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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., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective:: To compare the patterns of failure between rectal cancer patients with negative and positive circumferential resection margin (CRM) after surgery following preoperative chemoradiation., Methods:: Of 944 stage II-III rectal cancer patients treated with radical surgery following preoperative chemoradiation, 74 patients (7.8%) showed positive CRM. Each 72 patients from negative and positive CRM groups were identified by propensity score matching and compared in terms of survival outcomes and patterns of failure. Local failure was defined as recurrence at the anastomosis site or adjacent to the mesorectal fascia., Results:: The median follow-up was 46 months (range, 4-155). No difference was observed in 5-year local recurrence-free survival (93.4% vs 89.6%, p = 0.442) in the negative and positive CRM groups. There was statistically significant difference in relapse-free survival (57.1% vs 39.1%, p = 0.042). Negative CRM group showed favorable outcomes than positive CRM in distant metastasis-free survival (59.4% vs 43.3%, p = 0.069) and overall survival (67.5% vs 55.8%, p = 0.186), but the difference was not statistically significant. As the initial failure pattern, there were 30 and 43 recurrences in the negative and positive CRM groups (local 6.6 and 7.3%, regional 12.8 and 14.4%, and distant 38.5 and 54.9%). Isolated local recurrence was identified in two with negative CRM and in none with positive CRM (p = 0.497)., Conclusion:: Distant metastasis was the major pattern of failure regardless of CRM involvement in rectal cancer patients treated with surgery following preoperative chemoradiation. It would be taken account of our finding on adjuvant treatment for the patient with positive CRM., Advances in Knowledge:: Investigation of the patterns of failure in patients with CRM involvement after preoperative chemoradiation followed by surgery can be conducive to selecting the appropriate approach to additional treatment for them.

Purpose: Preoperative chemoradiation therapy (CRT) followed by total mesorectal excision (TME) in locally advanced rectal cancer is the standard of care. To date, the role of consolidation chemotherapy after CRT has rarely been addressed through randomized trials. This study aimed to evaluate the efficacy of CRT followed by consolidation chemotherapy compared with CRT alone., Methods and Materials: This study enrolled patients with adenocarcinoma of the rectum and cT3 or cT4 disease with any N category and no metastasis. In arm A (control arm), we planned CRT (50.4 Gy in 28 fractions) with capecitabine followed by TME. In arm B, 2 cycles of capecitabine and oxaliplatin were administered 1 week after the completion of CRT before TME (capecitabine, 1700 mg/m 2 per day from day 1 to 14, and oxaliplatin, 100 mg/m 2 on day 1, every 3 weeks). The downstaging rate (the proportion of ypT0 to ypT2 and ypN0M0) was the primary endpoint, which was to be tested with a 1-sided type I error of 15% and with 85% power., Results: From September 2014 to February 2016, 110 patients (56 in arm A and 54 in arm B) were randomized and 108 (55 in arm A and 53 in arm B) started CRT. TME was conducted per protocol in 96 patients (52 in arm A and 44 in arm B). In arms A and B, downstaging was achieved in 21.2% and 36.4% (P = .077), respectively, and the pathologic complete response rate was 5.8% and 13.6% (P = .167), respectively. Grade ≥3 adverse events occurred in 3.6% of patients in arm A and 9.4% of patients in arm B during the preoperative treatment phase and in 1.9% and 9.0%, respectively, during the postoperative recovery phase., Conclusions: Consolidation chemotherapy with 2 cycles of capecitabine and oxaliplatin demonstrated a marginal improvement in the downstaging rate. However, a phase 3 trial of this strategy is discouraged because of the high dropout rate and safety issues., (Copyright © 2018. Published by Elsevier Inc.)

Objective: The phase II randomized controlled trial aimed to compare the outcomes of robot-assisted surgery with those of laparoscopic surgery in the patients with rectal cancer., Background: The feasibility of robot-assisted surgery over laparoscopic surgery for rectal cancer has not been established yet., Methods: Between February 21, 2012 and March 11, 2015, patients with rectal cancer (cT1-3NxM0) were enrolled. Patients were randomized 1:1 to either robot-assisted or laparoscopic surgery, and stratified per sex and administration of preoperative chemoradiotherapy. The primary outcome was the quality of total mesorectal excision (TME) specimen. Secondary outcomes were the circumferential and distal resection margins, the number of harvested lymph nodes, morbidity, bowel function recovery, and quality of life., Results: A total of 163 patients were randomly assigned to the robot-assisted (n = 81) and laparoscopic (n = 82) surgery groups, and 139 patients were eligible for the analyses (73 vs 66, respectively). One patient (1.2%) in the robot-assisted group was converted to open surgery. The TME quality did not differ between the robot-assisted and laparoscopic groups (80.3% vs 78.1% complete TME, respectively; 18.2% vs 21.9% nearly complete TME, respectively; P = 0.599). The resection margins, number of harvested lymph nodes, morbidity, and bowel function recovery also were not significantly different. On analyzing quality of life, scores of the European Organization for Research and Treatment of Cancer Quality of Life (EORTC QLQ C30) and EORTC QLQ CR38 were similar in the 2 groups, but in the EORTC QLQ CR 38 questionnaire, sexual function 12 months postoperatively was better in the robot-assisted group than in the laparoscopic group (P = 0.03)., Conclusions: Robot-assisted surgery in rectal cancer showed TME quality comparable with that of laparoscopic surgery, and it demonstrated similar postoperative morbidity, bowel function recovery, and quality of life.

