INTRODUÇÃO: O tratamento padrão do Carcinoma Epidermoide do Ânus (CEDA) é a quimiorradioterapia ou radioterapia exclusiva. Os pacientes em que a terapêutica conservadora falha são tratados com Ressecção Abdominoperineal do Reto (RAP) de resgate. OBJETIVOS: Avaliar a sobrevivência com a RAP de resgate no CEDA, identificando os descritores favoráveis para sobrevivência maior e as características do agrupamento de variáveis relacionadas a descritores independentes de risco para mortalidade. MÉTODOS: Foram levantados dados através de 111 prontuários de portadores de CEDA, tratados inicialmente com quimiorradioterapia combinada ou radioterapia exclusiva e submetidos à RAP no período de outubro de 1982 a janeiro de 2011. RESULTADOS: A média de idade foi de 58 anos, 93 (83,8%) pacientes eram do sexo feminino e 80 (72,1%) da raça branca. O estadio cT3-4 compôs 66,7% e cN0 39,6% da casuística. A RAP foi indicada por persistência da doença (PD) em 61 (55%) pacientes e por recidiva (RD) em 50 (45%) pacientes. A ressecção cirúrgica sem resíduos tumorais (R0) foi realizada em 86 (77,5%) pacientes. O tempo médio de permanência hospitalar pós-operatório foi de 14 dias. A morbidade cirúrgica foi de 64,9%, sendo 78,3% dela devida às complicações da região perineal. Recidiva após RAP ocorreu em 68 (61,2%) pacientes, sendo 40 (58,8%) no primeiro ano do pós-operatório, a maioria locorregional (78%; 53/68). A mediana do seguimento foi de 16 meses (1,2-60 meses). Na análise multivariada, cirurgia R0 (p<0,001), invasão perineural vascular e/ou linfática negativa (p<0,0001) e linfonodo negativo na peça cirúrgica (p=0,03) foram estatisticamente associados à maior sobrevivência. CONCLUSÕES: A taxa de sobrevivência global estimada em cinco anos foi de 24,5%, com mediana de sobrevivência de 32 meses. O subgrupo de pacientes submetidos a cirurgias R0 em cujas peças cirúrgicas não foram encontrados invasão perineural vascular e/ou linfática nem linfonodos comprometidos apresentou taxa de sobrevivência estimada em três e cinco anos de 74,4% e 55,0%, respectivamente, com mediana de sobrevivência de 87 meses. Não houve diferença significativa entre pacientes que evoluíram com PD ou RD. Identificou-se a cirurgia R1-2, invasão perineural vascular e/ou linfática e linfonodo positivo na peça cirúrgica como fatores preditivos independentes de mortalidade / INTRODUCTION: The standard treatment for epidermoid carcinoma of the anus (ECA) is the association of chemotherapy (QT) and radiotherapy or exclusive radiotherapy (RT). When conservative treatment fails, patients are submitted to abdominoperineal resection of the rectum (APR). OBJECTIVES: To assess survival with salvage APR in ECA, identifying the most favorable independent descriptors for longer survival and the characteristics of the group of independent variables for mortality risk. METHODS: Data were collected from the medical records of 111 patients with ECA, initially treated with QT/RT or exclusive RT and later submitted to APR, from October 1982 to January 2011. RESULTS: Their mean age was 58 years, 93 (83.8%) patients were female, and 80 (72.1%) were Caucasian. The cT3-4 stage represented 66.7% of the case series and cN0, 39.6%. The APR was indicated due to persistence of disease (PD) in 61 (55%) patients and recurrence of disease (RD) in 50 (45%) patients. Surgical resection without residual tumor (R0) was performed in 86 (77.5%) patients. The mean postoperative hospital length of stay was 14 days. Surgical morbidity was 64.9%, of which, 78.3% related to perineal infection. Recurrence after APR was observed in 68 (61.2%) patients, 40 (58,8%; 40/68) of whom in the first postoperative year, mostly locoregional (78%; 53/68). The median follow-up was 16 months (1.2 - 60 months). On multivariate analysis, R0 surgery (p<0.001), absence of perineural and/or lymphovascular invasion (p<0.0001) and negative lymph node