INTRODUÇÃO: O câncer do reto médio e distal ainda é assunto bastante controverso, especialmente no que se refere ao estadiamento locorregional e opções terapêuticas. Busca-se um método sensível e específico para a avaliação da profundidade de invasão da parede retal e o envolvimento linfonodal. O adequado estadiamento da neoplasia do reto extraperitoneal é de suma importância no manejo terapêutico e prognóstico do paciente. Diversos métodos têm sido descritos para a avaliação da disseminação locorregional das neoplasias do reto, que variam desde o toque retal até a ressonância magnética da pelve e a ultrassonografia endorretal bi e tridimensional. OBJETIVO: Correlacionar os achados da profundidade de invasão tumoral na parede retal (T), comprometimento linfonodal (N), extensão e porcentagem de acometimento da lesão à ultrassonografia endorretal tridimensional (USER-3D) com o exame anatomopatológico (AP) de pacientes portadores de neoplasia de reto extraperitoneal submetidos a procedimento cirúrgico após o diagnóstico e estadiamento clínico prévio. MÉTODO: Estudo prospectivo foi realizado com pacientes portadores de neoplasia de reto médio e distal seguidos no Instituto Central (IC) e no Instituto do Câncer do Estado de São Paulo (ICESP), do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP) que foram submetidos a USER-3D pré-operatório. Os parâmetros analisados por meio do USER-3D foram comparados aos achados da anatomia patológica do espécime cirúrgico obtido após o procedimento. Os exames de USER-3D foram realizados pelo mesmo médico, sendo cego dos outros métodos diagnósticos e dos achados da patologia, a qual também não tinha os resultados do estadiamento clínico pré-operatório. Todos os pacientes foram submetidos a enema evacuatório no dia anterior e na manhã do exame. Foram avaliados a sensibilidade, especificidade, valores preditivos positivo e negativo, área sobre a curva e o índice Kappa do USER-3D em comparação ao anatomopatológico, considerado exame padrão ouro. O coeficiente de correlação intraclasse (CCI) foi utilizado para analisar a extensão e porcentagem de acometimento da lesão na parede retal. RESULTADOS: No período de 3 anos, 44 pacientes foram estudados, 27 mulheres, com idade média de 63,5 anos. Houve 12 lesões benignas e 32 malignas de reto, sendo 30 submetidas à ressecção local e 14 à radical. O USER-3D determinou a diferenciação da profundidade de invasão tumoral na submucosa com sensibilidade de 77,3% (CI95% - 54,6%-92,2%), especificidade de 86,4% (CI95% - 65.1%-97.1%), valor preditivo positivo de 85% (CI95% - 62,1%-96,8%), valor preditivo negativo de 79,2% (CI95% - 57,8%-92,9%) e área sobre a curva de 0,82% (CI95% - 0,7%-0,96%). O índice Kappa ponderado para profundidade de invasão da parede retal (T) foi de 0,672 (IC95%: 0,493; 0,850), considerado grau de concordância substancial. Para o envolvimento linfonodal (N) não houve concordância adequada entre o USER-3D e o anatomopatológico (k=-0,164) nos 14 casos analisados. A CCI calculada para extensão da lesão foi moderada (0,45) para a extensão em centímetros, mas adequada (0,66) para porcentagem de envolvimento da circunferência. O gráfico de Bland-Altman mostrou que lesões com extensão de até 5 cm e 50% de acometimento têm melhor correlação com o espécime cirúrgico. CONCLUSÕES: USER-3D foi eficaz para a determinação da invasão da parede retal, sendo seguro na determinação da extensão de lesões até 5 cm e porcentagem de acometimento da circunferência até 50%. O método mostrou baixa eficácia na avaliação linfonodal, em subgrupo limitado de pacientes / INTRODUCTION: Loco-regional staging and treatment of extra peritoneal rectal neoplasms is still a controversial subject. There is no perfect method, substantially sensitive and specific for staging rectal wall invasion and lymph node involvement. Adequate oncologic staging of rectal neoplasias has major importance in both, treatment and prognostic evaluation. Therefore, the use of supplementary diagnostic methods such as endorectal ultrasound (ERUS) and magnetic resonance imaging (MRI) of the pelvis can promote an accurate assessment of tumor invasion in the rectal wall and lymph node involvement. OBJECTIVE: To correlate the findings of three-dimensional (3D) ERUS with pathology specimen of extra peritoneal rectal neoplasia referred directly to surgery after diagnosis, in regards to depth of rectal wall invasion (T), lymph node involvement, percentage of circumferential rectal wall invasion and tumor extension. METHODS: A prospective study was performed in patients with middle and distal rectal tumors followed at University of São Paulo, School of Medicine and Cancer Institute of State of São Paulo (ICESP), who underwent 3D-ERUS for preoperative evaluation. The parameters analyzed with 3D-ERUS were compared with pathology findings of the surgical specimen obtained after the procedure. A single doctor who performed the exams reported the 3D-ERUS studies and was blind of other methods as well as the pathologic findings. All patients underwent retrograde bowel enema the day before and in the morning of the test. The authors evaluated