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1

FRANCESCHINI, FABIO GIULIO. « Correlazioni esistenti tra parodontologia e medicina orale. Lesioni delle mucose orali versus malattia parodontale. Aspetti diagnostici e terapeutici ». Doctoral thesis, Università degli Studi di Milano-Bicocca, 2011. http://hdl.handle.net/10281/19339.

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Our study describes the relationship between periodontal disease and oral mucosal lesions. At first we analysed classification criteria of oral lesions in order to provide a point of reference for an adequate description. In a second time we started to describe periodontal disease, that is a common pathology all over the world with high costs for therapy and rehabilitations. Also classification of periodontal disease is important, because there are different types of disease, with various clinical aspects. We used the AAP (American Academy of Periodontology) classification of 1999, that reports: gingivitis, chronic periodontitis, aggressive periodontitis, periodontitis related to systemic diseases, necrotizing periodontitis, periodontal abscess, periodontitis associated to endodontic lesions, acquired and developed deformities and conditions. In the second part we described oral mucosal lesions, starting with infective diseases on the basis of etiologic agents: bacterial, viral (with viral neoplasms), fungal, parasitic and syphilitic lesions. In the third part we described autoimmune lesions, in particular the erythema multiform. In the fourth part we analysed the neoplastic and pre-neoplastic diseases, in particular squamous cell carcinoma and leukoplakia. Fifth section is dedicated to “border lesions”, because they are studied both in periodontology and oral medicine. These diseases are the desquamative gingivitis, lichen planus, pemphigoid, pemphigus, linear IgA disease, chronic ulcerative stomatitis and epulid.
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Cesari, Valentina <1985&gt. « High sensitivity analysis of BRAF mutations in neoplastic and non-neoplastic thyroid lesions ». Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6360/1/Cesari_Valentina_tesi.pdf.

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The clonal distribution of BRAFV600E in papillary thyroid carcinoma (PTC) has been recently debated. No information is currently available about precursor lesions of PTCs. My first aim was to establish whether the BRAFV600E mutation occurs as a subclonal event in PTCs. My second aim was to screen BRAF mutations in histologically benign tissue of cases with BRAFV600E or BRAFwt PTCs in order to identify putative precursor lesions of PTCs. Highly sensitive semi-quantitative methods were used: Allele Specific LNA quantitative PCR (ASLNAqPCR) and 454 Next-Generation Sequencing (NGS). For the first aim 155 consecutive formalin-fixed and paraffin-embedded (FFPE) specimens of PTCs were analyzed. The percentage of mutated cells obtained was normalized to the estimated number of neoplastic cells. Three groups of tumors were identified: a first had a percentage of BRAF mutated neoplastic cells > 80%; a second group showed a number of BRAF mutated neoplastic cells < 30%; a third group had a distribution of BRAFV600E between 30-80%. The large presence of BRAFV600E mutated neoplastic cell sub-populations suggests that BRAFV600E may be acquired early during tumorigenesis: therefore, BRAFV600E can be heterogeneously distributed in PTC. For the second aim, two groups were studied: one consisted of 20 cases with BRAFV600E mutated PTC, the other of 9 BRAFwt PTCs. Seventy-five and 23 histologically benign FFPE thyroid specimens were analyzed from the BRAFV600E mutated and BRAFwt PTC groups, respectively. The screening of BRAF mutations identified BRAFV600E in “atypical” cell foci from both groups of patients. “Unusual” BRAF substitutions were observed in histologically benign thyroid associated with BRAFV600E PTCs. These mutations were very uncommon in the group with BRAFwt PTCs and in BRAFV600E PTCs. Therefore, lesions carrying BRAF mutations may represent “abortive” attempts at cancer development: only BRAFV600E boosts neoplastic transformation to PTC. BRAFV600E mutated “atypical foci” may represent precursor lesions of BRAFV600E mutated PTCs.
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Cesari, Valentina <1985&gt. « High sensitivity analysis of BRAF mutations in neoplastic and non-neoplastic thyroid lesions ». Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6360/.

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The clonal distribution of BRAFV600E in papillary thyroid carcinoma (PTC) has been recently debated. No information is currently available about precursor lesions of PTCs. My first aim was to establish whether the BRAFV600E mutation occurs as a subclonal event in PTCs. My second aim was to screen BRAF mutations in histologically benign tissue of cases with BRAFV600E or BRAFwt PTCs in order to identify putative precursor lesions of PTCs. Highly sensitive semi-quantitative methods were used: Allele Specific LNA quantitative PCR (ASLNAqPCR) and 454 Next-Generation Sequencing (NGS). For the first aim 155 consecutive formalin-fixed and paraffin-embedded (FFPE) specimens of PTCs were analyzed. The percentage of mutated cells obtained was normalized to the estimated number of neoplastic cells. Three groups of tumors were identified: a first had a percentage of BRAF mutated neoplastic cells > 80%; a second group showed a number of BRAF mutated neoplastic cells < 30%; a third group had a distribution of BRAFV600E between 30-80%. The large presence of BRAFV600E mutated neoplastic cell sub-populations suggests that BRAFV600E may be acquired early during tumorigenesis: therefore, BRAFV600E can be heterogeneously distributed in PTC. For the second aim, two groups were studied: one consisted of 20 cases with BRAFV600E mutated PTC, the other of 9 BRAFwt PTCs. Seventy-five and 23 histologically benign FFPE thyroid specimens were analyzed from the BRAFV600E mutated and BRAFwt PTC groups, respectively. The screening of BRAF mutations identified BRAFV600E in “atypical” cell foci from both groups of patients. “Unusual” BRAF substitutions were observed in histologically benign thyroid associated with BRAFV600E PTCs. These mutations were very uncommon in the group with BRAFwt PTCs and in BRAFV600E PTCs. Therefore, lesions carrying BRAF mutations may represent “abortive” attempts at cancer development: only BRAFV600E boosts neoplastic transformation to PTC. BRAFV600E mutated “atypical foci” may represent precursor lesions of BRAFV600E mutated PTCs.
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Kanter-Lewensohn, Lena. « Tumor progression in melanocytic lesions : biological and diagnostic implications / ». Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3623-4/.

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Nicholson, J. « Predicting malignancy in pre-neoplastic lesions detected during screening for pancreatic cancer ». Thesis, University of Liverpool, 2017. http://livrepository.liverpool.ac.uk/3008012/.

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Background: Screening is offered to individuals who have an identified increased risk of pancreatic cancer. Such risks may be increased because of a family history or a known genetic mutation which has been shown to confer increased risk. Amongst those being screened intraductal papillary mucinous neoplasm (IPMN) of the pancreas are increasingly common entities being detected incidentally; their risk of malignancy can be as high as 85%. Consensus guidelines exist for the management of these lesions – the morbidity associated with pancreas resection is as high as 50%. We set out to identify a marker which could be used to identify those IPMN which should be resected and those which may be safely observed. Methods: Individuals were identified from the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC) or patients identified in Liverpool or Hedielberg with cystic lesions and/or pancreatic cancer. Cancer screening was performed by imaging and with molecular analysis (including mutation analysis of TP53) of pancreatic juice obtained by endoscopic retrograde cholangiopancreatography (ERCP). Matched tissue sections and frozen sections of pancreatic tissue from 73 patients who underwent resection for IPMN were assessed histologically and for mutations in TP53 status using a novel limiting dilution Next Generation Sequencing technique. Results were assessed relative to clinical outcomes. Results: Amongst those 29 individuals who were screened with ERCP, 11 had IPMN, 7 IPMN with cancer (IPMC) and 3 pancreatic ductal adenocarcinoma (PDAC). The remaining cases were benign neoplastic or inflammatory conditions. Kaplan-Meier survival analysis at 5 years found that the presence of p53 mutation in the tissue was a better prognostic marker of survival than the histological diagnosis alone (p=0.0152 vs. p=0.0819). Sensitivity and specificity of p53 mutation as a predictor of survival was calculated as 0.89 and 0.95 respectively. There was 100% correlation between the p53 mutational status of the resected tissue and the pancreatic juice obtained at ERCP. When ERCP was assessed as a method for screening, however, there was found to be an unacceptably high incidence of post-ERCP pancreatitis (PEP) 7 cases of PEP in 16 ERCPs (44%). This rate was shown to be significantly reduced to 15% (6/40) with the use of pancreatic stent and diclofenac, but the overall prevalence of PEP was 23.2% over 14 years. There were no cases of PEP amongst those individuals being screened because of hereditary pancreatitis. Of 27 IPMN cases with frozen tissue 23 individuals had TP53 mutations. Seven cases died of pancreatic cancer after resection. Kaplan-Meier survival analysis revealed that one mutation p.L264R predicted survival regardless of histology (p= < 0.0001). The mutation was present in 6 of the 7 cases who died and in none of those who survived to 5 years. Mutation specific PCR was used to validate results showing that p.L264R discriminated between survivors and IPMN cases who died of cancer (AUC = 0.79). Conclusions: IPMN continues to cause concern and uncertainty among those individuals being screened for cancer who are largely well and asymptomatic. The p.L264R mutation could be used to differentiate those IPMN which result in poor survival to facilitate potentially curative surgery. The mutation may be present in pancreatic juice which can be collected endoscopically as a screening tool. The use of prophylactic measures to reduce PEP may be considered sufficient to bring the risk of complications to an acceptable level when compared to the relative certainty of prognosis afforded by a positive test for p.L264R.
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Giannoudis, Athina. « Human papillomaviruses in squamous intraepithelial lesions of the cervix ». Thesis, University of Liverpool, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.250230.

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Al-Bakkal, Ghasaq H. « Human papillomavirus type 16 E6 gene expression in neoplastic oral lesions of immunosuppressed individuals ». Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape17/PQDD_0002/MQ35050.pdf.

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Al-Kana, Randah. « Immunocytochemical detection of estrogen receptors in human breast cancer and in non-neoplastic lesions ». Thesis, McGill University, 1988. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=61739.

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Keenan, Stephen J. « Quantitative analyses and classification of cervical intraepithelial neoplasia (CIN) using automated machine vision ». Thesis, Queen's University Belfast, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.368597.

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Scopelliti, Michele. « Nuova tecnica di autotrapianto di fegato in un modello sperimentale porcino con preservazione del graft in machine perfusion : applicazione clinica per neoplasie epatiche non resecabili tramite chirurgia convenzionale ». Doctoral thesis, Università degli studi di Padova, 2015. http://hdl.handle.net/11577/3424160.

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A NEW LIVER AUTOTRANSPLANTATION TECHNIQUE USING SUBNORMOTHERMIC MACHINE PERFUSION FOR ORGAN PRESERVATION IN A PORCINE MODEL: CLINICAL INDICATION FOR THE TREATMENT OF UNRESECTABLE HEPATIC LESIONS WITH CONVENTIONAL SURGERY ! Abstract ! BACKGROUND: Hepatic resection is the gold standard of therapy for primary and secondary liver tumors, but few patients are eligible for this procedure because of the extent of their neoplasms. Improvements in surgical experience of liver transplantation (OLT), hepatic resection and preservation with sub-normothermic machine perfusion (MP) have prompted the development of a new model of large animal autotransplantation. This sperimental model allowed the clinical application of Ex situ ex vivo liver surgery to treat otherwise unresectable liver tumors. METHODS: Landrace pigs were used in this experiment. After intubation, hepatectomy was performed according to the classic technique. The intrahepatic caval vein was replaced with a homologous tract of porcine thoracic aorta. The liver was perfused with hypothermic Celsior solution followed by MP at 20 °C with oxygenated Krebs solution. An hepatectomy was performed during the period of preservation, which lasted 120 minutes, then the liver was reimplanted into the same animal in a 90° counterclockwise rotated position. The anastomoses were performed in the classic sequence. Samples of intravascular fluid, blood and liver biopsies were obtained at the end of the period of preservation in MP and again at 1 and 3 hours after liver reperfusion to evaluate graft function and microscopic damage. Then we report the clinical application of the model on 8 clinical cases described individually. After appropriate preoperative study and with the permission of the ethics committee, the patients underwent ex situ liver resection. RESULTS: All animals survived the procedure. The peak of aspartate aminotransferase was recorded 60 minutes after reperfusion and the peak of alanine aminotransferase and lactate dehydrogenase after 180 minutes. Histopathologic examination under the light microscope identified no necrosis or congestion. Intraoperative echo-color Doppler documented good patency of the anastomosis and normal venous drainage. Among the patients who underwent surgical treatment the overall mortality during the mean follow-up of 493 days , was 25 % ( 12.5 % for sepsis and 12.5 % for recurrence of disease ) . The 66.6 % of patients in life is alive and currently free of neoplastic disease , 33.3 % are alive with disease recurrence in chemotherapy and in good overall clinical condition . CONCLUSION: This system made it possible to perform hepatic resections and vascular reconstructions ex situ while preserving the organ with mechanical perfusion (ex vivo, ex situ surgery). Improving surgical techniques regarding autotransplantation and our understanding of ischemia-reperfusion damage may enable the development of interesting scenarios for aggressive surgical treatment (Ex situ, ex vivo liver surgery ) or radiochemotherapy options to treat primary and secondary liver tumors unsuitable for conventional in situ surgery.
NUOVA TECNICA DI AUTOTRAPIANTO DI FEGATO IN UN MODELLO SPERIMENTALE PORCINO CON PRESERVAZIONE DEL GRAFT IN MACHINE PERFUSION: APPLICAZIONE CLINICA PER NEOPLASIE EPATICHE NON RESECABILI TRAMITE CHIRURGIA CONVENZIONALE. !INTRODUZIONE : La resezione epatica rappresenta il gold standard per il trattamento dei tumori del fegato primitivi e secondari , tuttavia solo una minoranza di pazienti possono essere sottoposti a tale trattamento poichè spesso la diagnosi di neoplasia avviene in stadi di malattia neoplastica troppo avanzata. L’esperienza tecnica del nostro Centro legata alla chirurgia epatica resettiva e sostituitiva, associata ai nostri studi sul danno da ischemia-riperfusione e sull’allestimento di nuove metodiche di preservazione del graft tramite l’utilizzo della Machine Perfusion (MP), ci ha permesso di sviluppare un sistema di perfusione meccanica sub-normotermica per preservare il fegato, che consente di eseguire resezioni epatiche e complesse ricostruzioni vascolari ex-situ durante la perfusione meccanica (chirurgia ex-vivo, ex-situ). Questo modello sperimentale ha permesso l' applicazione clinica della chirurgia epatica ex vivo ex situ per il trattamento di tumori al fegato altrimenti non operabili . METODI : Per l’esecuzione dell’esperimento abbiamo utilizzato 5 maiali Landrace x Large White . Dopo l’ intubazione è stata eseguita l’ epatectomia secondo la tecnica classica . La vena cava intraepatica è stata sostituita con un omologo tratto di aorta toracica di suino. Il fegato è stato perfuso con soluzione di preservazione ipotermica (Celsior solution 60 mL/kg in aorta e 30 mL/kg in vena porta) a 4°C. Quindi il fegato veniva posto in un sistema di perfusione ossigenato e continuamente perfuso per 120 minuti con soluzione di Krebs (MP). Durante la preservazione in Machine Perfusion, veniva eseguita una epatectomia tramite dissezione a freddo con forbici. Dopo 120 minuti di preservazione in MP, il fegato veniva reimpiantato nello stesso animale (auto- trapianto) ruotato di 90° in senso antiorario. Le anastomosi sono state eseguite nella sequenza classica . Campioni sia di sangue che di liquido di preservazione venivano prelevati per determinare i livelli di AST, ALT, LDH e lattati dopo il termine del periodo di preservazione con MP e nuovamente a un ora e a tre ore dalla riperfusione epatica. Di seguito viene descritta l'applicazione clinica di questo modello sperimentale su 8 casi clinici descritti individualmente . Dopo adeguato studio preoperatorio e con il permesso del comitato etico , i pazienti sono stati sottoposti a resezione epatica ex situ. RISULTATI: Tutti gli animali sono sopravvissuti alla procedura . Il picco di aspartato aminotransferasi è stato registrato 60 minuti dopo la riperfusione e il picco di alanina aminotransferasi e lattico deidrogenasi dopo 180 minuti. L’indagine istopatologica alla microscopia ottica non ha documentato reperti significativi di necrosi e congestione all’analisi dei preparati esaminati. L’Eco color Doppler intraoperatorio ha documentato buona pervietà delle anastomosi e normale drenaggio venoso . Tra i pazienti sottoposti a trattamento chirurgico la mortalità globale su un follow-up medio di 493 giorni , è stata del 25 % ( 12,5 % per sepsi e 12,5% per recidiva di malattia ) . Il 66,6 % dei pazienti in vita è vivo e attualmente libero da malattia , il 33,3 % sono vivi con recidiva di malattia in trattamento chemioterapico. ! CONCLUSIONI : Questo modello sperimentale ha consentito di effettuare resezioni epatiche e ricostruzioni vascolari ex situ preservando l'organo con la perfusione meccanica ( chirurgia ex vivo-ex situ ) . Il miglioramento delle tecniche chirurgiche relative all’autotrapianto e la miglior comprensione del danno da ischemia-riperfusione potrebbe rendere possibile lo sviluppo di scenari interessanti per il trattamento di tumori epatici primitivi e secondari non suscettibili di trattamento chirurgico convenzionale.
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KYRIAKIDOU, KYRIAKI. « Medicina rigenerativa ossea : ipotesi di riparazioni ingegnerizzate di lesioni ossee neoplastiche ». Doctoral thesis, Università Politecnica delle Marche, 2008. http://hdl.handle.net/11566/241866.

