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1.
Histopathology ; 79(5): 720-730, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33991114

RESUMO

AIMS: Giant cell tumour of bone (GCTB) is histologically defined as a lesion containing reactive giant cells and a neoplastic mononuclear cell population; in up to 92% of cases, GCTB is characterised by a specific mutation of the histone gene H3F3A. The cellular composition ranges from giant-cell-rich to giant-cell-poor. The diagnosis of GCTB can be challenging, and several other lesions need to be excluded, e.g. aneurysmal bone cysts, non-ossifying fibromas, chondroblastomas, brown tumours, and giant-cell-rich osteosarcomas. Our aim was to analyse the clinical history, imaging, molecular pathology and histology of three H3F3A-mutated bone tumours without detectable giant cells. None of the patients received denosumab therapy. METHODS AND RESULTS: Diagnostic material was obtained by curettage or resection and/or biopsy. Common histomorphological features of all three reported lesions were fibrocytic, oval cells in a background of osteoid and an absence of multinuclear giant cells as confirmed with CD68 immunohistochemistry. We used immunohistochemistry and Sanger sequencing to demonstrate positivity for the H3.3 p.G34W mutation. Differential diagnoses were systematically excluded on the basis of histomorphology, immunohistochemistry, and fluorescence in-situ hybridisation. The imaging (radiography, computed tomography, and magnetic resonance imaging) for all three cases is presented and discussed. CONCLUSIONS: We believe that these GCTBs without giant cells expand one end of the heterogeneous range of GCTB. Because of the lack of giant cells, correct diagnosis of GCTB is challenging or even impossible on histological grounds alone. In these cases, detection of the characteristic H3F3A mutation (G34W-specific antibody RM263 or sequencing) is extremely helpful for diagnosing those lesions without giant cells as giant cell tumours of bone.


Assuntos
Tumor de Células Gigantes do Osso , Histonas , Adulto , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Osso e Ossos/patologia , Condroblastoma , Diagnóstico Diferencial , Feminino , Tumor de Células Gigantes do Osso/diagnóstico , Tumor de Células Gigantes do Osso/metabolismo , Tumor de Células Gigantes do Osso/patologia , Células Gigantes/patologia , Histonas/genética , Histonas/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Mutação , Osteossarcoma , Radiologia
2.
Lancet ; 384(9940): 337-46, 2014 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-24726477

RESUMO

BACKGROUND: Autologous native cartilage from the nasal septum, ear, or rib is the standard material for surgical reconstruction of the nasal alar lobule after two-layer excision of non-melanoma skin cancer. We assessed whether engineered autologous cartilage grafts allow safe and functional alar lobule restoration. METHODS: In a first-in-human trial, we recruited five patients at the University Hospital Basel (Basel, Switzerland). To be eligible, patients had to be aged at least 18 years and have a two-layer defect (≥50% size of alar subunit) after excision of non-melanoma skin cancer on the alar lobule. Chondrocytes (isolated from a 6 mm cartilage biopsy sample from the nasal septum harvested under local anaesthesia during collection of tumour biopsy sample) were expanded, seeded, and cultured with autologous serum onto collagen type I and type III membranes in the course of 4 weeks. The resulting engineered cartilage grafts (25 mm × 25 mm × 2 mm) were shaped intra-operatively and implanted after tumour excision under paramedian forehead or nasolabial flaps, as in standard reconstruction with native cartilage. During flap refinement after 6 months, we took biopsy samples of repair tissues and histologically analysed them. The primary outcomes were safety and feasibility of the procedure, assessed 12 months after reconstruction. At least 1 year after implantation, when reconstruction is typically stabilised, we assessed patient satisfaction and functional outcomes (alar cutaneous sensibility, structural stability, and respiratory flow rate). FINDINGS: Between Dec 13, 2010, and Feb 6, 2012, we enrolled two women and three men aged 76-88 years. All engineered grafts contained a mixed hyaline and fibrous cartilage matrix. 6 months after implantation, reconstructed tissues displayed fibromuscular fatty structures typical of the alar lobule. After 1 year, all patients were satisfied with the aesthetic and functional outcomes and no adverse events had been recorded. Cutaneous sensibility and structural stability of the reconstructed area were clinically satisfactory, with adequate respiratory function. INTERPRETATION: Autologous nasal cartilage tissues can be engineered and clinically used for functional restoration of alar lobules. Engineered cartilage should now be assessed for other challenging facial reconstructions. FUNDING: Foundation of the Department of Surgery, University Hospital Basel; and Krebsliga beider Basel.


