Quality of life in a randomized trial comparing two neoadjuvant regimens for locally advanced rectal cancer-INCAGI004.

BACKGROUND: Neoadjuvant chemoradiotherapy (neoCRT) followed by surgery is the standard of care for locally advanced rectal cancer (LARC), but the emergence of different drug regimens may result in different response rates. Good clinical response translates into greater sphincter preservation, but quality of life (QOL) may be impaired after treatment due to chemoradiotherapy and surgical side effects. OBJECTIVE: To prospectively evaluate the impact of clinical response and surgical resection on QOL in a randomized trial comparing two different neoCRT regimens. METHODS: Stage II and III rectal cancer patients were randomized to receive neoCRT with either capecitabine (group 1) or 5-Fu and leucovorin (group 2) concomitant to long-course radiotherapy. Clinical downstaging was accessed using MRI 6-8 weeks after treatment. EORTCs QLQ-C30 and CR38 were applied before treatment (T0), after neoCRT (T1), after rectal resection (T2), early after adjuvant chemotherapy (T3), and 1 year after the end of treatment or stoma closure (T4). The Wexner scale was used for fecal incontinence evaluation at T4. A C30SummaryScore (Geisinger and cols.) was calculated to compare QOL results. RESULTS: Thirty-two patients were assigned to group 1 and 31 to group 2. Clinical downstaging occurred in 70.0% of group 1 and 53.3% of group 2 (p = 0.288), and sphincter preservation was 83.3% in group 1 and 80.0% in group 2 (p = 0.111). No significant difference in QOL was detected when comparing the two treatment groups after neoCRT using QLQ-C30. However, the CR38 module detected differences in micturition problems (15.3 points), gastrointestinal problems (15.3 points), defecation problems (11.8 points), and sexual satisfaction (13.3 points) favoring the capecitabine group. C30SummaryScore detected significant improvement comparing T0 to T1 and deterioration comparing T1 to T2 (p = 0.025). The mean Wexner scale score was 9.2, and a high score correlated with symptoms of diarrhea and defecation problems at T4. CONCLUSIONS: QOL was equivalent between groups after neoCRT except for micturition problems, gastrointestinal problems, defecation problems, and sexual satisfaction favoring the capecitabine arm after. The overall QOL using the C30SummaryScore was improved after neoCRT, but decreased following rectal resection, returning to basal levels at late evaluation. Fecal incontinence was high after sphincter preservation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03428529.

Robotic transanal ressection for rectal tumor: a description of the technique / Ressecção transanal robótica para tumor retal: uma descrição da técnica

ABSTRACT Introduction: Robotic transanal surgery (RTS) is the analog of TAMIS and represents a new focus for the advancement of transanal platforms robotic transanal surgery is sometimes referred to as robotic TAMIS. Though limited to only a few centers world-wide, experience with robotic transanal surgery has been encouraging. Most research with robotic transanal surgery has concentrated on local excision of rectal neoplasia, although more complex procedures such as transanal proctectomy are possible using the robotic approach. This article reports the surgical technique of R-TAMIS performed in the Brazilian National Cancer Institute (INCA, Rio de Janeiro). Methods: 71-year-old, female with cardiologic disease (heart failure), with a 1.5 cm rectal neoplasm at 4 cm from the anal verge in the right anterolateral position. Biopsy revealed neuroendocrine tumor. A compete colonoscopy revealed no evidence of synchronous lesions. Work-up included 3D endorectal ultrasonography and magnetic resonance imaging, which demonstrated the lesion to be uT1uN0. The patient was counseled about surgical options − local excision versus low anterior resection. Due to the cardiologic condition, the patient was elected to proceed with local excision with robotic transanal surgery. Conclusion: Robotic TAMIS is a safe and effective operative procedure for high selected cases of rectal neoplasm. It enhances surgeon ergonomics and facilitates tumor removal and suture in the transanal approach.

