Search

Background: Endoscopic submucosal dissection (ESD) is a representative treatment modality for early gastric neoplasms. However, the learning curve for beginners performing ESD using a multibending endoscope has not been introduced., Objective: This study aimed to evaluate the learning curves of operators undergoing intensive training using a multibending endoscope., Design: This was a retrospective single center study., Methods: We retrospectively analyzed data of over 1500 consecutive gastric ESDs performed by two operators using a multibending endoscope. A change-point analysis with 50 cases of moving average speeds was used to determine the new target resection speed. Cumulative sum (CUSUM) analysis was used to identify the cases required for proficiency in ESD. Risk-adjusted CUSUM (RA-CUSUM) analysis was performed for each operator after adjusting for confounding factors influencing the resection speed., Results: In total, 1491 cases were enrolled, with early gastric cancer accounting for 43.2% ( n  = 644). Overall, the en bloc resection, R0 resection, and curability rates were 97.7%, 96.0%, and 92.3%, respectively. The mean resection speed was 19.8 cm 2 /h. Because both operators surpassed the commonly used benchmark resection speed of 9 cm 2 /h in the first 50-case block, we established a new target benchmark of 17.9 cm 2 /h in the change-point analysis. CUSUM analysis indicated that performing 166 cases overall was required to achieve the benchmark, with the 2 operators needing 153 and 69 cases to meet this target speed after RA-CUSUM analysis., Conclusion: Using a multibending endoscope for gastric ESD can help beginners achieve safe and excellent outcomes. These findings will serve as a useful guide for beginners attempting to use a multibending endoscope., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2025.)

Background/aims: Early diagnosis of esophageal cancer (EC) remains challenging despite the increasing frequency of endoscopic screenings globally. The rapidly increasing number of endoscopic screenings performed over a certain period might influence diagnostic performance. This study evaluated the association between the number of endoscopic screenings and EC detection rates in a nationwide cohort., Methods: This retrospective population-based study used the Korean National Cancer Screening Program database, comprising 32,774,742 males and females aged ≥40 years between 2015 and 2019. Negative binomial regression model and least-squares mean evaluation were used to assess the association between month of the year and EC detection rates., Results: This study enrolled 28,032,590 participants who underwent upper endoscopy. The number of participants in the fourth quarter (October to December: 10,923,142 [39.0%]) was 2.1 times higher than that in the first quarter (January to March: 5,085,087 [18.1%]); this trend continued for all 5 years. Contrarily, detection rates for EC in the fourth quarter (0.08/1,000 person) were half that in the first quarter (0.15/1,000 person). The odds of detecting EC were lowest in November; in 2015 the odds were 0.57 (95% confidence interval, 0.41 to 0.79; p=0.001) times lower and in 2016, they were 0.51 (95% confidence interval, 0.37 to 0.68; p<0.001) times lower compared to January. The predicted detection rates showed a decreasing trend toward the end of the year (p>0.05 for all)., Conclusions: The workload of endoscopists increased excessively with the rising number of endoscopies toward the end of the year, which was reflected by the decreased EC detection rates during this period.

Photodynamic therapy (PDT) employing two-photon (TP) excitation is increasingly recognized to induce cell damage selectively in targeted areas, underscoring the importance of developing TP photosensitizers (TP-PSs). In this study, we developed BSe-B, a novel PS that combines a selenium containing dye with biotin, a cancer-selective ligand, and is optimized for TP excitation. BSe-B demonstrated enhanced cancer selectivity, efficient generation of type-I based reactive oxygen species (ROS), low dark toxicity, and excellent cell-staining capability. Evaluation across diverse cell lines (HeLa, A549, OVCAR-3, WI-38, and L-929) demonstrated that BSe-B differentiated and targeted cancer cells while sparing normal cells. BSe-B displayed excellent in vivo biocompatibility. In cancer models such as three-dimensional spheroids and actual colon cancer tissues, BSe-B selectively induced ROS production and cell death under TP irradiation, demonstrating precise spatial control. These findings highlight the potential of BSe-B for imaging-guided PDT and its capability for micro treatment within tissues. Thus, BSe-B demonstrates robust TP-PDT capabilities, making it a promising dual-purpose tool for cancer diagnosis and treatment.

