We first studied factors associated with the rate of colonoscopy by primary care physicians (PCPs) in Ontario between the years 1996 and 2005. Next, we conducted an Instrumental Variable Analysis (IVA) to estimate the effect of colonoscopy on colorectal cancer (CRC) incidence and mortality on average-risk subjects aged 50-74 years. Finally, we explored two study cohorts, one by including subjects who had the outcomes during the exposure period (unselected cohort) and the other cohort by excluding those subjects (restricted cohort). We estimated the absolute risk reduction associated with colonoscopy in preventing CRC incidence and mortality using traditional regression analysis, propensity score analysis and IVA. PCPs who were Canadian medical graduates and with more years of experience were more likely to use colonoscopy. PCPs were more likely to use colonoscopy if their patient populations were predominantly women, older, had more illnesses, and if their patients resided in less marginalized neighborhoods (lower unemployment, fewer immigrants, higher income, higher education, and higher English/French fluency). Using PCP rate of discretionary colonoscopy as an instrumental variable, receipt of colonoscopy was associated with a 0.60% absolute reduction in 7-year CRC incidence and a 0.17% absolute reduction in 5-year risk of death due to CRC. The unselected cohort showed an increase in CRC incidence and mortality associated with colonoscopy, whereas the restricted cohort showed a reduction in CRC incidence and mortality associated with colonoscopy. In the restricted cohort, using different statistical models, the absolute risk reduction varied from 0.52-0.60% for CRC incidence and 0.08-0.17% for CRC mortality. There were social disparities in the use of colonoscopy by PCPs and this disparity increased as the overall use of colonoscopy increased over time. Colonoscopy is effective in reducing incidence and mortality due to CRC. Different methods of subject selection and statistical analysis provided different estimates of colonoscopy effectiveness.

abstract: Colorectal cancer is the second-highest cause of cancer-related deaths in the United States with approximately 50,000 estimated deaths in 2015. The advanced stages of colorectal cancer has a poor five-year survival rate of 10%, whereas the diagnosis in early stages of development has showed a more favorable five-year survival rate of 90%. Early diagnosis of colorectal cancer is achievable if colorectal polyps, a possible precursor to cancer, are detected and removed before developing into malignancy. The preferred method for polyp detection and removal is optical colonoscopy. A colonoscopic procedure consists of two phases: (1) insertion phase during which a flexible endoscope (a flexible tube with a tiny video camera at the tip) is advanced via the anus and then gradually to the end of the colon--called the cecum, and (2) withdrawal phase during which the endoscope is gradually withdrawn while colonoscopists examine the colon wall to find and remove polyps. Colonoscopy is an effective procedure and has led to a significant decline in the incidence and mortality of colon cancer. However, despite many screening and therapeutic advantages, 1 out of every 4 polyps and 1 out of 13 colon cancers are missed during colonoscopy. There are many factors that contribute to missed polyps and cancers including poor colon preparation, inadequate navigational skills, and fatigue. Poor colon preparation results in a substantial portion of colon covered with fecal content, hindering a careful examination of the colon. Inadequate navigational skills can prevent a colonoscopist from examining hard-to-reach regions of the colon that may contain a polyp. Fatigue can manifest itself in the performance of a colonoscopist by decreasing diligence and vigilance during procedures. Lack of vigilance may prevent a colonoscopist from detecting the polyps that briefly appear in the colonoscopy videos. Lack of diligence may result in hasty examination of the colon that is likely to miss polyps and lesions. To reduce polyp and cancer miss rates, this research presents a quality assurance system with 3 components. The first component is an automatic polyp detection system that highlights the regions with suspected polyps in colonoscopy videos. The goal is to encourage more vigilance during procedures. The suggested polyp detection system consists of several novel modules: (1) a new patch descriptor that characterizes image appearance around boundaries more accurately and more efficiently than widely-used patch descriptors such HoG, LBP, and Daisy; (2) A 2-stage classification framework that is able to enhance low level image features prior to classification. Unlike the traditional way of image classification where a single patch undergoes the processing pipeline, our system fuses the information extracted from a pair of patches for more accurate edge classification; (3) a new vote accumulation scheme that robustly localizes objects with curvy boundaries in fragmented edge maps. Our voting scheme produces a probabilistic output for each polyp candidate but unlike the existing methods (e.g., Hough transform) does not require any predefined parametric model of the object of interest; (4) and a unique three-way image representation coupled with convolutional neural networks (CNNs) for classifying the polyp candidates. Our image representation efficiently captures a variety of features such as color, texture, shape, and temporal information and significantly improves the performance of the subsequent CNNs for candidate classification. This contrasts with the exiting methods that mainly rely on a subset of the above image features for polyp detection. Furthermore, this research is the first to investigate the use of CNNs for polyp detection in colonoscopy videos. The second component of our quality assurance system is an automatic image quality assessment for colonoscopy. The goal is to encourage more diligence during procedures by warning against hasty and low quality colon examination. We detect a low quality colon examination by identifying a number of consecutive non-informative frames in videos. We base our methodology for detecting non-informative frames on two key observations: (1) non-informative frames most often show an unrecognizable scene with few details and blurry edges and thus their information can be locally compressed in a few Discrete Cosine Transform (DCT) coefficients; however, informative images include much more details and their information content cannot be summarized by a small subset of DCT coefficients; (2) information content is spread all over the image in the case of informative frames, whereas in non-informative frames, depending on image artifacts and degradation factors, details may appear in only a few regions. We use the former observation in designing our global features and the latter in designing our local image features. We demonstrated that the suggested new features are superior to the existing features based on wavelet and Fourier transforms. The third component of our quality assurance system is a 3D visualization system. The goal is to provide colonoscopists with feedback about the regions of the colon that have remained unexamined during colonoscopy, thereby helping them improve their navigational skills. The suggested system is based on a new 3D reconstruction algorithm that combines depth and position information for 3D reconstruction. We propose to use a depth camera and a tracking sensor to obtain depth and position information. Our system contrasts with the existing works where the depth and position information are unreliably estimated from the colonoscopy frames. We conducted a use case experiment, demonstrating that the suggested 3D visualization system can determine the unseen regions of the navigated environment. However, due to technology limitations, we were not able to evaluate our 3D visualization system using a phantom model of the colon. / Dissertation/Thesis / Doctoral Dissertation Biomedical Informatics 2015

