Clinical application and standardized implementation of intersphincteric resection / 中华胃肠外科杂志

Intersphincteric resection (ISR) is the ultimate sphincter-preserving surgical technique for low rectal cancer. To promote the standardized implementation of ISR, this review discusses the important issues regarding the clinical application of ISR with reference to the latest Chinese expert consensus on ISR. In terms of ISR-related pelvic anatomy of the rectum/anal canal, hiatal ligament is not identical with the anococcygeal ligament. At the level where the rectourethralis muscle continuously extends to the posteroinferior area of the membranous urethra from the rectum, the neurovascular bundle is identified between the posterior edge of rectourethralis muscle and the anterior edge of the longitudinal muscle of the rectum. This knowledge is crucial to detect the anterior dissection plane during ISR at the levator hiatus level. The indication criteria for ISR included: (1) stage I early low rectal cancer; (2) stage II-III low rectal cancer undergoing neoadjuvant treatment, and supra-anal tumors and juxta-anal tumors of stage ycT3NxM0, or intra-anal tumors of stage ycT2NxM0. However, signet ring cell carcinoma, mucinous adenocarcinoma and undifferentiated carcinoma should be contraindicated to ISR. For locally advanced low rectal cancer (especially anteriorly located tumor), neoadjuvant treatment should be carried out in a standardized manner. However, it should be recognized that neoadjuvant chemoradiotherapy was a risk factor for poor anal function after ISR. For surgical approaches for ISR, including transanal, transabdominal, and transanal transabdominal approaches, the choice should be based on oncological safety and functional consequences. While ensuring the negative margin, maximal preservation of rectal walls and anal canal contributs to better postoperative anorectal function. Careful attention must be paid to complications regarding ISR, with special focus on the anastomotic complications. The incidence of low anterior resection syndrome (LARS) was higher than 40%. However, this issue is often neglected by clinicians. Thus, management and rehabilitation strategies for LARS with longer follow-ups were required.

Anal canal lymphoma: Case report and literature review / Linfoma de canal anal, reporte de caso y revisión de la literatura

Abstract Introduction: Primary tumors of the anal canal other than carcinomas are rare entities; among them, anal canal lymphomas are extremely unusual and pose both a diagnostic and therapeutic challenge for the coloproctologist. Case presentation: A male patient with positive human immunodeficiency virus (HIV) with proctalgia and mass sensation at the perianal level. A concentric thickening of the walls of the lower rectum was documented by magnetic resonance imaging, with colonoscopy and biopsies with histopathology compatible with plasmablastic lymphoma. Therefore, a diverting colostomy was performed and, subsequently, the hematology service indicated chemotherapy with the EPOCH scheme. Discussion: Lymphoma of the anus represents 0.2 % of anorectal tumors, most of these are non-Hodgkin's lymphomas; Hodgkin's disease at the anorectal level is even rarer. The population with the highest risk of this entity is HIV-positive patients, such as the patient in this case, although other associated factors are described in the literature.

Resumen Introducción: los tumores primarios del canal anal diferentes a carcinomas son entidades poco frecuentes; dentro de estos, los linfomas del canal anal son extremadamente raros y generan un reto tanto diagnóstico como terapéutico para el coloproctólogo. Presentación de caso: se presenta a continuación un caso clínico de un paciente con virus de inmunodeficiencia humana (VIH) positivo con proctalgia y sensación de masa a nivel perianal, se documentó por resonancia magnética un engrosamiento concéntrico de las paredes del recto inferior, con realización de colonoscopia y biopsias con histopatología compatible con linfoma plasmablástico, por lo que se realizó una colostomía derivativa y, posteriormente, se indicó por el servicio de hematología una quimioterapia con esquema EPOCH. Discusión: el linfoma de ano representa el 0,2 % de los tumores anorrectales, la mayoría de estos corresponde a linfomas no Hodgkin, y es aún más rara la enfermedad de Hodgkin a nivel anorrectal. La población con mayor riesgo de presentar esta entidad es los pacientes con VIH positivo, como el paciente descrito en el caso, aunque existen otros factores asociados descritos en la literatura.

Melanoma del canal anal: a propósito de un caso / Melanoma of the anal canal: a propos of a case

RESUMEN Los melanomas mucosos son tumores poco frecuentes y de mal pronóstico. Presentan un comportamiento agresivo, y pueden tener varias localizaciones en el aparato digestivo. Este tipo de tumores es más frecuente en la región anorectal. Se presentó un caso de una paciente femenina de 59 años, con un cuadro de varios meses de evolución; caracterizado por ardor, prurito anal y sensación de masa que prolapsaba a través del ano. Se constató al examen físico masa tumoral aspecto polipoideo. Se realizó polipectomía donde la biopsia arrojó como resultados el aspecto histológico de un melanoma mucoso de canal anal.

ABSTRACT Mucous melanomas are few frequent and have a bad prognosis. They present an aggressive behavior and might have several locations in the digestive system. This kind of tumors is more frequent at the anus-rectal region. The authors presented the case of a female patient, aged 59 years, with clinical conditions of several months of evolution, characterized by burning, anal pruritus and the sensation of a mass prolapsing through the anus. A tumor mass of polypoid aspect was found at physical examination. Polypectomy was carried out and the biopsy showed the histologic aspect of a mucous melanoma of the anal canal.

