The Negative Prognostic Impact of Lymph Node Skip Metastasis in Stage III Colon Cancer With pN1 Disease: A Single-Center and Retrospective Cohort Study.

BACKGROUND: Lymph node skip metastasis is a subgroup of lymph node metastatic patterns with low incidence in node-positive colon cancer. Its clinical significance is still unclear. OBJECTIVE: This study aimed to investigate the prognostic impact of lymph node skip metastasis in stage III colon cancer. DESIGN: This is a retrospective observational analysis. SETTINGS: The study was conducted at the Taipei Veterans General Hospital. PATIENTS: This study included patients with stage III colon cancer who underwent D3 lymphadenectomy between 2006 and 2015. MAIN OUTCOME MEASURES: The patients were divided into a lymph node skip metastasis-positive group and a negative group. Recurrence-free survival and overall survival were compared using Kaplan-Meier curves and log-rank test. Cox regression was applied to identify related risk factors influencing survival. RESULTS: A total of 461 patients were reviewed, and lymph node skip metastasis-positive patients represented 13.2% of our sample. Patients with lymph node skip metastasis tended to present with a higher proportion of right-sided cancer, lower positive lymph nodes, lower lymph node ratio, and higher mean BMI. Liver recurrence was more prevalent in the lymph node skip metastasis group ( p = 0.028) than in the negative group. The presence of lymph node skip metastasis was a negative prognostic factor for 5-year recurrence-free survival (51.4% vs 68.7%; p = 0.002) and 5-year overall survival (66.4% vs 80.4%; p = 0.024) in Kaplan-Meier curves and multivariate Cox regression. Subgroup analysis revealed the survival significance of recurrence-free survival ( p = 0.001) and overall survival ( p = 0.011) in lymph node skip metastasis with pN1 disease. LIMITATIONS: This study was limited by its retrospective design, single-center nature, and sampling error. CONCLUSIONS: Lymph node skip metastasis is an independent negative prognostic factor in stage III colon cancer with pN1 disease. More intensive surveillance may be necessary for patients of this subgroup. See Video Abstract at https://links.lww.com/DCR/C60 . IMPACTO PRONSTICO NEGATIVO DE LAS METSTASIS DISCONTNUAS GANGLIONARES LINFTICAS EN CASOS DE CNCER DE COLON ESTADIO III CON ENFERMEDAD PN ESTUDIO DE COHORTES RETROSPECTIVO MONOCENTRICO: ANTECEDENTES:Las metástasis discontínuas ganglionares linfáticas, son un subgrupo de patrones metastásicos en los ganglios linfáticos con baja incidencia en el cáncer de colon con nódulos positivos. Su significado clínico aún no está claro.OBJETIVO:Estudio que tiene por objetivo el investigar el impacto pronóstico de las metástasis discontínuas de los ganglios linfáticos en el cáncer de colon de estadio III.DISEÑO:Análisis observacional retrospectivo.AJUSTES:El estudio se realizó en el Hospital General de Veteranos de Taipei.PACIENTES:Pacientes con cáncer de colon en estadio III que se sometieron a linfadenectomía D3 entre 2006 y 2015.PRINCIPALES MEDIDAS DE RESULTADO:Los pacientes se dividieron en un grupo positivo de metástasis discontínuas en los ganglios linfáticos y un otro grupo negativo. La sobrevida libre de recidiva y la sobrevida global, fueron comparadas mediante las curvas de Kaplan-Meier y la prueba de rango logarítmico. Se aplicó la regresión de Cox para identificar los factores de riesgo relacionados que influyeron en la sobrevida.RESULTADOS:Se revisaron un total de 461 casos, donde los pacientes positivos con metástasis en los ganglios linfáticos representaron el 13,2% de nuestra muestra. Los pacientes con metástasis discontínuas ganglionares linfáticas tendían a presentar una mayor proporción de cáncer localizado en el lado derecho del colon, presentar un menor numéro de ganglios linfáticos positivos y una proporción menor de ganglios linfáticos con un IMC promedio más alto. Las recidivas hepáticas fueron más prevalentes en el grupo de metástasis discontínuas ganglionares linfáticas ( p = 0,028) que en el grupo negativo. La presencia de metástasis discontínuas ganglionares linfáticas fué un factor de pronóstico negativo en la sobrevida libre de recidiva a 5 años (51,4% frente a 68,7%, p = 0,002) y la sobrevida general a 5 años (66,4% frente a 80,4%, p = 0,024) evaluada por las curvas de Kaplan-Meier y la regresión multivariada de Cox. El análisis de subgrupos reveló la importancia de la sobrevida libre de recidiva ( p = 0,001) y la sobrevida general ( p = 0,011) en los casos con metástasis discontínuas ganglionares linfáticas con enfermedad pN1.LIMITACIONES:Diseño retrospectivo, naturaleza de centro único y error de muestreo.CONCLUSIONES:Las metástasis discontínuas ganglionares linfáticas son un factor pronóstico negativo independiente en los casos de cáncer de colon estadio III con enfermedad pN1. Tal vez sea necesaria una mayor vigilancia de los pacientes en este subgrupo.Consulte Video Resumen en https://links.lww.com/DCR/C60 . (Traducción-Dr. Xavier Delgadillo ).