sensitivity, specificity, positive and negative predictive values, area under curve and kappa index of the 3D-ERUS as compared to pathologic findings, considered the gold standard. For extension and percentage of tectal wall involvement intraclass correlation index was applied. RESULTS: At 3-years period, 44 patients were studied, 27 females, with a mean age of 63.5 years, who had 12 rectal adenomas and 32 adenocarcinomas and underwent local resection (30) or radical resection (14). Value for 3D-ERUS to determine depth of rectal wall invasion sensitivity was 77.3% (CI95% - 54.6%-92.2%), specificity was 86.4% (CI95% - 65.1%- 97.1%), positive predictive value was 85% (CI95% - 62.1%- 96.8%), negative predictive value was 79.2% (CI95% - 57.8%-92.9%) and area under curve was 0,82% (CI95% - 0.7%-0.96%). The weighted kappa index for the depth of invasion in the rectal wall (T) evaluation was 0.67 (IC95%: 0.49; 0.85), considered substantial agreement. For N involvement there was any agreement between 3D-ERUS and histopathology, with K=-0.164. Intraclass correlation was calculated for lesion extension and was moderate (0.45) for extension in centimeters and adequate (0.66) for percentage of circumference involvement. A Bland-Altman graph was performed and showed that tumor extensions until 5 cm and 50% of wall involvement have a good correlation to specimen size. CONCLUSION: 3D-ERUS was effective for determining rectal wall invasion and evaluation of extension of lesions until 5 cm and 50% of rectal wall involvement. However, this method showed a lack of efficacy for evaluation of lymph node involvement for early rectal tumors in this limited subset of patients

Source: Masters Abstracts International, Volume: 47-01, page: 0318. Adviser: Janice Cormier. Includes bibliographical references

INTRODUÇÃO: O câncer do reto médio e distal ainda é assunto bastante controverso, especialmente no que se refere ao estadiamento locorregional e opções terapêuticas. Busca-se um método sensível e específico para a avaliação da profundidade de invasão da parede retal e o envolvimento linfonodal. O adequado estadiamento da neoplasia do reto extraperitoneal é de suma importância no manejo terapêutico e prognóstico do paciente. Diversos métodos têm sido descritos para a avaliação da disseminação locorregional das neoplasias do reto, que variam desde o toque retal até a ressonância magnética da pelve e a ultrassonografia endorretal bi e tridimensional. OBJETIVO: Correlacionar os achados da profundidade de invasão tumoral na parede retal (T), comprometimento linfonodal (N), extensão e porcentagem de acometimento da lesão à ultrassonografia endorretal tridimensional (USER-3D) com o exame anatomopatológico (AP) de pacientes portadores de neoplasia de reto extraperitoneal submetidos a procedimento cirúrgico após o diagnóstico e estadiamento clínico prévio. MÉTODO: Estudo prospectivo foi realizado com pacientes portadores de neoplasia de reto médio e distal seguidos no Instituto Central (IC) e no Instituto do Câncer do Estado de São Paulo (ICESP), do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP) que foram submetidos a USER-3D pré-operatório. Os parâmetros analisados por meio do USER-3D foram comparados aos achados da anatomia patológica do espécime cirúrgico obtido após o procedimento. Os exames de USER-3D foram realizados pelo mesmo médico, sendo cego dos outros métodos diagnósticos e dos achados da patologia, a qual também não tinha os resultados do estadiamento clínico pré-operatório. Todos os pacientes foram submetidos a enema evacuatório no dia anterior e na manhã do exame. Foram avaliados a sensibilidade, especificidade, valores preditivos positivo e negativo, área sobre a curva e o índice Kappa do USER-3D em comparação ao anatomopatológico, considerado exame padrão ouro. O coeficiente de correlação intraclasse (CCI) foi utilizado para analisar a extensão e porcentagem de acometimento da lesão na parede retal. RESULTADOS: No período de 3 anos, 44 pacientes foram estudados, 27 mulheres, com idade média de 63,5 anos. Houve 12 lesões benignas e 32 malignas de reto, sendo 30 submetidas à ressecção local e 14 à radical. O USER-3D determinou a diferenciação da profundidade de invasão tumoral na submucosa com sensibilidade de 77,3% (CI95% - 54,6%-92,2%), especificidade de 86,4% (CI95% - 65.1%-97.1%), valor preditivo positivo de 85% (CI95% - 62,1%-96,8%), valor preditivo negativo de 79,2% (CI95% - 57,8%-92,9%) e área sobre a curva de 0,82% (CI95% - 0,7%-0,96%). O índice Kappa ponderado para profundidade de invasão da parede retal (T) foi de 0,672 (IC95%: 0,493; 0,850), considerado grau de concordância substancial. Para o envolvimento linfonodal (N) não houve concordância adequada entre o USER-3D e o anatomopatológico (k=-0,164) nos 14 casos analisados. A CCI calculada para extensão da lesão foi moderada (0,45) para a extensão em centímetros, mas adequada (0,66) para porcentagem de envolvimento da circunferência. O gráfico de Bland-Altman mostrou que lesões com extensão de até 5 cm e 50% de acometimento têm melhor correlação com o espécime cirúrgico. CONCLUSÕES: USER-3D foi eficaz para a determinação da