National Cancer Institute®
Last Modified: June 1, 2002
UI - 11989552
AU - Fryczkowski M; Potyka A; Huk J
TI - Evaluation of organ sparing operation results from planned indications in patients with kidney cancer.
SO - Int Urol Nephrol 2001;32(4):621-7
AD - Department of Urology, Silesian Medical Academy, Zabrze, Poland.
An analysis in 53 patients with kidney cancer has been conducted, a group on which kidney sparing operations have been performed. 25 women and 28 men have been examined at the age of 53.7 in the postoperative period of 7 divided by 130 months. The average observation time without any recurrences or metastases was 48.8 months. 5.7% local and 1.9% remote decease related recurrences have been found. The stage of clinical progression and the degree of histological malignancy are factors determining the five-year survival being 98.0%, while without any recurrences or metastases being 88.4%.
UI - 10679647
AU - Fioretti F; Tavani A; Gallus S; Negri E; Franceschi S; La Vecchia C
TI - Menstrual and reproductive factors and risk of soft tissue sarcomas.
SO - Cancer 2000 Feb 15;88(4):786-9
AD - Istituto di Ricerche Farmacologiche "Mario Negri," Milan, Italy.
BACKGROUND: Soft tissue sarcomas (STS) are a heterogeneous group of neoplasms whose etiology remains largely undefined. A role for female hormones in the development of STS has been suggested. To investigate this possibility, the authors analyzed data from a hospital-based case-control study conducted in Northern Italy between 1983 and 1998. METHODS: Cases were 104 women aged < 79 years with incident STS who were admitted to the cancer institutes and major teaching and general hospitals. Controls were 505 women admitted to the same network of hospitals for acute, nonneoplastic, nongynecologic, and nonimmune-related conditions. RESULTS: The multivariate odds ratio (OR) for women aged >/= 15 years compared with those aged < 12 years at menarche was 1.94 (95% confidence intervals [95% CI], 0.80-4.74). No association with STS risk was observed for menstrual cycle pattern, age at menopause, parity, and abortions. Late age at first pregnancy and birth were found to be related to an increased risk of STS, with an OR of 3.16 (95% CI, 0. 96-10.44) and 2.79 (95%% CI, 0.79-9.90) for women aged >/= 30 years at first pregnancy and birth compared with those aged < 20 years. The trend in risk was significant for age at first pregnancy. No relation with the risk of STS emerged for age at last birth and time since first or last birth. CONCLUSIONS: The risk of STS was found to be weakly related to late age at first pregnancy or birth, but not to other menstrual and reproductive factors. Copyright 2000 American Cancer Society.
UI - 11984800
AU - Smith LM; Anderson JR; Coffin CM
TI - Cytodifferentiation and clinical outcome after chemotherapy and radiation therapy for rhabdomyosarcoma (RMS).
SO - Med Pediatr Oncol 2002 Jun;38(6):398-404
AD - Department of Radiation Oncology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA. firstname.lastname@example.org
BACKGROUND: Second-look surgery after therapy for rhabdomyosarcoma (RMS) may yield prognostic information regarding tumor responsiveness to treatment. Favorable outcome is suggested by tumor cells which have undergone maturation (cytodifferentiation).PROCEDURE: Specimens from patients treated on Intergroup RMS Study-IV (IRSG-IV) were studied before and after treatment. All patients received chemotherapy and most received radiation therapy. Post-treatment specimens were graded according to the quantity of tumor showing cytodifferentiation (0 = absent, 1 = mild, 2 = moderate, 3 = extensive). Proliferative activity by MIB-1, topoisomerase II-alpha, and p53 protein expression were measured. RESULTS: 19/31 cases from IRSG-IV were adequate for analysis. Six out of nineteen patients failed therapy within 1.3 years of treatment. Grade 3 cytodifferentiation was present in 10 cases (2 BRMS, 8 ERMS); none failed therapy. Grade 2 cytodifferentiation was present in 5 cases (1 ERMS, 2BRMS, 2ARMS); 2 patients with ARMS failed therapy. Grade 0-1 cytodifferentiation was present in 4 cases (1 ERMS and 3 ARMS); all failed therapy. Proliferative activity by MIB-1 and topoisomerase II-alpha immunohistochemistry decreased or was unchanged after treatment for all ERMS/BRMS, and 4/5 cases of ARMS. p53 immunohistochemistry showed no consistent pattern of reactivity. Sparse persistent tumor cells were present in 9/10 ERMS, 3/4 BRMS, 5/5 ARMS. CONCLUSIONS: Extensive cytodifferentiation is more commonly seen in ERMS/BRMS compared with less evidence for cytodifferentiation in ARMS suggesting fundamentally different mechanisms of cellular response to therapy in RMS. Sparse persistent tumor cells in post treatment ERMS/BRMS specimens does not appear to affect outcome. Copyright 2002 Wiley-Liss, Inc.
UI - 11984803
AU - Pohar-Marinsek Z; Anzic J; Jereb B
TI - Topical topic: value of fine needle aspiration biopsy in childhood rhabdomyosarcoma: twenty-six years of experience in Slovenia.
SO - Med Pediatr Oncol 2002 Jun;38(6):416-20
AD - Department of Cytopathology, Institute of Oncology, Ljubljana, Slovenia.