RESUMO Introdução: A cirurgia transanal robótica (RTS,Robotic Transanal Surgery) é análoga da TAMIS (cirurgia minimamente invasiva transanal) e representa um novo foco para o avanço das plataformas transanais. A cirurgia transanal robótica é algumas vezes chamada de TAMIS robótica. Embora limitada a apenas alguns centros em todo o mundo, a experiência com a cirurgia transanal robótica tem sido encorajadora. A maioria das pesquisas com cirurgia transanal robótica tem se concentrado na excisão local da neoplasia retal, embora procedimentos mais complexos, como a proctectomia transanal, sejam possíveis utilizando a abordagem robótica. Este artigo relata a técnica cirúrgica de R-TAMIS realizada no Instituto Nacional do Câncer (INCA, Rio de Janeiro). Métodos: paciente de 71 anos, sexo feminino, com doença cardiológica (insuficiência cardíaca), com neoplasia retal de 1,5 cm a 4 cm da borda anal em posição anterolateral direita. A biópsia revelou tumor neuroendócrino. Uma colonoscopia completa não revelou evidências de lesões sincrônicas. A investigação incluiu ultrassonografia endorretal em 3D e ressonância magnética, que demonstrou que a lesão era uT1uN0. A paciente foi aconselhada sobre as opções cirúrgicas - excisão localversus ressecção anterior baixa. Devido à condição cardiológica, optou-se por proceder à excisão local com cirurgia transanal robótica. Conclusão: A TAMIS robótica é um procedimento cirúrgico seguro e eficaz para casos altamente selecionados de neoplasia retal. Ela melhora a ergonomia do cirurgião e facilita a remoção do tumor e a sutura na abordagem transanal.

Laparoscopic versus robotic approach in rectal cancer / Abordagem laparoscópica ou robótica no câncer retal

Abstract The treatment of rectal cancer is complex and responsible for sequelae due to the various therapeutic modalities, especially the surgical resection. The advent of minimally invasive surgery provided a faster postoperative recovery and a lower complication rate when compared to conventional surgery. The implementation of laparoscopic approach in rectal cancer was responsible for these better results, but the limitations of this method added to the development of robotics, raised the question of which minimally invasive method would be more advantageous in the approach of rectal cancer. The present review will address the most recent data regarding the comparison between the laparoscopic and robotic approach in rectal cancer.

Resumo O tratamento do câncer de reto é complexo e responsável por sequelas causadas pelas diversas modalidades terapêuticas, principalmente a ressecção cirúrgica. O advento da cirurgia minimamente invasiva está associado a uma recuperação pós-operatória mais rápida e uma menor taxa de intercorrências do que as observadas na cirurgia convencional. A implementação da abordagem laparoscópica no câncer de reto foi responsável por esses melhores resultados, mas as limitações do método, bem como o desenvolvimento da cirurgia robótica, levantaram a questão de qual método minimamente invasivo seria mais vantajoso na abordagem desse tipo de câncer. A presente revisão apresenta os dados mais recentes na comparação entre a abordagem laparoscópica e robótica no câncer retal.

Colorectal robotic surgery: INCA's experience / Cirurgia robótica colorretal: experiência do INCA

ABSTRACT Introduction: Minimally invasive surgery has revolutionized surgical management in the treatment of colorectal neoplasms, reducing morbidity and mortality, hospitalization, inactivity time and minimizing cost, as well as providing adequate oncological results when compared to the conventional approach. Robotic surgery, with Da Vinci Platform, emerges as a step ahead for its potentials. The objective of this article is to report the single institutional experience with the use of Da Vinci Platform in robotic colorectal surgeries performed at a reference center in oncological surgery in Brazil. Materials and methods: A retrospective cohort study was conducted based on the prospective database of patients from the institution submitted to robotic surgery for treatment of colorectal cancer from July 2012 to September 2017. Clinical and surgical variables were analyzed as predictors of morbidity and mortality. Results: A total of 117 patients underwent robotic surgery. The complications related to surgery occurred in 33 patients (28%), the most frequent being anastomotic fistula and surgical wound infection, which corresponded to 11% and 3%, respectively. Conversion rate was 1.7%. Median length of stay was 5 days. The only variable associated with increase of complications and death risk was BMI >30, with p-value of 0.038 and 0.027, respectively. Conclusion: Robotic surgery is safe and feasible for approaching colorectal cancer surgeries, presenting satisfactory results regarding length of hospital stay and rate of operative complications, as well as presenting a low rate of conversion. Obesity has been shown to be a risk factor for surgical complication in robotic colorectal surgery.