Purpose: This study was designed to evaluate tumor regression endoscopic criteria for predicting the post-chemoradiotherapy (CRT) prognosis of patients with locally advanced rectal cancer., Material and Methods: A total of 425 patients with rectal cancer who received radical surgery after CRT were included in this study. All patients were divided into two groups according to post-CRT preoperative endoscopic findings: 1) good response (E-GR): scar, telangiectasia, or erythema; 2) minimal or no response (E-MR): nodules, ulcers, strictures, or remnant tumor. Cox proportional hazard models were used to analyze the effect of preoperative clinicopathological variables on disease-free survival (DFS) and overall survival (OS)., Results: The independent prognostic factors for DFS were tumor location less than 5 cm from anal verge (hazard ratio [HR] 1.92, 95% confidence interval [CI] 1.27 to 2.88), pre-CRT carcinoembryonic antigen (CEA) > 5 ng/mL (HR 2.10, 95% CI 1.41 to 3.14), histologic high grade (HR 2.96, 95% CI 1.51 to 5.81), and E-GR (HR 0.26, 95% CI 0.08 to 0.83). The independent prognostic factors for OS were age over 65 years, tumor location, pre-CRT CEA, histologic grade, and E-GR (HR 0.13, 95% CI 0.02 to 0.99)., Conclusions: Post-CRT endoscopic findings were predictors of prognosis in patients with rectal cancer. If endoscopic findings are simultaneously used with certain preoperative prognostic factors, rectal cancer patients will potentially have more treatment options., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Little is known about the effect of lateral pelvic node dissection after preoperative chemoradiotherapy on rectal cancer patients with initially suspected lateral pelvic nodes. The purpose of this study was to identify a subgroup of patients receiving preoperative chemoradiotherapy who can benefit from lateral pelvic node dissection., Methods: The study included 580 patients who underwent preoperative chemoradiotherapy and total mesorectal excision. The lateral pelvic node responses to preoperative chemoradiotherapy were divided: group I (no suspected lateral pelvic node), lateral pelvic node <5 mm pre- and post-chemoradiotherapy; group II (responsive lateral pelvic node), lateral pelvic node ≥5 mm pre-chemoradiotherapy but <5 mm post-chemoradiotherapy; and group III (persistent lateral pelvic node), lateral pelvic node ≥5 mm pre- and post-chemoradiotherapy. Prognostic factors for lateral pelvic node recurrence-free survival, locoregional recurrence-free survival, relapse-free survival, and overall survival were analyzed., Results: In a multivariate analysis, lateral pelvic node response was an independent factor associated with lateral pelvic node recurrence-free survival, locoregional recurrence-free survival, relapse-free survival, and overall survival (P < .05). Group III had significantly poorer lateral pelvic node recurrence-free survival, locoregional recurrence-free survival, relapse-free survival, and overall survival than groups II and I (74.1%, 93.4%, and 98.6%; 71.7%, 89.4%, and 97%; 56.9%, 76.6%, and 81.7%; 74.9%, 85.7%, and 89.1%, respectively; P < .05). Group II tended to have poorer lateral pelvic node recurrence-free survival, locoregional recurrence-free survival, relapse-free survival, and overall survival than group I, and the differences in relapse-free survival and overall survival between the 2 groups were not significant (P > .05)., Conclusion: Our data suggest that the subgroup with lateral pelvic nodes responsive to preoperative chemoradiotherapy may not benefit from lateral pelvic node dissection, and the subgroup with persistent lateral pelvic node may benefit from lateral pelvic node dissection., (Copyright © 2016 Elsevier Inc. All rights reserved.)

There is a strong need for murine gastric cancer cell line models recapitulating human gastric cancers. Here, we describe two murine gastric cancer cell lines designated as NCC-S1 and NCC-S3. They were generated from gastric adenocarcinomas that formed in a Villin-cre, Smad4(F/F) , Trp53(F/F) , Cdh1(F/wt) mouse and a Pdx1-cre, Trp53(F/F) , Cdh1(F/F) mouse, respectively. Molecular profiles of both cell lines were very similar to human gastric cancer. NCC-S1M and NCC-S3M subpopulation clones were isolated from pulmonary metastasis of heterotopic allografts of NCC-S1 and NCC-S3 cells, respectively. NCC-S1M and NCC-S3M showed enhanced in vivo growth rates and metastatic potentials and exhibited epithelial-to-mesenchymal transition features. NCC-S1M cells developed orthotopic and heterotopic tumors in immunocompetent mice in predictable manner, and were useful for testing the efficacy of an immunotherapeutic agent, anti-4-1BB antibody. NCC-S1M and NCC-S3M cells demonstrated Wnt/β-catenin pathway activation, and knockdown of Ctnnb1 reversed the metastatic phenotype of NCC-S1M. These results underscore the role of Wnt/β-catenin pathway in metastatic phenotype of gastric cancer. Taken together, our novel metastatic gastric cancer cell lines are useful resources for drug development and metastasis research., (© 2014 Wiley Periodicals, Inc.)

