Soft Tissue Sarcomas
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Soft tissue sarcomas are malignant tumours that may arise in any of the mesodermal tissues (muscles, tendons, vessels that carry blood or lymph, joints, and fat). Sarcomas are a diverse range of tumours, they are named after the type of soft tissue cell they arise from. Types of soft tissue sarcomas include; alveolar soft-part sarcoma, angiosarcoma, fibrosarcoma, leiomyosarcoma, liposarcoma, malignant fibrous histiocytoma, hemangiopericytoma, mesenchymoma, schwannoma, peripheral neuroectodermal tumours, rhabdomyosarcoma, synovial sarcoma, and other types. In terms of treatment these different sub-types are usually treated in the same way using a uniform soft tissue protocol.

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Information for Patients and the Public
Information for Health Professionals / Researchers
Latest Research Publications
Childhood Soft Tissue Sarcoma
Uterine Sarcoma
Kaposi Sarcoma
Gastrointestinal Stromal Tumors

Information Patients and the Public (16 links)

Information for Health Professionals / Researchers (19 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Limaiem F, Bouslama S, Bouraoui S, Mzabi S
Primary hepatic vascular tumours. A clinicopathologic study of 10 cases.
Acta Gastroenterol Belg. 2014; 77(3):347-52 [PubMed] Related Publications
BACKGROUND: Primary hepatic vascular neoplasms constitute a heterogeneous group of neoplasms with characteristic histology and variable tumour biology.
AIM: To provide an updated overview on clinicopathological features, treatment and outcome of primary hepatic vascular tumours.
PATIENTS AND METHODS: In our retrospective study, we reviewed 10 cases of primary hepatic vascular tumours that were diagnosed at the pathology department of Mongi Slim hospital over a thirteen-year period (2000-2012). Relevant clinical information and microscopic slides were available in all cases and were retrospec- tively reviewed.
RESULTS: Our study group included 4 men and 6 women (sex ra- tio M/F = 0.66) aged between 23 and 78 years (mean = 55.5 years). Based on imaging studies, preoperative diagnosis of hemangioma was accurately made in only three cases. Three cases were misdiagnosed preoperatively as having hydatid cyst and four cases of hemangiomas were misdiagnosed preoperatively as liver metastases. All our patients underwent surgical resection of the tumour. Histopathological examination of the surgical specimen established the diagnosis of angiosarcoma in one case, cavernous hemangioma in 8 cases and sclerosing hemangioma in one case.
CONCLUSION: Hepatic tumours are increasingly detected incidentally due to widespread use of modern abdominal imaging techniques. Therefore, reliable noninvasive characterization and differentiation of such liver tumours is of major importance for clinical practice. Definitive diagnosis is based on histopathologic examination.

Related: Liver Cancer

Kandemir M, Rubio JC, Schmidt U, et al.
Event detection by feature unpredictability in phase-contrast videos of cell cultures.
Med Image Comput Comput Assist Interv. 2014; 17(Pt 2):154-61 [PubMed] Related Publications
In this work we propose a novel framework for generic event monitoring in live cell culture videos, built on the assumption that unpredictable observations should correspond to biological events. We use a small set of event-free data to train a multioutput multikernel Gaussian process model that operates as an event predictor by performing autoregression on a bank of heterogeneous features extracted from consecutive frames of a video sequence. We show that the prediction error of this model can be used as a probability measure of the presence of relevant events, that can enable users to perform further analysis or monitoring of large-scale non-annotated data. We validate our approach in two phase-contrast sequence data sets containing mitosis and apoptosis events: a new private dataset of human bone cancer (osteosarcoma) cells and a benchmark dataset of stem cells.

Related: Osteosarcoma

Ki EY, Park JS, Mun JB, Hur SY
Primary ovarian malignant mixed mesodermal tumor: report of four cases.
Eur J Gynaecol Oncol. 2014; 35(5):584-8 [PubMed] Related Publications
Malignant mixed mesodermal tumors (MMMTs) are highly aggressive and usually diagnosed at advanced stages. MMMT originates from either the ovary or the uterus. Because this disease is relatively rare, an optimal treatment modality has not yet been established. The authors report four cases of ovarian MMMT (one heterologous MMMT and three homologous MMMTs) during 1990-2011. The patients underwent operation immediately after histopathologically confirmation and were treated with platinum-based combination chemotherapy. The extent of operation, the outcomes of radiation therapy, and the proper chemotherapeutic regimen are still controversial. The authors report herein four cases of ovarian MMMTs alone with a brief literature review.

Related: Ovarian Cancer

Wang X, Goldstein D, Crowe PJ, Yang JL
Impact of STAT3 inhibition on survival of osteosarcoma cell lines.
Anticancer Res. 2014; 34(11):6537-45 [PubMed] Related Publications
BACKGROUND/AIM: Osteosarcoma is often a fatal malignancy. Constitutive STAT3 activation is associated with various human cancers and commonly suggests poor prognosis. We aimed to investigate the effect and potential molecular mechanisms of STAT3 inhibition on osteosarcoma.
MATERIALS AND METHODS: STAT3 inhibitor S3I-201 was investigated in six osteosarcoma cell lines. Crystal violet colorimetric, clonogenic, cleaved caspase-3 assays and western blot were performed to measure the effect and mechanisms of STAT3 inhibition.
RESULTS: All osteosarcoma cell lines expressed phosphorylated STAT3. Anti-proliferative effects of S3I-201 were dose- and time-dependent. S3I-201 also inhibited colony-formation and induced apoptosis through the caspase cleavage pathway. Finally, molecular mechanism studies suggested that down-regulation of STAT3 phosphorylation and downstream STAT3-target genes such as cyclin D1 and survivin may contribute to S3I-201-mediated anti-proliferation and apoptosis.
CONCLUSION: Inhibition of STAT3 signalling suppressed osteosarcoma cell growth and induced apoptosis, and indicated that STAT3 targeted-therapy may have therapeutic potential in osteosarcoma.

