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Aim To provide dynamic guidance from a rigorous and up-to-date consensus on the safe implementation and application of transanal total mesorectal excision (TaTME) from an international panel of expert surgeons and educationalists supported by 14 international surgical societies. Method An adapted Delphi method and focus group discussion approach was implemented for this consensus process, with expert advice from a guidelines methodologist. Statements were generated focusing on three main topics relating to the safe implementation of TaTME: (1) indications, (2) quality and outcome measures, (3) training and implementation of TaTME. Results Five rounds of the Delphi consensus process were completed over a 13-month period. A total of 56 surgeons experienced in TaTME and surgical education participated in this project. By Delphi round four, 80.0% or greater agreement was reached for all statements except for two, which were further reviewed during a fifth round. More complex cases that are likely to benefit from TaTME were identified, with the recommendation that they should be referred to TaTME expert centres. The most agreed upon definition of expert centres is outlined. Conclusion We have provided a current framework of best practice related to implementation of TaTME. The statements are not indefinite and will continue to be 'dynamic' and updated as new evidence emerges.

Background Anastomotic leakage is a common complication that can be associated with catastrophic consequences. However, the risk factors and incidence of anastomotic leakage vary considerably among clinical studies because of the lack of a standardized definition, clinical course and appropriate treatment options. The aim of this study was to identify and classify the clinical manifestations and treatment of anastomotic leakage and analyse the possible risk factors after low anterior resection. Methods From January 2009 to June 2010, 632 patients underwent low anterior resection for primary colorectal cancer at Samsung Medical Center. Patients with only one colorectal anastomosis were included from this prospectively collected medical database. Results The overall leakage rate was 6.0% (n = 38). In cases of generalized leakage, the patients that selected surgical management, regardless of having protective enterostomy and time of occurrence, had better outcomes. Protective enterostomy did not have a preventive effect and was not associated with a lower rate of anastomotic leakage. However, protective enterostomy confined the inflammation to only the pelvic cavity (P = 0.045) and no surgical intervention was initially needed. Male gender (P = 0.021, relative risk (RR) = 2.680, 95% confidence interval (CI) = 1.164–6.171) and side-to-end/J pouch-to-end anastomosis (P = 0.012, RR = 2.696, 95% CI = 1.249–5.818) were significant risk factors that affected anastomotic leakage. Conclusion Surgical management is the best choice for generalized leakage. A protective enterostomy diminished the occurrence of generalized leakage and consequent surgical management; therefore, fragile patients at high risk for anastomotic leakage are recommended to undergo protective enterostomy.

Background The benefit of adjuvant chemotherapy for patients with locally advanced rectal cancer who have received neoadjuvant concurrent chemoradiation therapy (CCRT) and undergone curative resection remains unclear. Methods This study was a retrospective review of prospectively collected data. Patients with locally advanced rectal cancer who underwent curative surgery after neoadjuvant CCRT between January 2006 and March 2011 were identified. Four hundred forty-one patients who completed adjuvant chemotherapy (chemo group) were compared with 35 patients who did not receive any adjuvant treatment (nonchemo group). Results The 5-year disease-free survival (DFS) was significantly higher in the chemo group (78.5% vs. 63.1%, P = 0.016). After stratification of the patients according to nodal status, these differences were no longer significant, but there were trends toward inferior DFS in the nonchemo group in all survival curves. In multivariate Cox regression analysis, no adjuvant chemotherapy (HR, 2.306; 95% CI, 1.101–4.829; P = 0.027) emerged as an independent prognostic factor associated with decreased DFS. Conclusions Adjuvant chemotherapy was significantly associated with increased DFS among patients who had undergone neoadjuvant CCRT and radical resection for locally advanced rectal cancer. Adjuvant chemotherapy should be considered in every patient after neoadjuvant CCRT irrespective of the final pathology stage. J. Surg. Oncol. 2015 111:439–444. © 2014 Wiley Periodicals, Inc.

