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Liquid-based cytology (LBC) has replaced conventional smears in the UK. The National Institute for Health and Clinical Excellence (NICE) recommended the use of LBC in 2003. ThinPrepTM (TP) and SurePathTM (SP) LBC systems were adopted for use in the National Health Service Cervical Screening Programme (NHSCSP) in the UK. NICE recommended further review of any other technologies or other liquid-based cytology systems in the future. For any second-generation LBC systems to be considered for cervical screening in the NHSCSP, there must be an evaluation of technical requirements and clinical data relating to their sensitivity, specificity and the percentage of inadequate samples.The objective of the work undertaken for this thesis was to provide evidence to enable an informed decision on the use of second-generation liquid-based cytology systems for cervical screening in the UK. The decision to accept the second-generation LBC system in the NHSCSP is based on its reliability, clinical effectiveness and cost implications. This work will determine the reliability, microscopic quality and reproducibility of slides of the second-generation LBC system, and the results of this work will form the platform for progression to the clinical evaluation of the system.Initially, four second-generation LBC systems were considered suitable for evaluation. They were Seroa CYTO-screen, Shandon Papspin, LGM Liqui-PREP and CellSolution 120. However, the specifications of only one system (CellSolution 120TM) met NHSCSP technical requirements to start the evaluation. One hundred random, electronically generated colposcopy patient samples were used to assess the technical reliability of the CellSolution 120TM system. The technical evaluation consisted of pre-phase I and phase I. The results of these phases will decide whether the CS 120TM liquid-based cytology system could be carried further for clinical evaluation (phase II) or not.This study was sponsored by the NHS Purchasing and Supply Agency (PASA), the Centre for Evidence based Purchasing (CEP) on behalf of the NHSCSP. The Manchester Cytology Centre (MCC) was selected as the site for evaluation of CellSolution 120™ and the project was managed by Guildford Medical Device Evaluation Centre (GMEC) on behalf of CEP.

<p>Background and Aims: While a single &ldquo / high quality&rdquo / oral liquid based cytology (LBC) study has shown a high sensitivity and specificity for the technique in detection of oral dysplasia and malignancy, the high unit cost of this technology cannot be borne by the developing African countries. This study aims to evaluate the efficiency of an alternative cost-effective technique, Shandon PapSpin (PS) LBC in&nbsp / diagnosis of oral and oropharyngeal dysplasia and malignancy. Materials and Methods.We compared the diagnostic accuracy of Shandon PS LBC with that of scalpel biopsy in 69 patients. Transepithelial cytology specimens were obtained using a cervical Cytobrush. The cytology specimens were graded and scored using a novel oral cytologic grading and scoring system respectively. Results: Histological diagnosis of dysplasia or invasive squamous cell carcinoma was made in 51 of the 69 cases. Histology confirmed the cytological diagnosis of dysplasia or malignancy in 49 of the 51 cases. There were two false negative and no false positive cases. The sensitivity was 96% and the specificity 100%. The cytologic grade correlated positively with histologic grade. The best cut off value for distinguishing reactive/mildly dysplastic lesions from high 9 grade/invasive squamous cell carcinoma was determined as a cytologic score of 3, representing a sensitivity of 95% and a specificity of 96%. Conclusion: The Shandon PS LBC in association with transepithelial brush biopsy technique (TBBT) is a highly sensitive, specific and economical screening test in detection of oral and oropharyngeal dysplasia and malignancy. The proposed oral cytologic grading system correlates well with histology. The novel oral cytologic scoring system shows promise as a simple, reliable and reproducible scoring system. In addition, the liquid residual allows for immunocytochemical (Podoplanin) testing.</p>

<p>Background and Aims: While a single &ldquo / high quality&rdquo / oral liquid based cytology (LBC) study has shown a high sensitivity and specificity for the technique in detection of oral dysplasia and malignancy, the high unit cost of this technology cannot be borne by the developing African countries. This study aims to evaluate the efficiency of an alternative cost-effective technique, Shandon PapSpin (PS) LBC in&nbsp / diagnosis of oral and oropharyngeal dysplasia and malignancy. Materials and Methods.We compared the diagnostic accuracy of Shandon PS LBC with that of scalpel biopsy in 69 patients. Transepithelial cytology specimens were obtained using a cervical Cytobrush. The cytology specimens were graded and scored using a novel oral cytologic grading and scoring system respectively. Results: Histological diagnosis of dysplasia or invasive squamous cell carcinoma was made in 51 of the 69 cases. Histology confirmed the cytological diagnosis of dysplasia or malignancy in 49 of the 51 cases. There were two false negative and no false positive cases. The sensitivity was 96% and the specificity 100%. The cytologic grade correlated positively with histologic grade. The best cut off value for distinguishing reactive/mildly dysplastic lesions from high 9 grade/invasive squamous cell carcinoma was determined as a cytologic score of 3, representing a sensitivity of 95% and a specificity of 96%. Conclusion: The Shandon PS LBC in association with transepithelial brush biopsy technique (TBBT) is a highly sensitive, specific and economical screening test in detection of oral and oropharyngeal dysplasia and malignancy. The proposed oral cytologic grading system correlates well with histology. The novel oral cytologic scoring system shows promise as a simple, reliable and reproducible scoring system. In addition, the liquid residual allows for immunocytochemical (Podoplanin) testing.</p>