Background and Purpose: The Korean Radiation Oncology Group evaluated the significance of carcinoembryonic antigen (CEA) levels both as a predictor of tumor response after CRT and as a prognosticator for recurrence-free survival., Methods and Materials: 1804 rectal cancer patients, staged cT3-4N0-2M0, participated in a multicenter study. The patients were administered preoperative radiation of 50.4 Gy in 28 fractions with 5-FU or capecitabine, followed by total mesorectal excision. Patients with elevated CEA levels (>5 ng/mL) were matched at a 1 (n=595):1 (n=595) ratio with patients with normal CEA (⩽5 ng/mL). The tumor response after CRT and the recurrence-free survival (RFS) rates were evaluated and compared between two arms., Results: An elevated CEA level (p<0.001) was determined to be a significant negative predictor of downstaging after CRT. The downstaging rate was 42.9% for normal CEA and 23.4% for elevated CEA. A multivariate analysis also revealed that cT (p=0.021) and cN classification (p=0.001), tumor size (p=0.002), and tumor location from the anal verge (p=0.006) were significant predictors for tumor downstaging. The 5-year RFS rates were significantly higher for the normal CEA arm than for the elevated CEA arm (74.2 vs. 63.5%, p<0.001)., Conclusions: Elevated CEA (>5 ng/mL) is a negative predictor of tumor downstaging after CRT and also has a negative impact on RFS in rectal cancer., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection., Patients and Methods: A national consortium of 10 institutions was formed, and patients with ypT0-2N0 mid- and low-rectal cancer after PCRT and radical resection from 2004 to 2009 were included. Patients were categorized into 2 groups according to receipt of additional adjuvant chemotherapy: Adj CTx (+) versus Adj CTx (-). Propensity scores were calculated and used to perform matched and adjusted analyses comparing relapse-free survival (RFS) between treatment groups while controlling for potential confounding., Results: A total of 1016 patients, who met the selection criteria, were evaluated. Of these, 106 (10.4%) did not receive adjuvant chemotherapy. There was no overall improvement in 5-year RFS as a result of adjuvant chemotherapy [91.6% for Adj CTx (+) vs 87.5% for Adj CTx (-), P=.18]. There were no differences in 5-year local recurrence and distant metastasis rate between the 2 groups. In patients who show moderate, minimal, or no regression in tumor regression grade, however, possible association of adjuvant chemotherapy with RFS would be considered (hazard ratio 0.35; 95% confidence interval 0.14-0.88; P=.03). Cox regression analysis after propensity score matching failed to show that addition of adjuvant chemotherapy was associated with improved RFS (hazard ratio 0.81; 95% confidence interval 0.39-1.70; P=.58)., Conclusions: Adjuvant chemotherapy seemed to not influence the RFS of patients with ypT0-2N0 rectal cancer after PCRT followed by radical resection. Thus, the addition of adjuvant chemotherapy needs to be weighed against its oncologic benefits., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Voltage-gated potassium (Kv) channels are known to be involved in cancer development and cancer cell proliferation. KV9.3, an electronically silent subunit, forms heterotetramers with KV2.1 in excitable cells and modulates its electrophysiological properties. However, the role of KV9.3 alone in non-excitable cancer cells has not been studied. Here, we evaluated the effect of silencing KV9.3 on cancer cell proliferation in HCT15 colon carcinoma cells and A549 lung adenocarcinoma cells. We confirmed the expression of KV9.3 mRNA in HCT15 and A549 cells and showed that silencing KV9.3 using small interfering RNA caused G0/G1 cell cycle arrest and alterations in cell cycle regulatory proteins in both HCT15 and A549 cells without affecting apoptosis. Also, stable knockdown of KV9.3 expression using short-hairpin RNA inhibited tumor growth in SCID mouse xenograft model. Using a bioinformatics approach, we identified Sp1 binding sites in the promoter region of the gene encoding KV9.3. We further found that Sp1 bound to this region and showed that the Sp1 inhibitor, mithramycin A, induced a concentration-dependent decrease in KV9.3 expression. Taken together, these data suggest that knockdown of KV9.3 inhibits proliferation in colon carcinoma and lung adenocarcinoma cell lines and may be regulated by Sp1.

Background: To perform chemoradiotherapy (CRT) effectively, it is clinically beneficial to identify predictors of tumor response after CRT. This study examined the association between plasma fibrinogen level before preoperative CRT and tumor response in advanced rectal cancer., Methods: This was a retrospective study of 947 patients who received preoperative CRT followed by curative surgery for primary rectal cancer. We analyzed clinical factors that could be associated with pathologic tumor response in terms of downstaging (ypStage 0-I), primary tumor regression (ypT0-1), and complete response (ypT0N0)., Results: Downstaging was observed in 366 patients (38.6%), primary tumor regression in 187 patients (19.7%) and complete response in 138 patients (14.6%). Multivariate analysis found that pre-CRT carcinoembryonic antigen (CEA) level, fibrinogen level, hemoglobin level, clinical T and N classification, distance from anal verge, and histologic grade were significant predictive factors for downstaging; CEA level, fibrinogen level, and N classification predicted primary tumor regression; CEA level, and fibrinogen level were predictive for complete response., Conclusions: This study demonstrated that fibrinogen level was a significant predictor of pathologic tumor response after preoperative CRT.