¿Permiten la citología, el genotipado y la anoscopia de alta resolución establecer un protocolo para la detección precoz del carcinoma epidermoide de canal anal en población de riesgo? / Do cytology, genotyping, and high resolution anoscopy allow to establish a protocol for early detection of squamous cell carcinoma of the anal canal in risk population?

Introducción: El cáncer anal ha experimentado un aumento de incidencia en los últimos años. Está mediado por el VPH y precedido de cambios precancerosos planteando la posibilidad de dirigir los esfuerzos preventivos hacia los grupos de alto riesgo. Sigue siendo controvertida la indicación de cribado y los métodos de detección ideales. Objetivo: Validar las pruebas de cribado implementadas en la actualidad comparadas con la biopsia como "gold standard". Material y Métodos: Estudio transversal con recogida de datos prospectiva, en una cohorte de hombres VIH+ que tienen sexo con hombres, pertenecientes al Hospital Gregorio Marañón e Infanta Leonor en un periodo de 2 años. Resultados: Se seleccionaron 179 pacientes con 286 visitas a la consulta de screening en las que se llevaron a cabo 3 pruebas de cribado en paralelo (citología anal, genotipado del VPH y anoscopia de alta resolución (AAR) con toma de biopsia dirigida sobre zona sospechosa o aleatoria). La sensibilidad y especificidad para la detección de displasia de alto grado y cáncer y su grado de concordancia con la biopsia fue la siguiente: citología 3,23%/94,43% (k: 0,03), genotipado de VPH de alto riesgo 90,32%/27,45% (k: 0,05), AAR 32,26%/87,45 (k: 0, 17) siendo el rendimiento diagnóstico de las tres pruebas muy bajo. Conclusión: La citología presenta un rendimiento diagnóstico muy bajo comparado con el genotipado que representa el mayor. A la luz de nuestros resultados, los protocolos clínicos tal y como vienen desarrollándose en la actualidad deberían de ser abandonados.

Introduction: The incidence of anal cancer has increased in recent years. It is mediated by HPV and preceded by precancerous changes, raising the possibility of directing preventive efforts towards high-risk groups. The indication of screening remains controversial and which methods would be the ideal ones. Objective: To validate the screening tests established actually, comparing it with the biopsy considered as the "gold standard". Materials and Methods: A cross-sectional study was performed, with prospective data collection in a cohort of VIH+ patients, who have male homosexual anal relations, belonging to Gregorio Marañón and Infanta Leonor Hospitals in a period of 2 years. Results: A total of 179 patients were selected with 286 visits to the screening Outpatient Clinic in which 3 parallel screening tests were performed (anal cytology, HPV genotyping and high resolution anoscopy (AAR) with a biopsy directed on a suspicious or random area). The sensitivity and specificity for the detection of high-grade dysplasia and cancer and their degree of agreement with the biopsy was as follows: cytology 3.23%/94.43% (k: 0.03), high HPV genotyping. risk 90.32%/27.45% (k: 0.05), AAR 32.26%/87.45 (k: 0, 17), the diagnostic accuracy of the three tests being very low. Conclusion: Cytology shows a very low diagnostic accuracy compared to the genotype that represents the highest one. In light of our results, clinical protocols as they are currently being developed should be abandoned.

Tumor de Buschke-Löwenstein - Condiloma gigante acuminado / Buschke-Löwenstein's Tumor - Giant Condyloma Acuminatum

Presentamos el caso de un hombre de 21 años de edad, infectado por el virus de la inmunodeficiencia humana (VIH) que presenta lesiones verrucosas gigantes compatibles con un tumor de Buschke-Lowenstein (TBL) que afectaban la región perineal, anorrectal y genitales externos. También existía afectación del párpado superior derecho. (AU)

We report the case of a 21-year-old male patient, infected with human immunodeficiency virus (HIV) that presents giant warty lesions compatible with a Buschke-Lowenstein tumor (BLT) that affected the perineal, anorectal and external genital region. He also had a right upper eyelid lesion. (AU)

Anal canal squamous carcinoma / Carcinoma epidermóide do canal anal

ABSTRACT Background: Anal canal carcinoma is a rare neoplasm, representing 2% of the digestive tumors, and the most common is squamous cell carcinoma, with an increasing incidence. Objective: The study aims to elucidate the pathogenesis of an increasingly prevalent disease, as well as to update treatment and prognosis. Methods: A literature search in Pubmed database, including articles from 2005 to 2015 and cross-research articles with the initial research. Results: Several studies prove the role of HPV as a major risk factor in the development of squamous cell carcinoma of anal canal, as well as a greater prevalence of this neoplasia in HIV-positive people and in those who practice receptive anal intercourse. In the last two decades chemoradiotherapy remains the treatment of choice, and abdominoperineal resection is reserved for those cases of treatment failure or recurrence. Evidence advances in order to adapt the treatment to each patient, taking into account individual prognostic factors and biological tumor characteristics. Conclusions: Squamous cell carcinoma of the anal canal is a neoplasm associated with HPV; therefore, screening and vaccination programs of male individuals, by way of prevention, should be started. Many studies are needed in order to achieve development in the treatment as well as in the evaluation of the biological characteristics of the tumor.

