Open versus laparoscopic surgery for mid or low rectal cancer after neoadjuvant chemoradiotherapy (COREAN trial): 10-year follow-up of an open-label, non-inferiority, randomised controlled trial.

BACKGROUND: Laparoscopic surgery has been widely used for rectal cancer; however, its long-term outcomes remain controversial. This study aimed to assess the long-term oncological safety of laparoscopic surgery for rectal cancer using 10-year follow-up data of the Comparison of Open versus laparoscopic surgery for mid or low REctal cancer After Neoadjuvant chemoradiotherapy (COREAN) trial. METHODS: The COREAN trial is a, open-label, non-inferiority, randomised controlled trial. Eligible participants were aged 18-80 years, had cT3N0-2M0 middle or low rectal cancer with lesions located within 9 cm of the anal verge, and had been treated with preoperative chemoradiotherapy. Patients were randomly assigned (1:1) to open or laparoscopic surgery with a computer-generated random allocation sequence with a random permuted block design. Neither patients nor clinicians were masked to treatment assignment. Open or laparoscopic total mesorectal excision was done 6-8 weeks after the administration of preoperative concurrent chemoradiotherapy (fluoropyrimidines alone, doublet therapy, or triplet therapy) at a dose of 50·5 Gy over 5·5 weeks. Postoperative adjuvant chemotherapy was administered for 4 months. The primary endpoint of 3-year disease-free survival was published previously. Here, we report 10-year overall survival, disease-free survival, and local recurrence. Analyses were done in the modified intention-to-treat population of all participants who were randomly assigned and provided follow-up data. This study is registered with ClinicalTrials.gov, NCT00470951. FINDINGS: Of the 340 patients enrolled in the COREAN trial between April 4, 2006, and Aug 26, 2009 (170 patients in each group), two patients in the laparoscopic surgery group moved abroad and were lost to follow-up, so were not included in this 10-year analysis. The median duration of follow-up was 143 months (IQR 122-156). No differences were observed in 10-year overall survival (74·1% [95% CI 66·8-80·0] in the open surgery group vs 76·8% [69·6-82·5] in the laparoscopic surgery group; p=0·44), 10-year disease-free survival (59·3% [51·1-66·5] vs 64·3% [56·0-71·5]; p=0·20), or 10-year local recurrence (8·9% [5·2-15·0] vs 3·4% [1·4-7·9]; p=0·050) between the open surgery and laparoscopic surgery groups at 10 years after surgery. The stratified hazard ratios, adjusted for ypT and ypN classification and tumour regression grade, for open surgery versus laparoscopic surgery were 0·94 (95% CI 0·63-1·43) for overall survival, 1·05 (0·74-1·49) for disease-free survival, and 2·22 (0·78-6·34) for local recurrence. INTERPRETATION: The 10-year follow-up of the COREAN trial confirms the long-term oncological safety of laparoscopic surgery in patients with rectal cancer treated with preoperative chemoradiotherapy. Similar to open surgery, laparoscopic surgery does not compromise long-term survival outcomes in rectal cancer when performed by well trained surgeons. FUNDING: National Cancer Center, Goyang, South Korea.

Open versus laparoscopic surgery for mid-rectal or low-rectal cancer after neoadjuvant chemoradiotherapy (COREAN trial): survival outcomes of an open-label, non-inferiority, randomised controlled trial.