Clinical outcome of local treatment and radical resection for pT1 rectal cancer.

BACKGROUND: Rectal cancer is mainly cured by radical resection with neoadjuvant chemoradiation or adjuvant chemotherapy. Pathological T1 lesions can be managed by local treatment and radiotherapy thereafter. Lower morbidity is the key benefit of these local treatments. Since nodal metastasis is important for staging, radical resection (RR) is suggested. Rectal cancer has higher surgical morbidity than colon cancer; local treatment has been the preferred choice by patients. METHODS: We retrospectively enrolled data of 244 patients with pT1 rectal adenocarcinoma. A total of 202 patients (82.8%) underwent RR, including low anterior resection (LAR) and abdomino-perineal resection (APR), and 42 patients (17.2%) underwent LT, including transanal excision and colonoscopic polypectomy. RESULTS: In our study, seven patients (16.7%) had loco-regional recurrence and distant metastasis from the LT group while eight patients (4.0%) had distant metastasis without loco-regional recurrence from the RR group. The lymph node metastasis rate in RR group was 8.4%. Forty-seven patients (24.2%) underwent LAR with temporary stoma, and its reversal rate was 100%. In the RR group, postoperative complication rate was 10.4% with a mortality rate of 0.5%. Recurrence-free survival (RFS) was 95.7% for RR and 80.2% for LT (P = 0.001), and overall survival (OS) was 93.7% for RR and 70.0% for LT (P = 0.001). CONCLUSION: This study found that RFS and OS in patients of pT1 rectal adenocarcinoma that had received RR were better than receiving LT. Further adjuvant chemotherapy was possible for some RR patients. A higher recurrence rate after LT must be balanced against the morbidity and mortality associated with RR.

A novel machine learning-based algorithm to identify and classify lesions and anatomical landmarks in colonoscopy images.

OBJECTIVES: Computer-aided diagnosis (CAD)-based artificial intelligence (AI) has been shown to be highly accurate for detecting and characterizing colon polyps. However, the application of AI to identify normal colon landmarks and differentiate multiple colon diseases has not yet been established. We aimed to develop a convolutional neural network (CNN)-based algorithm (GUTAID) to recognize different colon lesions and anatomical landmarks. METHODS: Colonoscopic images were obtained to train and validate the AI classifiers. An independent dataset was collected for verification. The architecture of GUTAID contains two major sub-models: the Normal, Polyp, Diverticulum, Cecum and CAncer (NPDCCA) and Narrow-Band Imaging for Adenomatous/Hyperplastic polyps (NBI-AH) models. The development of GUTAID was based on the 16-layer Visual Geometry Group (VGG16) architecture and implemented on Google Cloud Platform. RESULTS: In total, 7838 colonoscopy images were used for developing and validating the AI model. An additional 1273 images were independently applied to verify the GUTAID. The accuracy for GUTAID in detecting various colon lesions/landmarks is 93.3% for polyps, 93.9% for diverticula, 91.7% for cecum, 97.5% for cancer, and 83.5% for adenomatous/hyperplastic polyps. CONCLUSIONS: A CNN-based algorithm (GUTAID) to identify colonic abnormalities and landmarks was successfully established with high accuracy. This GUTAID system can further characterize polyps for optical diagnosis. We demonstrated that AI classification methodology is feasible to identify multiple and different colon diseases.

