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Purpose/Objective(s) There is a paucity of data studying the significance of neutrophil-to-lymphocyte ratio (NLR) in peripheral blood of patients with locally advanced rectal cancer (LARC) planning to undergo preoperative RT. We aimed to investigate the prognostic impact of NLR in patients with LARC and whether there are modifiable factors in RT which influencing the level of NLR. Materials/Methods We studied 1366 patients treated with neoadjuvant RT with concurrent or sequential chemotherapy for LARC from 2006 to 2019. Most (97.8%) were treated with long-course RT (50-50.4 Gy in 25-28 fractions) with 3DCRT (n = 851) or helical tomotherapy (n = 504). Short-course RT (25 Gy in 5 fractions, followed by 6-week XELOX) was used in 30 cases (NCT03676517). The absolute neutrophil and lymphocyte counts were obtained from the sample collected at the time of initial diagnosis, before and during the course of preoperative RT and before surgery. The primary endpoint was distant metastasis-free survival (DMFS). Results With the median follow-up time of 61.3 months (4.1-173.7 months), the 5-year DMFS was 80.1%. 5-year DMFS was significantly associated with the level of NLR after RT, but not with the level of NLR before RT. In Cox multivariate model, post-RT NLR greater than 4 was independently correlated with worse DMFS (HR 1.37, 95% CI, 1.08-1.73), along with higher icT stage, ypT stage and ypN stage. The 5-year OS of patients with post-RT NLR > 4.0 was 83.2%, compared to 94.4% in post-RT NLR ≤ 4 patients (P 4.0) was more frequently developed after long-course RT (OR, 2.77, P = 0.032) or helical tomotherapy (OR, 1.29, P .05). Conclusion Elevation of NLR after neoadjuvant RT is associated with increased risk of DM development and poor OS in LARC. Development of high NLR following RT is directly related to RT fractionation and delivery modality, and tumor characteristics. Incorporation of SCRT with 3D-CRT or active bone marrow sparing-IMRT may be a modifiable factor that can indirectly affect DMFS by means of attenuating NLR in LARC patients, which needs further investigations.

Background The impact of compliance with anti-tumour necrosis factor (TNF) on the clinical outcomes of Crohn’s disease (CD) is not well unknown. We performed a nationwide population-based study to investigate the impact of adherence to anti-TNF therapy on clinical outcomes in CD patients. Methods Using the National Health Insurance claims data, we collected data on newly diagnosed patients with CD between 2004 and 2015. Given that infliximab was listed in the National Health Insurance Service in 2006 and adalimumab in 2010, data only after the listing date were extracted. A total of 2784 patients were included according to inclusion criteria. Medication adherence was measured based on the following three criteria, including the ratio of delayed visit, the ratio of the number of visits, and the ratio of actual administration, and was assessed at four-point in time from the initial administration: 14, 22, 39, and 48 weeks. Results A total of 2179 patients received infliximab, and 605 patients received adalimumab. The mean cumulative actual to predetermined prescription ratio (CAPPR) at 14 and 48 weeks was 1.07 and 1.17, respectively. CAPPRs of infliximab users were higher than those of adalimumab users (1.06 and 1.21 vs. 1.02 and 1.04 at 14 and 48 weeks, respectively). As hospital visits were delayed one more day, risk of perianal surgery (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.089–1.333), corticosteroid use (OR = 1.008, 95% CI 1–1.016), and hospitalisation (OR = 1.05,95% CI 1.002–1.108) at 48 weeks were significantly increased. Moreover, as CAPPR decreased by 1 percent point, risk of bowel resection (OR = 1.589, 95% CI 0.713–3.542), perianal surgery (OR = 1.246, 95% CI 0.868–1.79), and hospitalisation (OR = 1.128, 95% CI 0.998–1.276) at 14 weeks were significantly increased. Conclusion Our data indicate that adherence to anti-TNF therapy affects major clinical outcomes of CD in the short- and mid-term period. Intervention to improving adherence to anti-TNF therapy is highly needed for better clinical outcomes in CD.