BACKGROUND: Compared with open resection, laparoscopic resection of rectal cancers is associated with improved short-term outcomes, but high-level evidence showing similar long-term outcomes is scarce. We aimed to compare survival outcomes of laparoscopic surgery with open surgery for patients with mid-rectal or low-rectal cancer. METHODS: The Comparison of Open versus laparoscopic surgery for mid or low REctal cancer After Neoadjuvant chemoradiotherapy (COREAN) trial was an open-label, non-inferiority, randomised controlled trial done between April 4, 2006, and Aug 26, 2009, at three centres in Korea. Patients (aged 18-80 years) with cT3N0-2M0 mid-rectal or low-rectal cancer who had received preoperative chemoradiotherapy were randomly assigned (1:1) to receive either open or laparoscopic surgery. Randomisation was stratified by sex and preoperative chemotherapy regimen. Investigators were masked to the randomisation sequence; patients and clinicians were not masked to the treatment assignments. The primary endpoint was 3 year disease-free survival, with a non-inferiority margin of 15%. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00470951. FINDINGS: We randomly assigned 340 patients to receive either open surgery (n=170) or laparoscopic surgery (n=170). 3 year disease-free survival was 72·5% (95% CI 65·0-78·6) for the open surgery group and 79·2% (72·3-84·6) for the laparoscopic surgery group, with a difference that was lower than the prespecified non-inferiority margin (-6·7%, 95% CI -15·8 to 2·4; p<0·0001). 25 (15%) patients died in the open group and 20 (12%) died in the laparoscopic group. No deaths were treatment related. INTERPRETATION: Our results show that laparoscopic resection for locally advanced rectal cancer after preoperative chemoradiotherapy provides similar outcomes for disease-free survival as open resection, thus justifying its use. FUNDING: National Cancer Center, South Korea.

Prognostic impact of circumferential resection margin in rectal cancer treated with preoperative chemoradiotherapy.

BACKGROUND: The circumferential resection margin (CRM) is a strong prognostic factor in rectal cancer. The purpose of this study was to investigate the relationship between CRM distance and recurrence in patients with locally advanced rectal cancer who received preoperative chemoradiotherapy (CRT). METHODS: We analyzed data for 561 patients who underwent preoperative CRT and curative surgery for locally advanced rectal cancer between August 2001 and December 2008. CRM was divided into four groups: group 1, CRM > 2 mm; group 2, 1.1-2.0 mm; group 3, 0.1-1.0 mm; and group 4, 0 mm. We assessed the associations of CRM with local recurrence and disease-free survival. RESULTS: Groups 1, 2, 3, and 4 comprised 487, 36, 20, and 18 patients, respectively. The local recurrence rate was highest and the disease-free survival rate was lowest in group 4, followed by groups 3, 2, and 1. Survival was similar between groups 2 and 1. Local recurrence rates were lower in groups 3, 2, and 1 than in group 4 [hazard ratio (HR) 0.28, 95 % confidence interval (CI) 0.09-0.91, P = 0.035; HR 0.11, 95 % CI 0.03-0.46, P = 0.002; HR 0.18, 95 % CI 0.08-0.42, P < 0.0001, respectively]. Disease-free survival rates were higher in groups 3, 2, and 1 than in group 4 (HR 0.32, 95 % CI 0.13-0.75, P = 0.009; HR 0.24, 95 % CI 0.10-0.54, P = 0.001; HR 0.26, 95 % CI 0.14-0.48, P < 0.0001, respectively). CONCLUSIONS: After preoperative CRT, CRM distance provides useful information for risk stratification in the recurrence of rectal cancer.

Serpin B5 is a CEA-interacting biomarker for colorectal cancer.

Serpin B5 is a candidate tumour suppressor, but its oncogenic activity has also been reported. Its function may be affected by protein interactions. The aim of this study was to assess the relationship between serpin B5 and carcinoembryonic antigen (CEA) expression in colorectal cancer (CRC). We also analysed the clinicopathological significance of serpin B5 expression in patients with CRC. Downregulation of serpin B5 was identified in a CEA-suppressed LoVo cell line using two-dimensional gel electrophoresis (2-DE) and matrix-associated laser desorption ionisation-mass spectrometry (MALDI-MS). The specific interaction and co-localisation of serpin B5 with CEA were confirmed by co-immunoprecipitation and confocal microscopy. Western blot analysis and ELISAs revealed significant positive correlations between levels of serpin B5 and CEA in human colon cancer cell lines and in the blood of patients with CRC. Tissue expression of serpin B5 in 377 patients with CRC was significantly associated with serum CEA, histological grade, stage, lymph node metastasis, lymphatic and perineural invasion, and infiltrative border. Strong expression of serpin B5 was also associated with a reduced DFS (p = 0.001) and OS (p = 0.017). Together, these findings describe a relationship between serpin B5 and CEA expression in CRC. Strong expression of serpin B5 was associated with a worse prognosis in patients with CRC and its expression may correlate with CEA levels in CRC.

Comparison of peristomal adhesion formation between laparoscopic and open low anterior resection of rectal cancer.