RESUMO Introdução: A cirurgia minimamente invasiva revolucionou o tratamento cirúrgico no manejo das neoplasias colorretais, reduzindo a morbidade e mortalidade, a hospitalização, o tempo de inatividade e minimizando os custos, além de fornecer resultados oncológicos adequados quando comparada à abordagem convencional. A cirurgia robótica, com a Plataforma Da Vinci, surge como um passo à frente por seus potenciais. O objetivo deste artigo é relatar a experiência institucional única com o uso da Plataforma Da Vinci em cirurgias robóticas colorretais realizadas em um centro de referência em cirurgia oncológica no Brasil. Materiais e métodos: Foi realizado um estudo de coorte retrospectivo, baseado na base de dados prospectiva de pacientes da instituição que foram submetidos à cirurgia robótica para tratamento de câncer colorretal, de julho de 2012 a setembro de 2017. As variáveis clínicas e cirúrgicas foram analisadas como preditores de morbidade e mortalidade. Resultados: Um total de 117 pacientes foram submetidos à cirurgia robótica. As complicações relacionadas à cirurgia ocorreram em 33 pacientes (28%), sendo as mais frequentes fístula anastomótica e infecção da ferida cirúrgica, correspondendo a 11% e 3%, respectivamente. A taxa de conversão foi de 1,7%. O tempo mediano de permanência foi de 5 dias. A única variável associada ao aumento de complicações e risco de óbito foi o IMC >30, com p-valor de 0,038 e 0,027, respectivamente. Conclusão: A cirurgia robótica é segura e viável para a abordagem de cirurgias de câncer colorretal, apresentando resultados satisfatórios quanto ao tempo de internação hospitalar e taxa de complicações operatórias, além de apresentar baixo índice de conversão. A obesidade tem se mostrado um fator de risco para complicações cirúrgicas na cirurgia colorretal robótica.

Surgical and oncological short-term outcomes of prone extralevator abdominoperineal excision for low rectal cancer / Resultados cirúrgicos e oncológicos no curto prazo para a excisão abdominoperineal extra-levantador em pronação para câncer retal baixo

ABSTRACT Introduction: In recent years, a standardized surgical approach for low rectal cancer was proposed and adopted in many centres. The extralevator abdominoperineal excision introduce an extensive resection of the pelvic floor and demonstrated superiority if the procedure is done in the prone jack-knife position, especially regarding intraoperative perforation and circumferential resections margins. The aim of this study is to evaluate the surgical and oncological short-term outcomes of prone extralevator abdominoperineal excision. Methods: All patients registered in our institution from January 2003 to January 2015 who underwent abdominoperineal resection or prone extralevator abdominoperineal excision for low rectal cancer after preoperative chemoradiation were retrospectively included from prospective maintained data base and were compared regarding surgical and oncological outcomes. Results: Eighty-nine patients underwent curative intent resections. Abdominoperineal resection was performed in 67 patients and prone extralevator abdominoperineal excision in 22 patients. There were no statistical significant differences between groups regarding pathological stage, median number of harvested lymph node, intraoperative perforation, circumferential resections margins involvement and recurrence rates. Surgical outcomes were statistically different between groups. Twenty-six patients (29%) developed perineal complications, 21% of the abdominoperineal resection patients and 55% of the prone extralevator abdominoperineal excision (p < 0.001). Most of these complications were due to delayed perineal wound healing (12.4%), and wound abscesses (4.5%). However, the readmission rate and median length of hospital stay was higher in the abdominoperineal resection group (p < 0.001). Conclusion: Prone extralevator abdominoperineal excision is comparable to standard abdominoperineal resection. It was associated to a decrease in length of hospital stay and readmission rate, although more perineal complications occurred. We cannot recommend it as a standard technique for all low rectal cancer. Notwithstanding, prone extralevator abdominoperineal excision can be considered a more radical approach when there is sphincter complex or levators muscles invasion.

RESUMO Introdução: Nos últimos anos, foi proposta e adotada em muitos centros uma abordagem cirúrgica padronizada para o câncer retal baixo (CRB). A excisão abdominoperineal extra-levantador (ELAPE) introduz uma ampla ressecção do assoalho pélvico, tendo demonstrado superioridade, se ELAPE for realizada na posição de canivete (carpado) em pronação, especialmente no que tange à perfuração intraoperatória (PIO) e às margens das ressecções circunferenciais (MRCs). O objetivo desse estudo é avaliar os resultados cirúrgicos e oncológicos no curto prazo da excisão abdominoperineal extra-levantador em pronação (pELAPE). Métodos: Todos os pacientes registrados em nossa instituição desde janeiro de 2003 até janeiro de 2015 e tratados com ressecção abdominoperineal (RAP) ou com pELAPE para CRB em seguida à quimiorradiação pré-operatória foram retrospectivamente incluídos a partir da base de dados prospectiva mantida, tendo sido comparados com relação aos resultados cirúrgicos e oncológicos. Resultados: Oitenta e nove pacientes foram tratados com ressecção com intenção curativa. Sessenta e sete pacientes foram tratados com RAP e 22 com pELAPE. Não foi observada diferença estatística significativa entre grupos com relação ao estágio patológico, número mediano de linfonodos coletados, PIO, envolvimento das MRCs e percentuais de recorrência. Os resultados cirúrgicos foram estatisticamente diferentes entre os grupos. Vinte e seis pacientes (29%) evoluíram para complicações perineais: 21% dos pacientes tratados com RAP e 55% dos tratados com pELAPE (p < 0,001). Quase todas essas complicações foram decorrentes do retardo na cicatrização da ferida perineal (12,4%) e de abscessos na ferida (4,5%). Mas o percentual de reinternação e a duração mediana do tempo de internação hospitalar (TIH) foram maiores no grupo tratado com RAP (p < 0,001). Conclusão: pELAPE é comparável à RAP de rotina. O procedimento foi associado à redução no TIH e no percentual de reinternação, embora tenha ocorrido maior número de complicações perineais. Não recomendamos pELAPE como técnica padrão para todos os casos de CRB. Apesar disso, pELAPE pode ser considerada uma abordagem mais radical, como nos casos em que esteja presente uma complexa invasão esfinctérica, ou dos músculos levantadores.

