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Lymphatic invasion, vascular invasion, and perineural invasion are prognostic factors for colon cancer. However, the prognostic significance of those factors according to the location of permeation (intramural and extramural invasion) in stage II colon cancer is still unclear.This study aims to clarify whether the location of lymphatic invasion, vascular invasion, and perineural invasion could affect survival of stage II colon cancer patients.This was a retrospective cohort study.This study took place at a university teaching hospital.A total of 1130 patients with stage II colon cancers who underwent radical surgery at the Seoul National University Hospital between July 2003 and December 2015 were included.Patients were classified according to the location of lymphatic invasion, vascular invasion, and perineural invasion. Survival outcomes were compared among those without invasion, and those with intramural and extramural invasion. Primary end point is overall survival and secondary end point is disease free survival.Disease-free survival and overall survival of patients with extramural invasion were worse than those of patients without invasion and those with intramural invasion. Multivariate analysis for survival outcomes confirmed that extramural invasion were significant independent prognostic factors. However, both disease free survival and overall survival were not significantly different between patients without invasion and those with intramural invasion.This study was limited by its retrospective design.Extramural invasion was associated with worse prognosis in stage II colon cancer, but intramural invasion was not. Therefore, pathologic reports about the location of lymphatic invasion, vascular invasion, and perineural invasion might be helpful for predicting prognosis and for determining the need of adjuvant chemotherapy in stage II colon cancers. See Video Abstract at http://links.lww.com/DCR/B939.

BACKGROUND Obtaining an accurate pedigree is the first step in recognizing a patient with hereditary nonpolyposis colorectal cancer, or Lynch syndrome. However, lack of standardization of the degree of relationship included in the pedigrees generally limits obtaining a complete and/or accurate pedigree. DESIGN This study analyzed the extent of pedigree required to screen for colorectal cancer and to diagnose Lynch syndrome. SETTINGS The study was conducted at 2 tertiary care centers. PATIENTS A detailed family history was obtained from patients undergoing surgery for colorectal cancer from 2003 to 2016. A simplified pedigree that included only first-degree relatives was obtained and compared with the extended pedigree. MAIN OUTCOME MEASURES The eligibility of the 2 pedigrees was assessed for each proband. The proportion of patients who would be missed using a simplified rather than an extended pedigree was calculated based on the American Cancer Society guidelines for recommending screening for colorectal cancer, on the revised Bethesda guidelines and the revised suspected hereditary nonpolyposis colorectal cancer criteria for screening for hereditary colorectal cancer, and on the Amsterdam II criteria for diagnosis of Lynch syndrome. RESULTS The study examined 2015 families, including 41,826 individuals. Use of simplified and extended pedigrees was comparable in screening for colorectal cancer, with ratios of 183 of 185 (98.9%) for American Cancer Society guidelines, 295 of 295 (100%) for revised Bethesda guidelines, and 60 of 60 (100%) for revised suspected hereditary nonpolyposis colorectal cancer criteria. However, the use of simplified pedigrees missed a definitive diagnosis of Lynch syndrome in 6 of 10 patients fulfilling Amsterdam II criteria based on extended pedigrees. The mean ages at diagnosis of the 4 probands included and the 6 missed using simplified pedigrees differed significantly (60.8 vs 38.2 y). LIMITATIONS The study was limited by its recall bias, cross-sectional nature, lack of germline testing, and potential inapplicability to the general population. CONCLUSIONS A simplified pedigree is acceptable for selecting candidates to screen for hereditary colorectal cancer, whereas an extended pedigree is still required for a more precise diagnosis of Lynch syndrome, especially in younger patients. See Video Abstract at