Publications by authors named "Valter Penna"

14 Publications

  • Page 1 of 1

DIAGNOSIS AND MANAGEMENT OF PAGET'S DISEASE OF BONE - SERIES OF 8 CASES.

Acta Ortop Bras 2019 Jan-Feb;27(1):31-32

Universidade Estadual de São Paulo Júlio de Mesquita Filho (UNESP), Faculdade de Medicina de Botucatu, Botucatu, SP, Brazil.

Paget's disease of bone is a chronic condition characterized by focal abnormalities of absorption and formation of bone, and it may lead to anatomical deformities, pain, fractures, and malignant transformation. It is common in the UK, Australia, New Zealand, and North America and has a strong hereditary component, affecting first- to third-degree relatives. The etiology remains unclear and treatment is based on control of the disease with bisphosphonates, with the aim of relieving symptoms and correcting laboratory abnormalities. Surgical treatment may also be necessary to correct deformities or treat pathological fractures. This study evaluated the management and course of 8 patients with Paget's disease of bone, followed in the Orthopedic Clinic of this hospital. Among these patients, 1 had concomitant advanced prostate carcinoma, highlighting the association between Paget's disease and secondary bone diseases that can affect the differential diagnosis.
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http://dx.doi.org/10.1590/1413-785220192701161107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362702PMC
February 2019

What is the impact of local control in Ewing sarcoma: analysis of the first Brazilian collaborative study group - EWING1.

BMC Cancer 2017 Jun 15;17(1):420. Epub 2017 Jun 15.

Instituto do Câncer Infantil, Porto Alegre, RS, Brazil.

Background: Relapse in localized Ewing sarcoma patients has been a matter of concern regarding poor prognosis. Therefore, we investigated the impact of local control modality (surgery, surgery plus radiotherapy, and radiotherapy) on clinical outcomes such as survival and recurrence in patients with non-metastatic Ewing sarcoma treated on the first Brazilian Collaborative Group Trial of the Ewing Family of Tumors (EWING1).

Methods: Seventy-three patients with localized Ewing sarcoma of bone aged < 30 years were included. The treating physicians defined the modality of local control based on the recommendations of the coordinating center and the patient and tumor characteristics. Possible associations of local control modality with local failure (LF), disease-free survival (DFS), event-free survival (EFS), overall survival (OS), and clinical characteristics were analyzed.

Results: Mean patient age was 12.8 years (range, 2 to 25 years) and median follow-up time was 4.5 years (range, 2.3 to 6.7 years). Forty-seven patients underwent surgery, 13 received radiotherapy, and 13 received both. The 5-year EFS, OS, and DFS for all patients was 62.1%, 63.3%, and 73.1%, respectively. The 5-year cumulative incidence (CI) of LF was 7.6% for surgery, 11.1% for radiotherapy, and 0% for postoperative radiotherapy (PORT) (p = 0.61). The 5-year EFS was 71.7% for surgery, 30.8% for radiotherapy, and 64.1% for PORT (p = 0.009).

Conclusions: There was a significant effect of local control modality on EFS and OS in the study. Surgery and PORT modalities yielded very close results. The group treated with radiotherapy alone had considerably worse outcomes. This may be confounded by greater risk factors in these patients. There was no significant effect of local control modality on the CI of LF and DFS.
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http://dx.doi.org/10.1186/s12885-017-3391-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5472913PMC
June 2017

Centrosome amplification in chondrosarcomas: A primary cell culture and cryopreserved tumor sample study.

Oncol Lett 2017 Mar 23;13(3):1835. Epub 2017 Jan 23.

Molecular Oncology Research Center, Barretos Cancer Hospital, Pio XII Foundation, Barretos, São Paulo 14780-000, Brazil.

The genetics background underlying the aggressiveness of chondrosarcoma (CS) is poorly understood. One possible cause of malignant transformation is chromosomal instability, which involves an error in mitotic segregation due to numerical and/or functional abnormalities of centrosomes. The present study aimed to evaluate centrosome amplification in cryopreserved samples of tumor tissue from patients with CS. An analysis was performed on 3 primary cultures of tumors from patients who underwent surgery between January 2012 and December 2012 at the Department of Orthopedics at the Barretos Cancer Hospital (Barretos, Brazil). Additionally, cryopreserved tumor specimens were analyzed from 10 patients. The data were assessed using immunocytochemistry and immunohistochemistry staining techniques with monoclonal antibody anti-γ-tubulin. A total of 4 samples of CS cultured cells were obtained from 3 patients. A recurrence of a histological grade III tumor was detected in a female patient with Ollier's syndrome. The other 2 cases were grade I and III. The incidence of centrosome amplification in the primary cultures ranged from 15-64% of the cells. Whereas control cultured fibroblasts showed baseline levels of 4% amplified cells. For the cryopreserved specimens, two independent observers analyzed each sample and counted the cells stained with γ-tubulin, verifying the percentage of affected cells to be a mean of 14%, with the number of clusters ranging between 0-6 per slide. In conclusion, centrosome amplification was found to be a consistent biological feature of CS and may underlie chromosomal instability in this tumor.
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http://dx.doi.org/10.3892/ol.2017.5633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403437PMC
March 2017