RESUMO Introdução: O carcinoma do canal anal é uma neoplasia rara, representando 2% dos tumores digestivos, sendo o epidermóide o mais comum com uma incidência crescente. Objetivo: Este estudo pretende elucidar sobre a etiopatogenia desta patologia cada vez mais prevalente, assim como atualizar sobre o tratamento e prognóstico. Métodos: Pesquisa bibliográfica na base de dados Pubmed, incluindo artigos de 2005 a 2015, assim como artigos de pesquisa cruzada com os artigos iniciais. Resultados: Diversos estudos provam o papel do HPV como um fator de risco major no desenvolvimento de carcinoma epidermóide do canal, assim como uma maior prevalência desta neoplasia na população HIV positiva e nos que praticam sexo anal recetivo. O tratamento continua a ser desde há duas décadas a quimioradioterapia, reservando a resseção abdominoperineal para casos de falência do tratamento ou recorrência. A evidência avança no sentido de adequar o tratamento a cada doente, tendo em conta fatores prognósticos individuais e as características biológicas do tumor. Conclusões: O carcinoma epidermóide do canal anal é uma neoplasia associada ao HPV, logo deveria iniciar-se programas de rastreio e vacinar o sexo masculino como prevenção. Muitos estudos são necessários para evoluir no tratamento, assim como na avaliação das características biológicas do tumor.

Extended pelvic resections for the treatment of locally advanced and recurrent anal canal and colorectal cancer: technical aspects and morbimortality predictors aftet 24 consecutive cases / Ressecções pélvicas alargadas no tratamento do câncer colorretal e de canal anal localmente avançado ou recidivado: análise dos aspectos técnicos e fatores de morbimortalidade em 24 casos consecutivos

ABSTRACT Objective: to evaluate the profile of morbidity and mortality and its predictors related to extensive pelvic resections, including pelvic exenteration, to optimize the selection of patients and achieve better surgical results. Methods: we performed 24 major resections for anorectal pelvic malignancy from 2008 to 2015 in the Instituto do Câncer do Ceará. The factors analyzed included age, weight loss, resected organs, total versus posterior exenteration, angiolymphatic and perineural invasion, lymph node metastasis and overall and disease-free survival. Results: the median age was 57 years and the mean follow-up was ten months. Overall morbidity was 45.8%, with five (20.8%) serious complications. There were no deaths in the first 30 postoperative days. The median overall survival was 39.5 months, and disease-free survival, 30.7 months. Concomitant resection of the bladder was an isolated prognostic factor for higher risk of complications (87.5% vs. 26.7%, p = 0.009). Angiolymphatic invasion and lymph node metastasis did not reach significance with respect to disease-free survival. Conclusion: treatment of advanced anorectal tumors is challenging, often requiring combined resections, such as cystectomy and sacrectomy, and complex reconstructions. The magnitude of the operation still carries a high morbidity rate, but is a procedure considered safe and feasible, with a low mortality and adequate locoregional tumor control when performed in referral centers.

RESUMO Objetivos: avaliar o perfil de morbimortalidade e seus fatores preditivos relacionados às ressecções pélvicas extensas, incluindo a exenteração pélvica, com o intuito de otimizar a seleção dos pacientes e obtenção de melhores resultados cirúrgicos. Métodos: foram realizadas 24 grandes ressecções pélvicas por neoplasia maligna anorretal de 2008 a 2015 no Instituto do Câncer do Ceará. Os fatores analisados incluíram idade, perda de peso, órgão ressecados, exenteração total versus posterior, invasão angiolinfática e perineural, metástase linfonodal e sobrevida global e livre de doença. Resultados: a mediana de idade foi 57 anos e o tempo médio de seguimento foi dez meses. A morbidade global foi 45,8%, com cinco (20,8%) complicações graves. Não houve óbito nos primeiros 30 dias de pós-operatório. A sobrevida global média foi 39,5 meses e a sobrevida livre de doença foi 30,7 meses. A ressecção concomitante da bexiga foi fator prognóstico isolado com maior risco para complicações (87,5% vs. 26,7%, p=0.009). Invasão angiolinfática e metástase linfonodal não alcançaram significância com relação à sobrevida livre de doença. Conclusão: o tratamento dos tumores anorretais avançados é desafiador, necessitando frequentemente de ressecções combinadas, como a cistectomia e sacrectomia, além de reconstruções complexas. A magnitude da cirurgia ainda carrega uma elevada taxa de morbidade, porém é um procedimento considerado seguro e factível, com uma baixa mortalidade e adequado controle locorregional tumoral quando realizado em centros de referência.

Melanoma anorrectal / Anorectal melanoma

El melanoma anorrectal es infrecuente, su clínica inespecífica y su diagnóstico tardío, acompañándose de pronóstico ominoso. Se reporta el caso de melanoma anorrectal. Mujer de 62 años con historia de baja de peso y masa rectal, estudio histológico evidencia melanoma anorrectal, realizándose cirugía respectiva y posterior radioterapia hipofraccionada. La clínica del melanoma anorrectal dificulta el diagnóstico, presentándose en edades propias de patologías más frecuentes y benignas como hemorroides. El tratamiento de elección es quirúrgico. Se recomienda un elevado índice de sospecha para manejo oportuno.

