Sobrevida de pacientes com câncer colorretal em um Cancer Center / Survival of patients with colorectal cancer in a cancer center

ABSTRACT BACKGROUND: Hospital-based studies recently have shown increases in colorectal cancer survival, and better survival for women, young people, and patients diagnosed at an early disease stage. OBJECTIVE: To describe the overall survival and analyze the prognostic factors of patients treated for colorectal cancer at an oncology center. METHODS: The analysis included patients diagnosed with colon and rectal adenocarcinoma between 2000 and 2013 and identified in the Hospital Cancer Registry at A.C.Camargo Cancer Center. Overall 5-year survival was estimated using the Kaplan-Meier method, and prognostic factors were evaluated in a Cox regression model. Hazard ratios (HR) are reported with 95% confidence intervals (CI). RESULTS: Of 2,279 colorectal cancer cases analyzed, 58.4% were in the colon. The 5-year overall survival rate for colorectal cancer patients was 63.5% (65.6% and 60.6% for colonic and rectal malignancies, respectively). The risk of death was elevated for patients in the 50-74-year (HR=1.24, 95%CI =1.02-1.51) and ≥75-year (HR=3.02, 95%CI =2.42-3.78) age groups, for patients with rectal cancer (HR=1.37, 95%CI =1.11-1.69) and for those whose treatment was started >60 days after diagnosis (HR=1.22, 95%CI =1.04-1.43). The risk decreased for patients diagnosed in recent time periods (2005-2009 HR=0.76, 95%CI =0.63-0.91; 2010-2013 HR=0.69, 95%CI =0.57-0.83). CONCLUSION: Better survival of patients with colorectal cancer improves with early stage and started treatment within 60 days of diagnosis. Age over 70 years old was an independent factor predictive of a poor prognosis. The overall survival increased to all patients treated in the period 2000-2004 to 2010-2013.

RESUMO CONTEXTO: Estudos hospitalares recentes têm demonstrado aumento da sobrevida do câncer colorretal e melhor sobrevida para mulheres, jovens e pacientes diagnosticados em estágio precoce da doença. OBJETIVO: Descrever a sobrevida global e analisar os fatores prognósticos de pacientes tratados para câncer colorretal em um centro de oncologia. MÉTODOS: Foram incluídos pacientes com diagnóstico de adenocarcinoma de cólon e reto entre 2000 e 2013, identificados no Registro Hospitalar de Câncer do A.C.Camargo Cancer Center. A sobrevida global aos 5 anos foi estimada pelo método de Kaplan-Meier e os fatores prognósticos foram avaliados pelo modelo de Cox. As razões de risco (HR) são relatadas com intervalos de confiança (IC) de 95%. RESULTADOS: Dos 2.279 casos de câncer colorretal analisados, 58,4% eram de cólon. A taxa de sobrevida global aos 5 anos para pacientes com câncer colorretal foi de 63,5% (65,6% e 60,6% para câncer de cólon e retal, respectivamente). O risco de óbito foi elevado para pacientes na faixa etária de 50-74 anos (HR=1,24; IC95% =1,02-1,51) e ≥75 anos (HR=3,02; IC95% =2,42-3,78), para pacientes com câncer retal (HR=1,37; IC95% =1,11-1,69) e para aqueles cujo tratamento foi iniciado >60 dias após o diagnóstico (HR=1,22; IC95% =1,04-1,43). O risco diminuiu para pacientes diagnosticados em períodos recentes (2005-2009 HR=0,76; IC95% =0,63-0,91; 2010-2013 HR=0,69; IC95% =0,57-0,83). CONCLUSÃO: A sobrevida dos pacientes com câncer colorretal é maior naqueles em estágio inicial e com início do tratamento antes dos 60 dias.. Idade acima de 70 anos foi fator independente preditivo de mau prognóstico. A sobrevida global aumentou para todos os pacientes tratados no período de 2000-2004 a 2010-2013.

Adjuvant chemotherapy in locally advanced rectal cancer: deciding on the optimal strategy

ABSTRACT Background: Neoadjuvant therapy, followed by surgery, reduces the risk of local relapse in rectal cancer, but approximately 30% will relapse with distant metastases, highlighting the importance of adjuvant chemotherapy (aCT). Objective: The objective of the study was to study two regimens of adjuvant treatment in patients with locally advanced rectal cancer and analyze their efficacy and toxicity. Methods: Between January 2009 and December 2016, 193 patients with Stage II-III rectal cancer who had received neoadjuvant therapy were included by consecutive non-probability sampling. The decision to administer aCT, as well as the specific regimen, was at the discretion of the medical oncologist. Disease-free survival (DFS) and overall survival (OS) were calculated. Results: The mean DFS was 84.85 (95% confidence interval [CI]: 79-90) months in 164 patients receiving aCT, compared to 57.71 (95% CI: 40-74) months in 29 who did not receive aCT (p < 0.001). Then, mean OS was 92.7 (95% CI: 88-97) months and 66.18 (95% CI 51-81) months, respectively (p < 0.001). DFS was 83.6 (95% CI: 76-91) months in 74 patients receiving adjuvant 5-fluorouracil (5-FU), and 82.9 (95% CI: 75-90) months in 90 receiving 5-FU plus oxaliplatin (p = 0.49). OS was 87 (95% CI: 80-94) versus 93.65 (95% CI: 88-99) months, respectively (p = 0.76). The multivariate analysis identified aCT hazard ratio (HR) 0.30 (95% CI: 0.1-0.46), perineural invasion HR 3.36 (95% CI: 1.7-6.5), and pathological complete response HR 0.10 (95% CI; 0.01-0.75) as independent markers of DFS. Conclusions: In our study, aCT was associated with longer DFS and OS. 5-FU plus oxaliplatin showed greater toxicity with no added benefit in DFS or OS.

