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Summary 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.

The history of a yacht began with a sail attached to a vessel, and such yachting is the game competing Received (January 21, 2016), Review Result (February 4, 2016) Accepted (February 15, 2016), Published (March 31, 2016) 58245 DCRC, DongShin Univ., Geonjae-ro 185, Naju, Jeonnam, Korea email: jhyoun@dsu.ac.kr 58564 JCIA, Oryong 3-gil 2, Samhyang-eup, Muan-gun, Jeonnam, Korea email: Ochy1@naver.com (Corresponding Author) 58245 Dept., of Digital

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.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.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; p0·0001). 25 (15%) patients died in the open group and 20 (12%) died in the laparoscopic group. No deaths were treatment related.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.National Cancer Center, South Korea.

Background Reduced-volume bowel preparation with a low-residue diet prior to colonoscopy would result in better patient compliance and sufficient bowel preparation. Objective To compare the clinical efficacy of reduced-volume sodium picosulfate and a prepackaged low-residue diet with that of the standard bowel preparation using 4 L of PEG solution. Design Prospective, single center, single blind, active control, randomized study (NCCCTS-12-619, KCT0000470). Setting Ambulatory outpatient clinic at the National Cancer Center, Republic of Korea. Patients A total of 194 subjects were randomly assigned for this study, 97 in each group. After exclusions, 94 subjects in the Picolight group and 90 in the PEG group completed the study and were analyzed. Interventions Sodium picosulfate with a prepackaged low-residue, one-day diet or 4-L PEG for bowel preparation. Main outcome measures Success rate of the bowel preparation, tolerability, adverse events, cecal intubation time, polyp detection rate and adenoma detection rate. Results The bowel preparation success rate was significantly higher (91.5% vs. 81.1%, p = 0.04) and the rates of adverse events, including abdominal distension, pain, nausea, vomiting and abdominal discomfort, were significantly lower in the picosulfate group than the PEG group. Cecal intubation times and the polyp and adenoma detection rates were similar in the 2 groups. Limitations Single center, limited population, all colonoscopies were performed in the morning. Conclusions Bowel preparation with low-volume oral picosulfate and a prepackaged low-residue diet enhances colon cleansing and is better tolerated than the standard bowel preparation.

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).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, CRM2 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.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, P0.0001, 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, P0.0001, respectively).After preoperative CRT, CRM distance provides useful information for risk stratification in the recurrence of rectal 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.

Determination of theflow stress of materials at high strain rate is very important in automotive and military areas.The compressive flow stress at high strain rate can be obtained relativelyexactly by SHPB(Split Hopkinson Pressure Bars) tests. However, it is difficult to determinethe flow stressexactlyin the tensile state by using the SHPB tests. The difficulty in the tensile SHPB tests is how to fix a specimen on two bars. So, the design of a specimen and holders is needed to obtain more accurate measurement of the flow stress. In this study, the accuracy of the tensile SHPB tests results was numerically investigated. Finite element analyses of the tensile SHPB were carried out for various cases of fixing bolt location and bolting force. From the analysis results, a design guide for the fixing structure was obtained and the causes of error were investigated.

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. 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. 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

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.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.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.Fibrinogen as one of inflammatory markers may be considered a possible prognostic marker in colon cancer.

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.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.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.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.

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. 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. 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

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. 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

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. 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). 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. 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.

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.

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.

목적(Purpose) : 본 연구의 목적은 장폐쇄 증상이 있는 완전 절제가 불가능한 4기 대장암 환자에서 완화 목적의 자가팽창금속스텐트를 시술한 경우와 완화 목적으로 수술을 시행한 경우의 장기 임상 성적을 분석하는 것이다. 대상 및 방법(Methods) : 2002년 1월부터 2010년 5월까지, 완화 스텐트 삽입(n = 88)과 완화 수술을 시행한(n = 96)환자들을 대상으로 스텐트 삽입 및 수술의 성공률, 합병증, 재원기간, 합병증 발생까지의 기간, 항암치료까지의 기간, 전체 생존률을 분석하고, 생존률과 관련한 예후인자를 평가하였다. 결과(Results) : 스텐트군의 초기 합병증은 수술군보다 낮았으나(26.1% vs 47.9%, P = 0.002), 후기 합병증과 주요 합병증 발생률이 더 많았다(P ＜ 0.05). 또한, 스텐트 시술 후 발생하는 장관련 합병증의 비율은 수술군보다 더 많았다(P = 0.037). 수술군에서의 전체 생존기간 중앙값은 스텐트군보다 더 높았고(15.7개월 vs. 9.1개월), 시술 또는 수술 후 합병증으로 인해 추가로 치료를 받아야 하는 경우도 스텐트군에서 많았다(P＜0.001). 결론 (Conclusions) : 스텐트 삽입은 상대적으로 덜 침습적이며 빠른 증상 호전을 기대할 수 있다. 그러나, 완화 목적의 스텐트 삽입은 완화 수술 보다 후기 합병증 발생 빈도가 높아 환자의 원발 병소, 증상 정도, 등의 환자 상태를 고려하여 적절한 완화치료를 고려할 필요가 있다.

Park S Y, Chang H J, Kim D Y, Jung K H, Kim S Y, Park J W, Oh J H, Lim S-B, Choi H S & Jeong S-Y (2011) Histopathology59, 650–659 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.