Background and Aims: The rapid urease test (RUT) is widely used to detect Helicobacter pylori infection; however, it is not preferred as a monitoring strategy after eradication owing to its low sensitivity. In this study, we evaluated the diagnostic performance of RUT using the sweeping method, which overcomes the limitations of conventional tissue sampling methods after eradication., Methods: Patients who received H pylori eradication treatment were enrolled. Each of the sweeping and conventional methods was performed on the same patients to compare diagnostic performance. Urea breath test (UBT), histology, and polymerase chain reaction were performed to determine true infection. Logistic regression analysis was conducted to investigate reasons for discrepancies between the results of the 2 methods., Results: In 216 patients, the eradication success rate was 68.1%, and the sensitivity and specificity of the sweeping method were 0.812 and 0.912, respectively, whereas those of the conventional method were 0.391 and 0.993, respectively (P < .05 for all). The area under the receiver operating characteristic curve for the sweeping method was higher than that for the conventional method (0.862 vs 0.692, P < .001). The mean time to H pylori detection for the sweeping method was 4.7 ± 4.4 minutes and 12.3 ± 16.1 minutes for the conventional method (P < .001). The risk for inconsistent results between the 2 methods was the highest for UBT values of 1.4‰ to 2.4‰ (odds ratio, 3.8; P = .016)., Conclusions: The RUT with the sweeping method could potentially replace the tissue sampling method as a test to confirm H pylori eradication and be an alternative option to UBT for patients requiring endoscopy., Competing Interests: Disclosure All authors disclosed no financial relationships. This work was partly supported by the Korean College of Helicobacter and Upper Gastrointestinal Research Foundation Grant (no. KCHUGR-202101002)., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Genomic alterations in tumors play a pivotal role in determining their clinical trajectory and responsiveness to treatment. Targeted panel sequencing (TPS) has served as a key clinical tool over the past decade, but advancements in sequencing costs and bioinformatics have now made whole-genome sequencing (WGS) a feasible single-assay approach for almost all cancer genomes in clinical settings. This paper reports on the findings of a prospective, single-center study exploring the real-world clinical utility of WGS (tumor and matched normal tissues) and has two primary objectives: (1) assessing actionability for therapeutic options and (2) providing clarity for clinical questions. Of the 120 patients with various solid cancers who were enrolled, 95 (79%) successfully received genomic reports within a median of 11 working days from sampling to reporting. Analysis of these 95 WGS reports revealed that 72% (68/95) yielded clinically relevant insights, with 69% (55/79) pertaining to therapeutic actionability and 81% (13/16) pertaining to clinical clarity. These benefits include the selection of informed therapeutics and/or active clinical trials based on the identification of driver mutations, tumor mutational burden (TMB) and mutational signatures, pathogenic germline variants that warrant genetic counseling, and information helpful for inferring cancer origin. Our findings highlight the potential of WGS as a comprehensive tool in precision oncology and suggests that it should be integrated into routine clinical practice to provide a complete image of the genomic landscape to enable tailored cancer management., (© 2024. The Author(s).)

We aimed to evaluate the survival benefits of coadministering statins and multityrosine kinase inhibitors (TKIs) in patients with advanced hepatocellular carcinoma (HCC). Data from the Health Insurance Review and Assessment Service in Korea (2010-2020) were utilized. Statin use (≥28 cumulative defined daily doses) was analyzed, with 1534 statin users matched to 6136 non-users (1:4 ratio) using propensity scores. Primary and secondary outcomes were overall survival (OS) and progression-free survival (PFS). Statin use significantly improved OS (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.72-0.82, p < 0.001) and PFS (HR 0.78, 95% CI 0.74-0.84, p < 0.001). Continuous or post-TKI statin users had better OS, while discontinuation after TKI use led to poorer OS. Both lipophilic and hydrophilic statins improved OS and PFS, particularly with ≥730 cumulative defined daily doses. In conclusion, combining statins and TKIs in patients with advanced HCC yielded significant survival benefits, influenced by statin dosage and duration. Continuous statin administration post-TKI treatment is crucial for improving outcomes in patients with HCC.

