Treatment Response With Potassium-competitive Acid Blockers Based on Clinical Phenotypes of Gastroesophageal Reflux Disease: A Systematic Literature Review and Meta-analysis.

Background/Aims: Gastroesophageal reflux disease (GERD) is typically managed based on the clinical phenotype. We evaluated the efficacy and safety of potassium-competitive acid blockers (PCABs) in patients with various clinical GERD phenotypes. Methods: Core databases were searched for studies comparing PCABs and proton pump inhibitors (PPIs) in clinical GERD phenotypes of erosive reflux disease (ERD), non-erosive reflux disease (NERD), PPI-resistant GERD and night-time heartburn. Additional analysis was performed based on disease severity and drug dosage, and pooled efficacy was calculated. Results: In 9 randomized controlled trials (RCTs) evaluating the initial treatment of ERD, the risk ratio for healing with PCABs versus PPIs was 1.09 (95% CI, 1.04-1.13) at 2 weeks and 1.03 (95% CI, 1.00-1.07) at 8 weeks, respectively. PCABs exhibited a significant increase in both initial and sustained healing of ERD compared to PPIs in RCTs, driven particularly in severe ERD (Los Angeles grade C/D). In 3 NERD RCTs, PCAB was superior to placebo in proportion of days without heartburn. Observational studies on PPI-resistant symptomatic GERD reported symptom frequency improvement in 86.3% of patients, while 90.7% showed improvement in PPIresistant ERD across 5 observational studies. Two RCTs for night-time heartburn had different endpoints, limiting meta-analysis. Pronounced hypergastrinemia was observed in patients treated with PCABs. Conclusions: Compared to PPIs, PCABs have superior efficacy and faster therapeutic effect in the initial and maintenance therapy of ERD, particularly severe ERD. While PCABs may be an alternative treatment option in NERD and PPI-resistant GERD, findings were inconclusive in patients with night-time heartburn.

A survey of current practices in post-polypectomy surveillance in Korea.

BACKGROUND/AIMS: We investigated the clinical practice patterns of post-polypectomy colonoscopic surveillance among Korean endoscopists. METHODS: In a web-based survey conducted between September and November 2021, participants were asked about their preferred surveillance intervals and the patient age at which surveillance was discontinued. Adherence to the recent guidelines of the U.S. Multi-Society Task Force on Colorectal Cancer (USMSTF) was also analyzed. RESULTS: In total, 196 endoscopists completed the survey. The most preferred first surveillance intervals were: a 5-year interval after the removal of 1-2 tubular adenomas < 10 mm; a 3-year interval after the removal of 3-10 tubular adenomas < 10 mm, adenomas ≥ 10 mm, tubulovillous or villous adenomas, ≤ 20 hyperplastic polyps < 10 mm, 1-4 sessile serrated lesions (SSLs) < 10 mm, hyperplastic polyps or SSLs ≥ 10 mm, and traditional serrated adenomas; and a 1-year interval after the removal of adenomas with highgrade dysplasia, >10 adenomas, 5-10 SSLs, and SSLs with dysplasia. In piecemeal resections of large polyps ( > 20 mm), surveillance colonoscopy was mostly preferred after 1 year for adenomas and 6 months for SSLs. The mean USMSTF guideline adherence rate was 30.7%. The largest proportion of respondents (40.8%-55.1%) discontinued the surveillance at the patient age of 80-84 years. CONCLUSIONS: A significant discrepancy was observed between the preferred post-polypectomy surveillance intervals and recent international guidelines. Individualized measures are required to increase adherence to the guidelines.

Association between low-dose aspirin and the risk of gastric cancer and adenoma according to a family history of gastric cancer.

This study aimed to evaluate the association between low-dose aspirin use and the risk of GC and gastric adenoma according to a family history of GC. We conducted a population-based study of 7,596,003 participants screened for GC between 2013 and 2014. Aspirin users and non-users were matched in a 1:1 ratio through propensity score matching (PSM). After PSM, 51,818 participants with a family history of GC and 359,840 without a family history of GC were analyzed (mean follow-up periods: 4.9 ± 0.8 and 4.8 ± 0.8 years, respectively). In patients with a family history of GC, aspirin use was significantly associated with a reduced risk of GC (adjusted hazard ratio [aHR]=0.80; 95 % confidence interval [CI]=0.65-0.995) and gastric adenoma (aHR=0.81; 95% CI=0.69-0.94). In those without a family history of GC, aspirin use was associated with a reduced risk of gastric adenoma (aHR = 0.92; 95 % CI = 0.86-0.98), but not with that of GC (aHR = 0.99; 95 % CI = 0.90-1.08). Low-dose aspirin use was associated with a reduced risk of gastric adenoma, regardless of a family history of GC, and may play a role in the early stages of gastric carcinogenesis. However, the association between aspirin and GC was only observed in those with a family history of GC.