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

Purpose Preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer has shown benefit over postoperative CRT; however, a standard CRT regimen has yet to be defined. We performed a prospective concurrent CRT Phase II study with irinotecan and capecitabine in patients with locally advanced rectal cancer to investigate the efficacy and safety of this regimen. Methods and Materials Patients with locally advanced, nonmetastatic, and mid-to-lower rectal cancer were enrolled. Radiotherapy was delivered in 1.8-Gy daily fractions for a total of 45 Gy in 25 fractions, followed by a coned-down boost of 5.4 Gy in 3 fractions. Concurrent chemotherapy consisted of 40 mg/m 2 of irinotecan per week for 5 consecutive weeks and 1,650 mg/m 2 of capecitabine per day for 5 days per week (weekdays only) from the first day of radiotherapy. Total mesorectal excision was performed within 6 ± 2 weeks. The pathologic responses and survival outcomes were included for the study endpoints. Results In total, 48 patients were enrolled; 33 (68.7%) were men and 15 (31.3%) were women, and the median age was 59 years (range, 32–72 years). The pathologic complete response rate was 25.0% (11 of 44; 95% confidence interval, 12.2–37.8) and 8 patients (18.2% [8 of 44]) showed near-total tumor regression. The 5-year disease-free and overall survival rates were 75.0% and 93.6%, respectively. Grade 3 toxicities included leukopenia (3 [6.3%]), neutropenia (1 [2.1%]), infection (1 [2.1%]), alanine aminotransferase elevation (1 [2.1%]), and diarrhea (1 [2.1%]). There was no Grade 4 toxicity or treatment-related death. Conclusions Preoperative CRT with irinotecan and capecitabine with treatment-free weekends showed very mild toxicity profiles and promising results in terms of survival.

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 (distanceSB) and between the bladder and tumor or tumor bed (distanceBL) before and after OFT, respectively. Results The median distanceSB before and after OFT was 5 and 30 mm, respectively (P

Purpose We retrospectively evaluated the effects of clinical and pathologic factors on disease-free survival (DFS) with the aim of identifying the most discriminating factor predicting DFS in rectal cancer patients treated with preoperative chemoradiotherapy (CRT) and curative resection. Methods and Materials The study involved 420 patients who underwent preoperative CRT and curative resection between August 2001 and October 2006. Gender, age, distance from the anal verge, histologic type, histologic grade, pretreatment carcinoembryonic antigen (CEA) level, cT, cN, cStage, circumferential resection margin, type of surgery, preoperative chemotherapy, adjuvant chemotherapy, ypT, ypN, ypStage, and tumor regression grade (TRG) were analyzed to identify prognostic factors associated with DFS. To compare the discriminatory prognostic ability of four tumor response–related pathologic factors (ypT, ypN, ypStage, and TRG), the Akaike information criteria were calculated. Results The 5-year DFS rate was 75.4%. On univariate analysis, distance from the anal verge, histologic type, histologic grade, pretreatment CEA level, cT, circumferential resection margin, type of surgery, preoperative chemotherapeutic regimen, ypT, ypN, ypStage, and TRG were significantly associated with DFS. Multivariate analysis showed that the four parameters ypT, ypN, ypStage, and TRG were, consistently, significant prognostic factors for DFS. The ypN showed the lowest Akaike information criteria value for DFS, followed by ypStage, ypT, and TRG, in that order. Conclusion In our study, ypT, ypN, ypStage, and TRG were important prognostic factors for DFS, and ypN was the most discriminating factor.

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. J. Surg. Oncol. J. Surg. Oncol. 2010;102:94–99. © 2010 Wiley-Liss, Inc.

Laparoscopic colorectal resection is widely used because of its safety and effectiveness compared with conventional surgery; however, surgical assistants find it difficult to perform this surgery in mirror image. This study aimed to evaluate assistants’ learning curves in laparoscopic colorectal surgery. The subjects were three fellows who began their surgical fellowship training at the Center for Colorectal Cancer of the National Cancer Center, Korea, during 2008. We analyzed the data from 145 laparoscopic colorectal surgeries in which these assistants participated. A learning curve was generated for each assistant using the moving average method to assess the execution time and the error rate for grasping tissue. Assistants A, B, and C participated in 50, 45, and 50 laparoscopic colorectal surgeries, respectively. Learning curves indicated that the execution time reached a steady state after 38 cases for Assistant A, 29 cases for Assistant B, and 24 cases for Assistant C. Based on a decline in the error rate, the steady state was reached after approximately 44 cases for Assistant A, 32 cases for Assistant B, and 41 cases for Assistant C. Analysis of the assistants’ learning curves suggests that under reverse alignment conditions, assistants require participation in 30–40 cases before gaining surgical competence. These results have implications for training assistants for laparoscopic colorectal surgery.

The influence of obesity on surgical outcomes after laparoscopic colorectal surgery in Asian patients is unclear. The aim of this study was to evaluate the feasibility and safety of laparoscopic surgery in obese Asian patients with colorectal cancer.We retrospectively reviewed the prospectively collected data on 984 consecutive patients who underwent laparoscopic surgery for colorectal cancer between May 2001 and February 2008. Patients were classified according to the categories proposed by the International Obesity Task Force, as Nonobese (body mass index [BMI]25.0 kg/m(2)), Obese I (BMI 25.0-29.9 kg/m(2)), and Obese II (BMIor = 30 kg/m(2)). Surgical outcomes, including open conversion, operation time, postoperative complications, estimated blood loss, and postoperative hospital stay, were compared in Nonobese, Obese I, and Obese II patients.Of the 984 patients, 645 (65.5%), 312 (31.7%), and 27 (2.7%), were classified as Nonobese, Obese I, and Obese II, respectively. Clinicopathologic characteristics were similar among the three groups. The Obese II group had higher conversion rates (14.8% versus 2.6% and 2.9%, P = 0.001), longer operation time (258 versus 201 and 215 min, P = 0.001), and longer postoperative hospital stay (12.1 versus 9.5 and 9.2 days, P = 0.035) than the Nonobese and Obese I groups. However, the rates of intraoperative events (P = 0.634) and postoperative complications (P = 0.603) were similar in nonobese and obese patients. Independent risk factors for conversion were BMI group and operation type. Obese II patients had an 8.36-fold greater risk of conversion than had Nonobese patients (P = 0.001).With sufficient experience, laparoscopic colorectal surgery in obese Asian patients is feasible and safe, offering all the benefits of a minimally invasive approach. Management of Asian colorectal cancer patients with BMIor = 30 kg/m(2) requires meticulous perioperative care, and colorectal surgeons must be familiar with obesity-related challenges in such patients.