Anorrectal melanoma is rare, his clinic is unspecific and his diagnostic is late, accompanied by ominous prognosis. The case of anorrectal melanoma is reported. A 62 year old female presented weight loss and rectal mass, histology study showed melanoma anorrectal, resection surgery and radiotherapy hypofractionated were performed. Anorrectal melanoma clinical is a difficult diagnosis, this appears in ages where others diseases benign are more frequent, such as hemorrhoids. The treatment of choice is surgical. A high index of suspicion for timely management is recommended.

Prevalência de alterações citológicas anais em pacientes com citologia cervical anormal / Prevalence of cytological anal abnormalities in patients with abnormal cervical cytology

A incidência do carcinoma escamoso anal vem crescendo expressivamente. Principal fator associado a ele é o Papiloma Vírus Humano (HPV). Estudos epidemiológicos mostram fases pré-clínicas antes do início do câncer anal. Esse trabalho visou a estimar a prevalência de alterações citológicas anais em pacientes com citologia cervical anormal e sem lesão macroscópica HPV induzida na região anal. Foram selecionadas 70 mulheres com citologia cervical alterada, soronegativas para o Vírus da Imunodeficiência Humana (HIV) e sem lesão perianal macroscópica pelo HPV. As pacientes foram submetidas a um questionário e foram realizadas coletas de captura híbrida anal e cervical, bem como de uma amostra de citologia oncológica cervical e duas amostras anais. A prevalência das alterações citológicas anais encontrada foi de 71,4%, sendo que 57,1% apresentaram captura híbrida anal positiva. A prevalência de captura híbrida anal positiva para HPV de alto risco oncogênico em paciente com citologia cervical de atipia escamosa de significado indeterminado, provavelmente não neoplásico (ASC-US) e de lesão intraepitelial escamosa de baixo grau (LSIL) foi de 27,1% e, em pacientes com citologia cervical de atipia escamosa de significado indeterminado, não podendo excluir lesão intraepitelial de alto grau (ASC-H), lesão intraepitelial escamosa de alto grau (HSIL), e carcinoma epidermóide do colo do útero foi de 30%. Pacientes com captura cervical positiva tiveram 4 vezes mais chance de apresentar captura anal positiva (OR=4; p=0,018). Concluímos haver alta prevalência citológica anal alterada na população estudada. O risco de contaminação anal é significativo nas pacientes com HPV de alto poder oncogênico em cérvice, portanto todas as pacientes com citologia cervical anormal merecem investigação anal, independente da gravidade do laudo citológico

The incidence of anal squamous cell carcinoma has been growing significantly. The main risk factor associated with this injurie is the Human Papilloma Virus (HPV). As studies have shown preclinical stages before the onset of anal cancer. This study aimed to estimate the prevalence of anal cytological abnormalities in patients with abnormal cervical cytology and without macroscopic HPV induced lesions in the anal region. The sample consisted of 70 women with abnormal cervical cytology, seronegative for human immunodeficiency virus (HIV) and without macroscopic anal lesions. Patients answered a questionnaire a were submited to collection of anal and cervical hybrid capture assay and collection of a sample of cervical cytology of two anal samples. Prevalence of anal cytological abnormalities found in patients with cervical cytological abormalities without macroscopic anal lesions was 71.4% and 57.1% of patients showed positive anal capture. Prevalence of positive hybrid capture to oncogenic anal HPV in patients with cervical cytology of atypical squamous cells of undetermined significance (ASC-US) and of low grade squamous intraepithelial lesion (LSIL) was 27.1%. Prevalence in patients with cervical cytology of atypical squamous cells – cannot exclude (ASC-H), high grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma of the uterine cervix in situ or were 30%. Patients with positive cervical capture were 4 times more likely to present positive anal capture (OR=4, p=0.018). In conclusion, we found a high prevalence of anal cytology abnormalities in this population. The risk of anal contamination is significant in patients with oncogenic HPV in cervix, so all patients with abnormal cervical cytology deserve anal investigation, regardless of the severity of cytological report

Cáncer anal: lesiones precursoras y cáncer temprano. consideraciones sobre terminología, diagnostico y terapéutica / Anal cancer: precursor lesions and early cancer. considerations on terminology,diagnosis and treatment

Las lesiones precursoras y formas tempranas del cáncer de ano y de la zona perianal ha sido en los últimos años mejor reconocidas y definidas; ello ha ido en paralelo a un interés cada vez mayor en esta patología debido a su incidencia creciente. En esta revisión se analiza el tema, actualizando los aspectos patogénicos que vinculan las neoplasias anales con subtipos oncogénicos del Papilomavirus Humano, y correlacionándolo con la existencia de poblaciones en riesgo y de alteraciones inmunitarias predisponentes o asociadas. Se describe la expresión morfológica de las lesiones precursoras y tempranas, en el contexto mas amplio de las neoplasias intraepiteliales similares de la zona genital baja. Tambien se realiza una puesta al día de las diversas técnicas de diagnóstico disponibles en este momento desde el punto de vista proctológico y antomopatologico y finalmente, una actualización de las diversas opciones terapéuticas y los cambios de enfoque y conducta que se plantean en lesiones anales y perianales diagnosticadas en etapas relativamente tempranas de su evolución.