BACKGROUND: Postoperative adhesions appear to be less common following laparoscopic surgery than after conventional open surgery. The purpose of this study was to compare the impact of laparoscopic and conventional open rectal surgery on peristomal adhesion formation. METHODS: We enrolled 97 subjects who were participants in a trial comparing open versus laparoscopic surgery for mid and low rectal cancer after neoadjuvant chemoradiotherapy. These patients had undergone rectal cancer surgery with ileostomy formation. Peristomal adhesions were assessed during ileostomy takedown using an adhesion grading system: (1) no adhesions or fine, filmy adhesions separable by blunt dissection; (2) dense adhesions, separable by sharp dissection; (3) very dense adhesions, resulting in enterotomy and/or requiring extension of the abdominal wall incision. RESULTS: A total of 57 patients underwent laparoscopic resection (group A) and 40 underwent open resection (group B). Operating time for ileostomy dissection was shorter in group A than in group B (14.6 vs. 19.8 min, respectively; p = 0.047). Dense adhesions (grades 2 and 3) were more common in group B (22/40, 55 %) than in group A (12/57, 21 %; p < 0.001). In particular, grade 3 adhesions were present only in group B (6/40). CONCLUSIONS: The present findings suggest that laparoscopic rectal surgery results in less peristomal adhesion formation than does conventional open surgery.

Association between CASR polymorphisms, calcium intake, and colorectal cancer risk.

AIM: The current study aimed to assess the effect of dietary calcium intake and possible interactions with calcium-sensing receptor (CASR) gene polymorphisms on colorectal cancer risk. METHODS: A total of 420 colorectal cancer cases and 815 controls were included in the analysis. Calcium intake was investigated using a 103 item semi-quantitative food frequency questionnaire, and four single nucleotide polymorphisms (SNPs) within the CASR, rs10934578, rs12485716, rs2270916, and rs4678174, were evaluated. RESULTS: No SNPs were associated with colorectal cancer risk after adjusting for covariates. Overall, no significant effect modification by CASR polymorphisms on the association between calcium intake and colorectal cancer risk were detected. However, all 4 of the polymorphisms within the CASR showed significantly higher odds ratios for association with colorectal cancer risk in the low-calcium-intake group compared to the high-calcium-intake group. In the case of rs2270916, individuals with the CC genotype and low calcium intake showed an increased colorectal cancer risk compared to their counterparts with the TT genotype and high calcium intake (OR = 2.11, 95% CI = 1.27-3.51). CONCLUSIONS: Subjects with lower calcium intake exhibited a higher colorectal cancer risk compared with subjects with the same genotype who had higher calcium intake. Our results suggest that individuals who have low dietary calcium intake should be aware of their increased colorectal cancer risk and prevention strategies.

Preoperative plasma hyperfibrinogenemia is predictive of poor prognosis in patients with nonmetastatic colon cancer.

BACKGROUND: The outcomes of colorectal cancer are determined by host factors, including systemic inflammation. The purpose of this study was to evaluate the prognostic significance of fibrinogen and inflammation-based scores, as markers of the inflammatory response, in colon cancer. METHODS: We retrospectively reviewed the medical records of patients with nonmetastatic colon cancer who underwent curative resection between January 2005 and December 2007. Fibrinogen, albumin, C-reactive protein, neutrophil, lymphocyte, and platelet counts were measured at the time of diagnosis. Correlations between preoperative plasma fibrinogen levels and clinicopathologic characteristics were analyzed. Univariate and multivariate survival analyses were performed to identify factors associated with disease-free and overall survival. RESULTS: A total of 624 patients who underwent curative resection for colon cancer were eligible for this study. Mean preoperative plasma fibrinogen levels were 325.24±88.19 mg/dl. Higher preoperative plasma fibrinogen levels were associated with sex (male), old age, poorly/mucinous differentiated tumor, advanced tumor stage, elevated carcinoembryonic antigen (CEA) levels, higher modified Glasgow Prognostic Score, and higher neutrophil:lymphocyte and platelet:lymphocyte ratios. In multivariate analysis, elevated plasma fibrinogen level [disease-free survival: hazard ratio (HR) 1.999, 95% confidence interval (95% CI) 1.081-3.695, P=.027; overall survival: HR 3.138, 95% CI 1.077-9.139, P=.036], advanced tumor stage, and higher CEA levels were independently associated with worse disease-free survival and overall survival. None of the inflammation-based scores were significantly associated with survival. CONCLUSIONS: Fibrinogen as one of inflammatory markers may be considered a possible prognostic marker in colon cancer.

