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Recent evidence suggests that Fusobacterium nucleatum (Fn) is associated with the development and progression of colorectal cancer. We aimed to delineate the clinical implications of Fn in metastatic colon cancer. We performed quantitative polymerase chain reaction (qPCR) using DNA samples from synchronous metastatic colon cancer patients with either formalin-fixed paraffin-embedded (FFPE) archival primary site tumor samples or fresh colon tissues. Progression-free survival (PFS)1 and PFS2 were defined as PFS of first- and second-line palliative settings. qPCR for Fn was successfully performed using 112 samples (FFPE, n = 61; fresh tissue, n = 51). Forty-one and 68 patients had right-sided and left-sided colon cancer, respectively. Patients with Fn enriched right-sided colon cancers had shorter PFS1 (9.7 vs. 11.2 months) than the other subgroups (HR 3.54, 95% confidence interval [CI] 1.05–11.99; P = 0.04). Fn positive right-sided colon was also associated with shorter PFS2 (3.7 vs. 6.7 months; HR 2.34, 95% CI 0.69–7.91; P = 0.04). In the univariate analysis, PFS1 was affected by differentiation and Fn positive right-sided colon cancer. The multivariate analysis showed that differentiation (HR 2.68, 95% CI 1.40–5.14, P = 0.01) and Fn positive right-sided colon (HR 0.40, 95% CI 0.18–0.88, P = 0.02) were associated with PFS1. Fn enrichment in right sided colon was not associated with overall survival (OS). Fn enrichment has significantly worse prognosis in terms of PFS1 and PFS2 in patients with right-sided metastatic colon cancers.

Background and objectives This study aimed to investigate the clinical course and prognostic factors after isolated local recurrence (iLR) and to identify the predictive factors for R0 resection of locally recurrent rectal cancer (LRRC). Methods We retrospectively reviewed the medical records of 76 patients with iLR who had undergone radical surgery for a primary tumor from 2003 to 2015. Results The iLR rate was 2.5%. From 76 patients, 39 patients underwent R0 resection for iLR. Multivariate analysis revealed that initial open surgery, neoadjuvant chemoradiation, and p/ypT ≥ 3 were poor prognostic factors after iLR as regard to the variables related to the primary tumor; and symptom presence at the time of iLR diagnosis, higher fixity, and no chemotherapy after iLR were associated with shorter overall survival after iLR, and R0 resection of LRRC was the only favorable prognostic factor for progression-free survival after iLR as regard to the variables related to LRRC. Higher tumor level, negative pathologic circumferential margin of the primary tumor, and low fixity of LRRC were favorable factors in achieving R0 resection of LRRC. Conclusions Early detection of iLR before symptom development, use of chemotherapy after iLR and R0 resection of LRRC should be considered to improve survival outcomes after iLR.

BACKGROUND Comparable to circumferential resection margin in rectal cancer, radial margin is a potential prognostic factor in colon cancer that has just begun to be studied. No previous studies have investigated the influence of radial margin in the context of complete mesocolic excision. OBJECTIVE This study aimed to examine the impact of radial margin on oncologic outcomes after complete mesocolic excision for colon cancer. DESIGN We retrospectively reviewed patients with stage I to III colon cancer who underwent curative resection from October 2010 to March 2013. SETTINGS This study was conducted using the prospective colorectal cancer registry of Severance hospital. PATIENTS A total of 834 consecutive patients who underwent complete mesocolic excision for colon adenocarcinoma were included. INTERVENTIONS We assigned patients into 3 groups according to radial margin distance: group A, radial margin ≥2.0 mm; group B, 1.0 ≤ radial margin < 2.0 mm; group C, radial margin

Although studies of robotic rectal cancer surgery have demonstrated the effects of learning on operation time, comparisons have failed to demonstrate differences in clinicopathological outcomes between unadjusted learning phases. This study aimed to investigate the learning curve of robotic rectal cancer surgery for clinicopathological outcomes and compare surgical outcomes between adjusted learning phases. Study design We enrolled 506 consecutive patients with rectal adenocarcinoma who underwent robotic resection by a single surgeon between 2007 and 2018. Risk-adjusted cumulative sum (RA-CUSUM) for surgical failure was used to analyze the learning curve. Surgical failure was defined as the occurrence of any of the following: conversion to open surgery, severe complications (Clavien–Dindo grade ≥ 3a), insufficient number of harvested lymph nodes (LNs), or R1 resection. Comparisons between learning phases analyzed by RA-CUSUM were performed before and after propensity score matching. In RA-CUSUM analysis, the learning curve was divided into two learning phases: phase 1 (1st–177th cases, n = 177) and phase 2 (178th–506th cases, n = 329). Before matching, patients in phase 2 had deeper tumor invasion and higher rates of positive LNs on pretreatment images and preoperative chemoradiotherapy. After matching, phase 1 (n = 150) and phase 2 (n = 150) patients exhibited similar clinical characteristics. Phase 2 patients had lower rates of surgical failure overall and these components: conversion to open surgery, severe complications, and insufficient harvested LNs. For robotic rectal cancer surgery, surgical outcomes improved after the 177th case. Further studies by other robotic surgeons are required to validate our results.