status in the surgical specimen (p=0.03) were associated with increased survival. CONCLUSION: Estimated overall survival rate in 5 years was 24.5%, with median survival of 32 months. There was no significant difference in survival after APR in patients who had PD or RD after conservative treatment. The subgroup of patients who underwent R0 and whose surgical specimen showed absence perineural and/or lymphovascular invasion and negative lymph nodes had an estimated survival rate at 3 and 5 years of 74,4% and 55,0%, respectively, with a median survival of 87 months. The following were identified as independent predictors of mortality: R1-2 surgery; presence perineural and/or lymphovascular invasion; and positive lymph node in the surgical specimen

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Anismus is one of the most frequent disease in carrying patients of obstructed defecation and it is being present in about 50.0% of the constipated patients. The aim of this study is to demonstrate the use of the bi-dimensional anorectal ultrasound (2-D USD) for the diagnosis of anismus and comparing the results with the anus manometry and the three-dimensional anorectal ultrasound (3-D USD). Sixty adult women with obstructed defecation symptoms were evaluated in this prospective and comparative study, coming from Colorectal Unit of the Hospital UniversitÃrio Walter CantÃdio of the Universidade Federal do CearÃ, between September 2006 to March 2007. All the patients were initially submitted to anus manometry (BAD) and then divided in two groups with 30 patients each. Group I was formed by patients without anismus at the mean age of 48,63 (24 the 69) years, while group II with carrying patients with anismus at the mean age of 51,20 (27 the 78) years. After that, patients of both groups were submitted to the 3-D and 2-D USD by an examiner who was unaware of the results of the manometries. The average size of the gotten angle with the 3-D USD at rest position of group I was 87.28  0.80 (76,5Â-96,2Â) and of 87.87  0.99 (78,5Â-109,4Â) in group II. (p=0,3220). The average size of the angle during the evacuatory effort of group I was of 93.25  1.49 (74,9Â-106,9Â) and of 85.27  1.35 (72,0Â- 101,8Â) in group II, (p=0.007). The average size of the gotten angle with the USD 2-D at rest positions of group I was 62.61  1.15 (50,9Â-75,0Â) and of 65.51  0.89 (50,8Â-73,0Â) in group II (p=0,0257). The average size of the angle during the evacuating effort of group I was of 59.75  1.42 (44,0Â-73,0Â) and of 69.40  1.06 (52,6Â-79,5Â) in group II, (p< 0,001). Comparing the differences of the angles size at rest position and during evacuatory effort of the patients of group I with group II, using 2-D and 3-D USD, there was statistically significant difference (p< 0,0001). Comparing the results between the 2-D USD with the manometry, there was agreement in 86,67% and 83,33% of the patients of group I and group II respectivelly. Comparing the results between the 2-D and 3-D USD, there was agreement of 93,33% in the evaluation of the patients of group I and of 90,0% of the patients of group II. The agreement among the three methods was 86,67% as positive predictive value and 83.33% as negative predictive value. It is concluded that the use the 2-D USD was considered efficient in the diagnosis of anismus by the high indication of agreement among the three used methods / Anismus à uma das afecÃÃes mais freqÃentes em pacientes portadores de evacuaÃÃo obstruÃda, estando presente em cerca de 50.0% dos pacientes constipados. O objetivo deste trabalho à avaliar se o USD 2-D faz o diagnÃstico de anismus, quando comparado a manometria anal e ao USD 3-D. Foram avaliadas neste estudo prospectivo e comparativo 60 mulheres adultas com sintomas de evacuaÃÃo obstruÃda, provenientes do ServiÃo de Coloproctologia do Hospital UniversitÃrio Walter CantÃdio da Universidade Federal do