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  • 1
    Language: English
    In: European spine journal, 2020-12, Vol.29 (12), p.3157-3162
    Description: Percutaneous vertebroplasty (VTP) is a well-known surgical technique used for pain management and vertebral consolidation in the treatment of osteolytic metastases of the spine. While this indication is proven and commonly accepted, an antitumoral effect of polymethylmethacrylate (PMMA) has been proposed but not yet demonstrated. The aim of our study is to evaluate the evidences of antitumoral effect on anatomopathological examination. We present a small series of pathology findings after VTP for spine metastases that support the lack of antitumoral effect of PMMA. We have retrospectively analyzed three cases of patients treated for en bloc excision of recurrent spine metastases previously submitted elsewhere to VTP on the same levels. We discuss our results with the literature reporting of an antitumoral effect of VTP. In our series, after anatomopathological examination, a cement-induced tumor necrosis was never found. Conversely, a foreign-body reaction around the cement was found, inside vital tumor. These results are consistent with an immune reaction to a foreign body without evidences of an antitumoral effect of PMMA. The antitumoral effect of PMMA should not be taken into account as an indication for VTP in spinal metastases. It is important not to misuse VTP as a therapy aiming at tumor control. Other therapies such as radiotherapy, radiosurgery and open surgery are available for that purpose.
    Subject(s): Medical research ; Care and treatment ; Pain ; Polymethylmethacrylate ; Orthopedic surgery ; Surgery ; Analysis ; Medicine, Experimental ; Nervous system ; Metastasis ; Index Medicus
    ISSN: 0940-6719
    E-ISSN: 1432-0932
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 2
    Language: English
    In: Journal of clinical oncology, 2012-06-10, Vol.30 (17), p.2112-2118
    Description: We compared two chemotherapy regimens that included methotrexate (MTX), cisplatin (CDP), and doxorubicin (ADM) with or without ifosfamide (IFO) in patients with nonmetastatic osteosarcoma of the extremity. Patients age ≤ 40 years randomly received regimens with the same cumulative doses of drugs (ADM 420 mg/m(2), MTX 120 g/m(2), CDP 600 mg/m(2), and IFO 30 g/m(2)) but with different durations (arm A, 44 weeks; arm B, 34 weeks). IFO was given postoperatively when pathologic response to MTX-CDP-ADM was poor (arm A) or given in the primary phase of chemotherapy with MTX-CDP-ADM (arm B). End points of the study included pathologic response to preoperative chemotherapy, toxicity, and survival. Given the feasibility of accrual, the statistical plan only permitted detection of a 15% difference in 5-year overall survival (OS). From April 2001 to December 2006, 246 patients were enrolled. Two hundred thirty patients (94%) underwent limb salvage surgery (arm A, 92%; arm B, 96%; P = .5). Chemotherapy-induced necrosis was good in 45% of patients (48% in arm A, 42% in arm B; P = .3). Four patients died of treatment-related toxicity (arm A, n = 1; arm B, n = 3). A significantly higher incidence of hematologic toxicity was reported in arm B. With a median follow-up of 66 months (range, 1 to 104 months), 5-year OS and event-free survival (EFS) rates were not significantly different between arm A and arm B, with OS being 73% (95% CI, 65% to 81%) in arm A and 74% (95% CI, 66% to 82%) in arm B and EFS being 64% (95% CI, 56% to 73%) in arm A and 55% (95% CI, 46% to 64%) in arm B. IFO added to MTX, CDP, and ADM from the preoperative phase does not improve the good responder rate and increases hematologic toxicity. IFO should only be considered in patients who have a poor histologic response to MTX, CDP, and ADM.
