Increased risk of pancreatic, thyroid, prostate and breast cancers in men with a family history of breast cancer: A population-based study.

The association between a family history of breast cancer (FHBC) in female first-degree relatives (FDRs) and cancer risk in men has not been evaluated. This study aimed to compare the risks of overall and site-specific cancers in men with and without FHBC. A population-based study was conducted with 3 329 106 men aged ≥40 years who underwent national cancer screening between 2013 and 2014. Men with and without FHBC in their female FDRs were age-matched in a 1:4 ratio. Men without FHBC were defined as those without a family history of any cancer type in their FDRs. Data from 69 124 men with FHBC and 276 496 men without FHBC were analyzed. The mean follow-up period was 4.7 ± 0.9 years. Men with an FHBC in any FDR (mother or sister) had a higher risk of pancreatic, thyroid, prostate and breast cancers than those without an FHBC (adjusted hazard ratios [aHRs] (95% confidence interval [CI]): 1.35 (1.07-1.70), 1.33 (1.12-1.56), 1.28 (1.13-1.44) and 3.03 (1.130-8.17), respectively). Although an FHBC in any one of the FDRs was not associated with overall cancer risk, FHBC in both mother and sibling was a significant risk factor for overall cancer (aHR: 1.69, 95% CI:1.11-2.57) and increased the risk of thyroid cancer by 3.41-fold (95% CI: 1.10-10.61). FHBC in the mother or sister was a significant risk factor for pancreatic, thyroid, prostate and breast cancers in men; therefore, men with FHBC may require more careful BRCA1/2 mutation-related cancer surveillance.

Mutual association between family history of gastric and colorectal cancer and risk of gastric and colorectal cancer.

BACKGROUND AND AIM: We evaluated the associations between gastric cancer (GC) family history (FH) and colorectal cancer (CRC) risk and between CRC FH and GC/gastric adenoma risk. METHODS: We used data of participants who underwent national cancer screening between 2013 and 2014. Participants with GC or CRC FH in first-degree relatives (n = 1 172 750) and those without cancer FH (n = 3 518 250) were matched 1:3 by age and gender. RESULTS: Of the 1 172 750 participants with a FH, 871 104, 264 040, and 37 606 had FHs of only GC, only CRC, and both GC and CRC, respectively. The median follow-up time was 4.8 years. GC and CRC FHs were associated with increased GC and CRC risks, respectively. GC FH was associated with CRC risk (adjusted hazard ratio 1.05; 95% confidence interval [CI] 1.01-1.10), whereas CRC FH was not associated with the risk of GC or gastric adenoma. However, gastric adenoma risk increased 1.62-fold (95% CI 1.40-1.87) in participants with FHs of both GC and CRC, demonstrating a significant difference with the 1.39-fold (95% CI 1.34-1.44) increase in participants with only GC FH. Furthermore, GC risk increased by 5.32 times (95% CI 1.74-16.24) in participants with FHs of both GC and CRC in both parents and siblings. CONCLUSIONS: GC FH was significantly associated with a 5% increase in CRC risk. Although CRC FH did not increase GC risk, FH of both GC and CRC further increased the risk of gastric adenoma. FHs of GC and CRC may affect each other's neoplastic lesion risk.

Association Between Family History of Gastric Cancer and the Risk of Gastric Cancer and Adenoma: A Nationwide Population-Based Study.

INTRODUCTION: A family history of gastric cancer (GC) is a well-known risk factor for GC. However, the association between family history of GC and the risk of GC and gastric adenoma according to the affected family members is unclear. METHODS: We analyzed the data of participants aged ≥40 years who underwent national GC screening between 2013 and 2014. Participants with and without a family history of GC among first-degree relatives were matched by age and sex in a 1:4 ratio. RESULTS: During a median follow-up of 4.9 years, 0.96% and 0.46% of 896,721 participants with a family history of GC and 0.65% and 0.32% of 3,586,884 participants without a family history of GC developed GC and gastric adenoma, respectively. A family history of GC among any first-degree relative was a risk factor for GC (adjusted hazard ratio [HR] 1.48, 95% confidence interval 1.45-1.52) and gastric adenoma (HR 1.44, 95% confidence interval 1.39-1.50). The HRs for GC and gastric adenoma were higher in participants with a family history of GC in parents and siblings (2.26 and 2.19, respectively) than in those with a family history of GC in parents only (1.40 and 1.41, respectively) or siblings only (1.59 and 1.47, respectively). The HRs for GC in participants with vs without a family history of GC were 1.62, 1.55, and 1.42 in the 40-49, 50-59, and ≥60 years' age groups of participants, respectively. Similarly, the HRs for gastric adenoma increased with decreasing age of participants. DISCUSSION: A family history of GC was a risk factor for both GC and gastric adenoma. The risk of GC and gastric adenoma of the participants was higher when both parents and siblings had GC.