Assuntos
Cartilagens Nasais/cirurgia , Neoplasias Nasais/cirurgia , Neoplasias Cutâneas/cirurgia , Engenharia Tecidual/métodos , Idoso , Idoso de 80 Anos ou mais , Condrócitos/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica/métodos
3.
Oncology ; 88(1): 18-27, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25277324

RESUMO

The use of cancer-related therapies in cancer patients hospitalized at the end of life has increased in many countries over time. Given the scarcity of published Swiss data, the objective of this study was to evaluate the influence of hospital type and other factors on the delivery of health care during the last month before death. Claims data were used to assess health care utilization of cancer patients (identified by cancer registry data of four participating Swiss cantons) who deceased between 2006 and 2008. Primary endpoints were delivery of cancer-related therapies during the last 30 days before death. Multivariate logistic regression assessed the explanatory value of hospital type, patient and geographic characteristics. Of 3,809 identified cancer patients in the claims database, 2,086 patients dying from cancer were hospitalized during the last 30 days before death, generating 2,262 inpatient episodes. Anticancer drug therapy was given in 22.2% and radiotherapy in 11.7% of episodes. Besides age and cancer type, the canton of residence and hospital type showed independent, statistically significant associations with intensity of care, which was highest in university hospitals. These results should initiate a discussion among oncologists in Switzerland and may question the compliance with standard of care guidelines for terminal cancer patients.


Assuntos
Neoplasias/terapia , Assistência Terminal , Idoso , Feminino , Hospitalização , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Padrão de Cuidado , Suíça
4.
BMC Cancer ; 14: 306, 2014 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-24885104

RESUMO

BACKGROUND: The use of cancer related therapy in cancer patients at the end-of-life has increased over time in many countries. Given a lack of published Swiss data, the objective of this study was to describe delivery of health care during the last month before death of cancer patients. METHODS: Claims data were used to assess health care utilization of cancer patients (identified by cancer registry data of four participating cantons), deceased between 2006-2008. Primary endpoints were hospitalization rate and delivery of cancer related therapies during the last 30 days before death. Multivariate logistic regression assessed the explanatory value of patient and geographic characteristics. RESULTS: 3809 identified cancer patients were included. Hospitalization rate (mean 68.5%, 95% CI 67.0-69.9) and percentage of patients receiving anti-cancer drug therapies (ACDT, mean 14.5%, 95% CI 13.4-15.6) and radiotherapy (mean 7.7%, 95% CI 6.7-8.4) decreased with age. Canton of residence and insurance type status most significantly influenced the odds for hospitalization or receiving ACDT. CONCLUSIONS: The intensity of cancer specific care showed substantial variation by age, cancer type, place of residence and insurance type status. This may be partially driven by cultural differences within Switzerland and the cantonal organization of the Swiss health care system.


Assuntos
Neoplasias/epidemiologia , Neoplasias/terapia , Assistência Terminal , Bases de Dados Factuais , Humanos , Neoplasias/patologia , Suíça
5.
Am J Epidemiol ; 178(6): 877-84, 2013 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-23900553

RESUMO

Although persons infected with human immunodeficiency virus (HIV), particularly men who have sex with men, are at excess risk for anal cancer, it has been difficult to disentangle the influences of anal exposure to human papillomavirus (HPV) infection, immunodeficiency, and combined antiretroviral therapy. A case-control study that included 59 anal cancer cases and 295 individually matched controls was nested in the Swiss HIV Cohort Study (1988-2011). In a subset of 41 cases and 114 controls, HPV antibodies were tested. A majority of anal cancer cases (73%) were men who have sex with men. Current smoking was significantly associated with anal cancer (odds ratio (OR) = 2.59, 95% confidence interval (CI): 1.25, 5.34), as were antibodies against L1 (OR = 4.52, 95% CI: 2.00, 10.20) and E6 (OR = ∞, 95% CI: 4.64, ∞) of HPV16, as well as low CD4+ cell counts, whether measured at nadir (OR per 100-cell/µL decrease = 1.53, 95% CI: 1.18, 2.00) or at cancer diagnosis (OR per 100-cell/µL decrease = 1.24, 95% CI: 1.08, 1.42). However, the influence of CD4+ cell counts appeared to be strongest 6-7 years prior to anal cancer diagnosis (OR for <200 vs. ≥500 cells/µL = 14.0, 95% CI: 3.85, 50.9). Smoking cessation and avoidance of even moderate levels of immunosuppression appear to be important in reducing long-term anal cancer risks.