The precursor precancerous lesions and early invasive cancer of the anus and the perianal area have been better recognized and defined in the last decade; it has been also a greater interest in this kind of precancers and cancers because of their increasing incidence. We analyzed in this paper this subject, updating the knowledge about the pathogenic link between anal neoplasias and oncogenics subtypes of Human Paplilomavirus, and correlating this neoplasias with the populations at risk and associated/predisposing immune alterations. The morphologic expression of the precursor and early invasive lesions is described, in the full context of similar intraepithelial neoplasias of the low genital area. Also we made an update of the proctologic and cytopathologic diagnostic techniques available at this moment and, finally, the therapeutic options and the changes of approach in anal and perianal preneoplastic and neoplastic lesions diagnosed in early stages of their evolution were revised.

Clinicopathological aspects and prevalence of human papillomavirus in anal cancer / Aspectos clínico-patológicos e prevalência do papilomavírus humano (HPV) em carcinomas anais

Anal cancer is relatively rare; however, its incidence has increased in recent years. Several risk factors are associated with the development of anal cancer, including age older than 50 years, low-fiber diet, chronic anal fistulas, smoking, multiple partners, anal intercourse practice, Human Immunodeficiency Virus infection and immunosuppression. However, the presence of human papillomavirus represents the main risk factor for the development of anal cancer. The aim of this study was to evaluate the clinicopathological aspects of a series of patients with anal carcinomas diagnosed in Hospital Araújo Jorge, Goiânia-Goiás, as well as the prevalence of human papillomavirus genome in these tumors. Clinical, pathological and socio-demographic data were collected from the respective medical files and paraffin blocks containing anal carcinomas specimens were used for DNA extraction and detection of human papillomavirus, by means of polymerase chain reaction, using short PCR fragment primers. Forty-three cases were selected and had the data analyzed, while 38 cases were tested for human papillomavirus genome detection. Among the evaluated patients, 62.8% were women; 53.4% of tumors were squamous cell carcinoma and 46.5% of the patients were aged between 60 and 75 years. Risk factors, such as smoking (39.5%) and alcoholism (20.9%) were recorded in the studied group. Lymph node metastases were detected in 30.2% of cases and 7.0% had distant metastasis. The detection of human papillomavirus DNA was positive in 76% of cases assessed and this was significantly associated with squamous cell carcinomas. Aggressive behavior and advanced stage of anal cancer described in this study highlight the need for preventive measures that contemplate these tumors, including vaccination against human papillomavirus. (AU)

O câncer anal é relativamente raro, entretanto, sua incidência aumentou nos últimos anos. Vários fatores de risco são associados ao desenvolvimento do câncer anal, incluindo idade maior que 50 anos, dieta pobre em fibras, fístulas anais crônicas, tabagismo, múltiplos parceiros, prática de intercurso anal, infecção pelo HIV e imunossupressão. Entretanto, a presença do Papilomavírus Humano (HPV) representa o principal fator de risco para o desenvolvimento do câncer anal. O objetivo deste estudo consistiu em avaliar os aspectos clínico-patológicos de uma série de pacientes com carcinomas anais diagnosticados no Hospital Araújo Jorge, Goiânia/GO, bem como a prevalência do genoma do HPV nesses tumores. Dados clínico-patológicos e sóciodemográficos foram colhidos a partir dos respectivos prontuários e blocos de parafina contendo espécimes de carcinomas anais foram usados para extração de DNA e detecção de HPV, por meio da reação em cadeia da polimerase, usando oligonucleotídeos iniciadores SPF. Quarenta e três casos foram selecionados e tiveram os dados clinico-patológicos analisados, enquanto 38 casos foram testados para a detecção do genoma do HPV. Dentre os pacientes avaliados, 62,8% eram mulheres; 53,4% dos tumores eram carcinomas de células escamosas e 46,5% dos pacientes estavam na faixa etária entre os 60 e 75 anos. Fatores de risco, como tabagismo (39,5%) e etilismo (20,9%) foram registrados no grupo estudado. Metástases linfonodais foram detectadas em 30,2% dos casos e 7,0% apresentaram metástase à distância. A detecção de HPV foi positiva em 76,0% dos casos analisados e este significativamente associado aos carcinomas de células escamosas. O comportamento agressivo e o estágio avançado dos carcinomas anais descritos no presente estudo destacam a necessidade de medidas de prevenção que contemplem esses tumores, incluindo a vacinação contra o HPV. (AU)

Anal melanoma: a rare, but catastrophic tumor / Melanoma anal: tumor raro, mas catastrófico

INTRODUCTION: Malignant melanoma of the anal canal is a rare and aggressive disease, which early diagnosis is difficult. Its presentation with no specific symptoms leads to a late diagnosis at an advanced stage. The prognosis of anorectal malignant melanoma is poor and frequently related to distant metastasis and absence of response of chemoradiotherapy. Surgery remains the mainstay of therapy; otherwise, the best approach is controversial. Considering no survival benefits for APR, wide local excision should be considered as the treatment of choice. METHODS: This report collects nine cases of anorectal melanoma treated at our division from 1977 to 2006, as well as a review of the literature. RESULTS: There were eight females and one male, of medium age 69 years (range: 41-85 years). Most frequent presentation was bleeding. Wide Local Excision (WLE) was performed in seven of them. Mean survival was 24 months, and six of them died on account of metastatic disease. CONCLUSION: Anorectal melanoma remains challenging. Efforts should be taken to early diagnosis, and wide local excision with negative margins is the preferred treatment. Abdominoperineal resection (APR) is a reasonable option for bulky tumors or when the sphincter is invaded. (AU)