Magister Chirurgiae Dentium - MChD / Background and Aims: While a single “high quality” oral liquid based cytology (LBC) study has shown a high sensitivity and specificity for the technique in detection of oral dysplasia and malignancy, the high unit cost of this technology cannot be borne by the developing African countries. This study aims to evaluate the efficiency of an alternative cost-effective technique, Shandon PapSpin (PS) LBC in diagnosis of oral and oropharyngeal dysplasia and malignancy. Materials and Methods.We compared the diagnostic accuracy of Shandon PS LBC with that of scalpel biopsy in 69 patients. Transepithelial cytology specimens were obtained using a cervical Cytobrush. The cytology specimens were graded and scored using a novel oral cytologic grading and scoring system respectively. Results: Histological diagnosis of dysplasia or invasive squamous cell carcinoma was made in 51 of the 69 cases. Histology confirmed the cytological diagnosis of dysplasia or malignancy in 49 of the 51 cases. There were two false negative and no false positive cases. The sensitivity was 96% and the specificity 100%. The cytologic grade correlated positively with histologic grade. The best cut off value for distinguishing reactive/mildly dysplastic lesions from high 9 grade/invasive squamous cell carcinoma was determined as a cytologic score of 3, representing a sensitivity of 95% and a specificity of 96%. Conclusion: The Shandon PS LBC in association with transepithelial brush biopsy technique (TBBT) is a highly sensitive, specific and economical screening test in detection of oral and oropharyngeal dysplasia and malignancy. The proposed oral cytologic grading system correlates well with histology. The novel oral cytologic scoring system shows promise as a simple, reliable and reproducible scoring system. In addition, the liquid residual allows for immunocytochemical (Podoplanin) testing. / South Africa

Två huvudsakliga metodprinciper används inom cytologi för diagnostisering av cellförändringar, nämligen konventionell och vätskebaserad metod. De kan båda appliceras på såväl gynekologiska som icke-gynekologiska prover, där den senare bland annat omfattar olika sorters exsudat. Syftet med den här studien var att utveckla metoden för den vätskebaserade metoden så att etanolfixerade exsudat kunde prepareras och även påvisa bättre resultat än då de preparerats med konventionell metod. För att göra detta har 61 unika prover kategoriserade som exsudat preparerats totalt, varav 61 med konventionell metod, 54 med vätskebaserad metod och 22 med vätskebaserad metod med tillsats av ättiksyra. De färdiga glasen bedömdes sedan i mikroskop och gavs scorevärden utifrån fyra parametrar: mängden celler exklusive inflammatoriska celler; bedömbarheten av cellmorfologin; mängden inflammatorisk komponent samt mängden bakgrundsmaterial. Resultaten visade ingen förbättring mellan de glas som preparerats med konventionell eller vätskebaserad metod. Däremot visade resultaten för de ättiksyrabehandlade proverna på förbättrade scorevärden jämfört med de andra metoderna. Som slutsats drogs att vätskebaserad metod med tillsats av ättiksyra uppnår syftet eftersom det reducerar mängden bakgrundsmaterial, förekomst av ring på objektglasen samt vidhåller en god cellmorfologi, vilket gör proverna lättare att diagnostisera för cytodiagnostikerna. / Two main principles is used within cytology in order to diagnose cytological abnormalities; conventional and liquid-based cytology. Both methods can be applied on both gynaecological and non-gynaecological samples of which the later includes samples categorized as exudate. The aim of this study was to develop the method for liquid-based cytology so that exudate fixated with ethanol could be prepared and also achieve better results compared to conventional method. In order to do so, 61 unique samples were prepared of which 61 with conventional method, 54 with liquid-based method and 22 with liquid-based method with added acetic acid. The slides was then examined in microscope and was given score values within four parameters: amount of cells; cell morphology; amount of inflammatory component and amount of background. The results indicated no difference between the slides prepared with conventional or liquid-based method. However, the slides prepared with addition of acetic acid indicated more opportunistic score values when compared. The conclusion was that liquid-based method with the addition of acetic acid did satisfy the aim of this study as it reduces the amount of background, reduces “ring formation” on the slides and preserve the cells morphology well, which makes the samples easier to diagnose.