Background: Patients with Barcelona clinic liver cancer (BCLC) stage B hepatocellular carcinoma (HCC) are considerably heterogeneous in terms of tumor burden, liver function, and performance status. To improve the poor survival outcomes of these patients, treatment approaches other than transarterial chemoembolization (TACE), which is recommended by HCC guidelines, have been adopted in real-world clinical practice. We hypothesize that this non-adherence to treatment guidelines, particularly with respect to the use of liver resection, improves survival in patients with stage B HCC., Aim: To assess guideline adherence in South Korean patients with stage B HCC and study its impact on survival., Methods: A retrospective analysis was conducted using data from 2008 to 2016 obtained from the Korea Central Cancer Registry. Patients with stage B HCC were categorized into three treatment groups, guideline-adherent, upward, and downward, based on HCC guidelines recommended by the Asian Pacific Association for the Study of the Liver (APASL), the European Association for the Study of the Liver (EASL), and the American Association for the Study of Liver Diseases (AASLD). The primary outcome was HCC-related deaths; tumor recurrence served as the secondary outcome. Survival among the groups was compared using the Kaplan-Meier method and the log-rank test. Predictors of survival outcomes were identified using multivariable Cox regression analysis., Results: In South Korea, over the study period from 2008 to 2016, a notable trend was observed in adherence to HCC guidelines. Adherence to the EASL guidelines started relatively high, ranging from 77% to 80% between 2008 and 2012, but it gradually declined to 58.8% to 71.6% from 2013 to 2016. Adherence to the AASLD guidelines began at 71.7% to 75.9% from 2008 to 2010, and then it fluctuated between 49.2% and 73.8% from 2011 to 2016. In contrast, adherence to the APASL guidelines remained consistently high, staying within the range of 90.14% to 94.5% throughout the entire study period. Upward treatment, for example with liver resection, liver transplantation, or radiofrequency ablation, significantly improved the survival of patients with BCLC stage B HCC compared to that of patients treated in adherence to the guidelines (for patients analyzed according to the 2000 EASL guidelines, the 5-year survival rates were 63.4% vs 27.2%, P < 0.001), although results varied depending on the guidelines. Progression-free survival rates were also significantly improved upon the use of upward treatments in certain groups. Patients receiving upward treatments were typically < 70 years old, had platelet counts > 10 5 /μL, and serum albumin levels ≥ 3.5 g/dL., Conclusion: Adherence to guidelines significantly influences survival in South Korean stage B HCC patients. Curative treatments outperform TACE, but liver resection should be selected with caution due to disease heterogeneity., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Bile acid (BA) is a crucial determinant of the gut microbiome, and cholecystectomy can alter the physiology of BA. Physiological changes in BA resulting from cholecystectomy can also influence the gut microbiome. We aimed to identify the specific taxa associated with perioperative symptoms, including postcholecystectomy diarrhea (PCD), and to evaluate the effect of cholecystectomy on the microbiome by investigating the fecal microbiome of patients with gallstones., Methods: We analyzed the fecal samples of 39 patients with gallstones (GS group) and 26 healthy controls (HC group) to evaluate their gut microbiome. We also collected fecal samples from GS group 3 months postcholecystectomy. Symptoms of patients were evaluated before and after cholecystectomy. Further, 16S ribosomal RNA amplification and sequencing were performed to determine the metagenomic profile of fecal samples., Results: The microbiome composition of GS differed from that of HC; however, the alpha diversity was not different. No significant microbiome alterations were observed before and after cholecystectomy. Moreover, GS group showed a significantly lower Firmicutes to Bacteroidetes ratio before and after cholecystectomy than the HC group (6.2, P< 0.05). The inter-microbiome relationship was lower in GS than in HC and tended to recover 3 months after surgery. Furthermore, ~28.1% ( n =9) of patients developed PCD after surgery. The most prominent species among PCD (+) patients was Phocaeicola vulgatus. Compared with the preoperative state, Sutterellaceae , Phocaeicola , and Bacteroidals were the most dominant taxa among PCD (+) patients., Conclusion: GS group showed a different microbiome from that of HC; however, their microbiomes were not different 3 months after cholecystectomy. Our data revealed taxa-associated PCD, highlighting the possibility of symptom relief by restoring the gut microbiome., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

The long-term effect of Helicobacter pylori eradication on metachronous gastric neoplasm prevention after endoscopic submucosal dissection (ESD) of gastric adenoma is unclear. This study included patients with confirmed H. pylori infection after ESD with curative resection for gastric adenoma. Patients were divided based on the success of H. pylori eradication treatment into two groups: eradication and non-eradication. Patients with any newly detected lesion within 1 year after ESD and recurrence at the ESD site were excluded from the analysis. Further, 1:1 propensity score matching was also performed to eliminate baseline differences between the two groups. H. pylori eradication treatment was administered to 673 patients after ESD (163 in the successful eradication group and 510 in the non-eradication group). During the median follow-up periods of 25 and 39 months in the eradication and non-eradication groups, metachronous gastric neoplasm was identified in 6 (3.7%) and 22 patients (4.3%), respectively. Adjusted Cox analysis revealed that H. pylori eradication was not associated with increased risk of metachronous gastric neoplasm after ESD. Kaplan-Meier analysis in the matched population yielded similar findings ( p = 0.546). H. pylori eradication treatment was not associated with metachronous gastric neoplasm after ESD with curative resection for gastric adenoma.