INTRODUÇÃO: O melanoma maligno do canal anal é uma doença rara e agressiva, em que o diagnóstico precoce se torna difícil. Apresenta-se sem sintomas específicos, levando ao diagnóstico tardio e em fase avançada. O prognóstico é ruim e frequentemente relacionado a metástases a distância, bem como à ausência de resposta à rádio e à quimioterapia. A cirurgia permanece como terapia de escolha, no entanto a melhor abordagem ainda é controversa. Considerando não haver benefício na sobrevida da amputação abdômino-aerineal do aeto (AAPR), a excisão local ampla deve ser considerada o tratamento de escolha. MÉTODOS: São nove casos de melanoma anorretal tratados no serviço de coloproctologia do Hospital Naval Marcílio Dias (HNMD) de 1977 a 2006. RESULTADOS: Foram diagnosticados oito mulheres e um homem, com média de idade de 69 anos (41 - 85). A queixa mais frequente foi o sangramento anal. A excisão local ampla foi realizada em sete pacientes. A sobrevida média foi de 24 meses. CONCLUSÃO: O melanoma anorretal continua desafiante. Todos os esforços devem ser feitos para o diagnóstico precoce, tornando assim possível realizar a excisão local com margens negativas. A AAPR ainda é uma opção factível para tumores avançados ou quando o esfíncter anal está comprometido. (AU)

Evaluation of Langerhans cells counts comparing HIV-positive and negative anal squamous cell-carcinoma patients / Avaliação das células de Langerhans no carcinoma espinocelular do canal anal em pacientes HIV-positivo e negativo

PURPOSE: To investigate the differences in Langerhans cells (LCs) populations between HIV-positive and negative anal squamous cell carcinomas patients. METHODS: Twenty five patients (14 HIV-positive and 11 HIV-negative) were evaluated. Paraffin-block transversal thin sections from biopsies of anal squamous cell carcinomas (ASCC) were stained using the anti-CD1A antibody that identifies activated LCs. LCs counts were performed using histometry at 20 different sites, at baseline in the ASCC cases. These were then compared with LCs counts in anal canal specimens from HIV-negative and positive patients without ASCC (controls groups). RESULTS: In patients with ASCC, the LC count was greater among HIV-negative individuals than among HIV-positive individuals (p<0.05). The LC count was greater in the control HIV-negative group than in HIV-positive patients with ASCC (p<0.05). CONCLUSION: There was a lower amount of activated LCs in HIV-positive patients with anal squamous cell carcinomas than in HIV-negative patients, thereby suggesting worsening of the immune response.

OBJETIVO: Comparar a quantidade de células de Langerhans (CL) em pacientes portadores do carcinoma espinocelular (CEC) do canal anal HIV-positivo e negativo. MÉTODOS: Avaliamos 25 pacientes, sendo 11 HIV-negativo e 14 HIV-positivo portadores do CEC do canal anal. Realizamos estudo com a coloração imunoistoquímica anti-CD1A para avaliar as CL ativadas. Utilizamos as lâminas coradas e pelo método da histometria contamos em 20 campos diferentes as células coradas na camada basal da lâmina própria, onde era evidente a disseminação tumoral. Realizamos dois grupos controles compostos por pacientes submetidos à biopsia anal sem neoplasia (sete pacientes HIV-negativo e quatro HIV-positivo). Comparamos as contagens de CL. RESULTADOS: A quantidade de CL foi superior nos pacientes portadores do CEC do canal anal soronegativo para o HIV, em relação aos soropositivos (p<0,05). A quantidade de CL foi superior no grupo controle HIV-negativo em relação ao grupo composto por pacientes soropositivos portadores do CEC do canal anal (p<0,05). CONCLUSÃO: Houve aumento das células de Langerhans ativadas na área peritumoral dos pacientes soropositivos para o HIV, o que sugere diminuição da resposta imune local.

Avances en el diagnóstico precoz y tratamiento del cáncer de ano / Advances in the early diagnosis and treatment of anal cancer

El cáncer de ano es una neoplasia poco frecuente en la población general, pero, en poblaciones de riesgo, su incidencia sobrepasa al cáncer de cérvix en la era pre-Papanicolaou. El virus del HPV está directamente relacionado con su desarrollo, sumado a factores predisponentes, como infección por HIV, costumbres sexuales, hábito de fumar, inmunosupresión e infección genital por el primer virus. La detección precoz sólo está indicada a determinados grupos, con las muestras de citología anal y anoscopía de alta resolución como principales herramientas para diagnosticar y tratar las lesiones preneoplásicas. Un correcto diagnóstico histológico e imagenológico es indispensable para un tratamiento óptimo cuando estas lesiones progresan a cáncer, con nuevas técnicas radio-quimioterápicas, reservando cirugías de rescate con reconstrucciones perineales en caso de recaídas locales, que se diagnostican con un seguimiento adecuado.