Background and Objectives We compared clinical outcomes in patients who were treated with different chemotherapeutic regimens after resection of hepatic metastases from colorectal cancer (CRC). Methods Between August 2001 and June 2008, 156 patients who entered into chemotherapy of adjuvant intent after hepatic metastasectomy were reviewed retrospectively. Results Of the 156 patients, 58 patients were treated with oxaliplatin/fluoropyrimidines (group I), 48 with irinotecan/fluoropyrimidines (group II), and 50 with fluoropyrimidines alone (group III). In the univariate analysis, there was a marginally significant difference among the three groups with respect to the disease-free survival (DFS); 23.4 months in group I, 14.1 months in group II, and 16.3 months in group III, P = 0.088). Group I showed better DFS when compared to the other two groups combined (group II and III) (P = 0.03). Multivariable analysis showed a marginally significant gain in the DFS for group I (P = 0.068). Multiple metastases (P = 0.045) and positive resection margin (P = 0.003) were significantly associated with poorer DFS. Conclusion Postoperative combination chemotherapy of oxaliplatin/fluoropyrimidines seemed to show better DFS when compared to fluoropyrimidine monotherapy or irinotecan-based combination in patients who underwent liver metastasectomy. J. Surg. Oncol. 2009;100:713–718. © 2009 Wiley-Liss, Inc.

Background and Objectives The role of surgical resection in the treatment of metastatic ovarian tumors originating from colorectal cancer (CRC) remains uncertain. We sought to identify a subgroup of patients who would benefit from surgical resection. Methods We analyzed the clinicopathological and follow-up data on 34 patients who underwent surgical resection of metastatic ovarian tumors originating from CRC. Results Synchronous ovarian metastasis was detected in 27 patients (79.4%) and metachronous metastasis in 7 (20.6%). The histologic type of the primary CRC was adenocarcinoma in 26 patients (76.5%), mucinous carcinoma in 7 (20.6%), and signet ring cell carcinoma in 1 (2.9%). Complete cytoreduction was possible in 11 patients (32.4%). The 3-year overall survival (OS) rate was 25.1%. The median OS time was 19 months (range, 2–64 months) in all patients, and 36 months (range, 10–64 months) in patients who underwent complete cytoreduction. Cox's proportional hazards analysis showed that unilateral ovarian metastasis (relative risk [RR], 0.405; 95% confidence interval [CI], 0.171–0.959) and metastasis confined to the pelvic cavity (RR, 0.165; 95% CI, 0.031–0.878) were significantly associated with favorable prognosis. Conclusions Surgical resection may be beneficial in selected patients with ovarian metastasis arising from CRC, when metastasis is limited to the pelvis. J. Surg. Oncol. 2009;100:570–574. © 2009 Wiley-Liss, Inc.

In rectal cancer patients treated with preoperative chemoradiotherapy (CRT) and curative resection, we evaluated the influence of anemia on tumor response to preoperative CRT.Between August 2001 and July 2007, 490 patients underwent preoperative CRT, followed by curative-intent surgery. Tumor responses were evaluated based on tumor regression grade (TRG), T- and N-level downstaging, and volume reduction rates.The level of pretreatment hemoglobin (Hb) was 12.9 +/- 1.7 g/dl (range, 7.2-17.6 g/dl). Tumor response rates were significantly different below and above the Hb level of 9.0 g/dl. Specifically, patients with Hb levelsor=9.0 g/dl achieved better tumor responses than those with Hb levels9.0 g/dl (rates of TRG 3 or 4-29.0% vs. 0%, p0.001). In addition, there is no differences in tumor response between the nontransfusion and transfusion groups of patients with Hb levelsor=9.0 g/dl (rates of TRG 3 or 4-29.1% vs. 23.1%, p = 0.445).The serum Hb level could be a one of prognostic factors that influences the pathologic tumor response, and pretreatment anemia (below 9.0 g/dl of Hb) is associated with poor response to preoperative CRT.

Transanal endoscopic microsurgery (TEM) is a minimally invasive alternative to transanal excision, enabling complete local excision of selected benign or malignant rectal tumors. This study aimed to determine the surgical and oncologic results for rectal tumors excised by TEM.From November 2001 to October 2007, 45 patients underwent TEM for excision of adenoma (13 patients), carcinoid tumor (6 patients), and carcinoma (26 patients). The patients included 27 men and 18 women with a median age of 52 years (range, 22-72 years).The median tumor distance from the anal verge was 7 cm (range, 3-15 cm), and the median tumor size was 17 mm (range, 2-60 mm). There was no procedure-related morbidity or mortality. However, one patient with rectal carcinoma died of lung cancer during the follow-up period. Of 13 patients with adenomas, 1 patient (7.7%, 1/13) experienced local recurrence 5 months after surgery. No recurrence occurred for six patients with carcinoid tumors. Histologic examination of the carcinomas showed pathologic tumor (pT) stage 0 (ypT0) in 2 patients, pT1 in 17 patients (including ypT1 in 1 patient), pT2 in 6 patients, and pT3 in 1 patient. Immediate salvage surgery was performed for five patients (19%, 5/26). During a median follow-up period of 37 months (range, 5-72 months), one patient (3.8%, 1/26) experienced local recurrence. The overall and disease-free 5-year survival rates for patients with carcinoma were 96.2% and 88.5%, respectively.The TEM procedure is a safe and appropriate surgical treatment option for benign rectal tumors. With strict patient selection, it is oncologically safe for early-stage rectal carcinomas.