Shrimp miR-965 transfers tumoricidal mitochondria.

BACKGROUND: Micro RNA of Marsupenaeus japonicas has been known to promote apoptosis of tumor cells. However, the detailed mechanisms are not well understood. RESULTS: Using tomographic microscope, which can detect the internal structure of cells, we observed breast tumor cells following treatment of the miRNA. Intriguingly, we found that mitochondria migrate to an adjacent tumor cells through a tunneling nanotube. To recapitulate this process, we engineered a microfluidic device through which mitochondria were transferred. We show that this mitochondrial transfer process released endonuclease G (Endo G) into tumor cells, which we referred to herein as unsealed mitochondria. Importantly, Endo G depleted mitochondria alone did not have tumoricidal effects. Moreover, unsealed mitochondria had synergistic apoptotic effects with subtoxic dose of doxorubicin thereby mitigating cardiotoxicity. CONCLUSIONS: Together, we show that the mitochondrial transfer through microfluidics can provide potential novel strategies towards tumor cell death.

Suppressive effect of α-mangostin for cancer stem cells in colorectal cancer via the Notch pathway.

BACKGROUND: Since colon cancer stem cells (CSCs) play an important role in chemoresistance and in tumor recurrence and metastasis, targeting of CSCs has emerged as a sophisticated strategy for cancer therapy. α-mangostin (αM) has been confirmed to have antiproliferative and apoptotic effects on cancer cells. This study aimed to evaluate the selective inhibition of αM on CSCs in colorectal cancer (CRC) and the suppressive effect on 5-fluorouracil (5-FU)-induced CSCs. METHODS: The cell viability assay was performed to determine the optimal concentration of αM. A sphere forming assay and flow cytometry with CSC markers were carried out to evaluate the αM-mediated inhibition of CSCs. Western blot analysis and quantitative real-time PCR were performed to investigate the effects of αM on the Notch signaling pathway and colon CSCs. The in vivo anticancer efficacy of αM in combination with 5-FU was investigated using a xenograft mouse model. RESULTS: αM inhibited the cell viability and reduced the number of spheres in HT29 and SW620 cells. αM treatment decreased CSCs and suppressed the 5-FU-induced an increase in CSCs on flow cytometry. αM markedly suppressed Notch1, NICD1, and Hes1 in the Notch signaling pathway in a time- and dose-dependent manner. Moreover, αM attenuated CSC markers CD44 and CD133, in a manner similar to that upon DAPT treatment, in HT29 cells. In xenograft mice, the tumor and CSC makers were suppressed in the αM group and in the αM group with 5-FU treatment. CONCLUSION: This study shows that low-dose αM inhibits CSCs in CRC and suppresses 5-FU-induced augmentation of CSCs via the Notch signaling pathway.

Aging effects on the diurnal patterns of gut microbial composition in male and female mice.

