Risk factors for colorectal cancer in a fecal immunochemical test-positive group: The National Health Insurance Service-National Health Screening Cohort.

BACKGROUND AND AIM: Colorectal cancer (CRC) was the fourth most common cancer in Republic of Korea in 2019. It has a gradually increasing mortality rate, indicating the importance of screening for CRC. Among the various CRC screening test, fecal immunochemical test (FIT) is a simple yet most commonly used. Neverthelss, there have been only few long-term studies on subjects with FIT-positive. Therefore, in this study, we aimed to investigate the risk factors for CRC in FIT-positive patients using the National Health Insurance Service Bigdata database. METHODS: Among 1 737 633 individuals with a FIT screening result for CRC in 2009, 101 143 (5.82%) were confirmed to be FIT positive. The CRC incidence over 10 years (up to 2018) of these participants was investigated using the National Cancer Registry. RESULTS: Out of the 101 143 FIT-positive participants, 4395 (4.35%) were diagnosed with CRC. The FIT-positive patients who underwent a second round of screening showed a 5-year cumulative CRC incidence of approximately 1.25%, whereas those who did not showed an incidence of approximately 3.75%. Among the FIT-positive patients, the CRC incidence in the non-compliance group for the second round of screening was 2.8 times higher than that in the compliance group. CONCLUSIONS: In FIT-positive participants, non-compliance with the second round of screening was identified as a major risk factor for CRC development. It is necessary to establish appropriate strategies for managing risk factors for CRC in FIT-positive patients to increase the rate of compliance with the second round of CRC screening.

Effects of prior endoscopic resection on recurrence in patients with T1 colorectal cancer who underwent radical surgery.

PURPOSE: Endoscopic resection (ER) is a reliable treatment for early colorectal cancer without lymph node metastasis. We aimed to examine the effects of ER performed prior to T1 colorectal cancer (T1 CRC) surgery by comparing long-term survival after radical surgery with prior ER to that after radical surgery alone. METHODS: This retrospective study included patients who underwent surgical resection of T1 CRC at the National Cancer Center, Korea, between 2003 and 2017. All eligible patients (n = 543) were divided into primary and secondary surgery groups. To ensure similar characteristics between the groups, 1:1 propensity score matching was used. Baseline characteristics, gross and histological features, along with postoperative recurrence-free survival (RFS) between the two groups were compared. Cox proportional hazard model was used to identify the risk factors affecting recurrence after surgery. Cost analysis was performed to examine the cost-effectiveness of ER and radical surgeries. RESULTS: No significant differences were observed in 5-year RFS between the two groups in matched data (96.9% vs. 95.5%, p = 0.596) and in the unadjusted model (97.2% vs. 96.8%, p = 0.930). This difference was also similar in subgroup analyses based on node status and high-risk histologic features. ER before surgery did not increase the medical costs of radical surgery. CONCLUSION: ER prior to radical surgery did not affect the long-term oncologic outcomes of T1 CRC or significantly increased the medical costs. Attempting ER first for suspected T1 CRC would be a good strategy to avoid unnecessary surgery without concerns of worsening cancer-related prognosis.

Subpopulation analysis of survival in high-risk T1 colorectal cancer: surgery versus endoscopic resection only.

BACKGROUND AND AIMS: This study aimed to assess the long-term survival of patients with T1 colorectal cancer (CRC) after local or surgical resection considering the type and number of risk factors for lymph node metastasis. METHODS: This study included patients with high-risk T1 CRC who underwent therapeutic resection at the National Cancer Center, Korea between January 2001 and December 2014. Risk factors included positive resection margin, high-grade histology, deep submucosal invasion, vascular invasion, budding, and no background adenoma (BGA). We statistically divided the population into favorable or unfavorable subpopulations. The favorable subpopulation included the following 5 combinations of risk factors: positive margin only or unconditional for margin status, deep submucosal invasion only, budding only, no BGA only, and budding + no BGA. We analyzed the survival rate according to the resection type (local or surgical) in the total cohort and in each subpopulation. RESULTS: Eighty-one and 466 patients underwent local and surgical resections, respectively. The distant recurrence-free survival (DRFS) and overall survival (OS) rates were significantly high in the surgical group (hazard ratio [HR], .20; 95% confidence interval [CI], .06-.61; P = .0045 and HR, .41; 95% CI, .25-.70; P = .0010, respectively). In the favorable subpopulation, both DRFS and OS rates were not significantly different between the surgical and local groups (HR, .26; 95% CI, .02-4.19; P = .3431 and HR, .58; 95% CI, .27-1.23; P = .1534, respectively). CONCLUSIONS: Intensive surveillance without additional surgery may be another option in selected cases after of high-risk T1 CRC endoscopic resection.