Purpose Upfront systemic chemotherapy with target agents has been recommended for patients with stage IV colon cancer. Some with partial response are considered for curative resection. There is high risk of developing postoperative complications following upfront systemic chemotherapy. We aimed to evaluate short-term perioperative outcomes of curative surgery after upfront chemotherapy in comparison with upfront surgery in patients with metastatic colon cancer. Methods Between January 2010 and October 2015, 146 patients (80 in the surgery first group, 66 in the upfront chemotherapy group) who underwent surgical resection before or after systemic chemotherapy for metastatic colon cancer were included in the present study. All decisions for treatment were made through a multidisciplinary team. Postoperative clinical outcomes and complications were analyzed to compare the groups. Results There was no difference between the 2 groups in terms of postoperative clinical outcomes. Overall complication rates were not different between the groups (surgery first group: 46.3% vs. upfront chemotherapy group: 60.6%; P = 0.084). When classified according to the Clavien-Dindo method, there was no difference between the 2 groups in terms of major complications (grade 3 or more) (surgery first group: 18.9% vs. upfront chemotherapy group: 27.5%; P = 0.374). Conclusion There was no significant increase in major postoperative complications in metastatic colon cancer patients who received upfront chemotherapy followed by curative surgery. Careful patient selection and treatment planning are important.

Background The purpose is to investigate prognosis according to serum CEA levels before and after surgery in patients with stage IIA colon cancer who do not show high-risk features. Methods Among the patients diagnosed with colon adenocarcinoma between April 2011 and December 2017, 462 patients were confirmed as low-risk stage IIA after surgery and enrolled. The ROC curve was used to determine cut-off values of pre- and postoperative CEA. Patients were classified into three groups using these new cut-off values. Results All recurrence occurred in 52 of 463 patients (11.2%). However, recurrence in group H was 15.9%, which was slightly higher than the other two groups (P = 0.04). Group L and M showed 10.5% and 12.8% overall survival, group H was higher at 21.0% (P = 0.005). Recurrence was the only risk factor in group H was significantly higher in group L (HR 2.008, 95% CI, 1.123–3.589, P = 0.019). Mortality was similar to recurrence (HR 1.975, 95% CI 1.091–3.523, P = 0.044). Conclusion Among patients with low-risk stage IIA colon cancer, recurrence and mortality rates were higher when perioperative serum CEA levels were above a certain level. Therefore, high CEA level should be considered a high-risk feature and adjuvant chemotherapy should be performed.

With increasing rates of sphincter preservation because of advances in preoperative chemoradiation, restoration of bowel continuity has become a main goal of rectal cancer treatment. However, in many patients, postoperative bowel dysfunction negatively affects the quality of life.This study aimed to analyze predictors of bowel dysfunction after sphincter-preserving surgery in patients with rectal cancer.This was a cross-sectional study.Assessment of bowel dysfunction was conducted between November 2015 and June 2017 at our institution.A total of 316 patients with rectal cancer who underwent sphincter-preserving surgery between February 2009 and April 2017 and agreed with an interview for assessing bowel dysfunction were included.Bowel dysfunction was assessed with the Memorial Sloan Kettering Cancer Center Bowel Function Instrument and Wexner score. All the assessments were conducted face-to-face by the same interviewer.The median time interval between the restoration of bowel continuity and assessment was 10 months (interquartile range, 3-37), and the median total Memorial Sloan Kettering Cancer Center and Wexner scores were 65 (interquartile range, 58-73) and 6 (interquartile range, 0-11). The time interval was correlated with the Memorial Sloan Kettering Cancer Center scores (rho, 0.279) and Wexner scores (rho, -0.306). In a multivariate analysis, handsewn anastomosis and short time interval (≤1 year) were independently associated with poor bowel function (Memorial Sloan Kettering Cancer Center score ≤65). A short time interval (≤1 year), preoperative chemoradiation, and ileostomy were independently associated with major fecal incontinence (Wexner ≥8).Selection bias may be inherent.Bowel function recovers with time after the restoration of bowel continuity. A short time interval, handsewn anastomosis, preoperative chemoradiation, and ileostomy were significantly associated with poor bowel function or major fecal incontinence. Surgeons should discuss postoperative bowel dysfunction and its predictive factors with the patients. See Video Abstract at http://links.lww.com/DCR/A930.