Composition of the gut microbiota changes with aging and plays an important role in age-associated disease such as metabolic syndrome, cancer, and neurodegeneration. The gut microbiota composition oscillates through the day, and the disruption of their diurnal rhythm results in gut dysbiosis leading to metabolic and immune dysfunctions. It is well documented that circadian rhythm changes with age in several biological functions such as sleep, body temperature, and hormone secretion. However, it is not defined whether the diurnal pattern of gut microbial composition is affected by aging. To evaluate aging effects on the diurnal pattern of the gut microbiome, we evaluated the taxa profiles of cecal contents obtained from young and aged mice of both sexes at daytime and nighttime points by 16S rRNA gene sequencing. At the phylum level, the ratio of Firmicutes to Bacteroidetes and the relative abundances of Verrucomicrobia and Cyanobacteria were increased in aged male mice at night compared with that of young male mice. Meanwhile, the relative abundances of Sutterellaceae, Alloprevotella, Lachnospiraceae UCG-001, and Parasutterella increased in aged female mice at night compared with that of young female mice. The Lachnospiraceae NK4A136 group relative abundance increased in aged mice of both sexes but at opposite time points. These results showed the changes in diurnal patterns of gut microbial composition with aging, which varied depending on the sex of the host. We suggest that disturbed diurnal patterns of the gut microbiome can be a factor for the underlying mechanism of age-associated gut dysbiosis.

Genotype-based Treatment With Thiopurine Reduces Incidence of Myelosuppression in Patients With Inflammatory Bowel Diseases.

BACKGROUND & AIMS: Thiopurine-related myelosuppression (most frequently leukopenia) interferes with thiopurine therapy for patients with inflammatory bowel diseases (IBD). We investigated whether pretreatment analyses genetic variants associated with thiopurine-induced leukopenia could be used to effectively identify patients who required dose adjustments. METHODS: We performed a multicenter, prospective study of patients with IBD at 5 tertiary medical centers in Korea, from January 2016 through September 2018. Seventy-two patients were randomly assigned to a group that underwent genotype analysis for the NUDT15 variant (rs116855232) and FTO variant (rs79206939) and 3 common TPMT variants (rs1800460, rs1800462, rs1142345) associated with myelosuppression and 92 patients were assigned to a group that did not undergo genotype analysis (non-genotyping group). Patients heterozygous for any variant received 50 mg azathioprine equivalents, whereas those who were homozygous for any variant received alternative drugs. Patients who did not carry any of the genetic variants and patients in the non-genotyping group received 50 mg azathioprine equivalents followed by dose escalation up to 2-2.5 mg/kg. Myelosuppression was defined as white blood cell counts below 3000/µL, levels of hemoglobin 10 g/dL, or platelet counts below 100 K/µL. RESULTS: Twelve patients (16.7%) in the genotype analysis group and 33 patients (35.9%) in the non-genotyping group developed myelosuppression (P=.005). A multivariate analysis revealed that body mass indices above 21 kg/m2 (hazard ratio [HR], 0.43; 95% CI, 0.22-0.81; P = .009), pretreatment genotype analysis (HR, 0.37; 95% CI, 0.18-0.77; P = .008), and the maximum dose of thiopurines (HR, 0.34; 95% CI, 0.19-0.59; P < .001) independently decreased risk of myelosuppression. Pretreatment genotype analysis reduced numbers of outpatient clinic visit and numbers of patients with drug discontinuation or dose reductions. CONCLUSIONS: In a randomized controlled study of patients undergoing thiopurine therapy for IBD, we found that selection of therapy based on genetic variants associated with thiopurine-induced leukopenia significantly reduced the proportion of patients with myelosuppression during treatment. ClinicalTrials.gov no: NCT03719118.

Impacts of age and sedation on cardiocerebrovascular adverse events after diagnostic GI endoscopy: a nationwide population-based study.