Related: Apoptosis Bone Cancers Osteosarcoma STAT3

Tonak M, Becker M, Graf C, et al.
HDAC inhibitor-loaded bone cement for advanced local treatment of osteosarcoma and chondrosarcoma.
Anticancer Res. 2014; 34(11):6459-66 [PubMed] Related Publications
UNLABELLED: The treatment of osteosarcoma, especially wide resection, is challenging. An additional local drug therapy after resection using anti-neoplastic bone cement (Polymethylmethacrylate (PMMA)) could help improve the outcome of therapy. In this study, we evaluated the effects of PMMA loaded with valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA) on the cell activity of a SaOs-2 cell culture, as well as the elution rate of the drugs out of the bone cement.
MATERIALS AND METHODS: In our experiments, we used the SaOs-2 osteosarcoma and the SW1353 chondrosarcoma cell line. Bone cement clots (5 g) were prepared and loaded with different drug concentrations of VPA (25 mg and 50 mg) and SAHA (1 mg, 2.5 mg and 5 mg). Two control groups were established, one with a native cement clot, the other with human mesenchymal stem cells, in order to evaluate toxicity on non tumor-cells. Cell activity was measured using an Alamar Blue assay on days 1, 2, 3, 4 and 7. The cement clots were additionally examined in a material testing unit for biomechanical and structural changes.
RESULTS: Tumor cells showed a significant and complete reduction of activity under therapy with VPA and SAHA. Drug release of VPA was extensive between days 0 and 3 and decreased progressively to day 7. Cumulative drug concentration in the medium continuously increased. Biomechanical testing of the cement clots showed no differences in stability and architecture compared to the control group. SaOs-2 and SW1353 cells with medium from native cement clots without drug therapy presented a cell activity of 100% in all groups and during all measurements. Human mesenchymal stem cells were not significantly affected during therapy with VPA and low concentrations of SAHA. In contrast, cell activity of human mesenchymal stem cells was significantly reduced under therapy with higher concentrations of SAHA, with an approximately linear decrease between days 0-3 and a rapidly decreasing activity between days 4-7.
CONCLUSION: A local cytotoxic therapy in the treatment of osteosarcoma and chondrosarcoma might improve the rate of metastasis and survival of patients. Our results present an encouraging approach to loading PMMA with anti-neoplastic drugs.

Related: Apoptosis Bone Cancers Chondrosarcoma Osteosarcoma

Max D, Kühnöl CD, Burdach S, et al.
Indoleamine-2,3-dioxygenase in an immunotherapy model for Ewing sarcoma.
Anticancer Res. 2014; 34(11):6431-41 [PubMed] Related Publications
BACKGROUND/AIM: Interleukin-2 (IL2) transgenic Ewing sarcoma cells reduce tumor growth in vivo and in vitro. In the present study we analyzed the expression of immune suppressive indoleamine-2,3-dioxygenase (IDO) in this model.
MATERIALS AND METHODS: Expression of IDO was analyzed by polymerase chain reaction. The impact of the cluster of differentiation 137 (CD137)/CD137 ligand (CD137L) co-stimulatory system on expression of IDO and different cytokines was analyzed both in vivo and in vitro.
RESULTS: Tumors that developed in vivo in the presence of IL2 transgenic tumor cells expressed IDO. The presence of CD137L transgenic tumor cells led to down-regulation of IDO. Further in-vitro analysis of this phenomenon indicated that IDO was expressed in tumor cells as a consequence of interferon-gamma produced by lymphocytes in response to IL2. Depending on the concentration of IL2, stimulation of CD137 increased or reduced cytokine production in lymphocytes.
CONCLUSION: Our data indicate that the CD137/CD137L pathway can modulate the immune response against Ewing sarcoma cells.

Related: Bone Cancers Cytokines Interleukin 2 (Aldesleukin) Ewing's Sarcoma

Morii T, Ohtsuka K, Ohnishi H, et al.
BH3 mimetics inhibit growth of chondrosarcoma--a novel targeted-therapy for candidate models.
Anticancer Res. 2014; 34(11):6423-30 [PubMed] Related Publications
BACKGROUND: Chondrosarcoma is refractory to conventional chemotherapy. BH-3 mimetics ABT-737 and ABT-263 are synthetic small-molecule inhibitors of anti-apoptotic proteins B-cell lymphoma-2 (Bcl2) and Bcl-xL, which play a critical role in survival of chondrosarcoma cells.
MATERIALS AND METHODS: Chondrosarcoma cell lines SW-1353 and CS-1 were used as the disease model. We used immunoblotting to assess the expression of target molecules Bcl2 and Bcl-xL, and the apoptotic inducers Bcl2-associated X (Bax) and Bcl2-antagonist/killer (Bak). In vitro growth inhibition by BH-3 mimetics was confirmed by photomicroscopic cell counting and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. Apoptotic induction was confirmed by Enzyme-Linked ImmunoSorbent Assay (ELISA). In vivo growth inhibition was assessed in a non-obese diabetic/severe combined immunodeficient (NOD/SCID) mouse model.
RESULTS: Expression of the target and effector molecules was confirmed in chondrosarcoma cell lines. BH3 mimetics significantly inhibited cell growth and induced apoptosis in vitro. Administration of ABT-263 inhibited chondrosarcoma growth and improved survival in a mouse model.
CONCLUSION: BH3 mimetics represent a novel treatment modality for chondrosarcoma.

Related: Apoptosis Chondrosarcoma BAK1

Koch J, Hau J, Jensen HE, Rieneck K
Cancer resistance as an acquired and inheritable trait.
Anticancer Res. 2014; 34(11):6315-25 [PubMed] Related Publications
AIM: To induce cancer resistance in wild-type mice and detect if the resistance could be inherited to the progeny of the induced resistant mice. Furthermore to investigate the spectrum and immunology of this inherited cancer resistance.
MATERIALS AND METHODS: Resistance to with live S180 cancer cells in BALB/c mice was induced by immunization with inactivated S180 cancer cells. The immunization was performed by either frozen/thawed or irradiated cancer cells or cell-free ascitic fluid (CFAF).
RESULTS: In all instances the induced resistance was demonstrated to be inheritable. The phenotype was named HICR (heritable induced cancer resistance) and was defined as primary resistant progeny from mice immunized with frozen/thawed or irradiated S180 cells or CFAF obtained from mice with S180 induced ascites. Notably, this resistance was transferred from both male and female mice to the offspring of the immunized mice for at least two generations. Although inheritable, the frequency of cancer-resistant pups was lost over a few generations. Cells from the J774A.1 and RAW cancer cell lines did not induce inheritable cancer resistance, and C57BL/6 mice could not pass on cancer resistance fluorescence-activated cell sorting (FACS) analyses of the peritoneal cells revealed an increased fraction of macrophages. In necropsies of resistant mice no histological signs of cancer or other disease was found.
CONCLUSION: Only materials derived from S180 cells could give rise to HICR mice. The molecular basis of the resistance is unknown but may involve epigenetic mechanisms. Other examples of inheritability of acquired phenotypic changes exist but, to our knowledge, this is the first demonstration of acquired, inherited cancer resistance.