Predictive value of (18)FDG PET-CT for tumour response in patients with locally advanced rectal cancer treated by preoperative chemoradiotherapy.

PURPOSE: Although (18)fluorine-2-deoxy-D-glucose positron emission tomography-computed tomography ((18)FDG PET-CT) is considered a reliable modality for determining tumour response after neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC), the role of (18)FDG PET-CT for predicting pathologic complete response (pCR) remains unclear. The aim of this study was to evaluate whether (18)FDG PET-CT can predict tumour response after CRT in patients with LARC, in terms of downstaging and pCR. METHODS: Between March 2009 and February 2012, 151 patients with LARC treated with neoadjuvant CRT followed by radical surgery were reviewed retrospectively. Pre-CRT SUVmax (maximum standardized uptake value), post-CRT SUVmax, ΔSUVmax (difference between pre- and post-CRT SUVmax), and RI-SUV (response index) were measured before and after CRT. Univariate and multivariate analyses were used to analyse the association of PET-CT-related parameters and clinical variables, to assess downstaging and pCR. RESULTS: Downstaging occurred in 48 patients (31.7 %) and pCR in 19 patients (12.5 %). Univariate and multivariate analysis revealed post-CRT SUVmax as a significant factor for prediction of downstaging, with sensitivity of 60.4 %, specificity of 65.0 %, and accuracy of 55.9 %, for a cutoff value of 3.70. Regarding pCR, post-CRT SUVmax was again found as a significant parameter by univariate and multivariate analysis, with sensitivity of 73.7 %, specificity of 63.7 %, and accuracy of 64.9 %, for a cutoff value of 3.55. CONCLUSIONS: The results indicate that post-CRT SUVmax independently predicts downstaging and pCR. However, the predictive values of post-CRT SUVmax for tumour response after neoadjuvant CRT are too low in sensitivity and specificity to change the treatment plan for LARC.

Left-sided ileostomy at specimen extraction site in laparoscopic-assisted low anterior resection for rectal cancer.

BACKGROUND: Prophylactic ileostomy is usually created at the right lower quadrant (RLQ) because of its vicinity to the ileocecal valve. In the laparoscopic procedure, however, another wound is required for stoma, resulting in a scar after takedown. This study assessed the feasibility of left-sided ileostomy (LI) at the specimen extraction site in laparoscopic-assisted low anterior resection (LAR) for rectal cancer. SUBJECTS AND METHODS: One hundred five patients underwent laparoscopic LAR with diverting ileostomy for rectal cancer. Among them, 82 (78.1%) received preoperative chemoradiotherapy (CRT). Diverting stomas were created in the RLQ in 49 (46.7%) and in the left lower quadrant in 53 patients (53.3%). We compared surgical morbidity and recovery data between the right-sided ileostomy (RI) and LI groups. RESULTS: The two groups were similar with regard to age, sex, type of CRT, distance from the anal verge, and TNM stage. Parastomal hernia developed in 3 patients (1 in RI, 2 in LI) and postoperative ileus in 10 patients (4 in RI, 6 in LI). The frequency of complications showed no difference between the two groups (10.2% in RI, 14.3% in LI; P=.53). There was also no difference in terms of time to resumption of regular diet (2.9 versus 3.2 days; P=.25) or length of hospital stay (7.9 versus 7.7 days; P=.61). CONCLUSIONS: LI in laparoscopic LAR was not associated with increased postoperative morbidity or delay in postoperative recovery. Because it can provide better cosmesis, it would be a possible option for diversion in laparoscopic LAR.

Cost-comparison of laparoscopic and open surgery for mid or low rectal cancer after preoperative chemoradiotherapy: data from a randomized controlled trial.