Three-dimensional versus conventional two-dimensional laparoscopic colectomy for colon cancer: A 3-year follow-up study.

Background: Three-dimensional (3D) laparoscopy was developed to overcome the drawbacks of two-dimensional (2D) laparoscopy, namely lack of depth perception. However, the benefit of 3D laparoscopy in colorectal surgery is inconclusive. Here, we compare the 3-year follow-up outcomes of 3D and 2D laparoscopic colectomy. Patients and Methods: A total of 91 consecutive patients who underwent either 3D or 2D laparoscopy colectomy from October 2015 to November 2017 by a single surgical team for colon cancer were enrolled. Data were collected from a prospectively constructed database, including clinico-pathological features and operative parameters. The pathological results, recurrence, survival and systemic treatment were collected from the Taiwan Cancer Database. Results: There were 47 patients in the 3D group and 44 in the 2D group. There were no significant differences in characteristics of patients, operation data, pathological results, complications, operative time, blood loss or the number of lymph node harvested between the two groups. In addition, disease-free survival and overall survival were equal between the two groups. Conclusions: This is the first long-term result of a 3D laparoscopic colectomy. In our 3-year follow-up, there was no difference in long-term outcomes between 2D and 3D laparoscopy for colorectal surgery in an experienced centre.

The efficacy of anti-EGFR therapy in treating metastatic colorectal cancer differs between the middle/low rectum and the left-sided colon.

BACKGROUND: Clinically, metastatic rectal cancer has been considered a subset of left-sided colon cancer. However, heterogeneity has been proposed to exist between high and middle/low rectal cancers. We aimed to examine the efficacy of anti-epidermal growth factor receptor (EGFR) treatment for middle/low rectal and left-sided colon cancers. METHODS: This study enrolled 609 patients with metastatic colorectal cancer who were treated with anti-EGFR therapy. They were divided into groups based on primary tumour locations: the right-sided colon, the left-sided colon or the middle/low rectum. The efficacy of first-line and non-first-line anti-EGFR treatment was analysed. Genomic differences in colorectal cancer data from The Cancer Genome Atlas (TCGA) were investigated and visualised with OncoPrint and a clustered heatmap. RESULTS: On first-line anti-EGFR treatment, patients with middle/low rectal tumours had significantly lower progression-free survival, overall survival, and overall response rates (6.8 months, 27.8 months and 43%, respectively) than those with left-sided colon cancer (10.1 months, 38.3 months and 66%, respectively). Similar outcomes were also identified on non-first-line anti-EGFR treatment. In TCGA analysis, rectal tumours displayed genetic heterogeneity and shared features with both left- and right-sided colon cancer. CONCLUSIONS: Anti-EGFR treatment has lower efficacy in metastatic middle/low rectal cancer than in left-sided colon cancer.

Prognosticators of Long-Term Outcomes of TNM Stage II Colorectal Cancer: Molecular Patterns or Clinicopathological Features.

BACKGROUND: Patients with stage II colorectal cancer (CRC) have a higher risk of recurrence when they have certain risk factors, including clinical and pathological patterns. However, as the prognostic role of molecular patterns for stage II disease is still unclear, this study aimed to investigate it. METHODS: A total of 509 patients with stage II CRC were enrolled, and all clinical, pathological, and molecular data were collected. Molecular patterns included microsatellite instability (MSI); elevated microsatellite alterations at selected tetranucleotides (EMAST) status; and expression of RAS/RAF genes, genes of the APC pathway, and other gene mutations. The endpoints were oncological outcomes, including overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), local recurrence (LR), and distant recurrence (DR). Cox regression analysis was used. RESULTS: Numerous molecular patterns influenced the oncological outcomes on univariate analysis, but no variable reached significance in LR. On multivariate analysis, a mucinous component (MC) > 50% (P < 0.01) was significant for OS and CSS. Lymphovascular invasion (LVI; P< 0.01), MC > 50% (P < 0.01), and EMAST-H (P = 0.02) significantly influenced DFS, whereas LVI (P < 0.01), MC > 50% (P < 0.01), and TP53 mutation (P = 0.02) were significant for DR. CONCLUSIONS: In this study, MSI, EMAST, and RAS/RAF alterations did not influence the oncological outcomes. Overall, LVI and MC were two significant prognostic factors for DFS and DR. Thus, the histopathology, rather than the genes, plays a major role in the prognosis of patients with stage II CRC.

