Resultados quirúrgicos y oncológicos de pacientes operados por cáncer de recto con asistencia robótica / Surgical and oncological results of patients operated for rectal cancer with robotic assistance

Resumen Objetivo: Analizar los resultados quirúrgicos y oncológicos de pacientes con adenocarcinoma de recto (AR) operados con asistencia robótica. Materiales y Método: Cohorte prospectiva entre 2014-2019. Criterios de inclusión: pacientes con AR primario, sometidos a una resección de recto con asistencia robótica con intención curativa. Criterios de exclusión: histología no adenocarcinoma. Evaluación de datos clínico-quirúrgicos. Análisis estadístico descriptivo. Resultados: Se incluyeron 37 pacientes; 20 (54%) fueron hombres y la edad promedio fue 58,7 años. La distancia promedio desde el margen anal al borde distal del tumor fue 6,6 cm (i: 2-12 cm). La quimiorradioterapia (neoadyuvancia) se indicó en 26 pacientes. La cirugía más frecuente fue la resección anterior baja de recto y el tiempo operatorio promedio fue 266 min. Se realizaron dos conversiones a laparotomía. Una o más complicaciones se observaron en 17 (45,9%) pacientes, 9 de ellos fueron Clavien-Dindo III o IV y se reoperaron 5 pacientes (13%). No hubo transfusiones sanguíneas ni mortalidad posoperatoria. La estancia hospitalaria postoperatoria promedio fue 9,6 días (i: 3-34 d). El promedio de linfonodos resecados fue 15 (i 4-45). Los márgenes quirúrgicos fueron negativos en todos los pacientes. Se restituyó el tránsito intestinal en 28/32 (87,5%) pacientes. El promedio de seguimiento fue 21 meses (1-56), la sobrevida global y libre de enfermedad fue 100%. Discusión y Conclusión: La proctectomía con asistencia robótica ha demostrado ser segura en términos de resultados quirúrgicos tempranos y en criterios oncológicos de la pieza operatoria.

Aim: To analyze the surgical and oncological results of patients with rectal adenocarcinoma (RA) operated with robotic assistance. Materials and Method: Prospective cohort study, consecutive sample of patients between 2014-2017. Inclusion criteria: patients with primary RA, undergoing rectal resection, with robotic assistance with curative intention. Exclusion criteria: histology not adenocarcinoma. Evaluation of clinical-surgical data. Descriptive statistical analysis. Results: 37 patients were included; 20 (54%) were men and average age was 58.7 years. The average distance from the anal margin to the distal edge of the tumor was 6.6 cm (2-12 cm). Chemoradiotherapy (neoadyuvant) was indicated in 26 patients. The most frequent surgery was low anterior resection of the rectum and the average operating time was 266 minutes. Two conversions to laparotomy were performed. One or more complications were observed in 17 (45.9%) patients, 9 of them were Clavien-Dindo III or IV, 5 patients (13%) were reoperated. There were no blood transfusions and no postoperative mortality. The average postoperative hospital stay was 9.6 days (3-34). The average of resected lymph nodes was 15. Surgical margins were negative in all patients. Intestinal transit was restored in 28/32 (87.5%) patients. The average follow-up was 21 months (1-56), the overall and disease-free survival was 100%. Discussion and Conclusion: Proctectomy with robotic assistance has proved to be safe in terms of early surgical results and oncologic indicators of the surgical piece.

Test de sangre oculta en deposiciones para programas de cribado de cáncer colorrectal: actualización / Fecal occult blood test for colorectal cancer screening

Screening programs for colorectal cancer (CRC) are standard in most developed countries because they reduce mortality and are cost-effective. Within them, colonoscopy allows to directly visualize the colon and remove neoplastic lesions. However, it is an expensive exam with low adherence in asymptomatic individuals. The fecal occult blood test (FOBT) is a low-cost and risk-free method for the user, which results in a high rate of adherence, explaining its use in most screening programs. This article analyzes the effectiveness of different fecal occult blood tests in screening programs. The main conclusions are that the sensitivity of the guaiac-based chemical test for the detection of colorectal cancer is lower than that observed with qualitative and quantitative immunological tests. Automated quantitative methods allow objective readings independent of the operator and the reaction reading time, necessary for the analysis of large numbers of samples. The participation rate with immunological FOBTs is higher than with chemical ones, which is why they are preferred by the different countries that have screening programs. The use of quantitative tests allows stratification of symptomatic and asymptomatic patients at higher risk, in the screening programs.

Situación actual del cáncer de colon en Chile: una mirada traslacional / The present situation of colorectal cancer in Chile

Colorectal (CRC) is one of the most common types of cancer worldwide. Most tumors develop from an adenoma in a period of 10 to 15 years, but some may appear without previous adenomatous lesions. Seventy-five percent of colorectal cancers are sporadic, 20% have a family component (first or second-degree relatives with CRC) and 5% have a hereditary predisposition with a Mendelian pattern. The epidemiological evolution in the recent years in Chile has a worrisome evolution and the treatment costs of advanced stages are a burden for the healthcare system. We herein highlight the main Chilean medical and scientific contributions on the pathogenesis, early diagnosis, and treatment of CRC, which lead to its better understanding, and therefore better management, based on local evidence.