    Subject(s): Biological and medical sciences ; Medical sciences ; Diseases of the osteoarticular system ; Tumors of striated muscle and skeleton ; Tumors ; Osteosarcoma - drug therapy ; Femur - pathology ; Humans ; Child, Preschool ; Male ; Tibia - pathology ; Cisplatin - administration & dosage ; Humerus - pathology ; Disease-Free Survival ; Ifosfamide - administration & dosage ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Chemotherapy, Adjuvant - methods ; Adolescent ; Adult ; Female ; Methotrexate - administration & dosage ; Bone Neoplasms - drug therapy ; Child ; Doxorubicin - administration & dosage
    ISSN: 0732-183X
    E-ISSN: 1527-7755
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
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  • 3
    Language: English
    In: British journal of cancer, 2019-11, Vol.121 (11), p.979-982
    Description: Selection of cancer patients for treatment with immune checkpoint inhibitors remains a challenge due to tumour heterogeneity and variable biomarker detection. PD-L1 expression in 24 surgical chordoma specimen was determined immunohistochemically with antibodies 28-8 and E1L3N. The ability of patient-derived organoids to detect treatment effects of nivolumab was explored by quantitative and qualitative immunofluorescence and FACS analysis. The more sensitive antibody, E1L3N (ROC = 0.896, p = 0.001), was associated with greater tumour diameters (p = 0.014) and detected both tumour cells and infiltrating lymphocytes in 54% of patients, but only 1-15% of their cells. Organoids generated from PD-L1-positive patients contained both tumour cells and PD-1/CD8-positive lymphocytes and responded to nivolumab treatment with marked dose-dependent diameter reductions of up to 50% and increased cell death in both PD-L1-positive and negative organoids. Patient-derived organoids may be valuable to predict individual responses to immunotherapy even in patients with low or no immunohistochemical PD-L1 expression.
    Subject(s): Chordoma - surgery ; Immunotherapy - methods ; Apoptosis - drug effects ; Humans ; Middle Aged ; Chordoma - metabolism ; Programmed Cell Death 1 Receptor - metabolism ; Drug Discovery - methods ; Male ; Programmed Cell Death 1 Receptor - antagonists & inhibitors ; B7-H1 Antigen - immunology ; Chordoma - pathology ; Immunohistochemistry - methods ; B7-H1 Antigen - metabolism ; Nivolumab - pharmacology ; B7-H1 Antigen - antagonists & inhibitors ; Models, Biological ; CD8-Positive T-Lymphocytes - drug effects ; Organoids - drug effects ; Aged, 80 and over ; Female ; Aged ; Lymphocytes, Tumor-Infiltrating - immunology ; Index Medicus ; Drug discovery ; Brief Communication ; Cancer ; Molecular medicine
    ISSN: 0007-0920
    E-ISSN: 1532-1827
    Source: Nature Open Access
    Source: Nature Journals Online
    Source: PubMed Central
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 4
    Language: English
    In: Journal of bone and mineral research, 2020-10, Vol.35 (10), p.1974-1980
    Description: ABSTRACT Neoplastic transformation is a rare but serious complication of Paget's disease of bone (PDB), occurring in fewer than 1% of individuals with polyostotic disease. Their prognosis is poor, with less than 50% surviving 5 years. In 2016, the genetic alteration of giant cell tumor (GCT) complicating PDB was identified as a founder germline mutation (P937R) in the ZNF687 gene. However, the study population was exclusively of Italian descent, and patients of different ethnic origins were not studied. To fill this gap, herein we performed mutation analysis of ZNF687 in a GCT in the pelvis of a 45‐year‐old black American woman with polyostotic PDB. The P937R mutation in ZNF687 was found in her tumor but, as expected, the ancestral haplotype that characterizes the Italian GCT/PDB patients was not found. Furthermore, we identified two additional Italian GCT/PDB patients with this ZNF687 mutation, now constituting a cohort of 18 GCT/PDB cases, all harboring the identical mutation. We also searched for ZNF687 mutations in a unique collection of tumor tissues derived from Italian PDB patients, including 28 osteosarcomas (OS/PDB), 8 undifferentiated sarcomas (SRC/PDB), 1 fibrosarcoma (FS/PDB), and 1 chondrosarcoma (CS/PDB). We identified the P937R mutation in one SRC/PDB and a different ZNF687 mutation (R331W) in 1 of 28 pagetic osteosarcomas. Thus, whereas GCT/PDB pathogenesis globally seems to involve the P937R mutation in ZNF687, other neoplasms associated with PDB seem to be less related to mutations in this gene. Finally, we identified the G34W mutation in the H3F3A gene in the maxillary tumor masses of two PDB patients, defining them as conventional GCT rather than GCT/PDB. Thus, combined molecular analysis of H3F3A and ZNF687 is essential to clarify the origin and diagnosis of tumors in PDB. © 2020 American Society for Bone and Mineral Research.