Vijayakumar V, Lowery R, Zhang X, et al.
Pediatric osteosarcoma: a single institution's experience.
South Med J. 2014; 107(11):671-5 [PubMed] Related Publications
OBJECTIVES: The aim of the study was to evaluate outcomes with an examination of individual predictors influencing survival at a single institution.
METHODS: This was a retrospective review of the 28 pediatric osteosarcoma patients diagnosed and studied from 2000 through 2012. Twenty-eight patient charts and imaging studies were reviewed for age, race, sex, location, extent of disease at presentation, imaging results, histology, treatment options, and overall survival.
RESULTS: Of the 28 patients who were identified, the median age at diagnosis was 14 years. The majority of the patients were male African Americans with the tumor located in the lower long bones and most had conventional osteosarcoma histology. Four patients had metastasis at diagnosis. Of the 28 patients, 16 patients underwent limb salvage surgery, 6 underwent amputation, 4 had biopsy only, 1 had hip disarticulation, and 1 moved out of state and had no information available. All 28 patients received chemotherapy. Four patients received additional radiation therapy. On follow-up, 15 patients were still alive at last clinical contact and 13 died. Of the deceased, the median survival time was 2.3 years. The patient who lived the longest survived 8.3 years. Metastasis at diagnosis was associated with poorer outcome (P = 0.002). The 5-year overall survival rate was 40% (95% confidence interval 18-62) for our entire population of patients.
CONCLUSIONS: Survival in our patient cohort tended to be at the lower end of the spectrum reported by other contemporary treatment centers of excellence or Surveillance, Epidemiology, and End Results databases probably because of the large number of African American patients with associated poor socioeconomic status. Future studies should be conducted to explore biological and nonbiological factors that may affect the prognosis in this disease.

Related: Bone Cancers Osteosarcoma

De Meis E, Brandão BC, Capella FC, et al.
Catastrophic antiphospholipid syndrome in cancer patients: an Interaction of clotting, autoimmunity and tumor growth?
Isr Med Assoc J. 2014; 16(9):544-7 [PubMed] Related Publications
Thrombosis is a common phenomenon in patients with malignancies. It is believed that thrombosis is multifactorial and that in addition to mechanisms directly associated with cancer and its treatment, it may also be related to the interaction between the immune system and clotting. The present work describes four cancer patients (three adults and one child) whose clinical course was characteristic of catastrophic antiphospholipid syndrome (CAPS) in intensive care units of the National Cancer Institute of Rio de Janeiro. The presence of findings similar to those in CAPS can be attributed to an unbalanced interaction between the immune system and coagulation.

Related: Extra-Hepatic Bile duct cancer (cholangiocarcinoma) Bone Cancers Lung Cancer Ewing's Sarcoma

Kansara M, Teng MW, Smyth MJ, Thomas DM
Translational biology of osteosarcoma.
Nat Rev Cancer. 2014; 14(11):722-35 [PubMed] Related Publications
For the past 30 years, improvements in the survival of patients with osteosarcoma have been mostly incremental. Despite evidence of genomic instability and a high frequency of chromothripsis and kataegis, osteosarcomas carry few recurrent targetable mutations, and trials of targeted agents have been generally disappointing. Bone has a highly specialized immune environment and many immune signalling pathways are important in bone homeostasis. The success of the innate immune stimulant mifamurtide in the adjuvant treatment of non-metastatic osteosarcoma suggests that newer immune-based treatments, such as immune checkpoint inhibitors, may substantially improve disease outcome.

Related: Osteosarcoma

Folkert MR, Tong WY, LaQuaglia MP, et al.
20-year experience with intraoperative high-dose-rate brachytherapy for pediatric sarcoma: outcomes, toxicity, and practice recommendations.
Int J Radiat Oncol Biol Phys. 2014; 90(2):362-8 [PubMed] Related Publications
PURPOSE: To assess outcomes and toxicity of high-dose-rate intraoperative radiation therapy (HDR-IORT) in the management of pediatric sarcoma.
METHODS AND MATERIALS: Seventy-five pediatric patients underwent HDR-IORT for sarcoma from May 1993 to November 2013. The median age was 9 years old (36 patients were ≤ 6 years old). HDR-IORT was part of initial therapy in 37 patients (49%) and for recurrent disease in 38 patients (51%). Forty-one patients (55%) received HDR-IORT and postoperative external beam RT (PORT), and 22 patients (29%) were previously treated with external beam radiation therapy to the IORT site. Local control (LC), overall survival (OS) and event-free survival (EFS) were estimated using Kaplan-Meier methods.
RESULTS: At a median follow-up of 7.8 years for surviving patients, 5-year projected rates of LC, EFS, and OS were 63% (95% confidence interval [CI] 50%-76%), 33% (95% CI 21%-45%), and 43% (95% CI 30%-55%), with a median survival of 3.1 years. The 5-year LC, EFS, and OS rates for patients with recurrent disease were 46% (95% CI, 28%-64%), 30% (95% CI, 13%-46%), and 36% (95% CI, 18%-54%). Acute toxicity ≥ grade 3 occurred in 2 (2.5%) treatments; late toxicity ≥ grade 3 occurred in 4 (5.3%) patients 0.3-9.9 years after HDR-IORT. The incidence of toxicity ≥ grade 3 was not associated with HDR-IORT applicator size, HDR-IORT dose, prior RT or PORT, or prior or postoperative chemotherapy, but all toxicity ≥ grade 3 occurred in patients ≤ 6 years treated with HDR-IORT doses ≥ 12 Gy.
CONCLUSIONS: HDR-IORT is a well-tolerated component of multimodality therapy for pediatric sarcoma, allowing additional local treatment while reducing external beam exposure. Taking clinical considerations into account, doses between 8-12 Gy are appropriate for HDR-IORT in patients ≤ 6 years of age.

