Although gemcitabine-based regimens are widely used as an effective treatment for pancreatic cancer, acquired resistance to gemcitabine has become an increasingly common problem. Therefore, a novel therapeutic strategy to treat gemcitabine-resistant pancreatic cancer is urgently required. Piceamycin has been reported to exhibit antiproliferative activity against various cancer cells; however, its underlying molecular mechanism for anticancer activity in pancreatic cancer cells remains unexplored. Therefore, the present study evaluated the antiproliferation activity of piceamycin in a gemcitabine-resistant pancreatic cancer cell line and patient-derived pancreatic cancer organoids. Piceamycin effectively inhibited the proliferation and suppressed the expression of alpha-actinin-4, a gene that plays a pivotal role in tumorigenesis and metastasis of various cancers, in gemcitabine-resistant cells. Long-term exposure to piceamycin induced cell cycle arrest at the G0/G1 phase and caused apoptosis. Piceamycin alsoinhibited the invasion and migration of gemcitabine-resistant cells by modulating focal adhesion and epithelial-mesenchymal transition biomarkers. Moreover, the combination of piceamycin and gemcitabine exhibited a synergistic antiproliferative activity in gemcitabine-resistant cells. Piceamycin also effectively inhibited patient-derived pancreatic cancer organoid growth and induced apoptosis in the organoids. Taken together, these findings demonstrate that piceamycin may be an effective agent for overcoming gemcitabine resistance in pancreatic cancer.

Background/Aims: The prospective Crohn’s Disease Clinical Network and Cohort Study is a nationwide multicenter cohort study of patients with Crohn’s disease (CD) in Korea, aiming to prospectively investigate the clinical features and long-term prognosis associated with CD. Methods: Patients diagnosed with CD between January 2009 and September 2019 were prospectively enrolled. They were divided into two cohorts according to the year of diagnosis: cohort 1 (diagnosed between 2009 and 2011) versus cohort 2 (between 2012 and 2019). Results: A total of 1,175 patients were included, and the median follow-up duration was 68 months (interquartile range, 39.0 to 91.0 months). The treatment-free durations for thiopurines (p<0.001) and anti-tumor necrosis factor agents (p=0.018) of cohort 2 were shorter than those of cohort 1. Among 887 patients with B1 behavior at diagnosis, 149 patients (16.8%) progressed to either B2 or B3 behavior during follow-up. Early use of thiopurine was associated with a reduced risk of behavioral progression (adjusted hazard ratio [aHR], 0.69; 95% confidence interval [CI], 0.50 to 0.90), and family history of inflammatory bowel disease was associated with an increased risk of behavioral progression (aHR, 2.29; 95% CI, 1.16 to 4.50). One hundred forty-one patients (12.0%) underwent intestinal resection, and the intestinal resection-free survival time was significantly longer in cohort 2 than in cohort 1 (p=0.003). The early use of thiopurines (aHR, 0.35;95% CI, 0.23 to 0.51) was independently associated with a reduced risk of intestinal resection. Conclusions The prognosis of CD in Korea appears to have improved over time, as evidenced by the decreasing intestinal resection rate. Early use of thiopurines was associated with an improved prognosis represented by a reduced risk of intestinal resection.

Objective: This study aimed to investigate the characteristics of the high-risk group for dental caries among 12- and 15-year-old children in Laos. Methods: Oral health survey was conducted on 12-year-old (N=537) and 15-year-old (N=490) children in Laos. The oral examination data were listed from highest to highest based on the permanent caries experience index. Then the caries experience permanent index of the participants corresponding to the top third was calculated. In the final high-risk group, 179 and 163 children aged 12 and 15 years, respectively, were analyzed for the Significant Caries (SiC) Index. Results: The Decayed, Missing and Filled Teeth (DMFT) index of 12-year-old children in Laos was 1.59 (urban area 1.72, rural area 1.46), and the SiC index of the high-risk group for dental caries was 3.93 (urban area 4.01, rural area 3.85). DMFT index of the 15-year-old group was 2.04 (2.37 in urban areas, 1.74 in rural areas), and the SiC index of the high-risk group for dental caries was 5.17 (5.90 in urban areas, 4.49 in rural areas). Conclusions Children aged 12 and 15 in the high-risk group for dental caries in Laos showed a higher caries experience permanence index than the overall average in the high-risk group. Based on the outcome of the investigation that the high-risk group had a lot of experience with dental caries, it is thought that the priority dental caries prevention project for the high-risk group of dental caries should be carried out.