Background: We investigated whether routine elective irradiation of a clinically negative inguinal node (IGN) is necessary for patients with locally advanced distal rectal cancer and anal canal invasion (ACI)., Methods: We reviewed retrospectively 1,246 patients with locally advanced rectal adenocarcinoma managed using preoperative or postoperative chemoradiotherapy and radical surgery between 2001 and 2011. The patients' IGN was clinically negative at presentation and IGN irradiation was not performed. ACI was defined as the lower edge of the tumor being within 3 cm of the anal verge. Patients were divided into two groups, those with ACI (n = 189, 15.2%) and without ACI (n = 1,057, 84.8%)., Results: The follow-up period was a median of 66 months (range, 3-142 months). Among the 1,246 patients, 10 developed IGN recurrence; 7 with ACI and 3 without ACI. The actuarial IGN recurrence rate at 5 years was 0.7%; 3.5% and 0.2% in patients with and without ACI, respectively (p < 0.001). Isolated IGN recurrence occurred in three patients, all of whom had ACI tumors. These three patients received curative intent local treatments, and one was alive with no evidence of disease 10 years after IGN recurrence. Salvage treatments in the other two patients controlled successfully the IGN recurrence for >5 years, but they developed second malignancy or pelvic and distant recurrences. Seven patients with non-isolated IGN recurrence died of disease at 5-22 months after IGN recurrence., Conclusion: The low IGN recurrence rate even with ACI and the feasibility of salvage of isolated IGN recurrence indicated that routine elective IGN irradiation is not necessary for rectal cancer with ACI.

Unlabelled: Loss of E-cadherin (CDH1), Smad4, and p53 has been shown to play an integral role in gastric, intestinal, and breast cancer formation. Compound conditional knockout mice for Smad4, p53, and E-cadherin were generated to define and compare the roles of these genes in gastric, intestinal, and breast cancer development by crossing with Pdx-1-Cre, Villin-Cre, and MMTV-Cre transgenic mice. Interestingly, gastric adenocarcinoma was significantly more frequent in Pdx-1-Cre;Smad4(F/F);Trp53(F/F);Cdh1(F) (/+) mice than in Pdx-1-Cre;Smad4(F/F);Trp53(F/F);Cdh1(+/+) mice, demonstrating that Cdh1 heterozygosity accelerates the development and progression of gastric adenocarcinoma, in combination with loss of Smad4 and p53. Pdx-1-Cre;Smad4(F/F);Trp53(F/F);Cdh1(F) (/+) mice developed gastric adenocarcinomas without E-cadherin expression. However, intestinal and mammary adenocarcinomas with the same genetic background retained E-cadherin expression and were phenotypically similar to mice with both wild-type Cdh1 alleles. Lung metastases were identified in Pdx-1-Cre;Smad4(F/F);Trp53(F/F);Cdh1(F) (/+) mice, but not in the other genotypes. Nuclear β-catenin accumulation was identified at the invasive tumor front of gastric adenocarcinomas arising in Pdx-1-Cre;Smad4(F/F);Trp53(F/F);Cdh1(F) (/+) mice. This phenotype was less prominent in mice with intact E-cadherin or Smad4, indicating that the inhibition of β-catenin signaling by E-cadherin or Smad4 downregulates signaling pathways involved in metastases in Pdx-1-Cre;Smad4(F/F);Trp53(F/F);Cdh1(F) (/+) mice. Knockdown of β-catenin significantly inhibited the migratory activity of Pdx-1-Cre;Smad4(F/F);Trp53(F/F);Cdh1(F) (/+) cell lines. Thus, loss of E-cadherin and Smad4 cooperates with p53 loss to promote the development and metastatic progression of gastric adenocarcinomas, with similarities to human gastric adenocarcinoma., Implications: This study demonstrates that inhibition of β-catenin is a converging node for the antimetastatic signaling pathways driven by E-cadherin and Smad4 in Pdx-1-Cre;Smad4(F/F);Trp53(F/F);Cdh1(F) (/+) mice, providing novel insights into mechanisms for gastric cancer metastasis., (©2014 American Association for Cancer Research.)