BACKGROUND AND AIMS: Data are limited regarding the impact of age and sedation on cardiocerebrovascular disease (CCD) adverse events after GI endoscopy. We investigated the incidence of and risk factors for CCD adverse events after diagnostic GI endoscopy and the impact of age and sedation on these unfavorable outcomes. METHODS: In this nationwide population-based study, the incidence of and risk factors for newly diagnosed CCD within 14 days after diagnostic endoscopy were analyzed using Health Insurance Review and Assessment Service data from January to December 2015. RESULTS: Among 1,943,150 subjects, CCD adverse events occurred in approximately 2.23% within 14 days after endoscopy. According to the performance of sedation during endoscopy (60.1% nonsedation vs 39.9% sedation, midazolam alone [96.4%]), the incidence rates of CCD adverse events (per 10,000 persons) were 275.8 versus 302.8 for EGD, 116.9 versus 143.8 for colonoscopy, and 230.4 versus 243.2 for EGD + colonoscopy, respectively. On multivariate analysis, older age (70-99 years) and sedation were independent risk factors for CCD adverse events. Regarding CCD risk stratified by age and sedation, older age had a significant impact on CCD adverse events in individuals who underwent EGD only or EGD + colonoscopy, but sedation did not. However, both older age and sedation had considerable influence on CCD adverse events in individuals who underwent colonoscopy only. Sedation during endoscopy was significantly associated with minor but not major CCD adverse events. CCD adverse events were significantly higher for inpatients. CONCLUSION: CCD adverse events after diagnostic endoscopy were significantly frequent in individuals with older age (70-99 years) and/or sedation during endoscopy. Stratification by age and sedation shows that the impact of these 2 factors on CCD adverse events differs according to endoscopy type.

Gender Specific Differences in Prevalence and Risk Factors for Gastro-Esophageal Reflux Disease.

BACKGROUND: Gender-related factors might play an important role in the development of reflux esophagitis (RE) and symptomatic gastro-esophageal reflux disease (GERD). We aimed to evaluate the prevalence and risk factors for RE and symptomatic GERD and determine whether gender specific differences exist. METHODS: This study was conducted on a health cohort consisting of 10,158 participants who underwent comprehensive health screening. Lifestyles and gastrointestinal symptoms were investigated using a self-reported structured questionnaire. Questionnaires about menstrual status were added for the women. RESULTS: The prevalence of RE in men was significantly higher than that in women (10.6% vs. 2.0%, P < 0.001); however, symptomatic GERD showed predominance in women (6.2% vs. 2.5%, P < 0.001). Although the prevalence of RE gradually increased with the duration of menopause stratified by decade (P = 0.007), that of symptomatic GERD rapidly increased across the menopausal transit in women. Apart from common risk factors of obesity and current smoking for RE, over 70 years of age in women and hiatal hernia and hypertriglyceridemia in men were significant risk factors. In symptomatic GERD, high somatization was a common risk factor. Excessive alcohol drinking was a significant risk factor in men, but not in women. CONCLUSION: This study showed a predominance of RE in men, but a predominance of symptomatic GERD in women. In women, dynamic increase in the prevalence of GERD is closely related to the menopause conditions and its duration. There are specific risk factors for RE and symptomatic GERD according to gender differences.

Inflammatory hypoxia induces syndecan-2 expression through IL-1ß-mediated FOXO3a activation in colonic epithelia.

Chronic inflammation is known to be a key causative factor in tumor progression, but we do not yet fully understand the molecular mechanism through which inflammation leads to cancer. Here, we report that the dextran sulfate sodium (DSS)-induced mouse model of chronic colitis is associated with increases in the serum level of IL-1ß and the colonic epithelial expression of the cell-surface heparan sulfate proteoglycan, syndecan-2. We further show that IL-1ß stimulated the transcription of syndecan-2 via NF-κB-dependent FOXO3a activation in CCD841CoN normal colonic epithelial cells and early-stage HT29 colon cancer cells. Inflammatory hypoxia was observed in the colonic epithelia of mice with chronic colitis, suggesting that hypoxic stress is involved in the regulation of syndecan-2 expression. Consistently, experimental inflammatory hypoxia induced hypoxia inducible factor-1α-dependent FOXO3a expression and the p38 MAPK-mediated nuclear localization of FOXO3a. FOXO3a directly mediated syndecan-2 expression in both cell lines and the colonic epithelia of mice with DSS-induced colitis. Moreover, syndecan-2 expression was detected in azoxymethane/DSS-induced colon tumors. Together, these data demonstrate that inflammatory hypoxia up-regulates syndecan-2 via the IL-1ß-NF-κB-FOXO3a pathway. These findings provide new mechanistic insights into inflammatory hypoxia-mediated syndecan-2 expression to connect chronic inflammation and the development of colon cancer.-Choi, S., Chung, H., Hong, H., Kim, S. Y., Kim, S.-E., Seoh, J.-Y., Moon, C. M., Yang, E. G., Oh, E.-S. Inflammatory hypoxia induces syndecan-2 expression through IL-1ß-mediated FOXO3a activation in colonic epithelia.