Trends in colorectal cancer incidence according to an increase in the number of colonoscopy cases in Korea.

BACKGROUND: The incidence of colorectal cancer (CRC) and preinvasive CRC (e.g., early colon cancer and advanced adenoma) is gradually increasing in several countries. AIM: To evaluate the trend in incidence of CRC and preinvasive CRC according to the increase in the number of colonoscopies performed in Korea. METHODS: This retrospective cohort study enrolled Korean patients from 2002 to 2020 to evaluate the incidence of CRC and preinvasive CRC, and assess the numbers of diagnostic colonoscopies and colonoscopic polypectomies. Colonoscopy-related complications by age group were also determined. RESULTS: The incidence of CRC showed a rapid increase, then decreased after 2012 in the 50-75 year-age group. During the study period, the rate of incidence of preinvasive CRC increased at a similar level in patients under 50 and 50-75 years of age. Since 2009, the increase has been rapid, showing a pattern similar to the increase in colonoscopies. The rate of colonoscopic polypectomy in patients aged under 50 was similar to the rate in patients over 75 years of age after 2007. The rate of complications after colonoscopy and related deaths within 3 mo was high for those over 75 years of age. CONCLUSION: The diagnosis of preinvasive CRC increased with the increase in the number of colonoscopies performed. As the risk of colonoscopy-related hospitalization and death is high in the elderly, if early lesions at risk of developing CRC are diagnosed and treated under or at the age of 75, colonoscopy-related complications can be reduced for those aged 76 years or over.

Development of functional gastrointestinal disorder symptoms following laparoscopic cholecystectomy: a prospective cohort study.

Background: The casual relationship between the role of cholecystectomy and functional gastrointestinal disorders (FGIDs) are a controversial clinical challenge. This study aimed to investigate: (1) the overlap of FGIDs before cholecystectomy and its long-term outcome after surgery in patients with symptomatic cholelithiasis, and (2) the incidence of new-onset FGIDs after cholecystectomy. Methods: Patients with symptomatic gallstone disease who underwent elective, laparoscopic cholecystectomy were prospectively enrolled. Healthy populations who underwent medical check-ups were selected as age- and sex-matched controls. Questionnaires regarding sociodemographic characteristics, gastrointestinal symptoms and a somatization symptom checklist (SSC) were completed at baseline and 12 months thereafter. Results: The prevalence of all FGID symptoms before cholecystectomy were significantly higher in the group of patients with symptomatic cholecystolithiasis compared to the control group. In cholecystectomy group, the preoperative FGID symptoms improved after surgery, except for chronic diarrhea. Compared to the controls, the new-onset FGIDs, including functional dyspepsia (14.8% vs. 6.9%; p = 0.040), functional diarrhea (6.6% vs. 0.2%; p < 0.001), and chronic abdominal pain (11.9% vs. 4.4%; p = 0.024), were more common at 1 year after cholecystectomy. Somatization was independent predictors of new-onset dyspepsia and abdominal pain, while newly occurring diarrhea was not realted to somatization. Conclusion: Overlap of FGIDs was common in patients with symptomatic cholelithiasis before surgery and at follow-up 1 year after cholecystectomy. Furthermore, new-onset FGIDs could be occurred after cholecystectomy. Therefore, a delicate diagnostic approaches and appropriate treatments about co-existent FGIDs should be given in patients with cholelithiasis before and after cholecystectomy.

Effect of aging on the formation and growth of colonic epithelial organoids by changes in cell cycle arrest through TGF-ß-Smad3 signaling.

BACKGROUND: This study aimed to investigate how aging alters the homeostasis of the colonic intestinal epithelium and regeneration after tissue injury using organoid models and to identify its underlying molecular mechanism. METHODS: To investigate aging-related changes in the colonic intestinal epithelium, we conducted organoid cultures from old (older than 80 weeks) and young (6-10 weeks) mice and compared the number and size of organoids at day 5 of passage 0 and the growth rate of organoids between the two groups. RESULTS: The number and size of organoids from old mice was significantly lower than that from young mice (p < 0.0001) at day 5 of passage 0. The growth rate of old-mouse organoids from day 4 to 5 of passage 0 was significantly slower than that of young-mouse organoids (2.21 times vs. 1.16 times, p < 0.001). RNA sequencing showed that TGF-ß- and cell cycle-associated genes were associated with the aging effect. With regard to mRNA and protein levels, Smad3 and p-Smad3 in the old-mouse organoids were markedly increased compared with those in the young-mouse organoids. Decreased expression of ID1, increased expression of p16INK4a, and increased cell cycle arrest were observed in the old mouse-organoids. Treatment with SB431542, a type I TGF-ß receptor inhibitor, significantly increased the formation and growth of old-mouse organoids, and TGF-ß1 treatment markedly suppressed the formation of young-mouse organoids. In the acute dextran sulfate sodium-colitis model and its organoid experiments, the colonic epithelial regeneration after tissue injury in old mice was significantly decreased compared with young mice. CONCLUSIONS: Aging reduced the formation ability and growth rate of colonic epithelial organoids by increasing cell cycle arrest through TGF-ß-Smad3-p16INK4a signaling.