IL-6 and IL-8, secreted by myofibroblasts in the tumor microenvironment, activate HES1 to expand the cancer stem cell population in early colorectal tumor.

Interaction between a tumor and its microenvironment is important for tumor initiation and progression. Cancer stem cells (CSCs) within the tumor interact with a microenvironmental niche that controls their maintenance and differentiation. We investigated the CSC-promoting effect of factors released from myofibroblasts into the microenvironment of early colorectal cancer tumors and its molecular mechanism. By messenger RNA microarray analysis, expression of HES1, a Notch signaling target, significantly increased in Caco-2 cells cocultured with 18Co cells (pericryptal myofibroblasts), compared to its expression in Caco-2 cells cultured alone. Caco-2 cells cultured in 18Co-conditioned media (CM) showed a significant increase in CD133+CD44+ cells and HES1 expression compared to that in Caco-2 cells cultured in regular media. Significant amounts of interleukin-6 (IL-6) and IL-8 were detected in 18Co-CM compared to levels in regular media. The 18Co-CM-induced increase in CD133+CD44+ cells was attenuated by IL-6- and IL-8-neutralizing antibodies. Furthermore, these neutralizing antibodies and inhibitors of STAT3 and gamma-secretase reduced the expression of HES1 induced in Caco-2 cells cultured in 18Co-CM. Immunohistochemical analysis of human tissues revealed that IL-6, IL-8, and HES1 expression increased from normal to adenoma, and from adenoma to cancer tissues. In addition, IL-6 and HES1 expression was positively correlated in early colorectal cancer tissues. In conclusion, the increase of CSCs by myofibroblasts could be mediated by IL-6/IL-8-induced HES1 activation in the tumor microenvironment. Based on these data, the IL-6/IL-8-mediated Notch/HES1 and STAT3 pathway, through which CSCs interact with their microenvironment, might be a potential target for the prevention and treatment of colorectal tumors.

Comparison of endoscopic submucosal dissection and transanal endoscopic microsurgery for T1 rectal neuroendocrine tumors: a propensity score-matched study.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) and transanal endoscopic microsurgery (TEM) are the most effective endoscopic resection methods for T1 rectal neuroendocrine tumors (NETs). We aimed to compare the efficacy and safety of ESD and TEM for rectal NETs ≤20 mm. METHODS: Patients with rectal NETs ≤20 mm who underwent ESD or TEM were enrolled in this retrospective observational study. ESD and TEM groups were matched for pathologic tumor size and EMR history. We evaluated between-group differences in R0 resection rate, adverse event rate, procedure time, and hospital stay. RESULTS: We included 285 patients (ESD = 226, TEM = 59) in the final cohort, with 104 patients in the matched groups (ESD = 52, TEM = 52). The R0 resection rate was significantly higher for TEM (ESD 71.2% vs TEM 92.3%, P = .005). However, the median procedure time (ESD 22 [range, 11-65] vs TEM 35 [17-160] minutes, P < .001) and hospital stay (ESD 2.5 range 1-5] vs TEM 4 [3-8] days, P < .001) were significantly shorter for ESD. In the subgroup analysis of patients divided by tumor size <10 mm (ESD = 218, TEM = 49) and 10 to 20 mm (ESD = 8, TEM = 10)], there was no significant between-group difference in the R0 resection rate (83.5% vs 93.9%, P = .063 and 37.5% vs 80%, P = .145, respectively) or the rate of recurrence. CONCLUSIONS: Although TEM showed a better overall R0 resection rate for rectal NETs ≤20 mm, ESD could be a viable treatment modality concerning adverse events, procedure time, and hospital stay for rectal NETs <10 mm with similar R0 resection rates in comparison with TEM.