Assuntos
Terapia Antirretroviral de Alta Atividade/estatística & dados numéricos , Neoplasias do Ânus/etiologia , Infecções por HIV/complicações , Infecções por Papillomavirus/complicações , Fumar/efeitos adversos , Abuso de Substâncias por Via Intravenosa/complicações , Adulto , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Neoplasias do Ânus/epidemiologia , Neoplasias do Ânus/virologia , Contagem de Linfócito CD4 , Estudos de Casos e Controles , Comorbidade , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Homossexualidade Masculina/estatística & dados numéricos , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 16/patogenicidade , Humanos , Hospedeiro Imunocomprometido , Incidência , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/transmissão , Infecções por Papillomavirus/virologia , Fatores de Risco , Fumar/epidemiologia , Suíça/epidemiologia
6.
Cancers (Basel) ; 15(17)2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37686526

RESUMO

Giant cell tumor of bone (GCTB) is an osteolytic tumor driven by an H3F3A-mutated mononuclear cell with the accumulation of osteoclastic giant cells. We analyzed tissue from 13 patients with recurrence and 25 patients with denosumab therapy, including two cases of malignant transformation. We found a decrease in the total number of cells (p = 0.03), but not in the individual cell populations when comparing primary and recurrence. The patients treated with denosumab showed induction of osteoid formation increasing during therapy. The total number of cells was reduced (p < 0.0001) and the number of H3F3A-mutated tumor cells decreased (p = 0.0001), while the H3F3A wild-type population remained stable. The KI-67 proliferation rate dropped from 10% to 1% and Runx2- and SATB2-positive cells were reduced. The two cases of malignant transformation revealed a loss of the H3F3A-mutated cells, while the KI-67 rate increased. Changes in RUNX2 and SATB2 expression were higher in one sarcoma, while in the other RUNX2 was decreased and SATB2-positive cells were completely lost. We conclude that denosumab has a strong impact on the morphology of GCTB. KI-67, RUNX2 and SATB2 expression differed depending on the benign or malignant course of the tumor under denosumab therapy.

7.
Mod Pathol ; 25(4): 522-8, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22173290

RESUMO

Hematogenous spread determines the outcome of osteosarcoma (OS) patients, but the pathogenesis of developing metastatic disease is still unclear. Chemokines are critical regulators of cell trafficking and adhesion, and have been reported to be aberrantly expressed and to correlate with an unfavorable prognosis and metastatic spread in several malignant tumors. The chemokine receptors CXCR4 and CXCR7 together with their common ligand CXCL12 form one of the most important chemokine axes in this context. To investigate a potential role of these chemokines in OSs, we analyzed their expression in a series of 223 well-characterized and pretherapeutic OS samples. Interestingly, we found the expression of CXCL12 and CXCR4 to correlate with a better long-term outcome and with a lower prevalence of metastases. These findings suggest a distinct role of CXCR4/CXCR7/CXCL12 signaling in the tumors of bone, as has also been previously described in acute leukemia. As many malignant tumors metastasize to bone, and tumor cells are thought to be directed to bone in response to CXCL12, OS cells expressing both CXCL12 and the corresponding receptors might be detained at their site of origin. The disruption of CXCR4/CXCR7/CXCL12 signaling could therefore be crucial in OSs for the migration of tumor cells from bone into circulation and for developing systemic disease.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Ósseas/imunologia , Quimiocina CXCL12/análise , Osteossarcoma/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Neoplasias Ósseas/terapia , Criança , Pré-Escolar , Feminino , Alemanha , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Osteossarcoma/mortalidade , Osteossarcoma/secundário , Osteossarcoma/terapia , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Receptores CXCR/análise , Receptores CXCR4/análise , Fatores de Tempo , Análise Serial de Tecidos , Resultado do Tratamento , Vimentina/análise , Adulto Jovem
8.
J Cell Biochem ; 112(11): 3206-15, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21732412