BACKGROUND: The purpose of the present study was to compare the direct costs of laparoscopic surgery (LS) and open surgery (OS) in the treatment of mid or low rectal cancer after preoperative chemoradiotherapy in patients in Korea. METHODS AND RESULTS: The records of 130 LS patients and 125 OS patients were reviewed. Hospital stay after surgery and overall complication rates within three months of surgery were not significantly different. The LS group had significantly higher median costs than the OS group ($7,467.30 vs. $5,667.00; P < 0.001). The median hospital costs during hospitalization for surgery were higher in the LS group ($7,436.60 vs. $5,626.60; P < 0.001), but hospital costs for management of early postoperative complications were similar. The higher direct costs of LS were mainly due to the more expensive consumables and equipment needed for LS. CONCLUSIONS: Further study is needed to determine whether the higher direct costs of LS for rectal cancer are balanced by advantages of LS over OS, such as better short-term outcomes and cosmetic effect.

Factors associated with complete local excision of small rectal carcinoid tumor.

PURPOSE: Although small rectal carcinoid tumors can be treated using local excision, complete resection can be difficult because tumors are located in the submucosal layer. We evaluate the factors associated with pathologically complete local resection of rectal carcinoid tumors. METHODS: Data were analyzed of 161 patients with 166 rectal carcinoid tumors who underwent local excision with curative intent from January 2001 to December 2010. A pathologically complete resection (P-CR) was defined as an en bloc resection with tumor-free lateral and deep margins. The study classified treatments into three categories for analysis: conventional polypectomy (including strip biopsy, snare polypectomy, and hot biopsy), advanced endoscopic techniques (including endoscopic mucosal resection with cap and endoscopic submucosal dissection), and surgical local excision (including transanal excision and transanal endoscopic microsurgery). We evaluated the P-CR rate according to treatment method, tumor size, initial endoscopic impression and the use of endoscopic ultrasound (EUS) or transrectal ultrasound (TRUS). RESULTS: The mean tumor size was 5.51 ± 2.43 mm (range 2-18 mm) and all lesions were confined to the submucosal layer. The P-CR rates were 30.9, 72.0, and 81.8 % for conventional polypectomy, advanced endoscopic techniques, and surgical local excision, respectively. Univariate analysis showed that P-CR was associated with treatment method, use of EUS or TRUS, and initial endoscopic impression. Multivariate analysis showed that only treatment method was associated with P-CR. CONCLUSION: Pathologically complete resection of small rectal carcinoid tumors was more likely to be achieved when using advanced endoscopic techniques or surgical local excision rather than conventional polypectomy.

Laparoscopic versus open surgery for stage I rectal cancer: long-term oncologic outcomes.

BACKGROUND: Laparoscopic resection is increasingly being performed for rectal cancer. However, few data are available to compare long-term outcomes after open versus laparoscopic surgery for early-stage rectal cancer. METHODS: Included in this retrospective study were 160 patients who underwent surgery for stage I rectal cancer between 2001 and 2008. Perioperative outcomes, overall survival (OS), and disease-free survival (DFS) were compared for open versus laparoscopic surgery. RESULTS: Altogether, 85 patients were treated using open surgery and 80 with laparoscopic surgery. Postoperative mortality (0 vs. 1.3%; p = 1.00), morbidity (31.3 vs. 25.0%; p = 0.38), and harvested lymph nodes (22.5 vs. 20.0; p = 0.84) were similar for the two groups. However, operating time was longer (183.8 vs. 221.0 min; p = 0.008), volume of intraoperative bleeding was less (200.0 vs. 150.0 ml; p = 0.03), time to first bowel movement was shorter (3.54 vs. 2.44 days; p < 0.001), rate of superficial surgical-site infection was lower (7.5 vs. 0%; p = 0.03), and postoperative hospital stay was shorter (11.0 vs. 8.0 days; p < 0.001) in the laparoscopy group than in the open surgery group. At 5 years, there was no difference in OS (98.6 vs. 97.1%; p = 0.41) or DFS (98.2 vs. 96.4%; p = 0.30) between the open and laparoscopy groups. CONCLUSIONS: Long-term outcomes of laparoscopic surgery for stage I rectal cancer were comparable to those of open surgery. Laparoscopic surgery, however, produced more favourable short-term outcomes than open surgery.

New application of dual point 18F-FDG PET/CT in the evaluation of neoadjuvant chemoradiation response of locally advanced rectal cancer.