High Expression of HULC Is Associated with Poor Prognosis in Osteosarcoma Patients.

PLoS One 2016 2;11(6):e0156774. Epub 2016 Jun 2.

Pediatric Oncology Laboratory, Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil.

Osteosarcoma (OS) is the most common primary bone cancer in childhood. OS is an aggressive disease, and metastatic patients evolve with very poor clinical outcomes. Genetically, OSs are extremely complex tumors, and the related metastatic process is not well understood in terms of the biology of the disease. In this context, long non-coding RNAs (lncRNAs) have emerged as an important class of gene expression regulators that play key roles in the invasion and metastasis of several human tumors. Here, we evaluated the expression of HULC, which is an lncRNA that is associated with the tumor metastatic process, and assessed its potential role as a prognostic marker in OS. HULC expression was evaluated in primary OS samples using real-time RT-PCR. HULC expression status was determined by receiver operating characteristic (ROC) analysis, and its association with survival was assessed using the Kaplan-Meier method. The HULC expression level was not significantly associated with the clinicopathological characteristics of the OS patients. However, our data demonstrated that higher levels of expression of HULC were associated with lower survival rates in OS patients, both in terms of overall and event-free survival. Elevated HULC expression was associated with poor clinical outcomes among the OS patients, which suggests that HULC could be a potential prognostic biomarker in OS.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0156774PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4890737PMC
July 2017

Raf Kinase Inhibitor Protein Expression and Prognostic Value in Soft Tissue Sarcomas.

Pathobiology 2016 10;83(1):41-6. Epub 2016 Feb 10.

Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.

Objective: Soft tissue sarcomas (STSs) are heterogeneous tumors displaying multiple and complex molecular abnormalities with no specific pattern. Despite current therapeutic advances, the patients with STS still have a poor outcome, which makes it necessary to find out new prognostic markers. The Raf kinase inhibitory protein (RKIP) has been associated with prognosis in several human neoplasms; however, its role in STS is unknown.

Methods: In the present study RKIP expression was assessed by immunohistochemistry in a series of 87 STSs, and its expression profile was associated with the patients' pathological parameters.

Results: We found that RKIP is expressed in the cytoplasm of the great majority of cases, and absent in only approximately 18% of cases (16/87). Importantly, we observed that loss of RKIP expression was associated with poor outcome, constituting an independent prognostic marker.

Conclusion: This is the first study assessing RKIP expression levels in STS. We showed that loss of RKIP expression is present in a small subset of cases; however, its absence was associated with poor survival and may be a potential marker for STS prognosis.
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http://dx.doi.org/10.1159/000441227DOI Listing
November 2016

TERT promoter mutations in soft tissue sarcomas.

Int J Biol Markers 2016 Feb 28;31(1):e62-7. Epub 2016 Feb 28.

Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo - Brazil.

Introduction: Oncogenic hotspot mutations in the promoter region of the TERT gene have been identified in several cancer types as being associated with a worse outcome. Additionally, a polymorphism (rs2853669) in the TERT promoter region was reported to modify the survival of TERT-mutated patients. Our aim is to determine the frequency of c.-124 C>T and c.-146 C>T TERT mutations and to genotype the rs2853669 polymorphism in a series of 68 soft tissue sarcomas (STS) comprising 22 histological subtypes.

Methods: PCR was performed, followed by direct sequencing of a fragment of TERT containing the hotspots and the rs2853669.

Results: We found TERT mutations in 4/68 (5.9%) STSs including 1 pleomorphic liposarcoma (1/1), 1 dedifferentiated liposarcoma (1/1) and 2 myxoid liposarcomas (2/9). The variant C allele of rs2853669 was found in 54.8% (34/62) of all STSs and in 75% (3/4) of TERT-mutated cases. TERT mutations were associated with younger age, and the C allele of the rs2853669 was associated with high histological grade (2 and 3). No association was found between TERT mutation status or rs2853669 genotype and patient prognosis.