Individualized threshold for tumor segmentation in 18F-FDG PET/CT imaging: The key for response evaluation of neoadjuvant chemoradiation therapy in patients with rectal cancer? / Individualização na segmentação tumoral de imagens de 18F-FDG PET/CT: a chave para avaliação de resposta terapêutica neoadjuvante em pacientes com câncer retal?

Summary Introduction: The standard treatment for locally advanced rectal cancer (RC) consists of neoadjuvant chemoradiation followed by radical surgery. Regardless the extensive use of SUVmax in 18F-FDG PET tumor uptake as representation of tumor glycolytic consumption, there is a trend to apply metabolic volume instead. Thus, the aim of the present study was to evaluate a noninvasive method for tumor segmentation using the 18F-FDG PET imaging in order to predict response to neoadjuvant chemoradiation therapy in patients with rectal cancer. Method: The sample consisted of stage II and III rectal cancer patients undergoing 18F-FDG PET/CT examination before and eight weeks after neoadjuvant therapy. An individualized tumor segmentation methodology was applied to generate tumor volumes (SUV2SD) and compare with standard SUVmax and fixed threshold (SUV40%, SUV50% and SUV60%) pre- and post-therapy. Therapeutic response was assessed in the resected specimens using Dworak's protocol recommendations. Several variables were generated and compared with the histopathological results. Results: Seventeen (17) patients were included and analyzed. Significant differences were observed between responders (Dworak 3 and 4) and non-responders for SUVmax-2 (p<0.01), SUV2SD-2 (p<0.05), SUV40%-2 (p<0.05), SUV50%-2 (p<0.05) and SUV60%-2 (p<0.05). ROC analyses showed significant areas under the curve (p<0.01) for the proposed methodology with sensitivity and specificity varying from 60% to 83% and 73% to 82%, respectively. Conclusion: The present study confirmed the predictive power of the variables using a noninvasive individualized methodology for tumor segmentation based on 18F-FDG PET/CT imaging for response evaluation in patients with rectal cancer after neoadjuvant chemoradiation therapy.

Resumo Introdução: O câncer retal (RC) é uma doença de importância global, e o tratamento padrão para o câncer retal localmente avançado compreende quimiorradiação neoadjuvante seguida de cirurgia radical. Independentemente do uso extensivo da captação tumoral mais intensa do 18F-FDG (conhecida como SUVmax) como representativo do consumo glicolítico do tumor nas imagens de PET, há uma tendência para aplicar volume metabólico. Dessa forma, o objetivo do presente estudo foi avaliar um método não invasivo de segmentação tumoral utilizando a 18F-FDG PET para predizer a resposta à quimiorradioterapia neoadjuvante em pacientes com câncer de reto. Método: A amostra consistiu em pacientes com câncer retal em estádios II e III submetidos ao exame de 18F-FDG PET/CT antes e oito semanas após a terapia neoadjuvante. Foi aplicada uma metodologia de segmentação tumoral individualizada para gerar volumes tumorais (SUV2SD). A resposta terapêutica foi avaliada nos espécimes ressecados utilizando as recomendações do protocolo de Dworak. Várias variáveis foram geradas e comparadas com os resultados histopatológicos. Resultados: Dezessete (17) pacientes foram incluídos e analisados. Foram observadas diferenças significativas entre os respondedores (Dworak 3 e 4) e não respondedores para SUVmax-2 (p<0,01), SUV2SD-2 (p<0,05), SUV40%-2 (p<0,05), SUV50%-2 (p<0,05) e SUV60%-2 (p< 0,05). As análises ROC mostraram áreas significativas sob a curva (p<0,01) para a metodologia proposta, com sensibilidade e especificidade variando de 60% a 83% e 73% a 82%, respectivamente. Conclusão: O presente estudo confirmou o poder preditivo das variáveis utilizando uma metodologia não invasiva individualizada para segmentação tumoral baseada em imagens 18F-FDG PET/CT para avaliação da resposta em pacientes com câncer retal após tratamento com quimiorradiação neoadjuvante.

Clinical factors of post-chemoradiotherapy as valuable indicators for pathological complete response in locally advanced rectal cancer

OBJECTIVES: Pathological complete response has shown a better prognosis for patients with locally advanced rectal cancer after preoperative chemoradiotherapy. However, correlations between post-chemoradiotherapy clinical factors and pathologic complete response are not well confirmed. The aim of the current study was to identify post-chemoradiotherapy clinical factors that could serve as indicators of pathologic complete response in locally advanced rectal cancer. METHODS: This study retrospectively analyzed 544 consecutive patients with locally advanced rectal cancer treated at Sun Yat-sen University Cancer Center from December 2003 to June 2014. All patients received preoperative chemoradiotherapy followed by surgery. Univariate and multivariate regression analyses were performed to identify post-chemoradiotherapy clinical factors that are significant indicators of pathologic complete response. RESULTS: In this study, 126 of 544 patients (23.2%) achieved pathological complete response. In multivariate analyses, increased pathological complete response rate was significantly associated with the following factors: post-chemoradiotherapy clinical T stage 0-2 (odds ratio=2.098, 95% confidence interval=1.023-4.304, p=0.043), post-chemoradiotherapy clinical N stage 0 (odds ratio=2.011, 95% confidence interval=1.264-3.201, p=0.003), interval from completion of preoperative chemoradiotherapy to surgery of >7 weeks (odds ratio=1.795, 95% confidence interval=1.151-2.801, p=0.010) and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml (odds ratio=1.579, 95% confidence interval=1.026-2.432, p=0.038). CONCLUSIONS: Post-chemoradiotherapy clinical T stage 0-2, post-chemoradiotherapy clinical N stage 0, interval from completion of chemoradiotherapy to surgery of >7 weeks and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml were independent clinical indicators for pathological complete response. These findings demonstrate that post-chemoradiotherapy clinical factors could be valuable for post-operative assessment of pathological complete response.