Transanal minimally invasive surgery for total mesorectal excision (ETM) through transanal approach (TaETM) with robotic and Transanal Endoscopic Operations (TEO) combined access: step by step surgery.

RATIONAL: In the treatment of colorectal cancer, from 1982 Heald proposed standardization of the total mesorectal excision, with a significant reduction in the recurrence rate. But the treatment of lower rectal lesions is still a challenge. AIM: To describe the association of robotic low anterior resection- TATA (Transanal Abdominal Transanal Resection), with transanal access using Transanal Endoscopic Operations - TEO in the treatment of lower rectal cancer. METHOD: The TATA performs robotic abdominal approach and the TEO performs the perineal approach, developing total mesorectal excision (TME) transanally (TaETM). RESULT: The TaETM technique was applied in a woman with rectal adenocarcinoma 5 cm from the anal verge that had been submitted to chemoradiation. The procedure was performed with satisfatory operative time and favorable oncological outcome (grade 3 mesorectal excision). CONCLUSION: This is a promising minimally invasive procedure in the armamentarium of rectal cancer treatment, specially in challenging scenarios such as narrow pelvis, obesity and very low rectal tumors.

Transanal minimally invasive surgery for total mesorectal excision (ETM) through transanal approach (TaETM) with robotic and Transanal Endoscopic Operations (TEO) combined access: step by step surgery / Operação minimamente invasiva transanal para excisão total do mesorreto (ETM) através de acesso transanal (TaETM) com uso da robótica e de operações endoscópicas transanais (TEO) combinadas: passo a passo do procedimento

RATIONAL: In the treatment of colorectal cancer, from 1982 Heald proposed standardization of the total mesorectal excision, with a significant reduction in the recurrence rate. But the treatment of lower rectal lesions is still a challenge. AIM: To describe the association of robotic low anterior resection- TATA (Transanal Abdominal Transanal Resection), with transanal access using Transanal Endoscopic Operations - TEO in the treatment of lower rectal cancer. METHOD: The TATA performs robotic abdominal approach and the TEO performs the perineal approach, developing total mesorectal excision (TME) transanally (TaETM). RESULT: The TaETM technique was applied in a woman with rectal adenocarcinoma 5 cm from the anal verge that had been submitted to chemoradiation. The procedure was performed with satisfatory operative time and favorable oncological outcome (grade 3 mesorectal excision). CONCLUSION: This is a promising minimally invasive procedure in the armamentarium of rectal cancer treatment, specially in challenging scenarios such as narrow pelvis, obesity and very low rectal tumors. .

RACIONAL: No tratamento do câncer colorretal, a partir de 1982 Heald propôs padronização da excisão total do mesorreto, com redução importante no índice de recidivas. Apesar disso, o tratamento das lesões do reto inferior ainda permanecem um desafio. OBJETIVO: Descrever a associação da abordagem robótica por via abdominal - TATA (Transanal Abdominal Transanal Resection), com o acesso transanal utilizando o Transanal Endoscopic Operations - TEO no tratamento do câncer de reto inferior. MÉTODO: A TATA realiza o tempo abdominal por robótica e o TEO o tempo perineal, desenvolvendo a excisão total do mesorreto (ETM) por via transanal (TaETM). RESULTADO: A técnica TaETM foi aplicada em mulher com adenocarcinoma de reto a 5 cm da margem anal que tinha sido submetida à radioquimioterapia. O procedimento foi realizado com um tempo cirúrgico satisfatório bem como resultado oncológico favorável (ressecção mesorretal grau 3). Paciente obteve alta no segundo dia pós-operatório com seguimento ambulatorial satisfatório. CONCLUSÃO: Trata-se de um procedimento minimamente invasivo bastante promissor no arsenal terapêutico do câncer de reto, principalmente em situações de maior dificuldade técnica como pelve estreita, obesidade e lesões do reto distal. .