Comparison of underwater endoscopic mucosal resection and endoscopic submucosal dissection of rectal neuroendocrine tumors (with videos).

BACKGROUND AND AIMS: The first choice of treatment for rectal neuroendocrine tumors (NETs) ≤10 mm in size is endoscopic resection. However, because rectal NETs usually invade the submucosal layer, achieving R0 resection is difficult. Endoscopic submucosal dissection (ESD) has a high R0 resection rate, and underwater endoscopic mucosal resection (UEMR) was recently introduced to ensure a negative resection margin easily and safely. The aim of this study was to evaluate the efficacy and safety of UEMR versus ESD for rectal NETs ≤10 mm in size. METHODS: This retrospective observational study enrolled 115 patients with rectal NETs ≤10 mm in size who underwent ESD or UEMR between January 2015 and July 2019 at the National Cancer Center, Korea. The differences in R0 resection rate, adverse event rate, and procedure time between the ESD and UEMR groups were evaluated. RESULTS: Of the 115 patients, 36 underwent UEMR and 79 underwent ESD. The R0 resection rate was not different between the UEMR and ESD groups (UEMR vs ESD, 86.1% vs 86.1%, P = .996). The procedure time was significantly shorter with UEMR (UEMR vs ESD, 5.8 ± 2.9 vs 26.6 ±13.4 minutes, P < .001). Two patients (2.5%, 2/79) experienced adverse events in the ESD group and but there were no adverse events in the UEMR group; however, this difference was not statistically significant. CONCLUSION: UEMR is a safe and effective technique that should be considered when removing small rectal NETs. Further studies are warranted to define its role compared with ESD.

Analysis of metachronous colorectal neoplasms and survival following segmental or extended resection in patients with hereditary non-polyposis colorectal cancer.

PURPOSE: The high incidence of metachronous colorectal tumours in patients with hereditary non-polyposis colorectal cancer (HNPCC) encourages extended resection (ER); however, the optimal surgical approach remains unclear. We evaluated the incidences of metachronous colorectal neoplasms following curative colorectal cancer segmental resection (SR) vs ER in patients with HNPCC and investigated patients' oncologic outcomes according to surgical modality and mismatch repair status. METHODS: We retrospectively investigated medical records of patients with HNPCC (per the Amsterdam II criteria) treated for primary colon cancer at our institution between 2001 and 2017. All patients underwent intensive endoscopic surveillance. RESULTS: We included 87 patients (36 who underwent SR and 51 who underwent ER). The cumulative incidence of metachronous adenoma was higher in the SR group. One patient in the SR group (2.8%) and 3 in the ER group (5.9%) developed metachronous colon cancer; the difference was not significant (P = 0.693). Four patients in the SR group (11.1%) and 1 in the ER group (2.0%) developed distant recurrences; again, the difference was not significant (P = 0.155). Moreover, no significant differences were observed in the 5-year overall survival rates of patients in the SR and ER groups (88.2% vs 95.5%, P = 0.446); the same was true for 5-year disease-free survival rates (79.5% vs 91.0%, P = 0.147). CONCLUSION: The incidence of metachronous cancer was not significantly different between the ER and SR groups; however, that of cumulative metachronous adenoma was higher in the SR group. Hence, intensive surveillance colonoscopy may be sufficient for patients with HNPCC after non-extensive colon resection.

Risk of recurrence after endoscopic resection of early colorectal cancer with positive margins.

BACKGROUND AND STUDY AIM: Additional surgery is recommended if an endoscopically resected T1 colorectal cancer (CRC) specimen shows a positive resection margin. We aimed to investigate the significance of a positive resection margin in endoscopically resected T1 CRC. PATIENTS AND METHODS: We enrolled 265 patients with T1 CRC who underwent endoscopic resection between January 2001 and December 2016. The inclusion criteria were: 1) complete resection by endoscopy, and 2) pathology of a positive margin. Among the 265 patients, 213 underwent additional surgery and 52 did not. In the additional surgery group, various clinicopathological factors were evaluated with respect to the presence or absence of residual tumor. The follow-up results were assessed in the group that did not undergo additional surgery. RESULTS: In the 213 patients who underwent additional surgery, residual tumor was detected in 13 patients (6.1 %), and none of the clinicopathological factors was significantly associated with the presence of residual tumor. Among the 52 patients who did not undergo additional surgery, recurrence was detected in 4 (7.7 %), and all 4 underwent salvage surgery. Among these four patients, three had no risk factors for lymph node metastasis and recurrence was at the previous resection site; pathology was high grade dysplasia, rpT3N0M0, and rpT1N0M0, respectively. CONCLUSIONS: A positive resection margin in endoscopically resected T1 CRC is related to a relatively low incidence of residual tumor (6.1 %). Although current guidelines recommend additional surgery for such cases, surveillance and timely salvage surgery could be another option in selected cases.