Objective: Early detection and endoscopic removal of metachronous neoplasms are important preventive strategies for patients with colorectal cancer (CRC) after curative tumor resection. We aimed to determine the incidence of and the risk factors for metachronous colorectal neoplasms after curative resection for CRC., Methods: We retrospectively reviewed clinical data of patients who underwent curative resection for CRC at the National Cancer Center, Korea, from July 2004 to July 2007 and were followed up for a mean duration of 40.7 months. The incidence of and the risk factors for developing metachronous neoplasms were analyzed., Results: A total of 1049 patients were included in this study. A follow-up colonoscopy showed that 454 (43.3%) patients developed metachronous neoplasms, including 46 (4.4%) with advanced adenoma or cancer. Univariate analyses revealed that age ≥ 60 years, male gender, diabetes mellitus, hypertension, synchronous adenoma, synchronous multiple adenoma and synchronous advanced adenoma were associated with the development of metachronous neoplasms. Baseline risk factors associated with metachronous advanced neoplasm were age ≥ 60 years, synchronous multiple adenoma and synchronous advanced adenoma. Multivariate analysis showed that age ≥ 60 years, synchronous adenoma and diabetes mellitus were risk factors for the development of metachronous neoplasms. The cumulative incidence of metachronous neoplasms was higher in patients with these risk factors than in those without., Conclusions: Elder age, synchronous adenoma and diabetes mellitus are risk factors for developing metachronous neoplasia. Therefore, careful surveillance colonoscopy are necessary for these patients., (© 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

Purpose: A prospective phase 2 multicenter trial was performed to investigate the efficacy and safety of preoperative short-course concurrent chemoradiation therapy (CRT) followed by delayed surgery for patients with locally advanced rectal cancer., Methods and Materials: Seventy-three patients with cT3-4 rectal cancer were enrolled. Radiation therapy of 25 Gy in 5 fractions was delivered over 5 consecutive days using helical tomotherapy. Concurrent chemotherapy was administered on the same 5 days with intravenous bolus injection of 5-fluorouracil (400 mg/m(2)/day) and leucovorin (20 mg/m(2)/day). After 4 to 8 weeks, total mesorectal excision was performed. The primary endpoint was the pathologic downstaging (ypStage 0-I) rate, and secondary endpoints included tumor regression grade, tumor volume reduction rate, and toxicity., Results: Seventy-one patients completed the planned preoperative CRT and surgery. Downstaging occurred in 20 (28.2%) patients, including 1 (1.4%) with a pathologic complete response. Favorable tumor regression (grade 4-3) was observed in 4 (5.6%) patients, and the mean tumor volume reduction rate was 62.5 ± 21.3%. Severe (grade ≥3) treatment toxicities were reported in 27 (38%) patients from CRT until 3 months after surgery., Conclusions: Preoperative short-course concurrent CRT followed by delayed surgery for patients with locally advanced rectal cancer demonstrated poor pathologic responses compared with conventional long-course CRT, and it yielded considerable toxicities despite the use of an advanced radiation therapy technique., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background/aims: Endoscopic submucosal dissection (ESD) has been accepted as a standard treatment of early gastric cancer (EGC). However, the indication of ESD in undifferentiated-type EGC was controversial. The aim of this study was to evaluate the therapeutic outcomes of ESD in undifferentiated-type EGC according to expanded indication., Methods: At Soonchunhyang University Bucheon Hospital, a total of 82 lesions in 81 patients with undifferentiated-type EGC were treated with ESD. The therapeutic outcomes of ESD were evaluated by resection method (en bloc resection; piecemeal resection), histologic curative resection, complications and recurrence rates after ESD., Results: The rate on en bloc resection and complete resection rate were 87.8% (72/82) and 80.5% (66/82), respectively. In signet ring cell carcinoma, the complete resection rate was higher than those in poorly differentiated adenocarcinoma and poorly differentiated adenocarcinoma with signet ring cell features, but there was no statistical significance (89.3% vs. 75.0%, 76.7%; p=0.347). The lateral margin positivity rate in poorly differentiated adenocarcinoma, signet ring cell carcinoma and poorly differentiated adenocarcinoma with signet ring cell features were 12.5%, 3.6% and 13.3%, respectively (p=0.395). The vertical margin positivity rate were 12.5%, 3.6% and 10.0%, respectively (p=0.485). The overall recurrence rate was 3.0% during a mean follow-up period of 37.4 months., Conclusions: ESD may be considered as a feasible treatment for undifferentiated-type EGC according to expanded indication. The therapeutic outcome of ESD in undifferentiated-type EGC is likely to be favorable, though further longer follow-up studies are needed.

Aims and Background: The pretreatment serum carcinoembryonic antigen (CEA) level is an independent prognostic factor in colorectal cancer. We aimed to investigate the significance of CEA as a prognostic or predictive factor in rectal cancer patients receiving preoperative chemoradiotherapy (CRT)., Methods and Study Design: In total, 609 patients with locally advanced (cStage II-III) mid to distal rectal cancer who underwent preoperative CRT and radical surgery between 2001 and 2008 were analyzed retrospectively. Predictive factors for pathologic CRT response were determined using multivariate logistic regression. A prognostic factor analysis was performed using the log-rank test and Cox proportional hazards regression., Results: Elevated CEA levels (>5 ng/mL) were observed in 201 (33.0%) patients at diagnosis. Following preoperative CRT, downstaging (ypStage 0-I) occurred in 255 (41.9%) patients, of whom 88 had pathologic complete tumor regression. Pretreatment CEA was significantly associated with pathologic CRT response in terms of downstaging and tumor regression grade, and was the most relevant predictive factor. After a median follow-up period of 60 months, the 5-year disease-free and overall survival rates were 76.2% and 84.6%, respectively. Prognostic factors independently associated with recurrence or survival included ypStage, circumferential resection margin, and histologic grade., Conclusions: In patients with rectal cancer who received preoperative CRT, the pretreatment CEA level was a significant and independent predictor of pathologic CRT response. However, it may not be able to predict long-term outcomes independently of ypStage.