invasão da parede retal, sendo seguro na determinação da extensão de lesões até 5 cm e porcentagem de acometimento da circunferência até 50%. O método mostrou baixa eficácia na avaliação linfonodal, em subgrupo limitado de pacientes / INTRODUCTION: Loco-regional staging and treatment of extra peritoneal rectal neoplasms is still a controversial subject. There is no perfect method, substantially sensitive and specific for staging rectal wall invasion and lymph node involvement. Adequate oncologic staging of rectal neoplasias has major importance in both, treatment and prognostic evaluation. Therefore, the use of supplementary diagnostic methods such as endorectal ultrasound (ERUS) and magnetic resonance imaging (MRI) of the pelvis can promote an accurate assessment of tumor invasion in the rectal wall and lymph node involvement. OBJECTIVE: To correlate the findings of three-dimensional (3D) ERUS with pathology specimen of extra peritoneal rectal neoplasia referred directly to surgery after diagnosis, in regards to depth of rectal wall invasion (T), lymph node involvement, percentage of circumferential rectal wall invasion and tumor extension. METHODS: A prospective study was performed in patients with middle and distal rectal tumors followed at University of São Paulo, School of Medicine and Cancer Institute of State of São Paulo (ICESP), who underwent 3D-ERUS for preoperative evaluation. The parameters analyzed with 3D-ERUS were compared with pathology findings of the surgical specimen obtained after the procedure. A single doctor who performed the exams reported the 3D-ERUS studies and was blind of other methods as well as the pathologic findings. All patients underwent retrograde bowel enema the day before and in the morning of the test. The authors evaluated sensitivity, specificity, positive and negative predictive values, area under curve and kappa index of the 3D-ERUS as compared to pathologic findings, considered the gold standard. For extension and percentage of tectal wall involvement intraclass correlation index was applied. RESULTS: At 3-years period, 44 patients were studied, 27 females, with a mean age of 63.5 years, who had 12 rectal adenomas and 32 adenocarcinomas and underwent local resection (30) or radical resection (14). Value for 3D-ERUS to determine depth of rectal wall invasion sensitivity was 77.3% (CI95% - 54.6%-92.2%), specificity was 86.4% (CI95% - 65.1%- 97.1%), positive predictive value was 85% (CI95% - 62.1%- 96.8%), negative predictive value was 79.2% (CI95% - 57.8%-92.9%) and area under curve was 0,82% (CI95% - 0.7%-0.96%). The weighted kappa index for the depth of invasion in the rectal wall (T) evaluation was 0.67 (IC95%: 0.49; 0.85), considered substantial agreement. For N involvement there was any agreement between 3D-ERUS and histopathology, with K=-0.164. Intraclass correlation was calculated for lesion extension and was moderate (0.45) for extension in centimeters and adequate (0.66) for percentage of circumference involvement. A Bland-Altman graph was performed and showed that tumor extensions until 5 cm and 50% of wall involvement have a good correlation to specimen size. CONCLUSION: 3D-ERUS was effective for determining rectal wall invasion and evaluation of extension of lesions until 5 cm and 50% of rectal wall involvement. However, this method showed a lack of efficacy for evaluation of lymph node involvement for early rectal tumors in this limited subset of patients

Introdução: A identificação de mecanismos genéticos envolvidos no processo de carcinogênese do câncer colorretal levou ao surgimento de novas estratégias terapêuticas como a terapia gênica. Através do bloqueio ou estímulo de determinados alvos genéticos ou moleculares seria possível interromper o ciclo celular de células transformadas. Uma das estratégias sugeridas foi a utilização de seqüências anti-sense do gene da ciclina G que revelou resultados iniciais clínicos e experimentais promissores em diversas neoplasias, inclusive na colorretal. Assim seria esperado que a expressão da ciclina G estivesse freqüentemente alterada de maneira seletiva nas células do câncer colorretal quando comparado às células normais. Por estas razões, decidiu-se estudar a expressão da ciclina G em pacientes com câncer do reto. Métodos: Dados clínicos, epidemiológicos, anátomo-patológicos e de sobrevivência de 36 pacientes com câncer do reto foram obtidos e correlacionados com os resultados de expressão imunohistoquímica da ciclina G. O tecido neoplásico e normal distante da lesão primária foram submetidos a reação imunohistoquímica com anticorpo monoclonal anti-ciclina G e quantificados através de três métodos: (1) quantitativo, obtido a partir da contagem de células determinando a razão entre o número de células positivas e o número total de células contadas em 10 campos; (2) semi-quantitativo (cruzes), obtido a partir da pontuação em sistema de cruzes conforme a intensidade e quantidade de células positivas em áreas de maior impregnação do corante; (3) semi-quantitativo (escore), obtido a partir da pontuação em sistema de escore (alto ou baixo) conforme a intensidade e quantidade de