Laparoscopic approaches have become increasingly used in selected patients with either colorectal or liver cancer. However, the feasibility of laparoscopic-assisted combined colon and liver resection in primary colorectal cancer with synchronous liver metastases remains unknown. The aim of the present study was to determine the feasibility of laparoscopic-assisted combined colon and liver resection for primary colorectal cancer with synchronous liver metastases. Laparoscopic surgery involving intestinal anastomosis was performed for primary colorectal cancer. The liver was then mobilized with the assistance of a hand inserted through the upper midline incision. For minor resections, the parenchymal transection was performed laparoscopically. For major resection involving a hilar dissection, transection was performed according to the standard open techniques under direct vision through the incision. Resected specimens were retrieved directly through the midline incision. Ten patients with primary colorectal cancer and synchronous liver metastases underwent the above procedure between September 2006 and April 2007. Surgical procedures for colorectal cancer included 5 low anterior resections, 3 anterior resections, 1 right hemicolectomy, and 1 subtotal colectomy. Combined hepatic surgery included 6 major hepatectomies, 3 segmentectomies, and 1 tumorectomy. All procedures were successful, with no conversions to open surgery required. The median operation time was 439 min (range: 210–690 min), and the median estimated blood loss was 350 ml (range: 300–1,200 ml). There was no surgical mortality or major morbidity, except in one patient in whom postoperative bleeding at the site of para-aortic node dissection was promptly controlled. Laparoscopic-assisted combined colon and liver resection is a feasible and safe procedure for the treatment of primary colorectal cancer with synchronous liver metastases.

Three-drug combination of fluoropyrimidine, irinotecan and oxaliplatin has shown survival benefits in patients with metastatic colorectal cancer (mCRC). Recently we performed a phase II study of a new 3-drug regimen, TIROX (S-1 plus irinotecan and oxaliplatin) to evaluate efficacy and safety in refractory mCRC patients. Patients with refractory to all of 3 drugs, ageor = 18 years, PS 0-2,or = 1 measurable lesion(s) and adequate organ functions were eligible. S-1 was given 40 mg/m(2) twice a day on D1-14, oxaliplatin 85 mg/m(2) and irinotecan 150 mg/m(2) on D1 every 3 weeks. The primary endpoint was overall response rate (ORR). Between Mar 2007 and Nov 2007, 19 patients (of 18 planned) were enrolled; median age 50 years; M/F 12/7; PS 0/1/2 5/13/1; colon/rectum 11/8. By intent-to-treat analysis, ORR was 21.1% (95% CI, 8.7-43.7) and disease control rate was 52.6% (95% CI 31.5-72.8) with four PRs and six SDs. Median duration of disease control was 4.3 months (95% CI 1.7-6.9). Median PFS was 2.6 months (95% CI 2.2-2.9) and median OS was 9.8 months (95% CI 5.3-14.4) after median F/U of 15.4 months. G3/4 toxicities per pt included neutropenia (five, 26.3%), febrile neutropenia (two, 10.5%), thrombocytopenia (one, 5.3%), diarrhea (two, 10.5%) and fatigue (two, 10.5%). TIROX seemed to be feasible and efficacious for refractory mCRC patients, and could be an alternative for patients with good PS but no further treatment options.

Objective To evaluate the effect of the time interval between chemoradiotherapy (CRT) and surgery on CRT response and surgical outcomes. Summary background data Although preoperative CRT is a standard component of multimodal treatment for locally advanced rectal cancers, the optimal time for surgery after CRT has yet to be established. This study analyzed outcomes in 397 prospectively enrolled patients with locally advanced rectal cancer who underwent fractionated CRT involving 50.4 Gy radiotherapy followed by surgical resection between 4 and 8 weeks later. Methods Patients were divided into 2 groups according to the time that elapsed between CRT and surgery: group A (28-41 day interval) and group B (42-56 day interval). CRT responses and surgical outcomes were analyzed. Results Of the 397 patients, 217 (54.7%) were in group A and 180 (45.3%) in group B. The 2 groups were similar in terms of pretreatment characteristics other than a slight difference in mean age (A: 55.3 years vs. B: 57.5 years, P = 0.042). Analysis of CRT responses showed that the 2 groups were similar in terms of T-level downstaging rate (A: 47.5% vs. B: 44.4%, P = 0.548), volume reduction rate (A: 34.6% vs. B: 34.2%, P = 0.870) and complete response rate (A: 13.8% vs. B: 15.0%, P = 0.740). Analysis of surgical outcomes showed that the 2 groups were also similar in terms of sphincter-preservation rate (A: 83.9% vs. B: 82.2%, P = 0.688) and anastomosis-related complication rate (A: 5.5% vs. B: 3.9%, P = 0.453). The median follow-up period was 31 months (range, 5-63), and both groups showed similar local recurrence-free survival rates (P = 0.1165). Conclusion The present findings suggest that compared with a 4 to 6 week interval, delaying surgery for 6 to 8 weeks after completion of fractionated radiotherapy with concurrent chemotherapy does not improve CRT response or the sphincter-preservation rate, and does not decrease morbidity or local recurrence.

The present study investigated the feasibility of a single-stage operation consisting of self-expandable metallic stent (SEMS) placement followed by laparoscopic surgery for obstructive left colorectal cancer. From July 2002 to March 2007, 17 consecutive patients with primary obstructive left colorectal cancer underwent SEMS placement followed by laparoscopic surgery. Data were collected retrospectively regarding clinicopathological findings, SEMS placement, operative procedures, and perioperative outcomes. Technical success was defined as successful stent deployment across the obstructive lesion, and clinical success as the possibility of performing a single-stage operation without creating a stoma. In the laparoscopic group, the technical success rate was 100% (17/17) and there was no morbidity associated with SEMS placement. The median interval to laparoscopic surgery was 7 (range, 2–11) days, and the procedures included 11 anterior resections, 3 left hemicolectomies, 2 Hartmann’s procedures, and 1 subtotal colectomy. All procedures were completed laparoscopically without conversion to open surgery. The median operating time was 178 (range, 93–377) minutes, and the median estimated blood loss was 100 (range, 50–400) ml with no cases requiring intraoperative transfusions. The clinical success rate was 82.4% (14/17), and there was no surgical morbidity other than two patients in whom chyloperitoneum and ileus were controlled by using conservative management. The median postoperative hospital stay was 9 (range, 7–49) days. A single-stage operation consisting of SEMS placement followed by laparoscopic surgery seems to be a feasible and safe treatment option for obstructive left colorectal cancer.