CearÃ, no perÃodo entre setembro de 2006 a marÃo de 2007. Todas as pacientes foram inicialmente submetidas à manometria anal (MA) e, distribuidas em dois grupos com 30 pacientes cada. O grupo I foi constituÃdo por pacientes sem anismus e com mÃdia de idade 48,63 (24 a 69) anos, enquanto o grupo II com pacientes portadoras de anismus e com mÃdia de idade 51,20 (27 a 78) anos. Em seguida, as pacientes de ambos os grupos foram submetidas à USD 3-D E 2-D por um examinador que desconhecia o resultado da manometria. O tamanho mÃdio do Ãngulo obtido com o USD 3-D no repouso do grupo I foi 87.28  0.80 (76,5Â-96,2Â) e de 87.87  0.99 (78,5Â-109,4Â) no grupo II. (p=0,3220). O tamanho mÃdio do Ãngulo no esforÃo evacuatÃrio do grupo I foi de 93.25  1.49Â(74,9Â-106,9Â) e de 85.27  1.35Â(72,0Â-101,8Â) no grupo II, (p=0.007). O tamanho mÃdio do Ãngulo obtido com a USD 2-D no repouso do grupo I foi 62.61  1.15Â(50,9Â-75,0Â) e de 65.51  0.89Â(50,8Â-73,0Â) no grupo II (p=0,0257). O tamanho mÃdio do Ãngulo no esforÃo evacuatÃrio do grupo I foi de 59.75  1.42Â(44,0Â-73,0Â) e de 69.40  1.06Â(52,6Â-79,5Â) no grupo II, (p<0.001). Comparando a diferenÃa do tamanho dos Ãngulos no repouso e no esforÃo evacuatÃrio dos pacientes do grupo I com o grupo II, ao USD 2-D e 3-D, foi observado diferenÃa estatisticamente significante (p< 0,0001). Comparando os resultados obtidos ao USD 2-D com a manometria, houve concordÃncia em 86,67% das pacientes de ambos os grupos. Comparando os resultados obtidos entre o USD 2-D com o 3-D, houve concordÃncia de 93,33% na avaliaÃÃo das pacientes do grupo I e de 90,0% das pacientes do grupo II.A concordÃncia entre os trÃs mÃtodos foi de 86,67% como valor preditivo positivo e 83,33% como valor preditivo negativo. Conclui-se que a o USD 2-D foi eficaz em averiguar o diagnÃstico do anismus pelo elevado Ãndice de concordÃncia entre os trÃs mÃtodos utilizados

Se presenta el caso de un paciente de 60 años de edad que presenta dolor y sensación de cuerpo extraño en la región anal, asociado a deposiciones con restos de sangre. Al tacto rectal se palpó una lesión indurada en la cara anterior del conducto anal. En la colonoscopía se evidenció una lesión proliferante elevada, pigmentada “negruzca”, de aproximadamente 2 cm de diámetro, compatible con neoplasia maligna de canal anal. Se procedió a una biopsia e inmunohistoquímica, que dio como resultado el S-100 positivo y HMB-45 negativo. Una tomografía helicoidal multicorte toraco-abdomino-pélvico descartó tumoraciones y adenomegalias metastásicas. El paciente fue sometido a una resección local parcial transanal de la tumoración pigmentada. El resultado histopatológico posquirúrgico confi rmó el diagnóstico de melanoma maligno anal amelanótico (MMAA); el S-100 fue positivo; el Melan-A, positivo débil, y el KI-67, positivo. El paciente presentó una evolución favorable y fue dado de alta a los tres días de la cirugía / We present the case of a 60 year old patient suffering pain and the sensation of a foreign body in the anal region associated with traces of blood in stools. Digital rectal exam (DRE) revealed a hardened lesion located on the wall of the anal canal. Colonoscopy revealed a raised proliferating lesion with a blackish color which was about 2 inches in diameter. This was compatible with an anal canal malignancy. We proceeded to a biopsy and immunohistochemistry study which tested positive for S-100 and negative for HMB-45. A multislice helical chest, abdominal and pelvic CAT scan ruled out metastatic tumors and lymphadenopathy. The patient underwent local transanal excision of the partially pigmented tumor. Post- surgical histopathological results confi rmed the diagnosis of malignant anal amelanotic melanoma positive for S-100. The sample tested weakly positive for Melan-A and positive for KI-67. The favorable outcome of the procedure led to the patient’s discharge 3 days after surgery.