Conclusions: We showed that TERT promoter mutation is not a recurrent event in STS and is present in particular histological subtypes.
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http://dx.doi.org/10.5301/jbm.5000168DOI Listing
February 2016

Absence of Microsatellite Instability In Soft Tissue Sarcomas.

Pathobiology 2015 28;82(1):36-42. Epub 2015 Feb 28.

Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.

Objective: Here, we analyze a series of soft tissue sarcomas (STS), which are a heterogeneous group of mesenchymal neoplasms, for the presence and frequency of microsatellite instability (MSI). MSI has been proposed to be clinically relevant for colorectal cancer, yet on STS its role is not consensual, partly due to the limited number of cases analyzed and methodology issues.

Methods: The detailed evaluation of MSI in tumor samples from 71 STS patients was performed by pentaplex PCR of the MSI markers NR-27, NR-21, NR-24, BAT-25, and BAT-26, followed by capillary electrophoresis. The expression of DNA mismatch repair (MMR) proteins (MLH1, MSH2, MSH6, and PMS2) was also evaluated in suspected MSI-positive cases by immunohistochemistry.

Results: The MSI analysis showed instability of one MSI marker in a total of 3 cases (4.2%). However, MMR protein expression was not affected, demonstrating that all cases were microsatellite stable.

Conclusion: Our results suggest that MSI does not play a role in STS tumorigenesis. © 2015 S. Karger AG, Basel.
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http://dx.doi.org/10.1159/000369906DOI Listing
February 2015

Characterization of monocarboxylate transporters (MCTs) expression in soft tissue sarcomas: distinct prognostic impact of MCT1 sub-cellular localization.

J Transl Med 2014 May 9;12:118. Epub 2014 May 9.

Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, 4710-057 Braga, Portugal.

Background: Soft tissue sarcomas (STSs) are a group of neoplasms, which, despite current therapeutic advances, still confer a poor outcome to half of the patients. As other solid tumors, STSs exhibit high glucose consumption rates, associated with worse prognosis and therapeutic response. As highly glycolytic tumors, we hypothesized that sarcomas should present an increased expression of lactate transporters (MCTs).

Methods: Immunohistochemical expression of MCT1, MCT2, MCT4 and CD147 was assessed in a series of 86 STSs and the expression profiles were associated with patients' clinical-pathological parameters.

Results: MCT1, MCT4 and CD147 were mainly observed in the plasma membrane of cancer cells (around 60% for MCTs and 40% for CD147), while MCT2 was conspicuously found in the cytoplasm (94.2%). Importantly, we observed MCT1 nuclear expression (32.6%). MCT1 and MCT4, alone or co-expressed with CD147 in the plasma membrane, were associated with poor prognostic variables including high tumor grade, disease progression and shorter overall survival. Conversely, we found MCT1 nuclear expression to be associated with low grade tumors and longer overall survival.

Conclusions: The present work represents the first report of MCTs characterization in STSs. We showed the original finding of MCT1 expression in the nucleus. Importantly, opposite biological roles should be behind the dual sub-cellular localization of MCT1, as plasma membrane expression of MCT1 is associated with worse patients' prognosis, while nuclear expression is associated with better prognosis.
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http://dx.doi.org/10.1186/1479-5876-12-118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4036386PMC
May 2014

Fifteen Years' Experience of the Brazilian Osteosarcoma Treatment Group (BOTG): A Contribution from an Emerging Country.

J Adolesc Young Adult Oncol 2013 Dec;2(4):145-52

1 Instituto de Oncologia Pediátrica/GRAACC-Universidade Federal de São Paulo , São Paulo, Brazil .

Purpose: Little information is available regarding the tumor features, prognostic factors, and treatment results in children and adolescents and young adults (AYAs) with osteosarcoma diagnosed in developing countries. We reviewed the results of three observational cohorts of osteosarcoma patients treated in an emerging country.

Methods: A total of 604 patients below the age of 30 years with high-grade osteosarcoma were prospectively enrolled in the Brazilian Osteosarcoma Treatment Group (BOTG) studies III, IV, and V. Gender, age, time from onset of symptoms to diagnosis, primary tumor site, presence or absence of metastases at diagnosis, tumor size, type of surgery (limb-sparing or amputation), treatment protocol, and histological response were correlated with survival.

Results: The estimated 5-year overall survival and event-free survival (EFS) rates for the 553 eligible patients were 49% and 39% respectively; of the 390 non-metastatic patients included in the total, overall- and event-free survival were 59% and 48% respectively. Metastases at diagnosis, primary tumor site, type of surgery, and histological response were significant predictors of overall survival and EFS in univariate and multivariate analysis, whereas tumor size and treatment protocol lost prognostic significance in multivariate analysis.

