Predictors of Choledocholithiasis in Cholecystectomy Patients and Their Cutoff Values and Prediction Model in Korea in Comparison with the 2019 ASGE Guidelines.

Background/Aims: : In 2019, the American Society for Gastrointestinal Endoscopy (ASGE) established clinical predictors for choledocholithiasis. Our study was designed to evaluate these predictors within the Korean clinical context, establish cutoff values, and develop a predictive model. Methods: : This retrospective study analyzed patients who underwent laparoscopic cholecystectomy. The relationships between choledocholithiasis and predictors including age, blood tests, and imaging findings were assessed through univariate and multivariate logistic regression analyses. We established Korean cutoff values for these predictors and developed a scoring system for choledocholithiasis using a multivariate logistic regression. The performance of this scoring system was then compared with that of the 2019 ASGE guidelines through a receiver operating characteristic curve. Results: : We established Korean cutoff values for age (>70 years), alanine aminotransferase (>26.5 U/L), aspartate aminotransferase (>28.5 U/L), gamma-glutamyl transferase (GGT; >82.5 U/L), alkaline phosphatase (ALP; >77.5 U/L), and total bilirubin (>0.95 mg/dL). In the multivariate analysis, only age >70 years, GGT >77.5 U/L, ALP >77.5 U/L, and common bile duct dilatation remained significant. We then developed a new Korean risk stratification model from the multivariate analysis, with an area under the curve of 0.777 (95% confidence interval, 0.75 to 0.81). Our model was stratified into the low-risk, intermediate-risk, and high-risk groups with the scores being <1.0, 1.0-5.5, and >5.5, respectively. Conclusions: : Predictors of choledocholithiasis in cholecystectomy patients and their cutoff values in Korean should be adjusted and further studies are needed to develop appropriate guidelines.

Factors Affecting Adherence to National Colorectal Cancer Screening: A 12-Year Longitudinal Study Using Multi-Institutional Pooled Data in Korea.

BACKGROUND: Consistent uptake of colorectal cancer (CRC) screening is important to reduce the incidence and mortality from advanced-stage CRC and increase the survival rate of the patients. We conducted a longitudinal study to determine the factors affecting CRC screening compliance in Korean adults using individual-level linked data from the Korean National Health and Nutrition Examination Survey, Korean National Health Insurance Service, and Korean Health Insurance Review and Assessment Service. METHODS: We selected 3,464 adults aged 50-79 years as the study population and followed them for 12 years (January 2007-December 2018). The outcome variable was the level of adherence to CRC screening, categorized as nonadherent, intermittently adherent, and consistently adherent. An ordinal logistic regression model was designed to determine the socioeconomic factors, family history of CRC, and medical conditions that could facilitate the consistent uptake of CRC screening. RESULTS: The results showed a significant and positive association between consistent uptake of CRC screening and the 100-150% income category (odds ratio [OR], 1.710; 95% confidence interval [CI], 1.401-2.088); clerical, sales and service job category (OR, 1.962; 95% CI, 1.582-2.433); residency at medium-sized cities (OR, 1.295; 95% CI, 1.094-1.532); high-school graduation (OR, 1.440; 95% CI, 1.210-1.713); married status (OR, 2.281; 95% CI, 1.946-2.674); use of employment-based national health insurance (OR, 1.820; 95% CI, 1.261-2.626); use of private insurance (OR, 2.259; 95% CI, 1.970-2.589); no disability (OR, 1.428; 95% CI, 1.175-1.737); family history of CRC (OR, 2.027; 95% CI, 1.514-2.714); and history of colorectal neoplasm (OR, 1.216; 95% CI; 1.039-1.422). CONCLUSION: The lack of regular participation in CRC screening programs in the Republic of Korea was found to be an issue that requires attention. Policies on CRC screening must place increased emphasis on strengthening educational and public relations initiatives.

Three cases of jejunal tumors detected by standard upper gastrointestinal endoscopy: A case series.