La función principal del anorecto es el control voluntario, de la continencia fecal y la evacuación fecal. Esta tesis incluye tres publicaciones.Primera publicación. Los parámetros en la práctica clínica no pueden aclarar los mecanismos asociados al tratamiento de la incontinencia anal. Nuestra hipótesis fue que el músculo puborectal juega un papel fundamental en la continencia anal y el objetivo del estudio fue desarrollar un sistema original para medir la contracción puborectal y valorar el papel del músculo en la continencia. Se estudiaron 53 pacientes con incontinencia, 30 pacientes con estreñimiento (grupo de enfermos control) y 15 controles sanos. La severidad clínica se evaluó mediante una escala de 0-12, la función anorectal mediante manometría anorectal, y la contracción del puborectal con un dinamómetro perineal. Los pacientes con incontinencia presentaban varias alteraciones fisiológicas (3.2±0.3 por paciente), y el análisis multivariable demostró que el puborectal es el factor independiente con relación más intensa con la severidad de la incontinencia (R= -0.84; p<0.0001), y también se asocia a la respuesta al tratamiento (R= 0.53; p<0.01). La mejoría clínica observada tras el tratamiento (4.4±0.5 score post vs 7.9 ±0.5 score pretratamiento; p<0.001) se asocia a un significativo aumento de la fuerza del puborectal (448±51 g post vs 351± 35 g pretratamiento;p<0.05). Conclusión. Este estudio demuestra la importancia de la insuficiencia del músculo puborectal en la incontinencia anal y en la predicción de la respuesta al tratamiento. Segunda publicación. El biofeedback es un tratamiento eficaz de la incontinencia anal. Nuestro objetivo fue establecer la eficacia clínica del tratamiento mediante biofeedback e identificar los factores asociados a la respuesta. Se analizaron de forma retrospectiva 145 pacientes con incontinencia anal tratados con biofeedback. Se evaluó la clínica con un cuestionario estructurado y los parámetros de la función anorectal. De 126 pacientes con seguimiento (104 mujeres; rango de edad 17-82 años), el 84% presentó respuesta positiva. En el análisis multivariable logístico la edad y la maniobra defecatoria fueron factores asociados a la respuesta. La combinación de ambos factores proporciona la mejor sensibilidad y especificidad Conclusión. En pacientes con incontinencia anal, especialmente en jóvenes, se debe investigar y corregir la presencia de posibles alteraciones de la maniobra defecatoria. Tercera publicación. El biofeedback es un tratamiento eficaz del estreñimiento por dificultad expulsiva. Nuestro objetivo fue establecer la eficacia del tratamiento y determinar los factores predictivos de respuesta. Se analizaron 148 pacientes tratados con biofeedback. Se evaluó la clínica con un cuestionario estructurado y los parámetros de la función anorectal. De los 112 pacientes con seguimiento (86 mujeres, 26 varones; 8-67 años) el 66 % presentaron una buena respuesta al tratamiento con biofeedback. La respuesta del tratamiento depende de la severidad de la disfunción defecatoria. El análisis univarible mostró que la mala respuesta clínica se asociaba con la ausencia de relajación anal durante la defecación y la incapacidad de expulsión de un balón rectal de 1 ml. Conclusión. El biofeedback es una opción terapéutica eficaz en el estreñimiento por dificultad expulsiva, pero la respuesta clínica depende de la severidad de la alteración funcional. / The main function of the anorectum is the voluntary control, of fecal continence and anal defecation. This thesis includes three manuscripts.First manuscript. The pathophysiology of anal incontinence may be elusive using current parameters. Our aim was to establish the role of puborectalis muscle in anal continence. In 53 patients with anal incontinence and 30 with constipation (disease controls) and 15 healthy controls we evaluated incontinence severity (by a 0-12 scale), anorectal function (by standard manometric tests), and puborectalis contraction (by a perineal dynamometer). Patients with incontinence exhibited various physiological abnormalities (3.2±0.3 per patient), but multiple regression analysis showed that puborectalis contraction was the independent variable with strongest relation to the severity of incontinence (R = -0.84; p<0.0001), as well as a predictive factor of the response to treatment (R = 0.53; p<0.01). Furthermore, clinical improvement in response to treatment (4.4±0.5 score vs 7.9±0.5 score pre; p<0.001) was associated to a marked and significant