Factors associated with pregnancy-related knowledge in women of reproductive age with inflammatory bowel disease.

OBJECTIVE: Inflammatory bowel disease (IBD) usually develops at a young age, and many women experience marriage, pregnancy, and delivery during the disease course. We aimed to evaluate the pregnancy-related knowledge of women with IBD in Korea and investigate the associated factors. MATERIAL AND METHODS: A total of 270 women with IBD, aged 19-45 years, from four tertiary hospitals in Korea were administered a questionnaire comprising 17 questions from the validated Crohn's and Colitis Pregnancy Knowledge Score (CCPKnow) that were translated into Korean. RESULTS: The average CCPKnow score of the 270 patients was 7.47 ± 3.07; and most of the patients (51.5%) exhibited a poor knowledge level. Younger age at diagnosis, Crohn's disease rather than ulcerative colitis, longer disease duration, anti-TNF-α medication history, higher household income, and delivery after diagnosis were associated with an appropriate level of pregnancy-related knowledge. Younger age at diagnosis (odds ratio [OR], 1.87; p = .036), anti-TNF-α therapy (OR, 1.87; p = .047), and delivery while suffering from IBD (OR, 3.07; p = .002) were independent factors affecting the pregnancy-related knowledge level. Approximately 69.6% of patients acquired related knowledge from their gastroenterology doctor, whereas 19.4% of patients intended to remain childless. CONCLUSIONS: To our knowledge, this is the first study to assess the pregnancy-related knowledge of women of reproductive-age with IBD and their perceptions by using a questionnaire in Asia. As more than half of the patients showed a poor knowledge level of IBD, a general education program should be conducted by gastroenterology doctors.

Triple therapy versus sequential therapy for the first-line Helicobacter pylori eradication.

BACKGROUND: The eradication rate of Helicobacter pylori (H. pylori) with triple therapy which was considered as standard first-line treatment has decreased to 70-85%. The aim of this study is to compare 7-day triple therapy versus 10-day sequential therapy as the first line treatment. METHODS: Data of 1240 H. pylori positive patients treated with triple therapy or sequential therapy from January 2013 to December 2015 were analyzed retrospectively. The patients who had undertaken previous H. pylori eradication therapy or gastric surgery were excluded. RESULTS: There were 872 (74.3%) patients in the triple therapy group, and 302 (25.7%) patients in the sequential therapy group. There was no significant difference between the two groups regarding age, residence, comorbidities or drug compliance, but several differences were noted in endoscopic characteristics and indication for the treatment. The eradication rate of H. pylori by intention to treat analysis was 64.3% in the triple therapy group, and 81.9% in the sequential therapy group (P = 0.001). In per protocol analysis, H. pylori eradication rate in the triple therapy and sequential therapy group was 81.9 and 90.3%, respectively (P = 0.002). There was no significant difference in overall adverse events between the two groups (P = 0.706). For the rescue therapy, bismuth-containing quadruple therapy showed comparable treatment efficacy after sequential therapy, as following triple therapy. CONCLUSIONS: The eradication rate of triple therapy was below the recommended threshold. Sequential therapy could be effective and tolerable candidate for the first-line H. pylori eradication therapy.

High serum alanine aminotransferase is associated with the risk of colorectal adenoma in Korean men.