    Subject(s): ZNF687 MUTATION ; NEOPLASTIC TRANSFORMATION ; PAGET's DISEASE OF BONE ; Index Medicus
    ISSN: 0884-0431
    E-ISSN: 1523-4681
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 5
    Language: English
    In: Journal of cutaneous pathology, 2021-05, Vol.48 (5), p.637-643
    Description: Mixed histiocytoses are a rare and recently recognized subset of histiocytic disorders that may involve the skin, characterized by the synchronous or metachronous development of lesions with Langerhans and/or non‐Langerhans cell histiocytosis histopathological features. Around 10% of patients diagnosed with histiocytosis may develop a hematological malignancy, often with dramatic prognostic consequences. We hereby describe the exceptional case of a patient developing a MAP2K1‐driven mixed histiocytosis with Langerhans cell histiocytosis, Rosai‐Dorfman‐Destombes disease, and Erdheim‐Chester disease features and cutaneous involvement, progressing to a fatal and clonally‐related acute myeloid leukemia. We reviewed the literature on similar cases and discussed the histopathological difficulties in their diagnosis and their clinical‐pathological features.
    Subject(s): acute myeloid leukemia ; clonal relation ; Langerhans cell histiocytosis ; Rosai‐Dorfman‐Destombes disease ; Erdheim‐Chester disease ; Histiocytosis ; Skin
    ISSN: 0303-6987
    E-ISSN: 1600-0560
    Source: Alma/SFX Local Collection
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  • 6
    Language: English
    In: Journal of translational medicine, 2013-10-24, Vol.11 (1), p.268-268
    Description: Major goals in translational oncology are to reduce systemic toxicity of current anticancer strategies and improve effectiveness. An extremely efficient cancer cell mechanism to avoid and/or reduce the effects of highly cytotoxic drugs is the establishment of an acidic microenvironment, an hallmark of all malignant tumors. The H +-rich milieu that anticancer drugs meet once they get inside the tumor leads to their protonation and neutralization, therefore hindering their access into tumor cells. We have previously shown that proton pump inhibitors (PPI) may efficiently counterattack this tumor advantage leading to a consistent chemosensitization of tumors. In this study, we investigated the effects of PPI in chemosensitizing osteosarcoma. MG-63 and Saos-2 cell lines were used as human osteosarcoma models. Cell proliferation after pretreatment with PPI and subsequent treatment with cisplatin was evaluated by using erythrosin B dye vital staining. Tumour growth was evaluated in xenograft treated with cisplatin after PPI pretreatment. Subsequently, a multi-centre historically controlled trial, was performed to evaluate the activity of a pre-treatment administration of PPIs as chemosensitizers during neoadjuvant chemotherapy based on methotrexate, cisplatin, and adriamycin. Preclinical experiments showed that PPI sensitize both human osteosarcoma cell lines and xenografts to cisplatin. A clinical study subsequently showed that pretreatment with PPI drug esomeprazole leads to an increase in the local effect of chemotherapy, as expressed by percentage of tumor necrosis. This was particularly evident in chondroblastic osteosarcoma, an histological subtype that normally shows a poor histological response. Notably, no significant increase in toxicity was recorded in PPI treated patients. This study provides the first evidence that PPI may be beneficially added to standard regimens in combination to conventional chemotherapy.
    Subject(s): Osteosarcoma - drug therapy ; Young Adult ; Humans ; Adolescent ; Cell Line, Tumor ; Adult ; Female ; Male ; Drug Evaluation, Preclinical ; Proton Pump Inhibitors - therapeutic use ; Child ; Osteosarcoma - pathology ; Proton pump inhibitors ; Chemotherapy ; Methotrexate ; Osteosarcoma ; Cancer ; Index Medicus
    ISSN: 1479-5876
    E-ISSN: 1479-5876
    Source: BioMedCentral Open Access
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 7
    Language: English
    In: Journal of magnetic resonance imaging, 2018-04, Vol.47 (4), p.1034-1042