células positivas em áreas de maior impregnação do corante. O estudo estatístico incluiu teste T de student, Qui-quadrado, exato de Fisher, teste t pareado, Wilcoxon, log-rank e curva ROC sendo considerados significativos quando o valor de p<0,05. Resultados: A expressão da ciclina G foi positiva em 76,5±30% da células contadas, com média de 3,2±1,1 cruzes e escore alto em 32 pacientes no tecido tumoral. No tecido normal dos pacientes a positividade foi de 42,2±27,4%, com média de 1,9±1,1 cruzes e escore alto em 16 casos. Quando comparados os tecidos tumoral e normal de cada paciente, o resultado tumor>normal foi obtido em 28 (77,8%) pacientes (quantitativa), 27 (75%) pacientes (semi-quantitativa/cruzes) e 18 (50%) pacientes (semi-quantitativa/escore). A diferença de expressão entre tecido tumoral e tecido normal maior que 10% apresentou correlação com ausência de metástases sistêmicas enquanto que a diferença maior que 38% apresentou correlação com a ausência de metástases linfonodais (área da curva 0,69 nos dois casos). Houve correlação entre o resultado tumor>normal e a ausência de metástases linfonodais quando o método de quantificação foi semi-quantitativo (cruzes e escore;p=0,02 e 0,04). Não houve correlação entre o resultado tumor>normal e as demais características. Não houve influência do resultado tumor>normal nas curvas de sobrevivência (3 anos). Conclusões: A expressão da ciclina G é maior no tecido neoplásico do câncer colorretal quando comparada ao tecido normal. Apesar disso, a expressão da ciclina G é raramente nula no tecido normal. A expressão de ciclina G tumor>normal esteve associada a ausência de metástases linfonodais quando mensurada através de métodos semi-quantitativos. Apesar disso, a expressão alterada da ciclina G não tem influência sobre sobrevivência precoce em pacientes com câncer do reto. / Introduction: Identification of genetic mechanisms involved in colorectal cancer carcinogenesis led to the development of new treatment strategies such as gene therapy. The aim of this strategy is to interrupt cell-cycle of transformed malignant cells by blocking or stimulating specific gene expression. Utilization of cyclin G antisense constructs has been suggested with clinical and experimental promising results in various neoplasias, including colorectal cancer. In this setting, one would expect that cyclin G would be selectively overexpressed in colorectal cancer cells as opposed to normal tissue. For this reason, we decided to study cyclin G expression in patients with rectal cancer. Methods: Clinical, epidemiological, pathological and survival data from 36 patients with rectal cancer was collected and correlated with Cyclin G immunohistochemical expression. Neoplastic and non-adjacent normal tissue were stained with monoclonal anti-Cyclin G antibody and quantified according to 3 different methods: (1) quantitative, obtained from cell count and determined by the ratio between positive counted cells and total number of counted cells observed in 10 microscopic fields; (2) semi-quantitative (crosses), obtained from a scoring system that takes into account both quantity and intensity of most strongly stained areas; (3) semi-quantitative (score), obtained from a scoring system that takes into account both quantity and intensity of most strongly stained areas. Statistical analysis included ROC curves, student\'s T, Chi-square, Fisher\'s exact, log rank, Wilcoxon, and paired t test. Significant differences were considered for p<0.05. Results: In tumor-tissue, positive Cyclin G expression was observed in 76.5±30% of counted cells, with a mean number of 3.2±1.1 crosses and high expression score in 32 patients (89%). In normal tissue, positive cyclin G expression was observed in 42.2±27.4% of counted cells, with a mean of 1.9±1.1 crossed and high expression score in 16 patients. When comparing tumor and normal tissue within each patient, a result of tumor>normal cyclin G expression was observed in 28 (77.8%) patients (quantitative method), 27 (75%) patients (semi-quantitative crosses) and 18(50%) patients (semi-quantitative score). A difference of cyclin G expression between tumor and normal tissue greater than 10% was associated with the absence of metastatic disease. A difference of cyclin G expression between tumor and normal tissue greater than 38% was associated with the absence of lymph node metastases (ROC curve area of 0.69 in both cases). There was significant association between cyclin G expression tumor>normal result and the absence of lymph node metastases when using semi-quantitative quantification methods (p=0.02 for crosses; p=0.04 for score). There was no association between cyclin G expression and other patient\'s characteristics or survival. Conclusion: Cyclin G expression is greater in tumor tissue when compared to normal tissue in patients with rectal cancer. However, cyclin G expression in normal tissue is rarely absent. Tumor>normal cyclin G expression is significantly associated with absence of lymph node metastases when quantified using semiquantitative methods. However, cyclin G expression had no influence in short-term survival.