Endoscopically, rectal carcinoids have a variety of sizes and features which may assist in determining treatment plans. The present study was performed to assess the relationship between endoscopic features and metastasis in rectal carcinoids.A total of 115 rectal carcinoids of 112 patients with rectal carcinoids were enrolled, and the medical records were retrospectively reviewed. All tumors were classified according to size (longest diameter), and then according to endoscopic features such as shape, color, and surface changes including depressions, erosion, and ulceration. The relationship between endoscopic features and metastasis was evaluated.11 cases (9.6%) of the 115 rectal carcinoids presented with metastatic disease. Tumor size was associated with metastasis (p0.001). Endoscopic features associated with metastasis were tumor shape, surface change, and color (p0.001). Atypical endoscopic features occurred more frequently as the size of the tumor increased (p0.001). For tumors 10-19 mm in diameter, atypical surface change was associated with metastasis (p = 0.007).Endoscopic features were found to be associated with metastasis in rectal carcinoids. In particular, atypical surface change may be useful in determining treatment plans for tumors 10-19 mm in diameter.

Since the Clinical Outcomes of Surgical Therapy (COST) trial data were reported in May 2004, the laparoscopic technique for primary colorectal cancer has been increasingly used and become the approach of choice at our center. This study aimed to evaluate our laparoscopic experience of 570 consecutive patients between October 2000 and December 2006, and assess the feasibility of this technique as the surgical approach of choice for primary colorectal cancer.The study times were divided into three periods based on the COST trial report and the time when the laparoscopic technique was accepted as the surgical approach of choice at our center (period I: October 2000 to May 2004, II: June 2004 to December 2005, III: January to December 2006). Data regarding clinicopathological, surgical, and perioperative outcomes were collated from registry and compared between periods.The use of laparoscopic surgery increased from 2.4% in period I, to 19.2% in period II, to 66.1% in period III. Over the periods, the proportion of rectal cancer and right colon cancer increased (p0.001), T- and N-stage became more advanced (p0.001, p = 0.011 respectively), and operative time decreased (p0.001). The overall open conversion and morbidity rates were 3.5% and 9.8%, respectively, and these did not differ between periods.It was possible to apply laparoscopic approach in two-thirds of primary colorectal cancer patients. The short-term favorable outcomes support the feasibility of laparoscopic technique as surgical approach of choice for colon cancer. Laparoscopic resection for rectal cancer may require a randomized clinical trial prior to gain similar acceptance.

The nonlifting sign is widely used for evaluating the invasion depth of colorectal tumors, and it is commonly accepted that EMR is contraindicated for colorectal tumors with a nonlifting sign because of the probability of massive submucosal invasion.To identify the clinicopathologic factors that affect the nonlifting sign in submucosal invasive colorectal carcinoma (SICC).Details regarding a history of biopsy, postbiopsy days, tumor location, tumor configuration, tumor size, depth of submucosal invasion, histologic type, adenomatous remnants, and angiolymphatic invasion were studied in relation to the nonlifting sign.National Cancer Center, Korea.The study involved 76 patients with SICC treated by endoscopic or surgical resection, in whom the tumor was examined for the nonlifting sign from 2001 to 2006.The nonlifting sign was observed in 15 cases (19.7%). A deep submucosal invasion, a history of biopsy, and the absence of adenomatous remnants were identified as factors affecting the nonlifting sign in univariate and multivariate analyses (P.05). An increase in the number of postbiopsy days was associated with the nonlifting sign in endoscopically resectable SICC, and all 11 sm1 cancer cases with fewer than 21 postbiopsy days showed lifting.A history of biopsy and the absence of adenomatous remnants, in addition to deep submucosal invasion, were found to influence the nonlifting sign in SICC. It may be best that mechanical stimulation such as forceps biopsies are minimized before EMR, and EMR should be tried as soon as possible if biopsy was performed.

To identify pretreatment clinical parameters that could predict pathologic tumor response to preoperative chemoradiotherapy (CRT) for rectal cancer.The study involved 351 patients who underwent preoperative CRT followed by surgery between October 2001 and July 2006. Tumor responses to preoperative CRT were assessed in terms of tumor downstaging and tumor regression. Statistical analyses were performed to identify clinical factors associated with pathologic tumor response.Tumor downstaging (defined as ypT2 or less) was observed in 167 patients (47.6%), whereas tumor regression (defined as Dworak's Regression Grades 3 or 4) was observed in 103 patients (29.3%) and complete regression in 51 patients (14.5%). Multivariate analysis found that predictors of downstaging were pretreatment hemoglobin level (p = 0.045), cN0 classification (p0.001), and serum carcinoembryonic antigen (CEA) level (p0.001), that predictors of tumor regression were cN0 classification (p = 0.044) and CEA level (p0.001), and that the predictor of complete regression was CEA level (p = 0.004).The data suggest that pretreatment CEA level is the most important clinical predictor of pathologic tumor response. It may be of benefit in the selection of treatment options as well as the assessment of individual prognosis.