BACKGROUND A survival paradox of stage IIB/IIC and IIIA colon cancer has been consistently observed throughout revisions of the TNM system. This study aimed to understand this paradox with clinicopathological and molecular differences. METHODS Clinicopathological characteristics of patients with pathologically confirmed stage IIB/IIC or IIIA colon cancer were retrospectively reviewed from a database. Publicly available molecular data were retrieved, and intrinsic subtypes were identified and subjected to gene sets enrichment analysis (GSEA). RESULTS Among the 159 patients included in the clinicopathological analysis, those at stage IIB/IIC had worse 3-year disease-free and overall survival than those at stage IIIA (59.3% vs 91.7%, P

Background The introduction of complete mesocolic excision (CME) with central vascular ligation (CVL) for right-sided colon cancer has improved the oncologic outcomes. Recently, we have introduced a modified CME (mCME) procedure that keeps the same principles as the originally described CME but with a more tailored approach. Some retrospective studies have reported the favourable oncologic outcomes of laparoscopic mCME for right-sided colon cancer; however, no prospective multicentre study has yet been conducted. Methods This study is a multi-institutional, prospective, single-arm study evaluating the oncologic outcomes of laparoscopic mCME for adenocarcinoma arising from the right side of the colon. A total of 250 patients will be recruited from five tertiary referral centres in South Korea. The primary outcome of this study is 3-year disease-free survival. Secondary outcome measures include 3-year overall survival, incidence of surgical complications, completeness of mCME, and distribution of metastatic lymph nodes. The quality of laparoscopic mCME will be assessed on the basis of photographs of the surgical specimen and the operation field after the completion of lymph node dissection. Discussion This is a prospective multicentre study to evaluate the oncologic outcomes of laparoscopic mCME for right-sided colon cancer. To the best of our knowledge, this will be the first study to prospectively and objectively assess the quality of laparoscopic mCME. The results will provide more evidence about oncologic outcomes with respect to the quality of laparoscopic mCME in right-sided colon cancer. Trial registration ClinicalTrials.gov ID: NCT03992599 (June 20, 2019). The posted information will be updated as needed to reflect protocol amendments and study progress.

Summary: Background/objective: Some locally advanced rectal cancer (LARC) patients treated with neoadjuvant chemoradiotherapy (CRT) prior to total mesorectal excision (TME) show early recurrence with a short disease-free interval. This is unacceptable for patients and their families, necessitating re-evaluation of the treatment process. We aimed to evaluate the risk factors and prognostic impact of early recurrence in patients who received preoperative CRT (pCRT) followed by TME for LARC. Methods: Of 714 patients who underwent curative resection after pCRT for LARC from January 2010 to December 2016, we included 139 who developed recurrence after resection. Patients were divided into an early recurrence group, diagnosed

Although multiple studies have examined anastomotic leakage (AL) after low anterior resection (LAR), their definitions of AL varied, and few have studied late diagnosed AL after surgery. This study aimed to characterize late AL after anal sphincter saving surgery (SSS) for rectal cancer by examining clinical characteristics, risk factors, and management of patients with late AL compared with early AL. Data from January 2005 to December 2014 were collected from a total of 1903 consecutive patients who underwent anal sphincter saving surgery for rectal cancer and were retrospectively reviewed. Late AL was defined as AL diagnosed more than 30 days after surgery. Variables and risk factors associated with early and late diagnosed AL were analyzed by multivariate logistic regression. Overall, early, and late rates of AL were 13.7%, 6.7%, and 7%, respectively. Receiving neoadjuvant chemoradiotherapy (nCRT) was a risk factor for developing late AL, but not early AL (OR, 3.032; 95% CI, 1.947–4.722; p

Tumor location and KRAS mutational status have emerged as prognostic factors of colorectal cancer. We aimed to define the prognostic impact of primary tumor location and KRAS mutational status among synchronous colorectal liver metastases (CRLM) patients who underwent simultaneous curative-intent surgery (SCIS). We compared the clinicopathologic characteristics and long-term outcomes of 227 patients who underwent SCIS for synchronous CRLM, according to tumor location and KRAS mutational status. We cross-classified tumor location and KRAS mutational status and compared survival outcomes between the four resulting patient groups. Forty-one patients (18.1%) had right-sided (RS) tumors and 186 (81.9%) had left-sided (LS) tumors. One-third of tumors (78/227) harbored KRAS mutations. The KRAS mutant-type (KRAS-mt) was more commonly observed among RS tumors than among LS tumors [21/41 (51.2%) vs. 57/186 (30.6%), p = 0.012]. Median follow-up time was 43.4 months. Patients with RS tumors had shorter survival times than those with LS tumors [median disease-free survival (DFS): RS, 9.9 months vs. LS, 12.1 months, p = 0.003; median overall survival (OS): RS, 49.7 months vs. LS, 88.8 months, p = 0.039]. RS tumors were a negative prognostic factor for DFS [hazard ratio (HR) 1.878, p = 0.001] and OS (HR 1.660, p = 0.060). RS KRAS-mt and LS KRAS wild-type (KRAS-wt) tumors had the worst and best oncological outcomes, respectively. Tumor location has a prognostic impact in patients who underwent SCIS for CRLM, and RS KRAS-mt tumors yielded the worst oncological outcome. These results may allow for more tailored multimodality treatments.