RESUMO

The expression of the HOX gene network in mid-stage human tooth development mostly concerns the epithelial tooth germ compartment and involves the C and D HOX loci. To further dissect the HOX gene implication with tooth epithelium differentiation we compared the expression of the whole HOX network in human ameloblastomas, as paradigm of epithelial odontogenic tumors, with tooth germs. We identified two ameloblastoma molecular types with respectively low and high number of active HOX C genes. The highly expressing HOX C gene ameloblastomas were characterized by a strong keratinized phenotype. Locus C HOX genes are located on chromosome 12q13-15 in physical contiguity with one of the two keratin gene clusters included in the human genome. The most posterior HOX C gene, HOX C13, is capable to interact with hair keratin genes located on the other keratin gene cluster in physical contiguity with the HOX B locus on chromosome 17q21-22. Inside the HOX C locus, a 2.2 kb ncRNA (HOTAIR) able to repress transcription, in cis, along the entire HOX C locus and, in trans, at the posterior region of the HOX D locus has recently been identified. Interestingly both loci are deregulated in ameloblastomas. Our finding support an important role of the HOX network in characterizing the epithelial tooth compartment. Furthermore, the physical contiguity between locus C HOX and keratin genes in normal tooth epithelium and their deregulation in the neoplastic counterparts suggest they may act on the same mechanism potentially involved with epithelial tumorigenesis.


Assuntos
Ameloblastoma/genética , Genes Homeobox , Neoplasias Maxilomandibulares/genética , Queratinas/genética , Adulto , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real
9.
Blood ; 113(23): 5737-42, 2009 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-19336755

RESUMO

Hodgkin lymphoma (HL) risk is elevated among persons infected with HIV (PHIV) and has been suggested to have increased in the era of combined antiretroviral therapy (cART). Among 14,606 PHIV followed more than 20 years in the Swiss HIV Cohort Study (SHCS), determinants of HL were investigated using 2 different approaches, namely, a cohort and nested case-control study, estimating hazard ratios (HRs) and matched odds ratios, respectively. Forty-seven incident HL cases occurred during 84,611 person-years of SHCS follow-up. HL risk was significantly higher among men having sex with men (HR vs intravenous drug users = 2.44, 95% confidence interval [CI], 1.13-5.24) but did not vary by calendar period (HR for 2002-2007 vs 1995 or earlier = 0.65, 95% CI, 0.29-1.44) or cART use (HR vs nonusers = 1.02, 95% CI, 0.53-1.94). HL risk tended to increase with declining CD4(+) cell counts, but these differences were not significant. A lower CD4(+)/CD8(+) ratio at SHCS enrollment or 1 to 2 years before HL diagnosis, however, was significantly associated with increased HL risk. In conclusion, HL risk does not appear to be increasing in recent years or among PHIV using cART in Switzerland, and there was no evidence that HL risk should be increased in the setting of improved immunity.


Assuntos
Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Doença de Hodgkin/complicações , Doença de Hodgkin/epidemiologia , Adulto , Biomarcadores , Estudos de Coortes , Feminino , Infecções por HIV/imunologia , Doença de Hodgkin/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Suíça/epidemiologia
10.
Histopathology ; 59(3): 390-6, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22034879

RESUMO

AIMS: Simple bone cysts (SBC) are benign tumour-like lesions, generally occurring in the metaphyses of long bones before skeletal maturity. Remarkably, in 10-70% of cases, a peculiar, amorphous and hypocellular matrix is found in the walls of SBCs which is usually regarded to consist of (calcified) fibrin clots in the literature. Because these deposits are strongly fuchsinophilic in routine van Gieson stains, the aim of this study was to investigate a series of SBCs using immunohistochemistry and electron microscopy. METHODS AND RESULTS: A comprehensive panel of antibodies against fibrin as well as collageneous and non-collageneous proteins of bone was used, and detected substantial amounts of collagen and decorin as the main components of the investigated matrix. Electron microscopy clearly underlined the immunohistochemical results and also showed abundant fibrils with a periodic banding characteristic of collagen. Adjacent to and in between these collagen deposits runx-2- and osterix-expressing cells were detectable, most probably representing immature osteoprogenitor cells. CONCLUSIONS: Although still stated in the literature and most current textbooks, we were not able to detect any evidence of fibrin as a component of the respective matrix deposits that seem to consist predominantly of collagen and decorin.