A colonoscopia com magnificação de imagem (CMI), associada à cromoendoscopia, tem mostrado a possibilidade de se diferenciar lesões neoplásicas e não-neoplásicas. Duzentas e treze lesões colorretais foram magnificadas e analisadas, através da classificação de Kudo, por 3 observadores distintos e também comparadas com os resultados histopatológicos. Houve bom grau de concordância entre os observadores (Kappa = 0,561) para os diversos padrões de criptas. Não houve diferenças entre eles com relação à chance de acerto (p = 0,121; 0,500; 0,405). A acurácia do método foi de 84%, sensibilidade de 91,4%, especificidade de 67,2%, valores preditivos positivo e negativo de 86,6% e 79,3%, índice de Kappa de 0,61. Esses resultados mostram que a CMI não deve ser utilizada na definição de conduta frente a lesões polipóides / Magnifying colonoscopy (MC) associated with chromoendoscopy has showed the possibility of differentiating neoplastic from non-neoplastic lesions. Two hundred and thirteen lesions were magnifyied and analysed, according to Kudo's classification, by 3 observers and compared with histopathological results. There was a good agreement index among them (Kappa = 0.561) with respect to the aspects of the pits. No differences were found in relation to the possibility of being correct (p = 0.121; 0.500; 0.405). Accuracy of method was 84%, sensitivity of 91.4%, specificity of 67.2%, positive and negative predictive values of 86.6% and 79.3%; Kappa index of 0.61. These results show that MC must not be used to define what should be done with polypoid lesions

Submitted by Irene Nascimento (irene.kessia@ufpe.br) on 2016-07-13T16:53:32Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) LUIZ GUSTAVO DE QUADROS TESE.pdf: 9881637 bytes, checksum: d6ffb41dcf9858105a4bb9088ff3fd0f (MD5) / Made available in DSpace on 2016-07-13T16:53:32Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) LUIZ GUSTAVO DE QUADROS TESE.pdf: 9881637 bytes, checksum: d6ffb41dcf9858105a4bb9088ff3fd0f (MD5) Previous issue date: 2015-12-14 / Introdução: Não existe atualmente uma terapia para tratamento de pacientes com Doença de Crohn refratária quando os tratamentos convencionais como antiinflamatórios, esteroides, imunossupressores e agentes biológicos anti-TNF alfa falham. Neste contexto o Transplante Autólogo de Células Tronco Hematopoiéticas (TACTH) pode ser uma alternativa. Objetivos: O objetivo do estudo foi determinar, após o TACTH, os resultados clinicos e endoscópicos e a toxicicidade imediata nos pacientes com Doença de Crohn (DC) refratários na primeira série brasileira de dez (10) casos realizados em uma única instituição. Casuística e Métodos: Foram estudados retrospectivamente dez pacientes com DC refratários submetidos ao TACTH. O critério de inclusão foi um Índice de Atividade da Doença de Crohn (CDAI) maior que 240, Índice Crônico de Gravidade Craig (CSI) maior que 17, Harvey Bradshaw indice maior que quatro, doença comprovada colonoscopicamente e não respondedores a, pelo menos, dois agentes biológicos anti TNF alfa. O tratamento foi feito com ciclofosfamida e timoglobulina, seguido de infusão de células-tronco de sangue periférico não manipuladas e não selecionados, colhidas por leucaférese após condicionamento com Ciclofosfamida. Avaliação do TACTH durante o período de mobilização e condicionamento até os primeiros 30 dias após o procedimento foi feita utilizando os Critérios NCI Common Toxicity Criteria Questionnaire, CDAI e questionário de qualidade de vida (QV) Short Form 36. Avaliação por colonoscopia foi realizada utilizando como parâmetros as classificações de Rutgeerts, Índice de Gravidade Endoscópica da Doença de Chron (CDEIS) e escore endoscópico simples para Crohn (SES-CD), seis meses após o procedimento em sete pacientes. Resultados: A análise foi disponíveis para 10 pacientes (6 femininos e 4 masculinos), a idade média foi de 34 ± 8 anos (24-50), com CDAI no momento do transplante com mediana 311,6 (240 - 450,2), doença grave em quatro (57 , 1%) e três (42,9%) com doença moderada. Classificação Montreal, Idade: A1 28,6%, A2 57,1% e A3 14,3%; principais manifestações extraintestinais doenças autoimunes associadas: 42,9% B1, B2 42,9% e B1P: 14,3%; distúrbio gastrointestinal locais: L1: 14,3%, L3: 71,4%, L4: 14: 3. Apenas a toxicidade hematológica foi observada em todos os pacientes nas fases de mobilização e condicionamento: leucopenia, granulocitopenia, linfocitopenia, trombocitopenia e hipotensão em um paciente. Como toxicidade gastrointestinal, foi comum o surgimento de náuseas durante alguns dias em todo o período de mobilização e condicionamento. Também foram encontrados febre sem infecção em dois pacientes, assim como farmacodermia e infecção fúngica após enxerto, diagnosticada por CT de tórax, em um mesmo paciente. Nos primeiros 30 dias, apenas um paciente parecia ter reativação de CMV mas não confirmada. Qualidade de vida foi melhor em todos os pacientes e, em três domínios, esta melhora foi estatisticamente significativa. Conclusão: O procedimento foi seguro, com baixa toxicidade hematológica e com impacto clínico no CDAI e na QV. / Introduction: Currently no therapy exists to treat refractory Crohn disease when the conventional treatments based in anti-inflammatory, steroids, immunosuppressant and/or a biologic anti-TNF-α failed. In this scenario, Autologous Hematopoietic Stem cell Transplantation (AHSCT) may be an alternative. Goals: The objective of study was to determine, after AHSCT, the clinic and endoscopy outcome, as well as the immediate toxicity of patients with refractory Crohn’s disease in the first Brazilian case series of ten (10) patients from a single institution. Patients and Methods: Were studied ten patients retrospectively. The inclusion criteria were Crohn Disease Activity Index (CDAI) greater than 240, Craig Chronic severity index (CSI) greater than 17, Harvey Bradshaw index greater than four, comproved active disease by endocolonoscopy and lack of response to at least two anti TNFα biologic agents. The treatment was done with Cyclophosphamide and Thymoglobulin followed by infusion of unmanipulated and unselected peripheral blood stem cells, obtained by leukapheresis after Cyclophosphamide conditioning. The evaluation the Autologous Hematopoietic Stem Cell Transplantation during mobilization and conditioning period until the first 30 days after the procedure was performed using the NCI Common Toxicity Criteria Questionnaire, Chronic Disease Activity Index (CDAI) and Quality of Live (QoL) Short Form 3 questionnaire and Clinical