Helicobacter pylori infection is an independent risk factor for colonic adenomatous neoplasms.

PURPOSE: Helicobacter pylori infection is considered to have a positive association with colorectal neoplasms. In this study, we evaluated the association between H. pylori infection and colorectal adenomas, based on the characteristics of these adenomas in Korea, where the prevalence of H. pylori infection is high and the incidence of colorectal cancer continues to increase. METHODS: The study cohort consisted of 4,466 subjects who underwent colonoscopy and esophagogastroduodenoscopy during screening (1,245 colorectal adenomas vs. 3,221 polyp-free controls). We compared the rate of H. pylori infection between patients with adenoma and polyp-free control cases, using multivariable logistic regression analysis. RESULTS: The overall rate of positive H. pylori infection was higher in adenoma cases than in polyp-free control cases (55.0 vs. 48.5%, p < 0.001). The odds ratio (OR) of positive H. pylori infection in patients with adenoma compared to polyp-free controls was 1.28 (95% CI 1.11-1.47). The positive association of H. pylori infection with colorectal adenomas was more prominent in advanced adenomas (OR 1.84, 95% CI 1.25-2.70) and multiple adenomas (OR 1.72, 95% CI 1.26-2.35). Based on the location of these adenomas, the OR was significant only in patients with colonic adenomas (OR 1.31, 95% CI 1.13-1.52) and not in those with rectal adenoma (OR 0.85, 95% CI 0.58-1.24). CONCLUSION: Helicobacter pylori infection is an independent risk factor for colonic adenomas, especially in cases of advanced or multiple adenomas, but not for rectal adenomas.

The Significance of the Prognostic Nutritional Index for All Stages of Pancreatic Cancer.

Nutritional status affects the prognosis of various tumors. The prognostic nutritional index (PNI) is the known predictor of postoperative outcome in resectable pancreatic cancer patients. This study aimed to validate the prognostic value of PNI in all stages of pancreatic cancer. We retrospectively reviewed 499 patients with pancreatic cancer who were diagnosed at Severance Hospital between January 2006 and December 2011. The PNI value was calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (/mm3) at initial diagnosis. The median patient age was 62 yr, and 289 were men. The study group comprised resectable disease (n = 121), locally advanced disease (n = 118), and metastatic disease (n = 260). Univariate and multivariate analysis revealed that PNI ≤ 49.5 at initial diagnosis, together with performance status, platelet count, and clinical stage, was significantly associated with overall survival (hazard ratio, 1.562; all P < 0.05). Patients with PNI ≤ 49.5 (n = 208) had shorter median overall survival compared to patients with high PNI (9.8 vs. 14.2 mo; log rank, P < 0.001). In clinical stage subgroup analysis, initial PNI ≤49.5 independently predicted shorter overall survival, especially in resectable and metastatic disease (P = 0.041, P = 0.002, respectively).

Visceral Adipose Tissue Volume and the Occurrence of Colorectal Adenoma in Follow-up Colonoscopy for Screening and Surveillance.