Peritoneal carcinomatosis (PC) was previously considered an incurable disease with a poor survival outcome. As our understanding of its biology evolved, the paradigm of the management of PC from colorectal cancer (CRC) has changed, including the combination of macroscopic disease control, cytoreductive surgery (CRS), maximal regional chemotherapy to treat residual microscopic disease, and hyperthermic intraperitoneal chemotherapy (HIPEC). As with many surgical innovations, CRS with HIPEC has evolved faster than data to support it, leaving many skeptics and critics. This review highlights the recent evidence of current practice and outcome of CRS with HIPEC. Furthermore, it also summarizes the ongoing clinical trials and potential future progress of this treatment modality.

Introduction There was no report for comparing long-term survival group with short-term survival group in patients who underwent liver resection for colorectal cancer with liver metastasis. Here, we compared the difference between the short-term and long-term survivors and analyzed the factors that influence the prognosis. Methods From January 2016 to December 2018, liver resections were performed for 478 patients of liver metastasis at the Yonsei University Severance Hospital. Except 111 patients due to lack of data, total 367 patients were analyzed retrospectively. Patients were divided into two groups: those who survived less than 24 months (short-term survival group, n = 87) and those who survived more than 24 months (long-term survival group, n = 280). Results In the short-term survival group, there were more patients with tumor size of 2 cm or more than the long-term survival group (p = 0.017). And the short-term survival group had more patients with margin positive than the long-term survival group (p < 0.05). The long-term survival group had more patients with single lesion than the short-term survival group (p = 0.028). In cox regression analysis, tumor size, tumor number, and resection margin were the prognostic factors effect survival. Conclusions For long-term survival of patients with liver metastasis of colorectal cancer, when deciding whether to undergo liver resection, whether a tumor smaller than 2 cm or a single lesion or curative resection is possible should be considered.

Purpose Previous studies have demonstrated the prognostic impact of the prognostic nutritional index (PNI), a proposed indicator of immunonutritional statuses of surgical patients, on patients with various gastrointestinal cancers. Although the prognostic impact of the PNI on patients with colorectal cancer has been well established, its value has not been studied in patients treated with preoperative chemoradiation (pCRT). This study aimed to evaluate the prognostic impact of PNI on patients receiving pCRT for locally advanced rectal cancer (LARC). Methods Patients with LARC who underwent curative pCRT followed by surgical resection were enrolled. The PNI was measured in all patients before and after pCRT, and the difference in values was calculated as the PNI difference (dPNI). Patients were classified according to dPNI (10). Clinicopathologic parameters and long-term oncologic outcomes were assessed according to dPNI classification. Results No significant intergroup differences were observed in clinicopathologic parameters such as age, histologic grade, tumor location, tumor-node-metastasis stage, and postoperative complications. Approximately 53% of the patients had a mild dPNI (10). Univariate and multivariate analyses identified the dPNI as an independent prognostic factor for disease-free status (P < 0.01; hazard ratio [HR], 2.792; 95% confidence interval [CI], 1.577–4.942) and for cancer-specific survival (P = 0.012; HR, 2.469; 95%CI, 1.225–4.978). Conclusion The dPNI is predictive of long-term outcomes in pCRT-treated patients with LARC. Further prospective studies should investigate whether immune-nutritional status correction during pCRT would improve oncologic outcomes.

Background Despite acceptable oncologic outcomes of sphincter preserving surgeries for low rectal cancer, bowel dysfunction occurs. This study aimed to compare the oncologic and functional bowel outcomes between ultralow anterior resection (ULAR) and intersphincteric resection (ISR) for low rectal cancer. Methods One hundred sixty-four patients who underwent ULAR with or without ISR for low rectal cancer between December 2010 and May 2018 were included. The Wexner and Memorial Sloan Kettering Cancer Center (MSKCC) scores were used to evaluate the bowel function of patients. Overall survival (OS) and disease-free survival (DFS) were compared between patients. Results The ISR group had higher incidence of major fecal incontinence than the ULAR group (75.9% vs 49.3%; P = .016). The median Wexner score decreased from 12 to 9 (P = .062) at 1-year follow-up. However, the frequency and urgency/soilage subscales of MSKCC score improved significantly in the ULAR group. ISR and follow-up interval less than 1-year significantly increased the major incontinence risk. The OS in the ULAR and ISR groups was 91.4% and 91.7%. Whereas the DFS in both groups was 79% and 79.2%, respectively. Conclusion ULAR and ISR are comparable in oncologic outcomes. Severe bowel dysfunctions and major incontinence were noted in ISR group. Careful selection of patients is mandatory.