Risk factors for delayed perineal wound healing and its impact on prolonged hospital stay after abdominoperineal resection.

BACKGROUND: Perineal wound complications are a long-lasting issue for abdominoperineal resection (APR) patients. Complication rates as high as 60% have been reported, with the most common complication being delayed perineal wound healing. The aim of this study was to identify risk factors for delayed perineal wound healing and its impact on prolonged hospital stay. METHODS: We included low rectal tumor patients who underwent APR at a referral medical center from April 2002 to December 2017; a total of 229 patients were included. The basic characteristics and surgical outcomes of the patients were analyzed to identify risk factors for delayed perineal wound healing (> 30 days after APR) and prolonged hospital stay (post-APR hospital stay > 14 days). RESULTS: All patients received primary closure for their perineal wound. The majority of patients were diagnosed with adenocarcinoma (N = 213, 93.1%). In the univariate analysis, patients with hypoalbuminemia (albumin < 3.5 g/dL) had an increased risk of delayed wound healing (39.5% vs. 60.5%, P = 0.001), which was an independent risk factor in the multivariable analysis (OR 2.962, 95% CI 1.437-6.102, P = 0.003). Patients with delayed wound healing also had a significantly increased risk of prolonged hospital stay (OR 6.404, 95% CI 3.508-11.694, P < 0.001). CONCLUSIONS: Hypoalbuminemia was an independent risk factor for delayed wound healing, which consequently led to a prolonged hospital stay. Further clinical trials are needed to reduce the incidence of delayed perineal wound healing by correcting albumin levels or nutritional status before APR.

Differences in gene mutations according to gender among patients with colorectal cancer.

BACKGROUND: The incidence, site distribution, and mortality rates of patients with colorectal cancer differ according to gender. We investigated gene mutations in colorectal patients and wanted to examine gender-specific differences. METHODS: A total of 1505 patients who underwent surgical intervention for colorectal cancer were recruited from March 2000 to January 2010 at Taipei Veterans' General Hospital and investigated for gene mutations in K-ras, N-ras, H-ras, BRAF, loss of 18q, APC, p53, SMAD4, TGF-ß, PIK3CA, PTEN, FBXW7, AKT1, and MSI. RESULTS: There were significant differences between male and female patients in terms of tumor location (p < 0.0001) and pathological stage (p = 0.011). The female patients had significantly more gene mutations in BRAF (6.4 vs. 3.3%, OR 1.985, p = 0.006), TGF-ß (4.7 vs. 2.5%, OR 1.887, p = 0.027), and revealed a MSI-high status (14.0 vs. 8.3%, OR 1.800, p = 0.001) than male patients. Male patients had significantly more gene mutations in N-ras (5.1 vs. 2.3%, OR 2.227, p = 0.012); however, the significance was maintained only for mutations in BRAF (OR 2.104, p = 0.038), MSI-high status (OR 2.003 p = 0.001), and N-ras (OR 3.000, p = 0.010) after the groups were divided by tumor site. CONCLUSION: Gene mutations in BRAF, MSI-high status, and N-ras differ according to gender among patients with colorectal cancer.

Improved outcomes of colorectal cancer patients with liver metastases in the era of the multidisciplinary teams.