Assuntos
Cistos Ósseos/patologia , Colágeno/ultraestrutura , Matriz Extracelular/química , Matriz Extracelular/ultraestrutura , Adolescente , Adulto , Cistos Ósseos/metabolismo , Criança , Pré-Escolar , Colágeno/metabolismo , Matriz Extracelular/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Lactente , Masculino , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Adulto Jovem
11.
Pediatr Blood Cancer ; 56(5): 771-6, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21370409

RESUMO

BACKGROUND: Solitary skeletal osteosarcoma (OS) manifestations distant from the site of the primary tumor rarely arise as only sign of disease recurrence. METHODS: This report reviews 38 patients with high-grade central OS of the limbs or axial skeleton and initial complete surgical remission (CR) who developed first recurrences as solitary osseous lesions distant from the primary tumor. The Cooperative Osteosarcoma Study Group (COSS) database was used to evaluate patient-, tumor-, and treatment-related variables and outcomes. RESULTS: Thirty-eight patients (27 males and 11 females; 36 limb and 2 axial primaries) developed solitary osseous recurrences a median of 2.1 years (range: 0.5-14.3) from primary diagnosis. Relapses involved axial (24), extremity (10), or craniofacial bones (4). Treatment for recurrence included surgery (28), radiotherapy (10), and chemotherapy (27). After a median follow-up of 1.9 years (range: 0.1-21.2) from first recurrence for all 38 patients and 5.5 years (0.3-21.2) for 16 survivors (10 in continuous second CR), 2- and 5-year overall and event-free survival (EFS) probabilities were 55% and 34% and 34% and 27%, respectively. A long interval to recurrence (>1.5 years) predicted for better overall (P < 0.001) and EFS (P = 0.005). For 21 patients achieving a second CR, 2- and 5-year overall and EFS probabilities were 81% and 61% and 52% and 49%, respectively, while only 1/17 others survived beyond 5 years (P < 0.001). Survivors (14/16) had also received second-line chemotherapy. CONCLUSION: First solitary skeletal recurrences of OS should be treated with curative intent. Some presumed bone metastases may represent second primary OSs.


Assuntos
Neoplasias Ósseas/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Segunda Neoplasia Primária/diagnóstico , Osteossarcoma/diagnóstico , Adolescente , Adulto , Neoplasias Ósseas/terapia , Criança , Pré-Escolar , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/terapia , Segunda Neoplasia Primária/terapia , Osteossarcoma/terapia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
12.
Clin Cancer Res ; 15(7): 2456-62, 2009 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-19293259

RESUMO

PURPOSE: Phosphatase and tensin homologue deleted from chromosome 10 (PTEN) and p27(kip1) proteins are key players of the Akt pathway, which is nutritionally regulated by insulin receptor signaling and influenced by estrogens. In this study, the prognostic relevance of the PTEN/p27(kip1) protein expression in endometrial carcinoma in relationship to the body mass index (BMI) was determined. EXPERIMENTAL DESIGN: BMI and prognosis of 452 surgically treated patients with endometrial carcinoma were correlated with histologic subtype, International Federation of Gynecology and Obstetrics (FIGO) stage, and differentiation grade. The expression of PTEN and p27(kip1) was examined in 257 tumors by immunohistochemistry using a tissue microarray approach. RESULTS: Lack of PTEN was observed in 136 of 257 (53%) tumors and absence of p27(kip1) expression was observed in 106 of 225 (47%) tumors. Absence of both proteins was significantly associated with well-differentiated tumors [PTEN (P < 0.02) and p27(kip1) (P < 0.009)]. Differentiation grade, tumor stage, and histologic type were independent of an increased BMI. Importantly, tumors of obese women expressed significantly less PTEN (P < 0.008) and less p27(kip1) (P < 0.01) than tumors from nonobese patients. Combined absence of both PTEN and p27(kip1) expression characterized a group of 75 (32%) tumors with favorable clinical outcome, particularly in the FIGO stages I and II (P = 0.003) of obese patients. Cox regression analysis revealed that PTEN/p27(kip1) phenotype, FIGO stage, and histologic grade were independent predictors of prognosis in endometrioid endometrial carcinoma. CONCLUSIONS: Inactivation of PTEN/p27(kip1) proteins is a specific feature in the progression of endometrial carcinoma in obese patients. The phenotype of the combined loss of PTEN/p27(kip1) protein expression in obese patients is associated with a significantly better prognosis in endometrioid endometrial carcinoma.