Anal cancer is an unusual neoplasia in the general population, but, in at-risk populations, its incidence surpasses the cervical cancer in the pre-Papanicolaou test era. The HPV virus is directly related to its development, in addition to other predisposing factors such as infection caused by HIV, sexual behavior, smoking habit, immunosuppression and genital infection caused by the first virus. The early detection is only indicated to certain groups, with the anal cytology samples and the high resolution anoscopy being the main tools to diagnose and treat preneoplastic lesions. When these lesions develop into cancer, a proper histological and imaging diagnosis is essential to carry out an ideal treatment with new radiation therapy techniques, reserving salvage surgeries with perineal reconstructions for the cases of local reIapse, which are diagnosed with an appropriate monitoring.

Morphometric analysis of dendritic cells from anal mucosa of HIV-positive patients and the relation to intraepithelial lesions and cancer seen at a tertiary health institution in Brazil / Análise morfométrica das células dendríticas da mucosa anal de pacientes HIV-positivos e relação com as lesões intraepiteliais e o câncer numa instituição de saúde terciária no Brasil

PURPOSE: To morphometrically quantify CD1a+ dentritic cells and DC-SIGN+ dendritic cells in HIV-positive patients with anal squamous intraepithelial neoplasia and to evaluate the effects of HIV infection, antiretroviral therapy and HPV infection on epithelial and subepithelial dendritic cells. METHODS: A prospective study was performed to morphometrically analyze the relative volume of the dendritic cells and the relationship between anal intraepithelial neoplasia and cancer in HIV-positive patients from the Tropical Medicine Foundation of Amazonas, Brazil. All patients were submitted to biopsies of anorectal mucosa to perform a classic histopathological and immunohistochemical analysis, employing antibodies against CD1a and DC-SIGN for the morphometric quantification of dendritic cells. RESULTS: HIV-negative patients displayed a CD1a DC density significantly higher than that of HIV-positives patients (3.75 versus 2.54) (p=0.018), and in patients with severe anal intraepithelial neoplasia had correlated between DC CD1a density with levels of CD4 + cells (p: 0.04) as well as the viral load of HIV-1 (p: 0.035). A not significant rise in the median density of CD1a+ DC was observed in the HIV positive/ HAART positive subgroup compared to the HIV positive/ HAART negative subgroup. The CD1a+ DC were also significantly increased in HIV-negative patients with anorectal condyloma (2.33 to 3.53; p=0.05), with an opposite effect in HIV-positive patients. CONCLUSIONS: Our data support an enhancement of the synergistic action caused by HIV-HPV co-infection on the anal epithelium, weakening the DC for its major role in immune surveillance. Notoriously in patients with severe anal intraepithelial neoplasia, the density of CD1a+ epithelial dendritic cells was influenced by the viral load of HIV-1. Our study describes for the first time the density of subepithelial DC-SIGN+ dendritic cells in patients with anal severe anal intraepithelial neoplasia and points to the possibility that a specific therapy for HIV induces the recovery of the density of epithelial DC.

OBJETIVO: Quantificar morfometricamente as células dendríticas DC CD1a+ e DC DC-SIGN+ em pacientes HIV positivos portadores de neoplasia escamosa intraepitelial anal e avaliar os efeitos da infecção pelo HIV, da terapia antirretroviral e da infecção pelo HPV sobre as células dendríticas epiteliais e subepiteliais. MÉTODOS: Um estudo prospectivo foi realizado para analisar morfometricamente o volume relativo das células dendríticas e as relações entre neoplasia intraepitelial anal e o câncer em pacientes HIV positivos da Fundação de Medicina Tropical do Amazonas, Brasil.Todos os pacientes foram submetidos a biópsia da mucosa retal para realizar uma análise clássica histopatológica e imunohistoquímica utilizando anticorpos contra anti-CD1a e anti-DC-SIGN, para a quantificação morfométrica das células dendríticas. RESULTADOS: Os pacientes HIV negativos apresentaram densidade das DC CD1a+ significativamente maior do que a dos pacientes HIV positivos (3,75 versus 2,54) (p:0,018), e os pacientes com severa apresentaram correlação das DC CD1a com os níveis de células TCD4(p:0,04) assim como a carga viral do HIV-1 (p:0,035). Observamos no subgrupo HIV-positivo/HAART positivo elevação não significativa na mediana da densidade das DC CD1a+ em relação ao grupo HIV-positivo/HAART negativo. As DC CD1a+ também se elevaram nos pacientes HIV negativo portadores de condiloma anorretal(2,33 para 3,53; p:0,05), com efeito inverso nos pacientes HIV positivos. CONCLUSÕES: Nossos dados confirmam a potencialização da ação sinérgica representada pela coinfecção HIV-HPV sobre o epitélio anal, fragilizando as DC em sua função primordial de vigilância imune. Notoriamente nos pacientes com neoplasia intraepithelial anal grave, a densidade das DC CD1a+ epiteliais sofreu influência da carga viral do HIV-1. Nosso estudo descreveu pela primeira vez a densidade das DC subepiteliais DC-SIGN+ em pacientes com neoplasia intraepithelial anal severa e apontamos para a possibilidade de que a terapia específica para o HIV induza a recuperação da densidade das DC epiteliais.