Purpose: To compare chemotherapy alone with chemoradiation therapy in stage III-IV(M0) gastric cancer treated with R0 gastrectomy and D2 lymph node dissection., Methods and Materials: The chemotherapy arm received 5 cycles of fluorouracil and leucovorin (FL), and the chemoradiation therapy arm received 1 cycle of FL, then radiation therapy of 45 Gy concurrently with 2 cycles of FL, followed by 2 cycles of FL. Intent-to-treat analysis and per-protocol analyses were performed., Results: Between May 6, 2002 and June 29, 2006, a total of 90 patients were enrolled. Forty-four were randomly assigned to the chemotherapy arm and 46 to the chemoradiation therapy arm. Treatment was completed as planned by 93.2% of patients in the chemotherapy arm and 87.0% in the chemoradiation therapy arm. Overall intent-to-treat analysis showed that addition of radiation therapy to chemotherapy significantly improved locoregional recurrence-free survival (LRRFS) but not disease-free survival. In subgroup analysis for stage III, chemoradiation therapy significantly prolonged the 5-year LRRFS and disease-free survival rates compared with chemotherapy (93.2% vs 66.8%, P=.014; 73.5% vs 54.6%, P=.056, respectively)., Conclusions: Addition of radiation therapy to chemotherapy could improve the LRRFS in stage III gastric cancer treated with R0 gastrectomy and D2 lymph node dissection., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To investigate the prognostic significance of tumor volume reduction rate (TVRR) after preoperative chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC)., Methods and Materials: In total, 430 primary LARC (cT3-4) patients who were treated with preoperative CRT and curative radical surgery between May 2002 and March 2008 were analyzed retrospectively. Pre- and post-CRT tumor volumes were measured using three-dimensional region-of-interest MR volumetry. Tumor volume reduction rate was determined using the equation TVRR (%) = (pre-CRT tumor volume--post-CRT tumor volume) × 100/pre-CRT tumor volume. The median follow-up period was 64 months (range, 27-99 months) for survivors. Endpoints were disease-free survival (DFS) and overall survival (OS)., Results: The median TVRR was 70.2% (mean, 64.7% ± 22.6%; range, 0-100%). Downstaging (ypT0-2N0M0) occurred in 183 patients (42.6%). The 5-year DFS and OS rates were 77.7% and 86.3%, respectively. In the analysis that included pre-CRT and post-CRT tumor volumes and TVRR as continuous variables, only TVRR was an independent prognostic factor. Tumor volume reduction rate was categorized according to a cutoff value of 45% and included with clinicopathologic factors in the multivariate analysis; ypN status, circumferential resection margin, and TVRR were significant prognostic factors for both DFS and OS., Conclusions: Tumor volume reduction rate was a significant prognostic factor in LARC patients receiving preoperative CRT. Tumor volume reduction rate data may be useful for tailoring surgery and postoperative adjuvant therapy after preoperative CRT., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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., (2011 Blackwell Publishing Limited.)

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., (Copyright © 2011 Wiley-Liss, Inc.)

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.

Background: To investigate whether whole-liver radiotherapy (RT) is beneficial in end-stage colorectal cancer with massive liver metastases and severe hepatic dysfunction., Methods: Between June 2004 and July 2008, 10 colorectal cancer patients, who exhibited a replacement of over three quarters of their normal liver by metastatic tumors and were of Child-Pugh class B or C in liver function with progressive disease after undergoing chemotherapy, underwent whole-liver RT. RT was administered using computed tomography-based three-dimensional planning and the median dose was 21 Gy (range, 21-30) in seven fractions. Improvement in liver function tests, defined as a decrease in the levels within 1 month after RT, symptom palliation, toxicity, and overall survival were analyzed retrospectively., Results: Levels of alkaline phosphatase, total bilirubin, aspartate transaminase, and alanine transaminase improved in 8, 6, 9, and all 10 patients, respectively, and the median reduction rates were 42%, 68%, 50%, and 57%, respectively. Serum carcinoembryonic antigen level decreased after RT in three of four assessable patients. For all patients, pain levels decreased and acute toxicity consisted of nausea/vomiting of grade ≤ 2. Further chemotherapy became possible in four of 10 patients. Mean survival after RT was 80 ± 80 days (range, 20-289); mean survival for four patients who received post-RT chemotherapy was 143 ± 100 days (range, 65-289), versus 38 ± 16 days (range, 20-64) for the six patients who did not receive post-RT chemotherapy (p = 0.127)., Conclusions: Although limited by small case number, this study demonstrated a possible role of whole-liver RT in improving hepatic dysfunction and delaying mortality from hepatic failure for end-stage colorectal cancer patients with massive liver metastases. Further studies should be followed to confirm these findings.