Colorectal cancers (CRCs) with microsatellite instability-high (MSI+) but without detectable germline mutation or hypermethylation in DNA mismatch repair (MMR) genes can be classified as Lynch-like syndrome (LLS). The underlying mechanism and clinical significances of LLS are largely unknown. We measured MSI and MMR protein expression in 4,765 consecutive CRC cases. Among these, MSI+ cases were further classified based on clinical parameters, germline sequencing of MMR genes or polymerase e (POLE) and δ (POLD1) and promoter methylation analysis of MLH1 and MSH2. We found that MSI+ and MMR protein-deficient CRCs comprised 6.3% (N = 302) of this cohort. On the basis of germline sequencing of 124 cases, we identified 54 LS with MMR germline mutation (LS-MMR), 15 LS with EPCAM deletions (LS-EPCAM) and 55 LLS patients. Of the 55 LLS patients, six (10.9%) had variants of unknown significance in the genes tested, and one patient had a novel somatic mutation (p.S459P) in POLE. In patients with biallelic deletions of EPCAM, all tumors and their matched normal mucosa showed promoter hypermethylation of MSH2. Finally, we found that patients with LLS and LS-EPCAM shared clinical features that differed from LS-MMR patients, including lower frequency of fulfillment of the revised Bethesda guidelines (83.6 and 86.7% vs. 98.1% for LS-MMR) and older mean age at CRC diagnosis (52.6 and 52.7 years vs. 43.9 years for LS-MMR). We identified somatic mutation in POLE as a rare underlying cause for MMR deficiency in LLS. The similarity between LLS and LS-EPCAM suggests LLS as a subset of familial MSI+ CRC.

Background Perineural invasion (PNI) may influence the prognosis of colon cancer, but little is known about its predictive value. The aim of this study was to reveal the role of PNI in predicting prognosis after curative resection of colon cancer, especially T3N0. Methods Two hundred and fifty-five patients who underwent curative resection for colon cancer at Samsung Medical Center and were later diagnosed with stage T3N0 by a pathological report between November 2004 and December 2007 were retrospectively recruited into the study. Results Among the 255 patients, 156 were male and 99 were female. The mean age was 61 years (range, 25 to 88 years). The most common tumour location was the sigmoid colon (93 patients, 36.5%). The median follow-up period was 61 months (range, 1 to 98 months). PNI was detected in 18 patients (7.1%). Adjuvant chemotherapy was performed in 205 patients (80.4%). The 5-year disease-free survival rate was greater for patients with PNI negative tumours compared with those with PNI positive tumours (92.0% versus 76.0%, P = 0.025). Adjuvant chemotherapy was not associated with significant differences in survival rate (94.8% versus 96.9%, P = 0.625). On multivariate analysis, PNI was an independent prognostic factor for disease-free and overall survival (P = 0.046, hazard ratio (HR) = 3.113, 95% confidence interval (CI) = 1.020–9.505 and P = 0.019, HR = 9.395, 95% CI = 1.453–60.755 respectively). Conclusions PNI is the only significant prognostic factor affecting disease-free and overall survival in patients with T3N0 colon cancer.

Background and Objectives The purpose of this study was to determine the risk factors for requirement of surgical or endoscopic interventions for complications caused by the primary tumor during chemotherapy in patients with unresectable metastatic colorectal cancer. Methods A total of 259 patients were diagnosed with uncomplicated colorectal cancer with unresectable metastatic disease and underwent chemotherapy as an initial treatment. Among them, 57 (22.0%) patients underwent palliative interventions because of complications caused by the primary tumor during chemotherapy, including bypass surgery or diverting enterostomy for 22 patients, insertion of colonic stent for 22, and resection of primary tumor for 13. Results Multivariate analysis revealed that rectal lesion (RR, 2.132; 95% CI, 1.080–4.210; P = 0.029) and tumor size larger than 5 cm (RR = 3.644, 95% CI = 1.923–6.902; P

Background Although a single incision laparoscopic (SIL) technique has been used increasingly in colorectal surgery, there are only a few reports on the clinical availability of this approach coupled with low anterior resection (SIL–LAR) for colorectal cancers. We report here 96 consecutive cases of SIL–LAR and reduced port LAR cases, of which the initial approach was SIL. Methods This is a retrospective review of prospectively collected data of SIL–LAR cases performed by a single surgeon in Samsung Medical Center between June 2011 and June 2012. Results Out of 96 cases, 28 were finished as ‘pure’ SIL–LAR. Sixty-four cases were performed with one additional port, and four needed two more ports. There was no open conversion. The median duration of operation was 165 min. Proximal and distal resection margins were negative in all cases. Circumferential resection margins were positive in four cases. The median duration of postoperative stay was 7 days and the complication rate was 20%. There were six cases of anastomosis leakage (6%). Conclusion The SIL–LAR technique can be applied safely with the optional use of an additional port. One additional port in the right suprapubic area is useful for obtaining a secure distal division and a safe total mesorectal excision, especially in patients with lower lesions or history of neoadjuvant chemoradiation.