Photovoltaic thermal (PVT) collectors are widely used to harness a large fraction of the solar spectrum to generate electricity and heat from a single collector. The circulation of the working medium will pass through the collector which cools down the PV cell temperature and also increases the water temperature, which will increase the electrical and thermal performance at the same time. PVT is an emerging technology and is demonstrated for domestic and industrial applications. There has also been a major gap for the techno-economic analysis of PVT system in different climatic conditions and further developing reliable financial models that can be applied in different regions. This thesis paper presents a techno-economic evaluation of a liquid-based PVT collector system developed by Abora Solar, Spain across a wide range of climatic conditions and contexts. The various performance indicators are visualized by digital mapping approach for 86 different locations all over the world. The databank obtained from the analysis is further used to establish a general correlation between collector performance and meteorological parameters such as Global horizontal irradiation and ambient temperature. The collector energetic performance is simulated using a validated and proprietary simulation tool developed by Abora Solar company. The complete energy system consists of a PVT collector, a water storage tank, and the associated DHW demand simulator. The collector energetic performance has reflected following the analysed Global horizontal irradiation and ambient temperature trend. The highest and lowest energy utilization ratio of the collector has been recorded in Reykjavik, Iceland (63%) and Medina, Saudi Arabia (54%) respectively. The highest and lowest exergetic efficiency of the collector has been recorded in Reykjavik, Iceland (23%) and Medina, Saudi Arabia (17%) respectively. The exergetic efficiency collector has shown better performance with the less ambient temperature and less quality of work in high ambient temperatures. Furthermore, the energy utilization ratio and exergetic efficiencies of collector production are analysed. The economic analysis is carried out in realistic approach using two different financial scenarios: mode (1) The total system cost is capital investment in the first year; mode (2) Only 25 % of total system cost is a capital investment and remaining 75 % investment is considered with financing period with certain interest rate. The economic performance of the collector has been decided mainly based on the Net Present Value per unit collector area, whereas it expressed high dependency on thermal energy savings. The average NPV per unit collector area of 86 geographical cities for first financial model 1 and financial model 2 are 1886€ and 2221€ respectively. Besides, the Payback Period has also been estimated for the first financing model in all selected locations. The first financial model (1) has shown better results in locations with a high interest rate and highly recommended for the locations with interest rate. The significant work of understanding of PVT components behaviour at the system level, the collector energetic and economic performance at different climatic conditions across the world have been highlighted which reflects the concrete developments to this research subject area and helps market decision-makers for market penetration.

Small cell (neuroendocrine) carcinoma of the uterine cervix (SMCC) is a rare, highly aggressive malignant neoplasm. Both conventional and liquid-based cytology (LBC) cervical smears have low sensitivity in diagnosing SMCC, requiring immunocytochemical (ICH) confirmation. We present the first series of SMCC primarily diagnosed in cytology specimens, and ICH studies performed on the residual LBC specimens with subsequent confirmation of the diagnosis on surgical pathology specimens. Immunocytochemical stains for keratin, p16INK4, and neuroendocrine markers (synaptophysin, chromogranin, CD56) were performed on additional ThinPrep slides. HPV test used chromogenic in situ hybridization high risk HPV DNA probe. The Pap smears in all three specimens were highly cellular with a mixture of squamous cells and numerous well-preserved single or small cohesive clusters of malignant epithelial cells. Tumor cells were small, monomorphic with minimal cytoplasm and high nuclear/cytoplasmic ratio. There was significant nuclear overlap, but no nuclear molding, or smudging of nuclear chromatin. The chromatin pattern was stippled. A background tumor diathesis was prominent. Atypical squamous cells of undetermined significance (ASCUS) were noted in one case, and markedly abnormal squamous cells were seen in another case. The main cytology differential diagnoses included high-grade squamous intraepithelial lesion and an endometrial adenocarcinoma. Immunocytochemical positivity for the neuroendocrine markers supported the diagnoses of SMCC in all three cases. The morphologic features of the concurrent surgical pathology specimens were typical of SMCC. The tissue diagnoses were also confirmed by immunohistochemistry. Our study allows us to conclude that SMCC can be primarily diagnosed in LBC specimens using a panel of immunocytochemical stains.