Exenteración pélvica total por cáncer primario del recto: resultados inmediatos y alejados / Total pelvic exenteration for locally advanced rectal tumors: experience in 10 patients

Objetivo: El objetivo de este estudio es mostrar los resultados inmediatos y alejados de la exenteración pélvica total (EPT) en el manejo de tumores primarios de recto localmente avanzados. Se describe una alternativa técnica en los casos de EPT supraelevador. La EPT puede ser la única oportunidad de curación en pacientes con tumores pélvicos de gran volumen. Material y método: Se incluyen tumores T4 por la estadificación clínica o los hallazgos operatorios sometidos a una EPT con intención curativa. Resultados: En un periodo de 16 años se intervienen con esta técnica 10 pacientes, 6 de los cuales recibieron radioquimioterapia neoadyuvante. La técnica clásica se empleó en 3 pacientes y la EPT supraelevador, en 6. El promedio de hospitalización fue de 36 días (rango, 18-97) y la morbilidad alcanzó el 80%. El estudio de la pieza operatoria confirmó un tumor T4 en 6 pacientes, T3 en 3 y T0 en uno. Los 6 pacientes con neoadyuvancia son 1 ypT0N0M0, 2 ypIIA, 2 ypIIC y 1 ypIIIB. El resto eran 2 pIIC y 2 pIIIC. En el seguimiento hay 5 pacientes vivos entre 30 y 180 meses, y 3 fallecen por metástasis a distancia sin recidiva local. Conclusión: La EPT es una intervención asociada a una elevada morbilidad y larga estadía hospitalaria. La EPT supraelevador protegida mediante una ileostomía transitoria evitó una colostomía definitiva en 6 de 10 casos. La ileostomía urinaria muestra resultados funcionales satisfactorios en el largo plazo. La sobrevida prolongada en la mitad de los pacientes justifica la indicación de la técnica en casos seleccionados.

Aim: To report the results of total pelvic exenteration (TPE) in patients with locally advanced primary rectal tumors. Material and method: We report 10 patients with stage 4 rectal tumors subjected to a potentially curative TPE in a period of 16 years. Results: Six patients received also adjuvant chemoradiotherapy. A classic technique was used in 3 patients and a supra-elevator technique in 6. Mean hospitalization length was 36 days, and 80% of patients had complications. The pathological study of the surgical piece confirmed a T4 tumor in 6 patients, T3 in 3 and T0 in one. Among patients who received chemoradiotherapy, one was in stage ypT0N0M0, 2 in ypIIA, 2 in ypIIC, one in ypIIIB, 2 in pIIC and 2 in pIIIC. During follow up 3 patients survived between 30 and 180 months and three died due to distant metastases without local relapse. Conclusion: TPE requires long hospital stays and has a high rate of complications. Supra-elevator TPE protected with a transitory ileostomy avoided definitive colostomy in 6 of 10 cases. Urinary ileostomy had satisfactory long term functional results. The prolonged survival of half of the patients justifies the use of this surgical technique.

Transanal endoscopic operation for rectal cancer after neoadjuvant therapy

PURPOSE: In this paper we report the oncological outcomes from clinical series of patients with rectal cancer submitted to local excision after neoadjuvant therapy and discuss the indications for local excision in partial clinical responders. METHODS: We analysed a prospective database of 39 patients submitted to a transanal endoscopic operation for rectal cancer after neoadjuvant chemoradiation between 2006 and 2015, comparing clinical and pathological variables, perioperative complications, recurrence rate and overall survival. RESULTS: We obtained 15.4% ypT0, 17.9% ypT1, 35.9% ypT2 and 28.2% ypT3. After a median follow-up of 24 months, tumoral recurrence was observed in 4 patients, one of them with isolated pulmonary metastasis. R0 resection was achieved in 79.5%, and postoperative complications were observed in 30.2% patients and no perioperative mortality occur. Compromise surgical margins do not affect recurrence rate, and 94.9% of patients are alive nowadays. CONCLUSION: Local excision could be associated with low recurrence rate and good overall survival. Short hospitalization time and low level of serious complications observed could be an interesting option for patients who would not tolerate a radical procedure or for those who declined a total mesorectal excision. A strict long-term follow-up must be warranted to detect early tumoral recurrence.