Dynamic changing smoking habits and cardiovascular events in patients newly diagnosed with hypertension, diabetes, or dyslipidemia: a national cohort study.

Background and aims: This study aimed to examine the association between dynamic smoking habit change and cardiovascular risk in a population newly diagnosed with hypertension, diabetes, and dyslipidemia. Methods: This study included 49,320 individuals who had received health examinations provided by the Korea National Health Insurance Service. To determine the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident major adverse cardiac events (MACE) and all-cause mortality based on dynamic smoking habit changes for 2 years, multivariable Cox proportional hazard models were utilized. Results: During the follow-up, there were 1,004 (2.2%), 3,483 (7.6%), and 334 (0.7%) cases of myocardial infarction, stroke events, and cardiovascular death, respectively. The group with worsening smoking habits had an increased risk of cardiovascular events and death (HR: 1.33, 95% CI: 1.26-1.40) compared to improved smoking habits. The robustness of the results determined by a series of sensitivity analyses further strengthened the main findings. Conclusions: Our findings suggest that worsening of smoking habits, even for a short period of time, may increase the risk of myocardial infarction, stroke, and cardiovascular death in patients diagnosed with hypertension, diabetes, and dyslipidemia. For the primary prevention of cardiovascular events in patients with underlying diseases, dynamic modification of smoking habits should be actively considered.

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.

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.

Lethal effects of mitochondria via microfluidics.

Tumor cells can respond to therapeutic agents by morphologic alternations including formation of tunneling nanotubes. Using tomographic microscope, which can detect the internal structure of cells, we found that mitochondria within breast tumor cells migrate to an adjacent tumor cell through a tunneling nanotube. To investigate the relationship between mitochondria and tunneling nanotubes, mitochondria were passed through a microfluidic device that mimick tunneling nanotubes. Mitochondria, through the microfluidic device, released endonuclease G (Endo G) into adjacent tumor cells, which we referred to herein as unsealed mitochondria. Although unsealed mitochondria did not induce cell death by themselves, they induced apoptosis of tumor cells in response to caspase-3. Importantly, Endo G-depleted mitochondria were ineffective as lethal agents. Moreover, unsealed mitochondria had synergistic apoptotic effects with doxorubicin in further increasing tumor cell death. Thus, we show that the mitochondria of microfluidics can provide novel strategies toward tumor cell death.

Association between Age at Helicobacter pylori Eradication and the Risk of Gastric Cancer Stratified by Family History of Gastric Cancer: A Nationwide Population-Based Study.

INTRODUCTION: This study compares the risk of GC according to age at H. pylori eradication, stratified based on the presence of family history of GC using a population-based large cohort. METHOD: We analyzed individuals who underwent GC screening between 2013 and 2014 and received H. pylori eradication therapy before screening. RESULTS: Among 1,888,815 H. pylori-treated patients, 2610/294,706 and 9332/1,594,109 patients with and without a family history of GC, respectively, developed GC. After adjusting for confounders, including age at screening, the adjusted hazard ratios (95% confidence intervals) for GC comparison, 70-74, 65-69, 60-64, 55-59, 50-54, 45-49, and <45 years with ≥75 years at H. pylori eradication were 0.98 (0.79-1.21), 0.88 (0.74-1.05), 0.76 (0.59-0.99), 0.62 (0.44-0.88), 0.57 (0.36-0.90), 0.38 (0.22-0.66), and 0.34 (0.17-0.67), respectively, among patients with a family history of GC (p < 0.001) and 1.01 (0.91-1.13), 0.95 (0.86-1.04), 0.86 (0.75-0.98), 0.67 (0.56-0.81), 0.56 (0.44-0.71), 0.51 (0.38-0.68), and 0.33 (0.23-0.47), respectively, among patients without a family history of GC (p < 0.001). CONCLUSION: In patients with and without a family history of GC, young age at H. pylori eradication was significantly associated with a reduced risk of GC, suggesting that the early treatment of H. pylori infection can maximize GC prevention.