Le Spina Bifida est une maladie congénitale rare due à anomalie de fermeture du tube neural ayant des conséquences physiques et fonctionnelles multiples. La prise en charge des séquelles digestives du Spina Bifida ne fait l’objet d’aucun consensus national ou international. Les objectifs de cette thèse translationnelle étaient de caractériser les plaintes anorectales des patients adultes ayant un Spina Bifida, d’en préciser les mécanismes physiopathologiques sous-jacents à partir des données de la manométrie anorectale et du barostat rectal et en étudiant les fonctions de la barrière épithéliale intestinale. Les plaintes anorectales des patients adultes ayant un Spina Bifida représentent leur deuxième plainte en terme de fréquence et sont l’incontinence fécale, et la constipation. Ces troubles peuvent évoluer au cours du temps ce qui justifie un suivi digestif au long cours. Le niveau lésionnel neurologique n’est ni associé aux troubles digestifs ni à à leur évolution. Les patients ayant un Spina Bifida ont une atteintede la fonction anale (défaut de contraction) et des fonctions rectales (diminution du tonus et de la compliance rectale). Ils ont également une hyperperméabilité paracellulaire et une diminution de la densité du tissu conjonctif; ces 2 anomalies étant corrélées entre elles. L’augmentation de la perméabilité paracellulaire était négativement corrélée avec la compliance rectale. Enfin, les patients ayant un Spina Bifida ont une augmentation de l’expression de TGFBeta1. Les anomalies des fonctions anorectales et de la barrière épithéliale intestinale pourraient être des cibles thérapeutiques potentielles dans la prise en charge des troubles anorectaux des patients adultes ayant un Spina Bifida. / Spina Bifida is a rare congenital disorder caused by an abnormal neural tube closure with multiple physical and functional consequences. The management of the digestive disorders of Spina Bifida is not consensual. The objectives of this present work were to characterize the anorectal complaints of adult patients with Spina Bifida, to specify the underlying pathophysiological mechanisms from the data of anorectal manometry and rectal barostat and to study the functions of the intestinal epithelial barrier. The anorectal complaints of adult patients with Spina Bifida represent their second complaint and are faecal incontinence and constipation. These disorders can change over time which justifies long-term digestive follow-up. The level of neurological lesion is neither associated with digestive disorders nor with their evolution. Patients with Spina Bifida have impaired anal function (lack of contraction) and rectal function (decreased tone and rectal compliance). They also have paracellular hyperpermeability and decreased connective tissue density ; these 2 anomalies are interrelated. The increase in paracellular permeability was negatively correlated with rectal compliance. Finally, patients with Spina Bifida have an increased expression of TGFBeta1. Abnormalities of anorectal function and intestinal epithelial barrier may be potential therapeutic targets in the management of anorectal disorders in adult patients with Spina Bifida.

Background Parastomal hernia is a common stoma complication causing the patient considerable inconvenience. The patient becomes aware of a bulge around the stoma, but a bulge is not always a parastomal hernia and diagnostics must be performed to enable differential treatment. It is difficult to distinguish between a bulge and a hernia. Results based on clinical examination and computerised tomography (CT) in the supine position, have not been convincing. Three-dimensional intrastomal ultrasonography (3D US) is a novel technique shown to be promising in the assessment of stoma complaints. Two studies were performed to determine inter- and intra-observer reliability as well as the validity of 3D US as an alternative to CT when assessing stoma complaints. There are numerous options for the treatment of parastomal hernia, but none has been shown superior. In the recent decades the use of mesh in the repair of incisional and inguinal hernia has become routine. New materials must be evaluated as there are potential morbidity and even mortality risks with mesh repair. As recurrence of a parastomal hernia is an even greater challenge, the method of choice should have a low risk for recurrence. A prospective multicenter study was performed to evaluate safety and recurrence rate when using Parastomal Hernia Patch BARDTM (PHP), a mesh specially designed for parastomal hernia repair. A stoma has a profound impact on the patient´s daily life, both physical and psychological. A parastomal hernia with its associated risk for leakage and incarceration worsens the situation. Patient driven assessment of healthcare outcome is important if we are to improve medical care. A quality of life (QoL) survey was performed to assess the impact of parastomal bulging and hernia on the patient´s daily life. Methods Forty patients were investigated and the 3D US images were twice evaluated by two or three physicians to assess inter- and intra-observer reliability. Totally 20 patients with stoma complaints requiring surgery were examined with CT and 3D US prior to surgery. The findings were compared with the intraoperative findings – regarded as the true outcome. Fifty patients with parastomal hernia requiring surgery were enrolled from three hospitals. Patients were followed up one month and one year after repair using PHP. Patients still alive in 2008 who had been operated between1996 and 2004 for rectal cancer in Uppsala/Örebro-, Stockholm/Gotland-, and Northern Regions (986 patients) and registered in the Swedish Rectal Cancer Registry (SRCR) were invited to fill in four QoL questionnaires. Results Inter-observer agreement using 3D US reached 80% for the last 10 patients examined, with a kappa value of 0.70. Intra-observer agreement for two examiners was 80% and 95%. The learning curve levelled out at 30 patients. Both CT and 3D US showed high sensitivity and specificity when compared with intraoperative findings. After surgery for parastomal hernia with a PHP, the complication rate at one month was 30% and recurrence rate at one year was 22%. Twelve patients were reoperated within one year. In the QoL study, 31.5% of the patients with a stoma reported a bulging or a hernia. 11.7% had been operated for parastomal hernia. A hernia or a bulge gave rise to significantly more pain and impaired stoma function. Overall QoL was inferior in patients with a permanent stoma compared to a group without a stoma.