BACKGROUND AND AIM: An elevated alanine aminotransferase (ALT) is frequently observed in subjects with metabolic syndrome, which is associated with the risk of colorectal adenoma (CRA). However, the relationship between ALT and CRA remains unclear. Therefore, we aimed to investigate whether high serum ALT is associated with the risk of CRA in a metabolically healthy population. METHODS: We conducted this cross-sectional study in 27,717 asymptomatic Korean adults who underwent a health checkup. Subjects were categorized as adenoma-free, hyperplastic polyp, low-risk adenoma, or high-risk adenoma. High-risk adenoma was defined as three or more adenomas, any adenoma ≥ 10 mm, or adenoma with high-grade dysplasia or villous features. RESULTS: Among all participants, 10.3% and 1.5% of cases were categorized as low-risk and high-risk adenoma, respectively. In multivariate analyses adjusting for age, sex, body mass index, smoking habits, alcohol intake, regular exercise, aspirin and analgesics use, family history of colon cancer, education level, fatty liver, high-sensitivity C reactive protein, homeostasis model assessment of insulin resistance, total cholesterol, and triglyceride, an increase in ALT was positively associated with the prevalence of low-risk and high-risk adenoma (P for trend = 0.029 and 0.027, respectively). The highest quartile group of ALT level showed a significantly increased prevalence in low-risk (odds ratio, 1.17) and high-risk adenoma (odds ratio, 1.48) groups compared with the lowest quartile group. This phenomenon persisted in the subgroup analysis in men, but not in women. CONCLUSIONS: In the asymptomatic healthy population, high serum ALT is significantly associated with the risk of CRA.

Risks of colorectal advanced neoplasia in young adults versus those of screening colonoscopy in patients aged 50 to 54 years.

BACKGROUND AND AIM: The role of screening or diagnostic colonoscopy to detect advanced neoplasia in young cohorts of age < 50 is unclear. This study compared the risk of colorectal neoplasia in a young age cohort against that in 50-54s screening cohort. METHODS: A multi-center retrospective study was conducted at 14 university hospitals to compare the detection rates of neoplasia and advanced neoplasia in screening or diagnostic colonoscopy in the young cohort of < 50s against those in screening colonoscopy in the 50-54s cohort. RESULTS: Among 10 477 eligible subjects, 9765 subjects were enrolled after excluding 712 subjects. Advanced neoplasia detection rates in the young screening cohort was significantly lower than that in the 50-54s screening cohort (5.9% vs 9.3%, P < 0.001). Compared with 50-54s screening cohort, the risk of advanced neoplasia was significantly reduced by 23%, 53%, and 54% in the 45-49s, 40-44s, and 20-39s screening cohorts, respectively. The detection rates of advanced neoplasia in the young diagnostic cohort was 5.0%, which was much lower than 11.8% in 50-54s screening cohort (P < 0.001). Compared with the 50-54s screening cohort, the risk of advanced neoplasia was significantly reduced by 50%, 66%, and 71% in the 45-49s, 40-44s, and 20-39s diagnostic cohorts, respectively. CONCLUSIONS: Colonoscopy to detect advanced neoplasia in young adults aged < 50 years should be reconsidered as their risk of advanced neoplasia on screening or diagnostic colonoscopy was much lower than those of 50-54s screening cohort; however, colonoscopy screening may be justified for high-risk 45-49s cohorts.

Endoscopic Resection of Cecal Polyps Involving the Appendiceal Orifice: A KASID Multicenter Study.

BACKGROUND: Endoscopic resection of polyps located at the appendiceal orifice (AO) is challenging, and the feasibility and outcomes of endoscopic resection for cecal polyps involving AO are unconfirmed. AIMS: We evaluated the feasibility and outcomes of endoscopic resection for cecal polyps involving AO. METHODS: In this retrospective, multicenter study involving nine tertiary referral centers, we evaluated 131 patients who underwent endoscopic resection for cecal polyps involving AO. RESULTS: The median size of polyps resected was 10 mm (range 3-60 mm). Endoscopic mucosal resection, endoscopic piecemeal mucosal resection, and endoscopic submucosal dissection were performed in 75 (57.3%), 31 (23.7%), and 5 (3.8%) patients, respectively. The en bloc resection rate was 68.7%. Endoscopic complete resection was achieved in 123 lesions (93.9%). Intraprocedural and delayed bleeding occurred in 14 (10.7%) and three patients (2.3%), respectively, and perforation occurred in two patients (1.5%). Seven patients (5.3%) underwent additional surgery because of treatment failure or recurrence. Polyps of ≥20 mm in size showed significantly higher rates of perforation and additional surgery (p < 0.05), and a lower rate of en bloc resection (p < 0.005). Patients with polyps involving ≥75% of AO circumference exhibited a significantly lower rate of en bloc resection (p < 0.001), and significantly higher rates of surgery and recurrence (p < 0.05). Recurrence during follow-up occurred in 12 patients (15.6%); polyps involving ≥75% of AO circumference were an independent risk factor for recurrence. CONCLUSION: Endoscopic resection of cecal polyps involving AO is safe and effective in select patients.