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Willaime, Julien Michel Yvon. « Use of intensity- and spatial-based image descriptors to characterise and quantify neoplastic lesions in positron emission tomography ». Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/18787.

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Intra-tumour biological heterogeneity is a characteristic shared by all cancers and is thought to contribute to treatment failure. Within-lesion spatial heterogeneity can be qualitatively visualised in Positron Emission Tomography (PET) imaging. Quantifying the variability of the biological processes and the complexity of the signal being measured in PET oncology is essential. The aim of this thesis was to develop and validate intensity- and spatial-based metrics to quantitatively account for the complexity of radiotracer uptake and to annotate intra-tumour PET heterogeneity. Texture analysis was employed to characterise the in vivo tumour heterogeneity of cell proliferation in breast tumours using 18F-fluorothymidine (18F-FLT) PET. The repeatability of the feature measurements was assessed in patients who had two PET scans prior to therapy. Associations between features at baseline and clinical response measured after three cycles of chemotherapy were explored. Associations between feature changes at one week after the start of chemotherapy and clinical response were also explored. Furthermore, the influence of analysis parameters and imaging protocols were studied. A subset of textural features produced reliable measurements and were associated with treatment response. A technique based on multifractal analysis was also developed for characterising the space-filling properties of an object of interest in PET imaging. The derived spatial index was further combined with intensity metrics and the technique was shown to correct for partial volume effects. The method was illustrated on mathematical objects, validated on test-retest 18F-FLT PET clinical data and applied to realistic PET simulations. This work contributes to the demonstration that intensity- and spatial-based image analysis methods can supplement existing methods in PET quantification studies. These techniques provide some improvements on existing methods to derive classical quantitative PET indices and permit extraction of additional information to further characterise patient populations in the clinical setting and in relation to therapy.
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Tate, David James. « Endoscopic Resection Of Early Neoplastic Colonic Lesions – Towards A Safe, Minimally-Invasive, Evidence-Based Endoscopic Alternative To Surgery ». Thesis, The University of Sydney, 2018. http://hdl.handle.net/2123/20817.

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Colorectal cancer (CRC) arises from pre-malignant polyps, a process effectively interrupted by colonoscopic polypectomy (CP). Incomplete or poor-quality CP attenuates this effect. Large sessile colorectal polyps (≥20mm) [laterally spreading lesions – LSL] harbour a greater risk of malignancy versus smaller polyps but the majority can be safely and effectively removed in a single session by CP. This thesis contains four themes all relating to colonoscopic polypectomy. Theme 1 is entitled quality and safety in colonoscopic polypectomy. Within this theme Chapter 2 describes a published prospective imaging study of 141 sessile serrated polyps (SSP). The study concluded that the accuracy of a standardised protocol for endoscopic assessment of dysplasia within SSP was 95.0% as compared to the gold standard of blinded specialist gastrointestinal pathologists. This may be an important important tool for reducing rates of interval cancer after colonoscopy via the recognition and complete resection of dysplastic SSP. Chapter 3 contains a published pilot study of 41 SSP successfully removed using piecemeal cold snare polypectomy. There was no incidence of delayed bleeding or perforation. If confirmed in larger studies, this finding could reduce the burden of removing SSPs on patients and healthcare systems, particularly by the avoidance of clinically significant post-endoscopic bleeding. Chapter 4 contains a published study demonstrating that a simple score to determine the complexity of polypectomy (the SMSA score) could predict robust outcomes after polypectomy of large colorectal polyps. Lower SMSA scores (SMSA 2 versus 4) predicted a greater likelihood of EMR success (OR 13.34 [95% confidence interval {95% CI} 1.85-96.27]) and a lesser likelihood of adverse events including delayed bleeding (OR 0.36 [95% CI 0.22-0.58]), adenoma recurrence (OR 0.19 [95% CI 0.09-0.41]) and need for surgery at 2 weeks (OR 0.53 [95% CI 0.4-0.71]) (SMSA 3 versus 4). This information is highly relevant for patient consent since it can be determined by simple criteria known prior to the procedure, often present in referring endoscopy report. In addition, this data lends itself to the establishment of polyp-specific key performance metrics for those performing endoscopic resection. It can also be applied to time and resource management at an endoscopy unit level, for example to determine the estimated procedure length for a particular polyp or the suitability of a particular polyp for training purposes. Chapter 5 contains an unpublished study of the responses of 707 endoscopists in 7 countries to an online survey indicating that cold snare polypectomy is underutilised for diminutive and small polypectomy, submucosal invasive cancer is underappreciated by endoscopists and benign large colorectal polyps are routinely referred for surgery. Theme 2 is entitled refining the management of complex large colonic laterally spreading lesions (LSL). Within this theme Chapter 7 contains a published study of two-stage endoscopic mucosal resection. This describes a technique where, if a resection cannot be completed in a single session, the LSL may be removed at a second session within 2-3 months, with 81.8% of cases avoiding surgery to long-term follow up. Chapter 8 contains a published study on cold-forceps avulsion and adjuvant snare-tip soft coagulation (CAST). This is a simple cost-effective technique to resect non-lifting adenoma, a situation which often results in failed or incomplete resection of LSL. Of lesions completely resected using this technique, 99% eligible for surveillance avoided surgery to long-term follow up. Chapter 9 contains a published prospective study of LSL at the appendiceal orifice (AO). These LSL are traditionally described as difficult to resect endoscopically and are often an indication for surgery. The study demonstrated that if the distal margin of an LSL can be visualised within the AO and there is no endoscopic imaging evidence of submucosal invasive cancer that 91% of patients undergoing surveillance avoided surgery to a median of 18 months. Theme 3 is entitled mitigating recurrence after endoscopic resection of large colonic laterally spreading lesions. Within this theme Chapter 10 contains a published randomised controlled study of 400 lesions demonstrating that the technique of thermal ablation of the post EMR defect resection margin reduces the risk of polyp recurrence by four times. Chapter 11 contains a published study demonstrating that the temporal pattern of adenoma recurrence after EMR more likely if the LSL is ≥40mm in maximum dimension, contains high grade dysplasia or there was bleeding during the procedure requiring endoscopic control methods. Finally theme 4 is entitled future tools and methods for collaborative research in clinical endoscopic practice. Within this theme Chapter 12 contains details of a next-generation validated data collector for endoscopic resection procedures which in the future may allow greater collaboration between centres undertaking endoscopic resection, quality of data captured, correlation of endoscopic imaging, histologic and procedural data and the co-ordination of high quality observational and randomised studies. This thesis therefore contains 8 published studies that iterate the effectiveness of colonoscopic polypectomy. The future of the management of early neoplastic colonic lesions is endoscopic via an evidence-based patient and polyp specific approach.
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Middleton, Kate. « Analysis of papillomavirus E1^E4 expression with respect to epithelial proliferation and differentiation in productive and neoplastic papillomavirus lesions ». Thesis, University College London (University of London), 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.405554.

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Marconi, Barbara. « Analisi delle complicanze dermatologiche e valutazione dell'efficacia della PDT sulle lesioni neoplastiche nei pazienti trapiantati ». Doctoral thesis, Università Politecnica delle Marche, 2009. http://hdl.handle.net/11566/242013.

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Distler, Marius, Daniela E. Aust, Jürgen Weitz, Christian Pilarsky et Robert Grützmann. « Precursor Lesions for Sporadic Pancreatic Cancer : PanIN, IPMN, and MCN ». Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-147337.

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Pancreatic cancer is still a dismal disease. The high mortality rate is mainly caused by the lack of highly sensitive and specific diagnostic tools, and most of the patients are diagnosed in an advanced and incurable stage. Knowledge about precursor lesions for pancreatic cancer has grown significantly over the last decade, and nowadays we know that mainly three lesions (PanIN, and IPMN, MCN) are responsible for the development of pancreatic cancer. The early detection of these lesions is still challenging but provides the chance to cure patients before they might get an invasive pancreatic carcinoma. This paper focuses on PanIN, IPMN, and MCN lesions and reviews the current level of knowledge and clinical measures.
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Zaccaro, Cristina <1987&gt. « Evaluation of Tumor M2 Pyruvate Kinase and Endocannabinoid System Expression in Colorectal Preneoplastic and Neoplastic Lesions : Possible Use for non Invasive Diagnosis ». Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2016. http://amsdottorato.unibo.it/7357/4/Zaccaro_Cristina_tesi..pdf.

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Colorectal cancer (CRC) is a multistep process that goes through adenoma-carcinoma sequence. Many forms of CRC may be prevented by routine control, which can detect precancerous neoplasm before they undergo malignant transformation (123). For this reasons we hypothesized that a combination of simple faecal tests, may help to identify patients with higher risk of adenomas and/or CRC. The aim of this study is to clarify whether FOBT, enzyme Tumor M2-PK and endocannabinoid system molecules (CB1, CB2, FAAH), could represent diagnostic non-invasive markers, alone or in combination, for early diagnosis of CRC and its precancerous lesions. In a pivotal study we analyzed a selected population, using i-FOBT and quantitative ELISA stool test for t-M2-PK detection. i-FOBT showed the highest specificity and PPV (88.8% and 52.7% respectively); M2-PK had the best sensitivity (87.2%); the best results it obtained with combination tests; in fact if our patients had been subjected only to the i-FOBT test, 33 high risk adenoma and 14 CRC would not have been diagnosed. Supported by these findings, we analyzed a consecutive population: patients with both positive tests have only 31.6% risk of developing CRC; in contrast, patients negative to both markers, cancer risk was less than 2% (VPN 98.5%). We confirmed, also with immuoistochemistry, that increase of tumour M2-PK in patients with CRC, as well as in stool samples, is correlated with pre neoplastic stages. To investigate the expression of endocannabinoid system in CRC, CB1, CB2 and FAAH markers were studied immunochemically in different stages and normal tissue. CB receptors and their ligands, as well as FAAH inhibitions, showed to have a protective role in colorectal cancer. They, in combination with other markers (such as t-M2-PK and FOBT), could be indicated to develop a non-invasive test for an early diagnosis of cancerous and pre-cancerous colorectal lesions.
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Zaccaro, Cristina <1987&gt. « Evaluation of Tumor M2 Pyruvate Kinase and Endocannabinoid System Expression in Colorectal Preneoplastic and Neoplastic Lesions : Possible Use for non Invasive Diagnosis ». Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2016. http://amsdottorato.unibo.it/7357/.