Trata-se de um estudo caso-controle de câncer de reto como parte do \"Estudo Epidemiológico de Câncer de Esôfago e de Reto no Município de são Paulo\". O estudo compreendeu 92 casos de cancer de reto e 200 controles categorizados em 3 sub-conjuntos (amostra pareada, global e estratificada). Foram objeto de análise as variáveis: local de nascimento do indivíduo e de seus pais, zona de nascimento (rural/urbana) consumo de alimentos (carnes, ovos, verduras, temperos) características do hábito intestinal, tabagismo e consumo de bebidas (cerveja, vinho e pinga). As estimativas dos Riscos Relativos (RR) por ponto e respectivos testes de significância foram calculados para cada tipo de amostra. Utilizou-se análise multivariada, através do procedimento de máxima verossimilhança condicional para a amostra estratificada e os procedimentos clássicos para as amostras pareada e global. A análise estatística dos resultados evidenciou associação positiva apenas entre o consumo de queijo e câncer de reto (RR = 1,41 I--------I 4,30). Não está afastada a possibilidade de que a significância encontrada seja devido a um artefato estatístico, dada a multiplicidade de testes efetuados. A possível associação entre o consumo queijo e câncer de reto, portanto, deve ser interpretada com reserva. / This is a case-control study of rectal cancer and is part of \"The Epidemiological Study of Esophagus and Rectal Cancers in the City of são Paulo, Brazil\". The study included 92 cases of rectal cancer and 200 controls (classified in three types: matched, global and stratified samples). The analised variables were: state of birth classified in great regions of Brazil, place of birth (rural/urban) ,food consumption (meats, eggs, fruits, vegetables, cereals, beans, seasonings, dairy products) caracteristics of the bowel movements, smoking habits and alcohol consumption (beer, wine and hard liquor-\"pinga\"). The point estimates of the Relative Risks and their significance tests were calculated for each type of sample. Multivariate analysis was done, for the stratified sample the conditional maximum likelihood procedure was used and classical procedures (Me Nemar and Cross Ratio estimate) for the other samples. The statistical analysis indicated a positive/association only between cheese consumption and cancer of the rectum (RR = 1,41 I------I 4,30). There is the possibility that the observed statistical significance is a statistical artefact due to the multiplicity of tests that have been perfomed. Because of this, the possible association between cheese consumption and cancer of the rectum must be viewed with caution.