Resultados a largo plazo de pacientes con adenocarcinoma de recto inferior tratados con resección anterior ultrabaja interesfintérica / Long-term results of patients with adenocarcinoma of the lower rectum treated with anterior intersphinteric ultra-low-resection

INTRODUCCIÓN: La resección anterior ultrabaja interesfintérica (RAUBIE), permite preservar la función esfinteriana en pacientes seleccionados con cáncer de recto (CR). No obstante, puede producir alteraciones en la función evacuatoria y esfinteriana. OBJETIVO: Analizar los resultados oncológicos y funcionales luego de una RAUBIE. MATERIAL Y MÉTODO: Estudio observacional, analítico, transversal, durante el período 2007 a 2016. Criterios de inclusión: Pacientes sometidos a RAUBIE por CR con intención curativa. Todos los pacientes tuvieron un seguimiento el año 2017. Para la evaluación funcional se usó la escala de Jorge-Wexner, LARS y Kirwan. Análisis estadístico: Estadística descriptiva y método de Kaplan-Meier. RESULTADOS: De 21 pacientes; catorce (67%) fueron varones, edad promedio: 59 años. Ubicación tumoral: 4 cm (2-6 cm) del margen anal. Dieciocho (85,7%) pacientes recibieron neoadyuvancia. Todos los márgenes quirúrgicos distales y radiales fueron negativos. Un paciente (4,8%) tuvo metástasis a distancia y no hubo recurrencia locorregional. Con una mediana de seguimiento de 76,3 (9,8-126,8) meses, la sobrevida global y libre de enfermedad a 5 años fue de: 100% y 95% (IC: 90,1-99,9%), respectivamente. Con una mediana de seguimiento de 90 meses (21,7-124,2); se realizó la evaluación funcional a 15/21 pacientes. El puntaje de Jorge-Wexner tuvo una mediana de 13 (4-17) puntos, la escala de LARS de 34 puntos y en la escala de Kirwan, cuatro pacientes (26,7%) mostraron una buena función (Kirwan I-II). CONCLUSIÓN: Si bien los resultados oncológicos de los pacientes sometidos a una RAUBIE son satisfactorios, se debería tomar en cuenta los resultados funcionales al momento de proponer esta alternativa quirúrgica.

INTRODUCTION: Intersphinteric resection (ISR) allows preserve sphincter function in selected patients with rectal cancer (RC). Notwithstanding, it can produce alterations in defecation. AIM: To analyze the oncological and functional results after an ISR. MATERIAL AND METHOD: Observational, analytical, cross-sectional study, in the period 2007-2016. Inclusion criteria: Patients submitted to ISR by RC with curative intention. All the patients had a follow-up in 2017. Analysis of functional evaluation were performed by Jorge-Wexner, LARS and Kirwan scale. Statistical analysis: Descriptive statistics and Kaplan-Meier method. RESULTS: Of 21 patients; Fourteen (67%) were male, average age: 59 years. Tumor location: 4 cm (2-6 cm) from anal verge. Eighteen (85.7%) patients received neoadjuvant therapy. All distal and radial margins were negative. One patient (4.8%) had distant metastases and there was no locoregional recurrence. With a median follow-up of 76.3 (9.8-126.8) months, the 5-year global and disease-free survival was: 100% and 95% (CI: 90.1-99.9%), respectively. With a median follow-up of 90 months (21.7-124.2); Functional evaluation was performed on 15/21 patients. The Jorge-Wexner score had a median of 13 (4-17) points, the LARS scale of 34 points and in Kirwan scale, four patients (26.7%) showed good function (Kirwan I-II). CONCLUSION: The oncological results of patients undergoing ISR are satisfactory, however, functional results should be taken into account when proposing this surgical procedure.

Programa multicéntrico de cribado de cáncer colorrectal en Chile / Results of a multicentric colorectal cancer screening program in Chile

Background: Colorectal Cancer Screening Programs (CRCSP) are widely accepted in developed countries. Unfortunately, financial restrictions, low adherence rate and variability on colonoscopy standardization hamper the implementation of CRCSP in developing countries. Aim: To analyze a multicentric pilot model of CRCSP in Chile. Material and Methods: A prospective model of CRCSP was carried out in three cities, from 2012 to 2015. The model was based on CRC risk assessment and patient education. Health care personnel were trained about logistics and protocols. The endoscopy team was trained about colonoscopy standards. A registered nurse was the coordinator in each center. We screened asymptomatic population aged between 50 and 75 years. Immunological fecal occult blood test (FIT) was offered to all participants. Subjects with positive FIT underwent colonoscopy. Results: A total of 12,668 individuals were enrolled, with a FIT compliance rate of 93.9% and 2,358 colonoscopies were performed. Two hundred and fifty high-risk adenomas and 110 cancer cases were diagnosed. One patient died before treatment due to cardiovascular disease, 74 patients (67%) underwent endoscopic resection and 35 had surgical treatment. Ninety one percent of patients had an early stage CRC (0-I-II). Among colonoscopy indicators, 80% of cases had an adequate bowel preparation (Boston > 6), cecal intubation rate was 97.7%, adenoma detection rate was 36.5%, and in 94.5% of colonoscopies, withdrawal time was adequate (> 8 min). Conclusions: This CRCS pilot model was associated to a high rate of FIT return and colonoscopy quality standards. Most CRCs detected with the program were treated by endoscopic resection.

Caracterización de pacientes con cáncer colorrectal esporádico basado en la nueva subclasificación molecular de consenso / Characterization of patients with sporadic colorectal cancer following the new Consensus Molecular Subtypes (CMS)

Background: Colorectal cancer (CRC) is an heterogeneous disease. Three carcinogenic pathways determine its molecular profile: microsatellite instability (MSI), chromosomal instability (CIN) and CpG island methylator phenotype (CIMP). Based on the new molecular classification, four consensus CRC molecular subtypes (CMS) are established, which are related to clinical, pathological and biological characteristics of the tumor. Aim: To classify Chilean patients with sporadic CRC according to the new consensus molecular subtypes of carcinogenic pathways. Material and Methods: Prospective analytical study of 53 patients with a mean age of 70 years (55% males) with CRC, operated at a private clinic, without neoadjuvant treatment. From normal and tumor tissue DNA of each patient, CIN, MSI and CIMP were analyzed. Combining these variables, tumors were classified as CMS1/MSI-immune, CMS2/canonical, CMS3/metabolic and CMS4/mesenchymal. Results: CMS1 tumors (19%) were located in the right colon, were in early stages, had MMR complex deficiencies and 67% had an activating mutation of the BRAF oncogene. CMS2 tumors (31%) were located in the left colon, had moderate differentiation, absence of vascular invasion, lymphatic and mucin. CMS3 tumors (29%) were also left-sided, with absence of vascular and lymphatic invasion, and 29% had an activating mutation of the KRAS oncogene. CMS4 tumors (21%) showed advanced stages and presence of metastases. Conclusions: This new molecular classification contributes to understanding the heterogeneity of tumors. It is possible to differentiate molecular subgroups of a single pathological diagnosis of adenocarcinoma, opening the door to personalized medicine.