Tumores estromais do trato gastrointestinal: avaliação prognóstica e sobrevida em relação às margens cirúrgicas ressecadas / Gastrointestinal stromal tumors: prognosis and survival according to surgically resected margins

Introdução: o tratamento cirúrgico do GIST para fins curativos baseia-se na ressecção completa do tumor com margens livres, sem ruptura tumoral com linfadenectomia de amostragem. Objetivo: análise e comparação do impacto na sobrevida dos pacientes tratados por cirurgia que tiveram margens livres (R0) e margens microscopicamente comprometidas (R1). Material e métodos: análise retrospectiva de todos os casos de GIST tratados no INCA (Instituto Nacional do Câncer) no período de 1997 a 2010, com ênfase na margem cirúrgica definida como R1, doença residual microscópica e R0 sem comprometimento de margens. Resultados: estudamos 190 pacientes e encontramos comprometimento microscópico das margens em 4 casos vs. 129 com margens livres. A sobrevida global média dos casos R0 foi de 48 meses, enquanto a do grupo R1 foi de 46 meses. Não encontramos diferença estatisticamente significativa. Conclusão: este estudo sugere que a margem cirúrgica microscopicamente comprometida não é um fator prognóstico adverso.

Introduction: surgical treatment of GIST for curative purposes is based on complete tumor resection with free margins, without rupturing the tumor, with lymph node sampling. Objective: analysis and comparison of the impact on survival of patients treated by surgery who had clear margins (RO) and margins microscopically involved (R1). Methods: retrospective analysis of all cases of GIST treated at INCA for the period 1997 to 2010 with emphasis on surgical margin defined as R1, and R0 microscopic residual disease without compromising margins. Results: we studied 190 patients and found microscopic involvement of margins in cases vs 4. 129 with free margins. The median overall survival of cases R0 was 48 months while the R1 group was 46 months. We found no significant difference. Conclusion: this study suggests that surgical margins microscopically committed is not as adverse prognostic factor.

Involvement of signaling molecules in the prediction of response to imatinib treatment in metastatic GIST patients.

Imatinib therapy has undoubtedly contributed to the treatment of metastatic gastrointestinal stromal (GIST) tumors that were previously untreatable. However, disease progression during treatment with tyrosine kinase inhibitors remains an issue in clinical practice not fully explained by KIT and PDGFRA mutation status. We investigated the role of three important signaling molecules (insulin-like growth factor 1 receptor [IGF1R], protein kinase C-θ [PKCθ], and Raf kinase inhibitor protein [RKIP]) that have been implicated in GIST pathogenesis as potential biomarkers for prediction of response to imatinib treatment. We retrospectively reviewed 76 patients with metastatic GIST submitted to imatinib treatment between 2002 and 2007, and analyzed 63 of them. Insulin-like growth factor 1, total PKCθ, phosphorylated PKCθ, and RKIP immunohistochemical expression were correlated with objective response to imatinib treatment and progression-free and overall survival. Median follow-up was 31.2 mo (95% confidence interval, 26.3-36.1 mo). There was a statistically significant association between IGF1R expression and type of response to imatinib treatment (P = 0.05)-that is, higher IGF1R expression was related to lower objective response. However, IGF1R higher expression did not affect progression-free and overall survival. Insulin-like growth factor 1, but not PKCθ and RKIP, emerges as a potential biomarker for prediction of response to imatinib treatment in metastatic GISTs. Validation studies are warranted.

Tumor estromal gastrointestinal: análise de 146 casos do centro de referência do Instituto Nacional do Câncer - INCA / Gastrointestinal stromal tumor: analysis of 146 cases of the center of reference of the National Cancer Institute - INCA

OBJETIVO: Avaliar os resultados do tratamento de GIST no INCA. MÉTODOS: Análise retrospectiva de todos os casos de GIST tratados no INCA no período de 1997 a 2009. RESULTADOS: Analisamos 146 pacientes, com média de idade de 44,5 anos e predomínio do sexo feminino. O principal sintoma foi dor abdominal. Tivemos ocorrência de segundo primário em 22 por cento dos casos e na imuno-histoquímica, 92 por cento foram positivos para CD117. A localização mais frequente foi estômago e predominou o grupo de alto risco. A cirurgia foi R0 (extenso) em 70 por cento e os principais sítios de metástases foram fígado e peritônio. A sobrevida global foi, respectivamente, em dois e cinco anos de 86 por cento e 59 por cento. Houve significante diferença entre a sobrevida global (p=0,29) do grupo de alto risco versus os demais. CONCLUSÃO: Os nossos pacientes apresentam-se principalmente sob forma de doença de alto risco com repercussão óbvia na sobrevida. O uso de Imatinib melhorou a sobrevida dos pacientes com doença metastática e recidivada. Devemos estudar seu uso no cenário de adjuvância e neoadjuvancia visando melhorar os índices do grupo de alto risco. A criação de centros referenciais é uma necessidade para o estudo de doenças pouco frequentes.