Submitted by Isaac Francisco de Souza Dias (isaac.souzadias@ufpe.br) on 2016-03-04T17:16:30Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) MICHELINE OLIVEIRA LOBO PEREIRA DA COSTA- TESE DOUTORADO -23-10-2015.pdf: 15371820 bytes, checksum: 4afd4b560150641ba2dc59721bbb563e (MD5) / Made available in DSpace on 2016-03-04T17:16:30Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) MICHELINE OLIVEIRA LOBO PEREIRA DA COSTA- TESE DOUTORADO -23-10-2015.pdf: 15371820 bytes, checksum: 4afd4b560150641ba2dc59721bbb563e (MD5) Previous issue date: 2015-01-23 / CAPES / O presente estudo avaliou o desempenho da metodologia citológica de base líquida (ThinPrep-TP) com o da citologia convencional de Papanicolaou (CC) no diagnóstico de alterações citopatológicas e de resultados insatisfatórios, sob a visão de um serviço público no estado de Pernambuco (LACEN-PE) e da Fundação Oncocentro de São Paulo (FOSP-SP). Também foram avaliadas as associações entre a presença de coinfecções genitais dos subtipos de Human papillomavirus (HPV) com Chlamydia trachomatis (CT) e/ou outras microfloras, com os diferentes estágios de alterações cervicais das pacientes. A população do estudo foi de 525 mulheres na faixa etária dos 18-65 anos, atendidas por demanda espontânea, pelas Unidades Básicas de Saúde no Estado de Pernambuco, no período de abril a novembro de 2011. Um questionário padronizado com informações sobre características sociodemográficas, sexuais, reprodutivas e de hábitos (tabagismo, consumo de bebidas alcoólicas e uso de drogas) foram obtidos de todas as pacientes do estudo. A presença de DNA do HPV e da CT foram diagnósticadas através da reação em cadeia da polimerase (PCR) e o exame citológico foi realizado para detecção das demais infecções. Para avaliar a relação das infecções genitais com a presença de alterações intraepiteliais cervicais, foi utilizado o teste exato de Fisher. Os resultados mostraram que 11,05% das pacientes tinham menos de 25 anos, 30,86% eram solteiras, 6,86% tiveram mais de 5 parceiros sexuais, 44% não faziam uso de métodos contraceptivos, 38,85% eram usuárias de álcool, 24,38% eram fumantes e 3,24% haviam consumido drogas. Além disso, 42,01% tinham queixas ginecológicas; e 12,19% história pregressa de doenças sexualmente transmissíveis (DST). Quando comparadas a eficiência das técnicas TP e CC sob a visão do LACEN-PE, observou-se que as duas metodologias avaliadas apresentaram fraca concordância entre os métodos (k=0,19;95%IC(0,11-0,26); p<<0,001). A metodologia TP reduziu a taxa de resultados insatisfatórios de 4,38% para 1,71% (×2= 5,28; p=0,02), e o número de alterações citopatológicas diagnosticadas aumentaram de 2,47% para 3,04%. Porém sob a avaliação da FOSP-SP, as duas metodologias apresentaram concordância (k=0,39;95%IC(0,29-0,50); p<<0,001). A metodologia TP apresentou taxas insatisfatórias e praticamente semelhantes de 3,20% para 3,60% (×2= 5,00; p=0,17), e de alterações citopatológicas de 5,60% para 4,20%. Em 87 casos, foram observadas alterações cervicais por uma das metodologias utilizadas; destas, em 83,91% foram detectados CT e 82,76% foram positivas para HPV, ocorrendo coinfecção em 65 casos (74,7%). Em 93,1% dos casos houveram alterações colposcópicas, observando-se uma associação estatisticamente significativa entre coinfecção HPV-CT e presença de lesão (p=0.037). Outras microfloras encontradas foram Gardnerella vaginalis (35,6%), cocos (18,4%), Candida sp (9,2%), Trichomonas vaginalis (6,9%), Lactobacillus sp (4,6%) e herpesvírus (1,15%). Flora mista (coinfecção por várias microfloras – com exceção de CT simultaneamente) ocorreram em 41,38% dos casos. No entanto, nenhuma associação da presença desses microrganismos não-virais e os herpesvírus com a gravidade das lesões intraepiteliais foram encontradas. Os subtipos de HPV mais frequentes foram 16 e 31 (34,3% e 17,15%, respectivamente). Porém nas lesões de maior gravidade, os mais prevalentes foram 16 e 18. Desta forma, concluimos que este estudo demonstra a superioridade da metodologia TP no diagnóstico citológico das amostras