PURPOSE: The use of multidisciplinary teams (MDTs), which address colorectal cancer treatment planning through weekly regular group meetings, was begun in October 2007. We analyzed and compared the outcomes of colorectal cancer patients with metastatic disease before and after the era of MDTs. METHODS: From 2001 to 2010, 1075 patients who presented with stage IV disease and were treated in Taipei Veterans General Hospital were enrolled in the study. Among these patients, 439 (40.8%) were diagnosed after MDTs had been established. The percentage of patients receiving surgical treatment for metastatic disease was calculated and compared before and after MDTs were established, and the survival rate was compared using a log-rank test, with a significance of P < 0.05. RESULTS: A significantly improved survival rate in patients with stage IV disease was observed after establishment of MDTs, with the 3-year survival rate increasing from 25.6 to 38.2% (P < 0.001). Based on multivariate analysis, establishment of a MDT was an independent prognostic factor in patients with stage IV disease (hazard ratio = 0.74, 95% confidence interval = 0.624∼0.866, P < 0.001). The percentage of liver resection in patients with liver metastasis increased from 19.6 to 35.2% after the establishment of MDTs, whereas the percentage of lung resection in patients with lung metastasis remained stationary from 12.4 to 14.3%. CONCLUSIONS: In the era of MDTs, intensive cooperation between different specialists has increased the referral rate for metastasectomy, resulting in significantly improved outcomes of colorectal patients in initial stage IV disease.

Concordance of Carcinoembryonic Antigen Ratio and Response Evaluation Criteria in Solid Tumors as Prognostic Surrogate Indicators of Metastatic Colorectal Cancer Patients Treated with Chemotherapy.

BACKGROUND: Carcinoembryonic antigen (CEA) is widely used as a tumor marker in colorectal cancer (CRC). This study aimed to evaluate the role of the degree of change in CEA levels during the treatment period and found that the degree of change highly correlated with disease survival and Response Evaluation Criteria in Solid Tumors (RECIST) criteria in evaluating therapy response. METHODS: A total of 447 metastatic CRC patients treated with surgery of the primary tumor followed by systemic therapy at a single center from the year 2000 through 2011 were reviewed. The degree of change in CEA levels was expressed as the CEA ratio (post-CEA/pre-CEA) and classified into four groups during the treatment period for further evaluation. The imaging change of the same population was also compared with the CEA ratio during the treatment period. RESULTS: The CEA ratio was significantly correlated with different chemotherapy regimens (p < 0.001), pre-treatment CEA level (p < 0.001), lymphovascular invasion (p = 0.006), and tumor differentiation (p = 0.018). CEA ratio and imaging change according to RECIST criteria were both correlated with overall survival (p < 0.001). These two methods for evaluating treatment response were highly correlated (p < 0.001). CONCLUSIONS: CEA ratio was found to be a reliable prognostic factor in stage IV CRC, and was highly correlated with the imaging survey according to RECIST criteria. Further prospective studies are essential to validate these findings.

Mutations in the RAS and PI3K pathways are associated with metastatic location in colorectal cancers.

BACKGROUND AND OBJECTIVES: Identification of mutations in the downstream epidermal growth factor receptor (EGFR) signaling pathway could provide important insights of EGFR-targeted therapies in colorectal cancers. We analyzed the mutation spectra of the PI3K/PTEN/AKT and RAS/RAF/MAPK pathways in colorectal cancers and the associations of these mutations with sites of metastases or recurrence. METHODS: The study population comprised 1,492 retrospectively collected stages I-IV colorectal cancer specimens. Tissue was obtained between 2000 and 2010 at a single hospital. We analyzed 61 hot spots using MALDI-TOF mass spectrometry for nucleic acid analysis. RESULTS: Mutations were found in the RAS pathway in 47.3% of patients and in the PI3K pathway in 14.3% of patients, with 9.2% of patients carrying mutations in both pathways. Both the RAS and PI3K pathway mutations were significantly associated with proximal tumors, mucinous tumors, and microsatellite instability. Tumors carrying a RAS pathway mutation exhibited a higher frequency of lung and peritoneal metastasis than did tumors with a wild-type gene (P = 0.025 and 0.009, respectively). NRAS gene mutation was significantly associated with lung metastasis (P = 0.001). CONCLUSIONS: Somatic mutations in the RAS pathway of the primary tumor in colorectal cancer can influence patterns of metastasis and recurrence.

Synchronous and Metachronous Colorectal Cancers: Distinct Disease Entities or Different Disease Courses?