Preoperative chemoradiotherapy is widely used to improve local control and sphincter preservation in patients with locally advanced rectal cancer. In the present study, we investigated whether microarray gene expression analysis could predict complete response to preoperative chemoradiotherapy in rectal cancer. Tumor tissues were obtained from 46 patients with rectal cancer (31 for training and 15 for validation testing). All patients underwent preoperative chemoradiotherapy involving 50.4 gray radiotherapy, followed by surgical excision 6 weeks later. Response to chemoradiotherapy was evaluated according to Dworak’s tumor regression grade. Tumor regression Grades 1, 2, and 3 were considered partial responses, and tumor regression Grade 4 was considered a complete response. By using the 31 training samples, genes differentially expressed between partial response and complete response were identified, and clustering analysis was performed. Prediction analysis of response to chemoradiotherapy was performed on the 31 training samples by using a selected set of 95 “predictor” genes. Those findings were validated by independent analysis of the 15 test samples. The 31 training samples comprised 20 partial response and 11 complete response cases. A primary set of 261 genes was identified as differentiating between partial response and complete response. By supervised clustering using these 261 genes, 30 of 31 training samples were clustered correctly according to tumor response. A gene set comprising the top-ranked 95 genes displaying differential expression between partial response and complete response was applied to predict response to chemoradiotherapy. Complete response and partial response were accurately predicted in 84 percent (26/31) of training samples and 87 percent (13/15) of validation samples. Microarray gene expression analysis was successfully used to predict complete responses to preoperative chemoradiotherapy in patients with advanced rectal cancer.

Background Laparoscopic surgery for colorectal neoplasm requires precise tumor localization. The authors have assessed the safety and efficacy of colonoscopic tattooing using a saline test injection method with prepackaged sterile India ink for tumor localization in laparoscopic colorectal surgery. Methods Between July 2004 and January 2007, 63 patients underwent colonoscopic tattooing using prepackaged sterile India ink before laparoscopic surgery of colorectal tumors. Patient medical records and operation videos were retrospectively assessed. Results Tattoos were visualized intraoperatively in 62 (98.4%) of the 63 patients, and colorectal tumors were accurately localized in 61 patients (96.8%). In one patient, the tattoo could not be detected, whereas in another patient, it was visualized but the serosal surface of the rectosigmoid colon was stained diffusely. Both of these patients underwent intraoperative colonoscopy. Localized leakages of ink were identified in six patients (9.5%) during surgery. However, five of these patients had no symptoms, and the sixth patient, who underwent polypectomy and tattooing simultaneously, felt mild chilling without fever or abdominal pain. Conclusions Preoperative colonoscopic tattooing using a saline test injection method with prepackaged sterile India ink is a safe and effective method for tumor localization in laparoscopic colorectal surgery.

Most investigations on MutY human homolog (MYH)-associated polyposis (MAP) have been conducted in Western countries. Limited data on MAP in Asia are currently available. The present study investigated germline mutations of the MYH gene among patients with 10 to 99 adenomatous colorectal polyps and familial adenomatous polyposis (FAP) without adenomatous polyposis coli (APC) germline mutations in Korea.The study population included 46 patients with 10 to 99 adenomatous polyps in the colorectum and 16 FAP patients with no identified APC germline mutations. Subjects were screened for MYH germline mutations, and we additionally screened for MYH mutations in 96 normal control individuals.Two of 46 (4.3%) patients with multiple polyps displayed heterozygous biallelic germline mutations of the MYH gene. A 39-year-old male patient with biallelic MYH mutations (p.G272E and p.A359V) received total proctocolectomy for rectal cancer and 36 colorectal polyps. A 58-year-old female patient with biallelic MYH mutations (p.Q253X and p.Q440P) received right hemicolectomy for ascending colon cancer and 16 colonic polyps. The frequency of biallelic MYH mutation in 14 of 46 multiple-polyp patients, who had 15 to 99 polyps, was 14.3% (2 of 14). No biallelic MYH mutations were detected in the 32 patients with 10 to 14 colorectal polyps, 16 FAP patients, or 96 normal controls.We identified biallelic MYH germline mutations in 2 of 14 (14.3%) Korean patients with 15 to 99 colorectal polyps. In this study, there was no Y165C or G382D hot-spot mutation, which had been reported most frequently in previous studies.

Purpose: To describe our experience with a bolus injection of 5-fluorouracil and leucovorin (FL) vs. capecitabine in terms of radiologic and pathologic findings in preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer. Methods: The study enrolled 278 patients scheduled for preoperative CRT using two protocols with different chemotherapeutic regimens. Pelvic radiotherapy (50.4 Gy) was delivered concurrently with FL ( n = 145) or capecitabine ( n = 133). Surgery was performed 6 weeks after CRT completion. Tumor responses to CRT were measured using both radiologic and pathologic examination. Magnetic resonance volumetry was performed at the initial workup and just before surgery after completion of preoperative CRT. Post-CRT pathology tests were used to determine tumor stage and regression. Results: Radiologic examination showed that tumor volume decreased by 68.2% ± 20.5% in the FL group and 68.3% ± 22.3% in the capecitabine group ( p = 0.970). Postoperative pathologic T stage determination showed that downstaging occurred in 44.3% of FL and 49.9% of capecitabine patients ( p = 0.571). The tumor regression grades after CRT were Grade 1 (minimal response) in 22.6% and 21.0%, Grade 2 (moderate response) in 53.2% and 50.0%, Grade 3 (near-complete response) in 12.9% and 12.9%, and Grade 4 (complete response) in 11.3% and 16.1% of the FL and capecitabine groups, respectively ( p = 0.758). Conclusion: In the present study, the radiologic and pathologic findings did not reveal significant differences in short-term tumor responses between preoperative FL and capecitabine CRT for locally advanced rectal cancer. Long-term results and a prospective randomized trial are needed.