Marcadores e mecanismos de resistência à terapia neoadjuvante e o papel das vesículas extracelulares secretadas pelas células tumorais no câncer de reto / Biomarkers and mechanisms of resistance to neoadjuvnat therapy and the role of extracelular vesicles secreted by tumor cells in rectal cancer

O câncer de reto é o segundo tumor mais comum no intestino grosso correspondendo a um terço do total de casos de câncer colorretal (CCR). Pacientes com câncer de reto em estádios II e III são tratados com radioquimioterapia neoadjuvante seguida de ressecção cirúrgica do tumor. Análises das peças cirúrgicas ressecadas mostraram que apenas 10-45% dos pacientes obtém resposta patológica completa (RCp) à terapia neoadjuvante, estando essa associada com uma diminuição da recorrência local, melhora da sobrevida livre de doença e aumento na preservação esfincteriana. Apesar da melhora na sobrevida nas últimas décadas, a resposta à terapia neoadjuvante continua variável e imprevisível e não é possível identificar e separar clinicamente os grupos de pacientes que terão ou não resposta completa ao tratamento neoadjuvante. Além disso, os mecanismos de resistência à radioquimioterapia nos tumores de reto são pouco compreendidos. Dessa forma, o objetivo principal deste estudo foi identificar marcadores e mecanismos celulares relacionados à resistência à terapia neoadjuvante em adenocarcinoma de reto e o papel das vesículas extracelulares (VEs) nesse processo. O estudo proteômico comparativo entre biópsias obtidas de tumores pré-tratamento com o tumor residual removido cirurgicamente pós-tratamento radioquimioterápico mostrou uma importante alteração no perfil de expressão proteica. Entre as proteínas que aumentam a expressão após a neoadjuvância estão as proteínas de reparo de dano de DNA, Ku70 e Ku80, e a proteína de tráfego intracelular Rab5C. Em um modelo in vitro, foi demonstrado que Rab5C orquestra um mecanismo de resistência à radioterapia nos tumores de reto através da modulação da internalização de EGFR promovida por radiação ionizante (RI). O EGRF intracelular por sua vez é essencial para regular a expressão de Ku70 e Ku80 e a resistência celular à RI. Estes dados apontam Rab5C e EGFR como potenciais alvos terapêuticos para sensibilizar células de câncer de reto resistentes ao tratamento neoadjuvante. Também foi observado que a RI promove alterações epigenéticas predominantemente de hipometilação, e entre os genes alterados estão SPG20 e TBC1D16, sendo o primeiro importante para a internalização de EGFR e o segundo para a regulação de Rab5C e modulação de EGFR. O perfil de expressão proteica foi ainda comparado entre biópsias pré-tratamento de pacientes com RCp e sem resposta patológica, e o resultado mostrou que esses dois grupos de pacientes apresentam um diferente perfil de expressão proteica. Nos pacientes com RCp as proteínas com aumento da expressão estão atuando em vias que favorecem a resposta à terapia, como a detoxificação de glutationa e degradação de glicogênio, enquanto as proteínas com aumento da expressão em pacientes sem RCp estão envolvidas em vias do metabolismo energético do tumor as quais contribuem para a resistência tumoral à terapia. As diferenças observadas nestes grupos devem ser amplamente exploradas uma vez que podem ser marcadores preditivos de resposta ao tratamento radioquimioterápico. A realização de estudos funcionais foi viabilizada pela geração de um modelo celular de tumor de reto resistente à radioterapia. Ao analisar as VEs secretadas por estas células foi observado que a RI não altera a quantidade e o tamanho médio das VEs secretadas, porém é capaz de alterar o carregamento proteico das mesmas. De fato, as VEs de células irradiadas apresentam um perfil proteico diferente quando comparadas as VEs de células não irradiadas, onde encontramos aumento da expressão de Ku70, Ku80 e Rab5C, além das metiltransferases NSUN2 e GLYM nas VEs de células pós RI. Interessantemente, as VEs secretadas por células irradiadas são capazes de transmitir a resistência à RI às células não irradiadas. Além disso os resultados mostraram que o tratamento com VEs de células irradiadas promove metilação em 98% do DNA avaliado em células SW837 em comparação ao tratamento com VEs de células não irradiadas. Os genes hipermetilados estão envolvidos em vias relacionadas ao sistema imune, como a apresentação de antígeno, sinalização de imunodeficiência primária e maturação de células dendríticas. Por fim, foi identificado que a expressão da proteína A33 está relacionada ao grau de diferenciação dos tumores colorretais, e que essa proteína está presente em VEs secretadas por células de adenocarcinoma de reto, indicando que a mesma pode ser usada para isolar VEs específicas do tecido colorretal. Os dados obtidos neste trabalho apontam mecanismos relacionados à resistência à terapia neoadjuvante no adenocarcinoma de reto e que em conjunto permitirão identificar novos alvos terapêuticos com potencial de melhorar a resposta à radioquimioterapia, além de identificar marcadores de resposta à terapia neoadjuvante antes do tratamento e dessa forma, poupar os pacientes não respondedores de terapias tóxicas e melhorar a sustentabilidade na saúde poupando os custos com drogas não eficientes para um grupo de pacientes.