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Colorectal cancer (CRC) is a multistep process that goes through adenoma-carcinoma sequence. Many forms of CRC may be prevented by routine control, which can detect precancerous neoplasm before they undergo malignant transformation (123). For this reasons we hypothesized that a combination of simple faecal tests, may help to identify patients with higher risk of adenomas and/or CRC. The aim of this study is to clarify whether FOBT, enzyme Tumor M2-PK and endocannabinoid system molecules (CB1, CB2, FAAH), could represent diagnostic non-invasive markers, alone or in combination, for early diagnosis of CRC and its precancerous lesions. In a pivotal study we analyzed a selected population, using i-FOBT and quantitative ELISA stool test for t-M2-PK detection. i-FOBT showed the highest specificity and PPV (88.8% and 52.7% respectively); M2-PK had the best sensitivity (87.2%); the best results it obtained with combination tests; in fact if our patients had been subjected only to the i-FOBT test, 33 high risk adenoma and 14 CRC would not have been diagnosed. Supported by these findings, we analyzed a consecutive population: patients with both positive tests have only 31.6% risk of developing CRC; in contrast, patients negative to both markers, cancer risk was less than 2% (VPN 98.5%). We confirmed, also with immuoistochemistry, that increase of tumour M2-PK in patients with CRC, as well as in stool samples, is correlated with pre neoplastic stages. To investigate the expression of endocannabinoid system in CRC, CB1, CB2 and FAAH markers were studied immunochemically in different stages and normal tissue. CB receptors and their ligands, as well as FAAH inhibitions, showed to have a protective role in colorectal cancer. They, in combination with other markers (such as t-M2-PK and FOBT), could be indicated to develop a non-invasive test for an early diagnosis of cancerous and pre-cancerous colorectal lesions.
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Schlecht, Nicolas. « Longitudinal relationship between human papillomavirus infection and the incidence and progression of precursor lesions of cervical neoplasia ». Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=84431.

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Introduction. Human papillomavirus (HPV) infection is now believed to be the central cause of cervical cancer. However, most of the epidemiological evidence has come from retrospective, case-control studies, which do not provide information on the dynamics of a cumulative or persistent HPV infection.
Objectives. (1) To measure the risk of incident neoplastic cervical lesions over time related to prior cumulative and persistent HPV infections. (2) To evaluate the influence of HPV viral burden on lesion risk longitudinally. (3) To estimate the progression rates and sojourn time for precursor squamous intraepithelial lesions (SILs) and how they relate to HPV infection status.
Design and methods. In 1993, the Ludwig-McGill study team began a large longitudinal study of the natural history of HPV infection and cervical neoplasia in the city of Sao Paulo, Brazil. Follow-up involved repeated measurements on individual subjects over time. 2462 women were enrolled into the study and were seen every 4 months in the first year (0, 4, 8 and 12 months), and twice yearly thereafter for a period of up to eight years. In addition to obtaining risk factor information via questionnaire, cervical specimens were taken for Pap cytology and HPV testing at every visit. Statistical analyses entailed: (1) using different modalities for defining HPV persistence by type and intensity; (2) using modeling approaches that take into account the repeated measurements of HPV and SIL over time within individuals; (3) analyzing changes in transition states between different cervical lesion grades and the rate of progression from one state to the next.
Rationale. A longitudinal, repeated measurement cohort investigation, such as this one, permits an accurate and unbiased assessment of the relationship between cumulative HPV exposure and lesion incidence. An elevated relationship between persistent HPV infections and SIL incidence supports the proposal for the application of type-specific molecular HPV DNA testing as a screening tool for the detection of cervical neoplasia. Better understanding of the natural history of disease can help in developing effective and efficient public health programs in prevention for cervical cancer.
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Gardella, Gaia. « Progetto e realizzazione di un sistema di catalogazione dell'eterogeneita di lesioni neoplastiche polmonari in immagini di tc perfusionali ». Bachelor's thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amslaurea.unibo.it/7084/.

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Progettare e realizzare un sistema di catalogazione delle varie tipologie di eterogeneità tissutale di lesioni neoplastiche polmonari, a partire dall’analisi di immagini TCp, in quanto non risulta presente in letteratura una classificazione dell’eterogeneità basata sull’analisi visuale del radiologo.
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Ho, Kam-tai, et 何金娣. « To reveal the gene copy status of MUC1 in cervical neoplasia and precursor lesions by real-time PCR ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B44659799.

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Karnik, Ketaki. « Accuracy of Computed Tomography in Determining Lesion Size in Canine Osteosarcoma of the Appendicular Skeleton ». The Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1306272071.

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Galdi, Francesca. « Studio dell'espressione delle Protein Chinasi C (PKC) alpha, beta 2, delta e theta nelle lesioni pre-neoplastiche e neoplastiche dello stomaco e correlazioni clinico patologiche con l'infezione da Helicobacter pylori ». Doctoral thesis, Università degli studi di Padova, 2010. http://hdl.handle.net/11577/3426912.

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With more than 933,937 new cases in 2002 and 700,349 deaths in the world, gastric cancer is the fourth commonest tumor and the second leading cause of cancer death after liver neoplasm (Parkin et al., 2005; Crew and Neugut, 2006). The histological evolution of gastric cancer has been characterized as progressing through a number of sequential steps. These steps begin with gastritis wich progresses to mucosal atrophy (atrophic gastritis) followed by intestinal metaplasia, dysplasia and carcinoma with subsequent metastatic dissemination (Correa, 1992). Gastric cancers are frequently deadly because symptoms do not occur until the desease is advanced, so patients generally present with locally invasive or metastatic desease. The identification of new molecular target to select those patients whith a high risk for cancer, is necessary to develop new therapeutic strategies.Our purpose was to compare the phosphoproteomic profile expression of a kinases group in epithelial gastric cell in healthy and metaplastic tissues with neoplastic gastric cells of patient affected by gastric cancer with and without metastases. Precisely, we collected 10 normal gastric biopsies and 9 metaplastic specimens from atrophic metapastic gastritis patients by gastroscopy. Further, we collected 18 neoplastic specimens during the resection surgery (9 with no lymph node metastases and 9 with lymph node metastases). All the patients (except the healthy) had in the past an infection by Helicobacter pylori. Using Reverse Phase Protein Array (RPPA) we analyzed the activity of 50 protein kinases involved in apoptosis and cell proliferation. With Kruskal Wallis test we found that PKC α, β2, δ and θ have the same profile of activation. Precisely, there is a strong signal increase between normal tissue and neoplastic tissue and this finding could suggest a real involment of these protein in cancerogenesis. Furthermore, we analyzed other protein involved in the PKC pathway and we observed the activation of P13/AKT and NF-kβ pathway. The activation of these pathway could be strongly correlate to the H. pylori infection.
Con una frequenza stimata nel 2002 di 933,937 nuovi casi e 700,349 decessi a livello mondiale, il tumore gastrico risulta essere il quarto tumore più comune nel mondo e il secondo come causa di morte correlata al cancro dopo il tumore epatico (Parkin et al., 2005; Crew and Neugut, 2006). La sequenza delle variazioni istologiche attraverso le quali si sviluppa il carcinoma gastrico è estremamente complessa. Le conoscenze attuali sui precursori del carcinoma gastrico consentono di ricostruirne l’istogenesi che conferma nella maggior parte dei casi la sequenza atrofia-metaplasia-displasia-neoplasia (Correa, 1992). L’aggressività legata alla precoce metastatizzazione di tale neoplasia, rende spesso la prognosi infausta e attualmente nessun biomarcatore (o set di biomarcatori) è considerato sufficientemente affidabile per essere utilizzato nella pratica clinica. L’identificazione di nuovi bersagli molecolari per l’individuazione dei pazienti ad alto rischio di sviluppare il tumore rappresenta dunque una necessità per lo sviluppo di nuove strategie terapeutiche più efficaci. L’obbiettivo del progetto è stato lo studio dei profili di espressione fosfoproteomica delle cellule dell’epitelio gastrico in soggetti sani e pazienti con gastrite atrofica metaplasica e il loro confronto con i profili delle cellule neoplastiche, in pazienti con carcinoma dello stomaco con e senza metastasi linfonodali. In particolare, sono state prelevate 10 biopsie di mucosa normale e 9 metaplasie mediante EGDS e 18 campioni tumorali durante l’intervento di resezione chirurgica (di cui 9 senza metastasi linfonodali “N-” e 9 con metastasi linfonodali “N+”). Tutti i pazienti affetti da metaplasia e tumote N- ed N+ hanno presentato nella loro storia clinica un’infezione da parte di Helicobacter pylori. I campioni sono stati processati mediante la tecnica dei Reverse Phase Protein Array e sono stati analizzati i livelli di fosforilazione di 50 proteine chiave coinvolte principalmente nell’apoptosi, nella sopravvivenza e nella differenziazione cellulare. Dall’analisi statistica eseguita mediante test di Kruskal Wallis è emerso un identico andamento dei segnali di fosforilazione in tutte le isoforme delle protein chinasi C analizzate (PKC α, β2, δ e θ). Più precisamente, è stato possibile osservare un incremento dei livelli di fosforilazione dal tessuto sano a quello tumorale facendo presupporre che le proteine in esame possano avere un ruolo centrale nella progressione tumorale. Inoltre, analizzando le proteine incluse nei pathway cellulari in cui sono coinvolte le protein chinasi C si è osservata l’attivazione delle vie di segnale P13/AKT e NF-kβ/Bcl2 da cui emerge una forte inibizione dei segnali apoptotici cellulari. La presenza di questi profili risulterebbe essere compatibile con una possibile attivazione delle proteine da parte di H. pylori mediata dai propri fattori di virulenza.
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Pereira, Patrícia dos Santos. « Avaliação do perfil de referenciação dos doentes com neoplasia oral para o Instituto Português de Oncologia do Porto no ano de 2013 ». Master's thesis, [s.n.], 2015. http://hdl.handle.net/10284/5236.

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Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Medicina Dentária
Introdução: O cancro oral em Portugal no passado era diagnosticado tardiamente, porém atualmente, existe um número elevado de profissionais de saúde com capacidades de realizarem o diagnóstico de cancro oral. O objetivo principal deste estudo foi conhecer o perfil de referenciação dos doentes com cancro oral, no ano de 2013 no Instituto Português de Oncologia do Porto, com o intuito de avaliar se o diagnóstico é realizado mais precocemente. Materiais e Métodos: O estudo descritivo de caso efetuado envolveu 215 doentes com neoplasias orais, a colheita de dados foi realizada através do recurso à base de dados do IPO-Porto (Registo Oncológico Hospitalar), onde foram selecionados os doentes com neoplasias orais, do ano 2013. Resultados: Dos 215 doentes com neoplasias orais, (74%) são do género masculino. Em relação à idade média foi de 61,5 anos (SD 13,7), esta era no género masculino significativamente mais baixa que no género feminino. A língua foi a localização topográfica mais prevalente com (33,0%) dos casos. Em 207 casos as neoplasias eram malignas, apenas 8 doentes tinham neoplasias benignas. O tipo histológico o mais observado foi o carcinoma espinocelular com (86%). O profissional que referenciou mais doentes com cancro oral ao IPO-Porto foi a especialidade de otorrinolaringologia (29,8%). No que diz respeito ao estádio, a maioria dos doentes encontrava-se no estádio IV (48,4%). Conclusão: Apesar de existir um número considerável de profissionais potencialmente habilitados para o diagnóstico do cancro oral, os resultados obtidos mostram que o diagnostico do cancro oral em 2013, foi realizado na maior parte dos casos tardiamente.
Introduction: Oral Cancer in Portugal last was diagnosed late, but currently, there is a high number of health professionals with capabilities to conduct the diagnosis of oral cancer. The aim of this study was to know the profile referral of patients with oral cancer in 2013 at the Portuguese Institute of Oncology of Porto, in order to assess whether the diagnosis is made earlier. Materials and Methods: The descriptive case study carried out involving 215 patients with oral cancers, the data collection was performed through the IPO-Porto database to use (Hospital Cancer Registry), where patients were selected with oral cancers, the year 2013. Results: Of the 215 patients with oral cancers, (74%) are males. Compared to the average age was 61.5 years (SD 13.7), this was significantly lower in males than in females. The language was the most prevalent topographical location with (33.0%) of cases. In 207 cases the tumors were malignant, only 8 patients had benign tumors. The histological type as squamous cell carcinoma was observed with (86%).The professional referenced more patients with oral cancer to IPO-Porto was the specialty of otolaryngology (29,8%). With respect to the stage, most of the patients was at the stage IV (48.4%). Conclusion: Although there is a potentially large number of qualified professionals in the diagnosis of oral cancer, the obtained results show that the diagnosis of oral cancer in 2013 was carried out in most cases later.
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Quispe, Machaca Liz Pilar. « Utilidad de la broncofibroscopía en el diagnóstico de neoplasia pulmonar en lesiones endoscópicamente visibles como signos de neoplasia, Hospital Nacional Edgardo Rebagliati Martins, enero – diciembre 2012 ». Bachelor's thesis, Universidad Nacional Mayor de San Marcos, 2013. https://hdl.handle.net/20.500.12672/14142.

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Determina la utilidad diagnóstica de la broncofibroscopía en el diagnóstico de cáncer pulmonar en lesiones endoscópicamente visibles como signos de neoplasia. Estudio descriptivo, observacional, transversal y retrospectivo. Se revisaron Informes de broncofibroscopía correspondientes al periodo enero a diciembre 2012 de la Unidad de broncofibroscopía del HNERM realizadas a pacientes en estudio de cáncer pulmonar. Se seleccionaron los Informes que consignaban el diagnóstico de lesión endoscópicamente visible como signos de neoplasia pulmonar (directo o indirecto). Se revisaron 772 informes de broncofibroscopía, fueron seleccionados 123 informe. En relación al tipo de alteraciones visibles por broncofibroscopía más frecuente de los signos directos: masa exofítica 38 (69.1%), irregularidad de la mucosa 12 (21.8%), y de los Signos Indirectos: estrechez de la luz: 57 (83.8%), enrojecimiento 5 (7.4%). En cuanto a los pacientes con diagnóstico definitivo de neoplasia pulmonar por cualquier método diagnóstico, encontramos que en los pacientes con diagnostico positivo de neoplasia pulmonar el PAP por aspirado bronquial fue positivo en el 57.6%, el PAP post aspirado bronquial fue positivo en el 47.8%; y el PAP por cepillado bronquial fue positivo en el 57.6% de los casos. Además encontramos que la neoplasia de mayor frecuencia fue el adenocarcinoma (56.5%), y el carcinoma escamoso (27.2%). En cuanto a la utilidad diagnóstica de la biopsia de las lesiones endoscópicamente visibles, según diagnostico endoscópico encontramos que del total de pacientes con signos directos de neoplasia maligna el 72.7% tuvieron biopsia positiva. En relación a los tipos histológicos más frecuentes del resultado de la biopsia bronquial tenemos que el tipo histológicos de mayor frecuencia fue el adenocarcinoma (42.3%), seguido del carcinoma escamoso (20.3%). La broncofibroscopía muestra utilidad diagnóstica en el cáncer pulmonar en lesiones endoscópicamente visibles como signos de neoplasia, especialmente la citología.
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Nagasaka, Tetsuro, Nobuo Nakashima, Tomoko Harada, Tomomitsu Okamoto, Shigehiko Mizutani et Hiroaki Ishiko. « Squamous Cell Carcinoma of the Vulva and Adjacent Lesions Treated at Nagoya University Hospital from 1965 to 1997 ». Nagoya University School of Medicine, 2001. http://hdl.handle.net/2237/5373.

