Molecular characterization of dysplasia-initiated colorectal cancer with assessing matched tumor and dysplasia samples.

PURPOSE: Ulcerative colitis (UC) is known to have an association with the increased risk of colorectal cancer (CRC), and UC-associated CRC does not follow the typical progress pattern of adenoma-carcinoma. The aim of this study is to investigate molecular characteristics of UC-associated CRC and further our understanding of the association between UC and CRC. METHODS: From 5 patients with UC-associated CRC, matched normal, dysplasia, and tumor specimens were obtained from formalin-fixed paraffin-embedded (FFPE) samples for analysis. Genomic DNA was extracted and whole exome sequencing was conducted to identify somatic variations in dysplasia and tumor samples. Statistical analysis was performed to identify somatic variations with significantly higher frequencies in dysplasia-initiated tumors, and their relevant functions were investigated. RESULTS: Total of 104 tumor mutation genes were identified with higher mutation frequencies in dysplasia-initiated tumors. Four of the 5 dysplasia-initiated tumors (80.0%) have TP53 mutations with frequent stop-gain mutations that were originated from matched dysplasia. APC and KRAS are known to be frequently mutated in general CRC, while none of the 5 patients have APC or KRAS mutation in their dysplasia and tumor samples. Glycoproteins including mucins were also frequently mutated in dysplasia-initiated tumors. CONCLUSION: UC-associated CRC tumors have distinct mutational characteristics compared to typical adenoma-carcinoma tumors and may have different cancer-driving molecular mechanisms that are initiated from earlier dysplasia status.

Incidentally Detected Asymptomatic Perianal Abscess in an Adolescent during Crohn's Disease Diagnosis: Is Routine Pelvic Imaging Required in Korean Pediatric Patients at Diagnosis?

Perianal fistulizing diseases, namely perianal fistulas and/or abscesses, are well-known complications of Crohn's disease (CD). These are known to develop more frequently in Asian children with CD, especially in the early stages of the disease course. Approximately half of the pediatric CD cases in Korea present with perianal fistulizing diseases at diagnosis. We report a rare case of a 12-year-old boy with CD with an incidental discovery of a perianal abscess on pelvic magnetic resonance imaging during CD diagnosis. No symptoms or signs of perianal fistulizing disease were identified. The early diagnosis of the perianal abscess enabled timely and effective treatment. Considering the high incidence of concomitant perianal CD in Korean children at diagnosis, perianal imaging may be useful and should be considered during diagnostic evaluation, even in patients with no subjective or objective findings indicating perianal CD.

The real-world outcomes of vedolizumab in patients with ulcerative colitis in Korea: a multicenter retrospective study.

AIM: This study examined the real-world effectiveness and safety outcomes of vedolizumab in ulcerative colitis (UC) patients who had failed anti-tumor necrosis factor (anti-TNF) therapy in Korea. METHODS: A retrospective chart review study was conducted in adults with moderate to severely active UC who had failed anti-TNF agents and subsequently received vedolizumab. Clinical response and clinical remission at week 6 and 14 after vedolizumab initiation was evaluated. Safety outcomes were also reported. Outcome rates were compared with a matched sub-cohort derived from the open-label sub-cohort of the GEMINI 1 trial using the optimal matching method. RESULTS: A total of 105 patients (mean age, 45.3 years; 63.8% male) were included. At week 6, 55.8% (n = 43/77) achieved a clinical response and 18.2% (n = 14/77) achieved clinical remission. At week 14, 73.2% (n = 52/71) achieved a clinical response and 39.4% (n = 28/71) achieved clinical remission. When non-response imputation was used, the clinical response rate at week 6 and week 14 were 40.1% (n = 43/105) and 49.5% (n = 52/105) respectively. Of the 105 patients, 16 (15.2%) experienced at least one adverse event. The matched analysis showed that the clinical response rate at week 6 was higher in the matched sub-cohort of this study (24/47, 51.1%) versus the matched sub-cohort from the GEMINI 1 open-label cohort (12/47, 34.3%, p = 0.019). The clinical remission rates at week 6 were similar (7/47, 14.9% versus 9/47, 19.1%, p = 0.785). CONCLUSIONS: In the real-world setting, vedolizumab is effective and well tolerated within the first 14 weeks of use in Korea. The proportion of patients experiencing clinical response and clinical remission at 6 and 14 weeks appeared to be largely consistent with that observed in real-world studies from other regions and populations.