Related: Brachytherapy

Hayashi T, Horiuchi A, Sano K, et al.
Potential diagnostic biomarkers: differential expression of LMP2/β1i and cyclin B1 in human uterine leiomyosarcoma.
Tumori. 2014 Jul-Aug; 100(4):99e-106e [PubMed] Related Publications
AIMS AND BACKGROUND: Whilst most uterine smooth muscle neoplasms are benign, uterine leiomyosarcoma (Ut-LMS) is extremely malignant with a high incidence of metastasis and recurrence. Gynecological tumors are often associated with female hormone secretion, but no strong link has been detected between human Ut-LMS and the hormonal environment. In fact, the risk factors for Ut-LMS are poorly understood. In addition, no diagnostic biomarkers for differentiating between leiomyoma, a benign tumor, and malignant Ut-LMS have been found. Interestingly, mice that were homozygously deficient for LMP2/β1i were found to spontaneously develop Ut-LMS and exhibited a Ut-LMS prevalence of ~40% by 14 months of age. Thus, analyzing potential risk factors for Ut-LMS (such as LMP2/β1i) might aid the development of diagnostic biomarkers and clinical treatments for the condition.
METHODS AND STUDY DESIGN: Fifty-seven patients (age range: 32-83 years) who had been diagnosed with uterine mesenchymal tumors were chosen from a pathological archive. Tissue samples from these patients were fixed in 10% buffered formalin, incubated in 4% paraformaldehyde for 8 hours, and embedded in paraffin. Tissue sections were stained with hematoxylin and eosin for standard histological examination or were subjected to further processing for immunohistochemical (IHC) examination. Serial Ut-LMS, bizarre leiomyoma, leiomyoma, and myometrium sections were subjected to IHC staining of β-smooth muscle actin, estrogen receptor, cyclin B1, LMP2/β1i, calponin h1, ki-67, tumor protein p53, and progesterone receptor.
RESULTS: The Ut-LMS samples were positive for cyclin B1 and negative for LMP2/β1i, while the opposite result was obtained for bizarre leiomyoma, leiomyoma, and myometrium samples.
CONCLUSIONS: The expression pattern of LMP2/β1i and cyclin B1 might be a diagnostic biomarker for human Ut-LMS. Studies of the biological roles of LMP2/β1i and/or cyclin B1 could lead to the elucidation of new targets for therapies against Ut-LMS.

Nguyen NP, Vock J, Vinh-Hung V, et al.
Feasibility of tomotherapy for postoperative irradiation of lower extremity sarcomas.
Tumori. 2014 Jul-Aug; 100(4):466-9 [PubMed] Related Publications
AIMS AND BACKGROUND: To evaluate the effectiveness of helical tomotherapy-based image-guided radiotherapy (IGRT) following surgery for lower extremity sarcoma.
METHODS AND STUDY DESIGN: A retrospective review of three patients undergoing postoperative irradiation with tomotherapy for lower extremity sarcoma was conducted. Planning target volume (PTV) coverage, acute side effects, long-term complications and functional results were assessed.
RESULTS: Tomotherapy allows adequate coverage of the PTV without an excessive radiation dose to the normal adjacent structures. Radiotherapy side effects were acceptable with no treatment breaks. All patients were disease free with no complications and no impairment of their daily activity at the last follow-up.
CONCLUSION: IGRT delivered by tomotherapy may be ideally suited for sarcoma of the extremities because of its ability to achieve a high radiation dose along with excellent normal tissue sparing. Further prospective studies should be conducted to confirm this hypothesis.

Oksüz DC, Tural D, Dincbas FÖ, et al.
Non-metastatic Ewing's sarcoma family of tumors of bone in adolescents and adults: prognostic factors and clinical outcome-single institution results.
Tumori. 2014 Jul-Aug; 100(4):452-8 [PubMed] Related Publications
AIMS AND BACKGROUND: There is limited data regarding outcomes of Ewing's sarcoma family of tumors in adolescents and adults compared with the same tumors in childhood. The aim of the study was to analyze prognostic factors and treatment results in a cohort of adolescents and adults with non-metastatic skeletal Ewing's sarcoma family of tumors.
METHODS AND STUDY DESIGN: From 1992-2008, 90 adolescents and adults with Ewing's sarcoma family of tumors of the bone were referred to our institution. Sixty-five (72%) non-metastatic patients with analyzable data and treated in our institution were retrospectively evaluated. All patients were treated with alternated chemotherapy regimens administered every 3 weeks. The local treatment modality was selected according to tumor and patient characteristics.
RESULTS: The median age was 21 years (range, 13-50). Most patients (74%) were >17 years of age. Forty-six percent of the tumors were located in the extremities. Local therapy was surgery in 45 patients and radiotherapy alone in 19 patients. Twenty-one patients received preoperative and 13 patients postoperative radiotherapy. Median follow-up was 43 months (range, 7-167). The 5-year event-free and overall survival rates for all patients were 44% and 49%, respectively. On univariate survival analysis, event-free and overall survival were worse for patients >17 years of age, tumor size >8 cm in diameter, an axial location, positive surgical margins, and poor histopathological response (<90% necrosis). Age, tumor site and tumor size on event-free and overall survival remained significant on multivariate analysis.
CONCLUSIONS: We identified age, tumor size, and tumor site as independent prognostic factors, in accord with the Western literature. These patients require novel treatment modalities.

Related: Bone Cancers Ewing's Sarcoma

Husain A, Eigl BJ, Trpkov K
Composite chromophobe renal cell carcinoma with sarcomatoid differentiation containing osteosarcoma, chondrosarcoma, squamous metaplasia and associated collecting duct carcinoma: a case report.
Anal Quant Cytopathol Histpathol. 2014; 36(4):235-40 [PubMed] Related Publications
BACKGROUND: Chromophobe renal cell carcinoma (ChRCC) is a morphologically distinct renal cell carcinoma type which may rarely show composite morphology.
CASE: A 61-year-old man presented with a composite ChRCC with sarcomatoid transformation containing osteosarcomatous, chondrosarcomatous and squamous metaplastic differentiation and associated with a high-grade collecting duct carcinoma (CDC). The patient presented with a metastatic disease in the regional lymph nodes, comprised only of CDC, and died after 21 months.
CONCLUSION: Although ChRCC associated with sarcomatoid change has been well documented, the presence of osteosarcoma has been previously reported in only 5 ChRCCs, 2 of which also contained chondrosarcoma. Squamous differentiation has been previously found in only 2 ChRCCs with sarcomatoid change, and ChRCC associated with CDC has been previously reported in only 3 cases, but none with heterologous elements. To our knowledge this represents a previously unreported composite type of RCC, with an aggressive clinical behavior.