Background & Aims: The faecal immunochemical test (FIT), a non-invasive test for screening colorectal cancer (CRC), is being increasingly understood to reflect heightened inflammation. We aimed to investigate the association between abnormal FIT results and onset of inflammatory bowel disease (IBD), a disease characterized with chronic gut mucosal inflammation., Methods: Participants in the Korean National Cancer Screening Program for CRC between 2009-2013 were analysed and divided into positive and negative FIT result groups. The incidence rates of IBD after screening were calculated after excluding cases of haemorrhoids, CRC, and IBD at baseline. Cox proportional hazard analyses were used to identify independent risk factors for IBD occurrence during follow-up, and 1:2 propensity score matching was performed as a sensitivity analysis., Results: In total, 229,594 and 815,361 participants were assigned to the positive and negative FIT result groups, respectively. The age- and sex-adjusted incidence rates of IBD in participants with positive and negative test results were 1.72 and 0.50 per 10,000 person-years, respectively. Adjusted Cox analysis revealed that FIT positivity was associated with a significantly higher risk of IBD (hazard ratio 2.93, 95% confidence interval: 2.46, 3.47, P <.001), which was consistent for both disease subtypes of ulcerative colitis and Crohn's disease. The results of Kaplan-Meier analysis in the matched population yielded identical findings., Conclusions: Abnormal FIT results could be a preceding sign of incident IBD in the general population. Those with positive FIT results and suspected IBD symptoms could benefit from regular screening for early disease detection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lee, Lee, Park, Ahn and Noh.)

Background: Accumulating evidence now indicates that the presence of faecal haemoglobin, in the absence of gastrointestinal bleeding, may be an indicator of systemic inflammation and is linked to the development of human diseases. We evaluated whether a positive faecal immunochemical test (FIT) is associated with the development of immune-mediated inflammatory diseases (IMIDs)., Methods: Data from the nationwide colorectal cancer screening programme from 2009 to 2013 were used. Participants (n=8,646,887) were divided into FIT (+) and FIT (-) groups by performing a 1:1 random sampling matched by age and sex. Participants with concurrent haemorrhoids, colorectal cancer (CRC), inflammatory bowel disease (IBD), and missed CRC and IBD were excluded using the colonoscopy results, ICD-10 codes, and the special exemption code (V code). Endpoints were the incidence of IMIDs (rheumatoid arthritis [RA], systemic lupus erythematosus [SLE], and psoriatic arthritis [PsA]) after FIT., Results: Of the 1,044,955 eligible participants, 229,594 and 815,361 individuals were included in the FIT (+) and the FIT (-) groups, respectively. During the mean follow-up period of 7.59 years, a total of 7645 (incidence rate [IR] 9.56/10,000 person-years [PY]), 208 (IR 0.26/10,000 PY), and 101 (IR 0.13/10,000 PY) patients were diagnosed with RA, SLE, and PsA, respectively. An adjusted Cox analysis demonstrated that FIT positivity conferred a 1.16 (95% confidence interval [CI] 1.09-1.24, p<0.001) times greater risk of developing RA. Kaplan-Meier analysis in the 1:2 propensity-score matched population also confirmed these results (hazard ratio [HR] 1.18, 95% CI 1.10-1.27, p<0.001)., Conclusions: Positive FIT is associated with increased risk of RA in the general population, corroborating that aberrancies of gut mucosa are associated with the development of IMIDs. Vigilant monitoring and early referral to a specialist upon medical suspicion is required in this population., Trial Registration: Retrospectively registered., (© 2022. The Author(s).)

Competing Interests: Competing interests: None declared.