Conclusion: We report on the outcome of three consecutive studies for the treatment of osteosarcoma carried out in Brazil over 15 years. Although the survival rates presented are below those reported in current literature, it represents the result of a favorable experience gathered from the national collaborative work.
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http://dx.doi.org/10.1089/jayao.2013.0012DOI Listing
December 2013

Ki-67 and CD100 immunohistochemical expression is associated with local recurrence and poor prognosis in soft tissue sarcomas, respectively.

Oncol Lett 2013 May 5;5(5):1527-1535. Epub 2013 Mar 5.

Molecular Oncology Research Center, Barretos Cancer Hospital, Pio XII Foundation, Barretos 14780-000;

Soft tissue sarcomas (STSs) are a heterogeneous group of mesenchymal tumors of >50 subtypes. However, STSs represent <1% of types of cancer. Despite this low frequency, the disease is aggressive and treatment, when possible, is based on traditional chemotherapies. A number of cases of resistance to adjuvant therapies have been reported. Metastases are commonly identified in STS patients during diagnosis and the development of effective clinical parameters is crucial for correct management of the disease. The use of biological markers in cancer is a useful tool to determine patient prognosis. Ki-67 is a protein marker for proliferation of somatic cells and is widely used in prognostic studies of various types of tumor, including STSs. Cluster of differentiation 100 (CD100) is a member of the semaphorin family. The family was initially described as axon guidance molecules important for angiogenesis, organogenesis, apoptosis and neoplasia. CD100 was previously utilized as a prognostic factor in tumors and also in STSs. In the present study, protein expression of Ki-67 and CD100 was analyzed by immunohistochemistry in samples of STS patients of the Barretos Cancer Hospital (Barretos, Brazil) to establish prognostic criteria of the disease. Results demonstrate a correlation between CD100 expression and poor prognosis, consistent with a previous study. Moreover, the expression of Ki-67 was identified to correlate with presence of local or locoregional recurrence. To the best of our knowledge, no large casuistic study has revealed this correlation between Ki-67 and local recurrence in STSs. The use of Ki-67 and CD100 as markers in clinical pathological analysis may be suitable as a prognostic criterion in disease progression.
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http://dx.doi.org/10.3892/ol.2013.1226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678859PMC
May 2013

RESULTS FROM CLINICAL AND RADIOLOGICAL FOLLOW-UP, AFTER SURGICAL TREATMENT OF CHONDROBLASTOMA.

Rev Bras Ortop 2011 Sep-Oct;46(5):561-4. Epub 2015 Dec 6.

Resident Physician in the Orthopedic Oncology Service, Barretos Cancer Hospital, Pius XII Foundation, Barretos, SP, Brazil.

Objectives: To evaluate the long-term clinical and radiological results from patients who underwent surgical treatment of chondroblastoma, between 2003 and 2009, by the same surgical team, using the same operative technique.

Methods: A retrospective study was conducted on 12 patients with histological diagnoses of chondroblastoma, who were attended between 2003 and 2009 at the Pius XII Foundation (Barretos Cancer Hospital, Barretos, State of São Paulo). These patients underwent surgical treatment with intralesional resection of the tumor, adjuvant electrocauterization and replacement with methyl methacrylate (11 cases) or an autologous graft from the iliac crest (one case). The preoperative evaluation included physical examination, plain radiographs of the site, magnetic resonance imaging, computed axial tomography and bone scintigraphy. The patients were assessed clinically and radiologically according to a predefined protocol, with a series of plain radiographs, and a functional assessment in accordance with the Enneking functional score.

Results: The average age at the time of diagnosis was 14 years and 4 months. The most frequent location affected was the distal femoral epiphysis (75%), followed by the proximal tibial epiphysis (16.6%) and the calcaneus (8.4%). There was higher prevalence among the female patients than among the male patients (3:1). In three cases, preoperative biopsy was necessary. During the follow-up, there was no evidence of local tumor recurrence, and all the patients presented an excellent functional result from the surgical technique used, with Enneking scores ranging from 20 to 30.

Conclusion: Surgical treatment of chondroblastoma, using intralesional resection, adjuvant electrocauterization and replacement with methyl methacrylate or bone graft produced good results.
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http://dx.doi.org/10.1016/S2255-4971(15)30412-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4799312PMC
March 2016

A NEW APPROACH TO PARTIALKNEE ENDOPROSTHESIS IN PRIMARY BONE SARCOMAS.

