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Rodrigues I.S.,Camargo Cancer Center | Lavorato-Rocha A.M.,Camargo Cancer Center | De M Maia B.,Camargo Cancer Center | Stiepcich M.M.A.,Fleury Institute | And 4 more authors.
British Journal of Cancer | Year: 2013

Background:Epithelial-to-mesenchymal transition (EMT) still remains an obscure event in vulvar squamous cell carcinoma (VSCC).Methods: Immunohistochemistry (IHC) expression of E-cadherin, β-catenin, Snail, Slug, Twist and Vimentin was analysed in 87 VSCC, controlled for human papillomavirus (HPV) positivity, considering tumour front and central tumour as different morphological categories from the same tumour.Results:Lower β-catenin and higher Vimentin expression was associated with invasive front when compared with the central tumour (P=0.013 and P≤0.001, respectively). Higher expression of E-cadherin in central tumour was significantly related to absence of vascular and perineural invasion, lower invasion depth and ≤2 lymph node involvement. Loss of β-catenin and high Slug, Snail and Twist expression was associated with HPV-negative tumours. Moreover, β-catenin lower expression associated with gain in Slug expression predicts a subgroup with worst outcome (P=0.001). Lower expression of β-catenin in both central tumour and invasive front correlated with lower overall survival (P=0.021 and P=0.011, respectively). Also, multivariate analysis showed that lower β-catenin expression was independently associated with poorer outcome (P=0.044).Conclusion:Human papillomavirus-related tumours show better prognosis and outcome; besides, they do not progress through EMT phenomenon. Immunohistochemical analysis of β-catenin in invasive tumour front is a key issue for establishing prognosis of vulva cancer. © 2013 Cancer Research UK. All rights reserved.


Da Silva S.D.,Camargo Cancer Center | Da Silva S.D.,Lady Davis Institute for Medical Research | Da Silva S.D.,McGill University | Alaoui-Jamali M.A.,Lady Davis Institute for Medical Research | And 6 more authors.
Cancer | Year: 2014

Background Locoregional recurrence and distant metastases are ominous events in patients with advanced oral squamous cell carcinoma (OSCC). The objective of this study was to identify functional biomarkers that are predictive of OSCC progression to metastasis. Methods The expression profile of a network of epithelial-mesenchymal transition (EMT) genes was investigated in a large cohort of patients with progressive OSCC using a complimentary DNA microarray platform coupled to quantitative reverse transcriptase-polymerase chain reaction and immunohistochemical analyses. Therapeutic potential was investigated in vitro and in vivo using an orthotopic mouse model of metastatic OSCC growing in the tongue microenvironment. Results Among deregulated EMT genes, the Twist-related protein 1 (TWIST1) transcription factor and several of its regulated genes were significantly overexpressed across advanced stages of OSCC. This result was corroborated by the clinical observation that Twist1 up-regulation predicted the occurrence of lymph node and lung metastases as well as poor patient survival. In support of Twist1 as a driver of OSCC progression, the up-regulation of Twist1 was observed in cells isolated from patients with metastatic OSCC. The inhibition of Twist1 in these metastatic cells induced a potent inhibition of cell invasiveness in vitro as well as progression in vivo. Conclusions The current results provide evidence for the prognostic value and therapeutic potential of a network of Twist genes in patients with advanced OSCC. © 2013 American Cancer Society.


Jardim J.F.,University of Campinas | Francisco A.L.N.,National Institute of Science and Technology in Oncogenomics INCITO | Gondak R.,Federal University of Santa Catarina | Damascena A.,International Center for Cancer Research | And 2 more authors.
International Journal of Oral and Maxillofacial Surgery | Year: 2015

Perineural invasion (PNI) and lymphovascular invasion (LVI) have been associated with the risk of local recurrences and lymph node metastasis. The aim of this study was to evaluate the prognostic impact of PNI and LVI in patients with advanced stage squamous cell carcinoma of the tongue and floor of the mouth. One hundred and forty-two patients without previous treatment were selected. These patients underwent radical surgery with neck dissection and adjuvant treatment. Clinicopathological data were retrieved from the medical charts, including histopathology and surgery reports. Univariate analysis was performed to assess the impact of studied variables on survival. Overall survival was negatively influenced by six tumour-related factors: increasing T stage (P = 0.003), more than two clinically positive nodes (P = 0.002), extracapsular spread of lymph node metastasis (P < 0.001), tumour thickness (P = 0.04), PNI (P < 0.001), and LVI (P = 0.012). Disease-free survival was influenced by PNI (P = 0.04), extracapsular spread of lymph node metastasis (P = 0.008), and N stage (P = 0.006). Multivariate analysis showed PNI to be an independent predictor for overall survival (P = 0.01) and disease-free survival (P = 0.03). Thus the presence of PNI in oral carcinoma surgical specimens has a significant impact on survival outcomes in patients with advanced stage tumours submitted to radical surgery and adjuvant radiotherapy/radiochemotherapy. © 2014 International Association of Oral and Maxillofacial Surgeons.