BACKGROUND/AIMS: This study aimed to investigate the clinicopathological characteristics of synchronous and metachronous colorectal cancers (CRCs). METHODOLOGY: From January 1, 2001 to December 31, 2010, 5898 patients who underwent surgical resection for CRCs were enrolled. Synchronous CRC was defined as presence of more than one primary CRC within 6 months of resection of the primary tumor; while CRC that occurred at least 6 months later was regarded as metachronous CRC. RESULTS: 5346 patients were eligible for the study and divided into three groups: solitary, synchronous and metachronous CRC. The overall prevalence of the synchronous CRC was 2.2% and the 10-year cumulative incidence of metachronous cancer was 0.84%. 29 (64%) metachronous cancers were diagnosed within 3 years of the index cancer and the mean time interval was 3.2 years. Male gender and presence of associated adenoma were significant risk factors for both synchronous and metachronous CRC. Synchronous and metachronous CRC patients shared similar clinicopathological features except that the former were older than the latter by 3.7 years. The five-year survival rates were not different among the three groups. CONCLUSIONS: Our study indicates that synchronous and metachronous CRC might represent similar disease entity with different courses.

Synchronous and metachronous colorectal cancers: distinct disease entities or different disease courses?

BACKGROUND/AIMS: This study aimed to investigate the clinicopathological characteristics of synchronous and metachronous colorectal cancers (CRCs). METHODOLOGY: From January 1, 2001 to December 31, 2010, 5898 patients who underwent surgical resection for CRCs were enrolled. Synchronous CRC was defined as presence of more than one primary CRC within 6 months of resection of the primary tumor; while CRC that occurred at least 6 months later was regarded as metachronous CRC. RESULTS: 5346 patients were eligible for the study and divided into three groups: solitary, synchronous and metachronous CRC. The overall prevalence of the synchronous CRC was 2.2% and the 10-year cumulative incidence of metachronous cancer was 0.84%. 29 (64%) metachronous cancers were diagnosed within 3 years of the index cancer and the mean time interval was 3.2 years. Male gender and presence of associated adenoma were significant risk factors for both synchronous and metachronous CRC. Synchronous and metachronous CRC patients shared similar clinicopathological features except that the former were older than the latter by 3.7 years. The five-year survival rates were not different among the three groups. CONCLUSIONS: Our study indicates that synchronous and metachronous CRC might represent similar disease entity with different courses.

Genetic variations are associated with lymph node metastasis in colorectal cancer patients.

BACKGROUND AND OBJECTIVES: Regional lymph nodes (LNs) are believed to be a first-line barrier against tumor metastasis. However, it remains unclear whether underlying genetic factors exist and affect LN metastasis risk. We therefore evaluated inherited risk variants using single nucleotide polymorphisms (SNPs) in pathological T3 colorectal cancer patients in the absence or presence of LN metastasis. METHODS: The study population comprised 629 retrospectively collected colorectal cancer samples between 2000 and 2009 in a single hospital, including 273 patients with LN metastasis and 355 control subjects without LN metastasis. We analyzed 87 SNPs in genes that are associated with susceptibility to carcinogenesis or metastasis in colorectal or other cancers. RESULTS: Only 11 SNPs were found to have significant genotype distribution differences between the cases and controls. The average number of risk alleles carried by patients with LN metastasis was 7 (6.6 ± 1.4; range 2-10), which was significantly higher than the 6 risk alleles that were carried on average by patients without LN metastasis (6.0 ± 1.6; range 0-10; P < 0.001). CONCLUSIONS: Certain SNPs can increase genetic susceptibility to LN metastasis. As the number of risk alleles increases, the risk of LN metastasis also increases, although the difference is subtle.

The prognostic role of microsatellite instability, codon-specific KRAS, and BRAF mutations in colon cancer.

BACKGROUND: This study aimed to establish a correlation between MSI, KRAS mutations, and BRAF(V600E) in colon cancer and to investigate the prognostic effect. METHODS: Colon cancer patients who underwent surgical intervention were enrolled. MSI status was identified by genotyping, and the mutational statuses of KRAS and BRAF were determined by MassARRAY, targeting 22 mutations. The clinicopathological differences and correlations between these factors were analyzed. RESULTS: Among 1,063 patients, tumors with MSI-H were significantly associated with BRAF(V600E) (P = 0.001). KRAS and BRAF mutations were mutually exclusive (P = 0.001). Patients with MSI-H tumors had significantly improved overall survival compared with patients that had microsatellite instability-low/stable (MSI-L/MSS) tumors (hazard ratio 0.686: 95% confidence interval: 0.479-1.162, P = 0.040). In addition, the BRAF(V600E) mutation was a poor prognostic factor in tumors with MSI-L/MSS (P = 0.020). KRAS mutations were not prognostic factors, but sub-group analysis demonstrated that mutations in KRAS codon 12 were associated with significantly worse survival than wild-type KRAS, mutations in KRAS codon 13, or mutations elsewhere. CONCLUSIONS: MSI and the BRAF(V600E) mutation have a prognostic impact in colon cancer. Variable KRAS mutations may have different effects on colon cancers; further studies are needed to verify these results.