Clinical outcomes of acute upper gastrointestinal bleeding according to the risk indicated by Glasgow-Blatchford risk score-computed tomography score in the emergency room.

BACKGROUND/AIMS: Acute upper gastrointestinal (UGI) bleeding is a significant emergency situation with a mortality rate of 2% to 10%. Therefore, initial risk stratification is important for proper management. We aimed to evaluate the role of contrast-enhanced multidetector computed tomography (MDCT) for risk stratification in patients with acute UGI bleeding in the emergency room (ER). METHODS: This retrospective study included patients with UGI bleeding in the ER. Glasgow-Blatchford risk score-computed tomography (GBS-CT) was assessed using a combination of GBS and the MDCT scan scoring system. RESULTS: Of the 297 patients with UGI bleeding, 124 (41.8%) underwent abdominal MDCT. Among them, 90.3% were classified as high-risk by GBS, and five patients died (4.0%). Rebleeding occurred in nine patients (7.3%). The high-risk GBS-CT group had significantly higher in-hospital mortality (10.5% in high-risk vs. 1.4% in moderate risk vs. 0% in low-risk, p = 0.049), transfusion amount (p < 0.001), and endoscopic hemostasis (p < 0.001) compared to the moderate- and low-risk groups. CONCLUSION: Adding MDCT scans to the existing validated prognosis model when predicting the risk of UGI bleeding in patients in the ER plays a significant role in determining in-hospital mortality, transfusions, and the need for endoscopic hemostasis.

Association between A Family History of Colorectal Cancer and the Risk of Colorectal Cancer: A Nationwide Population-Based Study.

Large-scale Asian studies on this topic are lacking. We evaluated the CRC risk associated with family history in the Korean population. We analyzed the data of participants aged ≥40 years who underwent national cancer screening between 2013 and 2014. During a mean follow-up of 4.7 ± 0.8 years, 0.43% of the 292,467 participants with family history and 0.28% of the 1,169,868 participants without family history developed CRC. Participants with a family history in any FDR, parents only, and siblings only had a higher risk of CRC than those without family history; adjusted hazard ratios (HRs) were 1.53, 1.46, and 1.61, respectively. Participants with a family history comprising both parents and siblings had an even higher risk of CRC than those without a family history (HR, 2.34). The HRs for CRC in the 40−49, 50−59, 60−69, 70−79, and ≥80 age groups with family history were 1.72, 1.74, 1.50, 1.30, and 0.78, respectively (p < 0.001). A family history of CRC in any FDR and both parents and siblings was associated with an approximately 1.5- and 2.3-fold increased risk of CRC. The effect of family history was relatively greater in the younger than the older age group.

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.

Bowel Preparation and Subsequent Colonoscopy Is Associated with the Risk of Atrial Fibrillation: A Population-Based Case-Crossover Study.

This study aimed to clarify the association of the risk of atrial fibrillation (AF) with bowel preparation and subsequent colonoscopy through population-based case-crossover analysis. Patients who developed new-onset AF after undergoing colonoscopy following bowel preparation were included. For each patient, one hazard period and four control periods were matched at specified time windows. Among 189,613 patients with AF, 84 patients (mean age: 72.4 years) finally met the inclusion criteria. Most patients used polyethylene glycol (PEG)-based solutions (2 L PEG + ascorbic acid (n = 56), 4 L PEG (n = 21)) as purgatives and had hypertension (n = 75). A significant association of bowel preparation and colonoscopy with AF occurrence was found in all time windows. The proportion of patients with bowel preparation and colonoscopy was higher during the hazard period than during the control periods. In the 1-, 2-, 4-, 8-, and 12-week time windows, the proportions were 11.9% vs. 4.2%, 13.1% vs. 4.8%, 16.7% vs. 6.3%, 28.6% vs. 11.9%, and 29.8% vs. 14.0%, and the odd ratios (ORs) were 3.11, 3.01, 3.00, 2.96, and 2.61, respectively. Bowel preparation and undergoing colonoscopy was associated with the risk of AF and this examination need to be performed with caution especially in elderly patients with hypertension.

Association Between Gut Regulatory Hormones and Post-operative Weight Loss Following Gastrectomy in Patients With Gastric Cancer.