BACKGROUND: Chemotherapy (Cht) for rhabdomyosarcoma (RMS) given before local treatment can prevent mutilating surgery and high-dose irradiation (RT). Fine needle aspiration biopsy (FNAB) can confirm the diagnosis and neoadjuvant treatment can start without delay. The purpose of our study was to assess the role of FNAB in the management of childhood RMS in Slovenia. PROCEDURE: A total of 78 children and young adults were included. FNAB provided the pre-treatment diagnosis in 37 and surgical biopsy in 41 patients. In 61 cases recurrent/metastatic disease was aspirated. Cytological diagnoses were compared to the original histological diagnoses. All case histories, cytological and histological material were reviewed and immunocytochemical staining performed when necessary. RESULTS: FNAB provided a correct diagnosis of malignancy in all 37 primary tumours, a specific diagnosis of RMS was given in 29 (78%). With the use of immunocytochemistry during the last 15 years, the accuracy has risen to 87%. FNAB provided the diagnosis of recurrence/metastasis in 57/61 cases. No complications of FNAB were noted. Review of histology reclassified five original diagnoses of RMS into one malignant rhabdoid tumour and four sarcomas NOS. In review of cytology we were able to sub classify 80% of RMS. CONCLUSIONS: FNAB is a safe method, which enables us to establish the pre-treatment diagnosis of RMS, and to some extent even its type, without delay. In our study, FNAB successfully replaced surgical biopsy in 87% of RMS patients during the last 15 years. Neoadjuvant Cht was started immediately, surgery was delayed and more conservative. Consequently, the risk for treatment sequelae was considerably reduced. Copyright 2002 Wiley-Liss, Inc.
UI - 11902487
AU - Sugarbaker PH
TI - Review of a personal experience in the management of carcinomatosis and sarcomatosis.
SO - Jpn J Clin Oncol 2001 Dec;31(12):573-83
AD - Washington Cancer Institute, Washington Hospital Center, DC 20010, USA. email@example.com
BACKGROUND: Peritoneal surface malignancy can result from seeding of gastrointestinal cancer or abdomino-pelvic sarcoma; it can also occur as a primary disease, such as peritoneal mesothelioma. In the past, this clinical situation was treated only with palliative intent. METHODS: An aggressive approach to peritoneal surface malignancy involves peritonectomy procedures, perioperative intraperitoneal chemotherapy and knowledgeable patient selection. The clinical assessments necessary for valid clinical judgements include the cancer histopathology (invasive vs expansive progression), the preoperative abdominal and pelvic CT, the peritoneal cancer index and the completeness of cytoreduction score. Proper patient selection is mandatory for optimizing the results of treatment. RESULTS: In a series of phase II studies, appendiceal tumors with peritoneal seeding became the paradigm for success with an 85% long-term survival in selected patients. Carcinomatosis from colon cancer had an overall 5-year survival of 50% with selected patients. Also, sarcomatosis patients overall had a 40% 5-year survival in selected patients. Peritoneal mesothelioma showed a 36% 5-year survival. In all malignancies, early aggressive treatment of minimal peritoneal surface dissemination showed the greatest benefit. CONCLUSIONS: Oncologists must accept responsibility for knowledgeable management of peritoneal surface dissemination of cancer because a curative approach has been demonstrated in large phase II studies and all historical controls show 0% long-term survival. Adjuvant phase III studies with perioperative intraperitoneal chemotherapy in diseases where peritoneal surface spread occurs are indicated.
UI - 11830587
AU - Liu L; Eby MT; Rathore N; Sinha SK; Kumar A; Chaudhary PM
TI - The human herpes virus 8-encoded viral FLICE inhibitory protein physically associates with and persistently activates the Ikappa B kinase complex.
SO - J Biol Chem 2002 Apr 19;277(16):13745-51
AD - Hamon Center for Therapeutic Oncology Research and Division of Hematology-Oncology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-8593, USA.
The human herpesvirus 8 (HHV8, also called Kaposi's sarcoma-associated herpesvirus) has been linked to Kaposi's sarcoma and primary effusion lymphoma (PEL) in immunocompromised individuals. We demonstrate that PEL cell lines have a constitutively active NF-kappaB pathway, which is associated with persistent phosphorylation of IkappaBalpha. To elucidate the mechanism of NF-kappaB activation in PEL cell lines, we have investigated the role of viral FLICE inhibitory protein (vFLIP) in this process. We report that stable expression of HHV8 vFLIP in a variety of cell lines is associated with persistent NF-kappaB activation caused by constitutive phosphorylation of IkappaBalpha. HHV8 vFLIP gets recruited to a approximately 700-kDa IkappaB kinase (IKK) complex and physically associates with IKKalpha, IKKbeta, NEMO/IKKgamma, and RIP. HHV8 vFLIP is incapable of activating NF-kappaB in cells deficient in NEMO/IKKgamma, thereby suggesting an essential role of an intact IKK complex in this process. Our results suggest that HHV8 vFLIP might contribute to the persistent NF-kappaB activation observed in PEL cells by associating with and stimulating the activity of the cellular IKK complex.
UI - 11967286
AU - Chung YH; Means RE; Choi JK; Lee BS; Jung JU
TI - Kaposi's sarcoma-associated herpesvirus OX2 glycoprotein activates myeloid-lineage cells to induce inflammatory cytokine production.
SO - J Virol 2002 May;76(10):4688-98
AD - Department of Microbiology and Molecular Genetics and Tumor Virology Division, New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772-9102, USA.