Background: The clinical outcomes of endoscopic submucosal dissection (ESD) for undifferentiated (UD) intramucosal early gastric cancer (EGC) compared with those of surgery, regardless of lesion size, are not well known. Furthermore, there is a concern regarding the treatment plan before and after ESD in cases of UD intramucosal EGC within expanded indications., Aim: To evaluate clinical outcomes of ESD compared with those of surgery in UD intramucosal EGC patients regardless of tumor size., Methods: We enrolled patients with UD intramucosal EGC after ESD with complete resection or surgery from January 2005 to August 2020 who met the within or beyond expanded indications with lesion size > 2 cm (the only non-curative factor). Overall, 123 and 562 patients underwent ESD and surgery, respectively. After propensity-score matching, clinical and long-term outcomes, i.e ., recurrence-free survival (RFS) and overall survival (OS), were analyzed. The multivariable Cox proportional hazard model with treatment modality and ESD indication was used to evaluate the recurrence risk., Results: After matching, 119 patients each were finally enrolled in the ESD and surgery groups. The median length of hospital stay was shorter in the ESD group than surgery group (4.0 vs 9.0 days, P < 0.001). Four cases of recurrence after ESD were local recurrences, all of which occurred within 1 year. Total recurrence was seven (5.9%) and two (1.7%) in the ESD and surgery groups, respectively. No difference was observed between the two groups with respect to OS ( P = 0.948). However, the ESD group had inferior RFS compared with the surgery group ( P = 0.031). ESD was associated with the risk of recurrence after initial treatment in all enrolled patients (hazard ratio, 5.2; 95% confidence interval: 1.0-25.8, P = 0.045)., Conclusion: Although OS was similar between the two groups, surveillance endoscopy was important for the ESD than for the surgery group because RFS was inferior and local recurrence was an issue., Competing Interests: Conflict-of-interest statement: No potential conflicts of interest were disclosed., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Although regular endoscopic screening may help in early detection of gastric cancer, interval cancer remains a problem in the screening program. This study evaluated the association between regular endoscopic screening and interval cancer detection in the Korean National Cancer Screening Program (KNCSP). We defined three groups (regularly, irregularly, and not screened) according to the screening interval, and the trends in the interval cancer rate (ICR) between the groups were tested using the Cochran-Armitage test. The influence of regular endoscopic screening on the risk of interval cancer was evaluated using multivariable logistic regression. Among the 11,642,410 participants who underwent endoscopy, the overall ICR was 0.36 per 1000 negative screenings. The ICR of the not screened group (0.41) was the highest among the three groups and the risk of interval cancer in this group was 1.68 times higher ( p < 0.001) than that in the regularly screened group. Women in their 40s who had regular screening with no history of intestinal metaplasia and gastric polyps would have the lowest probability of having interval cancer (0.005%). Regular participation in endoscopic screening programs for reducing the risk of interval cancer may help to improve the quality of screening programs.

Inappropriate cancer management can be prevented by simultaneous cancer diagnosis, treatment, and real-time assessment of therapeutic processes. Here, we describe the design of a two-photon (TP) photosensitizer (PS), ACC-B , for high temporal and spatioselective near-infrared cancer therapy. ACC-B consisting of a biotin unit significantly enhanced the cancer sensitivity of the PS. Upon TP irradiation, ACC-B generated reactive oxygen species (ROS) through the type I photodynamic therapy (PDT) process and triggered highly selective cancer ablation. In addition, fluorescence microscopy images revealed that ACC-B -loaded live human colon tissues showed a marked difference in ACC-B uptake between normal and cancer tissues, and this property was used for real-time imaging. Upon 770 nm TP treatment, ACC-B generated ROS efficiently in live colon cancer tissues with high spatial selectivity. During PDT, ACC-B can provide in situ spatioselective visualization of cellular behavior and molecular information for therapeutic assessment in specific regions.

To date, there exists no established endoscopic surveillance interval strategy after endoscopic submucosal dissection (ESD) for gastric adenoma. In this study, we suggest a risk factor-based statistical model for optimal surveillance intervals for gastric adenoma after ESD with curative resection. A cox proportional hazard model was applied to identify risk factors for recurrence after ESD. Patients (n = 698) were categorized into groups based on the identified risk factors. The cumulative density of recurrence over time was computed using a cubic splined baseline hazard function, and the customized surveillance interval was modeled for each risk group. The overall cumulative incidence of recurrence was 7.3% (n = 51). Risk factors associated with recurrence were male (hazard ratio [HR], 2.60, P = 0.030), protruded scar (HR, 3.18, P < 0.001), and age ≥ 59 years (HR, 1.05, P < 0.001). The surveillance interval for each group was developed by using the recurrence limit for the generated risk groups. According to the developed schedule, high-risk patients would have a maximum of seven surveillance visits for 5 years, whereas low-risk patients would have biennial surveillance for cancer screening. We proposed a simple and promising strategy for determining a better endoscopic surveillance interval by parameterizing diverse and group-specific recurrence risk factors into a well-known survival model., (© 2021. The Author(s).)