Incidence and Prevalence Trends of Pediatric Inflammatory Bowel Disease in the Daegu-Kyungpook Province From 2017 to 2020.

Background and Aim: There is paucity of data regarding the epidemiology of pediatric IBD in Asia compared to that of Western countries. We aimed to investigate the incidence and prevalence trends of pediatric inflammatory bowel disease (IBD) in the Daegu-Kyungpook province of South Korea from 2017 to 2020. Methods: This study was a multicenter, retrospective study conducted in eight IBD referral centers located in the Daegu-Kyungpook province. Children and adolescents of ≤18 years who were initially diagnosed with IBD between 2017 and 2020 were included. The annual number of children and adolescents newly diagnosed with IBD and the annual resident population of children and adolescents ≤18 years of age in the Daegu-Kyungpook province were investigated to calculate the annual incidence and prevalence in the region. Results: A total 304 children and adolescents that had been diagnosed with IBD were included in this study. Among these patients, 71.4% had been diagnosed with Crohn's disease (CD), and 28.6% with ulcerative colitis (UC). The population based annual incidences of IBD from 2017 to 2020 were each 7.24, 6.82, 10.27, and 13.33 per 100,000, respectively (P for trend <0.001), 4.48, 5.26, 7.39, and 9.8 per 100,000, respectively, for CD (P for trend <0.001), and 2.76, 1.56, 2.88, and 3.53 per 100,000, respectively, for UC (P for trend = 0.174). Conclusion: Pediatric IBD, especially CD has significantly increased recently in the Daegu-Kyungpook province. Epidemiology studies from other regions of Asia are required to better elucidate this trend of increase in Asia.

Characteristics and management of patients with inflammatory bowel disease between a secondary and tertiary hospitals: a propensity score analysis.

BACKGROUND/AIMS: This study aimed to compare the clinical characteristics and management patterns of inflammatory bowel disease (IBD) patients in a secondary hospital (SH) with those in tertiary referral centers (TRC). METHODS: Data from IBD patients in SH and 2 TRCs were retrospectively reviewed. The cumulative thiopurine use rate was compared between hospitals after controlling for different baseline characteristics using propensity score matching. RESULTS: Among the total of 447 patients with IBD, 178 Crohn's disease (CD) and 269 ulcerative colitis (UC) patients were included. Regarding initial CD symptoms, patients from SH were more likely to show perianal symptoms, such as anal pain or discharge (56.6% vs. 34.3%, P=0.003), whereas those from TRCs more often had luminal symptoms, such as abdominal pain (54.9% vs. 17.1%, P<0.001), diarrhea (44.1% vs. 18.4%, P<0.001), and body weight loss (9.8% vs. 1.3%, P=0.025). Complicating behaviors, such as stricturing and penetrating, were significantly higher in TRCs, while perianal disease was more common in SH. Ileal location was more frequently observed in TRCs. For UC, SH had a more limited extent of disease (proctitis 58.8% vs. 21.2%, P<0.001). The cumulative azathioprine use rate in SH was significantly lower than that in TRCs in both CD and UC patients after controlling for disease behavior, location, and perianal disease of CD and extent of UC. CONCLUSIONS: The clinical characteristics and management of the IBD patients in SH were substantially different from those in TRCs. Thiopurine treatment was less commonly used for SH patients.

The efficacy of infliximab combined with surgical treatment of fistulizing perianal Crohn's disease: Comparative analysis according to fistula subtypes.