Kaposi's sarcoma is an inflammatory cytokine-mediated angioproliferative disease which is triggered by infection by Kaposi's sarcoma-associated herpesvirus (KSHV). KSHV contains an open reading frame, K14, that has significant homology with cellular OX2, designated viral OX2 (vOX2). In this report, we demonstrate that vOX2 encodes a glycosylated cell surface protein with an apparent molecular mass of 55 kDa. Purified glycosylated vOX2 protein dramatically stimulated primary monocytes, macrophages, and dendritic cells to produce the inflammatory cytokines interleukin 1beta (IL-1beta), IL-6, monocyte chemoattractant protein 1, and TNF-alpha. Furthermore, expression of vOX2 on B lymphocytes stimulated monocytes to produce inflammatory cytokines in mixed culture. These results demonstrate that like its cellular counterpart, vOX2 targets myeloid-lineage cells, but unlike cellular OX2, which delivers a restrictive signal, KSHV vOX2 provides an activating signal, resulting in the production of inflammatory cytokines. Thus, this is a novel viral strategy where KSHV has acquired the cellular OX2 gene to induce inflammatory cytokine production, which potentially promotes the cytokine-mediated angiogenic proliferation of KSHV-infected cells.
UI - 11967335
AU - Curreli F; Cerimele F; Muralidhar S; Rosenthal LJ; Cesarman E;
TI - Friedman-Kien AE; Flore O Transcriptional downregulation of ORF50/Rta by methotrexate inhibits the switch of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 from latency to lytic replication.
SO - J Virol 2002 May;76(10):5208-19
AD - Department of Microbiology, New York University School of Medicine, New York, New York 10016, USA.
Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a cellular dihydrofolate reductase (DHFR) homologue. Methotrexate (MTX), a potent anti-inflammatory agent, inhibits cellular DHFR activity. We investigated the effect of noncytotoxic doses of MTX on latency and lytic KSHV replication in two KSHV-infected primary effusion lymphoma cell lines (BC-3 and BC-1) and in MTX-resistant BC-3 cells (MTX-R-BC-3 cells). Treatment with MTX completely prevented tetradecanoyl phorbol acetate-induced viral DNA replication and strongly decreased viral lytic transcript levels, even in MTX-resistant cells. However, the same treatment had no effect on transcription of cellular genes and KSHV latent genes. One of the lytic transcripts inhibited by MTX, ORF50/Rta (open reading frame), is an immediate-early gene encoding a replication-transcription activator required for expression of other viral lytic genes. Therefore, transcription of genes downstream of ORF50/Rta was inhibited, including those encoding the viral G-protein-coupled receptor (GPCR), viral interleukin-6, and K12/kaposin, which have been shown to be transforming in vitro and oncogenic in mice. Resistance to MTX has been documented in cultured cells and also in patients treated with this drug. However, MTX showed an inhibitory activity even in MTX-R-BC-3 cells. Two currently available antiherpesvirus drugs, cidofovir and foscarnet, had no effect on the transcription of these viral oncogenes and ORF50/Rta. MTX is the first example of a compound shown to downregulate the expression of ORF50/Rta and therefore prevent viral transforming gene transcription. Given that the expression of these genes may be important for tumor development, MTX could play a role in the future management of KSHV-associated malignancies.
UI - 12014461
AU - Chen VW; Schmidt BA; Wu XC; Correa CN; Andrews PA; Hsieh MC; Ahmed MN
TI - Childhood cancer in Louisiana 1988-1996.
SO - J La State Med Soc 2002 Mar-Apr;154(2):91-9
AD - Department of Public Health and Preventive Medicine/Louisiana Tumor Registery at Louisiana Health Sciences Center, New Orleans, USA.
Utilizing data from the Louisiana Tumor Registry, cancer incidence among children younger than 15 years of age is presented by major cancer type, according to the primarily histology-based International Classification of Childhood Cancer scheme. Cases include those diagnosed and/or treated at any hospitals and medical facilities in Louisiana, St. Jude Children's Research Hospital in Memphis, M.D. Anderson in Houston, and from neighboring states. Rates were age-adjusted, presented as rates per million, and were compared to the combined rates of the Surveillance, Epidemiology, and End Results (SEER) Program. The significance of rate differences were assessed at 0.05 level. From 1988-1996, about 125 children were diagnosed with cancer each year. In general, rates are higher in younger than older children, males than females, and white children than African-American children. The five most common childhood cancers are: leukemias (28% of total cases), central nervous system malignancies (22%), lymphomas (13%), renal tumors (8.4%), and soft tissue sarcomas (7.6%). Major findings of these cancers and their associated risk factors are presented.
UI - 11797301
AU - Shields CL; Shields JA; Honavar SG; Demirci H
TI - Primary ophthalmic rhabdomyosarcoma in 33 patients.