Rectal cancer is the second most common cancer in large intestine, corresponding to one third of total cases of colorectal cancer (CRC). Patients with rectal cancer in stage II and III are treated with neoadjuvant chemoradiation followed by surgical resection. Analyzes of the resected tumor demonstrated that only 10-45% of the patients achieve pathological complete response (pCR) after neoadjuvant therapy, which is associated with a decrease in local recurrence, improvement of disease free survival and increase in sphincter preservation. Despite the improvement in survival in the last decades, the response to neoadjuvant therapy is still variable and unpredictable, and before the surgery it is not possible to identify and separate clinically the group of patients that will or will not have complete response to neoadjuvant treatment. Moreover, the mechanisms of resistance of rectal tumors to chemoradiation are poorly understood. Thus, the main objective of this work was to identify biomarkers and cellular mechanisms related to the resistance to neoadjuvant therapy in rectal adenocarcinomas and the role of extracellular vesicles (EVs) in this process. The comparative proteomic study between biopsy obtained from tumors pretreatment with residual tumor, post chemoradiation treatment, removed by surgery showed an important alteration in the protein expression profile. Among the proteins with increased expression after neoadjuvant therapy are the DNA repair proteins Ku70 and Ku80, and the protein involved in the intracellular trafficking, Rab5C. It was demonstrated in vitro that Rab5C orchestrates a mechanism of radioresistance in rectal tumors by modulating the EGFR internalization promoted by ionizing radiation (IR). The intracellular EGFR is essential to regulate Ku70 and Ku80 expression and the cell resistance to IR. These data pointed Rab5C and EGFR as potential therapeutic targets to sensitize rectal cancer cells resistant to neoadjuvant treatment. It was also observed that IR promotes epigenetic alterations, predominantly hypomethylation, and between the altered genes are SPG20 and TBC1D16, the first is important to EGFR internalization, while the second regulates Rab5C and modulates EGFR. The protein expression profile was further compared between biopsy pretreatment of patients with and without pCR, and the results showed that these two groups of patients present a different protein expression profile. In patients with pCR the proteins with increased expression are involved in pathways favoring the response to therapy, as glutathione-mediated detoxification and glycogen degradation, while the proteins with increased expression in patients without pCR are involved in tumor energetic metabolism pathways that contribute to tumor resistance to therapy. The observed differences in these groups should be widely explored since they may be predictive markers of response to chemoradiation treatment. The performance of functional studies was possible by generation of a cellular model of rectal tumor resistant to radiotherapy. The analysis of the EVs secreted by these cells showed that IR does not alter the amount and the medium size of secreted EVs, but is able to change their protein content. EVs from irradiated cells presented a different protein profile when compared to EVs from non-irradiated cells, where it was found the increased expression of Ku70, Ku80 and Rab5C, besides the methyltransferases NSUN2 and GLYM in EVs after irradiation. Interestingly, the EVs secreted by irradiated cells are capable of transfering resistance to IR to non-irradiated cells. Moreover, the results showed that the treatment of SW837 cells with EVs from irradiated cells promoted methylation in 98% of the analyzed DNA in comparison with the treatment with EVs from non-irradiated cells. The hypermethylated genes are involved in pathways related to immune system, as antigen presentation, primary immunodeficiency signaling and dendritic cells maturation. Lastly, it was identified that the A33 expression is related to the colorectal tumors differentiation degree, and this protein is present in EVs secreted by rectal adenocarcinoma, indicating that it may be used to isolate EVs specific from colorectal tissues. The data obtained in this work pointed to mechanisms related to resistance to neoadjuvant therapy in rectal adenocarcinoma that together will allow to identify new therapeutic targets with the potential to improve the response to chemoradiation, as well as to identify markers of response to neoadjuvant therapy before the treatment, and, in this way, avoid the non-responder patients to receive toxic therapies and improve health sustainability, sparing cost with non-efficient drugs for a group of patients.

Transanal minimally invasive surgery (TAMIS) for local excision of selected rectal neoplasms: efficacy and outcomes in the first 11 patients / Cirurgia trans-anal minimamente invasiva (CTAMI) para excisão local de neoplasias retais selecionadas: eficácia e desfechos nos primeiros 11 pacientes

Disposable single-port surgery devices have been used for transanal minimally invasive surgery (TAMIS) with benefits, when compared to local resection and transanal endoscopic microsurgery (TEM). Objective: To show outcomes and details of the technique. Method: A series of patients with indication for local resection of rectal tumors were submitted to surgery using the TAMIS platform. Results: Eleven patients have been submitted to TAMIS. Distance from anal verge was from 1.5 to 8 cm and maximum tumor diameter was 6 cm. Initial diagnosis of adenoma was the most frequent indication for resection. One partial dehiscence was the only complication seen. Minimal setup time, low cost and the possibility of using regular laparoscopic instruments make TAMIS a good option for transanal resection. The results of this technique are encouraging, concerning the feasibility, maneuverability, upfront cost, setup time, resectability and complication rate. Because of its simplicity and similarity with conventional laparoscopic surgery, it can be learned easily. Although at the present time the appropriate use of local excision is still under debate, TAMIS is a technique that still expects a lot of growing and much remains to be learned. (AU)

Dispositivos cirúrgicos de porta única descartáveis têm sido utilizados para a Cirurgia Trans-anal Minimamente Invasiva (CTAMI) com benefícios, quando comparados com ressecção local e microcirurgia endoscópica trans-anal (MET). Objetivo: Apresentar os desfechos e detalhes da técnica. Método: Uma série de pacientes com indicação para ressecção local de tumores retais foi tratada cirurgicamente pela plataforma CTAMI. Resultados: Onze pacientes foram tratados por CTAMI. A distância a contar da margem anal variou de 1,5 até 8 cm, e o diâmetro máximo do tumor foi 6 cm. Um diagnóstico inicial de adenoma foi a indicação mais frequente para a ressecção. A única complicação ocorrida foi uma deiscência parcial. Mínimo tempo para preparação, baixo custo e a possibilidade do uso de instrumentos laparoscópicos convencionais fazem de CTAMI uma boa opção para a ressecção trans-anal. Os resultados dessa técnica são animadores, no que diz respeito à exeqüibilidade, manobrabilidade, custos iniciais, tempo de preparação, ressectabilidade e percentual de complicações. Graças à sua simplicidade e semelhança com a cirurgia laparoscópica convencional, CTAMI tem uma fácil curva de aprendizado. Embora atualmente ainda seja motivo de discussão o uso apropriado da excisão local, CTAMI é uma técnica que ainda provavelmente ainda crescerá muito–e há muito a ser aprendido. (AU)