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Bene, Alessia. « Progetto e realizzazione di un sistema di catalogazione di lesioni neoplastiche polmonari per la validazione visuale di mappe perfusionali da tomografia computerizzata ». Bachelor's thesis, Alma Mater Studiorum - Università di Bologna, 2015. http://amslaurea.unibo.it/9271/.

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La TC perfusionale (TCp) è un valido strumento per l'imaging funzionale dei tumori. Tale tecnica consente di misurare in modo oggettivo la perfusione tissutale, attraverso l'analisi matematica dei dati ottenuti effettuando scansioni TC ripetute nel tempo, dopo la somministrazione di un mezzo di contrasto iodato. Il principale obiettivo degli studi perfusionali in oncologia è la valutazione precoce dell’efficacia delle terapie anti-angiogenetiche utilizzate per bloccare la vascolarizzazione che alimenta le lesioni tumorali. Infatti, sin dal primo ciclo di terapie, è possibile rilevare se la vascolarizzazione tumorale si riduce, senza dover attendere i cambiamenti dimensionali che, in genere, avvengono tardivamente. Questa Tesi si focalizza sullo studio del carcinoma polmonare e perviene alla costruzione di un catalogo, completo di mappe colorimetriche, che sintetizza i casi analizzati, i dati relativi al paziente e alle lesioni. L'obiettivo è quindi quello di fornire uno strumento di facile consultazione che consenta di valutare vari aspetti relativi alla malattia, tra cui il tasso di accrescimento, il grado di malignità, presenza di invasione vascolare, al fine di andare sempre più verso una cura personalizzata e più efficace per i pazienti che, attualmente, sono sottoposti a soluzione terapeutica standard. Questa è, senza dubbio, la nuova frontiera della ricerca per tutte i tipi di neoplasie negli anni futuri.
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Fachini, Ana Maria Dias 1980. « Fatores de risco para diagnóstico histológico de lesão escamosa de alto grau em mulheres com resultado citológico de lesão de baixo grau = Risk factors for histological outcome of high-grade lesions in women with LSIL as shown by screening with cytology ». [s.n.], 2015. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310557.

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Orientador: Luiz Carlos Zeferino
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Introdução: A LIE-BG tem maior prevalência em mulheres jovens e a conduta expectante deve ser considerada ao invés da realização de testes para detecção de DNA-HPV. Mulheres com LIE-BG podem apresentar NIC 2 ou NIC 3 e, por este motivo, a conduta frente a este resultado deve selecionar as mulheres com maior risco para lesões mais graves. Objetivos: Avaliar a associação de alguns fatores de risco para diagnóstico histológico de lesão de alto grau em mulheres com resultado citológico de LIE-BG. Métodos: Este estudo incluiu 791 mulheres resultado de LIE-BG na citologia de rastreamento e que foram encaminhadas para colposcopia imediata. Ausência de neoplasia foi considerado o diagnóstico final em 235 mulheres nas quais a colposcopia foi normal. Outras 92 mulheres foram submetidas a excisão da zona de transformação. As variáveis analisadas foram: idade da mulher, idade de início de atividade sexual (IAS), tempo de atividade sexual (TAS) e adimplência ao rastreamento do câncer do colo útero. Resultados: Observou-se maior prevalência de NIC 3 e menor prevalência de casos sem neoplasia e NIC 1 nas mulheres com maior TAS. Inadimplência com o rastreamento está associada com maior prevalência de NIC 3 (OR=2.91; 1.27-6.63). A análise multivariada mostrou que NIC 3 está fortemente associado com TAS >10 anos quando comparado com TAS < 4 anos (OR=8.33; 1.82-33.33) e 5-9 anos (OR=7.69; 1.85-33.33) e essa associação foi limítrofe para a inadimplência com o rastreamento (OR=2.39; 0.96-5.92). A IAS não esteve associada a nenhum dos desfechos estudados. Conclusões: Mulheres com resultado citológico de LIE-BG têm maior probabilidade de revelar NIC 3 quando elas têm mais de 10 anos de tempo de atividade sexual e quando elas estão inadimplentes com o rastreamento do câncer do colo do útero. Essas mulheres devem ser encaminhadas imediatamente para colposcopia
Abstract: Introduction: LSIL shows higher prevalence in young women and conservative management should be considered other than HPV testing. Women with LSIL cytology may reveal CIN2 or CIN3 and for that reason the management should select the women with the higher risk for more severe lesions. Objectives: This study aimed to evaluate the association of some factors with histological outcome of women showing cytological LSIL. Methods: This study included 791 women with screening cytology showing LSIL who were referred to immediate colposcopy. The final diagnosis was considered "no neoplasia" for 235 women who had normal colposcopy. Other 92 women were undergone to excision of transformation zone. The variables analysed were woman's age, age of first sexual intercourse (FSI) and interval since FSI and screening compliance. Results: Higher interval since de FSI was associated with higher prevalence rate for CIN3 and lower prevalence rates for "no neoplasia" and CIN1. No screening compliance was associated with higher prevalence of CIN3 (OR=2.91; 1.27-6.63). Multivariate analysis showed that CIN 3 outcome was strongly associated with interval since FSI >10 years taking as reference <4 years (OR=8.33; 1.82-33.33) and 5-9 years (OR=7.69; 1.85-33.33) and it showed borderline association with no screening compliance (OR=2.39; 0.96-5.92). Age of FSI was not associated with any diagnosis. Conclusions: Women with LSIL screening cytology have higher probability to reveal CIN3 outcome when they have 10 or more years of since FSI and when they are non-compliant with cervical cancer screening. These women should have immediate colposcopy
Mestrado
Oncologia Ginecológica e Mamária
Mestre em Ciências da Saúde
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Resende, Leandro Santos de Araújo 1980. « Infecções simples e múltiplas por HPV em mulheres brasileiras de diferentes faixas etárias com lesões cervicais escamosas ou glandulares = Single and multiple HPV infections in Brazilian women of different age strata with squamous or glandular cervical lesions ». [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/312153.

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Orientadores: Sophie Françoise Mauricette Derchain, Silvia Helena Rabelo dos Santos
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Introdução: O câncer do colo uterino é o terceiro tipo mais prevalente no mundo e representa a quarta causa de morte por câncer entre as mulheres. No Brasil, estima-se que 17,540 mulheres foram diagnosticadas com essa neoplasia no ano de 2012. A infecção persistente pelo Papillomavirus humano (HPV) de alto risco (hr-HPV) e é considerada fator causal e necessário para lesões precursoras e câncer invasor. Já foram identificados mais de 100 tipos de HPVs. Os HPVs 16 e 18 são reconhecidos, no mundo, como os maiores responsáveis pelo desenvolvimento dessa doença. Objetivos: Descrever a prevalência e a distribuição, por idade, de infecções simples e múltiplas por diferentes tipos de HPV em mulheres com lesões cervicais escamosas e glandulares. Sujeitos e métodos: 328 mulheres com lesões escamosas, ou glandulares intraepiteliais ou invasoras do colo uterino. Todas as amostras foram submetidas à genotipagem por hibridização reversa com sondas de 21 tipos de HPV de alto risco (hr-HPV) e 16 tipos de HPV de baixo risco (lr-HPV). A prevalência de infecções simples e múltiplas pelo HPV foi comparada de acordo com as faixas etárias. Resultados: 287 (87%) mulheres apresentaram infecção por pelo menos um tipo de HPV e 149 (52%) tinham infecção múltipla. O HPV16 foi o tipo de vírus mais prevalente na amostra, detectado em 142 casos (49% de todos os casos positivos para HPV), seguido dos outros tipos de HPV do grupo alfa-9: HPVs 58, 52, 31, 35 e 33. Infecção simples ou múltipla pelo HPV18 foi positiva em 23 casos (8% dos casos de infecção por HPV de alto risco). Praticamente todas as lesões glandulares foram associadas à infecção simples por HPVs 16 e 18. Infecções múltiplas foram, significativamente, mais prevalentes nas lesões escamosas do que nas glandulares pelos HPVs 16 e 18 (P=0,04 e 0,03, respectivamente). A prevalência de infecções múltiplas seguiu um modelo de distribuição bimodal, com pico em mulheres com menos de 29 anos e naquelas com idade entre 50 e 59 anos. Conclusão: Esta amostra sugere que a estratégia para prevenção de lesões pré-invasivas e invasivas, escamosas ou glandulares, deve ser direcionada para o HPV16 e alguns tipos virais do grupo alfa-9. Ficou claro, na amostra deste estudo, que em mulheres jovens, a prevenção de infecção pelo HPV deve cobrir os HPVs 16 e 18, principalmente
Abstract: Background: Cervical cancer ranks third in prevalence and fourth as cause of death in women worldwide. In Brazil, 17,540 women were diagnosed in 2012 with the disease. Persistent infection with high-risk HPV types is a necessary condition for the development of pre-invasive and invasive cervical neoplasia. Currently, over 100 HPV types have been identified, but HPV16 and 18 are recognized as the mayor culprits in cervical carcinogenesis. Objectives: to assess the relationships between single- (ST) and multiple-type (MT) HPV infection with patients' age and lesion pathological status. Materials and Methods: 328 patients with either squamous or glandular intraepithelial or invasive cervical lesion were selected. All subjects were tested for HPV genotypes with reverse hybridization for 21 high- (hr-HPV) and 16 low-risk (lr-HPV) probes. Prevalence of ST and MT HPV infections was compared across and age strata. Results: 287 (87%) women had at least one HPV type detected and 149 (52%) had MT infections. The most prevalent HPV type was HPV16, present in 142 cases (49% of all HPV-positive cases), followed by the alpha-9 group HPV58, 52, 31, 35 and 33, all of them from alpha-9 HPV group. ST or MT HPV18, single or in multiple infections occurred in 23 cases (8% of hr-HPV cases). Almost all glandular lesions were associated with HPV16 and 18 alone. Multiple infections were significantly more prevalent in squamous than in glandular lesion for HPV16 and 18 (P=0.04 and 0.03 respectively). The prevalence of MT infections followed a bimodal distribution; peaking in women younger 29 years and in those aged 50 to 59. Conclusions: our data indicate that prevention strategies for pre-invasive and invasive squamous lesions should be focused on HPV16 and a few alpha-9 HPV types. It is clear to us that in young women, prophylaxis must cover a large amalgam of HPV types beyond classic HPV16 and 18
Mestrado
Oncologia Ginecológica e Mamária
Mestre em Ciências da Saúde
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Hawes, Stephen Edward. « HIV-1, HIV-2, and dual infection with HIV-1 and HIV-2 are associated with increased risk for human papillomavirus (HPV) and high grade squamous intraepithelial lesions (HSIL) in Senegal, West Africa / ». Thesis, Connect to this title online ; UW restricted, 2001. http://hdl.handle.net/1773/10881.

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Scherer, Heloisa Azevedo. « Estudo retrospectivo de dermatopatias em gatos através de diagnóstico histopatológico realizados no setor de Patologia Veterinária da UFRGS, Porto Alegre (1990 - 2012) ». reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2015. http://hdl.handle.net/10183/128888.