Background Colorectal cancer (CRC) screening can effectively reduce disease-related mortality by detecting CRC at earlier stages. We have previously demonstrated that the presence of SDC2 methylation in stool DNA is significantly associated with the occurrence of CRC regardless of clinical stage. The aim of this study was to evaluate the clinical performance of stool DNA-based SDC2 methylation test for CRC. Methods Aberrant SDC2 methylation in stool-derived DNA was measured by linear target enrichment (LTE)-quantitative methylation-specific real-time PCR (qMSP). Duplicate reactions of meSDC2 LTE-qMSP test were performed for stool samples obtained from CRC patients representing all stages (0–IV) and asymptomatic individuals who were subsequently underwent colonoscopy examination. To determine the diagnostic value of test in CRC and control groups, sensitivity and specificity were evaluated by receiver operating characteristic curve analysis. Results Of 585 subjects who could be evaluated, 245 had CRC, 44 had various sizes of adenomatous polyps, and 245 had negative colonoscopy results. Stool DNA-based meSDC2 LTE-qMSP showed an overall sensitivity of 90.2% with AUC of 0.902 in detecting CRC (0–IV) not associated with tumor stage, location, sex, or age (P > 0.05), with a specificity of 90.2%. Sensitivity for detecting early stages (0-II) was 89.1% (114/128). This test also detected 66.7% (2/3) and 24.4% (10/41) of advanced and non-advanced adenomas, respectively. Conclusions Results of this study validated the capability of stool DNA based-SDC2 methylation test by LTE-qMSP for early detection of CRC patient with high specificity. Trial registration ClinicalTrials.gov, NCT03146520, Registered 10 May 2017, Retrospectively registered; however, control arm was prospectively registered.

Classic colon cancer surgery refers to a wide resection of the tumor-bearing segment and the lymphatics draining along the named artery. The concept of TME has been applied to colon cancer and complete mesocolic excision (CME) in conjuction with central vascular ligation (CVL) has been introduced as the surgical treatment for colon cancer. Here, we discuss appropriate CME procedure with regard to the oncologic backgrounds, essential components, applied anatomy, laparoscopic technique, short-term, and oncologic outcomes. The introduction of CME has improved oncologic outcomes greatly in patients with colon cancer. The improved outcomes with CME can be attributed to underlying sound oncologic principles such as dissection through the proper plane of mesocolic excision, central vascular ligation, and sufficient length of proximal and distal margins. Thereby, CME technique can achieve en bloc removal of the diseased lesion with the increased amount of the colonic mesentery even though the length of for both bowel and mesentery resection remains a matter of debate. CME is a technically demanding operation thus, comprehensive understanding of the applied vascular anatomy is essential for successful CME. Favorable outcomes of open CME have been replicated with a laparoscopic approach. In future perspective, incorporating a structured education program on minimally invasive (laparoscopy or robot) CME would be beneficial.

The treatment strategy and benefit of extended lymph node dissection among patients with preoperatively diagnosed paraaortic lymph node metastasis (PALNM) in colon cancer remains highly controversial. In the current study, we analyzed the oncologic outcomes of patients who underwent extraregional lymph node dissection for colon cancer with isolated PALNM. From March 2000 to December 2009, the study group included 1082 patients who underwent curative surgery for colonic adenocarcinoma with pathological lymph node metastasis. Of 1082 patients who underwent curative surgery for colonic carcinoma, 953 (88.1 %) patients underwent regional lymphadenectomy, and 129 (11.9 %) patients underwent paraaortic lymph node dissection. Pathologic examination revealed N1 stage disease in 738 (68.2 %), N2 in 295 (27.3 %), and PALNM in 49 (4.5 %). Five-year overall survival (OS) and disease-free survival (DFS) rate were significantly better in the regional LNM group than in the PALNM group (OS 75.1 vs. 33.9 %, p