Assuntos
Carcinoma/patologia , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Neoplasias do Endométrio/patologia , Obesidade/complicações , PTEN Fosfo-Hidrolase/metabolismo , Índice de Massa Corporal , Carcinoma/complicações , Carcinoma/mortalidade , Neoplasias do Endométrio/complicações , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Prognóstico , Análise de Sobrevida
13.
Sarcoma ; 2010: 431627, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20396630

RESUMO

Sclerosing epithelioid fibrosarcoma (SEF) is a rare soft tissue sarcoma mostly occurring in extraosseous sites. SEF represents a clinically challenging entity especially because no standardized treatment regimens are available. Intraosseous localization is an additional challenge with respect to the therapeutical approach. We report on a 16-year-old patient with SEF of the right proximal tibia. The patient underwent standardized neoadjuvant chemotherapy analogous to the EURAMOS-1 protocol for the treatment of osteosarcoma followed by tumor resection and endoprosthetic reconstruction. Histopathological analysis of the resected tumor showed >90% vital tumor cells suggesting no response to chemotherapy. Therefore, therapy was reassigned to the CWS 2002 High-Risk protocol for the treatment of soft tissue sarcoma. To date (22 months after diagnosis), there is no evidence of relapse or metastasis. Our data suggest that SEF may be resistant to a chemotherapy regimen containing Cisplatin, Doxorubicin, and Methotrexate, which should be considered in planning treatment for patients with SEF.

14.
Artigo em Inglês | MEDLINE | ID: mdl-32714920

RESUMO

The first choice for reconstruction of clinical-size bone defects consists of autologous bone flaps, which often lack the required mechanical strength and cause significant donor-site morbidity. We have previously developed biological substitutes in a rabbit model by combining bone tissue engineering and flap pre-fabrication. However, spontaneous vascularization was insufficient to ensure progenitor survival in the core of the constructs. Here, we hypothesized that increased angiogenic stimulation within constructs by exogenous VEGF can significantly accelerate early vascularization and tissue in-growth. Bone marrow stromal cells from NZW rabbits (rBMSC) were transduced with a retroviral vector to express rabbit VEGF linked to a truncated version of rabbit CD4 as a cell-surface marker. Autologous cells were seeded in clinical-size 5.5 cm3 HA scaffolds wrapped in a panniculus carnosus flap to provide an ample vascular supply, and implanted ectopically. Constructs seeded with VEGF-expressing rBMSC showed significantly increased progenitor survivival, depth of tissue ingrowth and amount of mineralized tissue. Contrast-enhanced MRI after 1 week in vivo showed significantly improved tissue perfusion in the inner layer of the grafts compared to controls. Interestingly, grafts containing VEGF-expressing rBMSC displayed a hierarchically organized functional vascular tree, composed of dense capillary networks in the inner layers connected to large-caliber feeding vessels entering the constructs at the periphery. These data constitute proof of principle that providing sustained VEGF signaling, independently of cells experiencing hypoxia, is effective to drive rapid vascularization and increase early perfusion in clinical-size osteogenic grafts, leading to improved tissue formation deeper in the constructs.

15.
J Telemed Telecare ; 26(7-8): 488-494, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31007131

RESUMO

INTRODUCTION: We describe the use of telepathology in countries with restricted resources using two diagnosis assistance systems (Isabel and Memem7) in addition to the diagnoses made by experts in pathology via the iPath-Network. METHODS: A total of 156 cases, largely from Afghanistan, were analysed; 18 cases had to be excluded because of poor image quality. RESULTS: Of the remaining 138 cases (100%), a responsible physician provided a tentative diagnosis for 61.6% of them. With a diagnosis from a consultant pathologist, it was then possible to make a definite diagnosis in 84.8% of cases on the basis of images taken from hematoxylin and eosin staining sections alone. The use of the diagnosis assistance systems resulted in an ordered list of differential diagnoses in 82.6% (IsabelHealth) and in 74.6% (Memem7) of cases, respectively. Adding morphological terminology reduced the list of possible diagnoses to 52.2% (72 cases, Memem7), but improved their quality. DISCUSSION: In summary, diagnosis assistance systems are promising approaches to provide physicians in countries with restricted resources with lists of probable differential diagnoses, thus increasing the plausibility of the diagnosis of the consultant pathologist.