SO - Trans Am Ophthalmol Soc 2001;99():133-42; discussion 142-3
AD - Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
PURPOSE: To review the findings, management, and outcome in 33 cases of primary ophthalmic rhabdomyosarcoma. METHODS: The records of 33 consecutive patients from a single ocular oncology center were analyzed retrospectively for outcomes of final visual acuity, local recurrence, and distant metastasis. RESULTS: Rhabdomyosarcoma was primarily located in the orbit m 25 cases (76%), conjunctiva in 4 (12%), eyelid in 1 (3%), and uveal tract in 3 (9%). Findings had been present for a mean of 5 weeks and included proptosis in 10 patients (30%), eyelid swelling in 7 (21%), and blepharoptosis in 6 (18%). The initial diagnoses before referral to us included primarily rhabdomyosarcoma in 8 cases (24%), conjunctivitis in 5 (15%), cellulitis in 5 (15%), and pseudotumor in 4 (12%). Tumors were classified according to the Intergroup Rhabdomyosarcoma Study Group staging and treatment protocols as group I in 4 cases (12%), group II in 12 (36%), group III in 16 (48%), and group IV in 1 case (3%). Treatment included surgical debulking, chemotherapy, and radiotherapy. Local tumor recurrence was detected in 6 patients (18%), lymph node spread in 2 (6%), and distant metastasis in 2 (6%). Long-term visual outcome of the 28 patients who maintained their globe was 20/20 to 20/40 in 11 patients (39%), 20/50 to 20/100 in 5 (18%), and 20/200 or worse in 12 (43%). Mean follow-up was 8.3 years; tumor-related death occurred in 1 patients (3%). CONCLUSIONS: Rhabdomyosarcoma can present in the orbit, eyelid, conjunctiva, and uveal tract. Following treatment, local tumor recurrence occurs in 18% of cases, metastasis in 6%, and death in 3%.
UI - 11991973
AU - Ma YM; Vogt VM
TI - Rous sarcoma virus Gag protein-oligonucleotide interaction suggests a critical role for protein dimer formation in assembly.
SO - J Virol 2002 Jun;76(11):5452-62
AD - Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.
The structural protein Gag is the only viral product required for retrovirus assembly. Purified Gag proteins or fragments of Gag are able in vitro to spontaneously form particles resembling immature virions, but this process requires nucleic acid, as well as the nucleocapsid domain of Gag. To examine the role of nucleic acid in the assembly in vitro, we used a purified, slightly truncated version of the Rous sarcoma virus Gag protein, Delta MBD Delta PR, and DNA oligonucleotides composed of the simple repeating sequence GT. Apparent binding constants were determined for oligonucleotides of different lengths, and from these values the binding site size of the protein on the DNA was calculated. The ability of the oligonucleotides to promote assembly in vitro was assessed with a quantitative assay based on electron microscopy. We found that excess zinc or magnesium ion inhibited the formation of virus-like particles without interfering with protein-DNA binding, implying that interaction with nucleic acid is necessary but not sufficient for assembly in vitro. The binding site size of the Delta MBD Delta PR protein, purified in the presence of EDTA to remove zinc ions at the two cysteine-histidine motifs, was estimated to be 11 nucleotides (nt). This value decreased to 8 nt when the protein was purified in the presence of low concentrations of zinc ions. The minimum length of DNA oligonucleotide that promoted efficient assembly in vitro was 22 nt for the zinc-free form of the protein and 16 nt for the zinc-bound form. To account for this striking 1:2 ratio between binding site size and oligonucleotide length requirement, we propose a model in which the role of nucleic acid in assembly is to promote formation of a species of Gag dimer, which itself is a critical intermediate in the polymerizaton of Gag to form the protein shell of the immature virion.
UI - 11991980
AU - Lorenzo ME; Jung JU; Ploegh HL
TI - Kaposi's sarcoma-associated herpesvirus K3 utilizes the ubiquitin-proteasome system in routing class major histocompatibility complexes to late endocytic compartments.
SO - J Virol 2002 Jun;76(11):5522-31
AD - Department of Pathology, Harvard Medical School, Boston Massachusetts 02115, USA.
Human herpesvirus 8 (HHV8) downregulates major histocompatibility complex (MHC) class I complexes from the plasma membrane via two of its genes, K3 and K5. The N termini of K3 and K5 contain a plant homeodomain (PHD) predicted to be structurally similar to RING domains found in E3 ubiquitin ligases. In view of the importance of the ubiquitin-proteasome system in sorting within the endocytic pathway, we analyzed its role in downregulation of MHC class I complexes in cells expressing K3. Proteasome inhibitors as well as cysteine and aspartyl protease inhibitors stabilize MHC class I complexes in cells expressing K3. However, proteasome inhibitors differentially affect sorting of MHC class I complexes within the endocytic pathway and prevent their delivery to a dense endosomal compartment. In this compartment, the cytoplasmic tail of MHC class I complexes is cleaved by cysteine proteases. The complex is then cleaved within the plane of the membrane by an aspartyl protease, resulting in a soluble MHC class I fragment composed of the lumenal domain of the heavy chain, beta(2)-microglobulin (beta(2)m), and peptide. We conclude that K3 not only directs internalization, but also targets MHC class I complexes to a dense endocytic compartment on the way to lysosomes in a ubiquitin-proteasome-dependent manner.
UI - 11991991
AU - Li H; Nicholas J
TI - Identification of amino acid residues of gp130 signal transducer and gp80 alpha receptor subunit that are involved in ligand binding and signaling by human herpesvirus 8-encoded interleukin-6.
SO - J Virol 2002 Jun;76(11):5627-36
AD - Molecular Virology Laboratories, Department of Oncology, Johns Hopkins University, Baltimore, Maryland 21231, USA.