The role of adjuvant chemotherapy in stage II colorectal cancer patients.

PURPOSE: Adjuvant chemotherapy use in stage II colorectal cancer (CRC) is debated. We evaluated the prognostic significance of clinicopathological features recommended by most guidelines for identifying high-risk stage II CRC and adjuvant chemotherapeutic response. METHODS: We enrolled 1,039 stage II CRC patients who underwent curative surgery at Taipei Veterans General Hospital from January 2005 to December 2010. Seventy-seven patients who received radiotherapy were excluded. The endpoint was disease-free survival. RESULTS: Of 962 patients, 37 had stage T4 tumors; 50, lymphovascular invasion; 39, poor differentiation; 249, preoperative carcinoembryonic antigen (CEA) levels >5 ng/mL; and 53 underwent emergent operations. One hundred ninety-four patients received 5-fluorouracil-based adjuvant chemotherapy. During a median follow-up period of 60.2 months, recurrence developed in 110 patients (11.4 %). The 5-year disease-free survival (DFS) was 87.6 %. In multivariate analysis, preoperative CEA >5 ng/ml (p = 0.001), emergent operation for obstruction/perforation (p = 0.008), lymphovascular invasion (p = 0.014), and T4 disease (p = 0.030) were significantly associated with poor DFS. High-risk stage II patients (n = 484) benefited from adjuvant chemotherapy (5-year DFS with and without adjuvant chemotherapy, 87.3 vs. 78.9 %; p = 0.028). CONCLUSIONS: Adjuvant chemotherapy improved DFS in high-risk stage II CRC patients, but not in low-risk patients.

Clinicopathological analysis of colorectal carcinoid tumors and patient outcomes.

BACKGROUND: Colorectal carcinoid tumors are often described as being low-grade malignant. The objective of the current study was to address the clinicopathological features and outcomes of patients with colorectal carcinoid tumors. METHODS: A total of 63 patients with colorectal carcinoid tumors were identified and evaluated using surgical pathology files and medical records between January 2000 and June 2012 at the Veterans General Hospital, Taipei, Taiwan. RESULTS: The median age of the 63 patients was 57.0 years; 38 (60.3%) were male and 25 (39.7%) female. The rectum was the most common tumor site (90.5%). Tumor size was 10.8±7.4 mm, ranging from 2 to 50 mm in diameter. There were 40 patients (63.5%) who received endoscopic treatment for a tumor size of 7.7±4.0 mm, 15 (23.8%) who underwent transanal excision for a mean size of 9.2±4.5 mm and eight (12.7%) who underwent radical surgical resection (mean size: 29.5±13.0 mm). Lymph node metastasis was significantly associated with tumor size. Totally distant metastases (liver) were demonstrated in four (6.3%), patients with mean tumor size of 31.3±9.4 mm (20 to 50 mm). The extent of the disease was associated with survival and the five-year overall survival rate was 92.1%. CONCLUSIONS: With widespread colorectal cancer screening, heightened awareness and improved diagnostic modalities, the incidence of colorectal carcinoid tumors will continue to increase. We demonstrated that small-sized colorectal carcinoid tumors and those localized in the mucosa or submucosa may be safely and effectively removed via endoscopic or transanal local excision.

The Number of Risk Factors Determines the Outcome Of Stage II Colorectal Cancer Patients.