Background: High-fidelity simulators are highly useful in assessing clinical competency; they enable reliable and valid evaluation. Recently, the importance of peer assessment has been highlighted in healthcare education, and studies using peer assessment in healthcare, such as medicine, nursing, dentistry, and pharmacy, have examined the value of peer assessment. This study aimed to analyze inter-rater reliability between peers and instructors and examine differences in scores between peers and instructors in the assessment of high-fidelity-simulation-based clinical performance by medical students., Methods: This study analyzed the results of two clinical performance assessments of 34 groups of fifth-year students at Ajou University School of Medicine in 2020. This study utilized a modified Queen's Simulation Assessment Tool to measure four categories: primary assessment, diagnostic actions, therapeutic actions, and communication. In order to estimate inter-rater reliability, this study calculated the intraclass correlation coefficient and used the Bland and Altman method to analyze agreement between raters. A t-test was conducted to analyze the differences in evaluation scores between colleagues and faculty members. Group differences in assessment scores between peers and instructors were analyzed using the independent t-test., Results: Overall inter-rater reliability of clinical performance assessments was high. In addition, there were no significant differences in overall assessment scores between peers and instructors in the areas of primary assessment, diagnostic actions, therapeutic actions, and communication., Conclusions: The results indicated that peer assessment can be used as a reliable assessment method compared to instructor assessment when evaluating clinical competency using high-fidelity simulators. Efforts should be made to enable medical students to actively participate in the evaluation process as fellow assessors in high-fidelity-simulation-based assessment of clinical performance in situations similar to real clinical settings., (© 2021. The Author(s).)

Background: Endoscopy is the most important tool for gastric cancer diagnosis. However, it relies on naked-eye evaluation by endoscopists, and the histopathologic confirmation is time-consuming. We aimed to visualize and measure the activity of various enzymes through two-photon microscopy (TPM) using fluorescent probes and assess its diagnostic potential in gastric cancer., Methods: β-Galactosidase (β-gal), carboxylesterase (CES), and human NAD(P)H: quinone oxidoreductase (hNQO1) enzyme activities in the normal mucosa, ulcer, adenoma, and gastric cancer biopsy samples were measured using two-photon enzyme probes. The fluorescence emission ratio at long and short wavelengths (Ch2/Ch1) for each probe was comparatively analyzed. Approximately 8,000 - 9,000 sectional images in each group were obtained by measuring the Ch2/Ch1 ratio according to the tissue depth. Each probe was cross-validated by measuring enzymatic activity from a solution containing lysed tissue., Results: Total of 76 subjects were enrolled in this pilot study (normal 21, ulcer 18, adenoma 17, and cancer 20 patients, respectively). There were significant differences in the mean ratio values of β-gal (0.656 ± 0.142 vs . 1.127 ± 0.109, P < 0.001) and CES (0.876 ± 0.049 vs . 0.579 ± 0.089, P < 0.001) between the normal and cancer, respectively. The mean ratio value of cancer tissues was different compared to ulcer and adenoma ( P < 0.001). The hNQO1 activity showed no significant difference between cancer and other conditions. Normal mucosa and cancer were visually and quantitatively distinguished through β-gal and CES analyses using TPM images, and enzymatic activity according to depth, was determined using sectional TPM ratiometric images. The results obtained from lysis buffer-treated tissue were consistent with TPM results., Conclusions: TPM imaging using ratiometric fluorescent probes enabled the discrimination of gastric cancer from normal, ulcer, and adenoma. This novel method can help in a visual differentiation and provide quantitative depth profiling in gastric cancer diagnosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Noh, Lim, Lee, Cho, Lee, Roh, Kim, Lee, Park, Kim and Shin.)

Stomach cancer is a global health issue because of its incidence and mortality rates worldwide. We developed a near-infrared (NIR) emissive ratiometric two-photon (TP) probe ( HCC1 ) for the quantitative analysis of pH in live cells and human stomach tissues. The probe design is based on a restrained hemicyanine core that controls the intramolecular charge transfer from 2-naphthol, with a suitable p K a value (7.50) under physiological conditions. The probe exhibited improved quantum yield, stability, and TP activity under physiological conditions. In addition, intracellular pH titration (pH 4.0 to 10.0) of HCC1 revealed an ideal intracellular p K a of approximately 7.2, negligible cytotoxicity, and TP excited fluorescence in situ, thereby allowing direct imaging of the cellular pH in live cells and tissues. Ratiometric two-photon microscope imaging with HCC1 of human stomach tissue revealed a clear intratissue pH variation among normal, adenoma, and cancer tissues. Our results demonstrate that HCC1 is useful as an NIR imaging probe for in situ pH-related studies and in cancer research.

In this work, a multi-mode radar transceiver supporting pulse, FMCW and CW modes was designed as an integrated circuit. The radars mainly detect the targets move by using the Doppler frequency which is significantly affected by flicker noise of the receiver from several Hz to several kHz. Due to this flicker noise, the long-range detection performance of the radars is greatly reduced, and the accuracy of range to the target and velocity is also deteriorated. Therefore, we propose a transmitter that suppresses LO leakage in consideration of long-range detection, target distance, velocity, and noise figure. We also propose a receiver structure that suppresses DC offset due to image signal and LO leakage. The design was conducted with TSMC 65 nm CMOS process, and the designed and fabricated circuit consumes a current of 265 mA at 1.2 V supply voltage. The proposed transmitter confirms the LO leakage suppression of 37 dB at 24 GHz. The proposed receiver improves the noise figure by about 20 dB at 100 Hz by applying a double conversion architecture and an image rejection, and it illustrates a DC rejection of 30 dB. Afterwards, the operation of the pulse, FMCW, and CW modes of the designed radar in integrated circuit was confirmed through experiment using a test PCB.