Human herpesvirus 8-encoded interleukin-6 (vIL-6) signals through the gp130 signal transducer but is not dependent on the IL-6 receptor alpha subunit (IL-6R, gp80) that is required for signaling by endogenous IL-6 proteins; however, IL-6R can enhance vIL-6 activity and can enable signaling through a gp130 variant, gp130.PM5, that is itself unable to support vIL-6 signaling. These findings suggest that the vIL-6-gp130 interactions are qualitatively different from those of human IL-6 (hIL-6) and that vIL-6 signaling may be more promiscuous than that of hIL-6 but that IL-6R may play a role in vIL-6 signaling in vivo. To examine the receptor binding requirements of vIL-6, we have undertaken mutational analyses of regions of gp130 and IL-6R potentially involved in interactions with ligand or in functional complex formation and used these variants in functional, ligand-binding, and receptor dimerization assays. The data presented identify positions within two interstrand loops of the gp130 cytokine-receptor homology domain that are important for vIL-6 signaling and vIL-6-induced receptor dimerization and show that vIL-6, like hIL-6, can form complexes with IL-6R and gp130 but that the roles of putative cytokine-binding residues of IL-6R in ligand-induced functional complex formation are qualitatively different in the case of vIL-6 and hIL-6.
UI - 11290599
AU - Wang QJ; Jenkins FJ; Jacobson LP; Kingsley LA; Day RD; Zhang ZW; Meng
TI - YX; Pellett PE; Kousoulas KG; Baghian A; Rinaldo CR Jr; Pellet PE Primary human herpesvirus 8 infection generates a broadly specific CD8(+) T-cell response to viral lytic cycle proteins.
SO - Blood 2001 Apr 15;97(8):2366-73
AD - Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pennsylvania 15261, USA.
Human herpesvirus 8 (HHV-8) is a recently discovered gammaherpesvirus that is the etiologic agent of Kaposi sarcoma (KS). The natural history of primary HHV-8 infection, including clinical outcome and host immune responses that may be important in preventing disease related to HHV-8, has not been elucidated. The present study characterized the clinical, immunologic, and virologic parameters of primary HHV-8 infection in 5 cases detected during a 15-year longitudinal study of 108 human immunodeficiency virus type 1 seronegative men in the Multicenter AIDS Cohort Study. Primary HHV-8 infection was associated with mild, nonspecific signs and symptoms of diarrhea, fatigue, localized rash, and lymphadenopathy. There were no alterations in numbers of CD4(+) or CD8(+) T cells or CD8(+) T-cell interferon gamma (IFN-gamma) production to mitogen or nominal antigen. CD8(+) cytotoxic T-lymphocyte precursor (CTLp) and IFN-gamma reactivity were detected during primary HHV-8 infection, with broad specificity to 5 lytic cycle proteins of HHV-8 encoded by open reading frame 8 (ORF 8; glycoprotein B homolog of Epstein-Barr virus), ORF 22 (gH homolog), ORF 25 (major capsid protein homolog), ORF 26 (a minor capsid protein homolog), or ORF 57 (an early protein homolog), in association with increases in serum antibody titers and appearance of HHV-8 DNA in blood mononuclear cells. CD8(+) T-cell responses to HHV-8 decreased by 2 to 3 years after primary infection. This antiviral T-cell response may control initial HHV-8 infection and prevent development of disease.
UI - 11905672
AU - Singer S; Demetri GD; Baldini EH; Fletcher CD
TI - Management of soft-tissue sarcomas: an overview and update.
SO - Lancet Oncol 2000 Oct;1():75-85
AD - Division of Surgical Oncology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Soft-tissue sarcomas (STS) are relatively uncommon, especially when considered as individual histological subtypes (of which there are more than 50). Their incidence increases with age, although they are disproportionately common among children. When diagnosed and managed in a non-specialist environment, outcome is generally significantly poorer than if patients are managed by a multidisciplinary team in a tertiary centre of excellence. Prompt referral of patients with clinically suspicious masses is strongly advocated, before any type of intervention is attempted. This brief, opinion-based overview emphasises the team approach and provides a synopsis of the strategies used at our institution for pre-operative assessment and biopsy, surgical management, and the delivery of radiation therapy when appropriate (focusing on limb preservation and optimisation of function). Predictable variations in the natural history of these tumours, based on accurate histological subclassification, merit wider recognition. The role of systemic chemotherapy for soft-tissue sarcoma is still evolving, but at present the main aims are improved local control, disease-free survival, and quality of life. There are overall survival benefits for specific histological types, but this is a relatively small subgroup. Novel therapies, based on disease mechanisms at the molecular level, show promise for future advances.
UI - 11904345
AU - Fletcher CD
TI - Distinctive soft tissue tumors of the head and neck.
SO - Mod Pathol 2002 Mar;15(3):324-30
AD - Department of Pathology, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. firstname.lastname@example.org
Among soft tissue tumors as a whole, those in the head and neck region are relatively uncommon, and the proportion of all soft tissue sarcomas that arise in this region is
UI - 11972393
AU - Fowler JM; Blessing JA; Burger RA; Malfetano JH
TI - Phase II evaluation of oral trimetrexate in mixed mesodermal tumors of the uterus: a gynecologic oncology group study.
SO - Gynecol Oncol 2002 May;85(2):311-4
AD - Division of Gynecologic Oncology, Ohio State University, Columbus, OH 43210, USA.