BACKGROUND/AIMS: We evaluated the prognostic significance of clinicopathologic features recommended by the majority of guidelines for identifying high-risk stage it colon cancer patients. METHODOLOGY: We enrolled 665 stage II colorectal cancer patients at Taipei Veterans General Hospital in 2002-2006. Patients who received preoperative or postoperative chemotherapy were excluded (124). The measured endpoint was disease-free survival. RESULTS: Of 541 patients, 59 showed stage T4 tumors; 35, lymphovascular invasion; 19, poor differentiation, and 251, carcinoembryonic antigen levels of > 5 ng/mL; 53 underwent emergent operations. Colorectal cancer recurred in 84 patients. The 5-year disease-free survival rate was 84.5%. Univariate and multivariate analyses revealed 3 independent factors affecting the prognosis significantly tumor stage T4, high carcinoembryonic antigen level, and presence of lymphovascular invasion. Considering the cumulative effect of risk factors, the 5-year disease-free survival rate of patients with tumors without any risk factor was 90.2%, which was significantly better than that of patients with 1 or 2 risk factors (82.3%, 61.6%). CONCLUSIONS: Stage II colorectal cancer patients had excellent outcome. Ad juvant chemotherapy may be warranted for patients with multiple risk factors.

Impact of KRAS mutation on outcome of patients with metastatic colorectal cancer.

BACKGROUND/AIMS: KRAS mutation is present in 30%-50% of colorectal cancers and is associated with the inefficacy of anti-epidermal growth factor receptor therapy, while the impact of KRAS on survival is seldom discussed. The aim of this study was to elucidate the impact of KRAS status on the survival of patients with metastatic colorectal cancer. METHODOLOGY: Two hundred and one patients with metastatic colorectal cancer were enrolled. Amplification and sequencing of the KRAS gene were performed, with the overall survival according to KRAS status analyzed. RESULTS: KRAS mutations were present in 72 (35.8%) of patients, including 55 (27.3%) codon 12 mutations and 17 (8.5%) codon 13 mutations. Lymphovascular invasion (hazard ratio 1.841, 95% confidence interval 1.043-3.247, p = 0.035) and KRAS mutation (hazard ratio 1.919, 95% confidence interval 1.104-3.333, p = 0.021) were independent prognostic factors for overall survival. The median overall survival for patients with KRAS mutation at codon 12 was 27.3 months, and was similar to those with KRAS mutation at codon 13 (20.4 months, p = 0.628). CONCLUSIONS: KRAS mutation is a poor prognostic factor in patients with metastatic colorectal cancer. In KRAS mutation metastatic colorectal cancer, mutation at codon 12 or at codon 13 had no relationship with prognosis.

Short-term outcomes of short- and long-course chemoradiotherapy prior to total mesorectal excision for locally advanced rectal tumors: A single-center study in Taiwan utilizing propensity score matching.

BACKGROUND: Locally advanced rectal tumors are typically treated with neoadjuvant chemoradiotherapy. Short-course chemoradiotherapy (SCRT, 2,500 cGy in five fractions) is a convenient alternative to concurrent chemoradiotherapy with long-course radiotherapy (CCRT, 4,500 cGy in 25 fractions) without sacrificing efficacy. We aimed to compare the short-term outcomes of SCRT and CCRT in patients with mid- and low- rectal tumors who underwent total mesorectal excision using real-world data. METHODS: We retrospectively reviewed the data of patients with locally advanced rectal cancer who underwent radical resection after neoadjuvant chemoradiotherapy from 2011 to 2022. We analyzed the clinicopathological findings and prognostic factors for disease-free and overall survival in the SCRT and CCRT groups and compared the outcomes using propensity score matching. RESULTS: Among the 66 patients in the two groups, no disparities were noted in the demographic features, pathological remission, or downstaging rates. Nonetheless, the SCRT group exhibited superior 3-year disease-free survival (81.8% vs. 62.1%, p = 0.011), whereas the overall survival did not differ significantly between the two groups. The initial carcinoembryonic antigen (CEA) levels and neoadjuvant SCRT were associated with the recurrence rates [hazard ratio (HR) 1.13-4.10; HR 0.19-0.74], but the harvested lymph node count was not (HR 0.51-1.97). CONCLUSION: Among patients with locally advanced rectal cancer, SCRT combined with four cycles of FOLFOX was shown to enhance short-term disease-free survival. Factors impacting recurrence include the initial CEA level and SCRT, but not the harvested lymph node count.