Impacto de las filtraciones anastomóticas en cirugía colorrectal / Impact of anastomotic leak in colorectal surgery

Introducción: La filtración de anastomosis es una de las complicaciones de mayor impacto en cirugía colorrectal. Objetivo: Analizar la frecuencia e impacto de las filtraciones anastomóticas en cirugía laparoscópica colorrectal. Material y método: Estudio longitudinal de base de datos prospectiva de pacientes operados por cirugía colorrectal entre julio de 2007 y agosto de 2014. Resultados: De un total de 654 pacientes operados, 52,3% correspondían a hombres con una edad promedio de 57 años (42-72). La indicación más frecuente fue cáncer colorrectal con 244 pacientes, 159 (24,3%) operados por cáncer de colon y 85 (12,9%) por cáncer de recto, seguido por la enfermedad diverticular con 239 pacientes (36,5%) y 171 pacientes (26,1%) con otros diagnósticos. En 44 pacientes (6,7%) se objetivó filtración anastomótica, con una mediana de 4 días desde el postoperatorio para su diagnóstico. Como factores asociados a filtración se identificó al género masculino, riesgo anestesiológico según ASA, necesidad de conversión a laparotomía y la anastomosis ileoanal. En relación con el tratamiento, 15 pacientes (33,7%) fueron tratados de forma médica exitosa y 29 fue necesario reintervenirlos, de los cuales 23 (79,3%) requirieron una ostomía de protección. No hubo mortalidad asociada a la cirugía, y el promedio de hospitalización en los pacientes con filtración fue de 12 vs. 5 días para los pacientes sin filtración de la anastomosis. Conclusión: Este trabajo permite identificar a grupos de pacientes con mayor riesgo de filtraciones anastomóticas, quienes duplican su estadía hospitalaria y en un alto porcentaje deben ser reintervenidos. La sospecha y diagnostico precoz reducen la morbimortalidad.

Introduction: Anastomotic leak is the most important complication on colorectal surgery. Objective: Analyze the frequency and impact of anastomotic leaks in laparoscopic colorectal surgery. Material and methods: Longitudinal study of prospective database of patients undergoing colorectal surgery between July 2007 and August 2014. Results: 654 patients operated, 52.3% were men with an average age of 57 years (42-72). The most frequent indication was colorectal cancer in 244 patients, 159 (24.3%) operated for colon cancer and 85 (12.9%) for rectal cancer followed by diverticular disease in 239 patients (36.5%) and 171 patients (26.1%) with other diagnoses. In 44 patients (6.7%) anastomotic leakage was observed with a median of 4 days post surgery for diagnosis. As factors associated with filtration, we identified male gender, anesthesic risk according to ASA, need for conversion to laparotomy and ileoanal anastomosis. With regard to treatment, 15 (33.7%) were successfully treated with medical therapy alone and 29 required re-intervention, of which 23 (79.3%) required an ostomy protection. There was no mortality associated with surgery and average LOS was 12 vs. 5 days in patients with filtration compared with patients without anastomotic leakeage. Conclusion: This serie helps to identify patients groups with increased risk of anastomotic leakage who double their hospital LOS and in a higher percentage should need re-intervention. Suspicion and early diagnosis reduces morbidity and mortality.

Se justifica el seguimiento después de una colectomía en pacientes con poliposis adenomatosa familiar / The follow up after colectomy in patients with familial adenomatous polyposis is justified

phenotypic expression is the presence of múltiple colorectal adenomatous polyps (more than 100), with high probability developing colorrectal cancer (CRC) before the fifth decade of life. Prophylactic surgery (total colectomy or restorative proctocolectomy) reduces the risk of developing CRC. However, the risk of developing tumors in other organs remains present. Objetive: Analyze the frequency and type of tumors associated with classic familial adenomatous polyposis syndrome (FAPc) patients undergoing prophylactic colectomy. Material and Methods: Cohort study. From the registry of hereditary colorrectal cancer (CRC) at our institution, we identified patients with FAPc who underwent total colectomy with ileorrectal anastomosis (TC-IRA) or restorative proctocolectomy (RTPC), from 1999 to 2014. In the follow-up we analyzed related tumors and mortality. Results: 27 patients, of whom 18 (66.7%) underwent TC-IRA and 9 (33.3%) underwent RTPC. At the time of surgery, 4 patients had CRC (15%) and 5 had extracolonic tumors (osteomas). In a mean follow-up of 49, 4 months (i: 2 y 178) the following lesions were diagnosed: digestive tract adenomas in 17 (63%) patients, of these 2 required a proctectomy and 3 resection of duodenal adenomas. Eight patients developed desmoid tumors (30%), and 3 of them underwent surgery. One patient had an extradigestive tumor (thyroid cancer) and only 8/27 (29.6%) did not develop other tumors. One patient died due to progression of his CCR. Discussion: In this series it is confirmed that most patients will develop neoplasms FAPc after colectomy. conclusion: The removal of the colon and/or rectum is able to prevent the development of CRC. However, two thirds of the patients develop other tumors in which systematic surveillance allowed early detection and treatment.