BACKGROUND/OBJECTIVE: Infliximab is regarded as an effective therapeutic to treat Crohn's disease. This study aimed to assess the efficacy of infliximab combined with surgery and to analyze clinical manifestations according to fistula subtypes in patients with fistulizing perianal Crohn's disease. METHODS: From April 2013 to December 2015, 47 patients with perianal Crohn's disease in two hospitals of South Korea (Goo Hospital, Gangnam Severance Hospital) were evaluated retrospectively. Patients were categorized into two groups as simple fistula (n = 20) and complex fistula group (n = 27). All patients received 5 mg/kg of infliximab intravenously at 0, 2, and 6 weeks after surgical treatments. Then every eight weeks, the responders continued to receive 5 mg/kg infliximab for maintenance therapy. RESULTS: Complete response of induction therapy was 72.3%, and partial response was 27.7%. After maintenance therapy, complete response was 97.9% and partial response was 2.1%. There was no patient without a response to infliximab in this study. The median time to the first fistula closure was 6.00 ± 8.00 weeks. Infliximab was used on average 2.13 ± 0.71 times until the first fistula closure. The rate of recurrence was 8.5% and adverse events were 4.2%. In comparison with clinical manifestations between simple and complex fistula groups, there was no significant difference except for the coexistence of perianal abscess. CONCLUSIONS: Combined surgical and infliximab therapy was efficacious to treat fistulizing perianal Crohn's disease with rapid treatment response and favorable clinical outcomes. It is expected that this top-down strategy with combining surgeries can overcome previous limitations in treating perianal Crohn's disease.

Current Status and Trends in Inflammatory Bowel Disease Surgery in Korea: Analysis of Data in a Nationwide Registry.

PURPOSE: Inflammatory bowel disease (IBD) in Korea has been increasing in recent years, but accurate statistics about operations for IBD are lacking. The purpose of this study was to investigate the trends and current status of IBD surgeries in Korea. METHODS: Using a national database from the Korea Health Insurance Review and Assessment Service, we analyzed data from patients who underwent surgery for Crohn disease and ulcerative colitis from January 2009 to October 2016. RESULTS: The mean number of patients who underwent surgery for Crohn disease was 791.8 per year. Colorectal surgery, small bowel surgery, and anal surgery were performed fairly often (31.2%, 29.4%, 39.4%, respectively), and laparoscopic surgery continued to increase, recently exceeding 30%. About 50% of Crohn patients used biologics before and after surgery, and those patients also underwent a relatively high rate of anal surgeries (44.2%). The mean number of patients who underwent surgery for ulcerative colitis was 247.6 per year. Colorectal surgery accounted for more than half of all operations, and laparoscopic surgery has been increasing rapidly, having been performed in about 60% of patients in recent years. The incidence of colorectal cancer in patients with ulcerative colitis was very high and increased rapidly during the study period, reaching about 80%. CONCLUSION: The number of patients undergoing laparoscopic surgery for IBD in Korea has increased significantly. Biologics are actively used by patients with Crohn disease, with a high proportion of anal surgeries required. Many of the surgical indications for ulcerative colitis have shifted into colorectal cancer.

Effectiveness of Sodium Picosulfate/Magnesium Citrate (PICO) for Colonoscopy Preparation.

PURPOSE: Bowel preparation with sodium phosphate was recently prohibited by the U.S. Food and Drug Administration. Polyethylene glycol (PEG) is safe and effective; however, it is difficult to drink. To identify an easy bowel preparation method for colonoscopy, we evaluated three different bowel preparation regimens regarding their efficacy and patient satisfaction. METHODS: In this randomized, comparative study, 892 patients who visited a secondary referral hospital for a colonoscopy between November 2012 and February 2013 were enrolled. Three regimens were evaluated: three packets of sodium picosulfate/magnesium citrate (PICO, group A), two packets of PICO with 1 L of PEG (PICO + PEG 1 L, group B), and two packets of PICO with 2 L of PEG (PICO + PEG 2 L, group C). A questionnaire survey regarding the patients' preference for the bowel preparation regimen and satisfaction was conducted before the colonoscopies. The quality of bowel cleansing was scored by the colonoscopists who used the Aronchick scoring scale and the Ottawa scale. RESULTS: The patients' satisfaction rate regarding the regimens were 72% in group A, 64% in group B, and 45.9% in group C. Nausea and abdominal bloating caused by the regimens were more frequent in group C than in group A or group B (P < 0.01). Group C showed the lowest preference rate compared to the other groups (P < 0.01). Group C showed better right colon cleansing efficacy than group A or group B. CONCLUSION: Group A exhibited a better result than group B or group C in patient satisfaction and preference. In the cleansing quality, no difference was noted between groups A and C.