Whether obesity accelerates adenoma recurrence is not yet clear; therefore, we analyzed the risk factors for adenoma occurrence at follow-up colonoscopy, with a focus on visceral adiposity. In total, 1516 subjects underwent index colonoscopy, computed tomography, and questionnaire assessment from February to May 2008; 539 subjects underwent follow-up colonoscopy at the National Cancer Center at least 6 mo after the index colonoscopy. The relationships between the presence of adenoma at follow-up colonoscopy and anthropometric obesity measurements, including body mass index (BMI), waist circumference (WC), visceral adipose tissue (VAT) volume, and subcutaneous adipose tissue (SAT) volume, were analyzed. 188 (34.9%) had adenomatous polyps at follow-up colonoscopy. Multivariate analysis revealed that VAT volume ≥ 1000 cm3 and BMI ≥ 30 kg/m2 were related to the presence of adenoma at follow-up colonoscopy (VAT volume 1000-1500 cm3: odds ratio [OR] = 2.13(95% confidence interval, CI = 1.06-4.26), P = 0.034; VAT volume ≥ 1000 cm3: OR = 2.24(95% CI = 1.03-4.88), P = 0.043; BMI ≥ 30 kg/m2: OR = 4.22(95% CI = 1.12-15.93), P = 0.034). In contrast, BMI 25-29.9 kg/m2, SAT volume, and WC were not associated with the presence of adenoma at follow-up colonoscopy. In conclusion, excess VAT can contribute to the development and growth of new colorectal adenomas, and is a better predictor of colorectal adenoma occurrence at follow-up colonoscopy than BMI, WC, and SAT volume.

Comparative Evaluation of the Efficacy of Polyethylene Glycol With Ascorbic Acid and an Oral Sulfate Solution in a Split Method for Bowel Preparation: A Randomized, Multicenter Phase III Clinical Trial.

BACKGROUND: An adequate level of bowel preparation before colonoscopy is important. The ideal agent for bowel preparation should be effective and tolerable. OBJECTIVE: The purpose of this study was to compare the clinical efficacy and tolerability of polyethylene glycol with ascorbic acid and oral sulfate solution in a split method for bowel preparation. DESIGN: This was a prospective, multicenter, randomized controlled clinical trial. SETTINGS: Outpatients at the specialized clinics were included. PATIENTS: A total of 186 subjects were randomly assigned. After exclusions, 84 subjects in the polyethylene glycol with ascorbic acid group and 83 subjects in the oral sulfate solution group completed the study and were analyzed. INTERVENTIONS: Polyethylene glycol with ascorbic acid or oral sulfate solution in a split method was the included intervention. MAIN OUTCOME MEASURES: The primary end point was the rate of successful bowel preparation, which was defined as being excellent or good on the Aronchick scale. Tolerability and adverse events were also measured. RESULTS: Success of bowel preparation was not different between 2 groups (91.7% vs 96.4%; p = 0.20), and the rate of adverse GI events (abdominal distension, pain, nausea, vomiting, or abdominal discomfort) was not significantly different between the 2 groups. In contrast, the mean intensity of vomiting was higher in the oral sulfate solution group than in the polyethylene glycol with ascorbic acid group (1.6 ± 0.9 vs 1.9 ± 1.1; p = 0.02). LIMITATIONS: All of the colonoscopies were performed in the morning, and the subjects were offered enhanced instructions for bowel preparation. In addition, the results of tolerability and adverse effect may have a type II error, because the number of cases was calculated for confirming the efficacy of bowel preparation. CONCLUSIONS: Oral sulfate solution is effective at colonoscopy cleansing and has acceptable tolerability when it is compared with polyethylene glycol with ascorbic acid. The taste and flavor of oral sulfate solution still need to be improved to enhance tolerability.

Fecal calprotectin as a non-invasive biomarker for intestinal involvement of Behçet's disease.