PURPOSE: FDG PET/CT has been suggested as the most reliable modality to predict pathological tumor responses after neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC). However, several confounding factors including radiation-induced inflammation could not be easily avoided with the commonly used single-point FDG PET/CT. Our aim was to evaluate the accuracy of a dual-point PET/CT protocol in LARC response prediction to CRT. PATIENTS AND METHODS: Sixty-one LARC patients were enrolled and treated with neoadjuvant CRT. PET/CT was performed before and after CRT. Dual-point acquisition was applied to post-CRT PET/CT. Post-CRT SUVmax (postSUV), pre/post-CRT SUVmax change (RI), and dual-point index (DI) of post-CRT PET/CT were compared with the Dworak tumor regression grade (TRG) as a gold standard. Univariate and multivariate analyses, as well as receiver operating characteristic curve analysis, were used to evaluate the predictive ability of demographic, clinical, and metabolic PET parameters. RESULTS: Fifteen patients of TRG3-4 were defined as pathological responders, and 46 patients of TRG1-2 were nonresponders. The resulting response index (RI) ranged from -13 to 94.8% (59.1±22.0%), and delay index (DI) ranged from -45.2 to 25.0% (-9.1±12.1%). Univariate analysis resulted in PET parameters (postSUV, RI, and DI) as significant predictors (P=0.004, P<0.001, P<0.0001). According to multivariate analysis, RI and DI remained as significant predictors (P=0.04 and P=0.0004). Receiver operating characteristic analysis showed that DI had significantly higher area under the curve compared with RI (0.906 vs 0.696, P=0.018). Delay index had 86.7% sensitivity, 87.0% specificity, 68.4% positive predictive value, 95.2% negative predictive value, and 86.9% accuracy. CONCLUSIONS: Dual-point post-CRT PET/CT can predict pathological tumor response better than conventional single time point pre- and post-CRT PET/CT.

Tumor budding and recurrence in submucosal invasive colorectal cancers of favorable histology: case reports of two early colorectal cancers with advanced recurrences.

Complete resection of submucosal invasive colorectal cancer (SICC) showing favorable histology is regarded as curative. We report on two cases of SICC showing recurrence within 5 years despite complete resection. The first patient was a 68-year-old woman with well differentiated rectal adenocarcinoma invading the superficial submucosa, which recurred after 4.7 years. The second patient was a 53-year-old man with pT1N0 moderately differentiated colonic adenocarcinoma. He developed widespread tumor recurrence after 3.9 years. Retrospective pathologic review of the original tumors showed multiple foci of tumor budding at the invasive front. Immunohistochemical staining for D2-40 of deeper levels of the paraffin blocks showed rare foci of small lymphatic invasion. Tumor budding at the invasive front may be an important indicator for SICC aggressiveness or may reflect early lymphatic invasion. More aggressive pathologic examination and follow-up is required for patients with SICC showing tumor budding, even in the absence of unfavorable histologic findings.

Clinical outcomes of palliative self-expanding metallic stents in patients with malignant colorectal obstruction.

OBJECTIVE: Self-expanding metallic stents (SEMS) are useful palliative option and a bridge to surgery in malignant colorectal obstruction. The aim of this study was to evaluate the clinical outcomes of SEMS to palliate colorectal malignant obstruction. METHODS: Malignant colorectal obstructive patients who underwent SEMS insertion at the National Cancer Center, Korea from January 2004 to June 2008 were enrolled in the study. Patients' clinical characteristics, outcomes and complications for palliative SEMS insertion were retrospectively analyzed. RESULTS: A total of 54 patients were enrolled in the palliative SEMS group and 48 patients with obstructive CRC were included in the SEMS as the bridge to surgery group. Obstruction of the left colon occurred in 52 patients of the palliative SEMS group and all patients in SEMS as bridge to surgery group. For primary SEMS insertion, the technical success (TS) rate was 87.0% and the clinical success (CS) rate 89.4%, while the rates of early and late complications were 24.1% and 23.4%, respectively. There was no procedure-related mortality. Stent migration rate was higher in the cases treated with small diameter and covered type of stents. Median time to reobstruction and migration were 85 and 101 days, respectively. TS and CS rates for SEMS reinsertion were comparable to those for primary SEMS insertion. CONCLUSIONS: Palliative SEMS are effective and favorable procedures for malignant colorectal obstruction but with some complications. Stent migration is associated with covered type and small diameter stents while other factors including length of stent and chemotherapy do not affect stent complications in the present study.