Objetivo: Analizar la frecuencia y tipo de tumores asociados en pacientes con poliposis adenomatosa familiar clásica (PAFc) sometidos a una colectomía profiláctica. Materiales y Métodos: Estudio de cohorte. Desde el registro de cáncer colorrectal (CCR) hereditario, se identificaron las familias con PAFc, y de estas a los pacientes que se les practicó una colectomía total con anastomosis íleorrectal (CT-AIR) o proctocolec-tomía restauradora (PCTR), desde 1999 al 2014. En el seguimiento se analizaron los tumores asociados y su mortalidad. Resultados: Se identificaron 27 pacientes, de los cuales 18 (66,7%) fueron sometidos a CT-AIR y 9 (33,3%) a PCTR. Al momento de la cirugía, 4 pacientes presentaban CCR (15%) y 5 tenían tumores extracolónicos (osteomas). En un seguimiento promedio de 49,4 meses (i: 2 y 178) se diagnosticaron: adenomas del tracto digestivo en 17 (63%) pacientes, de éstos 2 requirieron una proctectomía y 3 resecciones de adenomas duodenales. Ocho pacientes desarrollaron tumores desmoides (30%), y 3 de ellos fueron sometidos a una cirugía. Un paciente presentó un tumor extradigestivo (cáncer de tiroides) y sólo 8/27 (29,6%) pacientes no desarrollaron otros tumores. Un paciente falleció por progresión de su CCR. Discusión: En esta serie se confirma que la mayoría de los pacientes con PAFc seguirán desarrollando neoplasias después de su colectomía. conclusiones: La extirpación del colon y/o recto permitió evitar el desarrollo de CCR. Sin embargo, dos tercios de los pacientes presentaron otros tumores en quienes su seguimiento permitió una detección y tratamiento temprano.

Análisis molecular del cáncer de colon esporádico / Molecular analysis of sporadic colon cancer

Background: In Chile, colorectal cancer (CRC) is often diagnosed in late stages. Thus, surgical treatment must be complemented with chemotherapy. KRAS mutations and microsatellite instability have been detected in these tumors. However, the response to treatment in patients without KRAS mutations varies and requires a better understanding. Aim: To determine the frequency and distribution of somatic point mutations in KRAS, BRAF and PIK3CA genes and microsatellite instability status (MSI) in patients with colon cancer (CC). Material and Methods: A prospective observational study of patients undergoing surgery for colon cancer. Tumor-derived DNA was analyzed by polymerase chain reaction (PCR) for the most frequent mutations of KRAS, BRAF and PIK3CA. PCR was also used to analyze MSI. Results: Fifty-eight patients with sporadic CC were analyzed, 16 showed KRAS mutations (G12R, G12D, G12V, G13D) and out of the 42 patients that did not show any mutation, 10 had mutations in BRAF (V600E) and PIK3CA (E542K, E545D, E545K, Q546E, H1047R). BRAF mutations alone or in combination with PIK3CA mutations were observed in 27% of high MSI tumors and in 2% of tumors without instability (p < 0.049). A higher percentage of high MSI tumors were located in the right colon (p < 0.001), and showed BRAF mutation (p < 0.020). Conclusions: The highest percentage of high MSI and BRAF mutations was observed in the right colon. Therefore, this study suggests the presence of different molecular features between right and left colon tumors that should be considered when defining the therapeutic management.

Caracterización del infiltrado linfocitario (CD, CD4, CD8, CD45RO y FOXP3) e inestabilidad microsatelital en pacientes con cáncer colorrectal / Lymphocyte infiltration and microsatellite instability in colorectal cancer patients

Background: In colorectal cancer (CRC) patients, lymphocyte infiltration (LI) and microsatellite instability (MSI) have been associated with better prognosis. Aim: To analyze the association between components of LI (CD3/CD4/CD8/CD45R0/FoxP3) and MSI status with metastatic stages in CRC patients. Material and Methods: Prospective study of 109 patients diagnosed with CRC. The expression of CD3, CD4, CD8, CD45R0 and FoxP3 markers, was evaluated by immunohistochemical analysis, and tumors were classified into negative, low and intense expression. The MSI was assessed with seven markers amplified by PCR from normal and tumoral DNA. Tumors were grouped in MSS (stable)/MSI-low and MSI-high. Statistical analysis was performed with Fischer's exact test. Results: 29 percent, 28 percent, 12 percent and 86 percent of tumors exhibits intense expression of CD3+, CD4+, CD8+ and CD45RO+ lymphocytes, respectively. 84 percent of the tumors presented MSS/ MSI-low and 16 percent had MSI-high. Tumors that show a high density of T cells (CD3+, CD4+ y CD45R0+) are associated with early stage tumors (I and II) (p = 0.023; p = 0.030 and p = 0.003, respectively). Additionally, there was a significant association between the MSS/MSI-low tumors and a reduced ability to recruit CD8+ cytotoxic T lymphocytes (p = 0.037) and CD3+ (p = 0.064). Conclusion: There is an association between high densities of CD3+, CD4+ and CD45RO+ lymphocytes and non-metastatic tumors. In addition, MSS/ MSI-low tumors are associated with a lower recruitment of CD8+ and CD3+ lymphocytes.

Introducción: En el cáncer colorrectal (CCR), se sugiere que un mejor pronóstico podría asociarse a una respuesta inmune antitumoral (del huésped) y/o a la presencia de una alta inestabilidad microsatelital (MSI). Objetivo: Determinar si los niveles de expresión de los marcadores de linfocitos T (CD3/CD4/CD8/ CD45RO/FoxP3) y el estado de MSI se asocian a estadios metastásicos en pacientes con CCR. Material y Método: Estudio prospectivo de 109 pacientes con diagnóstico de CCR. El análisis de expresión de los marcadores CD3/CD4/CD8/CD45RO/FoxP3 fue realizado por inmunohistoquímica; los tumores fueron clasificados en negativo, débil e intenso. La MSI fue evaluada con siete marcadores amplificados desde ADN normal y tumoral; los tumores fueron agrupados en: MSS (estable)/MSI-baja y MSI-alta. El análisis estadístico fue realizado con el test exacto de Fischer. Resultados: Una intensa expresión de los marcadores CD3+, CD4+, CD8+ y CD45RO+, fue observada en el 29 por ciento, 28 por ciento, 12 por ciento y 86 por ciento de los tumores, respectivamente. El 16 por ciento de los tumores presentó MSI-alta. Los tumores que presentan una alta densidad de linfocitos T (CD3+, CD4+ y CD45RO+) se asocian a estadios tempranos I-II (p = 0,023; p = 0,030 y p = 0,003, respectivamente). Adicionalmente, se identificó una asociación estadística significativa entre los tumores con MSS/MSI-baja y una menor capacidad de reclutar linfocitos T citotóxicos CD8+ (p = 0,037) y totales CD3+ (p = 0,064). Conclusión: Existe una asociación entre altas densidades de linfocitos T CD3+, CD4+ y CD45RO+ y tumores con estadios no metastásicos. Además, tumores con MSS/MSI-baja se asocian a un menor reclutamiento de linfocitos T CD8+ y CD3+.