Related: Chondrosarcoma Osteosarcoma

Hwang LR, Cha S, Jong JE, et al.
Acetylation changes at lysine 5 of histone H4 associated with lytic gene promoters during reactivation of Kaposi's sarcoma-associated herpesvirus.
Acta Virol. 2014; 58(3):282-6 [PubMed] Related Publications
Kaposi's sarcoma-associated herpesvirus (KSHV) is a pathogenic agent of Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman's disease in humans. Similarly to other gammaherpesviruses such as Epstein-Barr virus (EBV) and herpesvirus saimiri (HVS), KSHV displays two alternative life cycles, latent and lytic one. The transactivation from latency to the lytic phase is the result of transcriptional changes in the KSHV genome caused by the replication and transcriptional activator (RTA). During KSHV reactivation, epigenetic modifications of histone protein on the viral genome occur, which regulate the transcriptional activation of a number of lytic genes. The reactivation of EBV from latency to lytic cycle, induced by an immediate-early Zta protein, was shown to be accompanied by acetylation of specific lysines in histone H4. Accordingly, we hypothesized that the RTA-induced transactivation of KSHV could also be accompanied by histone acetylation. To validate this hypothesis, we assayed alterations of acetyl-histone H4-lysine 5 (acH4K5) during the RTA-mediated KSHV reactivation. While the modified histone protein in a total cell lysate was not distinguished between control and RTA-expressed cells, upregulated acH4K5 was detected on several lytic gene promoter regions during KSHV reactivation. Our results clearly indicate that this epigenetic change is related to transcription of genes expressed in the lytic cycle of KSHV.

Related: Kaposi Sarcoma

Martens T, Vandekerckhove K, François K, Bove T
Spindle cell sarcoma of the mitral valve: an unusual cause of acute coronary syndrome in a child.
Ann Thorac Surg. 2014; 98(4):1456-9 [PubMed] Related Publications
We present an unusual case of acute myocardial infarction by embolic obstruction of both the left anterior descending and right coronary arteries in a 14-year-old girl. Echocardiography showed mobile lesions on the mitral valve and into the left ventricular outflow tract with poor left ventricular function, eventually suggesting endocarditis. Successful surgery comprised mitral valve plasty after complete resection of the tumoral lesion, in association with coronary artery embolectomy. Histologic examination revealed a malignant spindle cell sarcoma treated with adjuvant chemotherapy. We emphasize here the differential diagnosis of acute coronary syndrome in children by a rare cardiac tumor.

Rastrelli M, Tropea S, Basso U, et al.
Soft tissue limb and trunk sarcomas: diagnosis, treatment and follow-up.
Anticancer Res. 2014; 34(10):5251-62 [PubMed] Related Publications
This review focuses on epidemiology, aetiology, clinical presentation, diagnosis, management, prognosis and follow-up of soft tissue sarcomas (STS) involving limbs and trunk. Any patient with a suspected STS should be referred to a specialized sarcoma centre and managed by a multidisciplinary group. The standard treatment is surgical excision followed by adjuvant radiotherapy (RT). Radiotherapy is recommended in patients with intermediate-or high-grade tumors, >5 cm of diameter or <5 cm. RT may be indicated in low grade, deep and large-size STS and/or in absence of adequate margins, after discussion within a multidisciplinary group. Neoadjuvant radiotherapy and chemotherapy should be taken into consideration for patients with borderline resectable tumors. In selected cases, amputation may be the only curative option. Isolated limb perfusion is a pre-operative treatment that may allow for amputation to be avoided. Adjuvant chemotherapy should be considered only in selected cases. Regular follow-up with clinical examination, ultrasound (US) or magnetic resonance imaging (MRI) to exclude local recurrences and chest-X-ray or chest computed tomography (CT) to exclude metastatic disease is recommended. For metastatic disease, doxorubicin is the first-line standard therapy. Second-line agents include trabectedin, ifosfamide, dacarbazine and the combination of gemcitabine-plus-docetaxel. Surgical resection of local recurrences or lung metastases should be evaluated in selected cases.

Salunke AA, Chen Y, Tan JH, et al.
Does a pathological fracture affect the prognosis in patients with osteosarcoma of the extremities? : a systematic review and meta-analysis.
Bone Joint J. 2014; 96-B(10):1396-403 [PubMed] Related Publications
Opinion remains divided as to whether the development of pathological fracture affects the prognosis of patients with an osteosarcoma of the extremities. We conducted a comprehensive systematic review and meta-analysis of papers which reported the outcomes of osteosarcoma patients with and without a pathological fracture. There were eight eligible papers for final analysis which reported on 1713 patients, of whom 303 (17.7%) had a pathological fracture. The mean age for 1464 patients in six studies was 23.2 years old (2 to 82). The mean follow-up for 1481 patients in seven studies was 90.1 months (6 to 240). The pooled estimates of local recurrence rates in osteosarcoma patients with and without pathological fractures were 14.4% (8.7 to 20.0) versus 11.4% (8.0 to 14.8). The pooled estimate of relative risk was 1.39 (0.89 to 2.20). The pooled estimates of five-year event-free survival rates in osteosarcoma patients with and without a pathological fracture were 49.3% (95% CI 43.6 to 54.9) versus 66.8% (95% CI 60.7 to 72.8). The pooled estimate of relative risk was 1.33 (1.12 to 1.59). There was no significant difference in the rate of local recurrence between patients who were treated by amputation or limb salvage. The development of a pathological fracture is a negative prognostic indicator in osteosarcoma and is associated with a reduced five-year event-free survival and a possibly higher rate of local recurrence. Our findings suggest that there is no absolute indication for amputation, as similar rates of local recurrence can be achieved in patients who are carefully selected for limb salvage.