strengthening of puborectalis contraction (448±47 g vs 351±35 g pre; p<0.05). Conclusion. This study demonstrate the importance of puborectalis failure in anal incontinence and its predictive response to treatment. Second study. Biofeedback is an effective treatment for anal incontinence. Our aim was to identify the key predictors of outcome. We retrospectively analyzed the clinical and physiological data of 145 patients consecutively treated by biofeedback. Clinical and anorectal parameters were evaluated. Biofeedback treatment was performed by a manometric technique. Of the 126 patients (104 F, 22 M; 17-82 years), 84 percent had a good response to treatment. By multivariate logistic regression only age and defecatory manoeuvre were independent predictors of the response. The association of both factors provided the best sensitivity and specificity. Conclusion. In patients with anal incontinence scheduled for biofeedback treatment potential alterations of defecation should be first be searched for and corrected, particularly in younger patients. Third study. Biofeedback is considered an effective treatment for anal constipation due to functional outlet obstruction. Our aim was to identify the key predictors of outcome using a comprehensive standardized evaluation. We retrospectively analyzed the clinical and physiological data of 148 patients consecutively treated for constipation due to functional outlet obstruction by biofeedback. Clinical and anorectal parameters were evaluated. Biofeedback treatment was performed by a manometric technique. Of 112 patients included (86 F, 26 M; 8-67 years) were followed-up, and 66 percent had a good response. The response to treatment depended on the severity of the defecatory dysfunction. By univariate analysis, lack of anal relaxation during straining and inability to evacuate a 1 ml intrarectal balloon were predictors of bad response Conclusion. Even in the presence of negative predictors, biofeedback is a valuable treatment option in a substantial proportion of constipated patients.

Las patologías anorectales benignas (fisura anal, incontinencia fecal, hemorroides) presentan una elevada prevalencia. De forma general, se desconoce la fisiopatología de estas enfermedades en las que se producen diversas alteraciones del esfínter anal interno (EAI). Los objetivos para esta tesis fueron: 1º Caracterizar los mecanismos y neurotransmisores implicados en el control del tono, la relajación y la contracción del EAI en dos modelos animales (cerdo y rata) y del músculo longitudinal del canal anal porcino. 2º Estudiar la fisiopatología de las alteraciones de la motilidad del canal anal (EAI) en pacientes con fisura anal. Pacientes, material y método. Se realizaron estudios in vitro en baño de órgano en tiras de EAI y músculo longitudinal del canal anal porcino para comparar el efecto de la estimulación neuronal por estimulación eléctrica de campo y a través de los receptores nicotínicos, purinérgicos y serotoninérgicos. Las tiras de EAI de rata fueron estudiados en la técnica de baño de órgano y microelectrodo para comparar la respuesta mecánica y eléctrica. En ambos modelos se realizó histopatología para estudiar la estructura del canal anal. Los pacientes con fisura anal fueron estudiados mediante manometría convencional y de alta resolución, EMG, ecografía endoanal e histopatología de biopsias de EAI. Resultados. A) Estudios animales: El EAI porcino desarrolla tono miogénico y actividad rítmica espontáneo. La estimulación neural produce una relajación antagonizada con inhibidores de la NOS y bloqueadores de los receptores P2Y1, y una contracción antagonizada por atropina y fentolamina. El músculo longitudinal del canal anal no presenta relajación y la estimulación neural solo provoca una contracción colinérgica. El EAI de rata también desarrolló tono miogénico, un potencial de membrana en reposo de -51mV e IJPs espontáneos y una relajación e hiperpolarización (IJP) en respuesta a la estimulación neural. El L-NNA produjo una despolarización y aumento del tono, no modificó los IJP espontáneos, y bloqueo la relajación y el componente lento del IJP. El MRS2500 (antagonista receptores P2Y1) sólo bloqueó los IJPs espontáneos y el componente rápido del IJP. La adición secuencial de L-NNA y MRS2500 bloqueó completamente la relajación neural y los IJPs. Los receptores P2Y1 fueron inmunolocalizados en la célula muscular lisa del EAI. B) Estudios en humanos. Los pacientes con fisura anal presentan hipertonía e hiperdinamia del esfínter