BACKGROUND AND AIM: The diagnostic and prognostic values of fecal calprotectin (FC) levels in patients with inflammatory bowel diseases have been proven. However, little is known about the usefulness of FC measurement in predicting intestinal involvement of Behçet's disease (BD). METHODS: Forty-four consecutive patients with systemic BD who underwent colonoscopy for the evaluation of gastrointestinal symptoms were prospectively enrolled between November 2012 and March 2014 in a single tertiary medical center. Fecal specimens from the patients were obtained the day before bowel cleansing and 3 months after colonoscopy. RESULTS: Twenty-five patients showed intestinal ulcerations on colonoscopy (12 [48.0%] typical and 13 [52.0%] atypical ulcerations). The median FC level in the intestinal BD group was significantly higher than that in the non-diagnostic group (112.53 [6.86-1604.39] vs 31.64 [5.46-347.60] µg/g, respectively, P = 0.003). Moreover, the typical ulceration group showed a significantly higher median FC level than the atypical ulceration group in patients with intestinal BD (435.995 [75.65-1604.39] vs 71.42 [6.86-476.94] µg/g, respectively, P = 0.033). Multivariate analysis revealed higher FC as an independent predictor of intestinal BD (OR = 38.776; 95% CI = 2.306-652.021; P = 0.011). The cut-off level of FC for predicting intestinal BD was 68.89 µg/g (76% sensitivity and 79% specificity). The absolute changes between fecal calprotectin levels and the disease activity index of intestinal BD from initial diagnosis of intestinal BD to 3 months after diagnosis were significantly correlated (Pearson's correlation coefficient = 0.470, P = 0.027). CONCLUSION: The FC level might serve as a non-invasive surrogate marker of intestinal involvement of BD.

Probe-based confocal laser endomicroscopy for evaluating the submucosal invasion of colorectal neoplasms.

BACKGROUND: Probe-based confocal laser endomicroscopy (pCLE) is a novel method for in vivo histological analysis of colorectal neoplasm mucosa, which provides meaningful information for the development of adequate therapeutic strategies. However, the in vivo histology of colorectal neoplasm submucosa has not been studied. We assessed the feasibility and safety of pCLE for evaluating colorectal submucosa, and identified and validated diagnostic criteria for submucosal carcinoma infiltration. METHODS: From March to July 2014, 83 pCLE videos of 51 lesions in 31 patients who underwent scheduled colonoscopic procedures for the removal of colorectal neoplasms were acquired consecutively. During the procedures, pCLE videos of the lesions and biopsy samples for histopathological analysis were acquired. Final histopathological results were used as the gold standard. RESULTS: Based on the confocal pattern, we classified colorectal submucosa findings as negative (superficial submucosa, deep submucosa, and submucosa with fibrosis) or indicative of carcinoma infiltration. Dark and irregular cell nests with irregular cell architecture and little or no mucin were seen in submucosal carcinoma infiltration. Based on rates of correlation with pathological findings, the sensitivity, specificity, and accuracy of the classification of submucosal carcinoma infiltration by two observers were 91.7, 86.8, and 88.0 %, respectively. In addition, the results showed good interobserver agreement for the detection of submucosal carcinoma infiltration (κ = 0.757, standard error = 0.102). No adverse events occurred during the procedures. CONCLUSIONS: Submucosa assessment by pCLE is feasible and safe. pCLE is useful for the differentiation of normal submucosa from carcinoma infiltration, particularly when infiltration is accompanied by severe fibrosis. Large-scale prospective studies are needed to further evaluate the clinical impact of the use of pCLE during endoscopy.

Visceral Obesity is Associated with Poor Prognosis in Pancreatic Adenocarcinoma.

An association between obesity and unfavorable outcomes for various types of malignancy has been established. Nevertheless, the impact of visceral obesity (VO) on outcomes in pancreatic cancer is still unknown and controversial. The aim of this study was to uncover an association between VO and pancreatic cancer outcomes. We retrospectively reviewed 499 patients with pancreatic cancer who were diagnosed and treated in Severance Hospital from January 2006 to December 2011. Compared to the low-VO group (n = 260), the high-VO group (n = 239) was mostly male (68.2% vs. 31.8%, P < 0.001) and was more likely to have current smoking status (29.7% vs. 17.7%, P < 0.001), current alcohol intake status (52.3% vs. 26.4%, P < 0.001) and diabetes mellitus (54.4% vs. 31.9%, P = 0.028). The progression free survival (PFS) and overall survival (OS) were found to be significantly shorter by the Kaplan-Meier method in the high-VO group than in the low-VO group (PFS; P = 0.044, OS: P = 0.013). In addition, the higher percentage of visceral fat was correlated with more lymph node metastasis and shorter OS (P = 0.011 and P = 0.017, respectively). In patients with pancreatic cancer, VO at the time of diagnosis is associated with negative outcomes, such as shorter PFS and OS.

Tumor characteristics associated with malignant large bowel obstruction in stage IV colorectal cancer patients undergoing chemotherapy.