Related: Bone Cancers Osteosarcoma

Dhinsa BS, Gregory JJ, Nawabi D, et al.
The outcome of resection of the distal ulna for tumour without soft-tissue or prosthetic reconstruction.
Bone Joint J. 2014; 96-B(10):1392-5 [PubMed] Related Publications
In patients with a tumour affecting the distal ulna it is difficult to preserve the function of the wrist following extensive local resection. We report the outcome of 12 patients (nine female, three male) who underwent excision of the distal ulna without local soft-tissue reconstruction. In six patients, an aggressive benign tumour was present and six had a malignant tumour. At a mean follow-up of 64 months (15 to 132) the mean Musculoskeletal Tumour score was 64% (40% to 93%) and the mean DASH score was 35 (10 to 80). The radiological appearances were satisfactory in most patients. Local recurrence occurred in one patient with benign disease and two with malignant disease. The functional outcome was thus satisfactory at a mean follow-up in excess of five years, with a relatively low rate of complications. The authors conclude that complex reconstructive soft-tissue procedures may not be needed in these patients.

Related: Bone Cancers

Ieremia E, Thway K
Myxoinflammatory fibroblastic sarcoma: morphologic and genetic updates.
Arch Pathol Lab Med. 2014; 138(10):1406-11 [PubMed] Related Publications
Myxoinflammatory fibroblastic sarcoma (MIFS) is a malignant mesenchymal neoplasm most frequently arising in the distal extremities of adults, which usually behaves in a low-grade manner but is capable of metastasizing to local and distant sites, rarely leading to death. It is a rare tumor whose unusual morphology can lead to erroneous histologic diagnosis, either as a nonneoplastic (infectious or inflammatory) process or as a variety of neoplastic diseases. While its exact origin is uncertain, ultrastructural studies have shown at least some of the constituent cells to be modified fibroblasts. Distinct and reproducible genetic abnormalities identified in MIFS are translocation t(1;10)(p22:q24), with rearrangements of the TGFBR3 and MGEA5 genes associated with increased levels of FGF8, and formation of marker/ring chromosome 3, with amplification of the VGLL3 locus. Because these genetic abnormalities are shared by both MIFS and hemosiderotic fibrohistiocytic lipomatous tumor, it is thought that these 2 morphologically distinct neoplasms may comprise a spectrum of disease defined by these genetics. We review the literature on MIFS and discuss morphology (including that of MIFS/hemosiderotic fibrohistiocytic lipomatous tumor hybrid lesions), immunohistochemistry, the differential diagnosis, and recent molecular genetic developments.

Related: Chromosome 1 Chromosome 10 MGEA5

Walterhouse DO, Pappo AS, Meza JL, et al.
Shorter-duration therapy using vincristine, dactinomycin, and lower-dose cyclophosphamide with or without radiotherapy for patients with newly diagnosed low-risk rhabdomyosarcoma: a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group.
J Clin Oncol. 2014; 32(31):3547-52 [PubMed] Article available free on PMC after 01/11/2015 Related Publications
PURPOSE: Intergroup Rhabdomyosarcoma Study Group (IRSG) studies III and IV showed improved failure-free survival (FFS) rates with vincristine, dactinomycin, and cyclophosphamide (VAC; total cumulative cyclophosphamide dose, 26.4 g/m(2)) compared with vincristine and dactinomycin (VA) for patients with subset-one low-risk embryonal rhabdomyosarcoma (ERMS; stage 1/2 group I/II ERMS or stage 1 group III orbit ERMS). The objective of Children's Oncology Group ARST0331 was to reduce the length of therapy without compromising FFS for this subset of low-risk patients by using VA in combination with lower-dose cyclophosphamide (total cumulative dose, 4.8 g/m(2)) plus radiotherapy (RT).
PATIENTS AND METHODS: This noninferiority prospective clinical trial enrolled newly diagnosed patients with subset-one clinical features. Therapy included four cycles of VAC followed by four cycles of VA over 22 weeks. Patients with microscopic or gross residual disease at study entry received RT.
RESULTS: With a median follow-up of 4.3 years, we observed 35 failures among 271 eligible patients versus 48.4 expected failures, calculated using a fixed outcome based on the FFS expected for similar patients treated on the IRSG D9602 protocol. The estimated 3-year FFS rate was 89% (95% CI, 85% to 92%), and the overall survival rate was 98% (95% CI, 95% to 99%). Patients with paratesticular tumors had the most favorable outcome. Three-year cumulative incidence rates for any local, regional, or distant failures were 7.6%, 1.5%, and 3.4%, respectively.
CONCLUSION: Shorter-duration therapy that included lower-dose cyclophosphamide and RT did not compromise FFS for patients with subset-one low-risk ERMS.

Related: Cyclophosphamide Dactinomycin Rhabdomyosarcoma Vincristine

Kunze K, Spieker T, Gamerdinger U, et al.
A recurrent activating PLCG1 mutation in cardiac angiosarcomas increases apoptosis resistance and invasiveness of endothelial cells.
Cancer Res. 2014; 74(21):6173-83 [PubMed] Related Publications
Primary cardiac angiosarcomas are rare tumors with unfavorable prognosis. Pathogenic driver mutations are largely unknown. We therefore analyzed a collection of cases for genomic aberrations using SNP arrays and targeted next-generation sequencing (tNGS) of oncogenes and tumor-suppressor genes. Recurrent gains of chromosome 1q and a small region of chromosome 4 encompassing KDR and KIT were identified by SNP array analysis. Repeatedly mutated genes identified by tNGS were KDR with different nonsynonymous mutations, MLL2 with different nonsense mutations, and PLCG1 with a recurrent nonsynonymous mutation (R707Q) in the highly conserved autoinhibitory SH2 domain in three of 10 cases. PLCγ1 is usually activated by Y783 phosphorylation and activates protein kinase C and Ca(2+)-dependent second messengers, with effects on cellular proliferation, migration, and invasiveness. Ectopic expression of the PLCγ1-R707Q mutant in endothelial cells revealed reduced PLCγ1-Y783 phosphorylation with concomitant increased c-RAF/MEK/ERK1/2 phosphorylation, increased IP3 amounts, and increased Ca(2+)-dependent calcineurin activation compared with ectopic expressed PLCγ1-wild-type. Furthermore, cofilin, whose activation is associated with actin skeleton reorganization, showed decreased phosphorylation, and thus activation after expression of PLCγ1-R707Q compared with PLCγ1-wild-type. At the cellular level, expression of PLCγ1-R707Q in endothelial cells had no influence on proliferation rate, but increased apoptosis resistance and migration and invasiveness in in vitro assays. Together, these findings indicate that the PLCγ1-R707Q mutation causes constitutive activation of PLCγ1 and may represent an alternative way of activation of KDR/PLCγ1 signaling besides KDR activation in angiosarcomas, with implications for VEGF/KDR targeted therapies.