Background The aim of this study was to evaluate the predictive role of the mismatch repair (MMR) system and p53 expression for lymph node metastasis and long-term survival in patients with T1 and T2 colorectal cancer. Methods A total of 543 patients with T1 or T2 colorectal cancers who underwent radical surgery with regional lymphadenectomy from December 2007 to December 2009 were analyzed. Predictive factors for lymph node metastasis and prognostic factors were analyzed. Results During the median follow-up period of 4 years, the 5-year disease-free survival rate for patients without lymph node metastasis was 94.8%, which was significantly higher than that for those with lymph node metastases (85.2%; P

Background This study evaluated the expression of p300 in colorectal cancer, its relationship with clinicopathological characteristics, and its potential prognostic significance. Methods The expression of p300 was measured using immunohistochemistry in tumors and surrounding normal mucosa from 199 patients with primary colorectal cancer. The patients were followed for a median period of 83 months. Results Nuclear p300 expression was significantly associated with histology (P = 0.031) and lymph node involvement (P = 0.019). When the low and high p300 groups were subdivided according to tumor location, the disease-free survival rate differed only for the patients with colon cancer (P = 0.008). In addition, the disease-free survival significantly differed with p300 expression for stage II disease (P = 0.038), but not for stage III disease. Multivariate analysis revealed that lymph node involvement (P = 0.014) and p300 expression (P = 0.032) were independent predictors of overall survival in adenocarcinomas. Conclusion The overexpression of p300 may be an independent favorable prognostic factor for disease-free survival in patients with colorectal cancer. J. Surg. Oncol. 2013; 108:374–377. © 2013 Wiley Periodicals, Inc.

Background and Objectives The 2010 NCCN clinical practice guidelines recommend radiation as a part of the standard adjuvant or neoadjuvant treatment for stage IV rectal cancer patients. This study evaluated the oncologic efficacy of postoperative radiotherapy (RTx) in loco-regional control after complete removal of primary and metastatic lesions in stage IV rectal cancer. Methods Sixty-eight patients with metastatic rectal cancer were enrolled and analyzed. Twenty-eight of the enrolled patients received concurrent postoperative RTx with chemotherapy (RTx group) and the remaining 40 received only postoperative systemic chemotherapy (CTx) without RTx (non-RTx group). The eligibility criteria were as follows: a primary rectal tumor located in the low or mid-rectum, no postoperative macroscopic and microscopic evidence of residual tumor in primary and metastatic sites, and no history of prior CTx or pelvic RTx. Results The recurrence rates were 75.0% in the RTx group and 72.5% in the non-RTx group. Local recurrence rates were 7.1% (RTx group) and 22.5% (non-RTx group) (P = 0.108). There were no differences in overall survival (OS), local recurrence-free survival, and disease-free survival between the two groups. The 2-year OS rates were 78.9% (RTx group) and 74.1% (non-RTx group) (P = 0.395). Conclusions Survival benefit of postoperative RTx in stage IV rectal cancer after complete removal of tumors was not apparent. RTx could be recommended for selected patients at high risk of local recurrence or for palliation of symptoms. J. Surg. Oncol. 2012; 105:244–248. © 2011 Wiley Periodicals, Inc.