Rehabilitación pelviperineal multimodal en pacientes con incontinencia fecal / Multimodal pelviperineal rehabilitation in patients with fecal incontinence

Fecal incontinence (FI) is associated with low self-esteem and quality of life. Nowadays, multimodal pelviperineal rehabilitation (MPPR) has become the preferred treatment. Purpose: To evaluate our results of multimodal pelviperineal rehabilitation (MPPR) in patients diagnosed with fecal incontinence (FI). Methods: Historic cohort study using a prospectively maintained database from patients with FI that underwent MPPR between years 1999 and 2012. FI was classified according to Jorge-Wexner´s scale, at the beginning (Winitial) and the end (Wfinal) of treatment. In July 2013 a survey was carried out to measure follow-up Wexner score (Wfollow-up) and pelvic muscle training. Statystical analysis was performed using Chi square test, Fisher Test, Mann-Whitney and Odds Ratio. Significant p value < 0.05. Results: One hundred and thirteen patients completed treatment, median age 67 years-old (r: 24-91) and 83 percent female. Median scores for Winitial and Wfinal were 9 points (r: 3-19) and 3 points (r: 0-13), respectively (p < 0.001). In July 2013, 68 (61 percent) patients were available for follow-up. Wexner score at the beginning, end and follow-up were as follows: 9 (i: 3-19), 3 (i:0-12) and 4 (i:0-19), respectively. There were significant differences between Winitial and Wfollow-up (p < 0.001), but not between Wfinal and Wfollow-up (p = 0.23). There were 20 patients (29 percent) who kept training their pelvic muscles and 48 (71 percent) who did it very rarely or did not do it at all. It was the latter group who showed an increased risk to obtain worst score in Wfollow-up (OR = 3.89; CI 95 percent: 1.26-11.9; p = 0.0175). Conclusion: FI patients treated with MPPR show good short and long-term results.

Introducción: La incontinencia fecal (IF) se asocia a menor calidad de vida en quienes la sufren. Actualmente, la rehabilitación pelviperineal multimodal (RPPM) es el tratamiento inicial de elección. Objetivo: Evaluar los resultados de la RPPM en pacientes con IF. Método: Estudio de cohorte histórica de pacientes con IF que recibieron RPPM entre 1999-2012. Se utilizó la escala de Jorge-Wexner para medir laIF, al inicio (Wi) y fin (Wf) del tratamiento. Se aplicó una encuesta en julio de 2013 para medir el Wexner de seguimiento (Ws) y mantención de ejercicios terapéuticos. Análisis estadístico: prueba de c2, prueba exacta de Fisher, Mann-Whitney y Odds Ratio. Significancia estadística p < 0,05. Resultados: Hubo 113 pacientes que completaron el tratamiento. La mediana de edad fue 67 años (i: 24-91) y 83 porciento género femenino. La mediana de Wi fue de 9 puntos (i: 3-19) y la mediana de Wf fue de 3 puntos (i: 0-13) (p < 0,001). Se logró contactar a 68 pacientes para el seguimiento, en ellos la mediana del puntaje de Wi, Wf y Wsfue de 9 (i: 3-19), 3 (i:0-12) y 4 (i:0-19), respectivamente. Hubo diferencia significativa entre Wi y Ws (p < 0,001), pero no entre Wf y Ws (p = 0,23). Veinte pacientes (29 por ciento) realizaron ejercicios terapéuticos regularmente y 48 (71 por ciento) nunca o raramente; este último grupo es factor de riesgo para obtener peores resultados (OR = 3,89; CI 95 porciento: 1,26-11,9; p = 0,0175). Conclusión: El tratamiento con RPPM en pacientes con IF tiene buenos resultados a corto y largo plazo.

Prevalencia y características de mutaciones somáticas del gen KRAS en pacientes chilenos con cáncer colorrectal / KRAS gene somatic mutations in Chilean patients with colorectal cancer

Background: The molecular testing of KRAS mutation status in metastatic colorectal cancer patients is mandatory to identify patients eligible for anti-epidermal growth factor receptor monoclonal antibody therapy. Aim: To report the frequency of KRAS gene mutations in Chilean patients with colorectal cancer (CRC). Material and Methods: A cohort of 262 Chilean patients with CRC aged 26 to 90 years (53% males), was studied. KRAS mutation status was analyzed by real-time polymerase chain reaction and correlated with clinicopathological data. Results: Ninety-eight patients (37%) were positive for KRAS mutations. G12D was the most common mutation with a frequency of 36.7%, followed by G12V (25.5%), G13D (17.3%), G12A (7.1%), G12C (6.1%), G12S (5.1%) and G12R (2%). The frequency of the mutation in left, right colon and rectal tumors was 37.8, 32.6 and 44.9%, respectively. Among tumors with mutations, 86.7% were well or moderately differentiated tumors and the rest were poorly differentiated. No significant associations between KRAS gene mutations and other clinicopathological features of the tumor were observed. Conclusions: The frequencies of KRAS mutations reported in this study are similar to frequencies reported for European and North-American populations, lower than in a Spanish study and higher than in a Peruvian study.