Assuntos
Telepatologia/organização & administração , Telepatologia/normas , Adolescente , Adulto , Afeganistão , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Países em Desenvolvimento , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem
16.
Cancer Treat Res ; 152: 289-308, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20213397

RESUMO

COSS, the interdisciplinary Cooperative German-Austrian-Swiss Osteosarcoma Study Group, was founded in 1977 and has since registered some 3,500 bone sarcoma patients from over 200 institutions. For the purpose of the Pediatric and Adolescent Osteosarcoma Conference in Houston, March 2008, the outcomes of 2,464 consecutive patients with high-grade central osteosarcoma, who had been diagnosed between 1980 and 2005 and had been treated on neoadjuvant COSS protocols, were reviewed. Intended treatment had included surgery and multidrug chemotherapy, with high-dose methotrexate, doxorubicin, cisplatin, and ifosfamide being used in most protocols. After a median follow-up of 7.31 years for 1,654 survivors, 5- and 10-year survival estimates were 0.748/0.695 for 2,017 patients with localized extremity tumors and 0.369/0.317 for 444 patients with axial tumors or/and primary metastases, respectively. Tumor response to preoperative chemotherapy was of independent prognostic significance. Over the years, there was a major shift from amputation towards limb-salvage. This development was least evident for patients below the age of 10. While survival expectancies improved from the first to the second half of the recruitment period, no further improvement was evident within the latter period. In the manuscript, the results described above are discussed based on the findings of the previous analyses of our group.


Assuntos
Neoplasias Ósseas/terapia , Osteossarcoma/terapia , Adolescente , Adulto , Idoso , Neoplasias Ósseas/mortalidade , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/terapia , Osteossarcoma/mortalidade , Prognóstico
17.
Oral Oncol ; 44(3): 286-94, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17467326

RESUMO

The aim of this retrospective analysis was to evaluate patient and tumor characteristics and treatment results and prognostic factors for patients with craniofacial osteosarcoma (CFOS). The COSS database was searched for patients with previously untreated, histologically confirmed craniofacial osteosarcoma with at least one follow-up examination. In a 28-year period extending from 1977 to 2004, 49 eligible patients were identified and their charts retrospectively analysed. The median age at diagnosis was 19.7 years (range: 4.6-57.2) with no gender predilection. Thirteen CFOS were second or even third primary malignancies. The jaws were the primary site in 27 patients (55% - mandible 15 (31%), maxilla 12 (24%)), while extragnathic bones were involved in 22 (45%). All 49 patients underwent surgery; in 37 (76%) combined with chemotherapy, in seven (14%) with chemotherapy and radiotherapy. Twenty-one patients (43%) received preoperative chemotherapy and the other 28 (57%) had primary surgery. A complete surgical remission was achieved in 32 patients, of whom 24 remained in local control. Actuarial five-year overall and event-free survival rates were 74% and 44%, respectively. Extragnathic site (p<.001) and documented postsurgical rest of the primary tumor (p<.001) were associated with inferior overall survival probabilities. All 24 patients who achieved and maintained local surgical control survived disease-free. Multidisciplinary treatment of CFOS within a multicenter setting resulted in long-term survival in well over two thirds of affected patients. Extragnathic sites and failure to achieve and maintain local surgical control emerged as strong negative prognostic factors.


Assuntos
Osteossarcoma/cirurgia , Neoplasias Cranianas/cirurgia , Adolescente , Adulto , Criança , Pré-Escolar , Bases de Dados Factuais , Ossos Faciais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia , Osteossarcoma/mortalidade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Estudos Retrospectivos , Neoplasias Cranianas/mortalidade , Análise de Sobrevida , Taxa de Sobrevida
18.
Virchows Arch ; 451(5): 923-8, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17694321

RESUMO

Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare low-grade sarcoma of the distal extremities characterized by a myxohyaline stroma, a dense inflammatory infiltrate and virocyte- and lipoblast-like giant cells. Up to now, only two cases have been investigated cytogenetically, showing complex and heterogeneous karyotypes, in part with supernumerary ring chromosomes. We characterized two further cases of MIFS immunohistochemically and performed comparative genomic hybridization as well as DNA image cytometry analyses. Both tumors showed the characteristic histomorphological pattern of MIFS and were positive for Vimentin and CD68. Moreover, both cases presented aberrant karyotypes including distinct DNA copy number changes involving chromosome 7 and disclosed DNA aneuploidy.