OBJECTIVES: This is a Phase II group-wide study of the Gynecologic Oncology Group to determine the toxicity and objective response rate of trimetrexate (TMTX) in patients with advanced, persistent, or recurrent mixed mesodermal tumors of the uterus who have failed higher priority treatment protocols. METHODS: TMTX was administered orally at a dose of 5 mg/m(2) BID for 5 days and repeated in 14 days. The maximum total dose was 50 mg/m(2)/week given every other week. The minimum treatment period was one course. Patients who had a complete response, partial response, or stable disease were continued on treatment for at least three courses. RESULTS: Twenty-eight patients were entered into the study. Three patients were ineligible based on review of pathologic materials. Twenty-five patients were evaluable for toxicity, and 21 were evaluable for response, as 4 patients did not complete one course of therapy. Eleven patients had heterologous mixed mesodermal tumor (MMT) and 10 had homologous MMT. Of the 25 evaluable for toxicity, one patient had grade 4 platelet toxicity. No patient had grade 4 neutropenia, while 4 patients had grade 3 decrease in absolute neutrophil count. One patient had grade 3 gastrointestinal toxicity, while 2 had grade 4 toxicity. There were no complete responses noted and only one partial response, for an overall response rate of 4.8%. The duration of the partial response was 15.2 months. CONCLUSION: Oral TMTX has insignificant activity in the treatment of advanced, persistent, and recurrent uterine MMT at the dose and schedule administered. (c) 2002 Elsevier Science (USA).
UI - 12001125
AU - Lohman RF; Nabawi AS; Reece GP; Pollock RE; Evans GR
TI - Soft tissue sarcoma of the upper extremity: a 5-year experience at two institutions emphasizing the role of soft tissue flap reconstruction.
SO - Cancer 2002 Apr 15;94(8):2256-64
AD - Section of Plastic Surgery, The University of Chicago, Chicago Illinois, USA.
BACKGROUND: The objective of this study was to define the impact of soft tissue flap reconstruction on multimodality therapy for patients with soft tissue sarcomas of the upper extremity. Treatment standards continue to evolve for these patients, and, with multimodality therapy, most of them are candidates for limb-preserving surgery. Consequently, the role of soft tissue flap reconstruction is expanding. METHODS: A review was conducted of 100 consecutive patients with soft tissue sarcomas of the upper extremity who underwent surgery at several institutions between 1992 and 1997. RESULTS: Seventy-one patients underwent direct closure of defects after tumor resection, and 29 patients required soft tissue reconstruction with flaps. These groups were similar in most respects, except that 52% of the patients who required soft tissue reconstruction presented with recurrent disease (P = 0.0004), and 79% of them had tumors measuring > 5 cm in greatest dimension (P = 0.0003). The patients who required flap reconstruction had larger skin deficits after undergoing tumor resection (140 cm2) compared with the patients who had wounds that were managed by direct closure (40 cm2; P < 0.00001). Margins around the resected tumors were larger (1.62 cm) when flaps were employed compared with margins when defects were closed directly (0.87 cm; P = 0.0005). However, the number of patients with intralesional, marginal, wide, and radical resections was the same regardless of wound management. Major complications occurred in 14% of patients, but none led to death or amputation. The median follow-up was 31 months, and 66% of patients had no evidence of disease at that time. Rates of local recurrence and survival were similar for patients who underwent flap reconstruction compared with patients who underwent direct closure. CONCLUSIONS: Soft tissue flap reconstruction facilitates therapy for patients with soft tissue sarcomas of the upper extremity, so that patients with larger tumors can undergo resection, limiting complications and limb sacrifice. Copyright 2002 American Cancer Society.
UI - 12001127
AU - Aigner T; Muller S; Neureiter D; Illstrup DM; Kirchner T; Bjornsson J
TI - Prognostic relevance of cell biologic and biochemical features in conventional chondrosarcomas.
SO - Cancer 2002 Apr 15;94(8):2273-81
AD - Department of Pathology, University of Erlangen-Nurnberg, Erlangen, Germany.
BACKGROUND: Conventional chondrosarcoma is the second most common malignant solid tumor of bone, and its management still poses a challenge for the orthopedic surgeon. Currently, tumor grade is the only parameter of prognostic significance besides stage and, possibly, resection margins. Additional independent prognostic markers therefore would be highly valuable for patient management. METHODS: In the current study, the authors evaluated biologic markers for various chondrocytic phenotypes by histochemical and immunohistochemical technology in a large series of clinically well defined cases of enchondromas and conventional chondrosarcomas, each with at least 5 years of clinical follow-up. RESULTS: The authors' results confirm the strong correlation between clinical behavior and cell differentiation as expressed by marker genes. The phenotypes of the tumor cells are the biologic substrate of the histopathologic appearance of the neoplasms and, thus, the biologic basis for classic tumor grading. Collagen Types II and X, as well as the proteoglycan aggrecan, suggest a mature neoplastic phenotype and good prognosis, i.e., low recurrence rate, rare metastasis, and long survival. Conversely, collagen Type I, together with cell spindling, indicates a transition to a more proliferative, so-called "dedifferentiated" phenotype, which clearly is associated with a poorer prognosis. The changes in cellular phenotypes are accompanied by changes in proliferative activity. Thus, low-grade neoplasms showing mainly mature and terminally differentiated (hypertrophic) chondrocytes display only scant proliferation whereas less differentiated chondrosarcomas with biologically dedifferentiated chondrocytes show significantly higher proliferative activity, a feature that is also highly correlated with prognosis. CONCLUSIONS: These data indicate that molecular markers are to a large extent the biologic basis of the conventional grading, rather than representing independent prognostic markers. The authors' results further indicate that COL1 has significant value in the distinction between enchondromas and low-grade chondrosarcomas including these that are histologically similar. Further understanding of chondrocytic phenotypes will be a promising way to provide new tumor markers for better understanding, diagnosis, and treatment of chondroid neoplasms. Copyright 2002 American Cancer Society.