Outcome Parameters. The evaluation by colonoscopy was dose through parameters Rutgeerts, Crohn’s Disease Endoscopic Index of Severity and Simple Endoscopic Score for Crohn’s six months after the procedure in seven patients. Results: The analysis was available for 10 patients (6 female and 4 male), with median age was 34 ± 8 years (24-50), with median CDAI at time of Transplantation of 311,6 (240 - 450,2) severe disease in four (57,1%) and moderate disease in three (42,9%). Montreal classification, Age: A1 28,6%, A2 57,1% e A3 14,3%; major extra intestinal manifestations associated autoimmune disorders: B1 42,9%, B2 42,9% e B1p:14,3%; gastrointestinal local disorder: L1: 14,3%, L3: 71,4%, L4: 14:3. Only hematologic toxicity was observed in all patients in mobilization and conditioning phases. Leukopenia, granulocytopenia, lymphocytopenia, thrombocytopenia, and hypotension were found in one patient. Concerning gastrointestinal toxicity, nausea was a frequent complaint for several days throughout the period of mobilization and conditioning. Further side-effects were fever without infection in two patients, as well as pharmacodermy and fungal infection after graft, diagnosed by chest CT, in the same patient. In the first 30 days, only one patient appeared to have CMV reactivation but it was not confirmed. Quality of life was better in all patients and the improvement in three domains was statistically significant. Conclusion: The procedure was safe, with low hematologic the toxicity, and has a clinical impact on CDAI and on QoL.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-10-18T12:19:11Z No. of bitstreams: 1 anapaulatellespiresdias.pdf: 1519258 bytes, checksum: 115fa6d893019191b30393d181c96383 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-10-25T12:07:25Z (GMT) No. of bitstreams: 1 anapaulatellespiresdias.pdf: 1519258 bytes, checksum: 115fa6d893019191b30393d181c96383 (MD5) / Made available in DSpace on 2016-10-25T12:07:26Z (GMT). No. of bitstreams: 1 anapaulatellespiresdias.pdf: 1519258 bytes, checksum: 115fa6d893019191b30393d181c96383 (MD5) Previous issue date: 2008-02-29 / O carcinoma colorretal (CCR) é a segunda neoplasia mais freqüente na população mundial. A alta incidência do CCR e a diferença nos resultados do tratamento desta neoplasia, de acordo com o estádio da doença, justificam os esforços para o rastreamento, prevenção e detecção precoce. Objetiva-se neste estudo descrever os aspectos: epidemiológicos, endoscópicos e anatomopatológicos das neoplasias colorretais em uma série de casos e avaliar o papel da colonoscopia na prevenção do CCR. Trata-se de estudo descritivo de série de casos atendida em centro especializado em endoscopia digestiva, no período de janeiro de 2002 a dezembro de 2006. Foram coletados dados sobre 1.962 colonoscopias realizadas em 1.491 indivíduos e, em 492 (33%) foram identificadas lesões polipóides. 408 indivíduos foram considerados para fins de análise. Na série de casos 70% dos indivíduos eram assintomáticos. A prevalência de neoplasias colorretais foi de 50% (60/120) em homens e de 42,4% em mulheres (122/288). As neoplasias foram detectadas em 138 dos 287 indivíduos (48%), com 50 anos ou mais, e a sua prevalência foi significantemente maior do que naqueles com menos de 50 anos (44/121) 36,3% (p=0,01). Verificou-se que 58,9% dos indivíduos com neoplasia e neoplasia avançada apresentavam história familiar positiva para câncer de mama, útero, ovário e/ou colorretal. Nos 408 indivíduos, foram realizadas 679 colonoscopias, com retirada de 959 lesões polipóides; destas, 463 (48,3%) eram neoplásicas, incluindo 13(1,35%) adenocarcinomas. Nas lesões menores que 5 mm, foi evidenciado displasia em 36% (346/959). No colon proximal, 21% (85/408) dos indivíduos apresentavam lesões neoplásicas e 2% (8/408), neoplasias avançadas, incluindo seis casos de adenocarcinoma sem qualquer evidência de lesão em colon distal. Dentre os 232 indivíduos que apresentavam lesões neoplásicas (benignas e ou avançadas), 130 (56%) apresentavam apenas lesões em colon proximal. Se o rastreamento fosse realizado apenas com a retossigmoidoscopia, a perda diagnóstica de lesões neoplásicas benignas seria de 76(62,3%) nas mulheres e 29(48,3%) nos homens. Em relação ao adenocarcinoma, a perda diagnóstica seria de 50% para ambos os sexos. Neoplasias colorretais são comuns em indivíduos assintomáticos. Sexo masculino, idade avançada e história familiar para câncer são fatores de risco para a detecção de lesões. A colonoscopia consiste em método eficaz de rastreamento para o CCR, a remoção de lesões neoplásicas colorretais interfere diretamente na história natural desta forma de câncer. / The colorectal carcinoma (CRC) is the second most frequent cancer in the world population. The high incidence of CRC and the difference in the results of the treatment of cancer, according to the stage of disease justify the efforts for screening, prevention and early detection. The objective of this study was to describe the epidemiological, endoscopic and pathological of polypoid lesions and colorectal cancers and assess the role of colonoscopy in preventing the CRC. This is a descriptive study of number of cases addressed in centre specializing in gastrointestinal endoscopy. In the period January 2002 to December 2006, colonoscopies were performed in 1962 and 1,491 individuals in 492 (33%) of these have been identified polypoid lesions; 408 individuals were considered for analysis. The data were included and analyzed in the Epi Info-2000. In a series of cases studied, 60% of the subjects were asymptomatic. The prevalence of colorectal cancers was 50% (60/120) in men and 42.4% in women (122/288). The cancers were detected on 138 of the 287 individuals (48%) with 50 years or more, and their prevalence was significantly higher than those with less than 50 years (44/121) 36.3% (p = 0.01). It was found that 58.9% of individuals with advanced cancer and cancer had positive family history for cancer of the breast, uterus, ovary, or colorectal. In 408 individuals, 679 colonoscopies were performed, with withdrawal of 959 polypoid lesions; these, 463 (48.3%) were neoplasms, included 13 adenocarcinomas. In lesions smaller than 5 mm, was shown dysplasia in 36% (346/959). In the proximal colon, 21% (85/408) of the subjects had neoplastic lesions in 2% (8 / 408), advanced malignancies, including six cases of adenocarcinoma without any evidence of damage in distal colon. The indication of colonoscopy only by the presence of lesions in the distal colon is controversial. Among the 232 individuals who had neoplastic lesions (benign, or advanced), 130 (56%) had only injuries in proximal colon. If the screening was done only with the retossigmoidoscopy, loss diagnosis of benign neoplastic lesions would be 76 (62.3%) in women and 29 (48.3%) in men. Regarding adenocarcinoma, the loss would be diagnostic of 50% for both sexes. Colorectal neoplasms are common even in asymptomatic subjects. Male, age and family history for cancer are risk factors for the detection of lesions. A colonoscopy is the most effective method of screening for the CRC, indicated for all individuals over 50 years old because, by identifying and removing neoplastic lesions, the colonoscopist have the ability to interfere directly in the natural history of this form of cancer.