Background: Bioelectrical impedance analysis provides information on body composition and nutritional status. However, it's unclear whether the preoperative edema index or phase angle predicts postoperative complication or mortality in patients with hepatocellular carcinoma (HCC). Thus, we investigated whether preoperative bioelectrical impedance analysis could predict postoperative complications and survival in patients with HCC., Methods: Seventy-nine patients who underwent hepatectomy for hepatocellular carcinoma were prospectively enrolled and bioelectrical impedance analysis was performed before surgery. Postoperative ascites or acute kidney injury and patients' survival were monitored after surgery., Results: Among 79 patients, 35 (44.3%) developed ascites or acute kidney injury after hepatectomy. In multivariate analysis, a high preoperative edema index (extracellular water/total body water) (>0.384) (odds ratio 3.96; 95% confidence interval: 1.03-15.17; P=0.045) and higher fluid infusion during surgery (odds ratio 1.36; 95% confidence interval: 1.04-1.79; P=0.026) were identified as significant risk factors for ascites or acute kidney injury after hepatectomy. Subgroup analyses showed that the edema index was a significant predictor of ascites or acute kidney injury in patients with cirrhosis. Tumor size was the only significant predictive factor for short-term survival after hepatectomy., Conclusions: The preoperative edema index using bioelectrical impedance analysis can be used as a predictor of post-hepatectomy complication, especially in patients with liver cirrhosis., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-5194). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Importance: The rapidly increasing number of gastric cancer examinations performed over a short period might influence screening performance. Accessing the association between calendar month and gastric cancer detection rates might improve policy and guide institutional support., Objective: To evaluate the association between the increased number of examinations over a certain period and gastric cancer detection rates among a large population included in the Korean National Cancer Screening Program (KNCSP)., Design, Setting, and Participants: This retrospective, population-based cohort study used data from the KNCSP comprising 26 765 665 men and women aged 40 years or older who participated in the screening program between January 1, 2013, and December 31, 2016. Data were analyzed from November 1, 2019, to March 31, 2020., Exposures: Gastric cancer screening with endoscopy., Main Outcomes and Measures: The primary outcome was monthly gastric cancer detection rates in the KNCSP. A negative binomial regression model was used to evaluate the association between the screening month and detection rates., Results: In total, 21 535 222 individuals underwent endoscopy (mean [SD] age, 55.61 [10.61] years; 11 761 709 women [54.62%]). The quarterly number of participants was the highest in the last quarter of the study period (2013-2014: 4 094 951 [41.39%], 2015-2016: 4 911 629 [42.19%]); this proportion was 2.48 to 2.84 times greater than that of the first quarter. Cancer detection rates were the lowest in December (2013-2014: 0.22; 95% CI, 0.22-0.23; 2015-2016: 0.21; 95% CI, 0.21-0.22); this was approximately a 40.0% to 45.0% reduction compared with the rates in January. The age group was the significant factor for monthly detection rates. After adjustment for the age group and taking account of the number of screenings, the estimated coefficient range for the screening month was negative and the detection rate in December was significantly different than in January for both the consequent cycles (2013-2014: -0.05 to -0.18; P < .001; and 2015-2016: -0.06 to -0.19; P < .001). In the multivariable logistic model, the association of calendar month with detected cancer remained after adjusting for other confounding factors (December, 2013-2014: odds ratio, 0.82; 95% CI, 0.76-0.87; P < .001; 2015-2016: odds ratio, 0.83; 95% CI, 0.79-0.89; P < .001)., Conclusions and Relevance: The findings of this cohort study suggest that the workload of endoscopists increased with the increasing number of examinations toward the end of the year, as demonstrated by the decreased cancer detection rates. These findings may help to improve gastric cancer detection rates of screening programs by controlling the monthly screening number and policy modifications.

