodes (12%), paranasal sinuses (10%), parameningeal (10%), parotid gland (6%), neck (6%), infratemporal fossa/zygoma (2%), buccal mucosa (2%), palate (2%), and larynx (2%). Metastatic disease at diagnosis (33% of all cases) occurred in the bone marrow (11%), cerebrospinal fluid (6%), peritoneal fluid (6%), lung (4%), parietal pleura (2%), pleural fluid (2%) and pericardial fluid (2%). Rhabdomyosarcoma types (IRS criteria) were: embryonal (60%), alveolar (classic and solid subtypes, 28%), botryoid (4%), undifferentiated (4%), spindle cell (2%) and anaplastic (2%). Immunocytochemical findings were: polyclonal desmin (96%); myogenin (96%); muscle-specific actin (74%), smooth muscle actin (12%). Nonmyogenic markers included: vimentin (100%), CD99 (16%), p53 (16%), pancytokeratin (10%), NSE (8%), LCA (6%), CD20 (6%), EMA (2%), and NB-84 (0%, neuroblastoma). Undifferentiated sarcoma expressed only vimentin. By ultrastructural examination, 44% had readily identified z-bands and myofilaments, 37% had infrequent to rare myofilaments and z-bands, and 19% had myotubular intermediate filaments. CONCLUSIONS: Distribution of H&N rhabdomyosarcoma IRS types is similar to that for all primary sites, with the exception that embryonal types are modestly increased while alveolar type is mildly decreased. There are many non-myogenic immunocytochemical markers that cross-react with rhabdomyosarcoma. Differentiation between favorable and unfavorable rhabdomyosarcoma types is important for appropriate therapy, and predicting prognosis and survival.

Adolescent↗

Mucinous cystadenocarcinoma in combination with hemangiosarcoma in the ovary.

The ovary is the sixth most frequent site of cancer in women in Denmark with an incidence of approximately 600 cases per year. Carcinomas predominate whereas sarcomas are rare. We describe a case of the combination mucinous cystadenocarcinoma and hemangiosarcoma in a 37-year old woman, who had a right-sited oophorectomy because of a cyst. Clinically there was no suspicion of malignancy. The macro- and microscopic findings are described as well as the immunohistochemical stainings performed to confirm the diagnosis. The case shows the importance of careful sampling at the macroscopic examination, especially from areas with a striking appearance.

Adult↗