Aims: The purpose of the research was to investigate the benefits of a hereditary colorectal cancer registry in the management of patients and families with Lynch syndrome. In study one, a systematic review was performed to quantify the impact of registration and screening on colorectal cancer (CRC) incidence and mortality, with comparison between familial adenomatous polyposis (FAP) and Lynch syndrome (LS). In study two, a regional Lynch syndrome registry was utilised to evaluate the uptake of predictive testing and colorectal screening among first-degree relatives (FDRs) and investigate novel methods for engaging at-risk relatives, including an enhanced role for the general practitioner (GP). In study three, the registry was used to investigate proposed associations between Lynch syndrome and prostate and bladder cancer. In study four, mismatch repair-deficient (dMMR) CRCs from Lynch syndrome patients and randomised-controlled trials (RCTs) were used to evaluate a novel prognostic biomarker, beta-2 microglobulin (B2M). Methods: An electronic database search was conducted to identify studies describing CRC incidence and/or mortality in FAP or LS, with comparison of either: 1) screened and unscreened patients or 2) patients ‘before and after’ establishment of the registry. Using the Manchester regional Lynch syndrome registry database, the uptake of predictive testing and colorectal screening among FDRs was assessed with Kaplan-Meier analysis. Novel strategies for improving engagement were explored via a patient advisory group discussion and a regional primary care questionnaire. Cases of prostate and bladder cancer in male mutation carriers and their male FDRs were identified, and cumulative and relative risks were calculated, using expected rates from cancer registry data. DNA from 350 dMMR CRC specimens from Lynch syndrome patients and RCTs were tested for B2M mutations using Sanger sequencing, and correlated with clinical outcome. Results: 43 studies were included in the systematic review (33 FAP; 10 Lynch). Registry-based screening was associated with a significant reduction in CRC incidence and in Lynch syndrome, CRC-related mortality was negligible in those undergoing surveillance. 242 Lynch syndrome families were recorded on the Manchester Lynch syndrome registry. 329 of 591 (55.7%) eligible FDRs had undergone predictive testing. Uptake was significantly lower in males and younger age groups (<25 yrs). Compliance with colorectal screening was excellent following a mutation positive predictive test but poor in untested individuals (97.3% vs 35.0%). Eight prostate cancers were identified in 821 male LS mutation carriers and male FDRs. MSH2 mutation carriers had a ten-fold increased risk of prostate cancer (RR 10.41; 95%CI 2.80, 26.65) but no association with bladder cancer was identified. 69/286 (24.1%) of dMMR CRCs contained significant B2M mutations. B2M mutations were associated with complete absence of recurrence (0/39) during follow-up in the QUASAR trial (stage II), compared with 14/77 (18.2%) in wild-type B2M (p=0.005). Conclusion: Studies consistently report that registration and screening result in a reduction of CRC incidence and mortality in FAP and LS (Level 2a evidence, Grade B recommendation). Funding and managerial support for registries should be made available. Uptake of predictive testing and colorectal screening in Lynch syndrome could be substantially improved, particularly among males and younger age groups, but this requires advances in communication with at-risk relatives. It is unlikely that GPs will actively participate without considerable support from genetics services. A trial of PSA screening in MSH2 mutation carriers from 50 years would be appropriate. B2M mutation status has potential clinical utility as a prognostic biomarker in stage II dMMR CRC.

Colonoscopy provides a minimally invasive tool for examining and treating the colon without surgery, but current endoscope designs still cause a degree of pain and injury to the colon wall. The most common colonoscopies are long tubes inserted through the rectum, with locomotion actuators, fiber optic lights, cameras, and biopsy tools on the distal end. The stiffness required to support these tools makes it difficult for the scopes to navigate the twisted path of the colon without damaging the inside wall of the colon or distorting its shape. In addition, little is known about how sharp and forceful endoscopes can be without accidentally cutting into tissue during navigation. In order to solve the requirements of stiffness (to support tools) and flexibility (to navigate turns), we expanded on a design by Zehel et al. [49], who proposed surrounding a flexible endoscope with an external exoskeleton structure, with controllable stiffness. The exoskeleton structure is comprised of rigid, articulating tubular units, which are stiffened or relaxed by four control cables. The stiffened or locked exoskeleton structure aids navigation and provides stability for the endoscope when it protrudes beyond the exoskeleton structure for examination and procedures. This research determined the design requirements of such an exoskeleton structure and simulated its behavior in a sigmoid colon model. To predict just how pointed an endoscope can be without damaging tissue under a given force, we extrapolated a strength model of the descending colon from published stress-strain curves of human colon tissue. Next we analyzed how friction, cable forces, and unit angles interact to hold the exoskeleton structure in a locked position. By creating two- and three-dimensional models of the exoskeleton structure, we optimized the dimensions of the units of an exoskeleton structure (diameter, thickness, and leg angle) and cable holders ( cable attachment location) to achieve the turns of the sigmoid colon, while still remaining lockable. Models also predicted the loss of force over the exoskeleton structure due to curving, further determining the required cable angles and friction between units. Finally we determined how the stiffness of the endoscope stem affected locking ability and wear inside the exoskeleton structure. / Ph. D.