Background Recent advances in next generation sequencing technology helped us to test multiple germline genetic mutations simultaneously. However, because of the low frequency of pathogenic/ likely pathogenic variants beyond BRCA1/2, modest risk of cancer in the carriers of moderate penetrance genes, and lack of proper preventive strategies for the carriers, clinical application of NGS multiple panel tests still has limitations. Methods In this study, we provided sequential genetic testing and counselling programs for BRCA1/2 mutation tests and multigene panels beyond BRCA, and investigated cancer worry, genetic knowledge, and attitude towards gene panels among the patients. Results As of 28 February 2019, we prospectively enrolled 149 Korean BRCA1/2 mutation-negative female breast cancer patients with high risk for hereditary breast cancer. Median age of the patients was 42.9 (range, 21.9∼74.5) years. Among the patients, we identified 15 cases with pathogenic/ likely pathogenic variants. After genetic counselling about multigene panel, patients showed slightly decreased concern about the possibility of cancer in the future (average score of pre-, 4.32±0.808 to post-, 4.07±1.017; P = 0.003) and lower influence on mood (average score of pre-, 3.31±0.669 to post-, 3.19±0.684; P = 0.005). However, there were no changes in the average score of genetic knowledge (pre-, 0.68±0.212 to post-, 0.69±0.214; P = 0.465), and the impact of cancer worries on daily activities (pre-, 3.06±0.810 to post-, 2.97±0.699; P = 0.074). In the survey on multigene panel, 143 (96.0%) patients reported that genetic testing and counseling about multigene panel were very much (55.0%) or much (40.9%) helpful for the patients and family. 63 (42.3%) patients wanted concurrent application of BRCA1/2 mutation testing and multigene testing beyond BRCA, and 71 (47.7%) patients wanted sequential application of the tests. Conclusions Multigene panel testing and genetic counselling may help to decrease cancer worry about the possibility of cancer in the future in BRCA1/2 mutation-negative patients with high risk for hereditary breast cancer. We need to find the appropriate sequence and methods for NGS multigene panel testing and counselling programs. Legal entity responsible for the study The authors. Funding National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIT)(NRF-2018R1C1B6009449). Disclosure All authors have declared no conflicts of interest.

The implications of anti-Saccharomyces cerevisiae antibody for the diagnosis and the clinical course of Crohn's disease have been reported in Western countries, but rarely in Korea with its very different environmental and genetic backgrounds. We aimed to evaluate whether anti-S. cerevisiae antibody expression is associated with diagnostic findings, stratified Vienna classification phenotypes, disease activity and clinical course in Korean patients with Crohn's disease.One hundred and fifteen patients with Crohn's disease, diagnosed and treated between 1990 and 2004 at Severance Hospital, Yonsei University and followed for at least 2 years, were included in this study. Anti-S. cerevisiae antibody was detected by an indirect immunofluorescence assay using EUROIMMUN kits. Information collected during treatment included demography, Vienna classification phenotype, clinical manifestation, laboratory tests, treatment modality and surgery rate. Disease activity was measured monthly using the Harvey-Bradshaw index.The anti-S. cerevisiae antibody prevalence was 38.3% in Crohn's disease patients. There was no difference in anti-S. cerevisiae antibody expression between genders. The mean age at diagnosis was younger for the anti-S. cerevisiae antibody positive group than the negative group (25.3 years versus 29.7 years, p0.05). Clinical manifestations and laboratory tests at diagnosis did not differ between the groups. The anti-S. cerevisiae antibody positive group had increased fibrostenosis (B2) and penetration (B3) compared to negative group, as determined by the Vienna classification (75.0% versus 53.5%, p0.05). Anti-S. cerevisiae antibody positive patients were admitted to the hospital more frequently than anti-S. cerevisiae antibody negative patients (p0.05). The yearly cumulative Harvey-Bradshaw index score was higher in the anti-S. cerevisiae antibody positive group than in the negative group during the follow-up period (p0.05). In addition, steroid (72.7% versus 52.1%, p0.05) and immunosuppressive (45.5% versus 23.9%, p0.05) treatments were more frequently given to the anti-S. cerevisiae antibody positive group.Our data demonstrate that anti-S. cerevisiae antibody positive Crohn's disease patients had a more severe clinical course and thus often required more aggressive medical treatment.