BACKGROUND: In patients with obscure gastrointestinal bleeding, re-examination with standard upper endoscopes by experienced physicians will identify culprit lesions in a substantial proportion of patients. A common practice is to insert an adult-sized forward-viewing endoscope into the second part of the duodenum. When the endoscope tip enters after the papilla, which is a marker for the descending part of the duodenum, it is difficult to endoscopically judge how far the duodenum has been traversed beyond the second part. CASE SUMMARY: We experienced three cases of proximal jejunal masses that were diagnosed by standard upper gastrointestinal endoscopy and confirmed with surgery. The patients visited the hospital with a history of melena; during the initial upper gastrointestinal endoscopy and colonoscopy, the bleeding site was not confirmed. Upper gastrointestinal bleeding was suspected; thus, according to guidelines, upper endoscopy was performed again. A hemorrhagic mass was discovered in the small intestine. The lesion of the first patient was thought to be located in the duodenum when considering the general insertion depth of a typical upper gastrointestinal endoscope; however, during surgery, it was confirmed that it was in the jejunum. After the first case, lesions in the second and third patients were detected at the jejunum by inserting the standard upper endoscope as deep as possible. CONCLUSION: The deep insertion of standard endoscopes is useful for the diagnosis of obscure gastrointestinal bleeding.

Bile Acids: Major Regulator of the Gut Microbiome.

Bile acids are synthesized from cholesterol and play an important role in regulating intestinal microflora. The different degrees of hydrophobicity and acidity of individual bile acids may affect their antimicrobial properties. We examined the antimicrobial effects of different bile acids on various microorganisms in vitro and confirmed whether these remain consistent in vivo. Using human bile acids, including ursodeoxycholic acid, cholic acid, chenodeoxycholic acid, deoxycholic acid, and lithocholic acid, a disc diffusion test was performed, and a rodent model was created to determine the antimicrobial effects of each bile acid. The fecal bacterial population was analyzed using a real-time polymerase chain reaction. Each bile acid showed different microbial inhibitory properties. The inhibitory activity of bile acids against microbiota which normally resides in the gastrointestinal tract and biliary system, was low; however, normal flora of other organs was significantly inhibited. Changes in microbial counts after bile acid administration in a rodent model differed in the colon and cecum. The in vivo and in vitro results show that the antimicrobial effects of bile acids against intestinal microbiota were similar. In conclusion, bile acids could be a novel treatment strategy to regulate gut microbiota.

Comparison of one-stage laparoscopic common bile duct exploration plus cholecystectomy and two-stage endoscopic sphincterotomy plus laparoscopic cholecystectomy for concomitant gallbladder and common bile duct stones in patients over 80 years old.

Purpose: This study was performed to compare the safety and efficacy of one-stage laparoscopic common bile duct exploration (LCBDE) plus laparoscopic cholecystectomy (LC) with those of endoscopic sphincterotomy (EST) plus LC for concomitant gallbladder (GB) and common bile duct (CBD) stones in elderly patients. Methods: This single-center retrospective study reviewed the medical records of patients aged >80 years who were diagnosed with concomitant GB and CBD stones between January 2010 and December 2020. Results: Of the 137 patients included in this study, 46 underwent one-stage LCBDE + LC and 91 underwent two-stage EST + LC. The frequency of previous gastrectomy (23.9% vs. 5.5%, p = 0.002) and multiple stones (76.1% vs. 49.5%, p = 0.003) was higher in the LCBDE + LC group than in the EST + LC group. Further, patients in LCBDE + LC group had larger CBD stones (11.9 mm vs. 6.0 mm, p < 0.001). There were no significant differences in the clearance (91.3% vs. 95.6%, p = 0.311) and recurrence (4.3% vs. 8.8%, p = 0.345) rates between the groups. The incidence of posttreatment overall complications (17.4% vs. 22.0%, p = 0.530) and total hospital stay (12.7 days vs. 11.7 days, p = 0.339) were similar in the two groups. Conclusion: One-stage LCBDE + LC is a safe and effective treatment for concomitant GB and CBD stones, even in elderly patients, and may be considered as the first treatment option in elderly patients with previous gastrectomy, multiple large (≥ 15 mm) CBD stones, or inability to cooperate with endoscopic procedures.

Single Use (Disposable) Duodenoscope: Recent Development and Future.

Unlike simple forward-viewing endoscopes such as gastroscope or colonoscope, duodenoscope houses much more complex design to fulfil its function. This design differences leave duodenoscopes more prone to contamination from inadequate disinfection process and potential dissemination of pathogens. Recent reports on dissemination of infection through the duodenoscope mandated an overhaul of duodenoscope utilization including development of a disposable duodenoscope. This article reviews the current state of disposable duodenoscope development, including reported early efficacy as well as its future direction and utilization.