No description available.

<p>UVOD: Kolorektalni karcinom je na trećem mestu po učestalosti oboljevanja od svih karcinoma uz porast incidencije CRC u visoko razvijenim zemljama.70% obolelih od CRC je starije od 65 godina uz veću incidenciju proksimalnih karcinoma u odnosu na distalne u svim uzrasnim grupama i kod oba pola. Smatra se da bi 66-75% slučajeva CRC moglo biti izbegnuto zdravim načinom života. 75% CRC nastaje iz adenomatoznih preko polip kancer sekvence i da vi&scaron;e od 90% adenoma neće progredirati u karcinom. U studijama skrining kolonoskopija prijavljeno je 6-12% neviđenih velikih polipa i ko 5% CRC na inicijalnom kolonoskopskom pregledu. Postoperativne periodične kolonoskopije nakon operacije kolorektalonog karicinoma imaju za cilj otkrivanje metahronih carcinoma polipa kao pojavu bolesti na anastomozi ali nije dokazani benefit u preživljavanju bolesnika koji su imali učestalije postoperativne kolonoskopije (na godinu dana) u odnosu na one koji su praćenina 3 ili 5 godina. CILJEVI ISTRAŽIVANJA: Prospektivno ispitivanje pojave intervalnih lezija kolona (malignih i premalignih) u periodu od 2-7 godine od prve negativne kolonoskopije bez obzira na razlog pregleda. Ispitivanje razlike u životnim navikama između ispitanika u zavisnosti od nalaza na ponovljenoj kolonoskopiji. Retrospektivna analiza svih dijagnostičkih i kontrolnih kolonoskopija. MATERIJAL I METODE: Ponavljana je kolonoskopija kod ispitanika koj su na dijagnostičkim kolonoskopijama rađenim na Institutu za onkologiju Vojvodine u periodu 2005-2011. imali uredan kolonoskopski nalaz. Od 160 pozvanih ispitanika na ponovnu kolonoskopiju se odazvalo 64 ispitanika a 151 ispitanik je popunio upitnik o životnim navikama. Urađena je i retospektivna analiza 2750 dijagnostičkih kolonoskopija. Analizirani su rezultati 1064 prvih postoperativnih kolonoskopija kao i nalazi sa 1147 ponovljenih kolonoskopija kod ispitanika operisanih od kolorektalnog carcinoma koji su imali uredan nalaz na prvoj kolonoskopiji. REZULTATI: Od 160 pozvanih ispitanika,njih 64 (42,3%) se odazvalo na ponovni pregled (45 žena i 19 mu&scaron;karaca) prosečne starosti60,13 godina. Kod 15 ispitanika(24.3%) nađeno je ukupno 22 polipa (10 žena i 5 mu&scaron;karaca) bez statistički značajne razlike u pozitivnosti nalaza u odnosu na pol (x2test; x2=0,014; p=0,904) i pozitivnu porodičnu anamnezu (x2test; x2=0,125; p=0,724). 12 slucajeva (14,06%) su bili polipi visokog rizika: 5 (41.6%) lokalizovano u proksimalnom kolonu i 7 (58.3% ) u distalnom kolonu. Nije dijagnostikovan nijedan intervalni karcinom. Nije dokazana statistički značajna razlika u pozitivnosti nalaza na ponovljenoj kolonoskopiji u odnosu na razmak posmatran u grupama do 3 i do 5 godina od predhodne kolonoskpije (x2test; x2=0,020; p=0,887) niti ukoliko se posmatra po grupama do 5 i preko 5 godina od negative kolonoskopije (x2test; x2=3,082; p=0,079). Nema statistički značajne razlike u pozitivnosti nalaza na ponovljenoj kolonoskopiji u odnosu na to da li su pacijenti konzumiraju alkohol ili ne (x2test; x2=0,113; p=0,911) kao i u odnosu na to da li su pacijenti imali redovnu fizičku aktivnost (x2test; x2=0,476; p=0,490). Na dijagnostičkim kolonoskopijama je uočena statistički značajna razlika u uzrastu pacijenata u zavisnosti od razloga kolonoskopije (F=7,111; p=0,000) kod pacijenata kod kojih su dijagnostikovani polipi. Oni sa pozitivnom porodičnom anamnezom i polipima su statistički značajno mlađi u odnosu na ostale osim onih koji su se na pregled javili zbog bola u trbuhu poremećaja ritma stolice. Nije bilo statistički značajne razlike po polu, uzrastu, u razlogu kolonoskopije kod osoba sa dijagnostikovanim polipima. Statistički je značajniji broj žena sa lokalizacijom polipa u distalnom delu debelog creva u odnosu na proksimalni (x2test; x2=18,495; p=0,000). Kod mlađih uzrasnih grupa statistički značajnije su zastupljeni polipi u rektumu(x2test; x2=79,963; p=0,000). Ispitanici sa proksimalnom lokalizacijom polipa imaju 1,724 puta veću &scaron;ansu za adenome visokog rizika u odnosu na one sa distalnom lokalizacijom. Nema statistički značajne razlike u distribuciji karcinoma u odnosuna pol (x2test; x2=3,2110; p=0,201). Na 1064 prvih postoperativnih kolonoskopija je bilo ukupno 346 (32,5%) pozitivnih nalaza. Dijagnostikovano je 60 karcinoma od kojih je 43,3 % lokalizovano na anastomozi a kod 286 ispitanika nađeno je ukupno 546 polipa. Mu&scaron;karci statistički značajnije če&scaron;će imaju pozitiva nalaz (x2 test; x2=17,252; p=0,000). Bonferroni post hoc testom je utvrđeno da su polipi proksimalne lokalizacije statistički značajno veći od onih u rektumu (p=0,043). Na kontrolnim kolonoskopijama rađenim u cilju praćenja nakon resekcije kolorektalnog karcinoma multivarijatnom analizom ( pol, uzrast i vreme od operacije) utvrđeno je da mu&scaron;karci imaju 1,4 puta veću &scaron;ansu (OR=1,457) od žena za pojavu promena (polipa i karcinoma).Ispitanici kod kojih je od operacije pro&scaron;lo od 3 do 5 godina imaju 1,6 puta veću &scaron;ansu za pojavu promene u odnosu na one kod kojih je pro&scaron;la 1 godina (OR=1,605). ZAKLJUČAK: Kod 24.3% pregledanih ispitanika dijagnostikovani su polipi(jedan hipeplastičnii 21 adenoma ). 14,06% svih polipa je imalo karakteristike polipa visokog rizika bez statistički značajne razlike u pojavi polipa kod ispitanika kod kojih je pregled rađen 3,5 ili nakon 5 godina od prve negativne kolonoskopije. Nije dijagnostikovan niti jedan karcinom &scaron;to znači da nema potrebe za ponavljanjem kolonoskopija u kraćem vremenskom intervalu od unapred planirane kolonoskopije kod ispitanika koji su imali uredan inicijalni kolonoskopski nalaz &scaron;to se odnosi i na ponavljane kolonoskopije kod ispitanika operisanih od CRC-a. Na dijagnostičkim kolonoskopijama statistički značajniji broj žena sa lokalizacijom polipa u distalnom delu debelog creva u odnosu na proksimalni i nije zapažena razlika u distribuciji karcinoma u odnosu na pol i uzrast ispitanika.