    Description: Purpose To assess the diagnostic performance of mean apparent diffusion coefficient (mADC) in differentiating benign from malignant bone spine tumors, using histology as a reference standard. Conventional magnetic resonance imaging (MRI) sequences have good reliability in evaluating spinal bone tumors, although some features of benign and malignant cancers may overlap, making the differential diagnosis challenging. Materials and Methods In all, 116 patients (62 males, 54 females; mean age 59.5 ± 14.1) with biopsy‐proven spinal bone tumors were studied. Field strength/sequences: 1.5T MR system; T1‐weighted turbo spin‐echo (repetition time / echo time [TR/TE], 500/13 msec; number of excitations [NEX], 2; slice thickness, 4 mm), T2‐weighted turbo spin‐echo (TR/TE, 4100/102 msec; NEX, 2; slice thickness, 4 mm), short tau inversion recovery (TR/TE, 4800/89 msec; NEX, 2; slice thickness, 4 mm, IT, 140 msec), axial spin‐echo echo‐planar diffusion‐weighted imaging (DWI) (TR/TE 5200/72 msec; slice thickness 5 mm; field of view, 300; interslice gap, 1.5 mm; NEX, 6; echo‐planar imaging factor, 96; no parallel imaging) with b‐values of 0 and 1000 s/mm², and 3D fat‐suppressed T1‐weighted gradient‐recalled‐echo (TR/TE, 500/13 msec; slice thickness, 4 mm) after administration of 0.2 ml/kg body weight gadolinum‐diethylenetriamine pentaacetic acid. Two readers manually drew regions of interest on the solid portion of the lesion (hyperintense on T2‐weighted images, hypointense on T1‐weighted images, and enhanced after gadolinium administration on fat‐suppressed T1‐weighted images) to calculate mADC. Histology was used as the reference standard. Tumors were classified into malignant primary tumors (MPT), bone metastases (BM), or benign primary tumors (BPT). Statistical tests: Nonnormality of distribution was tested with the Shapiro–Wilk test. The Kruskal–Wallis and Mann–Whitney U‐test with Bonferroni correction were used. Sensitivity and specificity of the mADC values for BM, MPT, and BPT were calculated. Approximate receiver operating characteristic curves were created. Interobserver reproducibility was evaluated using the intraclass correlation coefficient (ICC). Results The mADC values of MPT (n = 35), BM (n = 65), and BPT (n = 16) were 1.00 ± 0.32 (0.59–2.10) × 10−3 mm2/s, 1.02 ± 0.25 (0.73–1.96) × 10−3 mm2/s, 1.31 ± 0.36 (0.83–2.14) × 10−3 mm2/s, respectively. The mADC was significantly different between BPT and all malignant lesions (BM+MPT) (P 〈 0.001), BM and BPT (P = 0.008), and MPT and BPT (P = 0.008). No difference was found between BM and MPT (P = 0.999). An mADC threshold of 0.952 × 10−3 mm2/s yielded 81.3% sensitivity, 55.0% specificity. Accuracy was 76% (95% confidence interval [CI] = 63.9%–88.1%). Interobserver reproducibility was almost perfect (ICC = 0.916; 95% CI = 0.879–0.942). Conclusion DWI with mADC quantification is a reproducible tool to differentiate benign from malignant solid tumors with 76% accuracy. The mADC values of BPT were statistically higher than that of malignant tumors. However, the large overlap between cases may make mADC not helpful in a specific patient. Level of Evidence: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1034–1042.
    Subject(s): bone tumors ; apparent diffusion coefficient ; magnetic resonance imaging ; diagnostic performance ; spine ; Bone tumors ; Diagnosis ; Magnetic resonance imaging ; Body weight ; Cancer ; Index Medicus
    ISSN: 1053-1807
    E-ISSN: 1522-2586
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 8
    Language: English
    In: Annals of surgical oncology, 2014-12, Vol.21 (13), p.4090-4097
    Description: To identify the best surgical approach to atypical lipomatous tumors we reviewed 171 patients who underwent surgery at two sarcoma referral centers with different surgical policies.Of the 151 patients (88 %) with primary tumors, 95 were treated at Institution A and 76 were treated at Institution B. At Institution A, a wide surgical resection, including a slight cuff of soft tissue around the mass, was adopted, which was defined as marginal resection (MR) according to the Enneking classification. At Institution B, a simple tumor resection (SR), according to the Enneking classification, was employed. En bloc surgical resection was the goal in both centers. The primary outcomes of the study were local recurrence-free survival (LRFS), incidence of secondary dedifferentiation at recurrence, and presence of residual tumor after re-excision.Sixteen patients (9 %) had local recurrence. The 10-year LRFS was 82 %. No cases of secondary dedifferentiation were observed. Residual tumor after re-excision was found in 46 % of cases. In univariate analysis, sclerosing subtype, tumor rupture, and SR were unfavorable prognostic factors for LRFS. Sclerosing subtype and tumor rupture were independent prognostic factors for LRFS in multivariate analysis. SR was significantly associated with tumor rupture.Sclerosing subtype and tumor rupture are unfavorable prognostic factors for local recurrence. MR is associated with a lower risk of tumor rupture than SR. Neurovascular and major muscle resections are not necessary in principle. Re-excision after unplanned surgery is not always mandatory. A preoperative core needle biopsy could be useful in identifying the sclerosing subtype.