Diagnostic Value of Small Bowel Capsule Endoscopy in Isolated Ileitis: A CAPENTRY Study.

BACKGROUND: Capsule endoscopy (CE) has proven to be highly effective at detecting small bowel lesions, but studies regarding the diagnostic impact of CE on ileitis are rare. AIMS: We evaluated the diagnostic value of small bowel CE for isolated ileitis observed during ileocolonoscopy. METHODS: The CE results in 137 patients initially diagnosed with ileitis without colonic mucosal abnormalities on ileocolonoscopy at one of eight tertiary referral centers between October 2002 and June 2015 were retrospectively analyzed. RESULTS: Among the 137 patients with isolated ileitis observed on ileocolonoscopy, 117 (85.4%) revealed positive small bowel CE findings (85.4%). The rate of positive small bowel CE findings was 92.9% in cases of ileal aphthous ulcer or erosion, and 90.9% in cases of ileal ulcer. Among 117 positive CE cases, the most common final diagnosis by CE was Crohn's disease (CD) (n = 44, 32%). No findings were identified in 20 (14.6%) of 137 cases. Ileal erosion/ulcer, rather than findings such as nodularity and erythema or elevated erythrocyte sedimentation rate (ESR) (>10 mm/h), was significant predictive factors for positive CE findings in multivariate analysis. CONCLUSIONS: Small bowel CE showed a high diagnostic yield (85.4%) in symptomatic patients with isolated ileitis on ileocolonoscopy. Erosion or ulcer of the small bowel was a common finding on CE (66.4%), and approximately one-third of patients were diagnosed with CD. In patients with isolated ileitis on ileocolonoscopy, CE should be considered to evaluate small bowel lesions when the patient shows an elevated ESR or when the ileitis manifests as ileal ulcer or erosion rather than a nodular or erythematous lesion.

Multidisciplinary Approach to Refractory Upper Gastrointestinal Bleeding: Case Series of Angiographic Embolization.

Although medical and endoscopic hemostasis is now considered as the first-line therapy for nonvariceal upper gastrointestinal (UGI) bleeding, refractory bleeding still occurs in 5%-10% of the patients. In these patients, transcatheter arterial embolization (TAE) or surgery is required, but research on embolization for unmanageable UGI bleeding in Korea is scanty. We reviewed the medical records of 518 patients who underwent endoscopic hemostasis during 4 years. Among these subjects, 8 patients who required embolization due to failure of endoscopic hemostasis were enrolled. Mean patient age was 74.00 ± 8.25 years, and rebleeding occurred in 4 patients within 48 hours after TAE. Three patients with duodenal rebleeding underwent surgery, and the other patient with a gastric ulcer underwent endoscopic hemostasis. Nonvariceal UGI bleeding remains a serious clinical challenge, especially in older patients. A multidisciplinary approach including endoscopists, interventional radiologists, and surgeons may be important for the treatment of nonvariceal UGI bleeding.

Long-Term Clinical Outcomes of Rectal Neuroendocrine Tumors According to the Pathologic Status After Initial Endoscopic Resection: A KASID Multicenter Study.