Purpose Previous studies have reported conflicting results regarding the prognostic value of tumor sidedness in colon cancer. We investigated the oncologic impact of tumor location and examined whether recurrence patterns were related to tumor sidedness in colon cancer patients. Methods We identified stage I-III colon adenocarcinoma patients from a prospective colorectal cancer registry at Severance Hospital, Seoul, Korea, who underwent complete mesocolic excision between 2005 and 2012. Adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for predictors of cancer-specific survival (CSS), recurrence-free survival (RFS), and cumulative recurrence at specific anatomic sites were examined using Cox proportional hazard regression analysis. Results Overall, 1,912 patients, 1,077 (56.3%) with left-sided colon cancer (LCC), and 835 (43.7%) with right-sided colon cancer (RCC), at a median follow-up of 59 months, were eligible and included in the study. In univariate analysis, similar 5-year CSS and RFS were observed for LCC and RCC in the total patient population, and when stratified by stage for stage I and II patients. For stage III patients, an adjusted Cox regression analysis indicated that RCC patients had a higher risk of cancer-specific mortality (HR, 1.75; 95% CI, 1.07-2.86; P = 0.024) and recurrence (HR, 1.78; 95% CI, 1.22-2.60; P = 0.003). Furthermore, RCC was an independent predictor of peritoneal recurrence (HR, 1.86; 95% CI, 1.05-3.29; P = 0.031) in stage III patients. Conclusion RCC correlated with worse CSS and RFS than LCC. In stage III patients, RCC correlated with increased risk of peritoneal recurrence. The reasons for these differences remain to be investigated.

Systemic inflammatory response, as measured by C-reactive protein (CRP), is associated with prognosis in various types of human malignancies. However, to the best of our knowledge, the clinical significance of CRP in patients with locally advanced rectal cancer that undergo preoperative chemoradiation has not been investigated in detail. This retrospective study validates CRP as a potential predictive marker for survival outcomes in rectal cancer patients. In this study, we enrolled 125 patients that received total mesorectal excision after preoperative chemoradiation for rectal cancer between January 2003 and December 2010. We investigated the association between preoperative CRP and clinicopathological characteristics and assessed the prognostic value of CRP. The median follow-up was 41 months. Elevated CRP showed significant correlation with high histological grade (P = 0.009) and cancer recurrence (P = 0.027). The 5-year disease-free survival and cancer-specific survival were significantly lower in the elevated CRP group (P = 0.001). Moreover, CRP was the strongest predictive factor for cancer-specific survival in multivariate analysis (P = 0.001). In the subgroup analysis, elevated CRP was a significant prognostic factor in patients with node-positive disease (P = 0.025) and was associated with poorer tumor regression (TRG4–5; P = 0.011). The results of our study suggest that preoperative CRP level shows prognostic significance in rectal cancer patients that have undergone chemoradiation. Therefore, preoperative CRP may help clinicians to identify patients that need additional therapy to reduce systemic failure.

We measured systemic changes in the immune response in 92 patients receiving preoperative chemoradiation therapy (CRT) and subsequent surgery for rectal cancer. The peripheral blood was sampled five times from the onset of CRT until surgery. Lymphocytes decreased continuously during CRT but increased after CRT. The increased lymphocyte population was predominantly CD8+ T lymphocytes, which accounted for a significantly larger proportion in patients without residual lymph node metastasis than in those with residual lymph node metastasis. Neutrophils and monocytes decreased during the initial two weeks of CRT but were maintained or increased afterwards. Neutrophil and monocyte counts were significantly lower in patients with a pCR (pathologic complete response) than in those without a pCR two weeks after CRT began but not at the initiation of CRT. All cytokines showed dramatic changes one month after the termination of CRT. Cytokines related to the antitumour immune response increased, and those related to tumour progression decreased. The predictive value of cytokines was not clear. In short, we observed that immune components in peripheral blood are affected by CRT and show dynamic changes over time. We identified biomarker candidates to predict the pathologic response in the future.

Background Colorectal cancer (CRC) screening is the most efficient strategy to reduce disease-related mortality. Frequent aberrant DNA methylation is known to occur in selected genes and early during CRC development, which has emerged as a new epigenetic biomarker for early detection of CRC. Previously, we reported that we identified that CpG sites of SDC2 were aberrantly methylated in tumor tissues of most CRC patients through comprehensive methylation analysis and demonstrated a high potential of quantification of SDC2 methylation in blood for early detection of colorectal cancer. In this study, we aim to investigate the feasibility of quantifying SDC2 methylation in stool DNA for the early detection of CRC. The objective of this study was to confirm a high frequency of SDC2 methylation in tumor tissues at various stages of CRC and investigate the feasibility of a quantitative test for SDC2 methylation in fecal DNA by highly sensitive and accurate real-time PCR for early detection of CRC. Methods Bisulfite-pyrosequencing assay was performed to measure the SDC2 methylation status in tissue samples. For methylation analysis in stool DNA, a highly sensitive and accurate method was applied which implements consecutive two rounds of PCR consisting of unidirectional linear target enrichment (LTE) of SDC2 and quantitative methylation-specific real time PCR (qMSP) for SDC2, named as meSDC2 LTE-qMSP assay. Its limit of detection was 0.1% methylation (corresponding to ~ 6 copies in total ~ 6200 genome copies). Results Positive SDC2 methylation was observed in 100% of primary tumors, 90.6% of adenomatous polyps, 94.1% of hyperplastic polyps, and 0% of normal tissues. SDC2 methylation level also significantly (P