Morphological Transitions of a Photoswitchable Aramid Amphiphile Nanostructure.

Self-assembly of small amphiphilic molecules in water can lead to nanostructures of varying geometries with pristine internal molecular organization. Here we introduce a photoswitchable aramid amphiphile (AA), designed to exhibit extensive hydrogen bonding and robust mechanical properties upon self-assembly, while containing a vinylnitrile group for photoinduced cis-trans isomerization. We demonstrate spontaneous self-assembly of the vinylnitrile-containing AA in water to form nanoribbons. Upon UV irradiation, trans-to-cis isomerizations occur concomitantly with a morphological transition from nanoribbons to nanotubes. The nanotube structure persists in water for over six months, stabilized by strong and collective intermolecular interactions. We demonstrate that the nanoribbon-to-nanotube transition is reversible upon heating and that switching between states can be achieved repeatedly. Finally, we use electron microscopy to capture the transition and propose mechanisms for nanoribbon-to-nanotube rearrangement and vice versa. The stability and switchability of photoresponsive AA nanostructures make them viable for a range of future applications.

[Gut Microbiota and Pancreatobiliary System].

The gut microbiota is part of the human body that is involved in body metabolism and the occurrence of various diseases. Detecting and analyzing their genetic information (microbiome) is as important as analyzing human genes. The core microbiome, the key functional genes shared by all humans, helps better understand the physiology of the human body. Information on the gut microbiome of a diseased person can help diagnose and treat disease. The pancreatobiliary system releases functional antimicrobial substances, such as bile acids and antimicrobial peptides, which affect the gut microbiota directly. In response, the gut microbiota influences pancreatobiliary secretion by controlling the generation and emission of substances through indirect signaling. This crosstalk maintains homeostasis of the pancreatobiliary system secretion and microbiota. Dysbiosis and disease can occur if this fails to work properly. Bile acid therapy has been used widely and may affect the microbial environment in the intestine. An association of the gut microbiota has been reported in many cases of pancreatobiliary diseases, including malignant tumors. Traditionally, most pancreatobiliary diseases are accompanied by infections from the gut microbiota, which is an important target for treatment. The pancreatobiliary system can control its function through physical and drug therapy. This may be a new pioneering field in the study or treatment of the gut microbiota.

Bee Venom Phospholipase A2 Induces Regulatory T Cell Populations by Suppressing Apoptotic Signaling Pathway.

Bee venom phospholipase A2 is a lipolytic enzyme in bee venom that catalyzes hydrolysis of the sn-2 ester bond of membrane phospholipids to produce free fatty acid and lysophospholipids. Current evidence suggests that bee venom phospholipase A2 (bvPLA2) induces regulatory T cell expansion and attenuates several immune system-related diseases, including Alzheimer's disease. The induction of Treg cells is directly mediated by binding to mannose receptors on dendritic cells. This interaction induces the PGE2-EP2 signaling pathway, which promotes Treg induction in CD4+ T cells. In this study, we investigated the effects of bvPLA2 treatment on the apoptotic signaling pathway in Treg populations. Flow cytometry was performed to identify early apoptotic cells. As a result, early apoptotic cells were dramatically decreased in bvPLA2-treated splenocytes, whereas rapamycin-treated cells showed levels of apoptotic cells similar to those of PBS-treated cells. Furthermore, bvPLA2 treatment increased expression of anti-apoptotic molecules including CTLA-4 and PD-1. The survival rate increased in bvPLA2-treated Tregs. Our findings indicate that bvPLA2-mediated modulation of apoptotic signaling is strongly associated with the Treg induction, which exhibits protective effects against various immune-related diseases. To our knowledge, this study is the first to demonstrate that bvPLA2 is the major bee venom (BV) compound capable of inducing Treg expansion through altering apoptotic signal.

Rhus verniciflua Stokes attenuates cholestatic liver cirrhosis-induced interstitial fibrosis via Smad3 down-regulation and Smad7 up-regulation.