BACKGROUND AND STUDY AIMS The factors that more accurately predict the detection of colorectal cancers and adenomas at colonoscopy are different. We conducted a prospective multicenter study to evaluate which indications were most closely associated with advanced colorectal neoplasm (CRN), including colorectal cancer, in a group of patients undergoing colonoscopy. PATIENTS AND METHODS The 17 468 patients were enrolled in this study between July 2003 and March 2004, from 11 tertiary medical centers in Korea. They were recruited according to 11 itemized colonoscopic indications. The term "advanced adenoma" refers here to tubular adenomas of diameter of 11 mm or more, or to tubulovillous, villous, or severely dysplastic adenomas, irrespective of their size. Cancer was defined as the invasion of malignant cells beyond the muscularis mucosa. Advanced CRN was defined as advanced adenoma or invasive cancer. RESULTS Advanced CRN was found in 1227/17 307 patients (1176 advanced adenomas plus 51 carcinomas, 7.1 %). According to univariate and multivariate analysis, the factors associated with advanced CRN included age >60 years (odds ratio (OR) 2.1, 95 % confidence interval (CI) 1.8 - 2.4, P < 0.0001), male gender (OR 2.1, 95 %CI 1.7 - 2.7, P < 0.0001), referral for colonoscopy from primary care physician (OR 3.1, 95 %CI 2.5 - 3.7, P < 0.0001), and several other indications (OR 1.8, 95 %CI 1.5 - 2.3, P < 0.001). The yield of colonoscopy for advanced CRN was lower (2.2 %) than expected in patients with iron-deficiency anemia (OR 0.5, 95 %CI 0.2 - 0.9, P = 0.03). CONCLUSIONS Age, gender, and referral for colonoscopy from primary care physician constituted important independent predictors of advanced CRN in patients undergoing colonoscopy.

Background and study aims Intestinal Behcet's disease and Crohn's disease are chronic inflammatory bowel diseases that are difficult to distinguish from each other. We investigated their colonoscopic features and identified simple and valuable strategies for differential diagnosis. Patients and methods Between 1995 and 2006, 250 consecutive patients with ulcers on colonoscopy (115 Behcet's, 135 Crohn's cases) were reviewed. All patients with Behcet's fulfilled the criteria of the International Study Group for Behcet's Disease or of the Behcet's Disease Research Committee of Japan, while Crohn's disease was confirmed by clinicopathological data. Patients were randomly allocated to a training set (70 %) or a validation set (30 %). Ulcer shapes, distributions, numbers, margins, and border contours, and the presence of aphthous, cobblestone, perianal, and strictured lesions were compared, in the training set. Univariate and multivariate analysis were performed, using the X2-test and logistic regression. In addition, a classification and regression tree (CART) was then used to generate simplified algorithms for differential diagnosis. Results Round shape, five or fewer in number, focal distributions, and absence of aphthous and cobblestone lesions were significantly dominant features in Behcet's disease, according to multivariate analysis of the training set. The CART-generated algorithms proposed sequential use of shape (round, irregular/geographic, or longitudinal) and distribution (focal single/focal multiple, or segmental/diffuse). Diagnosis of Behcet's disease in the validation set produced sensitivity, specificity, and negative and positive predictive values of 94.3 %, 90.0 %, 94.7 %, and 89.2 %, respectively. Using the CART model, we made the correct diagnosis of intestinal Behcet's disease or Crohn's disease in 69 of 75 patients (92 %). Conclusion It was determined that round and longitudinal ulcers are suggestive of Behcet's disease and Crohn's disease, respectively. Irregular/geographic-shaped ulcers and focal distributions are suggestive of Behcet's disease, while segmental/diffuse lesions suggest Crohn's.

Although almost all primary colorectal lymphomas are of B-cell lineage in Western countries, primary colorectal T-cell lymphomas are not uncommon in the East. The aim of this study was to review the clinical characteristics and treatment outcomes of primary colorectal lymphomas, with special emphasis on the differences between T-cell and B-cell lymphomas. Ninety-five cases of primary colorectal lymphomas that satisfied Dawson's criteria were identified from the clinical databases of 13 university hospitals in Korea. The mean age at the time of presentation was 51.1 years and the male:female ratio was 64:31. The clinical information, including endoscopic and histological characteristics, was retrospectively analyzed. Of the primary colorectal lymphomas, 78 cases (82.1%) were of B-lineage and 17 cases (17.9%) were of T-cell lineage. Patients with T-cell lymphomas presented at a younger age than patients with B-cell lymphomas (42.8 vs 52.9 years, respectively; P = 0.016). The most common presenting symptom was abdominal pain (87.1%) for B-cell lymphomas, whereas hematochezia or night fever was more common for T-cell lymphomas (52.9% and 35.3%, respectively). The most common endoscopic type was fungating mass (54.0%) for B-cell lymphomas and ulcerative/ulcero-infiltrative lesions (80.0%) for T-cell lymphomas. Intussusception was more common in B-cell lymphomas than in T-cell lymphomas (30.8% vs 5.9%, respectively; P = 0.035), but perforation was more common in T-cell lymphomas than in B-cell lymphomas (23.5% vs 3.8%, respectively; P = 0.005). The prognosis was significantly worse for T-cell lymphomas than for B-cell lymphomas (P = 0.002). Primary colorectal T-cell lymphomas are characterized by multifocal ulcerative lesions in relatively young patients, a high rate of hematochezia, fever, or perforation, and a poor prognosis even for cases of localized disease.