PURPOSE: Little is known about predictable clinical factors associated with the occurrence of malignant large bowel obstruction (MLBO) in incurable stage IV colorectal cancer (CRC) patients undergoing medical treatment. This study investigates the clinical characteristics associated with MLBO that occurred while patients with stage IV CRC were receiving chemotherapy. METHODS: A total of 216 patients who were diagnosed with stage IV CRC without bowel obstruction and who received chemotherapy between May 2005 and June 2012 were retrospectively included in this study. Patients were divided into an "obstruction group" and a "non-obstruction group" based on whether they did or did not develop MLBO during chemotherapy or follow-up, respectively. The initial endoscopic findings and clinical information were retrospectively reviewed and compared between the two groups. RESULTS: Forty-six patients (21.3 %) developed MLBO during the treatment or follow-up periods. The mean duration between diagnosis and MLBO was 9.8 ± 9.3 months. After adjusting for clinically relevant factors, MLBO development was independently associated with the following factors: higher initial tumor-occupying circumference (HR 1.030 [95 % CI, 1.012-1.049], P = 0.001), longer initial horizontal tumor width (HR 1.035 [95 % CI, 1.011-1.059], P = 0.004), primary tumor location at a turning point in the colon (HR 2.404 [95 % CI, 1.185-4.877], P = 0.015), and the presence of primary tumor ulceration at presentation (HR 3.767 [95 % CI, 1.882-7.538], P < 0.001). MLBO development was not associated with tumor response to chemotherapy. CONCLUSION: In patients with stage IV CRC, MLBO development during chemotherapy treatment is associated with tumor ulceration, location, circumference, and width at diagnosis.

Crohn's disease prognosis and early immunomodulator therapy: Results from the CONNECT study.

BACKGROUND: It is unknown whether the treatment initiating time of immunomodulators such as thiopurines affects the course of Crohn's disease (CD). We evaluated the efficacy of early immunomodulator therapy (EIT) on the prognosis of patients with CD. METHODS: We retrospectively analyzed 1157 patients with CD who were enrolled in the CrOhn's disease cliNical NEtwork and CohorT study and received immunomodulator therapy. The patients were divided into an EIT group and a conventional therapy group based on whether immunomodulators were initiated within six months after being diagnosed with CD. We compared the rates of intestinal surgery, bowel complications, and hospitalization because of CD between the groups. RESULTS: Patient age at diagnosis and sex were not significantly different between the two groups. The mean duration of follow-up was 105.8 ± 51.5 months. A Kaplan-Meier analysis identified that the EIT group was superior to the conventional therapy group in terms of delaying surgery (P = 0.017). In multivariate analysis, EIT was an independent predicting factor associated with delaying the onset of complications (P = 0.050). Patients were divided into two groups based on the year of CD diagnosis: from 1982 to 1999 (A) and from 2000 to 2008 (B). In group A, the time from diagnosis to the start of immunomodulatory therapy was longer (P < 0.001), and the time to first intestinal surgery was shorter than group B (P = 0.002). CONCLUSIONS: The early use of immunomodulators was associated with a good prognosis as defined by a need for surgery and the occurrence of complications in CD in our multicenter study.

Combination of Corticosteroids with 5-Aminosalicylic Acids Compared to Corticosteroids Alone for Hospitalized Patients with Active Ulcerative Colitis.

BACKGROUND: Although 5-amino-salycilic acids (5-ASA) are often used with corticosteroid treatment in moderate-to-severe ulcerative colitis, the value of continuing/initiating 5-ASA in this clinical setting has not been explored. OBJECTIVES: To investigate the impact of a combination 5-ASA+corticosteroid therapy on the outcome of hospitalized patients with acute moderate-severe ulcerative colitis. METHODS: We conducted a retrospective study of patients hospitalized with moderate-severe ulcerative colitis in two centers, Israel and South Korea. Patients were classified into those who received 5-ASA and corticosteroids and those who received corticosteroids alone. Analysis was performed for each hospitalization event. The primary outcome was the rate of treatment failure defined as the need for salvage therapy (cyclosporin-A/infliximab/colectomy). The secondary outcomes were 30 days re-admission rates, in-hospital mortality rates, time to improvement, and length of hospitalization. RESULTS: We analyzed 209 hospitalization events: 151 patients (72%) received 5-ASA+corticosteroids and 58 (28%) corticosteroids alone. On univariate analysis the combination therapy group had a lower risk for treatment failure (11% vs. 31%, odds ratio 0.28, 95% confidence interval 0.13-0.59, P = 0.001). However, this difference disappeared on multivariate analysis, which showed pre-admission oral corticosteroid treatment to be the most significant factor associated with the need for salvage therapy. CONCLUSIONS: A signal for possible benefit of a combination 5-ASA and corticosteroids therapy was found, but was confounded by the impact of pre-admission corticosteroid treatment.