OBJECTIVE: To evaluate the treatment of GIST in INCA. METHODS: We conducted a retrospective analysis of all cases of GIST treated at INCA in the period from 1997 to 2009. RESULTS: We analyzed 146 patients with a mean age of 44.5 years and female predominance. The main symptom was abdominal pain. We observed the occurrence of a second primary tumor in 22 percent of cases and 92 percent of the immunohistochemistry exams were positive for CD117. The most frequent location was in the stomach and the high-risk group was predominant. Surgery was considered R0 (extensive) in 70 percent of the cases and the main sites of metastases were liver and peritoneum. Overall survival in two and five years was, respectively, 86 percent and 59 percent. There was a significant difference between overall survival (p = 0.29) of the high-risk group versus the other. CONCLUSION: Our patients presented mainly in the form of high-risk disease, with obvious impact on survival. The use of imatinib improved survival of patients with recurrent and metastatic disease. We should study its use in the setting of adjuvant and neoadjuvant therapy to improve results of the high risk group. The creation of reference centers is a need for the study of rare diseases.

Extragastrointestinal stromal tumors (EGIST): a series of case reports.

BACKGROUND/AIM: Gastrointestinal stromal tumors (EGIST) are mesenchymal tumors which may originate in sites outside the gastrointestinal tract with clinico-pathological and molecular profiles similar to GISTs. Here is a series of case reports from The National Cancer Institute (INCA) about this rare type of tumor. METHODOLOGY: We retrospectively analyzed 142 patients with a diagnosis of GIST who were treated at INCA between 1997 and 2009, among which 9 were confirmed as having EGIST. RESULTS: We identified 9 patients with a diagnosis of EGIST, 7 of which (77.8%) were female patients with an average age of 56.8 (36-81) years. All patients were symptomatic, with abdominal pain present in 55% of cases. The tumors were located in the pancreas (n=2), in the retroperitoneum (n=3), and in the mesocolon, in the mesentery of the small intestine, in the spleen and in the pelvis (all n=1), respectively. The average tumor size was 18(8.5-27)cm. Immunohistochemistry revealed CD 117 positive in 100% of cases and CD34 positive in 62.5%. Five patients were treated surgically, three of which were submitted to R0 resection. Among those patients, all recurred after 31, 23 and 17 months respectively, and the most frequent sites were the liver and the peritoneum. Out of these three recurrences, two were "rescued" surgically (66%). Five patients were given imatinib (three patients considered unresectable, one submitted to R2 resection and another patient with recurrent disease not amenable to surgery) two patients did not receive any treatment due to compromised clinical conditions. The average overall survival was 26.4 (04-114) months. CONCLUSION: The occurrence of EGIST is extremely rare and little is known about their actual origin. They manifest through bulky masses, which compromise the prognosis. Aggressive surgical intervention is the most effective treatment associated with the use of imatinib, and a strict followup is necessary due to high recurrence rates.

Tumores neuroendócrinos do intestino delgado: experiência do Instituto Nacional de Câncer em 12 anos / Neuroendocrine tumors of the small intestine: experience of the National Cancer Institute in 12 years

Introdução: os tumores neuroendócrinos do jejuno e íleo representam 23-28% de todos os tumores endócrinos gastrointestinais. A taxa de incidência varia de 0,28 a 0,8 por 100.000 habitantes. Objetivos: revisar o tema e a experiência do INCA, culminando com definição de rotina de serviço. Material e Métodos: procedemos ao estudo retrospectivo dos casos de tumores neuroendócrinos de intestino delgado tratados no Serviço de Cirurgia Abdomino-pélvica do Instituto Nacional de Câncer (INCA) no período de 1996 a 2008, além de revisão bibliográfica. Resultados: relatamos os dados dos 7 casos tratados. Conclusão: concluímos serem os fluxogramas da ENETS (European Neuroendrocrine Tumor Society) válidos e expomos o fluxograma de conduta para estes tumores adotados no INCA.