Purpose: This study was conducted to explore the experiences of adult cancer patients living with Chemotherapy-Related Cognitive Impairment (CRCI). Methods: Data were collected by using in-depth and audio-recorded interviews with seven patients of colorectal, stomach, and breast cancer. The participants were asked to describe their CRCI experience. The data were analyzed according to Colaizzi’s method for phenomenological analysis. Results: Three-theme clusters and six themes emerged: (1) Foggy daily life: brain health impairment; “I feel different from my usual self: cognitive impairment,” “Lost daily activities: work-related tasks affected,” (2) Struggle to retain memories; “Tried using all strategies I could to recall my memories,” “Need for concern and therapeutic communication,” (3) Expectation of a whole body: hope to live; “Expectations for cognitive rehabilitation,” “Reorganizing daily life.” Conclusion These results showed that patients did not consider CRCI important until symptoms affected daily activities and workrelated tasks and tried to use self-management strategies to manage CRCI. A two-way exchange of information between patients and health professionals can help patients understand and prepare for CRCI in dealing with symptoms.

Background/Aims: Escherichia coli Nissle 1917 (EcN) alone therapy is as effective as mesalamine in inducing and maintaining remission in ulcerative colitis (UC). The efficacy and safety of EcN in combination with standard therapies have not been studied.This study examined the changes in the inflammation markers and symptoms following the additional administration of EcN to patients showing the clinical remission of UC. Methods: UC patients who received EcN after being in clinical remission for more than 3 months at Kosin University Gospel Hospital between 2013 and 2018 were evaluated through the retrospective medical-record-based review. The partial Mayo score, fecal calprotectin (FC), BMI, hemoglobin, serum cholesterol, serum albumin levels, and the safety profiles were examined at 3rd and 6th months after initiating EcN. Results: Ninety-four patients were included. After 3 months of treatment, there was no significant change in FC (156.3 μg/g to 141.1 μg/g) (p=0.653). On the other hand, partial Mayo score decreased significantly from 0.085 to 0.014 (p=0.025), and the bodyweight (p=0.001), BMI (p<0.001), hemoglobin (p=0.009), and cholesterol level increased (p=0.148). One patient (1.1%) experienced a serious adverse event with UC flare-up, and 14 patients (14.9%) discontinued EcN due to adverse events; all developed within 3 months. Conclusions Additional administration of EcN to clinically remission-attained UC patients may improve the UC symptoms without changing the FC levels. EcN-associated adverse events develop within the early few weeks.

Purpose: This study was performed to compare the oncologic outcomes between nonradical management and total mesorectal excision in good responders after chemoradiotherapy. Methods: We analyzed 75 patients, who underwent 14 watch-and-wait, 30 local excision, and 31 total mesorectal excision, in ycT0–1N0M0 based on magnetic resonance imaging after chemoradiotherapy for advanced mid-to-low rectal cancer in 3 referral hospitals. The nonradical management group underwent surveillance with additional sigmoidoscopy and rectal magnetic resonance imaging every 3–6 months within the first 2 years. Results: Nonradical management group had more low-lying tumors (P < 0.001) and less lymph node metastasis based on magnetic resonance imaging (P = 0.004). However, cT stage, ycT, and ycN stage were not different between the 2 groups. With a median follow-up period of 64.7 months, the 5-year locoregional failure rate was higher in the nonradical management group than in the total mesorectal excision group (16.7% vs. 0%, P = 0.013). However, the 5-year overall survival and disease-free survival rates of the nonradical management and total mesorectal excision groups were not different (95.2% vs. 93.5%, P = 0.467; 76.4% vs. 83.6%, P = 0.665; respectively). Conclusion This study shows that nonradical management for ycT0–1N0 mid-to-low rectal cancer may be an alternative treatment to total mesorectal excision under proper surveillance and management for oncologic events.