Enfermedad inflamatoria intestinal a partir de una experiencia local / Inflammatory bowel disease. Experience in 316 patients

Background: The incidence and prevalence of Inflammatory Bowel Disease (IBD) has increased. Aim: To determine demographic and clinical characteristics of patients with IBD in a Chilean private hospital. Patients and Methods: Review of a prospective registry of patients with IBD, started on 2012. It includes clinical, imaging, endoscopical and pathological information of patients. Results: Data of 316 patients with IBD, aged 16 to 86 years (56% females), were analyzed. Ulcerative Colitis (UC), Crohn´s and non-classifiable IBD were diagnosed in 230, 77 and 9 patients, respectively. The disease was diagnosed in 82% of patients in the period between 2002 and 2012. There was a peak in the diagnosis of both UC and CD between 20 and 39 years of age, without gender differences. The disease switched from UC to CD in six patients. In four, there was a change in disease behavior. Thirty eight patients were treated with biological therapy. The median lapse between the diagnosis and the use of biological therapy was 1 year in patients diagnosed after 2007, compared with 5.5 years among those patients diagnosed before 2007 (p = 0.001). There was a trend towards a higher requirement of surgery until 2006. Subsequently there was a stabilization of the requirement, concomitant with the incorporation of biological therapy. Conclusions: An adequate registry of IBD patients is necessary to improve demographic and clinical characteristics. A national registry is needed to assess the epidemiological changes of IBD in Chile.

Tratamiento de la fístula perianal en la enfermedad de Crohn a partir de una experiencia local / Treatment of perianal fistulae in Crohn´s disease: a local experience

Background: Perianal fistula (PF) may be present in 40 percent of patients with Crohn´s Disease (CD). Due to its complexity, its management should be multidisciplinary. Purpose: To describe clinical treatment in patients with CD and PF in our institution. Materials and Methods: This is a descriptive retroprospective study, using a registry of CD patients. We selected patients with PF and further characterized those patients that received their treatment at Clínica las Condes (CLC). Results: From a total of 74 patients with CD in the registry, 23 (31 percent) had PF, 61 percent male, median of 7 years of disease and half with colonic extension. Twelve patients were treated in CLC, from these, seven had concomitant proctitis. Optimal diagnostic study (magnetic resonance imaging/endorectal ultrasound plus examination under anesthetic) was performed in eleven (92 percent) patients. Ten (83 percent) patients received an optimal treatment (drainage and installation of a loose seton + start or optimization of medical therapy). Complete clinical response was achieved in more than half of the patients under optimal treatment within the first 6 months. Six (50 percent) patients had one or more recurrences of PF with similar study and management in a median of 13 months. With a median follow-up of 29 months, eight out of 12 patients had complete clinical response. There was one patient with unfavorable course who required a proctectomy and terminal diversion. Conclusion: Treatment of PF in CD is complex and in our population, the first-line treatment includes the installation of a loose seton and medical therapy to achieve clinical response even though fistulous tracts may persist.

Introducción: La fístula perianal (FP) puede presentarse hasta en 40 por ciento de los pacientes con Enfermedad de Crohn (EC). Dada su complejidad el tratamiento debe ser multidisciplinario. Objetivo: Describir el tratamiento de los pacientes portadores de EC con FP. Métodos: Estudio descriptivo, utilizando un registro de pacientes con EC. Se seleccionaron los pacientes con FP y se caracterizaron aquellos que recibieron el tratamiento en Clínica Las Condes (CLC). Resultados: De un total de 74 pacientes con EC, 23 (31 por ciento) presentaban FP asociada, 61 por ciento de sexo masculino, mediana de duración de enfermedad 7 años y la mitad con extensión colónica. Doce pacientes fueron tratados en CLC, de ellos, siete presentaban proctitis al momento de la FP. En 11 (92 por ciento) pacientes se realizó un estudio diagnóstico óptimo (resonancia magnética/ endosonografía transrrectal y exploración bajo anestesia). Diez (83 por ciento) pacientes recibieron tratamiento óptimo biasociado (drenaje e instalación de sedal no cortante + inicio u optimización de terapia médica). Siete pacientes con tratamiento óptimo presentaron mejoría clínica completa dentro de los primeros 6 meses. Seis (50 por ciento) pacientes presentaron una o más recurrencia de FP con estudio y manejo similar en una mediana de 13 meses. Con una mediana de seguimiento de 29 meses, ocho de los 12 pacientes obtuvieron mejoría clínica completa. Una paciente evolucionó desfavorablemente, requiriendo proctectomía y ostomía terminal. Conclusión: El manejo del FP en EC es complejo, en nuestra población el tratamiento biasociado (sedal + fármacos) fue de elección para lograr una mejoría clínica aun cuando persistieron los trayectos fistulosos.

Resultados oncológicos a largo plazo de pacientes sometidos a resección laparoscópica por cáncer de recto / Long term oncological outcomes of patients undergoing laparoscopic resection for rectal cancer

Introducción: En la actualidad hay consenso en la seguridad oncológica en la cirugía laparoscópica para el tratamiento del cáncer de colon, sin embargo, en el cáncer de recto (CR) los resultados a largo plazo, continúan siendo objeto de estudio. El objetivo de este trabajo es analizar la sobrevida a largo plazo en pacientes operados por adenocarcinoma de recto por vía laparoscópica. Material y Métodos: Desde la base de datos prospectiva de cirugía colorrectal laparoscópica se seleccionaron los pacientes operados por CR en el periodo entre octubre 2000 y diciembre 2009. Se excluyó a los pacientes con cáncer colorrectal hereditario. Se analizaron los datos de seguimiento los cuales son obtenidos mediante registros clínicos y datos del registro civil. Se realizó un análisis de sobrevida con el método de Kaplan-Meier. Resultados: En el periodo mencionado, 60 pacientes fueron operados por CR, 2 (3,4%) pacientes fallecieron en el postoperatorio temprano y fueron excluidos en el análisis de sobrevida, por tanto, 58 pacientes fueron incluidos en el seguimiento. El 41% eran sexo femenino y la edad promedio fue de 60 ± 11,6 años. Los tumores se encontraban localizados en el recto superior, medio e inferior en un 28%, 28% y 44% respectivamente. Las cirugías realizadas fueron resección abdominoperineal, resección anterior ultrabaja interesfintérica, resección anterior ultrabaja y resección anterior baja en un 8%, 28%, 5% y 59% de los pacientes, respectivamente. El 50% de los pacientes recibieron neoadyuvancia. Tras la estadificación postoperatoria 4% fueron clasificados estadio 0, 38% estadio I, 17% estadio II, 28% estadio III y 13% estadio IV. El recuento de linfonodos de la pieza operatoria fue de 12,3 en promedio. A un seguimiento de 42,6 meses (r: 17 a 103 meses) la sobrevida global estimada a 5 años es de 85%. Según estadios la sobrevida estimada a 5 años fue de 100% para el estadio 0 y I, 88% para el estadio II, 74% para el estadio III... (TRUNCADO)