Objectives. The aim of this study was to assess the safety, efficacy and impact on survival of low anterior resection and primary anastomosis at the time of en bloc resection for primary and recurrent epithelial ovarian carcinoma. Methods. We performed a retrospective review of 46 primary and 14 recurrent epithelial ovarian carcinoma patients who underwent procedures between April 2001 and May 2005 in our center. Data were obtained from patient medical records and the cancer registry. Parameters for safety, efficacy and survival were considered as primary endpoints. Results. For primary advanced ovarian cancer patients, 43.5% showed no visible tumor at the completion of surgery and optimal cytorection (residual tumor [RT] less than or equal 5 mm) was achieved in 89.2%. Complications associated with en bloc resection occurred in two patients (1 leakage of anastomosis site and 1 rectovaginal fistula), and these were managed with diversion colostomy. Patients with no visible residual tumor had longer disease-free survival compared to those with visible RT (median, 30 vs. 7 months; P =0.0082) and longer overall survival (3-year survival rate, 82.03% vs. 66.63%; P =0.0437). Patients with rectal invasions up to the serosa/subserosa had longer disease-free survival than those with rectal invasion up to the muscle/mucosa ( P =0.0176) but did not differ significantly in terms of overall survival ( P =0.0880). For recurrent ovarian cancer patients, 42.9% showed no visible tumor at the completion of surgery and optimal cytorection was achieved in 64.3%. One patient experienced an en-bloc-resection-associated complication (a rectovaginal fistula), which was managed conservatively. Patients with no visible residual tumor (RT) had longer disease-free survival than visible RT patients (median, not reached vs. 5 months; P =0.0156) but did not differ significantly in terms of overall survival (median, 32 months for no visible RT vs. 24 months for visible RT patients; P =0.0833). There were no surgery-related deaths among the overall 60 primary and recurrent ovarian cancer patients. Conclusions. En bloc resection of primary and recurrent epithelial ovarian carcinomas with low anterior resection permits a high rate of complete debulking with acceptable morbidity and mortality rates. Patients with no visible RT after surgery had a survival advantage over patients with visible RT.

We determined the complete nucleotide and predicted amino acid sequence of the genomic RNA of PL97-1, the first Korean strain of porcine reproductive and respiratory syndrome virus (PRRSV), which was isolated from the serum of an infected pig in 1997. We found that the 15411-nucleotide genome of PL97-1 consisted of a 189-nucleotide 5′ noncoding region (NCR), a 15071-nucleotide protein-coding region, and a 151-nucleotide 3′NCR, followed by a poly (A) tail. The 5′-end of PL97-1 began with 1 ATG ACG TAT AGG12. Comparison of the PL97-1 genome with the 11 fully sequenced PRRSV genomes currently available revealed sequence divergence ranging from 0.3% (the VR-2332-derived vaccine MLV RespPRRS/Repro strain) to 38% (the Dutch Lelystad strain). To better understand the genetic relationships between these different strains, phylogenetic analyses were performed on the full-length PRRSV genomes. Significantly, the phylogenetic tree based on the ORF1b or ORF7 genes most closely resembled the tree based on the full-length genomes. Thus, these single genes will be the most useful in revealing the genetic relationships between the different strains relative to their geographical distribution. Extensive phylogenetic analyses using the ORF7 sequences of 111 PRRSV isolates available revealed that PL97-1 is most closely related to the North American genotype VR-2332, a VR-2332-derived vaccine strain, and Chinese BJ-4. It is distantly related to the European genotype Lelystad. This study provides the largest full-length genome phylogenetic analysis of PRRSV that has been published to date, and supports an earlier genetic grouping of the many temporally and geographically diverse PRRSV strains currently isolated.

Purpose: The aim of this study was to evaluate the clinical value of whole body F-fluorodeoxyglucose positron emission tomography (FDG-PET) in the patient with a recurrence of a previously treated colorectal malignancy. Materials and Methods: Fifty-eight cases were scanned using PET at the PET Center of Seoul National University Hospital between May 1995 and Aug 2002. All the patients had had a previous operation for a colorectal malignancy. The PET scans were performed for the following reasons: - investigation of a recurrence (n=12), investigation of the operability (n=38) and clinical follow up (n=8). In these 58 cases, 47 of the CT scans and 55 of the CEA (Carcinoembryonic antigen) were checked prior to the FDG- PET. The accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the PET scans were calculated, and compared with those of conventional CT scan and CEA, which were also compared with the previous reported data. Eight cases, whose managements were influenced by the PET findings, were analyzed. Results: Recurrences, or metastases, of colorectal cancer developed in 51 cases, with 49 of these being detected by the PET. The accuracy, sensitivity and specificity of the PET were 96.6 (56/58), 96.1 (49/51) and 100% (7/7), respectively. The PPV and NPV of the PET were 100 (49/49) and 77.8% (7/9), respectively. The accuracy and sensitivity of the PET were higher than those of the CT (85.1 and 88.1%), with the differences being statistically significant (p-value 0.001 and 0.003, respectively). Conclusion: It is concluded that a FDG-PET scan is a more accurate and sensitive diagnostic tool than a CT scan for the detection of a recurrence or metastasis in a colorectal malignancy. In addition, a FDG-PET may alter the management of patients with recurrent colorectal cancer. Therefore, it is recommended that a PET should be considered when a tumor recurrence is suspected during conventional follow up.

3518 Background: Laparoscopic surgery for rectal cancer has been used widely. However, recent two randomized trials raised concerns about short-term oncologic safety of laparoscopic surgery for rectal cancer. The aim of this study was to evaluate the long-term oncologic safety of laparoscopic surgery for rectal cancer based on 7-year data from the Comparison of Open versus laparoscopic surgery for mid or low REctal cancer After Neoadjuvant chemoradiotherapy (COREAN) trial. Methods: COREAN trial was a non-inferiority, randomized controlled trial. Between April, 2006, and Aug, 2009, eligible participants with mid or low rectal cancer treated with preoperative chemoradiotherapy were randomly assigned (1:1) to laparoscopic (n = 170) or open surgery (n = 170). Seven-year outcomes included overall and disease-free survival, and local recurrence. Log-rank test and stratified Cox regression analysis were used for survival analysis. Analysis was by intention to treat. Results: The median follow-up times were 84 months (IQR: 61.5-97.0). No differences were found between laparoscopic and open surgery group in terms of overall and disease-free survival, and local recurrence (7-year overall survival: 83.2% [laparoscopic] vs 77.3% [open], p = 0.48; 7-year disease-free survival: 71.6% [laparoscopic] vs 64.3% [open], p = 0.20; 7-year local recurrence: 3.3% [laparoscopic] vs 7.9% [open], p = 0.08). Stratified Cox regression analysis adjusted for ypT, ypN and tumor regression grade showed no significant difference between groups in terms of overall and disease-free survival, and local recurrence. The hazard ratios for overall survival, disease-free survival and local recurrence (open vs laparoscopic surgery) were 0.96 (95% CI = 0.58-1.57), 1.03 (95% CI = 0.70-1.53), and 2.28 (95% CI = 0.82-7.16), respectively. Conclusions: The 7-year analysis confirm the long-term oncological safety of laparoscopic surgery for rectal cancer treated with preoperative chemoradiotherapy. The use of laparoscopic surgery does not compromise the long-term survival outcomes in rectal cancer. Clinical trial information: NCT00470951.