UI - 12015769
AU - Bilimoria MM; Holtz DJ; Mirza NQ; Feig BW; Pisters PW; Patel S; Pollock
TI - RE; Benjamin RS; Papadopoulos NE; Plager C; Murphy A; Griffin JR; Burgess MA; Hunt KK Tumor volume as a prognostic factor for sarcomatosis.
SO - Cancer 2002 May 1;94(9):2441-6
AD - Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030-4095, USA.
BACKGROUND: The appropriate therapeutic interventions for sarcomatosis, or sarcoma characterized by intraabdominal dissemination, remain unclear. The authors performed a retrospective analysis of their recent experience with patients diagnosed with sarcomatosis to determine the overall survival and the effects of clinicopathologic features on survival rates at two and four years. METHODS: A query of the authors' prospective soft tissue sarcoma database identified 51 patients with a diagnosis of sarcomatosis who were evaluated at the authors' institution evaluated, and survival was calculated using a Kaplan-Meier survival analysis. Disease was categorized as low or high volume based on findings at surgical exploration or computed tomography scan evaluation. Disease was classified as low/intermediate grade or high grade based upon histologic examination. RESULTS: Twenty five patients were male and 26 were female. The median time from the initial diagnosis of sarcoma to the development of sarcomatosis was 0.9 years (range, 0-26 years). Thirty nine patients were treated with surgery, whereas 32 received primarily nonsurgical treatment. Histology revealed gastrointestinal stromal tumor (GIST) in 33 patients and other histologies in 18 patients. The two year overall survival rate of patients with GIST was similar to that of patients with other types of sarcoma (38% versus 42%, respectively, P = 0.77). Patients with low volume disease had an overall two year survival rate of 82%, compared with only 24% for patients with high volume disease (P = 0.008). There was no difference in the overall survival rates of patients with low grade (n = 18) versus high grade tumors (n = 33, P = 0.29). With a median followup of 2.7 years (range, 0.5-26.4 years), the median time from sarcomatosis to death was 13 months (range, 4-42 months). CONCLUSIONS: Evaluating volume of disease at the time of diagnosis permits stratification of patients into prognosis based subsets. We found no significant difference in two or four year survival rates in patients with GIST and those with non-GIST sarcomatosis. Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10504
UI - 12023578
AU - Folpe AL; Weiss SW
TI - Lipoleiomyosarcoma (well-differentiated liposarcoma with leiomyosarcomatous differentiation): a clinicopathologic study of nine cases including one with dedifferentiation.
SO - Am J Surg Pathol 2002 Jun;26(6):742-9
AD - Department of Pathology, Emory University, Atlanta, Georgia 30322, USA. email@example.com
Leiomyosarcomatous (LMS) differentiation is a rare event in liposarcoma (LPS) and may consist of either well-differentiated liposarcoma (WDL) with an intrinsic smooth muscle component, so-called "lipoleiomyosarcoma," (L-LMS) or dedifferentiated liposarcoma having smooth muscle differentiation in the dedifferentiated zones. The latter are high-grade sarcomas, whereas the behavior of the former group is uncertain. Specifically, it is not clear whether the presence of LMS negatively affects the prognosis. We present our experience with nine cases, the largest to date. The patients (seven male, two female) ranged in age from 42 to 65 years (mean 54 years). The tumors were usually large (2 to >40 cm [mean 17 cm]) tumors in the retroperitoneum (two cases), paratesticular-inguinal region (three cases), mediastinum (one case), lung (one case), abdomen (one case), and popliteal fossa (one case). The nine cases qualified as L-LMS and showed typical WDL with a multifocal, gradual transition into smooth muscle areas. The latter areas accounted for a variable portion of the lesions (range 5-90%) and were of low cellularity, mild to moderate nuclear atypia, and low mitotic activity. These areas seemed to arise from or blend with the smooth muscle in the walls of large vessels within the tumor. One case showed areas of dedifferentiation consisting of actin and desmin-negative, high-grade sarcoma. Follow-up in seven cases (range 26-312 months; mean 119 months) showed multiple local recurrences in seven patients and no metastases. Three patients are currently without evidence of disease (follow-up duration 26-312 months; mean 144 months) and four patients are alive with progressive disease (follow-up duration 60-132 months; mean 99 months). Our study suggests that L-LMS is a dual lineage sarcoma as evidenced by the fact that the smooth muscle component is often multifocal, not necessarily found in close association with the atypical changes in fat, and seemingly originates from atypical ("in situ") changes in the vessel wall. The LMS component, which is typically low grade, does not adversely affect the overall behavior of the tumor, which is similar to that of conventional WDL. LMS in L-LMS should not be misconstrued as evidence of low-grade dedifferentiation, a phenomenon that identifies a more unstable and potentially metastasizing lesion.
UI - 11941256
AU - Ducrey N; Nenadov-Beck M; Spahn B
TI - [Update of orbital rhabdomyosarcoma therapy in children]
SO - J Fr Ophtalmol 2002 Mar;25(3):298-302
AD - Service Universitaire d'ophtalmologie de Lausanne, Hopital Jules Gonin, 15 avenue de France, 1004 Lausanne.