Feasibility of endoscopic submucosal dissection for gastric and colorectal lesions: Initial experience from the Gastrocentro - Unicamp

OBJECTIVE: Endoscopic submucosal dissection is a technique developed in Japan for en bloc resection with a lower rate of recurrence. It is considered technically difficult and performed only in specialized centers. This study sought to report the initial experience from the Gastrocentro - Campinas State University for the treatment of gastric and colorectal lesions by endoscopic submucosal dissection. MATERIALS AND METHODS: The guidelines of the Japanese Association of Gastric Cancer were used as evaluative criteria. For colorectal lesions, the recommended standards proposed by Uraoka et al. and Saito et al. were employed. The practicability of the method, the development of complications and histological analysis of the specimens were evaluated. RESULTS: Sixteen patients underwent endoscopic submucosal dissection from June 2010 to April 2011; nine patients were treated for gastric lesions, and seven were treated for colorectal lesions. The average diameter of the gastric lesions was 28.6 mm, and the duration of resection was 103 min without complications. All lesions presented lesion-free margins. Of the seven colorectal tumors, four were located in the rectum and three were located in the colon. The average size was 26 mm, and the average procedure time was 163 min. Two complications occurred during the rectal resection procedures: perforation, which was treated with an endoscopic clip, and controlled bleeding. One of the lesions presented a compromised lateral margin without relapse after 90 days. Depth margins were all free of lesions. CONCLUSION: Endoscopic submucosal dissection at our institution achieved high success rates, with few complications in preliminary procedures. The procedure also made appropriate lesion staging possible.

Abdominoperineal resection does not decrease quality of life in patients with low rectal cancer

PURPOSE: Issues related to body image and a permanent stoma after abdominoperineal resection may decrease quality of life in rectal cancer patients. However, specific problems associated with a low anastomosis may similarly affect quality of life for patients undergoing low anterior resection. The aim of this study was to compare quality of life of low rectal cancer patients after undergoing abdominoperineal resection versus low anterior resection. METHODS: Demographics, tumor and treatment characteristics, and prospectively collected preoperative quality-of-life data for patients undergoing low anterior resection or abdominoperineal resection for low rectal cancer between 1995 and 2009 were compared. Quality of life collected at specific time intervals was compared for the two groups, adjusting for age, body mass index, use of chemoradiation, and 30 days postoperative complications. The short-form-36 questionnaire was used to determine quality of life. RESULTS: The query returned 153 patients (abdominoperineal resection = 68, low anterior resection = 85) with a median follow-up of 24 (3-64) mo. The after abdominoperineal resection group had a higher mean age (63 + 12 vs. 54 + 12, p < 0.001) and more American Society of Anesthesiologists classification 3/4 patients (65 percent vs. 43 percent, p = 0.03) than low anterior resection. Other demographics, tumor stage, use of chemoradiation, overall postoperative complication rates, and quality-of-life follow-up time were not statistically different in both groups. Patients undergoing abdominoperineal resection had a lower baseline short-form-36 mental component score than those undergoing low anterior resection. However, 6 mo after surgery this difference was no longer statistically significant and essentially disappeared at 36 mo after surgery. CONCLUSION: Patients undergoing abdominoperineal resection for low rectal cancer have a similar long-term quality of life as those undergoing low anterior resection. These findings can help clinicians to better counsel patients with low rectal cancer who are being considered for abdominoperineal resection.

Resultados del tratamiento quirúrgico del cáncer del tercio superior del recto y de colon sigmoides: análisis comparativo / Comparative results of the surgical treatment of tumors located in the upper third of the rectum and sigmoid colon

Background: Tumors located in the upper third of the rectum can be treated in the same way as sigmoid tumors. This means that mesorrectum excision and neoadjuvant therapies are not necessary. Aim: To compare the results in terms of relapse and survival of elective surgery for sigmoid and upper third rectal tumors. Material and Methods: Retrospective analysis of patients operated for an upper third rectal or sigmoid cancer that were prospectively included in a database and had a minimum follow up of 18 months. Clinical and pathological variables and staging using TNM classification were considered as covariates in the analysis. Results: Fifty patients with a tumor of the upper third of the rectum, aged 30 to 84 years (24 females), with a follow up ranging from 12 to 206 months, and 107 patients with a sigmoid tumor, aged 22 to 91 years (62 females), with a follow up ranging from 13 to 204 months, were analyzed. Seven patients with rectal tumors (14 percent) and 12 patients with sigmoid tumors (11 percent), died during follow up (p = NS). Ten years actuarial overall survival was 85 percent for both groups. Conclusions: No differences in survival or relapse were observed in this group of patients with tumors located in the upper third of the rectum or sigmoid colon. Therefore both types of tumors can be treated in the same way.