Laparoscopic surgery for colorectal cancer was first reported in 1991. However, early experiences with laparoscopic colectomy were unfavorable, with higher than expected rates of port-site recurrence and concerns about compromised long-term oncologic outcomes. These concerns have been resolved by the results of several large-scale European and American multicenter randomized controlled trials (RCTs) that reported no difference in oncologic clearance and survival between laparoscopic and open colectomy for colon cancer. / The role of laparoscopic surgery for rectal cancer, on the other hand, still remains controversial. Because laparoscopic surgery for rectal cancer is technically more difficult and has a higher morbidity rate than laparoscopic colectomy for colon cancer, most of the published large-scale multicenter RCTs comparing laparoscopic and open colorectal cancer did not include patients with rectal cancer. To date, good-quality data comparing laparoscopic and open surgery for rectal cancer are still scarce in the literature. The main objective of this thesis is to provide additional evidence to justify the role of laparoscopic surgery for rectal cancer. / To be justified, laparoscopic surgery for rectal cancer should have equal or better clinical outcomes than open surgery and improve quality of life. Furthermore, oncologic clearance as well as long-term survival should not be adversely affected by the laparoscopic approach. / In this thesis, a series of RCTs and comparative studies with long-term follow-up were conducted to address the above issues. Our results demonstrate that laparoscopic surgery for rectal cancer is associated with earlier postoperative recovery, better preservation of urosexual function and quality of life, and less late morbidity when compared with open surgery. Oncologic clearance in terms of resection margins and number of lymph nodes harvested are comparable between the laparoscopic and open groups. Most importantly, laparoscopic surgery does not adversely affect disease control or jeopardize long-term survival of rectal cancer patients. The benefits of the laparoscopic over the open approach remain the same regardless of the types of rectal cancer surgery (laparoscopic-assisted anterior resection, total mesorectal excision, or abdominoperineal resection) or the location of the tumor. It is therefore concluded that laparoscopic surgery for rectal cancer is safe and justified. Based on our results, we believe that laparoscopic surgery can be regarded as an acceptable alternative to open surgery for treating curable rectal cancer. / Ng, Siu Man Simon. / Thesis (M.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 323-366). / Dedication --- p.1 / Declaration of Originality --- p.2 / Abstract --- p.3 / Table of Contents --- p.5 / List of Tables --- p.8 / List of Figures --- p.10 / List of Abbreviations --- p.13 / PRÉCIS TO THE THESIS --- p.15 / Chapter PART I --- BACKGROUND --- p.37 / Chapter Chapter 1 --- Management of Colorectal Cancer: From Open to Laparoscopic Surgery --- p.38 / Chapter 1.1 --- Introduction to Colorectal Cancer --- p.39 / Chapter 1.2 --- A Brief History of Laparoscopic Surgery --- p.51 / Chapter 1.3 --- Laparoscopic Colorectal Surgery: The Beginning --- p.58 / Chapter 1.4 --- Evidence for the Safety and Efficacy of Laparoscopic Surgery for Colon Cancer --- p.62 / Chapter Chapter 2 --- Laparoscopic Surgery for Rectal Cancer: A Critical Appraisal of Published Literature --- p.71 / Chapter 2.1 --- Introduction --- p.72 / Chapter 2.2 --- Evidence from Single-Center Trials --- p.76 / Chapter 2.3 --- Evidence from Multicenter Trials --- p.82 / Chapter 2.4 --- Ongoing Trials --- p.89 / Chapter 2.5 --- Discussion --- p.92 / Chapter Chapter 3 --- Laparoscopic Surgery for Rectosigmoid and Rectal Cancer: Experience at The Prince of Wales Hospital, Hong Kong --- p.97 / Chapter 3.1 --- The Beginning of Laparoscopic Era in Hong Kong --- p.98 / Chapter 3.2 --- Early Experience of Laparoscopic Colorectal Surgery --- p.102 / Chapter 3.3 --- Nonrandomized Comparative Studies --- p.105 / Chapter 3.4 --- The Hong Kong Trial --- p.110 / Chapter PART II --- HYPOTHESES AND CLINICAL STUDIES --- p.116 / Chapter Chapter 4 --- Research Hypotheses and Objectives --- p.117 / Chapter 4.1 --- Research Hypotheses --- p.118 / Chapter 4.2 --- Research Plan and Objectives --- p.120 / Chapter Chapter 5 --- Laparoscopic-Assisted Versus Open Anterior Resection for Upper Rectal Cancer: Short-Term Outcomes --- p.122 / Chapter 5.1 --- Abstract --- p.123 / Chapter 5.2 --- Introduction --- p.125 / Chapter 5.3 --- Patients and Methods --- p.128 / Chapter 5.4 --- Results --- p.133 / Chapter 5.5 --- Discussion --- p.144 / Chapter 5.6 --- Conclusions --- p.148 / Chapter Chapter 6 --- Laparoscopic-Assisted Versus Open Anterior Resection for Upper Rectal Cancer: Long-Term Morbidity and Oncologic Outcomes --- p.149 / Chapter 6.1 --- Abstract --- p.150 / Chapter 6.2 --- Introduction --- p.152 / Chapter 6.3 --- Patients and Methods --- p.154 / Chapter 6.4 --- Results --- p.158 / Chapter 6.5 --- Discussion --- p.173 / Chapter 6.6 --- Conclusions --- p.179 / Chapter Chapter 7 --- Laparoscopic-Assisted Versus Open Abdominoperineal Resection for Low Rectal Cancer --- p.180 / Chapter 7.1 --- Abstract --- p.181 / Chapter 7.2 --- Introduction --- p.183 / Chapter 7.3 --- Patients and Methods --- p.185 / Chapter 7.4 --- Results --- p.190 / Chapter 7.5 --- Discussion --- p.201 / Chapter 7.6 --- Conclusions --- p.207 / Chapter