Background/Aims: Post-operative weight loss in patients with gastric cancer lead to a poor quality of life and long-term survival. This study aims to evaluate the effects of gut regulatory hormones on post-operative weight loss in patients with subtotal gastrectomy for gastric cancer. Methods: This prospective study was conducted for 12 months post-surgery in 14 controls and 13 gastrectomy patients who underwent subtotal gastrectomy for gastric cancer. Serum plasma ghrelin, glucagon-like peptide-1, gastric inhibitory peptide-1, peptide YY, insulin, and homeostatic model assessment for insulin resistance responses to a standardized test meal were recorded at multiple time points before and after gastrectomy at 4 and 12 months. Results: The mean weight difference between the pre-operative state and the 4-month period was significantly reduced to 6.6 kg (P = 0.032), but significant weight reduction was not observed from 4 months to 12 months. The plasma levels of glucagon-like peptide-1, gastric inhibitory peptide-1, and peptide YY were significantly increased 4 months postoperatively compared to the pre-operative state (all P = 0.035); however, pre-operative levels and relative changes over a period of 0-4 months of hormones were not correlated with body weight changes. Only the pre-operative ghrelin at peak had a negative correlation with changes in weight reduction in the 4 months after surgery (ρ = -0.8, P = 0.024). Conclusions: Significant weight reduction was common after subtotal gastrectomy for gastric cancer with a negative correlation pre-operative plasma ghrelin levels. Incretin hormones are modestly but significantly increased after subtotal gastrectomy; however, these changes did not affect the weight changes.

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.

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.

Positive fecal immunochemical test results are associated with non-colorectal cancer mortality.

BACKGROUND/AIMS: Studies have reported an association between fecal occult blood and increased all-cause, non-colorectal cancer (CRC) as well as CRC mortality. This study aimed to determine whether positive fecal immunochemistry test (FIT) results are associated with death from various causes in the South Korean population. METHODS: Using the Korean National Cancer Screening Program database, we collected data on patients who underwent FIT between 2009 and 2011. RESULTS: Of the 5,932,544 participants, 380,789 (6.4%) had positive FIT results. FIT-positive participants had a higher mortality rate than FIT-negative participants from CRC (1.33 and 0.21 per 1,000 person-years, p < 0.001, respectively) and non-CRC causes (10.40 and 7.50 per 1,000 person-years, p < 0.001, respectively). Despite adjusting for age, sex, smoking status, alcohol consumption habits, body mass index, comorbidity, and aspirin use, FIT positivity was associated with an increased risk of dying from all non-CRC causes (adjusted hazard ratio [aHR], 1.17; 95% confidence interval [CI], 1.15 to 1.18) and CRC (aHR, 5.61; 95% CI, 5.40 to 5.84). Additionally, FIT positivity was significantly associated with increased mortality from circulatory disease (aHR, 1.14; 95% CI, 1.11 to 1.17), respiratory disease (aHR, 1.14; 95% CI, 1.09 to 1.19), digestive disease (aHR, 1.57; 95% CI, 1.48 to 1.66), neuropsychological disease (aHR, 1.08; 95% CI, 1.01 to 1.16), blood and endocrine diseases (aHR, 1.10; 95% CI, 1.04 to 1.17), and external factors (aHR, 1.16; 95% CI, 1.11 to 1.20). CONCLUSION: Positive FIT results are associated with an increased risk of mortality from CRC and various other chronic diseases, suggesting that it could be a predictor of mortality independent of its association with CRC.

Fasting Blood Glucose Variability and Unfavorable Trajectory Patterns Are Associated with the Risk of Colorectal Cancer.

Background/Aims: The relationship between fasting blood glucose (FBG) variability and colorectal cancer (CRC) remains ill-defined. This study aimed to evaluate the association of FBG variability with CRC risk in the healthy population without overt diabetes. Methods: In the data from the Korean National Health Insurance Service-Health Screening Cohort, we included individuals examined by FBG testing at least 3 times between 2002 and 2007. FBG variability was calculated using standard deviation (SD) and coefficient of variation (CV). Results: Regarding FBG variability, an increase in the quintile of SD or CV was independently associated with CRC risk (all p for trend <0.01). When the change in FBG was classified into six trajectory patterns, unfavorable trajectory patterns (high stable and upward) were significantly associated with increased CRC risk (hazard ratio [HR] 2.30, p=0.003; HR 1.19, p=0.007, respectively). In subgroup analyses according to the sex, a significant association between FBG variability (SD or CV) and CRC risk was observed in men but not in women. The high stable and upward pattern were also associated with CRC risk in men (HR 2.47, p=0.002; HR 1.21, p=0.012) but not in women. Conclusions: This study identified that FBG variability and unfavorable trajectory patterns were significantly associated with increased CRC risk in the healthy population without overt diabetes. Our findings suggest that FBG variability as well as FBG itself may be a predictive factor for the development of CRC.