Assuntos
Osteossarcoma/genética , Neoplasias do Sistema Nervoso Periférico/genética , Neuropatia Tibial/genética , Idoso , Feminino , Dedos , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Hibridização de Ácido Nucleico , Osteossarcoma/patologia , Neoplasias do Sistema Nervoso Periférico/patologia , Neuropatia Tibial/patologia
19.
J Clin Oncol ; 23(3): 559-68, 2005 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-15659502

RESUMO

PURPOSE: To evaluate the impact of patient, tumor, and treatment-related factors on outcome in unselected patients with recurrent osteosarcoma. PATIENTS AND METHODS: Five hundred seventy-six consecutive patients who had achieved a first complete surgical remission (CR) during combined-modality therapy on neoadjuvant Cooperative Osteosarcoma Study Group (COSS) protocols and then developed recurrent osteosarcoma were analyzed (median time from biopsy to relapse, 1.6 years; range, 0.1 to 14.3 years). There were 501 patients with metastases, 44 with local recurrences, and 31 with both. Metastases involved lungs (469 patients), bones (90 patients), and/or other sites (54 patients). RESULTS: After a median follow-up of 1.2 years for all patients and 4.2 years for survivors, actuarial overall survival (OS) rates at 2, 5, and 10 years were 0.38, 0.23, and 0.18, respectively. Five-year OS was 0.39 for 339 patients with and 0.00 for 229 patients without a second surgical CR (P < .0001). A long time to relapse, a solitary lesion, and, in the case of pulmonary metastases, unilateral disease and the absence of pleural disruption, were of positive prognostic value in uni- and multivariate analyses, as were a second surgical CR and the use of second-line chemotherapy. Radiotherapy was associated with moderately prolonged survival in patients without a second CR. The very limited prognostic differences associated with the use of second-line chemotherapy appeared to be more pronounced with polychemotherapy. CONCLUSION: Time to relapse and tumor burden correlate with postrelapse outcome in osteosarcoma. Complete surgery is an essential component of curative second-line therapy. Chemotherapy, particularly chemotherapy with more than one agent, may contribute to limited improvements in outcome.


Assuntos
Neoplasias Ósseas/patologia , Neoplasias Ósseas/cirurgia , Recidiva Local de Neoplasia , Osteossarcoma/patologia , Osteossarcoma/cirurgia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/radioterapia , Criança , Pré-Escolar , Estudos de Coortes , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteossarcoma/tratamento farmacológico , Osteossarcoma/radioterapia , Prognóstico , Fatores de Risco , Análise de Sobrevida , Fatores de Tempo
20.
J Clin Oncol ; 21(10): 2011-8, 2003 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-12743156

RESUMO

PURPOSE: To determine demographic data and define prognostic factors for long-term outcome in patients presenting with high-grade osteosarcoma of bone with clinically detectable metastases at initial presentation. PATIENTS AND METHODS: Of 1,765 patients with newly diagnosed, previously untreated high-grade osteosarcomas of bone registered in the neoadjuvant Cooperative Osteosarcoma Study Group studies before 1999, 202 patients (11.4%) had proven metastases at diagnosis and therefore were enrolled onto an analysis of demographic-, tumor-, and treatment-related variables, response, and survival. The intended therapeutic strategy included pre- and postoperative multiagent chemotherapy as well as aggressive surgery of all resectable lesions. RESULTS: With a median follow-up of 1.9 years (5.5 years for survivors), 60 patients were alive, 37 of whom were in continuously complete surgical remission. Actuarial overall survival rates at 5 and 10 (same value for 15) years were 29% (SE = 3%) and 24% (SE = 4%), respectively. In univariate analysis, survival was significantly correlated with patient age, site of the primary tumor, number and location of metastases, number of involved organ systems, histologic response of the primary tumor to preoperative chemotherapy, and completeness and time point of surgical resection of all tumor sites. However, after multivariate Cox regression analysis, only multiple metastases at diagnosis (relative hazard rate [RHR] = 2.3) and macroscopically incomplete surgical resection (RHR = 2.4) remained significantly associated with inferior outcomes. CONCLUSION: The number of metastases at diagnosis and the completeness of surgical resection of all clinically detected tumor sites are of independent prognostic value in patients with proven primary metastatic osteosarcoma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Neoplasias Ósseas/cirurgia , Criança , Pré-Escolar , Cisplatino/administração & dosagem , Ensaios Clínicos como Assunto/estatística & dados numéricos , Terapia Combinada , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Europa (Continente) , Feminino , Humanos , Ifosfamida/administração & dosagem , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Terapia Neoadjuvante , Metástase Neoplásica , Osteossarcoma/mortalidade , Osteossarcoma/secundário , Osteossarcoma/cirurgia , Prognóstico , Modelos de Riscos Proporcionais , Análise de Sobrevida , Resultado do Tratamento
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