Chapter 8 --- Laparoscopic-Assisted Versus Open Total Mesorectal Excision with Anal Sphincter Preservation for Mid and Low Rectal Cancer --- p.208 / Chapter 8.1 --- Abstract --- p.209 / Chapter 8.2 --- Introduction --- p.211 / Chapter 8.3 --- Patients and Methods --- p.214 / Chapter 8.4 --- Results --- p.221 / Chapter 8.5 --- Discussion --- p.238 / Chapter 8.6 --- Conclusions --- p.246 / Chapter Chapter 9 --- Long-Term Oncologic Outcomes of Laparoscopic Versus Open Surgery for Rectal Cancer: A Pooled Analysis of Three Randomized Controlled Trials --- p.247 / Chapter 9.1 --- Abstract --- p.248 / Chapter 9.2 --- Introduction --- p.250 / Chapter 9.3 --- Patients and Methods --- p.254 / Chapter 9.4 --- Results --- p.258 / Chapter 9.5 --- Discussion --- p.272 / Chapter 9.6 --- Conclusions --- p.280 / Chapter Chapter 10 --- Prospective Comparison of Quality of Life Outcomes After Curative Laparoscopic Versus Open Sphincter-Preserving Resection for Rectal Cancer --- p.281 / Chapter 10.1 --- Abstract --- p.282 / Chapter 10.2 --- Introduction --- p.284 / Chapter 10.3 --- Patients and Methods --- p.287 / Chapter 10.4 --- Results --- p.292 / Chapter 10.5 --- Discussion --- p.308 / Chapter Chapter 11 --- Conclusions --- p.314 / Chapter 11.1 --- Conclusions --- p.315 / REFERENCES --- p.322 / LIST OF PUBLICATIONS RELATED TO THE THESIS --- p.367 / ACKNOWLEDGEMENTS --- p.373

External beam radiation therapy for prostate cancer can result in urinary, sexual, and rectal side effects, often impairing quality of life. A polyethylene glycol-based product, SpaceOAR hydrogel (SOH), implanted into the connective tissue between prostate gland and rectum can significantly reduce the dose received by the rectum and hence risk of rectal toxicity. The optimal way to manage the hydrogel and rectal structures for plan optimization is therefore of interest. A retrospective planning study was completed with 13 patients to examine optimal planning and treatment methods. Computerized tomography (CT) scans were taken pre- and post-SOH implant. Six hypofractionated (60 Gy in 20 fractions) treatment plans were produced per patient using either a structure of rectum plus the hydrogel, termed composite rectum wall (CRW), or rectal wall (RW) as the inverse optimization structure and intensity modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) as the treatment technique. Dose-volume histogram metrics were compared between plans to determine which optimization structure and treatment technique offered the maximum rectal dose sparing. RW structures offered a statistically significant decrease in rectal dose over CRW structures, whereas the treatment technique (IMRT vs VMAT) did not significantly affect the rectal dose. However, there was improvement seen in bladder and penile bulb dose when VMAT was used as a treatment technique over IMRT. Overall, treatment plans using the RW optimization structure offered the lowest rectal dose while VMAT treatment technique offered the lowest bladder and penile bulb dose. These treatment techniques and optimization structures have now been implemented at BC Cancer - Victoria based on this retrospective study. SOH implant has been shown not to be equally effective in all patients. Determining a priori patients in which the implant will offer most benefit allows for effective management of SOH resources. Several factors have been shown to be correlated to reduction in rectal dose including distance between rectum and planning treatment volume (PTV), volume of rectum in the PTV and change in rectum volume pre- to post-SOH. Several of these factors along with other pre-SOH CT metrics were found via multiple linear regression models to predict reduction of rectal dose using data from 21 patients who received SOH implant. Two high rectal dose metrics were modeled, change in the relative volume receiving 55 Gy and change in the partial high dose integral, integrating over the dose-volume histogram (DVH) from 55 Gy to 60 Gy. Models were also produced to predict pre-SOH RV55Gy. These models offered R-squared between 0.57 and 0.87 with statistical significance in each model. Applying a 3.5% lower limit on pre-SOH RV55Gy removed one third of patients as implant candidates. This may offer a clinically useful tool in deciding which patients should receive SOH implant given limited resources. Predictive models, nomograms and a workflow diagram were produced for clinical management of SOH implant. / Graduate

Interstitial laser thermal therapy is a novel local approach to treating prostate cancer. During treatment, thermal ablation may occur on the adjacent rectal wall. The aim of this thesis was therefore twofold: to study the effects of rectal cooling on lesion formation, and secondly, to engineer a computer controlled rectal cooling unit. To study the effects of the coolant temperatures and flow rate, thermal simulations were executed, followed by testing the phenomenon using agar gel phantoms which thermally mimic prostate tissue. Further simulations were run using a treatment planning software, which predicted the required coolant temperatures to protect the outer rectal wall while subsequently determining the shape and size of the resulting coagulated lesion at various laser settings. Results suggest that low coolant temperatures and low flow rates cause maximum cooling rates. Furthermore, the shape and size of the coagulated region is affected by coolant temperatures at specific laser powers and positions within the prostate.