Rev Bras Ortop 2009 Jan 6;44(1):46-51. Epub 2015 Dec 6.

Hospital de Cáncer de Barretos, SP.

Unlabelled: Partial knee endoprosthesis to bone sarcomas resections seems to be a good solution to treat this immature skeletal patients. The purpose of this study is to evaluate the functional score in fourteen patients, advantages and the technique indications.

Methods: Retrospective analysis was done to assess in this group of patients the functional evolution and the possible complications of the procedure. 14 patients between 10 and 22 years functionally evaluated in Ennekin/ISOLS (International Society of Limb Salvage) criteria, being all of them operated in the same institution by the same surgeon. Were used distal femur and proximal tibia partial endoprosthesis.

Results: General analysis demonstrated that the functional results were over than 67 percent (ISOLS criteria) in 78,6 percent of the patients, being considered excellent. 21,4 percent were considered good results, being between 50 and 66 percent. Bone storage was preserved when avoiding the adjacent segment resection. Surgery time was not prolonged in ligament reconstruction.

Conclusion: Knee partial endoprosthesis are less damage to bone storage in young patients. The critics about the bad functional results are being supplied by new surgical techniques, excellent rehabilitation protocols, implants technology and the consequent learning curve. This option of treatment permits the preservation of healthy bone and provides the possibility of a revision replacement less aggressive.
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http://dx.doi.org/10.1016/S2255-4971(15)30048-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4783592PMC
January 2009

Vascular reconstruction in limbs with malignant tumors.

Vasc Endovascular Surg 2004 Sep-Oct;38(5):423-9

Department of Vascular Surgery, Hospital do Câncer A.C. Camargo, São Paulo, Brazil.

Patients with tumors in limbs who undergo surgical treatment may present involvement of major vessels. Major arteries must be reconstructed for limb salvage. Major veins may be reconstructed to avoid the onset of venous hypertension. The objective of this study is to analyze the results from surgical treatment of malignant tumors associated with vascular reconstruction in limbs. A prospective follow-up was made of 20 patients with malignant tumors involving major vessels in limbs who underwent vascular reconstruction. Arterial and venous reconstructions were performed in 11 patients, arterial reconstruction in 7, and venous reconstruction in 2. The vascular substitutes utilized were: greater saphenous vein (21), expanded polytetrafluoroethylene (ePTFE) prosthesis (5), and Dacron prosthesis (5). Vascular complications occurred in 9 patients: 1 rupture of the arterial graft, 4 occlusions of the venous graft, and worsening of previous edema in 4 patients. Nonvascular complications occurred in 6 patients: infection (2), neurologic deficit (2), partial necrosis of the flap (1), and enteric fistula (1). Four patients presented local recurrence, and 1 of them underwent transfemoral amputation. Seven patients presented pulmonary metastases, of whom 4 died. Arterial revascularization in association with the resection of limb neoplasm is a safe procedure with a low rate of complications. Venous revascularization should be performed using an autologous substitute.
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http://dx.doi.org/10.1177/153857440403800505DOI Listing
February 2005

Vascular reconstruction in limbs associated with resection of tumors.

Ann Vasc Surg 2003 Jul;17(4):411-6

Department of Vascular Surgery, Hospital do Câncer A.C. Camargo, São Paulo, Brazil.

Patients with tumors in limbs who undergo surgical treatment may present involvement of major vessels. The artery must be reconstructed for limb salvage and the vein may be reconstructed to avoid the onset of venous hypertension. The objective of this study was to analyze the results from surgical treatment of tumors associated with vascular reconstruction in limbs. A prospective follow-up was made of 17 patients with tumors involving major vessels in limbs who underwent vascular reconstruction. Arterial and venous reconstructions were performed in nine patients, arterial reconstruction was performed in six, and venous reconstruction in two patients. The vascular substitutes used were greater saphenous vein (19), expanded polytetrafluoroethylene prosthesis (5), and Dacron prosthesis (2). Vascular complications occurred in seven patients: one arterial graft rupture, three venous graft occlusions, and lymphedema in five patients. The following nonvascular complications occurred in 10 patients: pulmonary metastasis (7), local recurrence (2), neurological deficit (2), infection (2), partial necrosis of the flap (1), and enteric fistula (1). Six patients with pulmonary metastasis died. One patient underwent transfemoral amputation. Major vessel reconstruction in limbs associated with resection of neoplasms is a safe procedure. Venous revascularization should be performed using an autologous substitute.
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http://dx.doi.org/10.1007/s10016-003-0031-0DOI Listing
July 2003
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