Purpose: To determine whether the tumor volume reduction rate (TVRR) measured using three-dimensional region-of-interest magnetic resonance volumetry correlates with the pathologic tumor response after preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer., Methods and Materials: The study included 405 patients with locally advanced rectal cancer (cT3-T4) who had undergone preoperative CRT and radical proctectomy. The tumor volume was measured using three-dimensional region-of-interest magnetic resonance volumetry before and after CRT but before surgery. We analyzed the correlation between the TVRR and the pathologic tumor response in terms of downstaging and tumor regression grade (TRG). Downstaging was defined as ypStage 0-I (ypT0-T2N0M0), and the TRG proposed by Dworak et al. was used., Results: The mean TVRR was 65.0% +/- 22.3%. Downstaging and complete regression occurred in 167 (41.2%) and 58 (14.3%) patients, respectively. The TVRRs according to ypT classification (ypT0-T2 vs. ypT3-T4), ypN classification (ypN0 vs. ypN1-N2), downstaging (ypStage 0-I vs. ypStage II-III), good regression (TRG 3-4 vs. TRG 1-2), and complete regression (TRG 4 vs. TRG 1-3) were all significantly different (p <.05). When the TVRR was categorized into three groups (<60%, 60-80%, and >80%), the rates of ypT0-T2, ypN0, downstaging, and good regression were all significantly greater for patients with a TVRR of >or=60%, as was the complete regression rate for patients with a TVRR >80% (p <.05)., Conclusion: The TVRR measured using three-dimensional region-of-interest magnetic resonance volumetry correlated significantly with the pathologic tumor response in terms of downstaging and TRG after preoperative CRT for locally advanced rectal cancer., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

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., (Copyright 2010 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the role of serum carcinoembryonic antigen (CEA) as a predictor of response to preoperative chemoradiotherapy (CRT) and prognostic factor for rectal cancer., Materials and Methods: The study retrospectively evaluated 352 locally advanced rectal cancer patients who underwent preoperative CRT followed by surgery. Serum CEA levels were determined before CRT administration (pre-CRT CEA) and before surgery (post-CRT CEA). Correlations between pre-CRT CEA levels and rates of good response (Tumor regression grade 3/4) were explored. Patients were categorized into three CEA groups according to their pre-/post-CRT CEA levels (ng/mL) (Group A: pre-CRT CEA 3, post-CRT CEA 3 ng/mL), and their oncologic outcomes were compared., Results: Of 352 patients, good responses were achieved in 94 patients (26.7%). The rates of good response decreased significantly as the pre-CRT CEA levels became more elevated (CEA [ng/mL]: 9, 7.8%; p < 0.001). The rates of good response were significantly higher in Group A than in Groups B and C (36.4% vs. 17.3% and 14.3%, respectively; p < 0.001). The 3-year disease-free survival rate was significantly better in Groups A and B than in Group C (82% and 79% vs. 57%, respectively; p = 0.005); the CEA grouping was identified as an independent prognostic factor (p = 0.025)., Conclusions: In locally advanced rectal cancer patients, CEA levels could be of clinical value as a predictor of response to preoperative CRT and as an independent prognostic factor after preoperative CRT and curative surgery.

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.

Purpose: To evaluate geometric shifting of the porta hepatis induced by liver regeneration during radiotherapy (RT) after partial hepatectomy for biliary tract cancer., Methods and Materials: Between August 2004 and August 2005, the study enrolled 10 biliary tract cancer patients who underwent hemihepatectomy or more extensive surgery and were scheduled to receive postoperative RT. All patients received 4500 cGy RT in 25 fractions with concurrent 5-fluorouracil. Before RT and in the third and fifth weeks during RT, the liver volume was determined using CT, and geometric location of the porta hepatis was determined using a conventional simulator., Results: The liver volume increase during RT was 246.6 +/- 118.2 cm(3). The overall actual shifting length of the porta hepatis was 9.8 +/- 2.5 mm, with right and left hepatectomy causing a 10.1 +/- 1.7 mm shift to the right or 9.2 +/- 4.3 mm shift to the left, respectively. The actual shifting length of the porta hepatis was proportional to the increase in liver volume during RT (r = 0.742, p = 0.014)., Conclusion: The results of this study have demonstrated that the porta hepatis can be shifted by liver regeneration after partial hepatectomy. We recommend an additional RT margin or adaptive RT (repeat planning at several intervals during the treatment course) to avoid exclusion of the porta hepatis from the RT target volume after partial hepatectomy for biliary tract cancer.