Variabilidade interobservadores no diagnóstico de lesões precursoras do câncer anal: estudo do cenário habitual / Interobserver variability in the diagnosis of anal cancer precursor lesions: study of the usual scenario

OBJETIVO: Analisar a variabilidade interobservadores no diagnóstico de lesões precursoras do câncer anal no cenário mais comum de um serviço constituído por patologistas sem experiência prévia no diagnóstico destas lesões. MÉTODOS: Quinhentas e duas lâminas histopatológicas com espécimes anais retirados de 372 pacientes HIV-positivos e HIV-negativos foram analisadas no Departamento de Patologia da Fundação de Medicina Tropical do Amazonas por três patologistas com ampla experiência no diagnóstico de doenças tropicais e infecciosas, mas sem experiência prévia importante no diagnóstico de lesões precursoras do câncer anal. As leituras individuais de cada patologista foram comparadas com a que se seguiu a diagnóstico de consenso em microscópio de ótica compartilhada. Os diagnósticos individuais foram confrontados com os de consenso mediante análise da estatística kappa. RESULTADOS: A concordância absoluta entre cada diagnóstico individual e o de consenso correspondente foi ruim (kappa=-0,002). Considerando os resultados apenas positivos ou negativos para lesões intraepiteliais escamosas anais, obteve-se concordância regular entre os observadores (kappa=0,35), enquanto que a concordância foi moderada quando os resultados histopatológicos foram considerados positivos ou negativos para lesão intraepitelial de alto grau ou câncer (kappa=0,52). CONCLUSÃO: A variabilidade interobservadores no diagnóstico histopatológico do câncer anal e de suas lesões precursoras entre patologistas sem grande experiência na área, apesar de experts em outras, é tal que os diagnósticos neste campo e neste cenário comum devem sempre ser de consenso.

OBJECTIVE: To assess interobserver variability in the diagnosis of anal cancer precursor lesions in the usual scenario of a service consisting of pathologists without previous experience in the diagnosis of these lesions. METHODS: Five hundred and two anal specimens taken from 372 HIV-positive and HIV-negative patients were analyzed at the Pathology Department of the Tropical Medicine Foundation of Amazonas by three pathologists with extensive experience in the diagnosis of infectious and tropical diseases, but without significant prior experience in the diagnosis of anal cancer precursor lesions. The individual readings of each pathologist were compared to the one following the consensus diagnosis in shared optical microscope by kappa statistics. RESULTS: The absolute agreement between each individual diagnosis and corresponding consensus was poor (kappa = -0.002). Considering only the positive or negative results for anal squamous intraepithelial lesions, we obtained a fair agreement between observers (kappa = 0.35), while the agreement was moderate when the histopathological findings were considered positive or negative for high-grade squamous intraepithelial lesion or cancer (kappa = 0.52). CONCLUSION: The interobserver variability in histopathologic diagnosis of anal cancer and its precursor lesions among pathologists with little experience in the area is such that the diagnoses in this field and this scenario should always be a consensus.

A citologia na prevenção do câncer anal / The cytology in anal cancer prevention

O câncer anal não tem sido considerado problema de saúde pública. No entanto, sua incidência vem aumentando em pessoas que praticam sexo anal receptivo, promíscuos e portadores de doenças sexualmente transmissíveis, principalmente HPV (papilomavírus humanos) e HIV (vírus da imunodeficiência humana). Nos últimos anos, em vários países, a incidência do câncer anal aumentou 1,5 vezes entre os homens e triplicou nas mulheres. Embora a literatura não reforce o rastreamento de rotina das lesões intraepiteliais anais nas populações de risco, seu uso racional baseia-se no sucesso obtido com o rastreamento por meio da citologia cervical na redução da incidência do câncer cervical. Neste artigo revisamos os métodos diagnósticos disponíveis e as possibilidades de tratamentos das lesões precursoras anais a fim de prevenir a evolução para o câncer anal. Os aspectos biológicos das lesões precursoras anais são semelhantes aos das lesões cervicais. Dessa forma, como o ginecologista é o principal responsável pelo acompanhamento das mulheres, poderia

Anal cancer was not considered a neoplasm of public health concern until recently. Nevertheless, it may be object of attention in groups in which its incidence is increasing: people who have anoreceptive intercourse, promiscuous people and people who have sexual transmitted diseases (HPV and HIV infection). The incidence of anal cancer increased 1.5 fold among men and tripled among women in recent years. Although there is no strong literature evidence that document the value of screening for ASILs (anal squamous intraepithelial lesions) in the risk population, the rationale screening relies upon the success of cervical cytology screening in the reduction of cervical cancer incidence. It was reviewed the availability of screening modalities that effectively diagnosis the precursor lesion and the possibility of treatments that can prevent ASILs from progressing to anal cancer. The biologic consequences of anal dysplasia or ASIL are considered analogous of those of cervical dysplasia so the gynecologists may contribute to this diagnosis and to the prevention of anal cancer.

HPV infection and intraepithelial lesions from the anal region: how to diagnose?

In the last years, the prevalence of HPV infection in the anal region has increased, especially in some groups like homosexual and HIV-positive people. Since this infection can be associated with the development of squamous anal cancer due to its progression from HPV infection to anal intraepithelial neoplasia (AIN) and finally to cancer, the screening and evaluation of these conditions are important. Anal cytology and high resolution anoscopy are good methods that are available and can be used. Although useful, these methods should be performed correctly and not indiscriminately in all patients. Patients for whom anal cytology screening is recommended are: HIV-infected patients, homosexuals, women who present with high-grade vulvar squamous intraepithelial neoplasia, vulvar cancer or cervical cancer. An abnormal anal cytology should be further evaluated with high resolution anoscopy.