Introducción: Se ha sugerido que los pacientes con un tumor del tercio superior del recto (RS) podrían tratarse en forma similar que los portadores de un cáncer de sigmoides (CS). Ello implica no realizar la resección total del mesorrecto ni someterlos a terapias neoadyuvantes. El objetivo de este estudio es comparar los resultados del tratamiento quirúrgico electivo de ambos tumores respecto de la recidiva y la sobrevida global. Pacientes y Método: Análisis retrospectivo de las características demográficas de los pacientes intervenidos por un adenocarcinoma de recto superior y de colon sigmoides con intención curativa en forma electiva en forma consecutiva con un seguimiento mínimo de 18 meses. Se considera variables clínicas (edad, género, enfermedades asociadas, antígeno carcinoembrionario (CEA) preoperatorio), histopatológicas (diferenciación y tamaño tumoral, número de ganglios examinados) y la estadificación de ambos grupos según TNM. Resultados: Se compara 50 pacientes portadores de un adenocarcinoma de RS en los estadios I a III con 107 pacientes intervenidos en el mismo período por un cáncer de CS con intención curativa. El seguimiento promedio de los pacientes con un tumor de RS fue de 88,62 meses (extremos 12-206), y de 71,67 meses en los casos de CS (extremos 13-204) (p = 0,05). Durante este período fallecen por la enfermedad 7 pacientes (14 por ciento) del grupo RS, 1 por recidiva locorregional y 6 por recidiva a distancia, con un rango entre 12 y 78 meses. En el grupo CS fallecen 12 pacientes (11,2 por ciento), 3 (2,8 por ciento) con recidiva locorregional y 9 con recidiva a distancia, entre 24 y 82 meses de seguimiento (p = 0,24). La sobrevida actuarial global a 10 años para ambos grupos fue de 85 por ciento. Conclusión: En este estudio no existen diferencias en cuanto a la recidiva global, la recidiva local ni la recidiva a distancia entre ambos grupos, lo que avala la estrategia de tratar en forma similar los tumores...

Microcirurgia endoscópica transanal no tratamento dos tumores do reto: estudo prospectivo em 50 pacientes / Transanal endoscopic microsurgery in the treatment of rectal tumors: a prospective study in 50 patients

RACIONAL: A literatura médica aceita ressecção local como opção válida em casos selecionados de tumores de reto. A seleção dos pacientes requer exata estimativa dos riscos e avaliação pré-operatória precisa, tanto no aspecto clínico como histopatológico. OBJETIVO: Avaliar os resultados da microcirurgia endoscópica transanal em seguimento de 18 meses. MÉTODOS: De abril de 2002 a abril de 2006, 50 pacientes com tumores de reto foram submetidos a microcirurgia endoscópica transanal, selecionados por suas características clínicas e histopatológicas. Os critérios de inclusão foram: adenomas sésseis maiores do que 3 cm e menores do que 8 cm não-circunferenciais; neoplasia intra-epitelial de alto grau; carcinoma retal pT1, e em casos especiais pT2. Todos esses tumores foram submetidos ao mesmo procedimento cirúrgico. RESULTADOS: O resultado histopatológico final revelou 9 adenomas, 26 neoplasias intra-epiteliais de alto grau, 13 carcinomas (9 pT1 e 4 pT2) e 2 carcinóides. A menor idade foi de 25 anos e a maior de 92. O menor tumor ressecado tinha 64 mm² (carcinóide) e o maior (adenoma) 90 mm². O tempo médio de operação foi de 90 minutos e o de internamento 5 dias. Houve uma morte não relacionada ao método. Um paciente com carcinoma de baixo risco pT1 apresentou recidiva 18 meses após microcirurgia endoscópica transanal e foi submetido a retossigmoidectomia curativa. Foi observado tumor residual em dois pacientes e a complicação mais grave foi uma fístula retovaginal. A taxa de complicação global foi de 9 por cento. CONCLUSÃO: Atualmente a microcirurgia endoscópica transanal é a técnica de escolha para o tratamento de adenomas sésseis, neoplasias intra-epiteliais de alto grau e carcinoma retal pT1 de baixo risco.

BACKGROUND: The medical literature accepts local resection as a valuable option in selected cases of rectal tumors. Selection of patients requires an exact perioperative estimation of risks with clinical and histopathological examination. Transanal endoscopic microsurgery aims a safe resection of the tumoral area which leads up to the cure. AIM: To evaluate transanal endoscopic microsurgery results in a follow-up time of 18 months. METHODS: From April 2002 to April 2006, 50 patients with rectal tumors were submitted to transanal endoscopic microsurgery, chosen by clinical history and lesion characteristics. The inclusion criteria were: sessile adenomas larger than 3 cm and smaller than 8 cm, not circumferentially distributed; intra epithelial neoplasia of high degree; and rectal carcinoma pT1, and special cases of pT2. All these rectal tumors were submitted to the same surgical act. RESULTS: The final histopathological results reveal 9 adenoma, 26 intra-epithelial neoplasia of high degree, 13 carcinoma (9 pT1-4 pT2) and 2 carcinoid. The lowest age was 25 and the higher, 92 years-old. The smallest resected tumor had 64 mm² (carcinoid) and the largest (adenoma), 90 cm². Operating time was in average 90 minutes and the overall time statement, 5 days. There was one death not related with the method. One patient with low risk carcinoma pT1 presented recurrence 18 months after transanal endoscopic microsurgery and was submitted to curative rectosigmoidectomy. It was proven a residual tumor after local surgery in two patients and the most important complication was one recto-vaginal fistula. The overall complications rate was 9 percent. CONCLUSION: Today transanal endoscopic microsurgery is chosen as the ideal technique for the treatment of sessile adenomas, intraepithelial neoplasia of high degree and rectal carcinoma pT1.