Association of colorectal adenoma with components of metabolic syndrome.

PURPOSE: Recently, some studies have shown that diabetes mellitus and metabolic syndrome increase the risk of colorectal neoplasms. Although the mechanism is not known, those have been proposed to contribute to this phenomenon, including insulin resistance, oxidative stress, and adipokine production. The objective of this study was to assess the association between metabolic risk factors and colorectal neoplasm. METHODS: Study participants visited the National Cancer Center, Korea, for screening (2007-2009). A total of 1,771 diagnosed adenoma patients and 4,667 polyp-free controls were included. The association between risk factors and colorectal neoplasm was evaluated using logistic regression models. RESULTS: High waist circumference, blood pressure, and serum triglyceride levels were associated with an increased risk of colorectal adenoma. Metabolic syndrome (MS) was associated with an increased risk of adenoma (OR = 1.44, 95 % CI = 1.23-1.70). The association between MS and colorectal adenoma was observed regardless of advanced/low-risk adenoma, and multiplicity. MS affected right colon adenomas (OR = 1.50, 95 % CI = 1.22-1.85), left colon adenomas (OR = 1.36, 95 % CI = 1.05-1.76), and adenomas in multiple anatomical locations (OR = 1.59, 95 % CI = 1.19-2.12), but was not associated with rectum. CONCLUSION: Central obesity, triglyceride level, and MS are risk factors for colorectal adenoma including advanced adenoma and multiplicity.

Stage-to-stage comparison of preoperative and postoperative chemoradiotherapy for T3 mid or distal rectal cancer.

PURPOSE: To investigate, in a comparative analysis, the prognostic implications of postchemoradiotherapy (post-CRT) pathologic stage (ypStage) vs. postoperative pathologic stage (pStage) in rectal cancer. METHODS AND MATERIALS: Between May 2001 and December 2006, 487 patients with T3 mid or distal rectal cancer were analyzed retrospectively. Concurrent CRT was administered preoperatively (n = 364, 74.7%) or postoperatively (n = 123, 25.3%). The radiation dose was 50.4 Gy in 28 fractions. All patients underwent a total mesorectal excision and received adjuvant chemotherapy. Disease-free survival (DFS) was estimated using the Kaplan-Meier method. Differences in DFS, stratified by ypStage and pStage, were compared using the log-rank test. RESULTS: For surviving patients, the median follow-up period was 68 months (range, 12-105 months). The 5-year local recurrence-free survival rate was not different, at 95.3% and 92.1% in preoperative and postoperative CRT groups, respectively (p = 0.402), but the 5-year distant metastasis-free survival rate was significantly different, at 81.6% (preoperative CRT) vs. 65.4% (postoperative CRT; p = 0.001). The 5-year DFS rate of 78.8% in the preoperative CRT group was significantly better than the 63.0% rate in the postoperative CRT group (p = 0.002). Post-CRT pathologic Stage 0-I occurred in 42.6% (155 of 364) of the patients with preoperative CRT. The 5-year DFS rates were 90.2% (ypStage 0-I), 83.5% (ypStage II), 77.3% (pStage II), 58.6% (ypStage III), and 54.7% (pStage III). The DFS rate of ypStage 0-I was significantly better than that of ypStage II or pStage II. Post-CRT pathologic Stage II and III had similar DFS, compared with pStage II and III, respectively. CONCLUSIONS: Disease-free survival predicted by each ypStage was similar to that predicted by the respective pStage. Improved DFS with preoperative vs. postoperative CRT was associated with the ypStage 0-I group that showed a similarly favorable outcome to pStage I rectal cancer.

Is step section necessary for determination of complete pathological response in rectal cancer patients treated with preoperative chemoradiotherapy?