Purpose: Long-term oncologic differences in outcome between groups of patients with Lynch syndrome (LS) colorectal cancer (CRC) and sporadic CRC with microsatellite instability-high (MSI-H) are the focus of investigation in the current study. Methods: Patients registered in the Korean Hereditary Tumor Registry and 2 tertiary referral hospitals treated for stage I– III CRC between 2005 and 2015 were retrospectively analyzed. Detection for both groups was performed using pedigree, microsatellite instability, and mismatch repair (MMR) gene testing. Multivariate analyses for overall survival (OS) and disease-free survival (DFS) were conducted. Results: Cases of LS (n = 77) and sporadic CRC with MSI-H (n = 96) were identified. LS CRC patients were younger in age and displayed tumor sidedness, typically involving left-sided colon and rectum, compared to patients with sporadic CRC with MSI-H. OS and DFS were lower for LS CRC relative to CRC with MSI-H (OS, 72.7% vs. 93.8%, P = 0.001; DFS, 71.4% vs. 88.5%, P = 0.001). In multivariate analyses, tumor sidedness, stage, and chemotherapy were independent factors for OS and DFS. LS CRC was a prognostic factor for poorer OS (hazard ratio, 2.740; 95% confidence interval, 1.003–7.487; P = 0.049), but not DFS. Conclusion Our findings indicate that LS CRC is associated with poorer outcomes compared to sporadic CRC with MSI-H, presenting distinct clinical features. In view of the current lack of knowledge on genetic and molecular mechanisms, appropriate management taking into consideration the difficulty of identification of CRC with hypermutable tumors harboring heterogeneity is essential.

Purpose: This study was performed to compare the oncologic outcomes between nonradical management and total mesorectal excision in good responders after chemoradiotherapy. Methods: We analyzed 75 patients, who underwent 14 watch-and-wait, 30 local excision, and 31 total mesorectal excision, in ycT0–1N0M0 based on magnetic resonance imaging after chemoradiotherapy for advanced mid-to-low rectal cancer in 3 referral hospitals. The nonradical management group underwent surveillance with additional sigmoidoscopy and rectal magnetic resonance imaging every 3–6 months within the first 2 years. Results: Nonradical management group had more low-lying tumors (P < 0.001) and less lymph node metastasis based on magnetic resonance imaging (P = 0.004). However, cT stage, ycT, and ycN stage were not different between the 2 groups. With a median follow-up period of 64.7 months, the 5-year locoregional failure rate was higher in the nonradical management group than in the total mesorectal excision group (16.7% vs. 0%, P = 0.013). However, the 5-year overall survival and disease-free survival rates of the nonradical management and total mesorectal excision groups were not different (95.2% vs. 93.5%, P = 0.467; 76.4% vs. 83.6%, P = 0.665; respectively). Conclusion This study shows that nonradical management for ycT0–1N0 mid-to-low rectal cancer may be an alternative treatment to total mesorectal excision under proper surveillance and management for oncologic events.

Purpose: Long-term oncologic differences in outcome between groups of patients with Lynch syndrome (LS) colorectal cancer (CRC) and sporadic CRC with microsatellite instability-high (MSI-H) are the focus of investigation in the current study. Methods: Patients registered in the Korean Hereditary Tumor Registry and 2 tertiary referral hospitals treated for stage I– III CRC between 2005 and 2015 were retrospectively analyzed. Detection for both groups was performed using pedigree, microsatellite instability, and mismatch repair (MMR) gene testing. Multivariate analyses for overall survival (OS) and disease-free survival (DFS) were conducted. Results: Cases of LS (n = 77) and sporadic CRC with MSI-H (n = 96) were identified. LS CRC patients were younger in age and displayed tumor sidedness, typically involving left-sided colon and rectum, compared to patients with sporadic CRC with MSI-H. OS and DFS were lower for LS CRC relative to CRC with MSI-H (OS, 72.7% vs. 93.8%, P = 0.001; DFS, 71.4% vs. 88.5%, P = 0.001). In multivariate analyses, tumor sidedness, stage, and chemotherapy were independent factors for OS and DFS. LS CRC was a prognostic factor for poorer OS (hazard ratio, 2.740; 95% confidence interval, 1.003–7.487; P = 0.049), but not DFS. Conclusion Our findings indicate that LS CRC is associated with poorer outcomes compared to sporadic CRC with MSI-H, presenting distinct clinical features. In view of the current lack of knowledge on genetic and molecular mechanisms, appropriate management taking into consideration the difficulty of identification of CRC with hypermutable tumors harboring heterogeneity is essential.