cervicais o que poderá contribuir na diminuição de possíveis perdas por repetição citológica e seguimento das pacientes. É importante chamar atenção para as infecções genitais, em especial a CT, que devem sem investigadas e tratadas adequadamente, haja vista, que coinfecções com o HPV estão associadas ao favorecimento de lesões cervicais, e podem evoluir a graus mais avançados. / This study evaluated the performance of cytological methodology net basis (ThinPrep-TP) with the conventional Pap cytology (CC) in the diagnosis of cytopathological findings and unsatisfactory results under the vision of a public service in the state of Pernambuco (LACEN -PE) and Oncocentro Foundation of São Paulo (FOSP-SP). We also evaluated whether there is an association between the presence of genital co-infections of human papillomavirus subtypes (HPV) with Chlamydia trachomatis (CT) and or other microflora, with the different stages of cervical abnormalities of patients. The study population of 525 women between the ages of 18-65 years, assisted by spontaneous demand, the Basic Health Units in the State of Pernambuco, in the period from April to November 2011. A standardized questionnaire with information on sociodemographic characteristics, sexual, reproductive habits (such as smoking, alcohol consumption and drug use) were obtained from all study patients. The presence of HPV DNA and CT were both diagnosed by polymerase chain reaction (PCR) and cytological examination was performed to detect other infections. To evaluate the relationship of genital infections with the presence of cervical intraepithelial changes, Fisher's exact test was used. The results showed that 11.05% of patients were under 25yrs, 30.86% were single, 6.86% had more than five sexual partners, 44% did not use contraception, 38.85% were users of alcohol, 24.38% smokers and 3.24% had used drugs before. Moreover, gynecological complaints were 42.01%; and 12.19% history of STD. When comparing the efficiency of two techniques used in diagóstico of cervical abnormalities in the view of LACEN-PE, it was observed that the two methodologies evaluated showed poor agreement between the methods (k = 0.19; 95% CI (0,11- 0.26), p << 0.001). TP method reduced the rate of unsatisfactory 4.38% to 1.71% (5.28 = 2 × p = 0.02) and the number of cytopathological changes diagnosed increased 2.47% to 3 04%. But in the assessment of FOSP-SP, the two methodologies showed reasonable agreement (k = 0.39; 95% CI (0.29 to 0.50); p << 0.001) .The TP methodology showed unsatisfactory results virtually rates similar 3.20% to 3.60% (× 2 = 5.00; p = 0.17), and cytological changes from 5.60% to 4.20%. In 87 cases, cervical abnormalities were observed by any of the methods used, and of these, 83.91% were detected CT, and 82.76% were positive for HPV, occurring co-infection in 65 cases (74.7%). In 93.1% of cases there were colposcopic changes, observing a statistically significant association between co-infection HPV-CT and presence of lesions (p = 0.037). Other microflora were found Gardnerella vaginalis (35.6%), coconut (18.4%), Candida sp (9.2%), Trichomonas vaginalis (6.9%), Lactobacillus sp (4.6%) and herpesviruses (1.15%). Mixed flora (co-infection with various microflora - CT exception with both) occurred in 41.38% of cases. However, no association between the presence of non-viral organisms and herpesviruses with the severity of intraepithelial lesions were found. The most common HPV subtypes there were 16 and 31 (34.3% and 17.15%, respectively). But in more severe injuries, the most prevalent were 16 and 18. Thus, we conclude that this study demonstrates the superiority of TP methodology in the cytological diagnosis of cervical samples which could contribute to decrease possible losses by repetition and cytologic follow-up of patients . It is important to draw attention to the genital infections, especially CT, which are not investigated and dealt with appropriately, given that co-infections with HPV are associated with the favoring of cervical lesions, and can progress to more advanced degrees.