AIMS: To assess the efficacy of the step section for determination of pathological complete response (pCR) in rectal cancer treated with preoperative chemoradiotherapy (CRT). METHODS AND RESULTS: Of 709 patients with rectal cancer who received preoperative CRT, 88 were initially diagnosed as having pCR. These 88 patients were re-evaluated after two-level step sections of the entire tumour by using Dworak's regression grade. Additional serial step sections revealed residual tumour cells in seven of 88 patients (7.95%), all of whom were upgraded to regression grade 3 (near total regression) from regression grade 4 (total regression). Of these seven patients, one (14.3%) showed tumour recurrence, compared with 11 of 81 (13.6%) patients with a final regression grade of 4. Neither recurrence rate nor disease-free survival rate differed significantly between these two groups (P > 0.5). Calcification was significantly more frequent in grade 3 than in grade four patients (71.4% versus 32.1%; P = 0.037), and acellular mucin pools were associated with better disease-free survival (P = 0.022). CONCLUSIONS: Stratifying patient outcome by final regression grade after step section did not yield different outcomes in patients with initial pCR. If residual tumour cells are not identified on initial meticulous examination, further processing of step sections is not necessary.

Is the N1c category of the new American Joint Committee on cancer staging system applicable to patients with rectal cancer who receive preoperative chemoradiotherapy?

BACKGROUND: Pericolorectal tumor deposits (TDs) are associated with adverse outcomes in patients with colorectal cancer, and the seventh edition of the American Joint Committee on Cancer (AJCC) staging system recently classified TDs without regional lymph node metastasis as category N1c. However, the definition of TDs has varied. Moreover, with the recent, widespread application of preoperative chemoradiotherapy (CRT) in rectal cancers, residual primary tumor confined to the mesorectum is not infrequent, and it is unclear whether the N1c category is appropriate for these tumors. METHODS: To evaluate the prognostic significance of the N1c classification in patients with rectal cancers after preoperative CRT, the authors reviewed the histologic features of 136 rectal cancers that were classified previously with a tumor classification of 3 [T3], negative lymph nodes [N0], and no metastasis [M0] based on the pathologic extent of disease (ypT3N0M0). These tumors were reclassified according to the new AJCC staging system, and patient outcomes were analyzed. RESULTS: Perirectal TDs were detected in 16 of 136 patients (11.8%). Patterns of TD included a separate nodule pattern in 6 patients (38%), a perivascular pattern in 4 patients (25%), a perineural pattern in 4 patients (25%), and a lymphatic pattern in 2 patients (12%). By using the new N1c category, 120 patients (88.2%) were classified with yp-stage IIA disease, 6 patients (4.4%) were classified with yp-stage IIIA disease, and 10 patients (7.4%) were classified with yp-stage IIIB disease. Kaplan-Meier survival analysis indicated that there were no significant differences between the TD-positive and TD-negative groups in disease-free survival (DFS) or overall survival (OS) (P = .48 for both; log-rank test). In addition, the reclassified TMN stage was not related to DFS (P = .17) or OS (P = .072). CONCLUSIONS: The category N1c may not be appropriate for patients with rectal cancer after preoperative CRT, because the definition of ypN1c was confusing and did not have prognostic significance.

Prognostic significance of distribution of lymph node metastasis in advanced mid or low rectal cancer.

BACKGROUND: Few studies have focused on distribution of lymph node metastasis. The aim of this study is to evaluate the prognostic significance of the location of involved lymph nodes in patients with advanced mid or low rectal cancer. METHODS: We defined proximal lymph node involvement (PLNp) as superior rectal and inferior mesenteric lymph node metastasis along the trunks of the supplying vessel, and mesorectal lymph node involvement (MLNp) as lymph node metastasis located within the mesorectum. RESULTS: PLNp was identified in 67 patients (8.4%) of total 797 patients. Age <60 years (P=0.02), poorly differentiated/mucinous histologic type (P=0.011), and positive perineural invasion (P<0.001) were risk factors of PLNp in patients with node positive rectal cancer. Patients with PLNp had poorer oncologic outcomes than those without PLNp in terms of overall survival (P<0.001). For patients with node-positive rectal cancer, there was significant difference in the overall survival rate between PLNp and MLNp groups, regardless of N stage (P=0.025 for N1, P=0.009 for N2). CONCLUSIONS: Our results suggest that PLNp is associated with adverse oncologic outcomes and has prognostic significance in patients with node positive mid or low rectal cancer.