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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Castleman's disease of the mesorectum: report of a case.

Castleman's disease is a benign lymphoid proliferative disorder, which most commonly presents as a solitary mass in the mediastinum, although extrathoracic sites have been reported in the neck, axilla, pelvis, mesentery, pancreas, and retroperitoneum. We report a case of asymptomatic, isolated Castleman's disease in the mesorectum, which is extremely rare. The patient was a 34-year-old woman who underwent investigations for vaginal spotting. A presacral mass was located on the left side of the rectum, 10 cm from the anal verge. Contrast-enhanced computed tomography showed a large, well-demarcated, strongly enhancing mass with internal radiating septa in the mesorectum. The mass was well circumscribed and isointense to muscle on T1-weighted magnetic resonance imaging, appearing as a slightly hyperintense mass on T2-weighted imaging. We performed laparoscopic mesorectal mass excision, and histological examination revealed features typical of the hyaline-vascular type of Castleman's disease. Thus, when a mesorectal mass is being investigated, Castleman's disease should be considered in the differential diagnosis.

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

BACKGROUND: The safety and short-term efficacy of laparoscopic surgery for rectal cancer after preoperative chemoradiotherapy has not been demonstrated. The aim of the randomised Comparison of Open versus laparoscopic surgery for mid and low REctal cancer After Neoadjuvant chemoradiotherapy (COREAN) trial was to compare open surgery with laparoscopic surgery for mid or low rectal cancer after neoadjuvant chemoradiotherapy. METHODS: Between April 4, 2006, and Aug 26, 2009, patients with cT3N0-2 mid or low rectal cancer without distant metastasis after preoperative chemoradiotherapy were enrolled at three tertiary-referral hospitals. Patients were randomised 1:1 to receive either open surgery (n=170) or laparoscopic surgery (n=170), stratified according to sex and preoperative chemotherapy regimen. Short-term outcomes assessed were involvement of the circumferential resection margin, macroscopic quality of the total mesorectal excision specimen, number of harvested lymph nodes, recovery of bowel function, perioperative morbidity, postoperative pain, and quality of life. Analyses were based on the intention-to-treat population. Patients continue to be followed up for the primary outcome (3-year disease-free survival). This study is registered with ClinicalTrials.gov, number NCT00470951. FINDINGS: Two patients (1.2%) in the laparoscopic group were converted to open surgery, but were included in the laparoscopic group for analyses. Estimated blood loss was less in the laparoscopic group than in the open group (median 217.5 mL [150.0-400.0] in the open group vs 200.0 mL [100.0-300.0] in the laparoscopic group, p=0.006), although surgery time was longer in the laparoscopic group (mean 244.9 min [SD 75.4] vs 197.0 min [62.9], p<0.0001). Involvement of the circumferential resection margin, macroscopic quality of the total mesorectal excision specimen, number of harvested lymph nodes, and perioperative morbidity did not differ between the two groups. The laparoscopic surgery group showed earlier recovery of bowel function than the open surgery group (time to pass first flatus, median 38.5 h [23.0-53.0] vs 60.0 h [43.0-73.0], p<0.0001; time to resume a normal diet, 85.0 h [66.0-95.0] vs 93.0 h [86.0-121.0], p<0.0001; time to first defecation, 96.5 h [70.0-125.0] vs 123 h [94.0-156.0], p<0.0001). The total amount of morphine used was less in the laparoscopic group than in the open group (median 107.2 mg [80.0-150.0] vs 156.9 mg [117.0-185.2], p<0.0001). 3 months after proctectomy or ileostomy takedown, the laparoscopic group showed better physical functioning score than the open group (0.501 [n=122] vs -4.970 [n=128], p=0.0073), less fatigue (-5.659 [n=122] vs 0.098 [n=129], p=0.0206), and fewer micturition (-2.583 [n=122] vs 4.725 [n=129], p=0.0002), gastrointestinal (-0.400 [n=122] vs 4.331 [n=129], p=0.0102), and defecation problems (0.535 [n=103] vs 5.327 [n=99], p=0.0184) in repeated measures analysis of covariance, adjusted for baseline values. INTERPRETATION: Laparoscopic surgery after preoperative chemoradiotherapy for mid or low rectal cancer is safe and has short-term benefits compared with open surgery; the quality of oncological resection was equivalent.

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.

Influence of preoperative chemoradiotherapy on the number of lymph nodes retrieved in rectal cancer.