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Dentre as especialidades veterinárias, a dermatologia, juntamente com oncologia foram as que se destacaram a partir de 1980. Cerca de 30% dos atendimentos clínicos de carnívoros domésticos são associados com alterações dermatológicas. A maior parte dos dados disponíveis inclui estudos de outros países o que pode não refletir a realidade brasileira. O objetivo deste estudo foi apresentar a prevalência das principais dermatologias neoplásicas e não neoplásicas registradas em gatos, através de diagnósticos histopatológicos de biópsias da pele, realizados no setor de Patologia Veterinária da Universidade Federal do Rio Grande do Sul (SPV-UFRGS). Um estudo retrospectivo incluiu os resultados de biópsias de pele em gatos registrados entre 1990 e 2012, nos arquivos de diagnósticos histopatológicos do SPV-UFRGS, Porto Alegre, RS, Brasil. De um total de 443 biópsias cutâneas em gatos, 308 casos foram lesões de origem neoplásica que ocorreram em maior prevalência (69%) e afetaram, mais frequentemente, gatos idosos, independente do sexo. Nessa categoria, destacaram-se carcinoma epidermoide 32,14% (99/308), fibrossarcoma 18,83% (58/308), tricoblastoma 12,66% (39/308) e mastocitoma 7,47% (23/308). Entre as lesões de causas não neoplásicas, foram analisadas as de causas micóticas 22,22% (30/135), das quais, a esporotricose apresentou maior ocorrência, com maior prevalência em machos. As lesões de causas alérgicas ocuparam a segunda posição 18,52% (25/135) em prevalência, na categoria não neoplásica. As três dermatopatias mais frequentes foram neoplásicas, micóticas e alérgicas. As neoplasias afetaram mais frequentemente gatos idosos, independentemente do sexo. O carcinoma epidermoide é a dermatopatia neoplásica de maior ocorrência, em gatos sem raça definida, sem predisposição sexual. A esporotricose é a dermatomicose mais frequente e afetou principalmente gatos machos. A escassez de dados registrados nas fichas de solicitação de biópsia reduziu conclusões adicionais. Partindo-se do princípio de que a dermatite solar pode evoluir para o carcinoma epidermoide, e considerando-se o expressivo número de diagnósticos desta alteração entre todas as amostras cutâneas 22,35% (99/443), pode-se reforçar a importância deste estudo ao dermatologista de um país tropical, dando subsídios para a indicação da prevenção à exposição solar, visando prevenir a ocorrência da doença, aumentando o bem-estar dos gatos.
Both dermatology and oncology are areas that showed high development since the 1980s. It is estimated that approximately 30% of the clinical services for domestic carnivores have been associated with dermatological alterations. Most of the available data include studies developed outside the country and may not reflect the local situation. This study aimed to presents the prevalence of the main dermatological alterations affecting domestic cats and that were diagnosed by histopathological analysis in the Setor de Patologia Veterinária of Universidade Federal do Rio Grande do Sul (SPV-UFRGS).A retrospective study included the findings observed in feline skin biopsies recorded between 1990 and 2012 in the histopathological files from the SPV-UFRGS. In a total of 443 biopsies, 308 cases showed neoplastic origin which corresponded to most lesions (69%) and affected mostly aged cats, regardless of sex. This category included epidermoid carcinoma 32,14% (99/308), fibrosarcoma 18,83% (58/308), trichoblastoma 12,66% (39/308) and mastocytoma 7,47% (23/308). Epidermoid carcinoma was the top neoplastic dermatopathy and affected mostly undefined breed cats without sexual predisposition. Among the non-neoplastic cases, the mycoses 22,22% (30/135) and the allergic lesions 18,52% (25/135) were the most prevalent. Sporotrichosis was the predominant mycotic alteration and affected especially male cats. Therefore, the three most prevalent categories of dermatopathies affecting cats were neoplasia, mycosis and allergy. Thelack of data recorded in the clinical sheets for biopsy request minimized additional conclusions. Results showed here are highlighted upon consideration that solar dermatitis may evolve to epidermoid carcinoma, which has occurred in a high prevalence in this tropical country, where the prevention to the exposition of these animals to the solar radiation assumes a great role for animal care.
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Saffi, Junior Mario Cezar. « Potencial dos fatores de risco associados aos marcadores biomoleculares RNAm IDO E RNAm CDKN2A/p16 na predição das lesões precursoras do câncer de colo uterino ». Universidade Nove de Julho, 2015. http://bibliotecadigital.uninove.br/handle/tede/1300.

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The cervical cancer is the first cancer of the female genital tract in Brazil and HPV is essential factor for carcinogenesis. The Brazilian program tracking proposes conventional cervical cytology as the primary method to detect cervical cancer, despite its low sensitivity. Risk factors associated with the spread of HPV are despised and not rely on a biomolecular tool that can increase the program offered by the Ministry of Health. The aim of this study was to determine whether the risk factors for cervical cancer may contribute to the conventional cervical cytology to increase diagnostic sensitivity and assess whether the mRNA indoleamine 2,3 dioxygenase (IDO) and mRNA CDKN2A / p16 may increase the diagnostic yield of this neoplasm. The logistic regression analysis was based on clinical variables (risk factors), cytological and biomolecular to seek an association with pathological results. The proportion of explained variance (PVE) for each variable studied was calculated by the formula omega, whereas the sensitivity, specificity, positive predictive value and negative predictive value were calculated by the formulas of Galen and Gambino. We conclude that oral contraceptive showed greater predictive power of high-grade lesions compared to other risk factors, and that both the IDO mRNA as CDKN2A mRNA / p16 may help screening of cervical cancer, either when used alone, or in conjunction with conventional cervical cytology, increasing their sensitivity and maintaining a considerable specificity.
O câncer de colo uterino apresenta-se como a principal neoplasia do trato genital feminino no Brasil, sendo o HPV fator essencial para a carcinogênese. O programa brasileiro de rastreamento propõe a citologia oncológica cervical convencional como principal método para detectar o câncer do colo uterino, apesar da sua baixa sensibilidade. Os fatores de risco associados ao contágio do HPV são desprezados e não contamos com uma ferramenta biomolecular que possa incrementar o programa oferecido pelo Ministério da Saúde. O objetivo desse trabalho foi verificar se os fatores de risco para o câncer de colo uterino podem contribuir com a citologia oncológica cervical convencional para aumentar a sensibilidade diagnóstica e avaliar se o RNAm Indoleamine 2,3 dioxigenase (IDO) e o RNAm CDKN2A/p16 podem incrementar a capacidade diagnóstica dessa neoplasia. A análise de regressão logística foi baseada nas variáveis clínicas (fatores de risco), citológicas e biomoleculares a fim de buscar uma associação com o resultado anatomopatológico. A proporção de variação explicada (PVE) por cada uma das variáveis estudada foi calculada pela fórmula ômega, enquanto que a sensibilidade, especificidade, valor preditivo positivo e o valor preditivo negativo foram calculados pelas fórmulas de Galen e Gambino. Concluímos que o uso do contraceptivo oral mostrou um maior poder de predição de lesões de alto grau em relação aos demais fatores de risco, e que tanto a RNAm IDO quanto o RNAm CDKN2A/p16 poderem auxiliar no rastreamento do câncer de colo uterino, seja quando usados de forma isolada, seja conjuntamente com a citologia cervical convencional, elevando sua sensibilidade e mantendo uma considerável especificidade.
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Rabachini, Tatiana. « Polimorfismo do códon 72 do gene p53 e risco de infecções persistentes por papiloma vírus humano (HPV) e neoplasia do colo uterino ». Universidade de São Paulo, 2002. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-14052018-121907/.

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Nos últimos anos, inúmeros estudos epidemiológicos evidenciaram a forte associação entre o carcinoma do colo uterino e a infecção por papilomavírus humano (HPV). Esta associação deriva do reconhecimento de que estes vírus codificam oncoproteínas, dentre as quais E6 e E7, que apresentam propriedades transformantes. O produto do gene E7 se liga ao produto do gene retinoblastoma que perde a sua função de regular negativamente o ciclo celular. O produto do gene E6 se liga ao produto do gene supressor de tumor p53 levando a sua degradação pela via de proteólise dependente de ubiquitina. O gene p53 é um supressor tumoral com função de regulação do ciclo celular que apresenta vários polimorfismos distintos em diversos grupos étnicos e tem sido amplamente estudado tanto em tecidos normais quanto em tecidos tumorais. O polimorfismo do códon 72 do gene i>p53 é o mais estudado e pode apresentar três alelos diferentes na população. Um alelo codifica arginina (Arg), um codifica prolina (Pro) e outro, raramente encontrado, codifica cisteína (Cys). Em 1993 foi iniciado um estudo epidemiológico da história natural da infecção por HPV e neoplasia da cérvice uterina em uma população feminina de baixa renda em São Paulo (Brasil), uma das áreas de maior risco em todo o mundo. O estudo focaliza a infecção persistente por tipos oncogênicos de HPV como evento precursor que leva à carcinogênese do colo do útero e visa entender os atributos da história natural da infecção viral e das doenças associadas ao colo uterino. Um dos objetivos deste estudo é avaliar se o polimorfismo do códon 72 do gene p53 pode, ou não, ser utilizado como marcador de predisposição ao câncer do colo do útero uma vez que um estudo inicial relatou que pacientes portando o genótipo p53Arg homozigoto seriam 7 vezes mais susceptíveis ao desenvolvimento de neoplasia da cérvice uterina que pacientes contendo o genótipo p53Pro e heterozigoto p53Pro/ Arg. Contudo, vários estudos posteriores contradizem e corroboram esses achados. O presente projeto teve como objetivos, portanto, verificar se o polimorfismo do códon 72 do gene p53 poderia estar associado a infecções persistentes por HPV e ao risco de neoplasia do colo do útero, além de comparar metodologias de detecção utilizadas por outros estudos, visando esclarecer se os motivos que levam à discordância dos resultados podem ser atribuídos a ocorrência de erros classificatórios metodológicos. Ao todo, sete metodologias de detecção foram comparadas. Apenas uma delas, PCR alelo-específica, apresentou resultado discordante das demais utilizadas. Coincidentemente, essa metodologia foi amplamente utilizada por muitos estudos que encontraram associações tanto positivas quanto negativas. Isso poderia nos dar indícios de que os erros classificatórios dependentes de metodologia poderiam influenciar os resultados de correlação entre o polimorfismo do códon 72 e o risco de neoplasia do colo do útero. As correlações observadas por este trabalho entre este polimorfismo do códon 72 e o risco de neoplasia do colo uterino não mostraram associação deste polimorfismo com o risco de infecções persistentes por HPV e as lesões precursoras do carcinoma do colo uterino.
In recent years, a number of epidemiological studies have pointed toward a strong association between cervical cancer and infection by Human Papillomavirus (HPV). This association derives from the discovery that these viruses code for oncoproteins, among them E6 and E7 that have transforming properties. The E7 gene product associates with the retinoblastoma gene product, causing the latter to lose its function as a negative regulator of the cell cycle. The E6 gene product interacts with the tumor suppressor p53 gene product, resulting in its degradation via ubiquitin dependent proteolysis. The p53 gene is a tumor suppressor that funcions in the regulation of the cell cycle. It presents a number of distinct polymorfisms in diverse ethnic groups, and has been widely studied, both in normal and tumor tissues. The polymorfism of codon 72 is the most studied, and may present three different alleles in the population. One allele codes for arginine (Arg), another codes for proline (Pro), and a third, rarely found, codes for cystein (Cys). In 1993 an epidemilogical study of the natural history of infection by HPV and its possible association with cervical neoplasia was initiated in a population of low income females in São Paulo, Brazil, one of the areas of greatest risk in the world. The study focuses on persistent infection by oncogenic types of HPV as a precursor to carcinogenesis of the cervix, and seeks to understand the attributes of the natural history of viral infection and of illnesses associated with the cervix. One of the objectives of the study is to evaluate if the polymorfisms of codon 72 of p53 can or not be used as a marker of predisposition to cervical cancer, given the finding in the initial study that patients who were homozygous for the p53Arg genotype were 7 times more susceptible to developing cervical neoplasias than those patients who were homozygous for p53Pro, or heterozygous p53 Pro/ Arg. Previous studies have been realized both supporting and disputing these findings. The current study had two main objectives: to verify if the polymorfism of p53 codon 72 could be associated with persistent infections of HPV and the risk of cervical neoplasia, as well as to compare methods of detection used by other studies, in an attempt to clarify if the discording results of past studies could be due to methodological classification errors. Seven detection methods were compared. Only one of these, allele specific PCR, presented discording results from the rest. Coincidentally, this method was widely used in a number of studies which found both positive and negative associations. This might indicate that the method-dependent classification errors could influence the results of correlation between codon 72 polymorphism and the risk of cervical neoplasia. The correlations observed by this study did not demonstrate an association between codon 72 polymorphism and the risk of persistent HPV infection and precursor lesions of cervical cancer.
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Gonzales, Espinoza Christian. « Frecuencia y caracterización anátomo-hispatológica de las lesiones encontradas en bovinos con hematuria en Oxapamapa-Pasco ». Bachelor's thesis, Universidad Nacional Mayor de San Marcos, 2003. https://hdl.handle.net/20.500.12672/1566.

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Se realizó el estudio anátomo-histopatológico de muestras de vejiga urinaria, así como hígado, riñón y bazo, de 41 vacunos con cuadros lesionales de una enfermedad conocida en la provincia de Oxapampa (Pasco) como “Hematuria“ o “Intoxicación por Machicura“. Estos fueron obtenidos a partir de la inspección de 173 animales en el camal municipal de esta provincia, buscando correlacionar esta enfermedad local con la Hematuria Vesical Enzoótica Bovina (HVEB), enfermedad del ganado vacuno de distribución mundial. En el presente trabajo, se reporta que las lesiones halladas en la vejiga urinaria fueron multifocales en el 85.37% (35/41), siendo las más frecuentes las formaciones nódulo-vasculares ulceradas, en 82.93% (34/41). En el diagnóstico histopatológico se empleó las tinciones Hematoxilina - Eosina (H.E.), e histoquímicas de Hale para mucopolisacáridos ácidos y tricrómico de Masson para tejido conectivo fibroso y/o muscular, con presencia de colágeno. Las lesiones microscópicas reportadas, corresponden a diversos procesos, tales como: los proliferativos donde destacaron los polipoides con 58.54% (24/41); entre los procesos circulatorios, resaltaron los hemorrágicos con 68.29% (28/41) y las yemas de proliferación vascular o “nidos angioblásticos” en el 46.34% (19/41); en los procesos inflamatorios fue importante la cistitis no supurativa con 70.73% (29/41). Por otro lado, los procesos neoplásicos se presentaron en el 68.30% (28/41), siendo el 41.70% de tipo epitelial y 58.30% no epitelial. Los epiteliales fueron representados por carcinomas in situ con 26.83% (11/41) y papilomas mucosos 9.76% (4/41) al igual que los carcinomas transicionales de Grado I, mientras que los no epiteliales, el hemangiosarcoma fue la neoplasia más frecuente con 34.15% (14/41), hemangiomas con 24.39% (10/41) y mixosarcoma con 14.63% (6/41). Finalmente, en una sola oportunidad se registraron: papiloma racemoso, rabdomiosarcoma, leiomiosarcoma, hemangiopericitosarcoma, carcinoma tubular, carcinoma escamoso, linfoma y una metástasis linfoide. El presente trabajo concluye que el proceso conocido como “Hematuria“ en Oxapampa, es realmente la HVEB, haciéndose el reporte oficial de esta enfermedad en nuestro país, basados en el estudio anátomo-histopatológico, asimismo se amplían los procesos reportados hasta el momento en las investigaciones sobre esta enfermedad. Esta gran variedad de lesiones vesicales, vienen a ser indicadores de una marcada alteración de los procesos celulares fisiológicos, los cuales estarían siendo originados por una o varias sustancias carcinogénicas como el Ptaquilósido (Pq), que ha sido aislado en diversos estudios del Pteridium aquilinum (Pa), helecho presente en la región del problema, pero que necesita de investigación toxicológica futura.
Anatomo-histopathologic study of urinary bladder, liver, kidney and spleen samples from 41 zebu and crossbreeding cattle with different lesions of a disease commonly named as “hematuria“ or Machicura´s intoxication in the Oxapampa province (Pasco) were done. Samples from 173 necropsied animals of abbatoir from the Municipality of this province in order to correlate Machicura´s intoxication with Bovine Enzootic Vesical Haematuria ( BEVH ), a world wide disease were obtained. It was found that the urinary bladder lesions were multifocal in 85.37% (35/41). The histopathologic diagnosis with Hematoxiline – Eosine (HE) stain, Hale´s histochemical stain for acid mucopolysaccharide and Masson trichromic for fibrous connective tissue with collagen or muscular was done. The most important microscopic lesions were proliferative polips ( 58.54% ); the circulatory process were hemorragia ( 68.29% ) and vascular proliferation or “angioblastic nests” ( 46.34% ); in the inflammatory process, the non suppurative cystitis ( 70.73% ) was the most important finding. On the other side, 68.30% were of neoplastic process and 41.70% of epithelial origen compared to 58.30% of non epithelial type. The epithelial type were composed of in situ carcinoma (26.83% ) and mucous papilomas ( 9.76 % ) the same as transitional cell carcinoma of Grade I; the non epithelial neoplastic type were distributed as follow: 34.45% by hemangiosarcoma, the most frecuent neoplasia, 24.39% by hemangioma and 14.63% by mixosarcoma. Finally, a racemous papiloma, squamous cell carcinoma, tubular carcinoma, rhabdomyosarcoma, leiomyosarcoma, hemangiopericytosarcoma, lymphoma and a lymphoid metastasis were observed in one opportunity. The conclusion was that the well known process of hematuria that occured in Oxapampa was the same as BEVH and the official report of this disease in our country based on anatomo-histopathologic study was done. The great variety of vesical lesions were the indicators of the marked alterations of the normal biological cell process that could be originated by one or various carcinogenic sustances as the ptaquiloside ( Pq ) which was isolated from the Pteridium aquilinum ( Pa ) a bracken fern presented in the studied region, but a lot of toxicologic studies need to be done.
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Maciag, Paulo Cesar. « Infecções por papilomavírus humano e neoplasia do colo uterino : efeito do polimorfismo dos genes HLA-DRB1 E -DQB1 e respostas linfoproliferativas contra peptídeos virais ». Universidade de São Paulo, 2002. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-31082018-143208/.