Background: Currently there is a consensus in oncological safety for laparoscopic surgery for colon cancer; however, in rectal cancer long term outcomes are still a subject of debate. The aim is to analyze long term survival in patients who underwent laparoscopic surgery for rectal cancer. Material and Methods: From the prospective database of laparoscopic colorectal surgery, we selected patients operated on between October 2000 and December 2009. Patients with hereditary colorectal cancer were excluded. Follow-up data was obtained by medical records and national vital records. Survival was analyzed using the Kaplan-Meier method. Results: In this period, 60 patients were operated on for rectal cancer. Two died in the early postoperative period and were excluded from the analysis; therefore, 58 patients were included in follow-up. Forty-one percent were female and mean age was 60±11.6 years old. Tumors were localized in the upper, mid and lower rectum in 28%, 28% and 44%, respectively. Surgeries performed were abdominoperineal resection, ultra-low intersphincteric resection, ultralow anterior resection and low anterior resection in 8%, 28%, 5% and 59% of patients, respectively. Fifty percent received neoadjuvant treatment. After postoperative staging 4% were classified as stage 0,17% as stage I, 28% as stage II, 28% as stage III, and 13% as stage IV. At a mean 42.6 month follow-up (r: 17-103 months) estimated overall 5-year survival was 85%. When analyzed according to stage, estimated overall 5-year survival was 100% for stages 0 and I, 88% for stage II, 74% for stage III, and 57% for stage IV. Conclusion: Long term survival in patients undergoing laparoscopic surgery for rectal cancer is satisfactory and is within the values reported by international centers.

Mutación homocigota en la línea germinal del gen MUTYH en una paciente chilena con poliposis adenomatosa familiar / Homozygous germline mutation in MUTYH gene in familial adenomatous polyposis

Recently, MUTYH mutations have been reported to predispose to the development of polyposis. However, polyposis caused by mutations in MUTYH has been characterized as an autosomal recessive hereditary disease, different from the autosomal dominant pattern observed in polyposis caused by APC mutations. We report a 41-year-old female consulting for anemia. Colonoscopy detected multiple sessile polyps and a cecal carcinoma. The patient was operated and in the surgical piece, the tumor invaded serosa and there was lymph node involvement. Approximately 100 polyps were found. The patient received 5-fluorouracil, as adjuvant therapy. The patient had a sister (of a total of 12 brothers) with a colorectal carcinoma. The genetic study identified a homozygous mutation of the MUTYH gene, called c.340T > C, that produces an amino acid change of tyrosine for histidine called p.Y114H. The sister with colorectal cancer was a heterozygous carrier of this mutation.

Síndrome de Lynch: selección de pacientes para el estudio genético mediante análisis de inestabilidad microsatelital e inmunohistoquímica / Lynch syndrome: selection of families by microsatellite instability and immunohistochemistry

Background: Selection of patients with Lynch Syndrome (LS) for a genetic study involves the application of clinical criteria. To increase the rate of identification of mutations, the use of molecular studies as Microsatellite Instability (MSI) and Im-munohistochemistry (IHC) in the tumor has been proposed. Aim: To demonstrate the usefulness of MSI and IHC in the detection of mutations in patients with LS. Material and Methods: From our Familial Colorectal Cancer Registry, families suspected of LS were selected according to Amsterdam or Bethesda clinical criteria. Screening of germline mutations of MLH1, MSH2 and MSH6 genes was performed. In addition, analysis of MSI and IHC were performed in colorectal tumors. Results: A total of 35 families were studied (19 met Amsterdam and 16 met Bethesda criteria). Twenty one families harbored a germline alteration in MLH1, MSH2 or MSH6 (18 Amsterdam and 3 Bethesda). In these families, eighteen different alterations were found, 15 of which were mutations and 3 corresponded to variants of uncertain pathogenicity. On the other hand, 80% of the tumors showed positive microsatellite instability (27 MSI-high and 1 MSI-low), and immunohistochemical testing showed that 77% of tumors had the loss of a protein. Correlation between results of tumor molecular studies and the finding of germline nucleotide change showed that IHC and MSI predicted mutations in 81 and 100% of patients, respectively. Conclusions: MSI and IHC can efficiently select patients with a high probability of carrying a mutation in DNA repair genes.

Caracterización clínica y genética de las poliposis intestinales hereditarias / Clinics and genetic characteristics in hereditary colon polyposis

Se denomina pólipo intestinal a una lesión visible elevada o tumor que se proyecta desde la superficie epitelial al lumen visceral. En relación al número, presencia de antecedentes familiares, manifestaciones extraintestinales y estudios genéticos es que se constituyen diversas poliposis intestinales. Si bien, las poliposis intestinales se manifiestan en general en la edad adulta, existen manifestaciones que pueden hacer sospechar la presencia de un síndrome poliposico hereditario en la infancia. Además en una proporción considerable estas poliposis presentan manifestaciones extraintestinales, tanto benignas como tumores en otros órganos. Es por esto, que una alta tasa de sospecha, en particular frente a pacientes con antecedentes familiares, puede conducir a un diagnóstico y tratamiento oportuno, además de considerar a la familia como potenciales pacientes e ingresar al grupo familiar a un registro de tumores hereditarios. Diversas técnicas de biología molecular han permitido la identificación de las mutaciones que son heredadas en estas enfermedades, permitiendo realizar conductas preventivas al saber el riesgo de cada persona en una familia afectada. El objetivo de esta revisión, es caracterizar las distintas poliposis intestinales, en cuanto a sus manifestaciones clínicas, clasificaciones, estudio genético y enfrentamiento multidisciplinario.