    Subject(s): Oncology ; Medicine & Public Health ; Surgical Oncology ; Surgery ; Follow-Up Studies ; Neoplasm, Residual - surgery ; Humans ; Liposarcoma - pathology ; Middle Aged ; Lipoma - surgery ; Male ; Treatment Outcome ; Lipoma - pathology ; Neoplasm Recurrence, Local - surgery ; Liposarcoma - surgery ; Neoplasm Recurrence, Local - pathology ; Female ; Italy ; Aged ; Retrospective Studies ; Surgical Procedures, Operative - methods ; Sarcoma ; Analysis ; Index Medicus
    ISSN: 1068-9265
    E-ISSN: 1534-4681
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 9
    Language: English
    In: International journal of molecular sciences, 2016-04-30, Vol.17 (5), p.656
    Description: The molecular mechanism responsible for Ewing's Sarcoma (ES) remains largely unknown. MicroRNAs (miRNAs), a class of small non-coding RNAs able to regulate gene expression, are deregulated in tumors and may serve as a tool for diagnosis and prediction. However, the status of miRNAs in ES has not yet been thoroughly investigated. This study compared global miRNAs expression in paraffin-embedded tumor tissue samples from 20 ES patients, affected by primary untreated tumors, with miRNAs expressed in normal human mesenchymal stromal cells (MSCs) by microarray analysis. A miRTarBase database was used to identify the predicted target genes for differentially expressed miRNAs. The miRNAs microarray analysis revealed distinct patterns of miRNAs expression between ES samples and normal MSCs. 58 of the 954 analyzed miRNAs were significantly differentially expressed in ES samples compared to MSCs. Moreover, the qRT-PCR analysis carried out on three selected miRNAs showed that miR-181b, miR-1915 and miR-1275 were significantly aberrantly regulated, confirming the microarray results. Bio-database analysis identified BCL-2 as a bona fide target gene of the miR-21, miR-181a, miR-181b, miR-29a, miR-29b, miR-497, miR-195, miR-let-7a, miR-34a and miR-1915. Using paraffin-embedded tissues from ES patients, this study has identified several potential target miRNAs and one gene that might be considered a novel critical biomarker for ES pathogenesis.
    Subject(s): Oligonucleotide Array Sequence Analysis ; Humans ; Sarcoma, Ewing - pathology ; Transcriptome ; Child, Preschool ; Mesenchymal Stromal Cells - metabolism ; Male ; MicroRNAs - metabolism ; Bone Neoplasms - pathology ; Paraffin Embedding ; Young Adult ; Mesenchymal Stromal Cells - cytology ; Adolescent ; Adult ; Female ; Bone Neoplasms - genetics ; MicroRNAs - genetics ; Sarcoma, Ewing - genetics ; Child ; Cluster Analysis ; Index Medicus ; microRNAs ; Ewing’s Sarcoma ; miRTarBase database ; human mesenchymal stem cells
    ISSN: 1422-0067
    E-ISSN: 1422-0067
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 10
    Language: English
    In: Journal of cutaneous pathology, 2017-07, Vol.44 (7), p.632-638
    Description: Desmoplastic melanoma (DM) and cutaneous malignant peripheral nerve sheath tumors (MPNST) reveal histological and immunohistochemical similarities, including S100 positivity and negative staining for conventional melanocytic markers. We present 3 cases of cutaneous S100‐positive spindle cell tumors in elderly patients, in which first findings led to initial misdiagnoses as cutaneous MPNST and benign peripheral sheath nerve tumor (neurofibroma). The identification of adjacent atypical melanocytic hyperplasia in the overlying skin along with tumor cell proliferation, also in the superficial dermis, the neurotropic component and the absence of any relationship between the tumor and a major nerve, pre‐existing neural benign tumor or the existence of stigmata suggestive of neurofibromatosis raised consideration of a DM. Careful attention should be paid to the presence of a firm dermal nodule and atypical scar lesions especially in sun‐exposed areas (mainly head and neck region) in elderly patients associated with S100‐positive spindle cell proliferation, solar elastosis and adjacent atypical melanocytic proliferation. In such cases, the possibility of a DM should be excluded with caution, especially if the tumor reveals a paucicellular morphology resembling various non‐melanocytic neoplasms including malignant or benign peripheral sheath nerve tumors.
    Subject(s): melanoma ; desmoplastic melanoma ; cutaneous malignant peripheral nerve sheath tumors ; Melanoma ; Tumors
    ISSN: 0303-6987
    E-ISSN: 1600-0560
    Source: Academic Search Ultimate
    Source: Alma/SFX Local Collection
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