OBJECTIVES: With advances in diagnostic endoscopy, the detection of rectal neuroendocrine tumors (NETs) has increased. However, clinical outcomes, especially after endoscopic treatment, are still unclear. The aim of this study was to determine the long-term clinical outcomes of endoscopically resected rectal NETs according to the pathologic status after initial resection. METHODS: In this large, multicenter, retrospective cohort study, we analyzed the medical records of patients who underwent endoscopic resection of rectal NETs and were followed for ≥24 months at 16 university hospitals. The outcomes of interest were local or distant recurrence and metachronous lesions. RESULTS: On the pathologic assessment of 407 patients, the resection margin status was positive in 76 (18.7%) and indeterminate in 72 (17.7%) patients. Patients whose rectal NETs were diagnosed or suspected as NETs before resection showed a much higher complete resection rate than those whose tumors were resected as polyps and then diagnosed (P<0.001). Fourteen patients received salvage treatment at 1.9±2.8 months after initial treatment. During a median follow-up period of 45.0 months, local recurrence occurred in 3 (0.74%) patients, but there was no recurrence in the lymph nodes or distant organs. Metachronous rectal NETs were diagnosed in 3 (0.74%) patients. According to the pathologic status after initial resection, local recurrence and metachronous lesions occurred in 1 (0.4%) and 2 (0.8%) patients, respectively, in the pathologic tumor-free group, whereas they occurred in 2 (1.4%) and 1 (0.7%) patients, respectively, in the indeterminate group. CONCLUSIONS: Considering the long-term prognosis including that for recurrences or metachronous lesions, endoscopic resection is an efficient and a safe modality for the treatment of rectal NETs. This treatment may result in favorable clinical outcomes in patients with tumors of indeterminate pathology, as well as in pathologic tumor-free cases after initial resection.

Importance of Patients' Knowledge of Their Prescribed Medication in Improving Treatment Adherence in Inflammatory Bowel Disease.

GOALS: To investigate the association between treatment nonadherence and patients' knowledge of the prescribed medication among individuals with inflammatory bowel disease (IBD), and evaluate the impact of nonadherence on relapse. BACKGROUND: The patient's knowledge of the prescribed medication has been identified as an important predictor of treatment adherence in chronic diseases. However, this association has not been examined in IBD. STUDY: In this prospective study, at baseline, 138 patients with IBD completed a self-reported survey on demographic data, knowledge of the prescribed medication, and candidate factors related to the degree of treatment adherence. To investigate the impact of nonadherence among patients in remission, relapse was analyzed for 18 months after enrollment. RESULTS: Nonadherence was observed in 50 (36.2%) of the 138 subjects. In multivariate analysis, nonadherence was significantly associated with younger age (less than 30 y) at participation [odds ratio (OR), 5.88; 95% confidence interval (CI), 1.51-22.94; P=0.011], longer intervals between outpatient clinic visits (≥3 mo) (OR, 30.31; 95% CI, 3.06-300.17; P=0.004), and limited knowledge of the prescribed medication (OR, 5.61; 95% CI, 1.60-19.67; P=0.038). Nonadherent patients had a significantly greater risk of relapse of IBD than adherent patients (relative risk, 2.9; 95% CI, 2.25-3.79; P=0.045). CONCLUSION: Younger age, longer intervals between outpatient clinic visits, and limited knowledge of the prescribed medication tended to be associated with nonadherence to treatment, which consequently also affects the risk of relapse.

Significance of calcium-sensing receptor expression in gastric cancer.

OBJECTIVE: The calcium-sensing receptor (CaSR) is known to have differential expression in various carcinomas and normal tissues. It has been shown to be involved in carcinogenesis or tumor suppression. However, its role in gastric cancer remains unknown. This study was performed to determine the CaSR expression level in gastric cancer and non-tumor gastric tissues and to examine the related clinicopathological factors. MATERIALS AND METHODS: Thirty-one pairs of gastric cancer tissues and matched non-tumor gastric tissues were obtained from surgical tissues after gastrectomy. Using real-time polymerase chain reaction, we measured CaSR mRNA expression. We evaluated the association between CaSR mRNA expression and clinicopathological variables based on the downregulation or upregulation of CaSR mRNA expression in gastric cancer tissues compared to those of matched non-tumor gastric tissues. By immunohistochemistry, we confirmed CaSR expression levels in gastric cancer tissues. RESULTS: Downregulation of CaSR mRNA was observed in 77.4% of gastric cancer tissues compared to their matched normal tissues. Downregulated CaSR was associated with a tendency for deeper invasion into the proper muscle (p = 0.028) and more advanced stage (II-IV; p = 0.012). CONCLUSION: We conclude that downregulation of CaSR may contribute to the prevention or suppression of tumor outgrowth.