Juvenile polyposis is an uncommon condition characterized by the development of multiple (usually more than 5) juvenile polyps in the gastrointestinal tract, especially in the colon. This disease usually occurs during childhood, and is inherited in an autosomal dominant fashion. It has been suggested that the dpc4 (deleted in pancreatic carcinoma, locus 4) gene, which is located on chromosome 18q21.1, might cause juvenile polyposis. The dpc4 (smad4) gene is a candidate tumor-suppressor gene and may play a role in the TGF-β-signaling pathway. To confirm the idea that alterations of the dpc4 gene may result in juvenile polyposis, we screened 5 Korean juvenile-polyposis patients by PCR-SSCP (single-strand conformation polymorphism) analysis and bi-directional sequencing. There were germline mutations of the dpc4 gene in 3 out of the 5 patients: 2 had a genetic alteration in exon 9 and the third had a mutation in exon 8. These germline mutations occurred in the C-terminus of the dpc4 gene, similar to most published mutations. One patient exhibited a non-sense mutation (codon 388), which changed a glutamine codon (CAG) to a stop codon (TAG). The second patient harbored a mis-sense mutation (codon 390), causing a non-conservative amino-acid change 〈glutamate (GAA) to lysine (AAA)〉. The third patient had a mis-sense mutation in exon 8 (codon 361), which altered an arginine codon (CGC) into a histidine codon (CAC). Int. J. Cancer 86:529–532, 2000. © 2000 Wiley-Liss, Inc.

Peutz-Jeghers syndrome is an autosomal dominant inherited disorder characterized by hamartomatous polyps in the small bowel and mucocutaneous pigmentation. Patients with Peutz-Jeghers syndrome often present as surgical emergencies with complications of the polyps, such as intussusception, bowel obstruction, and bleeding. Recently an increased risk of malignancies has also been reported. This study was initiated to determine the clinical features of Peutz-Jeghers syndrome in Korean patients, with special attention to the development of malignancies. Thirty patients with Peutz-Jeghers syndrome were investigated; their median age was 23.5 years, and symptoms appeared at a median age of 12.5 years. Family history was positive in one-half of cases, and mucocutaneous pigmentation was observed in almost all patients (93%). The jejunoileum was the most frequent site of the polyps, and there were generally 10-100 polyps. Multiple laparotomies were performed in a substantial portion of the patients, due mainly to polyp-induced bowel obstruction, and the surgical interventions were begun at a relatively young age (average 21.4 years). Four cases of small-bowel cancer and one case of breast cancer were detected in probands, at a relatively young age (mean 36 years). Cancers of the small bowel, stomach, colon, breast and cervix were diagnosed in the first relatives of the probands. Close follow-up from an early age should thus be performed in patients with Peutz-Jeghers syndrome as they are at high risk of surgical emergency and development of malignancy.

In order to investigate the changing pattern of rectal cancers in Korea and to identify prognostic factors, we investigated the case histories of 1446 rectal cancer patients who had received surgical treatment. During the study period there were trends toward a decrease in the ratio of rectal cancer to colon cancer, earlier detection (more Dukes' stages A and B and fewer C), a decrease in the number of abdominoperineal resections, and an increase in the number of sphincter-preserving operations. Univariate analysis of prognostic factors showed that gender, obstruction symptoms, preoperative serum carcinoembryonic antigen (CEA) level, tumor size, depth of bowel wall invasion, lymph node metastases (presence and number), tumor differentiation, operative method, and date of operation were significant, but age, symptom duration, and tumor location were not. The use of sphincter-saving operations did not adversely affect the clinical outcome. Multivariate analysis showed lymph node metastasis factor to be the most significant factor (P < 0.001); the depth of bowel wall invasion, differentiation, CEA level, and date of operation were also significant (0.001 < P < 0.05). This study shows that although anatomical extent of disease (depth of invasion and lymph node metastasis) is the most reliable prognostic predictor in rectal cancer, other factors such as preoperative CEA level and tumor differentiation also provide important information on the outcome and use of an anal-preserving operation does not adversely affect the patient survival.

Peutz-Jeghers syndrome is an autosomal dominant inherited disorder characterized by hamartomatous polyps in the small bowel and mucocutaneous pigmentation. Patients with Peutz-Jeghers syndrome often present as surgical emergencies with complications of the polyps, such as intussusception, bowel obstruction and bleeding. Furthermore, repeated operations may be needed in some patients, which may result in short bowel syndrome. Although early reports did not demonstrate a predisposition to cancer in patients with this syndrome, more recent studies have described an increased risk for both gastrointestinal and extra-gastrointestinal cancers. Women with the Peutz-Jeghers syndrome have the extremely high risk for breast and gynecologic cancer. Recently, Peutz-Jeghers syndrome susceptibility gene, encoding the serine threonine kinase STK11 (also called LKB1), was identified in families with Peutz-Jeghers syndrome. The identifications of germline mutations in families with Peutz-Jeghers syndrome could be a turning point in the management of Peutz-Jeghers syndrome.