Aloia T.A.,The Surgical Center | Jarufe N.,Pontifical Catholic University of Chile | Javle M.,University of Houston | Maithel S.K.,Emory University | And 4 more authors.
HPB | Year: 2015

An American Hepato-Pancreato-Biliary Association (AHPBA)-sponsored consensus meeting of expert panellists was convened on 15 January 2014 to review current evidence on the management of gallbladder carcinoma in order to establish practice guidelines. In summary, within high incidence areas, the assessment of routine gallbladder specimens should include the microscopic evaluation of a minimum of three sections and the cystic duct margin; specimens with dysplasia or proven cancer should be extensively sampled. Provided the patient is medically fit for surgery, data support the resection of all gallbladder polyps of >1.0 cm in diameter and those with imaging evidence of vascular stalks. The minimum staging evaluation of patients with suspected or proven gallbladder cancer includes contrasted cross-sectional imaging and diagnostic laparoscopy. Adequate lymphadenectomy includes assessment of any suspicious regional nodes, evaluation of the aortocaval nodal basin, and a goal recovery of at least six nodes. Patients with confirmed metastases to N2 nodal stations do not benefit from radical resection and should receive systemic and/or palliative treatments. Primary resection of patients with early T-stage (T1b-2) disease should include en bloc resection of adjacent liver parenchyma. Patients with T1b, T2 or T3 disease that is incidentally identified in a cholecystectomy specimen should undergo re-resection unless this is contraindicated by advanced disease or poor performance status. Re-resection should include complete portal lymphadenectomy and bile duct resection only when needed to achieve a negative margin (R0) resection. Patients with preoperatively staged T3 or T4 N1 disease should be considered for clinical trials of neoadjuvant chemotherapy. Following R0 resection of T2-4 disease in N1 gallbladder cancer, patients should be considered for adjuvant systemic chemotherapy and/or chemoradiotherapy. © 2015 International Hepato-Pancreato-Biliary Association.


Maia B.M.,University of Houston | Maia B.M.,Camargo Cancer Center | Rocha R.M.,Camargo Cancer Center | Calin G.A.,University of Houston
Epigenetics | Year: 2014

Non-coding RNAs and epigenetics are remarkable mechanisms of cellular control. In this review we underline the processes by which non-coding RNAs (ncRNAs), shown to be involved in various diseases, are capable of modifying and being modified by the epigenetic machinery, emphasizing the clinical importance of this network in cancer. Many ncRNAs have been described that play important roles in the establishment and maintenance of the epigenome. However, only a few studies deeply take into account the role of ncRNAs from a clinicopathological standpoint. The wide range of interactions between the non-coding RNome and the epigenome, and the roles of these networks in the pathogenesis, prognosis and early diagnosis of many diseases, present new challenges and opportunities for future studies regarding therapeutic strategies in oncology. © 2014 Landes Bioscience.


Lavorato-Rocha A.M.,Camargo Cancer Center | Anjos L.G.,Camargo Cancer Center | Cunha I.W.,Camargo Cancer Center | Vassallo J.,Camargo Cancer Center | And 2 more authors.
Methods | Year: 2015

Background: Pten encodes a well-characterized protein that is important in several cancers due to its tumor suppressor function. Yet, the detection and evaluation of PTEN by immunohistochemistry (IHC) for clinical practice have not been standardized. Thus, in this study, we performed a literature review of protocols for PTEN assessment by IHC and the possible differences in evaluation, based on our experience with vulvar carcinomas. Also, we report some of our most recent findings regarding the clinical impact of PTEN in this type of tumor. Methods: In total, 150 FFPE vulvar carcinoma samples in a tissue microarray were examined by IHC with regard to PTEN, PI3K, AKT, and mTOR. All evaluations were performed by slide digitalization and quantification using APERIO ImageScope software. All measurements were converted into HScore values for the statistical analysis. Results: Sharp and specific PTEN expression was observed in the nuclei and cytoplasmic compartments. Its HScore values ranged from 3.5 to 226, with a median of 92.5. mTOR expression was robust in all cases (mean HScore = 248.1). AKT and PI3K had median HScore values of 200.5 and 156.5, respectively. In addition, PTEN expression was associated with higher rates of patient survival. Conclusion: The preanalytical step is the first issue in the immunohistochemical evaluation of PTEN. With regard to the analytical procedure, the antigen retrieval step yielded better stains for protocols with high-pH buffers, and antibody clone 6H2.1 effected the most reliable results. PTEN is a good prognostic marker for vulvar cancer, correlating with higher rates of patient survival. Our data underscore the importance of technical standardization to ensure more reliable and reproducible evaluation of PTEN in clinical practice. © 2014 Elsevier Inc.