interno con ondas lentas (>90%) y superlentas (>65%). Los pacientes con ondas superlentas presentaban una mayor hipertonía y una disminución de la relajación del EAI y un incremento en la pos-contracción. Las biopsias de EAI de pacientes con fisura anal crónica muestran una marcada fibrosis con pérdida de tejido muscular liso y un infiltrado inflamatorio con neutrófilos y linfocitos. Conclusiones. La motilidad del EAI incluye un tono miogénico, una relajación mediada por oxido nítrico y una purina (ATP) que actúa a través de receptores P2Y1 situados en las células musculares lisas. Estos neurotransmisores realizan una función específica y complementaria. La contracción fásica del esfínter anal se debe a motoneuronas colinérgicas y fibras simpáticas a través de receptores alfa-adrenérgicos. La motilidad del músculo longitudinal del canal anal porcino se limita a una contracción mediada por neuronas colinérgicas sobre receptores muscarínicos. Estructural e histológicamente el canal anal porcino presenta una mayor similitud con el canal anal humano en comparación al de la rata, sin embargo, ambos modelos animales son útiles para su utilización en estudios de fisiología del EAI. Los pacientes con fisura anal presentan una alteración de la motilidad del EAI con una severa hipertonía y un aumento en la actividad rítmica espontánea representada por las ondas superlentas. Éstas son un marcador de severidad de la disfunción puesto que los pacientes que las desarrollan presentan mayor hipertonía, menor relajación del EAI y un incremento de la amplitud de la pos-contracción después de inducir el reflejo rectoanal inhibitorio. Nuestro estudio sugiere que el principal mecanismo para la disfunción del EAI en los pacientes con fisura anal sería una alteración en la vía nitrérgica inhibitoria de origen probablemente inflamatorio, ya que una alteración en la liberación tónica de óxido nítrico favorecería el desarrollo de las ondas superlentas y una hipertonía, mientras que un daño en la liberación fásica de este neurotransmisor sería el responsable de la disminución de la relajación del EAI.

Introduction: The incidence of anal cancer, whose primary cause is human papillomavirus (HPV) infection, has increased in United States (US) men almost three-fold in three decades; however, little is known about the epidemiology of anal HPV, especially in heterosexual men. Furthermore, advancements in knowledge about the epidemiology of anal HPV may be hampered by measurement error in the collection of sexual behavior data. Methods: From two US cities, behavioral data and anal biological specimens were collected from 253 men who acknowledged sexual intercourse with a woman in the previous year. PCR and genotyping were used to assess the presence of HPV DNA. In addition, two HPV questionnaires were assessed for test-retest reliability: the first was a self-administered questionnaire associated with the collection of the biological specimens while the second was a computer-assisted self-interview (CASI) with 1069 men in Brazil, Mexico, and the US. Results: Based on DNA analysis, overall anal HPV prevalence was 24.8% in 222 men who acknowledged no prior sexual intercourse with men. Risk factors independently associated with anal HPV were lifetime number of female sexual partners and frequency of sex with females in the past month. Based on kappa and intraclass correlation coefficients (ICC), both HPV questionnaires were found to be highly reliable with low refusal rates; however, three discrete measures in the multi-national interview asking for the number of sexual partners had lower reliability. The ICC of these questions increased to greater than or equal to 0.79 when a small number of extreme outliers (less than or equal to 3) were removed. Predictors of unreliable reporting were age and lifetime number of female sexual partners while years of education was inversely associated with unreliable reporting. Discussion: These results suggest anal HPV is common in heterosexual men. Risk factors associated with anal HPV did not explain how HPV was transmitted to the anal region. Both instruments used to collect sexual behavior data were highly reliable including the CASI instrument used in three culturally and linguistically distinct countries; however, caution is warranted with discrete measures that ask participants to report the number of sexual partners.

Thesis (DR. P.H.)--University of Michigan.

Thesis (DR. P.H.)--University of Michigan.

Resumo não disponível

Resumo não disponível