Background Ulcerative colitis (UC) harbours a high risk of UC-associated colorectal cancer (UCCC), which is important cause of morbidity and mortality in patients with inflammatory bowel disease. Overall Survival (OS) of patients with UCCC has not been addressed well in the literature. Thus, we compared oncologic outcome of UCCC and sporadic colorectal cancer (SCC) using propensity score matching analysis. Methods Propensity score matching was performed for 36 patients, a 1:1 matching method stratified into 18 in UCCC and 18 patients in SCC. Matched variables were sex, age, body mass index, tumour stage, histology, preoperative carcinoembryonic antigen (CEA) level, and adjuvant treatment status. Patients with SCC or UCCC were retrospectively retrieved from our database from March 2000 to December 2015. All patients had undergone either oncological segmental resection or total proctocolectomy. Results The majority of cancers were found in the sigmoid colon. Total proctocolectomy was performed only in the UCCC group; however, half of the UCCC group underwent a standard operation. Five cases of postoperative complication occurred within six months in the UCCC group compared to one case in the SCC group. There was no significant difference in recurrence rate (p = 0.361) or OS (p = 0.896) between the arms. Conclusion UCCC showed more postoperative complications than SCC, and equivalent oncology outcome, however the difference was not statistically significant. This study represents an experience of a single institution, thus further randomized studies are required to confirm our.

Anastomotic leakage (AL) after stapled anastomosis in rectal cancer surgery is a major concern. Various types of intraoperative anastomotic air leakage tests (ALTs) have been proposed to reduce AL. This study aimed to evaluate the impact of intraoperative colonoscopy (IOC) as an intraoperative ALT in low anterior resection for rectal cancer. A total of 1266 patients were retrospectively reviewed. Among them, 215 patients who underwent IOC as an ALT in rectal cancer surgery were identified. IOC was performed after anastomosis to visualize the anastomosis line and to perform an ALT by insufflating the neorectum. Propensity score matching was used to match this group at a 1:1 ratio with 215 patients who underwent ALT with a 250-mL bulb irrigation syringe. Anastomotic defects that were found intraoperatively were resolved either by means of primary repair of the anastomotic defect, if possible, or by performing a preventive diverting ileostomy. The patient characteristics, pathologic outcomes, and operation details showed no significant difference between the two groups. Comparison of the AL rate showed a significant difference between the groups (IOC group without intraoperative leaks vs. non-IOC group without intraoperative leaks 4.3 vs. 11.7%, P = 0.007). The incidence of preventive diverting ileostomy because of a positive ALT was significantly higher in the IOC group than in the non-IOC group (10 vs. 2 cases, P = 0.036). IOC can be a valuable method for the assessment of stapled anastomosis and has the additional benefit of directly visualizing the anastomosis line.

Background and objectives: Advanced rectal cancers require local and systemic control. Chemo radiotherapy (CRT) is adequate to achieve adequate local control. Systemic control, however, is a dominant obstacle remained in debates. We compared oncology outcome in both arms in patients with advanced rectal cancers in order to identify high-risk group of distant metastasis. Methods: Data for 723 patients for advanced rectal cancer from 2005 to 2013 retrieved retrospectively. Patients were classified to CRT (n=364) or no CRT (n=359) arms. Results: CRT group showed greater local control and achieved pT stage 0, 1, or 2 in 43.7% vs. 28.4% in no CRT (p

Preoperative chemoradiotherapy (CRT) is the standard of care for patients with stage II and III rectal cancer. This strategy leads to pathologic complete response (pCR) in a significant number of patients. Factors predictive of pCR are currently being extensively investigated. The aim of this study was to analyze clinical factors that might be predictive of pCR. This study was a retrospective analysis of rectal cancer patients from January 2004 through December 2012. A total of 332 stage II and III patients with middle and low rectal cancer (≤10 cm) who received CRT and underwent curative total mesorectal excision were eligible. The median radiation dose was 50.4 Gy, and 72.6% of patients received infusional 5-fluorouracil with leucovorin, whereas 19.6% of patients received TS-1 with irinotecan, and 7.8% of patients received xeloda only. Pathologic complete response was confirmed by using pathologic specimens and analyzed based on predictive clinical factors. Among the 332 patients, 27.4% (n = 91) achieved pCR. Age, sex, body mass index, clinical T and N stages, tumor differentiation, the chemotherapy agent for CRT, and the time interval between CRT and surgery did not differ between the pCR and non-pCR groups. Carcinoembryogenic antigen (CEA) levels before CRT were 4.61 ± 7.38 ng/mL in the pCR group and 10.49 ± 23.83 ng/mL in the non-pCR group (P = 0.035). Post-CRT CEA levels were 1.4 ± 1.07 ng/mL in the pCR group and 2.16 ± 2.8 ng/mL in the non-pCR group (P = 0.014), and the proportion of middle rectal cancer patients was higher in pCR group (54.9%, P = 0.028). The results from multivariate logistic regression analysis indicated that higher tumor location (odds ratio 2.151; P = 0.003) and low post-CRT CEA level (odds ratio 0.789; P = 0.04) were independent predictive factors for pCR. Tumor location and post-CRT CEA level were predictive factors in pCR for rectal cancer patients. Therefore, these factors may be important determinants in achieving pCR, and may also be used to predict oncologic outcomes.