http://links.lww.com/DCR/B97. EXTENSION DE PEDIGREE REQUERIDO EN LA DETECCION Y DIAGNOSTICO DE CANCER COLORRECTAL HEREDITARIO SIN POLIPOSIS: COMPARACION DE LOS PEDIGREES SIMPLIFICADO Y EL EXTENDIDO: La obtencion de un Pedigree exacto es el primer paso para reconocer un paciente con cancer colorrectal hereditario sin poliposis o sindrome de Lynch. Sin embargo, la falta de estandarizacion del grado de relacion incluido en los Pedigrees generalmente limita la obtencion de un Pedigree completo y / o preciso.Este estudio analizo el grado de Pedigree requerido para detectar el cancer colorrectal y diagnosticar el sindrome de Lynch.Se obtuvo una historia familiar detallada de pacientes sometidos a cirugia por cancer colorrectal desde 2003 hasta 2016. Se obtuvo tambien un Pedigree simplificado que incluia solo familiares de primer grado y se comparo con el Pedigree extendido.La elegibilidad de los dos Pedigrees se evaluo para cada sujeto de prueba (proband). La proporcion de pacientes que se perderian usando un Pedigree simplificado en lugar de extendido se calculo en base a las guias de la Sociedad Americana del Cancer y sus recomendaciones en la deteccion de cancer colorrectal, en las pautas revisadas de Bethesda y en los criterios revisados de cancer colorrectal hereditario sin poliposis para la deteccion hereditaria de cancer colorrectal y segun las normas de Amsterdam II para el diagnostico del sindrome de Lynch.El estudio examino a 2.015 familias, incluidas 41.826 personas. El uso de Pedigree simplificado y extendido fue comparable en la deteccion del cancer colorrectal, con proporciones de 183/185 (98,9%) comparadas con las recomendaciones de la American Cancer Society, 295/295 (100%) para las pautas revisadas de Bethesda y 60/60 (100%) para los criterios revisados de sospecha de cancer colorrectal hereditario sin poliposis. Sin embargo, el uso de Pedigree simplificado omitio un diagnostico definitivo del sindrome de Lynch en 6 de diez pacientes que cumplian las normas de Amsterdam II basados en Pedigrees extendidos. Las edades medias al diagnostico de los cuatro sujetos de prueba incluidos y los seis perdidos usando el Pedigree simplificado diferian significativamente (60.8 vs. 38.2 anos).Un Pedigre simplificado es aceptable en la seleccion de candidatos para la deteccion de cancer colorrectal hereditario, mientras que aun se requiere un Pedigree extendido para un diagnostico mas preciso de sindrome de Lynch, especialmente en pacientes mas jovenes. Consulte Video Resumen en http://links.lww.com/DCR/B97. (Traduccion-Dr. Edgar Xavier Delgadillo).

More than half of all rectal cancers are T3 lesions, but they are classified as a single-stage category.The aim of this study was to validate prognostic significance of mesorectal extension depth in T3 rectal cancer.This study is a retrospective analysis of oncologic outcomes of patients with T3 rectal cancer grouped by mesorectal extension depth (T3a,1 mm; T3b, 1-5 mm; T3c, 5-15 mm; T3d,15 mm).This study was conducted at a tertiary referral cancer hospital.From 2003 to 2009, 291 patients who underwent a curative surgery were included.Oncologic outcomes in terms of disease-free survival were analyzed.The 5-year disease-free survival rate according to T3 subclassification was 86.5% for T3a, 74.2% for T3b, 58.3% for T3c, and 29.0% for T3d. It was significantly higher in T3a,b tumors than that in T3c,d tumors (77.6% vs 55.2%, p0.001). On univariate and multivariate analysis, prognostic factors affecting recurrence were preoperative CEA level ≥ 5 ng/mL (HR 2.617, 95% CI 1.620-4.226), lymph node metastasis (HR 3.347, 95% CI 1.834-6.566), and mesorectal extension depth5 mm (HR 1.661, 95% CI 1.013-2.725). In subgroup analysis, independent prognostic factors were preoperative CEA level and mesorectal extension depth5 mm for 200 patients with ypT3 rectal cancer and preoperative CEA level and lymph node metastasis for 91 patients with pT3 rectal cancer.This study lacks quality of surgery plane evaluation because of its retrospective nature. Moreover, pathologic examination was not done with a whole-mount section.Depth of mesorectal extension5 mm is a significant prognostic factor in patients with T3 rectal cancer. Depth of mesorectal extension especially may be more important than the nodal status in predicting the oncologic outcome for patients who had received preoperative chemoradiotherapy.