BACKGROUND: The most reliable prognostic factor in colon cancer is the TNM classification. The objective of this study was to assess and compare the prognostic role of tumor-infiltrating lymphocytes (TILs) in stage II colon cancer. METHODS: Immunohistochemistry was used to assess the density of TILs that were positive for cluster of differentiation 3 (CD3) (T-cell coreceptor), CD45 isoform RO (CD45RO) (protein tyrosine phosphatase), nuclear transcription factor forkhead box P3 (FOXP3), and CD25 (a type I transmembrane protein) according to tumor site (intraepithelial and stromal) in samples from 87 patients who had stage II colon cancer. These variables were evaluated for their association with histopathologic features along with overall survival (OS) and disease-free survival (DFS). RESULTS: Intraepithelial CD3-posititve (CD3+), CD45RO+, CD25+, and FOXP3+ TILs were associated significantly with better DFS (P = .049, P = .009, P = .013, and P = .001, respectively). The estimated 5-year OS rates for patients who had high-density CD45RO+ and FOXP3+ expression was 100% for both compared with 79.2% and 78.8% for patients who had low-density CD45RO+ and FOXP3+ expression (P = .017 and P = .040, respectively). A significant prognostic factor for both OS and DFS was high-density stromal CD45RO+ lymphocytic infiltration (OS: P = .031; relative risk [RR], 0.134; 95% confidence interval [CI], 0.015-1.164; DFS: P = .013; RR, 0.198; 95% CI, 0.055-0.710); whereas intraepithelial FOXP3+ expression was an independent prognostic factor for DFS (P = .032; RR, 0.108; 95% CI, 0.014-0.821). CONCLUSIONS: FOXP3+ and CD45RO+ TILs demonstrated independent prognostic significance for survival in the current investigation. These results may help to improve the prognostication of early stage colon cancer. Cancer 2010. © 2010 American Cancer Society.

Background The aim of this study was to determine whether the different polymorphisms in the thymidylate synthase (TS) gene, novel G>C single nucleotide polymorphism (SNP) and variable number of tandem repeat (VNTR), may be related with disease-free survival (DFS) in patients with stage III colorectal cancer receiving adjuvant chemotherapy. Methods The study included 201 patients with pathologic TNM stage III colon cancer who received adjuvant 5-fluorouracil (5-FU)-based chemotherapy after surgery. DNA was extracted from fresh tumor tissue and sequenced. Patients with TS genotypes of 2R3G, 3C3G, or 3G3G were assigned to a high expression group, and those with 2R2R, 2R3C, or 3C3C, to a low expression group. Results Frequencies of the TS tandem repeat polymorphisms among the tumor genotypes were 6.0% in 2R2R, 25.4% in 2R3R, and 68.7% in 3R3R. The low expression group included 52 patients (25.9%), and the high expression group included 149 patients (74.1%). Groups classified according to possession of VNTR, SNP, and low- or high-expression genotypes did not differ significantly in DFS. In multivariate analysis, only tumor stage showed significant prognostic value (hazard ratio (HR) 2.05, 95% CI = 1.24–3.37, P = 0.005). Conclusions TS polymorphisms do not predict clinical outcome of colorectal cancer patients treated with adjuvant 5-FU-based chemotherapy. J. Surg. Oncol. 2010;101:22–27. © 2009 Wiley-Liss, Inc.

The solitary fibrous tumor (SFT) of peritoneum, especially arising in gastric serosa, is extremely rare. A case of SFT arising in gastric serosa of a 70-year-old man is reported. On abdominal computed tomography scan, an approximate 8.0 x 5.3 cm-sized solid mass with multiple nodular calcifications was noted in the omentomesentery of right upper abdomen, which was abutting to the gastric antral wall. At laparotomy the tumor was tightly attached to the gastric serosa and was completely excised by wedge resection of the stomach. The cut surfaces of the tumor were pale brown to pale yellow, firm, with multifocal yellowish, gritty, stony-hard nodules and cystic changes. Microscopically, the tumor was composed of mildly cellular benign-appearing spindle-shaped cells and bands of hyalinized collagen in varying proportions. The tumor revealed predominantly sclerosing pattern with extensive hyalinized fibrosis and multifocal dystrophic calcifications. The tumor was mainly located at the gastric serosa and subserosa, and its growth pattern was expansile with entrapping of muscularis propria and submucosa in the periphery of the tumor. By immunohistochemistry, the tumor cells were diffusely positive for CD34 and vimentin but negative for cytokeratin, desmin, smooth muscle actin, CD99 and c-kit. Although its occurrence is rare, SFT should be considered in the differential diagnosis of mesenchymal tumors of the stomach.