Related: Apoptosis Signal Transduction

Amita R, Sandhyamani S, Nair S, Kapilamoorthy TR
Intracranial ewings sarcoma/peripheral primitive neuroectodermal tumor.
Neurol India. 2014 Jul-Aug; 62(4):432-3 [PubMed] Related Publications
Central nervous system primitive neuroectodermal tumours (CNS PNET) are aggressive embryonal tumours composed of undifferentiated or poorly differentiated neuroepithelial cells seen in the pediatric age group. This is rare and only a handful of cases of ES/pPNET in CNS are reported. We report such a case in a 3 year old child. Reporting of more such cases is needed to better define these rare tumours of the dura.

Related: Ewing's Sarcoma

Mei J, Zhu XZ, Wang ZY, Cai XS
Functional outcomes and quality of life in patients with osteosarcoma treated with amputation versus limb-salvage surgery: a systematic review and meta-analysis.
Arch Orthop Trauma Surg. 2014; 134(11):1507-16 [PubMed] Related Publications
INTRODUCTION: To perform a meta-analysis for comparing the functional outcomes and quality of life (QOL) of osteosarcoma patients receiving amputation or limb-salvage surgeries.
MATERIALS AND METHODS: A search was conducted of the Medline, Cochrane, EMBASE, and Google Scholar on September 30, 2013. Studies were included in the analysis if there were patients who underwent amputation and limb-salvage surgery for osteosarcoma or Ewing's sarcoma, and for whom postoperative functional outcomes and QOL were evaluated. Outcomes were compared between participants who underwent limb-salvage operation and those who underwent amputation. The methodological quality of non-randomized comparative studies was assessed using the Newcastle-Ottawa Scale.
RESULTS: A total of 121 studies were identified and 6 were included in the meta-analysis. Quality assessment indicated that all six studies were of high quality. The mean age of the participants ranged from 17 to 37 years, and among them 118 underwent amputations and 138 underwent limb-salvage procedures. The mean length of follow-up ranged from 28 to 145 months. The meta-analysis indicated that functional outcomes and QOL were similar between patients who underwent amputation and those who underwent a limb-salvage procedure.
CONCLUSIONS: This meta-analysis including six high-quality studies indicates that amputation and limb-salvage surgery provide similar functional outcomes and quality of life for patients with osteosarcomas.

Related: Bone Cancers Osteosarcoma Ewing's Sarcoma

Gbabe OF, Okwundu CI, Dedicoat M, Freeman EE
Treatment of severe or progressive Kaposi's sarcoma in HIV-infected adults.
Cochrane Database Syst Rev. 2014; 8:CD003256 [PubMed] Article available free on PMC after 13/08/2015 Related Publications
BACKGROUND: Kaposi's sarcoma remains the most common cancer in Sub-Saharan Africa and the second most common cancer in HIV-infected patients worldwide. Since the introduction of highly active antiretroviral therapy (HAART), there has been a decline in its incidence.However, Kaposi's sarcoma continues to be diagnosed in HIV-infected patients.
OBJECTIVES: To assess the added advantage of chemotherapy plus HAART compared to HAART alone; and the advantages of different chemotherapy regimens in HAART and HAART naive HIV infected adults with severe or progressive Kaposi's sarcoma.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and , GATEWAY, the WHO Clinical Trials Registry Platform and the US National Institutes of Health's for ongoing trials and the Aegis archive of HIV/AIDS for conference abstracts. An updated search was conducted in July 2014.
SELECTION CRITERIA: Randomised trials and observational studies evaluating the effects of any chemotherapeutic regimen in combination with HAART compared to HAART alone, chemotherapy versus HAART, and comparisons between different chemotherapy regimens.
DATA COLLECTION AND ANALYSIS: Two review authors assessed the studies independently and extracted outcome data.We used the risk ratio (RR) with a 95% confidence interval (CI) as the measure of effect.We did not conduct meta-analysis as none of the included trials assessed identical chemotherapy regimens.
MAIN RESULTS: We included six randomised trials and three observational studies involving 792 HIV-infected adults with severe Kaposi's sarcoma.Seven studies included patients with a mix of mild to moderate (T0) and severe (T1) Kaposi's sarcoma. However, this review was restricted to the subset of participants with severe Kaposi's sarcoma disease.Studies comparing HAART plus chemotherapy to HAART alone showed the following: one trial comparing HAART plus doxorubicin,bleomycin and vincristine (ABV) to HAART alone showed a significant reduction in disease progression in the HAART plus ABV group (RR 0.10; 95% CI 0.01 to 0.75, 100 participants); there was no statistically significant reduction in mortality and no difference in adverse events. A cohort study comparing liposomal anthracyclines plus HAART to HAART alone showed a non-statistically significant reduction in Kaposi's sarcoma immune reconstitution inflammatory syndrome in patients that received HAART plus liposomal anthracyclines (RR 0.49; 95% CI 0.16 to 1.55, 129 participants).Studies comparing HAART plus chemotherapy to HAART plus a different chemotherapy regimen showed the following: one trial involving 49 participants and comparing paclitaxel versus pegylated liposomal doxorubicin in patients on HAART showed no difference in disease progression. Another trial involving 46 patients and comparing pegylated liposomal doxorubicin versus liposomal daunorubicin showed no participants with progressive Kaposi's sarcoma disease in either group.Studies comparing different chemotherapy regimens in patients from the pre-HAART era showed the following: in the single RCT comparing liposomal daunorubicin to ABV, there was no significant difference with the use of liposomal daunorubicin compared to ABV in disease progression (RR 0.78; 95% CI 0.34 to 1.82, 227 participants) and overall response rate. Another trial involving 178 participants and comparing oral etoposide versus ABV demonstrated no difference in mortality in either group. A non-randomised trial comparing bleomycin alone to ABV demonstrated a higher median survival time in the ABV group; there was also a non-statistically significant reduction in adverse events and disease progression in the ABV group (RR 11; 95% CI 0.67 to 179.29, 24 participants).An additional non-randomised study showed a non-statistically significant overall mortality benefit from liposomal doxorubicin as compared to conservative management consisting of either bleomycin plus vinblastine, vincristine or single-agent antiretroviral therapy alone (RR 0.93; 95% CI 0.75 to 1.15, 29 participants). The overall quality of evidence can be described as moderate quality. The quality of evidence was downgraded due to the small size of many of the included studies and small number of events.
AUTHORS' CONCLUSIONS: The findings from this review suggest that HAART plus chemotherapy may be beneficial in reducing disease progression compared to HAART alone in patients with severe or progressive Kaposi's sarcoma. For patients on HAART, when choosing from different chemotherapy regimens, there was no observed difference between liposomal doxorubicin, liposomal daunorubicin and paclitaxel.