</p> / <p>INTRODUCTION:Colorectal cancer is the third most frequent illness of all carcinomas with an increase in the incidence of CRC in highly developed countries. 70% of patients with CRC are older than 65 years with higher incidence of proximal cancers compared to distal in all age groups and in both sexes. It is believed that 66-75% of CRC could be avoided through healthy lifestyle. 75% of CRC arise from adenomatous polyp cancer via sequences, and that more than 90% of adenoma will not progress to carcinoma. In studies of screening colonoscopy was reported 6-12% of unobserved large polyps and approximately 5% of the CRC on the initial colonoscopy.Postoperative periodic colonoscopy after colorectal cancer surgery aim to detect metachronous cancer and polyps and disease occurrence anastomoses but not proven survival benefit in subjects who had more frequent postoperative colonoscopy (per year) compared to those who were followed for 3 or 5 years. AIM:Prospective study of interval colon lesions occurrence (malignant and pre-malignant) in the period from 2-7 years after initial negative colonoscopy regardless of the reason for the check. Test of differences in lifestyle between subjects depending on the findings of the repeated colonoscopy.A retrospective analysis of all the diagnostic and control colonoscopy. METHODOLOGY: Repeated colonoscopy in subjects who are at-made diagnostic colonoscopy at the Oncology Institute of Vojvodina in the period 2005-2011 had normal colonoscopy findings. Of the 160 subjects invited to re colonoscopy for review responded 64 subjects and 151 subjects filled out a questionnaire about life habits. Retrospective analysis of 2750 and diagnostic colonoscopy has been done. Results of the 1064 first postoperative colonoscopy and results of the 1147 repeated colonoscopy in patients operated on for colorectal cancer that had normal findings on the first colonoscopy has been analyzed. RESULTS:Of the 160 invited subjects, 64 of them (42.3%) responded to the repeated review (45 women and 19 men), mean age 60.13 years. In 15 subjects (24.3%) found a total of 22 polyps (10 women and 5 men) with no statistically significant differences in positivity findings in relation to sex (x2test; x2 = 0.014; p = 0.904) and a positive family anamnesis (x2test; x2 = 0.125; p = 0.724).12 cases (14.06%) were high risk of polyps: 5 (41.6%) localized in the proximal colon, and 7 (58.3%) in the distal colon. Not a single interval cancer diagnosed. There was no statistically significant difference in positivity findings with repeated colonoscopy in relation to the distance observed in groups of 3 to 5 years from the previous colonoscopy (x2test; x2 = 0.020; p = 0.887) or when observed in groups up to 5 and over 5 years of negative colonoscopy (x2test; x2 = 3.082; p = 0.079). No statistically significant differences in positivity findings with repeated colonoscopy in relation to whether the patients consume alcohol or not (x2test; x2 = 0.113; p = 0.911) as well as in relation to whether patients are regularly exercising (x2test; x 2 = 0.476; p = 0.490). Statistically significant difference is confirmed in the age of patients at the diagnostic colonoscopy, depending on the reason for colonoscopy (F = 7.111; p = 0.000) in patients who were diagnosed polyps. Those with a family anamnesis and polyps were statistically significant younger in comparison to others except those who have come forward for review because of abdominal pain and bowel movement rhythm disturbances.There were no statistically significant differences by sex, age, the reason for colonoscopy in patients diagnosed with polyps.Statistically is more significant number of women with the localization of polyps in the distal part of the colon comparing to the proximal (x2test; x2 = 18,495; p = 0.000).In younger age groups are represented statistically significant polyps in the rectum (x2test; x2 = 79.963, p = 0.000). Subjects with proximal localization of polyps are 1,724 times more likely for high-risk adenomas compared to those with distal localization.No statistically significant differences in the distribution of cancer in relation to sex (x2test; x2 = 3.2110; p = 0.201).On the first postoperative colonoscopy in 1064 subjects there were a total 346 (32.5%) positive findings. 60 carcinoma diagnosed of which 43.3% is localized on the anastomosis and in 286 of the subjects had a total of 546 of the polyps.Men statistically significantly more likely to have positive findings (x2 test; x2 = 17,252; p = 0.000). Bonferroni post hoc test showed that polyps proximal localization significantly bigger than those in the rectum (p = 0.043). On the control colonoscopy-made for the purpose of monitoring after resection of colorectal cancer by multivariate analysis (sex, age and time of surgery) it has been found that men are 1.4 times more likely (OR = 1.457) than women for the occurrence of changes (polyps and cancers).Subjects having passed since the operation of 3 to 5 years are 1.6 times more likely to develop a change with respect to those in which the more than one year elapsed (OR = 1.605). CONCLUSION:In 24.3% subjects were diagnosed polyps (one hyperplastic and 21 adenomas).14.06% of all polyps had the characteristics of high-risk polyps with no statistically significant difference in the occurrence of polyps in subjects where the examination was done after 3,5 or 5 years since the first negative colonoscopy. No cancers diagnosed, meaning there is no need to repeat colonoscopy in a shorter period of time than pre-planned colonoscopy in subjects who had normal initial colonoscopy findings which refers to the repeated colonoscopies in subjects operated on for CRC.For diagnostic colonoscopy statistically significant number of women with the localization of polyps in the distal part of the colon compared to proximal and was not observed differences in the distribution of carcinoma in relation to sex and age of the subject.</p>