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Infecção persistente por tipos oncogênicos de papilomavírus humano (HPV) é considerada como o principal fator de risco para desenvolvimento de carcinoma invasivo do colo uterino (CCU) e de lesões intraepiteliais cervicais (SIL). Fatores genéticos do hospedeiro, como o polimorfismos de genes HLA (human leukocyte antigen), também têm sido implicados na suscetibilidade a estas patologias e à infecção por (HPV), como observado em diversos estudos caso-controle. Neste estudo investigou-se em uma coorte de mulheres (Ludwig-McGill cohort) se a variabilidade dos genes HLA-DRB1 e -DQB1 influenciam na história natural das infecções por HPV e no risco de SIL. A tipificação de DRB1 e DQB1 foi realizada em 620 amostras provenientes de um estudo epidemiológico prospectivo. A positividade para HPV foi testada em amostras da mesma paciente coletadas a cada 4 meses, obtidos durante o primeiro ano de seguimento, enquanto os resultados de citologia perfazem os 2 primeiros anos de seguimento. Infecções persistentes de curta ou longa duração foram definidas como 2 e 3 resultados consecutivos positivos para o mesmo tipo de HPV, respectivamente. As associações foram estimadas através de razões de chance e intervalos de confiança de 95%, ajustadas para potenciais fatores de confusão. Os resultados obtidos indicam que a prevalência da infecção por HPV e o risco de persistência variam dependendo do haplótipo HLA. O haplótipo DRB1*0301-DQB1*0201 mostrou-se protetor contra a infecção por HPV, e DRB1*1102-DQB1 *0301 contra infecções persistentes. Já os haplótipos DRB1*1601-DQB1*0502 e DRB1 *0807-DQB1*0402 foram fatores de risco para infecções persistentes por HPV. Não foi observada uma forte concordância entre risco de infecção por HPV e risco de SIL associados a determinado HLA, em parte porque o número de pacientes com SIL foi um fator limitante neste estudo. Um risco aumentado de SIL, independente da infecção por HPV, foi associado com DRB1*0301 e DR12. Portadoras de DR4 e DQB1*0601 tiveram uma maior probabilidade de desenvolver SIL e HSIL, respectivamente. Uma associação negativa entre o alelo DQB1*0301 e HSIL foi verificada. Análise do dimorfismo na posição 86 da cadeia β de HLA-DR mostrou que valina nesta posição tem um efeito protetor para prevalência e persistência de infecção por HPV, e maior risco de SIL no grupo com infecções transitórias por HPV. Em outra análise, investigamos a distribuição de grupos alélicos de DRB1 em uma série independente de amostras provenientes de pacientes com CCU. Observamos um risco diminuído de desenvolvimento de CCU associado a DR3. Por outro lado, DR4 e DR8/12 mostraram-se fatores de risco para o CCU nesta população. Estes resultados sugerem que o polimorfismo de HLA desempenha um papel na história natural das infecções por HPV, SIL e CCU. Também analisamos respostas linfoproliferativas em pacientes com CCU, contra peptídeos derivados de E6 e E7 de HPV16. As respostas positivas foram mais freqüentes contra peptídeos de E6 do que E7. Não observamos resposta contra um peptídeo ou região em particular. Parte desta diversidade nas respostas linfoproliferativas pode ser relacionada com o polimorfismo de genes HLA e seu papel na seleção de epítopos.
Persistent infection with oncogenic human papillomavirus (HPV) is the major risk factor for the development of malignant lesions in the uterine cervix. Host factors have also been implicated in the pathogenesis of these diseases. Associations between human leukocyte antigen (HLA) polymorphisms and cervical cancer, precursor lesions or HPV infections have been reported by case-control studies in several populations. This study investigated through cohort analysis if human leukocyte antigen (HLA)-DRB1 and DQB1 variability is related to human papillomavirus (HPV) infection and squamous intraepithelial lesions (SIL) prevalence and persistence. HLA-DRB1 and DQB1 genes were typed in 620 samples from the Ludwig-McGill cohort. HPV positivity was tested in specimens collected every 4 months during the first year of follow-up. Persistent and long-term infections were defined as at least 2 or 3 consecutive positive results for the same HPV type, respectively. Analysis of SIL included data obtained during the two first years of follow-up. The magnitudes of associations were estimated by unconditional logistic regression analysis adjusted for potential confounders. Certain HLA alleles and haplotypes were associated with HPV either HPV prevalence or persistence. The DRB1*0301-DQB1*0201 haplotype was associated with a lower risk for HPV infection and DRB1*1102-DQB1*0301 for HPV persistence. DRB1*1601-DQB1*0502 and DRB1*0807-DQB1*0402 were associated with a increased risk for persistent HPV infection. It was not observed a strong concordance between the associations verified for HPV prevalence/persistence and SIL, possibly due to the limited number of SIL specimens. A higher risk for SIL, independent of HPV infection, was observed for DRB1*0301 and DR12. DR4 and DQB1*0601 carriers showed a higher frequency of SIL and HSIL, respectively. A negative association between DQB1*0301 and HSIL was verified. Valine at position 86 of the DRβ chain was associated with reduced risks of HPV positivity and persistence, as compared to glycine carriers. However, valine carriers had a higher risk of SIL if transiently infected by HPV. We also analyzed an independent sample of patients with invasive cervical, and a protective effect was observed for DR3. On the other hand, DR4 and DR8/12 were associated with a higher risk for cervical cancer in this population. Our results suggest that HLA class II polymorphisms and pocket 1 profile are involved in clearance and maintenance of HPV infection and the risk of SIL and CCU, consistent with the hypothesis that genetic background is important in the natural history of HPV infections and associated lesions. We also analyzed lymphoproliferative responses against HPV16 E6 and E7 peptides, in patients with invasive cervical cancer. Lymphoproliferative responses were more frequent for E6 peptides than for E7 peptides. The responses were not restricted to a particular peptide, which is expected based on HLA variability observed among patients.
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Cavalcante, Josà Roosivelt. « ImunoexpressÃo da Caderina-E nas cervicites, nas lesÃes intraepiteliais escamosas e no carcinoma invasor do colo uterino ». Universidade Federal do CearÃ, 2013. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=10546.

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O cÃncer do colo do Ãtero à um dos mais preocupantes problemas de saÃde pÃblica do planeta. SÃo esperados para 2013, no Brasil, 17.540 casos novos. Acredita-se atualmente que a maior parte dos cÃnceres cervicais se desenvolve a partir das neoplasias intraepiteliais cervicais. A aquisiÃÃo de propriedades invasivas dos tumores malignos està associada ao desequilÃbrio nas adesÃes intercelulares. As molÃculas de adesÃo tÃm papel fundamental nestas uniÃes e a caderina-E à uma das mais importantes. Està comprovada a sua presenÃa na membrana celular de tecidos epiteliais normais e foi demonstrado que esta proteÃna tem sua expressÃo diminuÃda na maioria dos tumores sÃlidos, o que favorece o processo de invasÃo. O objetivo, neste estudo, foi investigar a imunoexpressÃo da caderina-E nas Cervicites, nas LesÃes Intraepiteliais Escamosas (LIE) e no Carcinoma Invasivo do colo uterino. A amostra consistiu de 83 casos de biÃpsias e cones de colo do Ãtero obtidos dos arquivos do Departamento de Patologia e Medicina Legal da Universidade Federal do CearÃ, em 2007 e 2010, com os seguintes diagnÃsticos: Cervicite = 8 casos; LesÃo Intraepitelial Escamosa de Baixo Grau (LIEBG) = 24 casos; LesÃo Intraepitelial Escamosa de Alto Grau (LIEAG) = 28 casos; Carcinoma Invasor = 23 casos. A imunohistoquÃmica (IHQ) foi efetuada com o anticorpo monoclonal anti-caderina-E, tendo sido considerada positiva a presenÃa de expressÃo membranar, e negativa, a ausÃncia de expressÃo. O teste exato de Fisher foi utilizado para os cÃlculos das tabelas de contingencias. Os resultados da imunomarcaÃÃo foram: Cervicites = 1/8 (12%) negativos e 7/8 (88%) casos positivos para caderina-E; LIEBG = 7/24 (29%) casos negativos e 17/24 (71%) positivos; LIEAG = 7/28 (25%) negativos e 21/28 (75%) positivos; Carcinoma Invasor = 19/23 (83%) negativos e 4/23 (17%) positivos. A expressÃo negativa foi muito mais frequente nas LIEs (27%), comparadas com as Cervicites (12%) apesar de diferenÃa nÃo significante (p = 0,6657). Nas LIEs, uma maior perda da caderina-E foi notada nas cÃlulas menos diferenciadas do 1/3 basal da espessura epitelial. Finalmente, observou-se que a ausÃncia de expressÃo membranar da caderina-E foi muito mais frequente no carcinoma epidermÃide invasor do que nas lesÃes intraepiteliais escamosas do colo do Ãtero. Estes dados mostraram a importÃncia da caderina-E na carcinogÃnese do colo uterino, no entanto, muitos aspectos permanecem sem explicaÃÃo e novos estudos sÃo necessÃrios.
Cervical cancer is one of the most important public health problems around the world. About 17.540 new cases are expected, in Brazil, for 2013. Actually, itâs believed that the majority of cervical cancers begin with non invasive dysplastic lesions, the cervical intraepithelial neoplasias. The acquisition of invasive properties, in epithelial malignancies, is associated to the disruption of intercellular adhesions. The adhesion molecules play a pivotal role in these intercellular bindings and E-cadherin is considered one of the most important among them. In normal epithelial tissues its presence in cell membrane is recognized and it was shown that a down regulation of these proteins in the majority of solid tumors may contribute to facilitate the invasive process. The aim, of this research, was to investigate the E-cadherin immunoexpression in cervicitis, in SILs and in the invasive carcinomas of the uterine cervix. Samples specimens consisted of 83 cases of uterine cervical biopsies and conizations retrieved from the Department of Pathology and Forensic Medicine files of the Federal University of Cearà (Brazil) in 2007 and 2010, distributed, by diagnostic, as follows: Cervicitis = 8 cases; Low Squamous Intraepithelial Lesion (LSIL) = 24 cases; High Squamous Intraepithelial Lesion (HSIL) = 28 cases; and Invasive Carcinoma = 23 cases. Immunohistochemistry (IHC) was performed with the anti-E-cadherin monoclonal antibody and it was considered positive the membranar expression, and, negative, the absence of membranar expression. The Fisherâs exact test was the choice for the contingency tables calculations. The immunostaining results were: Cervicitis = (12%) negative and 7/8 (88%) positive cases to E-cadherin; LSILs = 7/24 (29%) negative cases and 17/24 (71%) positive; HSILs = 7/28 (25%) negative and 21/28 (75%) positive; Invasive Carcinoma = 19/23 (83%) negative and 4/23 (17%) positive. The negative expression was much more frequent in SILs (27%) when compared to cervicitis (12%), although no significant difference (p = 0,6657). In SILs, a bigger E-cadherin loss was noted in undifferentiated cells at the basal third of epithelial thickness. Finally it was shown that the absence of E-cadherin membranar expression was much more frequent in the uterine cervix invasive carcinoma when compared to LSILs and HSILs. These data showed the E-cadherin importance in cervical carcinogenesis, nonetheless, several aspects remain without explication and new researches are to be performed.
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VALENTE, ROBERTO. « Effects of aspirin, ace-inhibitors/sartans and statins on neoplastic and pre- neoplastic lesions of the pancreas ». Doctoral thesis, 2019. http://hdl.handle.net/11573/1210183.