A minimum of 12 harvested lymph nodes (hLNs) are recommended in colorectal cancer. However, a paucity of hLNs is frequently presented after preoperative chemoradiation (pCRT) in rectal cancer and the significance of this is still uncertain. The aim of this study is to analyze the impact of hLNs on long-term oncologic outcomes. A total of 302 patients with locally advanced rectal cancer who underwent pCRT and curative resection between 1989 and 2009 were reviewed. Patients were categorized into 2 groups according to the number of hLNs

Purpose Tumors at the level of the anorectal junction had required total levator-ani muscle excision to achieve an adequate resection margin. However, in the cases of tumor invading ipsilateral levator-ani muscle and intact external sphincter, en bloc resection of rectum with levator-ani muscle including tumor would be possible. This hemilevator excision (HLE) technique enables preserving the anal sphincter function while obtaining oncologic clearance and avoiding permanent colostomy in those patients. This study aimed to evaluate the surgical outcomes and feasibility of HLE. Methods Data on 13 consecutive patients who underwent HLE for pathologically proven low rectal cancer were retrospectively collected. All 13 patients presented low rectal cancer at the anorectal ring level that was suspected to invade or abut to the ipsilateral side of the levator-ani muscle. Results A secure resection margin was achieved in all cases, and anastomotic leakage occurred in 2 patients. During follow-up, 3 patients experienced tumor recurrence (2 systemic and 1 local). Among 6 patients who underwent diverting ileostomy closure after the index operation, 2 complained of fecal incontinence. The other 4 patients without fecal incontinence showed

A rectal carcinoma, including primary an adenosquamous and a squamous cell carcinoma (SCC), is a very rare disease, accounting for 0.025% to 0.20% of all large-bowel malignant tumors. Because SCCs have a higher mortality than adenosquamous carcinomas, determining whether the primary rectal cancer exhibits an adenomatous component or a squamous component is important. While differentiating between these 2 components, especially in poorly differentiated rectal cancer, is difficult, specific immunohistochemical stains enable accurate diagnoses. Here, we report the use of immunohistochemical stains to distinguish between the adenomatous and the squamous components in 2 patients with low rectal cancer, a 58-year-old man and a 73-year-old woman, who were initially diagnosed using the histopathologic results for a poorly differentiated carcinoma. These data suggest that using these immunohistochemical stains will help to accurately diagnose the type of rectal cancer, especially for poorly differentiated carcinomas, and will provide important information to determine the proper treatment for the patient.

Purpose: Recent studies have shown that cyclooxygenase (COX)-2 may be involved in tumor growth, invasion and apop-tosis in various carcinomas. Vascular endothelial growth factor (VEGF) has a potent angiogenic activity, and COX-2 pro-motes angiogenesis by modulating angiogenic factors, including VEGF. Endothelial growth factor receptor (EGFR) is con-sidered as a factor of cell growth, maturation and cell death. The current study was designed to investigate the possible roles of COX-2 in colorectal tumor progression and angiogenesis. Methods: Fifty colorectal adenomas and forty adenocarcinomas were investigated by using immunohistochemical stain-ing for COX-2, VEGF and EGFR. The correlations of COX-2, VEGF and EGFR with the grade of dysplasia, the size of the adenoma, and various clinicopathologic factors were studied. Results: The expressions of COX-2, VEGF and EGFR were each significantly correlated with carcinomatous transforma-tion, and the expressions of COX-2 and VEGF were significantly correlated. COX-2 and EGFR showed correlations with adenomas rather than adenocarcinomas. However, no correlations of COX-2, VEGF and EGFR expression to other clini-copathologic factors, except tumor size in EGFR expression, were detected. Conclusion: These results suggest that COX-2 may play an important role in carcinogenesis through interaction with VEGF and EGFR in human colorectal cancer. Keywords