O uso do propofol em sedação para colonoscopia e outros procedimentos endoscópicos é cada vez mais frequente, devido ao seu rápido início de efeito e curto período de recuperação, com poucos efeitos residuais, o que o torna um anestésico ideal para o uso em condutas médicas realizadas em regime ambulatorial. Seu perfil farmacológico o posiciona como um anestésico adequado a métodos de administração endovenosa contínuos ou titulados, possibilitando maior controle na sua concentração plasmática. Devido à sua alta lipossolubilidade, o propofol difunde-se rapidamente ao sistema nervoso e outros tecidos aonde exercerá seu efeito clínico, intimamente ligado à propofolemia, com diminuição da atividade do sistema nervoso central, que determinará tanto a sedação nos seus diversos níveis, quanto os indesejados efeitos depressores do sistema cardiovascular e respiratório, podendo levar a uma diminuição importante do débito cardíaco e pressão arterial e também a uma depressão central do sistema regulatório da respiração, que pode gerar apneia ou hipoventilação significativas. O presente estudo teve como objetivo avaliar clinicamente, e com dosagem sérica, o propofol em três esquemas diferentes de infusão endovenosa. Foram avaliados aleatoriamente 50 pacientes submetidos à colonoscopia nos Serviços de Endoscopia do Hospital Ana Costa (Santos - SP) e no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (São Paulo-SP). Os pacientes foram divididos em três grupos, conforme o esquema de sedação que foi utilizado. O Grupo 1 recebeu fentanil no início, uma dose inicial de propofol de um miligrama por quilo em um minuto na indução, posteriormente recebeu propofol em infusão intermitente de doses fracionadas de 30 mg (bolus) conforme necessidade clínica durante o exame. O Grupo 2 recebeu fentanil no início, uma dose inicial de propofol de 1 mg/kg em um minuto na indução, após essa, recebeu propofol contínuo em uma solução diluída a 0,2% em solução glicosada a 5%, em uma dose inicial de 1 gota/kg de peso do paciente, o que equivale a aproximadamente 100 ug/kg/min, controlada manualmente e alterada conforme a necessidade clínica do exame. O Grupo 3 recebeu fentanil no início do exame, e propofol com dose calculada e administrada por bomba eletrônica computadorizada (Diprifusor®) em esquema de infusão contínua alvo controlada, numa dose inicial de indução de 4 ug/mL administrada em um minuto, baixada a 2 ug/mL após a dose inicial completada, e alteradas para mais ou para menos conforme a necessidade clínica do exame. Os pacientes foram monitorizados com eletrocardiografia contínua, pressão arterial não invasiva medida de dois em dois minutos, oximetria de pulso, capnografia de aspiração lateral e índice bispectral (BIS). As dosagens séricas de propofol foram feitas em três amostras de sangue colhidas por paciente. A primeira amostra, cinco minutos após a indução, a segunda ao endoscopista alcançar o ceco durante o exame e a terceira a cinco minutos após a última dose de propofol administrada ou ao término da infusão contínua, no final do exame. Não houve diferença estatística significativa entre os Grupos em relação às características físicas pessoais dos pacientes como: sexo (p = 0,976), estado físico de acordo com a American Society of Anestesiology (ASA) (p = 0,945), idade (p = 0,896), peso (p = 0,340), altura (p = 0,947), índice de massa corpórea (IMC) (p = 0406), nos parâmetros clínicos observados como menor valor de índice BIS (p = 0,871) e o tempo para alcançá-lo (p = 0,052), tempo médio do exame (p = 0,123) e efeitos adversos observados como a queda da saturação de oxigênio abaixo de 90% (p = 0,054). Houve diferença estatisticamente significativa nas pressões arteriais iniciais dos Grupos 2 e 3, que foram ligeiramente elevadas em relação ao Grupo 1 a sistólica (p = 0,008), diastólica (p = 0,018) e média (p = 0,008), porém após a indução, a média das pressões arteriais sistólica (p = 0,440), diastólica (p = 0,960) e média (p = 0,815), e as menores pressões alcançadas não foram estatisticamente diferentes: sistólica (p = 0,656), diastólica (p = 0,783) e média (p = 0,993). Não houve diferença estatística em relação à frequência cardíaca inicial (p = 0,453), média após indução (p = 0,702), e menor frequência cardíaca alcançada (p = 0,788). Houve diferença entre o número de agitações médias entre os Grupos (p = 0,001), sendo maior no Grupo 1, porém este número foi relacionado ao esquema de administração do propofol no Grupo 1, que foi administrado após a indução quando o paciente apresentou algum grau de agitação que necessitou aprofundamento anestésico. Houve queda de saturação de oxigênio em seis pacientes (12%) da amostra avaliada, revertidas em tempo menor que cinco minutos com manobras de elevação da mandíbula do paciente ou utilização de cânula de Guedel para desobstrução das vias aéreas. Antes das quedas na saturação de oxigênio, foram percebidas alterações típicas de obstrução de vias aéreas, hipopneia ou apneia nas ondas de capnografia em 16 pacientes (32%), sendo que, em alguns pacientes por mais de uma vez, demonstrando esse ser um bom parâmetro de monitorização para prevenir hipóxia, não houve diferença entre os Grupos no parâmetro de obstrução de vias aéreas/apneia (p = 0,543). Em relação à propofolemia, o comportamento médio dos pacientes dos três Grupos foi estatisticamente igual ao longo dos momentos de avaliação (p = 0,830), não havendo diferença média estatisticamente significativa entre os Grupos (p = 0,964). Não houve diferença entre o consumo do propofol médio por minuto de exame (p = 0,748). Em relação à análise de custos com a administração do propofol, o Grupo 1 apresentou o menor valor médio para as colonoscopias avaliadas com gasto médio de R$ 7,00, o Grupo 2 gastou em média R$ 17,50 e o Grupo 3 gastou em média R$ 112,70 com diferença estatisticamente significativa entre eles (p < 0,001). A conclusão é que os esquemas de administração do propofol testados foram seguros, e houve semelhança entre os Grupos nos parâmetros avaliados incluindo a propofolemia, porém com custos diferenciados entre eles. Em relação ao Grupo 1, devido ao maior número de agitações por minuto este pode ser