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Aspirin, ace inhibitors/sartans and statins are largely used in primary or secondary cardiovascular prophylaxis. Such drugs have been suggested to play also a role in inhibiting cancer initiation and progression in several clinical and preclinical humoral models. So far, they role in the initiation and progression of pancreatic neoplastic and preneoplastic lesions has been poorly investigated. The aim of the current thesis is to evaluate the effect of such drugs on the progression of pancreatic BD-IPMNs, on the recurrence of cancer after surgery for IPMNs, as well as to evaluate a possible influence in modulating the incidence of pancreas cancer and neuroendocrine tumors.
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Kessler, Jessica Dawn. « Investigating the Fate of Pre-neoplastic Cells in a Mouse Model of Medulloblastoma ». Diss., 2009. http://hdl.handle.net/10161/1186.

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Studying the early stages of cancer can provide important insight into the molecular basis of the disease. In many human cancers, such as prostate, pancreatic, and colon cancer, a pre-neoplastic, or intermediate, stage of the disease has been identified. The pre-neoplastic stage is presumed to be a transition during which normal cells undergo malignant transformation. However, the link between the pre-neoplastic cells and end-stage disease has never been formally established. To investigate the fate of such cells, the patched (ptc) mutant mouse, a model for the brain tumor medulloblastoma was used. Pre-neoplastic cells (PNCs) are found in most ptc mutants during early adulthood, but only 15% of these animals develop tumors. Although PNCs are found in mice that develop tumors, the ability of PNCs to give rise to tumors has never been demonstrated directly, and the fate of cells that do not form tumors remains unknown. Genetic fate mapping and orthotopic transplantation provided definitive evidence that PNCs give rise to tumors and showed that the predominant fate of PNCs that do not form tumors is differentiation. Moreover, N-myc, a gene commonly amplified in medulloblastoma, can dramatically alter the fate of PNCs, preventing differentiation and driving progression to tumors. Importantly, N-myc allows PNCs to grow independently of hedgehog signaling, making the resulting tumors resistant to hedgehog antagonists. These studies provide the first direct evidence that PNCs can give rise to tumors, and demonstrate that identification of genetic changes that promote tumor progression is critical for designing effective therapies for cancer.


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Celestino, Ricardo dos Santos. « Structural and Functional Effects of Chromosomal Rearrangements in Solid Tumours : Neoplastic Thyroid Lesions as Model ». Doctoral thesis, 2012. https://repositorio-aberto.up.pt/handle/10216/65055.

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Celestino, Ricardo dos Santos. « Structural and Functional Effects of Chromosomal Rearrangements in Solid Tumours : Neoplastic Thyroid Lesions as Model ». Tese, 2012. https://repositorio-aberto.up.pt/handle/10216/65055.

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« Morphometric studies of intraepithelial neoplasia and associated lesions in the cervix uteri and the nasopharynx ». Chinese University of Hong Kong, 1990. http://library.cuhk.edu.hk/record=b5886634.

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by Wai Ching Wa, Gina.
Thesis (M.Phil.)--Chinese University of Hong Kong, 1990.
Bibliography: leaves 303-314.
Chapter 1. --- INTRODUCTION --- p.1
Chapter 2. --- LITERATURE REVIEW ON CERVIX UTERI
Chapter 2.1 --- HISTOLOGY OF CERVIX UTERI --- p.4
Chapter 2.2 --- CYTOLOGY OF CERVIX UTERI --- p.5
Chapter 2.3 --- CERVICAL EPITHELIAL LESIONS
Chapter 2.3.1 --- Squamous Metaplasia --- p.7
Chapter 2.3.2 --- Cervical Intraepithelial Neoplasia --- p.9
Chapter 2.3.3 --- Viral Infections --- p.17
Chapter 2.4 --- DIAGNOSTIC APPROACH TO CERVICAL LESIONS --- p.20
Chapter 2.5 --- DIAGNOSTIC VARIABILITY OF CERVICAL LESIONS --- p.21
Chapter 2.6 --- IMPORTANCE OF CERVICAL CARCINOMA IN HONG KONG --- p.21
Chapter 3. --- LITERATURE REVIEW ON NASOPHARYNX
Chapter 3.1 --- HISTOLOGY OF NASOPHARYNX --- p.22
Chapter 3.2 --- CYTOLOGY OF NASOPHARYNX --- p.24
Chapter 3.3 --- NASOPHARYNGEAL EPITHELIAL LESIONS
Chapter 3.3.1 --- 'Squamous Metaplasia' --- p.25
Chapter 3.3.2 --- Nasopharyngeal Intraepithelial Neoplasia --- p.26
Chapter 3.3.3 --- Viral Infections --- p.27
Chapter 3.4 --- DIAGNOSTIC APPROACH TO NASOPHARYNGEAL LESIONS --- p.28
Chapter 3.5 --- IMPORTANCE OF NASOPHARYNGEAL CARCINOMA IN HONG KONG --- p.29
Chapter 4. --- LITERATURE REVIEW ON MORPHOMETRY
Chapter 4.1 --- QUANTITATIVE ASSESSMENT OF CELL FEATURES --- p.30
Chapter 4.2 --- TERMINOLOGY --- p.31
Chapter 4.3 --- APPROACHES TO SAMPLING --- p.32
Chapter 4.4 --- SOURCES OF VARIATION --- p.32
Chapter 4.5 --- METHODOLOGY FOR MORPHOMETRY --- p.33
Chapter 4.6 --- FEATURES FOR MORPHOMETRY IN INTRAEPITHELIAL NEOPLASIA --- p.35
Chapter 4.7 --- PREVIOUS MORPHOMETRIC STUDIES ON INTRAEPITHELIAL NEOPLASIA --- p.36
Chapter 5. --- MATERIALS AND METHODS
Chapter 5.1 --- MATERIALS
Chapter 5.1.1 --- Cervix Uteri --- p.41
Chapter 5.1.2 --- Nasopharynx --- p.41
Chapter 5.2 --- METHODS
Chapter 5.2.1 --- Equipment --- p.42
Chapter 5.2.2 --- Pilot Study for Reproducibility --- p.43
Chapter 5.2.3 --- Estimation of Minimum Sample Size --- p.43
Chapter 5.2.4 --- Morphometric Procedures --- p.44
Chapter 5.2.5 --- Statistical Analysis --- p.48
Chapter 5.2.6 --- Comparison of Visual Diagnosis of Cervical smears and biopsies --- p.49
Chapter 5.2.7 --- Survey of Subjective Assessment Criteria for Cervical Biopsies and Smears --- p.50
Chapter 6. --- RESULTS
Chapter 6.1 --- PILOT STUDY
Chapter 6.1.1 --- Intraobserver Reproducibility --- p.52
Chapter 6.1.2 --- Minimum Sample Size --- p.52
Chapter 6.2 --- CERVIX
Chapter 6.2.1 --- Maturation Sequence of Cervical Epithelium --- p.53
Chapter 6.2.2 --- Differences of Morphometric Means between various groups of Cervical Biopsies --- p.56
Chapter 6.2.3 --- Discriminant Analysis of Cervical Biopsies --- p.58
Chapter 6.2.4 --- Differences of Morphometric Means between various groups of Cervical Smears --- p.60
Chapter 6.2.5 --- Discriminant Analysis of Cervical Smears --- p.61
Chapter 6.2.6 --- Comparison of Cervical Smears and Biopsies --- p.62
Chapter 6.2.7 --- Subjective Assessment Criteria for Cervical Biopsies and Smears --- p.63
Chapter 6.3 --- NASOPHARYNX
Chapter 6.3.1 --- Maturation Sequence of Nasopharyngeal Epithelium --- p.65
Chapter 6.3.2 --- Differences of Morphometric Means between various groups of Nasopharyngeal Biopsies --- p.68
Chapter 6.3.3 --- Discriminant Analysis of Nasopharyngeal Biopsies --- p.70
Chapter 6.4 --- COMPARISON OF CERVIX UTERI AND NASOPHARYNX --- p.71
Chapter 7. --- DISCUSSION
Chapter 7.1 --- CERVIX UTERI
Chapter 7.1.1 --- Maturation Sequence --- p.73
Chapter 7.1.2 --- Discrimination of different groups in Biopsies --- p.76
Chapter 7.1.3 --- Discrimination of different groups in Smears --- p.77
Chapter 7.1.4 --- Comparison of Smears and Biopsies --- p.78
Chapter 7.1.5 --- Subjective Assessment Criteria --- p.80
Chapter 7.1.6 --- Future directions --- p.81
Chapter 7.2 --- NASOPHARYNX
Chapter 7.2.1 --- Maturation Sequence --- p.81
Chapter 7.2.2 --- Discrimination of different groups --- p.84
Chapter 7.2.3 --- Nasopharyngeal Cytology --- p.84
Chapter 7.2.4 --- Future directions --- p.85
Chapter 7.3. --- COMPARISON OF CERVIX UTERI AND NASOPHARYNX
Chapter 7.3.1 --- Morphometric data --- p.85
Chapter 7.3.2 --- Discriminant Analysis --- p.87
Chapter 8. --- CONCLUSIONS --- p.89
Chapter APPENDIX A --- Survey of subjective assessment criteria for cervical biopsies and smears
Tables A1-A7 --- p.92
Chapter APPENDIX B --- Results of pilot study
Tables B1-B6 --- p.100
Chapter APPENDIX C --- Morphometric data and results of statistical tests for cervical biopsies
Fig. C1-C61 --- p.104
Tables C1-C19 --- p.166
Chapter APPENDIX D --- Morphometric data and results of statistical tests for cervical smears
Fig. D1-D2 6 --- p.179
Tables D1-D3 --- p.206
Chapter APPENDIX E --- Comparison of cervical smears and biopsies
Tables E1-E3 --- p.208
Chapter APPENDIX F --- Morphometric data and results of statistical tests for nasopharyngeal biopsies
Fig. F1-F61 --- p.211
Tables F1-F12 --- p.273
Chapter APPENDIX G --- Comparison of nasopharyngeal and cervical biopsies
Tables G1-G15 --- p.282
Chapter APPENDIX H --- Pictures of materials and equipment
Fig. H1-H21 --- p.291
REFERENCES --- p.303
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Martins, Ana Carolina Moreira. « Eficácia e Segurança da Mucosectomia Endoscópica Fragmentada no Tratamento de Neoplasias Superficiais Extensas do Cólon e Recto : Resultados a Longo Prazo ». Master's thesis, 2018. http://hdl.handle.net/10316/82391.

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Trabalho Final do Mestrado Integrado em Medicina apresentado à Faculdade de Medicina
O cancro colorretal corresponde a uma das principais causas de morte na actualidade, mundialmente. A sua deteção precoce é fundamental. A resseção de lesões pré-malignas tem sido realizada durante muitos anos com recurso a técnicas cirúrgicas. Com o aparecimento da técnica de mucosectomia fragmentada, é agora possível a excisão de lesões de grandes dimensões, de forma menos invasiva. Contudo, ainda existem algumas reservas em relação a este procedimento, nomeadamente potenciais taxas de lesão residual/recidivante elevadas e a necessidade de follow-up. O score SERT, criado recentemente, pode ser preditor da taxa de lesão residual e vir a revolucionar o acompanhamento e individualização do tempo até à primeira reavaliação endoscópica para cada doente.O principal objectivo deste trabalho é apurar a eficácia e a segurança a longo prazo da modalidade da mucosectomia fragmentada, no contexto do serviço de Gastrenterologia dos HUC, assim como averiguar a validade do score SERT na predição da taxa de lesão residual e individualização do tempo de follow-up.Trata-se de um estudo retrospetivo de validação externa, em que foram colhidos dados referentes a mucosectomias fragmentadas realizadas no Serviço de Gastrenterologia dos HUC no período de tempo de Janeiro de 2009 até Dezembro de 2014. Obteve-se informação relativa a factores demográficos, características endoscópicas e histopatológicas das lesões, condições durante o procedimento, complicações e resultados, taxas de lesão residual e recidivas e a aplicação do score SERT. Os dados foram analisados com recurso ao Microsoft Excel e SPSS.Dos 139 casos que compõem a população, apenas 15 (11,5%) apresentaram lesão residual no primeiro follow-up e posterior lesão recidivante em 12 (9,4%). No geral, foram sujeitas a retratamento endoscópico com sucesso, tendo apenas uma minoria ter necessitado de cirurgia complementar ou evoluído para uma neoplasia grave. As intercorrências associadas à técnica foram mínimas e resolvidas sem intercorrências. Quando aplicado o score SERT, pode-se inferir que a taxa de recidiva em doentes com score 0 é substancialmente inferior quando comparada com doentes com score entre 1 e 4.As taxas de lesão residual e lesão recidivante nos doentes submetidos a mucosectomias fragmentadas não são significativas, visto que a maioria foi tratada endoscopicamente, sem intercorrências. Este facto também é corroborado pela baixa taxa tanto de intercorrências durante o procedimento como de complicações a longo prazo. O score SERT também mostrou ser um bom preditor no que toca a probabilidade de lesão residual com os seus três factores (lesão ≥ 40 mm, hemorragia intra-procedimento e displasia de alto grau), validando estudos previamente realizados.Considero que a mucosectomia fragmentada representa uma alternativa eficaz e segura em relação a técnicas cirúrgicas, para além de ser menos invasiva e dispendiosa para o centro hospitalar. Apresenta mais benefícios do que riscos. Concluo, ainda, que com a aplicação do score SERT e caracterização da mucosectomia realizada, é possível prever a taxa de lesão residual/recidivante, podendo-se individualizar o tempo até ao follow-up para cada caso, evitando realizar colonoscopias com tanta frequência aos doentes e poupando recursos hospitalares.
Colorectal cancer is one of the leading causes of mortality worldwide, in our current days. The resection of pre-malignant lesions has been performed surgically for many years now. The onset of piecemeal endoscopic mucosal resection brought a new, less-invasive way to excise larger, lateral spreading lesions. However, there are still many concerns regarding this procedure, such as its potentially high residual and recurrent lesions’ rates and the need for an endoscopic follow-up. The SERT score may be a good tool to predict recurrence rates and can revolutionize the follow-up and aid with the individualization of the waiting time until the first reevaluation for each patient.The main objective of this study is to determine the long-term efficacy and safety of the piecemeal endoscopic mucosal resection modality regarding HUC’s Gastroenterology service, as well as to verify the validity of the SERT score as a recurrence predictor and in the individualization of the follow-up time.This is a retrospective study, with external validation, in which data was collected, regarding the piecemeal endoscopic mucosal resections performed in the HUC’s Gastroenterology service, from January 2009 to December 2014. The obtained information concerned demographic factors, lesions’ characteristics, conditions during the procedure, short and long-term complications, results, residual and recurrent lesions’ rates, and the employment of the SERT score. The collected data was analyzed using Microsoft Excel and SPSS.Of the 139 cases that make up the population, only 15 (11,5%) had residual lesions at the first follow-up and recurrent lesions appeared in 12 (9,4%) patients. In general, they underwent successful endoscopic re-treatment, with only a minority needing complementary surgery or developing into severe neoplasia. The short-term complications associated to the technique were minimal and resolved without any intercurrences. When the SERT score was applied, it could be deduced that the residual lesion’s rate in patients with score 0 is substantially lower when compared with patients with score between 1 and 4.The rates of residual lesion and recurrent lesion in patients submitted to piecemeal endoscopic mucosal resections are not significant, as their majority were re-treated endoscopically, without complications. This is also corroborated by the low rate of both complications during the procedure and long-term ones. The SERT score also proved to be a good predictor for the probability of residual lesion with its three factors (lesion ≥ 40 mm, intra-procedural hemorrhage and high-grade dysplasia), validating previous studies.As demonstrated, piecemeal endoscopic mucosal resection represents an effective and safe alternative to surgical techniques, as well as being less invasive and costly for the hospital. It has more benefits than risks. I also conclude that with the SERT score and the description of the initial mucosectomy, it is possible to predict the rate of residual/recurrent lesion, and it is possible to individualize the follow-up time for each case, avoiding unnecessary procedures for both patients and doctors and sparing hospital resources.
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SIMONELLI, Ilaria. « Le lesioni mammarie a potenziale neoplastico incerto (B3) diagnosticate su Core Needle Biopsy (CNB) : inquadramento clinico, out come e valutazione dell’opzione chirurgica ». Doctoral thesis, 2011. http://hdl.handle.net/11573/916822.