Risk factors for anastomotic leakage after preoperative chemoradiation therapy and low anterior resection with total mesorectal excision for locally advanced rectal cancer / Factores de riesgo para la fuga anastomótica después de quimio-radioterapia preoperatoria y resección anterior baja con excisión total de mesorrecto para cáncer de recto localmente avanzado

Background. Risk factors for anastomotic leakage after preoperative chemoradiation plus low anterior resection and total mesorectal excision remain uncertain. Objective. To analyze, the associated risk factors with colorectal anastomosis leakage following preoperative chemo-radiation therapy and low anterior resection with total mesorectal excision for rectal cancer. Materials and methods. Between January 1992 and December 2000, 92 patients with rectal cancer were treated with 45 Gy of preoperative radiotherapy and bolus infusion of 5-FU 450 mg/m² on days 1-5 and 28-32, six weeks later low anterior resection was performed. Univariate analysis was performed as to find the risk factors for colorectal anastomotic leakage. Results. There were 48 males and 44 females, mean age was 55.8 years. Mean tumor location above the anal verge was 7.4 ± 2.6 cm. Preoperative mean levels of albumin and lymphocytes were 3.8 g/dL and l,697/mL, respectively. Mean distal margin was 2.9 ± 1.4 cm. Multivisceral resection was performed in 11 patients (13.8%), 32 patients (35%) had diverting stoma. Mean preoperative hemorrhage was 577 ± 381 mL, and 27 patients (24%) received blood transfusion. Ten patients (10.9%) had anastomotic leakage. No operative mortality occurred. Risk factors for anastomotic leakage were: gender (male) and tumor size > 4 cm. Three patients of the group without colostomy required a mean of six days in the unit of intensive care; mean time of hospital stay of patients with and without protective colostomy was 12.4 ± 4.5 days vs. 18.3 ± 5.2 days (p = 0.01). Conclusion. In male patients with rectal adenocarcinoma measuring > 4 cm, treated by preoperative chemoradiotherapy + low anterior resection with total mesorectal excision, a diverting stoma should be performed to avoid major morbidity due to anastomotic leak.

Antecedentes. Los factores de riesgo para la fuga de anastomosis colo-rectal después de quimio-radioterapia preoperatoria con excisión total de mesorrecto permanecen aún inciertos. Objetivo. Analizar los factores de riesgo asociados con la fuga o filtración de anastomosis colorrectal que sigue a la terapia de radiación química y a la extirpación anterior baja con total excisión mesorrectal para el cáncer rectal. Materiales y métodos. Entre enero de 1992 y diciembre de 2000, 92 pacientes con cáncer rectal fueron tratados con 45 Gy de radioterapia preoperativa e infusión del bolo de 5'FU450 mg/m² administrados los días 1-5 y del 28-32; seis semanas más tarde, se realizó la extirpación anterior baja. Se llevó a cabo un análisis univariado en cuanto a encontrar los factores de riesgo de la fuga anastomótica colorrectal. Resultados. Se trató a 48 varones y 44 mujeres cuya media etaria fue de 55.8 años. La localización media del tumor arriba del borde anal fue de 7.4 ± 2.6 cm. Los niveles medios preoperativos de albúmina y linfocitos fueron de 3.8 g/dL y 1,697/mL, respectivamente. El margen distal medio fue de 2.9 ± 1.4 cm. La extirpación multivisceral fue realizada en 11 pacientes (13.8%); 32 pacientes (35%) tuvieron una colostomía derivativa. La hemorragia preoperativa media fue de 577 ± 381 mL, y 27 pacientes (24%) recibieron transfusión sanguínea. Diez pacientes (10.9%) tuvieron fuga anastomótica. No hubo ningún deceso quirúrgico. Los factores de riesgo para la fuga anastomótica fueron: el género (masculino) y el tamaño del tumor > 4 cm. Tres pacientes del grupo sin colostomía requirieron una media de seis días en la UTI (Unidad de Terapia Intensiva); el promedio media de la duración hospitalaria de pacientes con y sin colostomía protectiva fue de 12.4 ± 4.5 días contra 18.3 ± 5.2 días (p = 0.01). Conclusión. En pacientes masculinos con adenocarcinoma rectal que mide > 4 cm, tratados mediante radioterapia química preoperativa + extirpación anterior baja con excisión total mesorrectal, debería realizarse una abertura que se desvíe a fin de evitar una mayor mortalidad debida a fuga anastomótica.

Control de calidad de 135 informes histopatológicos de carcinoma colo-rectal / Quality control of 135 surgical pathology reports of colo-rectal carcinoma

Objetivo. Evaluar la calidad del contenido en informes de especímenes quirúrgicos con carcinoma de colon y recto. Tipo de estudio. Análisis retrospectivo y observacional. Material y métodos. Informes histopatológicos de piezas quirúrgicas con carcinoma de colon y recto resecados entre 1988 y 1994. De los informes se obtuvieron variables macroscópicos e histológicas con relevancia pronóstica y de acuerdo al sistema TNM que se vaciaron a hojas de cotejo. para definir la calidad del informe, el número de variables con valore pronóstico se cuantificó en relación con 11 características macroscópicas e histológicas que idealmente deben contener. Resultados. Se analizaron 135 informes. El tipo histológico, el grado de diferenciación y la invasión local fueron las variables anotadas con mayor frecuencia. El 90 por ciento de los informes contenían las características de los ganglios linfáticos y en 85 por ciento se evaluaron macro e histológicamante los bordes quirúrgicos. Otras variables con valor pronóstico no se anotaron, v.gr. la angioinvasión se estipuló en un caso (0.7 por ciento). Conclusiones. Con el uso de la hoja de cotejo con variables estandarizadas nuestros informes de especímenes con carcinoma colo-rectal mostraron ser adecuados en 113/135 (85 por ciento) ya que tenían más de ocho variables pronósticoas. Las diferencias detectadas Fueron: 1) descripción macroscópica inadecuada; 2) carencia del grado de diferenciación en 12 por ciento; y 3) omisión del sitio anatómico en 29 por ciento