Introduction: neuroendocrine tumors of the jejunum and ileum account for 23-28% of all gastrointestinal endocrine tumors. The incidence rate varies from 0.28 to 0.8 per 100,000 inhabitants. Objective: to review the theme and the experience of INCA cumino with definition of a routine service. Methods: we conducted the retrospective study of cases of neuroendocrine tumors of the small intestine treated at the Department of Surgery abdomino-pelvic National Cancer Institute (INCA) in the period 1996 to 2008, plus bibliographic review. Results: report the data of 7 cases treated. Conclusion: they are the flowcharts of ENETS valid and expose the flowchart of conduct adopted for these tumors in the INCA.

Gastrointestinal stromal tumor: analysis of 146 cases of the center of reference of the National Cancer Institute--INCA.

OBJECTIVE: To evaluate the treatment of GIST in INCA. METHODS: We conducted a retrospective analysis of all cases of GIST treated at INCA in the period from 1997 to 2009. RESULTS: We analyzed 146 patients with a mean age of 44.5 years and female predominance. The main symptom was abdominal pain. We observed the occurrence of a second primary tumor in 22% of cases and 92% of the immunohistochemistry exams were positive for CD117. The most frequent location was in the stomach and the high-risk group was predominant. Surgery was considered R0 (extensive) in 70% of the cases and the main sites of metastases were liver and peritoneum. Overall survival in two and five years was, respectively, 86% and 59%. There was a significant difference between overall survival (p = 0.29) of the high-risk group versus the other. CONCLUSION: Our patients presented mainly in the form of high-risk disease, with obvious impact on survival. The use of imatinib improved survival of patients with recurrent and metastatic disease. We should study its use in the setting of adjuvant and neoadjuvant therapy to improve results of the high risk group. The creation of reference centers is a need for the study of rare diseases.

Extragastrointestinal Stromal Tumors (EGIST): a series of case reports

Gastrointestinal stromal tumors(EGIST) are mesenchymal tumors whichmay originate in sites outside the gastrointestinal tract with clinico-pathological and molecular profilessimilar to GISTs. Here is a series of case reports from The National Cancer Institute (INCA) about this rare type of tumor.

Colorectal GISTs: from presentation to survival. An analysis of 13 cases.

This papers is a retrospective analysis of all cases of colorectal GIST treated at our institution. Considering the increased interest in this pathology, in 2008, we recently established a unit supported by Novartis in our department to research and treat GIST. Since then, there was a dramatic increase in the referral of this type of tumor to our center. Before initiating our research group, we had the permission of the ethics committee and the medical directors to study and publish the analysis of our cases. Now, we have a cohort of 98 patients treated during the last 10 years and from that, we selected all cases of Colorectal GIST's. They numbered 13 cases. We performed an analysis of these cases from the presentation to the results of treatment.

Occurrence of other tumors in patients with GIST.

OBJECTIVE: Evaluate the presence of other tumors in cohort of patients with GIST treated at a cancer treatment referral center - INCA. METHODS: We reviewed the medical records of patients diagnosed with GIST who were treated at INCA between 1998 and 2008. Immunohistological diagnosis was confirmed by a pathologist specialized in sarcomas. Patients presenting second non-GIST tumors were identified. Age, sex, tumor location, risk groups (according to the National Institutes of Health criteria), characteristics of non-GIST tumors and treatment results were analyzed. RESULTS: Among the 101 patients diagnosed with GIST who were evaluated during the study period, 14 (13.8%) had other non-GIST tumors, 9 females (64.3%), with a median age of 68 years (10-79 years). The stomach was the location of GISTs in 8 cases (57.1%), followed by the small bowel in 4 cases (28.5%), colon and mesentery with 1 case (7.1%) each. The mean size of lesions was 4.79 cm (0.3-15 cm), with malignant potential low/very low in 7 cases (50%), intermediate in 5 cases (35.7%) and high in 2 cases (14.3%). The diagnosis of GIST was incidental in 6 cases and in one case the non-GIST tumor was incidental. The non-GIST tumors were most frequent in the stomach (adenocarcinoma), in 4 cases (28.5%) and colon/rectum (adenocarcinoma) in 4 other cases. The other sites involved were breast (ductal carcinoma), kidney (clear cell carcinoma), prostate (adenocarcinoma), endometrium (adenocarcinoma), ovary (adenocarcinoma) and adrenal (neuroblastoma), with one case each. The tumors were synchronous in 7 cases (50%). With a median follow-up after GIST resection of 41 months (2-87 months), 9 patients were alive without evidence of disease, 2 died due to GIST, 2 died due to non-GIST tumors and the remaining patient died due to postoperative complications. CONCLUSIONS: We discovered a 13.8% incidence of non-GIST tumors in a series of 101 GIST cases under our care. This association should always be considered in the management of patients with GIST.

Prognostic relevance of KIT and PDGFRA mutations in gastrointestinal stromal tumors.