Cholestatic liver cirrhosis (CLC) eventually proceeds to end-stage liver failure by mediating overwhelming deposition of collagen, which is produced by activated interstitial myofibroblasts. Although the beneficial effects of Rhus verniciflua Stokes (RVS) on various diseases are well-known, its therapeutic effect and possible underlying mechanism on interstitial fibrosis associated with CLC are not elucidated. This study was designed to assess the protective effects of RVS and its possible underlying mechanisms in rat models of CLC established by bile duct ligation (BDL). We demonstrated that BDL markedly elevated the serological parameters such as aspartate aminotransferase, alanine transaminase, total bilirubin, and direct bilirubin, all of which were significantly attenuated by the daily uptake of RVS (2 mg/kg/day) for 28 days (14 days before and after operation) via intragastric route. We observed that BDL drastically induced the deterioration of liver histoarchitecture and excessive deposition of extracellular matrix (ECM), both of which were significantly attenuated by RVS. In addition, we revealed that RVS inhibited BDL-induced proliferation and activation of interstitial myofibroblasts, a highly suggestive cell type for ECM production, as shown by immunohistochemical and semi-quantitative detection of α-smooth muscle actin and vimentin. Finally, we demonstrated that the anti-fibrotic effect of RVS was associated with the inactivation of Smad3, the key downstream target of a major fibrogenic cytokine, i.e., transforming growth factor ß (TGF-ß). Simultaneously, we also found that RVS reciprocally increased the expression of Smad7, a negative regulatory protein of the TGF-ß/Smad3 pathway. Taken together, these results suggested that RVS has a therapeutic effect on CLC, and these effects are, at least partly, due to the inhibition of liver fibrosis by the downregulation of Smad3 and upregulation of Smad7.

Phylogenetics and Gene Structure Dynamics of Polygalacturonase Genes in Aspergillus and Neurospora crassa.

Polygalacturonase (PG) gene is a typical gene family present in eukaryotes. Forty-nine PGs were mined from the genomes of Neurospora crassa and five Aspergillus species. The PGs were classified into 3 clades such as clade 1 for rhamno-PGs, clade 2 for exo-PGs and clade 3 for exo- and endo-PGs, which were further grouped into 13 sub-clades based on the polypeptide sequence similarity. In gene structure analysis, a total of 124 introns were present in 44 genes and five genes lacked introns to give an average of 2.5 introns per gene. Intron phase distribution was 64.5% for phase 0, 21.8% for phase 1, and 13.7% for phase 2, respectively. The introns varied in their sequences and their lengths ranged from 20 bp to 424 bp with an average of 65.9 bp, which is approximately half the size of introns in other fungal genes. There were 29 homologous intron blocks and 26 of those were sub-clade specific. Intron losses were counted in 18 introns in which no obvious phase preference for intron loss was observed. Eighteen introns were placed at novel positions, which is considerably higher than those of plant PGs. In an evolutionary sense both intron loss and gain must have taken place for shaping the current PGs in these fungi. Together with the small intron size, low conservation of homologous intron blocks and higher number of novel introns, PGs of fungal species seem to have recently undergone highly dynamic evolution.

An effective instillation method for water-assisted colonoscopy as performed by in-training endoscopists in terms of volume and temperature.

BACKGROUND AND STUDY AIMS: There is general consensus that water instillation helps insert a colonoscope. However, the most effective method for water instillation has not yet been established, especially for endoscopists-in-training. The aim of this study was to determine volume and temperature for effective water instillation colonoscopy. PATIENTS AND METHODS: This is a prospective, randomized, controlled trial that was carried out at a single center, and a total of 207 consecutive subjects who underwent colonoscopic examination for health checkup were included in the study. Water instillation of supplied water was conducted under four different conditions: 100 and 300 ml at room temperature, 300 ml at 30 °C and no use of water instillation. The following parameters were recorded and analyzed: intubation success rate, independent predictors of successful intubation and intubation time to reach the cecum. RESULTS: The intubation success rate was not significantly different between individual groups. Independent predictors of successful intubation were younger age (P = 0.004) and later examined subjects (P = 0.016). The 300-ml warm water instillation during colonoscopy significantly reduced intubation time over the conventional method without water instillation (P = 0.034). CONCLUSIONS: Instillation of 300-ml warm (30 °C) water during colonoscopy can reduce cecal intubation time for in-training endoscopists without improving the intubation success rate.