Preoperative chemoradiotherapy is widely used to improve local control and sphincter preservation in patients with locally advanced rectal cancer. In the present study, we investigated whether microarray gene expression analysis could predict complete response to preoperative chemoradiotherapy in rectal cancer. Tumor tissues were obtained from 46 patients with rectal cancer (31 for training and 15 for validation testing). All patients underwent preoperative chemoradiotherapy involving 50.4 gray radiotherapy, followed by surgical excision 6 weeks later. Response to chemoradiotherapy was evaluated according to Dworak’s tumor regression grade. Tumor regression Grades 1, 2, and 3 were considered partial responses, and tumor regression Grade 4 was considered a complete response. By using the 31 training samples, genes differentially expressed between partial response and complete response were identified, and clustering analysis was performed. Prediction analysis of response to chemoradiotherapy was performed on the 31 training samples by using a selected set of 95 “predictor” genes. Those findings were validated by independent analysis of the 15 test samples. The 31 training samples comprised 20 partial response and 11 complete response cases. A primary set of 261 genes was identified as differentiating between partial response and complete response. By supervised clustering using these 261 genes, 30 of 31 training samples were clustered correctly according to tumor response. A gene set comprising the top-ranked 95 genes displaying differential expression between partial response and complete response was applied to predict response to chemoradiotherapy. Complete response and partial response were accurately predicted in 84 percent (26/31) of training samples and 87 percent (13/15) of validation samples. Microarray gene expression analysis was successfully used to predict complete responses to preoperative chemoradiotherapy in patients with advanced rectal cancer.

PURPOSE: This study was designed to investigate the frequency of mutations in DNA mismatch repair genes in sporadic colorectal cancers. METHODS: Genomic DNAs procured from paraffin blocks of the pathologic specimens from 230 consecutive patients with colorectal cancer were examined for their microsatellite instability status using a mononucleotide microsatellite marker, BAT-26, and also evaluated expressions of hMLH1, hMSH2, and hMSH6 proteins by immunohistochemical staining. Any of these 230 patients did not have family histories of hereditary nonpolyposis colorectal cancer, familial adenomatous polyposis, colorectal cancer, or hereditary nonpolyposis colorectalrelated cancers, such as endometrial, small bowel, and ureteral and renal pelvic cancers. When microsatellite instability was positive, mutations in the simple repeated sequences of TGF-βRII, BAX, IGF IIR, hMSH3, and hMSH6 genes were examined. In microsatellite instability–positive or staining-negative cases, polymerase chain reaction–single- strand conformation polymorphism and DNA sequencing detected mutations of hMLH1, hMSH2, and hMSH6 genes. If mutations were found in tumor tissue samples, we tested for a germline mutation with a microdissected corresponding normal tissue. RESULTS: Among 230 cases of sporadic colorectal cancer, 21 (9.1 percent) manifested microsatellite instability. In the immunohistochemical staining, 20 (8.6 percent) showed loss of expressions. All 20 staining-negative cases were microsatellite instability–positive. Only 1 of 21 (4.8 percent) microsatellite instability– positive cases showed intact staining for three proteins. The frame-shift mutations of the simple repetitive sequences were found in 17 cases (81.0 percent) in TGF-βRII, 11 (52.4 percent) in BAX, 5 (23.8 percent) in IGF IIR, 7 (33.3 percent) in hMSH3, and 8 (38.1 percent) in hMSH6 genes. Germline mutation was observed in only one case, which accounts for 4.8 percent among positive microsatellite instability and 0.4 percent of total patients, and was found in hMSH2. Five somatic mutations (2 in hMLH1, 2 in hMSH2, and 1 in hMSH6) also were found. CONCLUSION: The results indicated that a germline mutation of DNA mismatch repair gene was a rare event in sporadic colorectal cancers.