BACKGROUND: Prediction of biological behavior is crucial for selection of new therapeutic modalities in GIST. Here, we aimed to assess whether KIT and PDGFRA mutations have survival impact in gastrointestinal stromal tumors (GIST). PATIENTS AND METHODS: Fifty-five Brazilian patients with completely resected GIST were examined for KIT and PDGFRA mutations. The 5-year disease-free survival (DFS) was analyzed. RESULTS: KIT and PDGFRA mutations were identified in 74.5% and 7.3% of patients, respectively. The 5-year DFS rate for all patients was 52.8%. The 5-year DFS rate was lower in patients with tumors having in-frame deletions or concomitant in-frame deletions and insertions affecting codons 557-558 than in patients with tumors having other exon 11 KIT mutations (p=0.023). Conversely, when the patients with concomitant deletion-insertion mutations affecting codons 557-558 were excluded from the analysis, deletions involving codons 557-558 had no influence on 5-year DFS rates. CONCLUSION: Our findings indicate that a specific KIT mutation may be associated with unfavorable behavior in GIST. This finding may have implications on selecting patients for adjuvant therapy.

Cirurgia Adjuvante no tratamento do tumor estromal gatrointestinal metastático: um novo conceito / Adjuvant Surgery in the treatment of metastatic gastrointestinal stromal tumor's: a new concept

Os recentes avanços no tratamento dos tumores estromais gastrointestinais (GIST) foram responsáveis pela mudança da história natural da doença. O melhor conhecimento dos mecanismos moleculares foi fundamental para o desenvolvimento de droga alvo-molecular dirigida capaz de obter resultados, até então, não alcançados em nenhum tratamento de tumor sólido. A introdução do imatinibe na prática clínica modificou não só a sobrevida dos portadores de GIST metastático, como também foi responsável por quebras de paradigmas bem estabelecidos; porém, apesar de o tratamento da doença metastática ser baseado na utilização do imatinibe, o papel do cirurgião, nesse contexto, tem sido revisado, havendo alguns indícios de que a cirurgia de resgate na doença metastática possa trazer benefícios a grupos selecionados de pacientes. Dessa forma, um novo conceito se estabelece, o da Cirurgia Adjuvante; ou seja, uma estratégia terapêutica que visa a otimizar os resultados do tratamento do GIST metastático.

O papel atual do cirurgião no tratamento do GIST / The role of the surgeon in the management of GIST

Recent progress in gastrointestinal stromal tumor's (GIST) treatment were responsible for changing GIST's natural history. Knowlegde acquirement of molecular mechanism-based systemic therapy gave rise to the development of targeted antineoplastic drugs capable of reaching outcomes that had never been reached before. The introduction of imatinib in the clinical practice not only changed GIST's patients survival but also shifted paradigms. However, besides all these new advances and the improved results with imatinib, the surgeon still plays a pivotal role in the management of the primary GIST tumor and even in the metastatic setting.

Perfil dos portadores de GIST operados no Estado do Rio de Janeiro: estudo multicêntrico SBCO / Profile of GIST's patients operated in the State of Rio de Janeiro: SBCO multi-centric trial

Objetivo: o presente estudo tem como objetivo conhecer o perfil dos portadores de tumores estromais gastrointestinais (GISTs) tratados pelos cirurgiões no Estado do Rio de Janeiro. Método: estudo multicêntrico, retrospectivo, implementado pela Sociedade Brasileira de Cirurgia Oncológica (SBCO), tendo início em dezembrode 2006 e término em dezembro de 2007. Foram incluídos 47 casos de GIST tratados cirurgicamente. Resultados: houve predominância do sexo feminino (29 mulheres e 18 homens) e a idade variou de 10 a 81 anos, com mediana de idade de 62 anos. O estômago foi o sítio mais frequente de localização do tumor (44 casos), seguido do intestino delgado (2 casos) e do reto (1 caso). Os sintomas mais comuns foram dor abdominal (48,9 por cento dos casos), massa palpável (46,8 por cento) e sangramento digestivo (27,6 por cento). O tamanho tumoral variou de 0,8 cm a 28 cm, com mediana de 12 cm. A gastrectomia segmentar foi o procedimento cirúrgico mais empregado (21 casos). A incidência de metástase linfonodal foi de 4,2 por cento. A taxa de recidiva foi de 40,4 por cento (todos os casos classificados como GIST de alto risco). Conclusão: a presente casuística revela que o perfil dos portadores de GIST tratados por cirurgiões do Estado do Rio de Janeiro difere em alguns pontos dos relatos da literatura estrangeira, havendo necessidade de estudos nacionais com maior amostragem para confirmação dos dados.