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TITLE: "Uncertain malignant potential breast lesion (B3) diagnosed on core needle biopsy (CNB): clinical presentation, outcome and evaluating surgical option" INTRODUCTION Core needle biopsy (CNB) have been introduced to increase the accuracy of diagnosis of breast cancer and to exclude from surgery benign lesions, with savings of injured tissues. However, a fair percentage of CNB are still classified, according to European guidelines, in the B3 category, which includes a heterogeneous group of lesions with uncertain malignant potential. The aim of this study is to evaluate the positive predictive value (PPV) on excisional biopsies (EB) after the diagnosis of B3 in our experience at Campus Bio-Medico of Rome and compare them with data in the literature to evaluate the possibility of a different treatment for each histological subgroup. MATERIALS AND METHODS: From May 2003 to May 2011 were performed 808 CNB, stereo as well as US guided, at the Breast Unit of the Campus Bio-Medico. One hundred and sixteen of these (14.4%) were classified as B3. Ninety-five patients (81.9%) underwent BE. RESULTS It was confirmed the diagnosis of CNB in 47 cases (49.5%), in 31 (32.6%) definitive histology was of benign lesions, in 14 cases (14.7%) cancer in situ , ductal or lobular, was diagnosed, and in three (3.1%) an invasive cancer was detected. Overall, the PPV is of 17.9%. In particular, all malignant lesions were associated with atypia. Lobular Intraepithelial Neoplasia (LIN) grade 2 and 3 showed, at histological examination of EB, respectively PPV of 54.5% and of 66.7%, while LIN1 of 15.8%. In our series Ductal Intraepithelial Neoplasia (DIN) 1a and b have a PPV of 12.5% and 4%. Aftere the diagnosis of 6 papillary lesions, EB showed foci of carcinoma in situ inone case (PPV 16.7%). Two/8 radial scars, both associated with DIN1, were tumors in situ at the excisional biopsy. Excisional biopsy confirmed the other types of lesions (Phyllodes tumors, Fibroepithelial lesions). DISCUSSION AND CONCLUSIONS The European Guidelines for the Diagnosis of breast cancers define B3 "lesions that may be benign on histology of BE, but it is known that heterogeneity can show, or have an increased risk (although low) to be associated in malignant lesions. " In our series the PPV was 17.9% and is associated in all cases but one (papillary lesions) with ductal or lobular intraepithelial neoplasia (LIN and DIN1-b). At a review of the literature, we believe that with a diagnosis of B3 at the CNB is mandatory a EB if is present LIN2 and 3 and recommended in LIN1 and DINA-b. We also propose that should be sent to EB every atypical papillary lesions and phyllodes tumor, because of the natural history of these tumors. Instead the opportunity of EB in other types of lesions classified B3 should be discussed in multidisciplinary meetings. REFERENCES Bianchi S. “Positive predictive value for malignancy on surgical excision of breast lesions of uncertain malignant potential (B3) diagnosed by stereotactic vacuum-assisted needle core biopsy (VANCB): a large multi-institutional study in Italy” Breast 2011; 20; 264-270 European Commission Working Group on Breast Screening Pathology. Quality assurance guidelines for pathology. Perry N. Ed. Luxemburg: Office for official publications of the European Communities; 2006: 219-312
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Sim, Pheng Siew. « The role of plasminogen activators in neoplasia and inflammatory lesions of the human intestine ». Phd thesis, 1986. http://hdl.handle.net/1885/143982.

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Kornet, Katharina. « Läsionen mit unklarem biologischen Potential (B3-Läsionen) in der Bildgebung : Vorkommen, Erscheinungsbild, Konsequenzen ». Doctoral thesis, 2018. http://hdl.handle.net/11858/00-1735-0000-002E-E31A-4.

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Ferreira, Beatriz Maria da Rocha Sousa. « Choroidal Melanocytic Lesions : Clinical Predictors of Growth and Malignant Progression ». Master's thesis, 2019. http://hdl.handle.net/10316/89843.

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Trabalho Final do Mestrado Integrado em Medicina apresentado à Faculdade de Medicina
Introdução: Existe uma sobreposição entre as características clínicas dos nevus e domelanoma da coroideia que torna o seu diagnóstico diferencial bastante complexo. Estudosprévios mostraram uma relação entre determinadas características das pequenas lesõesmelanocíticas da coroideia e a sua progressão para a malignidade, o que motivam estainvestigação adicional.Objetivo: Avaliar as características clínicas e ecográficas de pequenas lesões melanocíticasda coroideia que se correlacionam significativamente com um maior potencial decrescimento e progressão para malignidade.Materiais e Métodos: Estudo observacional retrospectivo que inclui 58 doentes com odiagnóstico de pequena lesão melanocítica da coroideia. Os dados referentes àscaracterísticas demográficas, clínicas e ecográficas foram coletados a partir de uma base dedados pré-existente. Foi efectuada uma análise estatística univariável e multivariável paraidentificar fatores de risco e fatores protetores com significado estatístico, tendo em conta ocrescimento documentado das lesões.Resultados: A idade média dos doentes foi de 60 anos e a mediana do tempo deseguimento de 20,5 meses. A espessura média e o maior diâmetro basal na avaliação inicialforam de 2,61 mm e 7,28 mm, respetivamente. Em 20 dos 58 (34,5%) doentes foidocumentado crescimento da lesão. Sete fatores estatisticamente significativos associadosao crescimento da lesão na análise univariável foram: fluido subretiniano (p<0,001; OR=9,9),pigmento laranja (p<0,001; OR=29), distância da margem ao disco óptico <3 mm (p=0,015;OR=4,024), distância da margem à fóvea <3 mm (p=0,027; OR=3,578) e ecogenicidadeinterna de baixa refletividade (p<0,001; OR=não estimável). Foram encontrados dois fatoresprotetores: presença de halo amelanótico (p=0,001; OR=0,053) e de drusens sobrejacentes(p<0,001; OR=0,102). Na análise multivariável apenas 4 das 6 características incluídasmantiveram significado estatístico: fluido subretiniano (p=0,044; HR=5,071), pigmentolaranja (p=0,003; HR=24,899), presença de halo amelanótico (p=0,026; HR=0,085) epresença de drusens sobrejacentes (p=0,008; HR=0,155).Discussão e Conclusões: O fator preditivo mais significativo para crescimento etransformação maligna foi a ecogenidade interna de baixa refletividade, demonstrada naecografia, ultrapassando os factores clínicos apontados em estudos prévios. A ecografiadeve ser realizada cuidadosamente na observação inicial de todas as pequenas lesõesmelanocíticas da coroideia, assim como a avaliação de todas as outras características deforma a ser possível estimar o risco associado e permitir um tratamento precoce e ummelhor prognóstico.
Introduction: Overlapping features between benign choroidal nevi and choroidal melanomamake the differential diagnosis quite complex. Previous studies show a relation betweencertain features of small choroidal melanocytic lesions and their progression to malignancywhich would benefit from further investigation.Objective: To evaluate small choroidal melanocytic lesions features that correlatesignificantly with a higher potential of growth and progression to malignancy.Materials and Methods: Retrospective observational study including 58 patients with theinitial diagnosis of small choroidal melanocytic lesions. Data regarding demographic, clinicaland ultrasonographic features was collected from a pre-existing data base. Univariate andmultivariate statistical analysis were used to identify statistically significant risk and protectivefactors. The main outcome was documented lesion growth.Results: Mean patient age was 60 years and median follow-up time was 20.5 months. Meanthickness and largest basal diameter at initial assessment was 2.61 mm and 7.28 mm,respectively. 20 of the 58 (34.5%) patients had lesions that demonstrated growth. Univariateanalysis identified seven statistically significant factors associated with lesion growth:presence of subretinal fluid (p<0.001; OR = 9.9), presence of orange pigment (p<0.001;OR=29), nearest lesion margin distance to the optic disc <3 mm (p=0.015; OR=4.024),nearest lesion margin distance to the fovea <3 mm (p=0.027; OR=3.578) and hollowechogenicity (p<0.001; OR=non estimable). Two significant protective factors against lesiongrowth were found: presence of an amelanotic halo surrounding the lesion (p=0.001;OR=0.053) and presence of overlying drusens (p<0.001; OR=0.102). In the multivariateanalysis only 4 of the 6 features included maintained statistical significance, namely,presence of subretinal fluid (p=0.044; HR=5.071), presence of orange pigment (p=0.003;HR=24.899), presence of amelanotic halo (p=0.026; HR=0.085) and presence of overlyingdrusens (p=0.008; HR=0.155).Discussion and Conclusion: The most significant predictive factor pointing to growth andmalignant transformation was ultrasonographic low internal echogenicity, overcoming clinicalfactors found in previous studies. This feature should be carefully investigated in the initialevaluation of every small choroidal melanocytic lesion, along with the other features toestimate the associated risk. This will allow an early treatment and eventually a betterprognosis.
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Peng, Ya-Wen, et 彭雅汶. « Relationships between the presence of HPV 16/18 DNA in peripheral blood lymphocytes and p16INK4a protein expression in human papillomavirus-associated neoplastic cervical lesions ». Thesis, 2004. http://ndltd.ncl.edu.tw/handle/30087105479458993903.

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碩士
中山醫學大學
毒理學研究所
92
捌 英文摘要 Cervical cancer has been the major cause for cancer-related morbidity and mortality for females worldwide. The significant contribution of human papillomavirus to cervical carcinogenesis has also been intensively investigated, and many reports have shown that p16INK4a may serve as an early biomarker of cervical cancer since p16INK4a was up-regulated by E2F through Rb inactivation by HPV 16 E7. Our preliminary data showed that HPV DNA signals were detected in peripheral blood lymphocytes (PBL) of lung cancer and cervical cancer patients by in situ hybridization. In this study, we attempted to investigate the correlation between p16INK4a protein expression and human papillomavirus infection in PBL and tumor tissues from patients with high-grade squamous intraepithelial lesion (HSIL) or early invasive cervical cancer (EICC) to verify the presence of HPV DNA in PBL plays a crucial role in cervical carcinogenesis. Paired tissues and peripheral blood samples from 68 patients, including 36 HSIL patients and 32 EICC patients, were collected for studies. The presence of HPV type 16/18 DNA and E7 mRNA in tissue and PBL was examined by nested-PCR and PCR-RFLP, respectively. Results showed that the presence of HPV 16 and/or 18 DNA in tissues was significantly correlated with those in PBL from all cases (P = 0.005 for HPV 16, P = 0.022 for HPV 18 and P < 0.001 for HPV 16 or 18), especially those 26 patients with HPV DNA in both PBL and tissues. This result revealed that HPV infection in cervical tissues can be indirectly indicated by a direct detection of HPV DNA in blood circulation. Moreover, our data supported that HPV E7 mRNA expression was respectively correlated with Rb and p16 immunostainings in cervical tissues from patients with HSIL and EICC (P < 0.001). This result seemed to confirm the previous reports showing that p16 up-regulation may be mediated through Rb inactivation by HPV 16/18 E7. In addition, the positive p16 immunostaining was positively correlated with the presence of HPV 16 or 18 DNA in cervical tissues of HSIL (P < 0.001), but not in EICC. Interestingly, a positive correlation was also observed in PBL of HSIL (P = 0.044 for HPV 16, P = 0.009 for HPV 16 or 18), but still not in EICC. In conclusion, the present study clearly revealed the positive association between the presence of HPV 16 or 18 DNA in PBL and p16 overexpression in tissues of patients with cervical lesions.
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Paula, Arnaud Fabian da Cruz. « Characterization of different breast cancer stem cell phenotypes in proliferative, pre-malignant and neoplastic lesions of the breast : associations with breast cancer behavior and progression ». Doctoral thesis, 2016. https://hdl.handle.net/10216/86451.

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Paula, Arnaud Fabian da Cruz. « Characterization of different breast cancer stem cell phenotypes in proliferative, pre-malignant and neoplastic lesions of the breast : associations with breast cancer behavior and progression ». Tese, 2016. https://hdl.handle.net/10216/86451.

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Gonçalves, Gisela de Brito. « Clinicopathologic characteristics of patients with gastric superficial neoplasia in a Western country and risk factors for multiple lesions after endoscopic submucosal dissection ». Master's thesis, 2019. https://hdl.handle.net/10216/120798.

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