INTRODUCTION: Rhabdomyosarcoma is the most frequent primitive orbital malignant tumor in children. If the treatment is started as soon as possible after discovery of the disease, the vital prognosis is considerably better than otherwise. The goal of this paper is to present the new therapeutic protocol and to report our experience in this field. MATERIAL AND METHOD: During the past 35 years, 102 cases of orbital tumors were collected in children under 15 years of age: 5 cases of rhabdomyosarcoma were cared for in our department. At the time of tumor diagnosis, the age of our patients ranged from 3 weeks to 13 years. After a biopsy or excision biopsy, all our cases were treated by chemotherapy with or without radiotherapy. Medication was mostly vincristine, ifosfamide and actinomycine D. When the result of the treatment was not satisfactory, carboplatine and epirubicine, vincristine as well as ifosfamide were given. Radiotherapy was performed only in particular cases or in recurrences. CONCLUSION: Rhabdomyosarcoma is a highly malignant tumor. Although rare, it is the most frequent of malignant tumors in children. It is important to keep it in mind in order to perform a biopsy enabling quick diagnosis and treatment following the modern protocol giving the highest chances of survival to these patients: about 98% in 3 years.
UI - 11963481
AU - Mende U; Gutwein S; Krempien R; Wannenmacher M; Ewerbeck V; Worn H
TI - [Ultrasonography of tumors of the locomotor system]
SO - Orthopade 2002 Feb;31(2):156-64
AD - Abteilung Klinische Radiologie und Poliklinik, Radiologische Universitatsklinik, Im Neuenheimer Feld 400, 69120 Heidelberg. firstname.lastname@example.org
Sonography is an integral part of primary tumor diagnosis and follow-up for the great majority of organ systems. However, its value in the field of space-occupying processes of the locomotor system, especially of malignant bone tumors, has mostly been underestimated. The sonographic examination has to investigate the whole tumor region and the corresponding lymph nodes statically and dynamically. The examination procedure should be standardized and the documentation reliable. Evaluation criteria are the localization, dimensions, and volume of the tumors, echogenicity and homogeneity, peri- and intratumoral vascularization (vessel density and architecture), borders of the tumor, and neighboring structures. Pathologic changes not only of the soft tissues but also of the bones can be evaluated sonographically. Even subtle analysis does not permit definitive assessment of tumor status. Taking its physical limitations into consideration, high-resolution sonography, enhanced by color/PowerDoppler and three-dimensional techniques, is a valuable adjunct to improve diagnosis, therapy planning, monitoring, and posttherapeutic care of tumors of the locomotor system.
UI - 11943871
AU - Zhu FX; King SM; Smith EJ; Levy DE; Yuan Y
TI - A Kaposi's sarcoma-associated herpesviral protein inhibits virus-mediated induction of type I interferon by blocking IRF-7 phosphorylation and nuclear accumulation.
SO - Proc Natl Acad Sci U S A 2002 Apr 16;99(8):5573-8
AD - Department of Microbiology, University of Pennsylvania School of Dental Medicine, Philadelphia, PA 19104, USA.
Interferons constitute the earliest immune response against viral infection. They elicit antiviral effects as well as multiple biological responses involved in cell growth regulation and immune activation. Because the interferon-induced cellular antiviral response is the primary defense mechanism against viral infection, many viruses have evolved strategies to antagonize the inhibitory effects of interferon. Here, we demonstrate a strategy that Kaposi's sarcoma-associated herpesvirus uses to block virus-mediated induction of type I interferon. We found that a viral immediate-early protein, namely ORF45, interacts with cellular interferon-regulatory factor 7 (IRF-7). In consequence, IRF-7 phosphorylation is inhibited and the accumulation of IRF-7 in the nucleus in response to viral infection is blocked. IRF-7 is a transcription regulator that is responsible for virus-mediated activation of type I interferon genes. By blocking the phosphorylation and nuclear translocation of IRF-7, ORF45 efficiently inhibits the activation of interferon alpha and beta genes during viral infection. Inhibition of interferon gene expression through a viral protein blocking the activation and nuclear translocation of a crucial transcription factor is a novel mechanism for viral immune evasion.
UI - 11992546
AU - Panagopoulos I; Mertens F; Debiec-Rychter M; Isaksson M; Limon J; Kardas
TI - I; Domanski HA; Sciot R; Perek D; Crnalic S; Larsson O; Mandahl N Molecular genetic characterization of the EWS/ATF1 fusion gene in clear cell sarcoma of tendons and aponeuroses.
SO - Int J Cancer 2002 Jun 1;99(4):560-7
AD - Department of Clinical Genetics, Lund University Hospital, SE-221 85 Lund, Sweden. Ioannis.Panagopoulos@klingen.lu.se
Clear cell sarcoma (CCS) is a rare malignant soft tissue tumor particularly associated with tendons and aponeuroses. The cytogenetic hallmark is the translocation t(12;22)(q13;q12) resulting in a chimeric EWS/ATF1 gene in which the 3'-terminal part of EWS at 22q is replaced by the 3'-terminal part of ATF1 at 12q. To date, only 13 cases of CCS have been analyzed for fusion genes at the transcription level, and there is no information about the breakpoints at the genomic level. In the present study, we describe the molecular genetic characteristics of CCS from 10 patients. Karyotypes were obtained from 10 cases