OBJECTIVE: To evaluate the relation of preoperative chemoradiotherapy to the number of lymph nodes retrieved in curative intent surgery for rectal cancer. SUMMARY BACKGROUND DATA: Current guidelines recommend evaluation of least 12 to 14 lymph nodes in rectal cancer. It is well known that lymph nodes retrieval is affected by many factors. METHODS: This was a retrospective study of 615 patients who underwent curative intent surgery for primary rectal cancer. Preoperative chemoradiotherapy involving 50.4 Gy fractionated radiotherapy and concurrent chemotherapy was performed in patients with locally advanced rectal cancer (clinically T3 or T4). We explored associations between the number of lymph nodes retrieved in the pathologic specimen and patient demographics (age, gender, body mass index [BMI]), treatment (surgeon, sphincter-saving, preoperative chemoradiotherapy), and tumor-related variables (location, stage, histology). After adjustment for other factors, we compared the mean number of obtained lymph nodes between patients treated with preoperative chemoradiotherapy and those treated without preoperative chemoradiotherapy. RESULTS: Univariate analysis demonstrated that age, BMI, preoperative chemoradiotherapy, location, and stage significantly related the number of lymph nodes retrieved. Multivariate analysis revealed age, BMI, preoperative chemoradiotherapy, and stage as independent factors influencing the number of lymph nodes retrieved. The mean number of lymph nodes adjusted for age, BMI, and stage was significantly lower in patients treated with preoperative chemoradiotherapy than in those treated without preoperative chemoradiotherapy (14.5 vs. 21.5, P < 0.001). The reduction rate by preoperative chemoradiotherapy was 32.6% (7/21.5). In patients who underwent preoperative chemoradiotherapy, advanced age (P < 0.001) and high BMI (P = 0.037) were associated with decreased number of retrieved lymph nodes. CONCLUSIONS: Preoperative chemoradiotherapy significantly decreased the number of retrieved lymph nodes by approximately 33%. Therefore, the recommended number of retrieved lymph nodes should be adjusted when rectal cancer is treated with preoperative chemoradiotherapy.

Absence of hMLH1 or hMSH2 expression as a stage-dependent prognostic factor in sporadic colorectal cancers.

BACKGROUND: The predictive role of mismatch repair (MMR) status for survival after sporadic colorectal cancer remains a point of controversy. This study was designed to test the prognostic value of MMR status in sporadic colorectal cancers. METHODS: The study included 318 patients with sporadic colorectal cancer who underwent primary tumor resection. MMR status was determined by the immunohistochemical analysis of hMLH1 and hMSH2 expression. RESULTS: Thirty-six carcinomas (11.3%) showed abnormal MMR protein expression (22 hMLH1 negative and 14 hMSH2 negative) and were classified as MMR-defective tumors. An MMR defect was strongly associated with a reduced likelihood of lymph node (odds ratio, 0.32; 95% confidence interval [95% CI], 0.13-0.75) or distant organ metastases at diagnosis (odds ratio, 0.07; 95% CI, 0.01-0.62), independent of the clinicopathological features. Overall survival was significantly better in patients with MMR-defective tumors than in those with MMR-intact tumors (P = 0.013). In the subgroup analysis by stage, adjusted for other potential confounding variables, MMR status was not a statistically significant prognostic factor in stage I and II patients, while the MMR defect predicted a significantly better overall survival in stage III and IV patients (adjusted hazard ratio, 0.23; 95% CI, 0.06-0.97; P = 0.045). CONCLUSIONS: At initial diagnosis, metastases were found at lower rates in MMR-defective tumors. MMR status may be a stage-dependent prognostic factor in patients with sporadic colorectal cancer.

Intestinal complications after palliative treatment for asymptomatic patients with unresectable stage IV colorectal cancer.

BACKGROUND: The initial surgical management of asymptomatic patients with unresectable stage IV colorectal cancer (CRC) is still controversy. The aim of this study was to compare the incidence of major intestinal complications in asymptomatic patients who received palliative treatment for unresectable stage IV CRC, according to the type of treatment. METHODS: Between March 2001 and January 2008, we retrospectively analyzed 227 asymptomatic patients who underwent first-line resection of the primary tumor followed by chemotherapy (144 patients, resection group) or those who underwent first-line chemotherapy (83 patients, chemotherapy group). RESULTS: In the resection group, the incidences of intestinal obstruction, peritonitis, fistula, and intestinal hemorrhage were 14.6%, 0%, 0.7%, and 4.8%, respectively. In the chemotherapy group, these incidences were 15.2%, 1.2%, 0%, and 3.5%, respectively. There were no significant differences between the two groups in terms of intestinal complications. In multivariate analysis of overall survival, treatment type (resection group vs. chemotherapy group) was not a significant prognostic factor (P = 0.076). CONCLUSIONS: In asymptomatic patients with unresectable stage IV CRC, first-line chemotherapy may be considered safe, with no increased risk of major intestinal complications compared with primary tumor resection plus chemotherapy.

The role of omental flap transposition in patients with locoregional recurrent rectal cancer treated with reirradiation.

BACKGROUND AND OBJECTIVES: We performed reirradiation after omental flap transposition (OFT) in patients with locoregional recurrent rectal cancer (LRRC) and evaluated the effect of OFT on the irradiated small bowel by comparing the displacement of the small bowel from the radiation field before and after OFT. METHODS: Between October 2005 and October 2008, this study included 12 patients with LRRC who had previously received radiotherapy. To evaluate the effect of OFT on the irradiated volume of the small bowel and bladder, we measured the closest distances between the small bowel and the tumor or tumor bed (distance(SB)) and between the bladder and tumor or tumor bed (distance(BL)) before and after OFT, respectively. RESULTS: The median distance(SB) before and after OFT was 5 and 30 mm, respectively (P < 0.001). The median distance(BL) before and after OFT was 10 and 23 mm, respectively (P = 0.002). The respective overall survival and local control rates at 3 years were 50.9% and 54.6%, respectively. No severe complication occurred of grade 3 or higher involving the small bowel or bladder. CONCLUSIONS: In our study, OFT effectively excluded small bowel from the radiation field. In addition, selective reirradiation after OFT was feasible for patients with LRRC.