Polyps are solid or tumoral elevated lesions that arise from the intestinal epithelium so that they become visible in the intestinal epithelium so that they become visible in the intestinal lumen. Information regarding familial history, number, extraintestinal manifestations and genetic studies of polyps, assemble different types of intestinal polyposis. Generally, clinical manifestations occur in adult patients, although in children there are several signs that should make the physician suspect a hereditary polyposis syndrome. In addition it is important to know extraintestinal manifestations which are mostly benign but tumors may be present in other organs too. Bearing in mind that high clínical suspicion of hereditary polyposis syndrome especially if familial history is present, provides early diagnosis and appropriate treatment for the patient and eventually for the family members that could be affected, entering that family in a registry of hereditary tumors. Molecular biology has created different techniques to identify the presence of hereditary mutations that are specific for intestinal polyposis. Acknowledgment of these mutations establishes risks groups allowing adequate prevention strategies. The objective of this revision is to characterize and different types of intestinal polyposis, according to clinical manifestations, classification, genetic study and multidisciplinary approach.

El deporte y la actividad física en la prevención del cáncer / Sports and physical activity in cancer prevention

El cáncer es la primera causa de muerte en la mayoría de los países desarrollados. Chile se acerca cada vez más a esta realidad, ya que esta enfermedad es la segunda causa de muerte en el país. Lamentablemente, nuestra expectativa es al alza y de este modo debemos actuar con energía en la promoción de factores protectores. La práctica del deporte ha evidenciado múltiples ventajas en el estado general de quienes lo practican y en relación al cáncer, se han realizado estudios que demuestran que la práctica deportiva es relevante en distintos niveles. A nivel celular el deporte disminuiría la activación de cascadas inflamatorias que están implicadas en el desarrollo de diversos tipos de cánceres, como el de pulmón, colorrectal, gástrico y pancreático entre otros. Además, a nivel de prevención existe una relación inversa entre actividad física y el riesgo de desarrollar cáncer de mama y de colon. En pacientes oncológicos el ejercicio puede ser útil en la reducción de la fatiga y la depresión, y así contribuir a una mejor calidad de vida.

Cancer is the main cause of mortality in most developed countries. In Chile, cancer is the second cause of mortality and we expect further increases on the years to come. For this reason is imperative an active promotion of protective factors, such as sports. This practice has shown relevant benefits in patients affected with cancer in different levels, for example it has been demonstrated that sports decrease inflammatory cascade, usually over activated in patients with lung, pancreatic, gastric and colorectal cancer. Furthermore, evidence suggests an inverse relationship between physical activity and the risk of developing breast and colorectal cancer. Programmed and regular physical activity could be beneficial in patients with cancer, by reducing fatigue or depression, thus inducing an improvement in their quality of life.

Cáncer de recto: diagnóstico, estudio y estadificación / Rectal cancer: diagnosis, study and staging

Rectal cancer is defined as a tumour located between the anal verge and 15 cm within anal verge. In rectal cancer, a precise preoperative staging allows to categorize patients for different available treatments, as well as decide the best surgical treatment. Preoperative staging is performed by several radiological techniques. Currently available procedures are endorectal ultrasound (EUS), computed tomography (CT) magnetic resonance (MRI), positron emission tomography-computed tomography (PET/CT) and intraoperative ultrasound. EUS is a procedure performed by the colorrectal surgeon that allows the evaluation of the depth of tumour invasion as well as lymph node status; nevertheless its main shortcoming is the inability to assess mesorectal fascia involvement. Nowadays, MRI is the best method to assess mesorectal fascia involvement in addition to tumour invasion and lymph nodes involved. CT is a widely available procedure, and its main use is evaluation of distant metastases, with lower accuracy to assess tumour invasion and lymph node status. PET/CT is currently gaining importance, however its role in preoperative staging it's not widely accepted. IOUS allows evaluation of liver metastases during surgery, and therefore determines management and prognosis. Consequently, is necessary for surgeons to maintain an up-to-date knowledge of current methods, its advantages and limitations.

El cáncer rectal se define como el tumor ubicado entre el margen anal y los 15 cm hacia proximal. En el cáncer de recto, una precisa estadificación preoperatoria permite clasificar correctamente a los pacientes para las diversas terapias existentes, así como seleccionar el mejor tratamiento quirúrgico. La estadificación preoperatoria se realiza con el apoyo de métodos imagenológicos. Dentro de los métodos actualmente disponibles están la endosonografía rectal (EUS), tomografía computada (TC), resonancia magnética (RM), tomografía por emisión de positrones (PET/CT) y ultrasonido intraoperatorio (IOUS). La EUS es un método realizado por el cirujano colorrectal, que permite la evaluación de la invasión de la pared, así como también de los linfonodos, sin embargo, su principal limitación es la evaluación del compromiso de la fascia mesorrectal. La RM es, hasta el momento, el mejor método para evaluar el compromiso de la fascia mesorrectal, además de informar el compromiso de pared y una adecuada evaluación de linfonodos comprometidos. La TC es un método ampliamente disponible, cuya principal utilidad es la evaluación de metástasis a distancia. El PET/CT está cobrando actualmente mayor importancia, sin embargo, su uso en estadificación preoperatoria aún no es ampliamente aceptado. La IOUS permite evaluar el compromiso metastásico del hígado durante la cirugía y por lo tanto, determina conducta y pronóstico. Por lo anterior, es necesario un conocimiento actualizado del cirujano en cuanto a esta metodología, sus ventajas y limitaciones.