The efficacy of topical bupivacaine and triamcinolone acetonide injection in the relief of pain after endoscopic submucosal dissection for gastric neoplasia: a randomized double-blind, placebo-controlled trial.

BACKGROUND: Although pain is a common complication of endoscopic submucosal dissection (ESD), management strategies are inadequate. The aim of this study was to evaluate the efficacy of topical bupivacaine and triamcinolone acetonide for abdominal pain relief and as a potential method of pain control after ESD for gastric neoplasia. METHODS: In this randomized, double-blind, placebo-controlled trial, 111 eligible patients with early gastric neoplasm were randomized into one of three groups: bupivacaine (BV) only, bupivacaine with triamcinolone (BV-TA), or placebo. The present pain intensity (PPI) score and the Short-Form McGill Pain Questionnaire (SF-MPQ) were used to evaluate pain at 0, 6, 12, and 24 h after ESD. RESULTS: The mean values for the 6-hour PPI in the BV-TA and BV groups were lower than those of the placebo group (1.57 ± 1.09 and 1.97 ± 1.09 vs. 2.63 ± 0.98, p < 0.001). The 12-hour PPI of the BV-TA group (1.20 ± 0.83) was the lowest among the three groups (p = 0.001). The total 6-hour SF-MPQ score, especially in the sensory domain, was higher in the placebo group than in BV and BV-TA groups. The 12-hour SF-MPQ score was the lowest in the BV-TA group. Multivariate analysis demonstrated that BV-TA injection protocol, fibrosis, and size of residual ulcer were independently associated with the PPI score at 6 h. CONCLUSION: Bupivacaine after ESD was effective for pain relief at 6 h postoperatively. Particularly, topical infiltration of bupivacaine mixed with triamcinolone acetonide was helpful for producing a more long-lasting benefit of pain relief after gastric ESD.

Endoscopic quality indicators for esophagogastroduodenoscopy in gastric cancer screening.

BACKGROUND: Quality indicators of screening esophagogastroduodenoscopy are essential to improve the detection rate of gastric cancer. However, a reliable, practical indicator of the performance of endoscopists in screening esophagogastroduodenoscopy has not yet been identified. AIMS: We aimed to identify quality indicators of esophagogastroduodenoscopy for the detection of early gastric neoplasms, including gastric dysplasia and early gastric cancer, focusing on the endoscopic findings. METHODS: The records of 54,889 individuals who underwent esophagogastroduodenoscopy for gastric cancer screening at the Yonsei University Severance Hospital Health Promotion Center, Seoul, Korea, between February 2006 and July 2013 were analyzed. The detection rates for various gastric lesions including early gastric neoplasms were analyzed for each endoscopist. RESULTS: Gastric dysplasia, early gastric cancer, and advanced gastric cancer were detected in 97 (0.18 %), 54 (0.10 %), and 21 (0.04 %) of 54,889 individuals, respectively. Multivariate analysis showed that the detection rates of gastric subepithelial lesions and gastric diverticuli were independent factors associated with the detection rate of early gastric neoplasms (regression coefficients of 0.096 and 0.532, respectively). A quality score formula was deduced using these regression coefficients to predict the ability of an endoscopist to detect early gastric neoplasms. A trend test confirmed that the group of endoscopists with a higher quality score showed a significantly higher rate of early gastric neoplasm detection (P < 0.001). CONCLUSIONS: The detection rates of gastric subepithelial lesions and gastric diverticuli are well correlated with that of early gastric neoplasms. In addition, the proposed quality scoring system could be a good quality indicator for the detection of early gastric neoplasms.