um bom método para procedimentos mais curtos, para procedimentos mais longos os Grupos 2 e 3 se mostraram mais confortáveis para o responsável pela sedação / The use of propofol sedation for colonoscopies and other endoscopic procedures is increasing due to the rapid onset of effect and short recovery time with few residual effects, which makes it an ideal anesthetic for usingin outpatient medical procedures. Its pharmacological profile places it as a suitable anesthetic to continuous or titred intravenous administration, providing increased control in its plasma levels. Due to its high liposolubility, propofol diffuses rapidly to the central nervous system and other tissues where it shall perform its clinical effects, closely related to plasma concentration, and providing sedation at different levels, as much as the unwanted depressant effects of the cardiovascular and respiratory system, it may lead to a significant reduction in cardiac output and blood pressure and also a central regulatory breathing system depression, that can result in significant apnea or hypoventilation. This study aimed to evaluate clinically and serum, propofol in three different regimens of intravenous infusion. 50 patients submitted to colonoscopy in the endoscopy centers at Hospital Ana Costa (Santos - SP), and Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (São Paulo-SP), have been randomly assessed. Such patients were divided into three groups, according to the sedation scheme that was used for them. Group 1 received fentanyl at first, then a one milligram per kilogram propofol dose, at induction, in a minute, later they received intermittent infusion of propofol in fractionated doses of 30 mg (Bolus) according to clinical needs during the test. Group 2 received fentanyl in the beginning, a starting dose of propofol 1 mg/kg at induction in one minute, after that received propofol in a 0.2% solution diluted in 5% glucose solution at an initial 1 drop/kg of patient weight dose, equivalent to about one 100 u100/min, manually controlled and changed according to clinical need of the examination. Group 3 received in the beginning of the examination fentanyl and propofol calculated by target controlled continuous infusion electronic device (Diprifusor®), an initial loading dose of 4 ug/mL was administered in one minute, reduced at 2 ug/mL after the initial dose, changed up or down according to clinical needs of examination. Patients were monitorized with continuous electrocardiography, non-invasive blood pressure measured every two minutes, pulse oximetry, side suction capnography and bispectral index (BIS). Serum levels of propofol were performed on three samples of blood taken by each patient. The first sample, five minutes after the induction, the second when the endoscopist reached the cecum during the examination and the third sample five minutes after the last administered dose or the end of continuous infusion of propofol, at the end of the test. No statistically significant difference between groups with respect to personal physical characteristics of patients as: sex (p = 0.976), physical state according to the American Society of Anesthesiology (ASA) (p = 0.945), age (p = 0.896), weight (p = 0.340), height (p = 0.947), body mass index body (BMI) (p = 0.406) in clinical parameters observed as a minor reached bispectral index value (BIS) (p = 0.871) and time to reach it (p = 0.052), mean procedure time (p = 0.123) and adverse effects observed as a drop in oxygen saturation below 90% (p = 0.054). There was a difference between the number of averages agitations between groups (p = 0.001), being higher in Group 1, but that number was related to propofol administration scheme in Group 1, as this was administered after induction when the patient had some agitation that required deeper anesthesia. There was a statistically significant difference in initial blood pressures of groups 2 and 3, which were slightly higher compared to Group 1: systolic (p = 0.008), diastolic (p = 0.018) and mean (p=0.008), but after induction, the average systolic (p = 0.440), diastolic (p = 0.960) and average (p = 0.815), and lower pressures achieved: systolic (p = 0.656) and diastolic (p = 0.783) and average (p = 0.993), were not statistically different. There was no statistical difference from the initial heart rate (p = 0.453), average heart rate after induction (p=0.702), and lower heart rate achieved (p = 0.788). There was oxygen dessaturation below 90% in six patients (12%) of the study sample, reversed in less than five minutes with patient jaw thrust maneuver or use of Guedel cannula, for airway clearance. Before the declines in oxygen saturation, typical tract obstruction, hypopnea or apnea wave changes were noted in capnography in sixteen patients (32%), and in some patients for more than once, showing this to be a good monitoring parameter to prevent hypoxia in patients, there was no difference between Groups in the airway obstruction/apnea parameter (p = 0.543). Regarding serum propofol, the average behavior of patients in the three Groups were statistically similar over the time (p = 0.830), with no statistically significant mean difference between groups (p = 0.964). There was no difference between the average propofol consumption per minute examination (p = 0.748). Regarding cost analysis with the administration of propofol, Group 1 had the lowest average value for colonoscopies evaluated with an average expense of R$ 7.00, Group 2 spent on average R$ 17.50 and the Group spent 3 on average R$ 112.70 with a statistically significant difference (p < 0.001). The conclusion is that propofol administration schemes tested were safe and there was similarity between the Groups in the evaluated parameters including propofolemia, but with different costs among them. With respect to Group 1 due to the larger number of agitations per minute, this is a good method for shorter procedures, for longer procedures groups 2 and 3 were more comfortable for the person responsible for sedation