Background: It is well known that the risk of lymph node involvement increases according to pathologic T classification in rectal cancers, but to the authors' knowledge, the correlation between risk of lymph node involvement and ypT classification in rectal cancers treated with preoperative chemoradiotherapy (CRT) remains unclear. The current study investigated the correlation between tumor involvement in regional lymph nodes and rectal mural tumor status in patients who underwent preoperative CRT for rectal cancer., Methods: Between October 2001 and February 2005, 282 patients underwent preoperative CRT followed by proctectomy for locally advanced rectal adenocarcinoma. Correlations between lymph node status and ypT classification, Dworak regression grade, and magnetic resonance (MR) volumetry findings were explored., Results: Lymph nodes harboring tumors were found in 87 of 282 (30.9%) patients. The rate of lymph node involvement was found to be correlated with ypT-classification (P < .001); positive lymph nodes were detected in 1 of 45 (2.2%) ypT0 patients, 1 of 13 (7.7%) ypT1 patients, 13 of 77 (16.9%) ypT2 patients, 69 of 140 (49.3%) ypT3 patients, and 3 of 7 (42.9%) ypT4 patients. The rate of lymph node involvement decreased as Dworak regression grade increased (P < .001); tumor-harboring lymph nodes were found in 62.3% of Grade 1 patients, 31.4% of Grade 2 patients, 16.1% of Grade 3 patients, and 2.2% of Grade 4 patients. There were no differences noted with regard to MR volumetry findings, including mean volume of pre- or post-CRT tumor and the tumor volume reduction rate between lymph node-negative and lymph node-positive patients., Conclusions: Pathologic T classification is still the most reliable predictor of lymph node metastasis in rectal cancer patients who have undergone preoperative CRT. The risk of lymph node metastasis was found to be 3.4% in rectal cancer that had regressed to ypT0 or ypT1., (2006 American Cancer Society)

Purpose: To compare the effect of reducing the irradiated small-bowel volume with the use of belly board, bladder distension or both methods combined, in patients with rectal cancer undergoing postoperative pelvic radiotherapy., Patients and Methods: This study enrolled 20 consecutive patients with rectal cancer who were scheduled to receive postoperative pelvic radiotherapy. All patients underwent four sets of CT scans under four different methods as follows: group I: empty bladder without the use of a belly board; group II: empty bladder with the use of a belly board; group III: bladder distension without the use of a belly board; group IV: bladder distension with the use of a belly board. The conventional three-field treatment plan was made using a three-dimensional treatment planning system. The irradiated small-bowel volume was calculated at 10% intervals from 10% to 100% of the prescribed dose., Results: The volume of the irradiated small bowel decreased in the order of group I, group II, group III, and group IV at all dose levels (p < 0.001). In comparison to group I, the mean absolute volume reductions (relative volume reduction) of the irradiated small bowel were 41.5 +/- 20.1 cm(3) (33.9 +/- 12.9%) in group II, 76.6 +/- 30.5 cm(3) (55.1 +/- 17.8%) in group III, and 98.5 +/- 36.7 cm(3) (70.7 +/- 14.5%) in group IV., Conclusion: Bladder distension was a more effective method than the belly board for reducing the irradiated small-bowel volume in postoperative pelvic radiotherapy of rectal cancer patients. The combination of the belly board and bladder distension showed an additive effect and was the most effective method for reducing the irradiated small-bowel volume.

Granular cell tumor (GCT) is uncommon in the colon and rectum. Here we report a case of GCT in the transverse colon. A 48-year-old male patient underwent a screening colonoscopy. A yellowish sessile lesion, about 4 mm in diameter, was found in the transverse colon. An endoscopic snare resection was performed without complication. Histological examination revealed the tumor consisted of plump neoplastic cells with abundant granular eosinophilic cytoplasm containing acidophilic periodic acid Schiff-positive, diastase-resistant granules. Immunohistochemical analysis showed the tumor cells expressed S-100 protein and neuron-specific enolase. Thus, the resected tumor was diagnosed as a GCT. Since GCTs are usually benign, endoscopic resection constitutes an easy and safe treatment. Colonoscopists should consider the possibility of GCT in the differential diagnosis of submucosal tumors of the colon.

Background and Aim: Debate that Helicobacter pylori might play a causative role in gastric carcinogenesis still exists in spite of the World Health Organization's definition of H. pylori as a class I carcinogen. In order to define the exact role of H. pylori infection in gastric carcinogenesis, we established a mice model of H. pylori infection., Methods: One hundred and forty-four female C57BL/6 mice were divided into nine groups according to N-methyl-N-nitrosourea (MNU) treatment and H. pylori infection. All mice were killed at the 50th or 80th week after treatment, and their histopathological changes were evaluated according to group., Results: The incidence of gastric adenocarcinoma at the 50th week was 80% in mice treated with both MNU 240 microg/L and H. pylori infection, whereas the incidence was only 27% in mice treated with only MNU 240 microg/L. Although H. pylori caused marked expansion of the proliferative zone at the surface epithelium, H. pylori infection alone caused only chronic atrophic gastritis without any evidence of carcinomas until 80 weeks. The combination of MNU and H. pylori infection also resulted in a significantly higher incidence of gastric adenoma and adenocarcinoma. Significantly higher expressions of proliferating cell nuclear antigen were noted in the gastric mucosa infected with H. pylori compared to controls., Conclusions: These results clearly demonstrated the role of H. pylori infection, rather than direct carcinogens, in promoting gastric carcinogenesis in a mice model., (Copyright 2002 Blackwell Science Asia Pty Ltd)