Related: Bleomycin Doxorubicin Etoposide Kaposi Sarcoma Skin Cancer Vincristine

Panda KG, Hale MJ, Kruger D, Luvhengo TE
Comparison between preoperative biopsy and post-excision histology results in sarcoma: experience at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa.
S Afr J Surg. 2014; 52(2):45-8 [PubMed] Related Publications
BACKGROUND: Tumour size, grade and subtype are the main prognostic factors in adult patients presenting with soft-tissue sarcoma. Planning for appropriate management, including the need for additional staging investigations and neoadjuvant therapy, is dependent on reliable preoperative histopathological results.
OBJECTIVES: To determine whether there is agreement between preoperative and post-excision histological findings in patients presenting with soft-tissue sarcoma, and whether the agreement is influenced by the subtypes of sarcomas.
PATIENTS AND METHODS: Records of adult patients who had soft-tissue sarcomas excised were reviewed. Kaposi's sarcoma and gastrointestinal stromal tumours were excluded. Data were retrieved from the Department of Anatomical Pathology of the National Health Laboratory Service and theatre records at Chris Hani Baragwanath Academic Hospital, and included patient demography, tumour sites and size, HIV status, biopsy types and post-excision histological findings.
RESULTS: Records of 153 patients were found (median age 44 years). The majority of the sarcomas were >5 cm in diameter, deep seated and localised in extremities. The commonest subtype, irrespective of HIV status, was dermatofibrosarcoma protuberans. Fine-needle aspiration biopsy (FNAB) results were inaccurate in determining the malignant nature, grade and subtype of sarcoma. Rates of accurate tumour subtype classification following core needle and incision biopsies when compared with post-excision histological findings were 73.1% and 78.3%, respectively.
CONCLUSION: FNAB should not be used in the primary evaluation of soft-tissue tumours. A report of spindle cells on the FNAB smear should be followed by core needle or incision biopsy. Incision biopsy is superior to core needle biopsy in the classification of sarcomas by subtype.

Wang F, Ke ZF, Wang R, et al.
Astrocyte elevated gene-1 (AEG-1) promotes osteosarcoma cell invasion through the JNK/c-Jun/MMP-2 pathway.
Biochem Biophys Res Commun. 2014; 452(4):933-9 [PubMed] Related Publications
Osteosarcoma is the most common primary malignant bone tumour in children and adolescents and is characterised by high malignant and metastatic potentials. However, the molecular mechanism underlying this invasiveness remains unclear. In this study, we determined that PD98059 and SP600125, the two mitogen-activated protein kinase (MAPK) family inhibitors, decreased the osteosarcoma cell U2OS-AEG-1 migration and invasion that was enhanced by astrocyte elevated gene-1 (AEG-1) in an in vitro wound-healing and Matrigel invasion assay independently of cell viability. These findings indicate that AEG-1 promoted osteosarcoma cell invasion is relevant to the MAPK pathways. The up-regulation of AEG-1 increased the levels of phosphor-c-Jun N-terminal kinase (JNK) and phosphor-c-Jun; however, there were no marked changes in the levels of phosphor-extracellular regulated kinase (ERK) 1/2 or phosphor-c-Fos due to the activation of AEG-1 in U2OS. SP600125 (a JNK inhibitor) decreased phosphor-c-Jun and MMP-2 in U2OS-AEG-1, while PD98059 (a ERK1/2 inhibitor) had no influence on the levels of phosphor-c-Jun or MMP-2 in U2OS-AEG-1. Further study revealed that the down-regulation of phosphor-c-Jun not only obviously decreased the MMP-2 protein level and the MMP-2 transcriptional activity that were up-regulated by AEG-1 in Western-blot and luciferase reporter assays, but also inhibited the migration and invasion abilities of the U2OS-AEG-1 cells, which suggests that AEG-1 mediated U2OS invasion at least partially via the JNK/c-Jun/MMP-2 pathway. Consistent with these observations, immunohistochemical (IHC) staining revealed that AEG-1 expression was associated with the protein levels of phosphor-c-Jun and MMP-2 in needle biopsy paraffin-embedded archival human osteosarcoma tissues. Taken together, our findings suggest that AEG-1 plays a crucial role in the aggressiveness of osteosarcoma via the JNK/c-Jun/MMP-2 pathway.

Related: MMP2 Osteosarcoma

Tao J, Jiang MM, Jiang L, et al.
Notch activation as a driver of osteogenic sarcoma.
Cancer Cell. 2014; 26(3):390-401 [PubMed] Article available free on PMC after 08/09/2015 Related Publications
Osteogenic sarcoma (OS) is a deadly skeletal malignancy whose cause is unknown. We report here a mouse model of OS based on conditional expression of the intracellular domain of Notch1 (NICD). Expression of the NICD in immature osteoblasts was sufficient to drive the formation of bone tumors, including OS, with complete penetrance. These tumors display features of human OS; namely, histopathology, cytogenetic complexity, and metastatic potential. We show that Notch activation combined with loss of p53 synergistically accelerates OS development in mice, although p53-driven OS is not Rbpj dependent, which demonstrates a dual dominance of the Notch oncogene and p53 mutation in the development of OS. Using this model, we also reveal the osteoblasts as the potential sources of OS.

Related: Bone Cancers Osteosarcoma

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