Pompeo A.C.L.,ABC Medical School | Zequi S.D.C.,Camargo Cancer Center | Pompeo A.S.F.L.,ABC Medical School
Current Opinion in Urology | Year: 2015

Penile cancer is a devastating disease, usually diagnosed late, that requires wide excisions, which causes alterations in self-esteem and body image, affecting sexual and urinary functions, which compromise quality of life. Recently, an increasing interest in penile-sparing surgeries (PSSs) has emerged, aiming to spare patients from these complications. RECENT FINDINGS: Several options of PSS have been popularized for selected cases (Ta-1, Tis and some T2), such as wide local excision, circumcision, partial penectomy, total or partial glansectomies with or without glans-resurfacing procedures, as well as new glans reconstructions using spatulated urethral advances or free skin grafts. These options, in general, achieve good local control, with adequate functional results and satisfactory cosmetic appearance. The local recurrences, however, are slightly higher than amputations. Contemporary techniques such as laser or cryotherapy can be performed in selected cases. SUMMARY: PSS must be indicated only for superficial penile cancer cases, such as Tis and Ta-1, and for selected invasive lesions (small distal pT2 tumors). Candidates for PSS should be adherent to follow-up requirements, allowing early detection of local recurrences. Prompt and effective salvage procedures are mandatory in these situations. © 2015 Wolters Kluwer Health, Inc.


Baiocchi G.,Camargo Cancer Center | Rocha R.M.,Camargo Cancer Center
Current Opinion in Obstetrics and Gynecology | Year: 2014

PURPOSE OF REVIEW: Surgical treatment of vulvar cancer has been shifted from ultraradical procedures associated with huge morbidity to less extensive surgery with better psychosexual result and less morbidity, without compromising survival. The authors review and discuss the recent literature regarding the surgical management of vulvar squamous cell carcinoma. RECENT FINDINGS: Surgery remains the cornerstone in the treatment of vulvar cancer. Radical vulvectomy with inguinofemoral lymphadenectomy has been replaced by radical local excision with sentinel node procedure for early disease. However, the role and distance of pathological margins are still on debate. Recent results from a large prospective trial corroborate the safety of sentinel node biopsy for early disease, even after primary tumor resection. An experienced team should perform sentinel node procedure using combined technique (blue dye and lymphoscintigraphy) and ultrastaging pathology. Moreover, midline tumors still need lymph node biopsy from both groins. SUMMARY: Primary vulvar cancer may be safely treated with radical/wide local resection. In case of other suspicious lesion or multifocal disease, radical vulvectomy is performed. Patients with unifocal disease, tumor size less than 4 cm, and clinically negative groins are candidates to sentinel node procedure. In the case of clinically positive node or sentinel node metastasis, a systematic inguinofemoral lymphadenectomy should be performed. © 2014 Wolters Kluwer Health.


Das Gracas Silva Matsubara M.,Camargo Cancer Center | de Domenico E.B.L.,Federal University of São Paulo
Journal of Cancer Education | Year: 2015

Nurses working in oncology require continuing education and nowadays distance education is a possibility. To compare learning outcomes of the professionals participating in classroom learning versus distance learning; describing the sociodemographic characteristics and digital fluency of participants; comparing learning outcomes with independent variables; assessing the adequacy of educational practices in Virtual Environment Moodle Learning through the constructivist online learning environment survey. An experimental, randomized controlled study; conducted at the A C Camargo Cancer Center, located in São Paulo, SP, Brazil. The study included 97 nurses, with average training of 1 to 2 years. A control group (n = 44) had face to face training and the experiment group (n = 53) had training by distance learning, both with identical program content. The dependent variable was the result of learning, measured by applying a pre-assessment questionnaire and post-intervention for both groups. The sociodemographic and digital fluency data were uniform among the groups. The performance of both groups was statistically significant (p 0.005), and the control group had a greater advantage (40.4 %). Distance education has proven to be an effective alternative for training nurses, especially when they have more complex knowledge, more experience in the area and institutional time. Distance Education may be a possibility for the training of nurses for work in oncology. The association of age, training time and the institution, and the experience in Oncology interfered in the performance of both groups. © 2015 American Association for Cancer Education


The treatment strategies for adult soft tissue sarcomas of the extremities place an emphasis on local control, maintenance of limb function, and quality of life. Surgery is the mainstay of treatment for soft tissue sarcomas. Radiotherapy and chemotherapy are also both important treatments used in these patients to optimize the outcomes of limb sparing surgery. Compared to external beam radiation therapy, brachytherapy has the advantage of delivering a concentrated dose to the tumor, whilst sparing the normal tissues. Consequently, early and late complications such as bone fractures and subcutaneous fibrosis are potentially avoided by using brachytherapy. The evidence and clinical outcomes of HDR brachytherapy in soft tissue sarcomas of the extremities are described in this paper by means of a literature review. © 2014 Termedia Sp. z o.o. All rights reserved.

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