Background/aim: Currently, there are no standard guidelines for the waiting time from the diagnosis of gastric neoplasms to endoscopic submucosal dissection (ESD)., Patients and Methods: A total of 1,605 patients who had undergone ESD for early gastric cancer (EGC) or high-grade dysplasia (HGD) were enrolled. Waiting time for ESD was defined as the time from the first diagnosis to ESD. Multivariable logistic regression analysis was conducted., Results: The curative resection rate was 86.8% and the mean waiting time was 36.8 days. In the multivariable model, longer waiting time did not significantly affect non-curative resection, whereas age >70 years, submucosal fibrosis, and initial cancer diagnosis were significantly associated with non-curative resection. Waiting time was still not identified as a risk factor for non-curative resection in EGC and HGD groups., Conclusion: A longer waiting time from diagnosis to ESD was not associated with non-curative resection., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Although the rapid urease test (RUT) is a simple method for detecting Helicobacter pylori (H. pylori) infection, it requires sufficient biopsy samples and its sensitivity varies depending on the site and condition of H. pylori infection. We compared the diagnostic performance of a "sweeping method" for H. pylori detection with the conventional biopsy sampling method in atrophic gastric conditions which can reduce RUT accuracy. This prospective study included 279 patients who underwent upper endoscopy to determine the presence of H. pylori infection. Gastric mucosa of both the antrum and the corpus were swabbed, and we named this method the "sweeping method". Biopsy sampling for the conventional method, histologic evaluation, and polymerase chain reaction were performed at the same time. The sensitivity, specificity, and accuracy of the sweeping method were 0.941, 0.826, and 0.903, respectively, compared to 0.685, 0.859, and 0.742, respectively, for the conventional biopsy method. The area under the receiver operating curve for the sweeping method was 0.884 versus 0.772 for the conventional method (P < 0.001). The sweeping method had a faster detection time than the conventional method. Compared to conventional biopsy sampling, the sweeping method with the RUT provided higher sensitivity and accuracy for the detection of H. pylori, with a faster detection time.

Background/aims: Low baseline impedance levels (BILs) have been suggested to be evidence of GERD. The aim of this study is to investigate the usefulness of esophageal BILs for the diagnosis of nonerosive reflux disease (NERD) and the proper time for measurement in endoscopy-negative Korean patients with esophageal or supraesophageal symptoms., Methods: Endoscopy-negative patients with esophageal or supraesophageal symptoms who underwent esophageal multichannel intraluminal impedance-pH monitoring were included. BILs were measured in the proximal and distal esophagus around 10 minutes before meals, 10 minutes and 30 minutes after meals, 30 minutes before the start of nighttime sleep, and 30 minutes and 60 minutes after the start of nighttime sleep., Results: A total of 104 patients were included in the study. Distal and proximal esophageal BILs were decreased after meal ingestion. The BILs of the distal esophagus were significantly lower at all time points in the NERD group, but not in the reflux hypersensitivity (RH) group, compared with the functional group. The area under the receiver operating characteristic curve for the diagnosis of NERD was significant at all time points, but that for the diagnosis of RH was not. The cut-off value of 2375 Ω or 2125 Ω measured around 30 minutes before or 60 minutes after the start of nighttime sleep, respectively, were appropriate for the diagnosis of NERD., Conclusion: The BILs of the distal esophagus measured at time points before or after the start of nighttime sleep appear to be useful for the diagnosis of NERD, but not for the diagnosis of RH, in endoscopy-negative Korean patients with esophageal or supraesophageal symptoms.

Background/aims: The pathophysiology of functional abdominal bloating and distention (FABD) is unclear yet. Our aim is to compare the diversity and composition of fecal microbiota in patients with FABD and healthy individuals, and to evaluate the relationship between small intestinal bacterial overgrowth (SIBO) and dysbiosis., Methods: The microbiota of fecal samples was analyzed from 33 subjects, including 12 healthy controls and 21 patients with FABD diagnosed by the Rome IV criteria. FABD patients underwent a hydrogen breath test. Fecal microbiota composition was determined by 16S ribosomal RNA amplification and sequencing., Results: Overall fecal microbiota composition of the FABD group differed from that of the control group. Microbial diversity was significantly lower in the FABD group than in the control group. Significantly higher proportion of Proteobacteria and significantly lower proportion of Actinobacteria were observed in FABD patients, compared with healthy controls. Compared with healthy controls, significantly higher proportion of Faecalibacterium in FABD patients and significantly higher proportion of Prevotella and Faecalibacterium in SIBO (+) patients with FABD were found. Faecalibacterium prausnitzii , was significantly more abundant, but Bacteroides uniformis and Bifidobacterium adolescentis were significantly less abundant in patients with FABD, compared with healthy controls. Significantly more abundant Prevotella copri and F. prausnitzii , and significantly less abundant B. uniformis and B. adolescentis were observed in SIBO (+) patients, compared with healthy controls., Conclusion: The fecal microbiota profiles in FABD patients are different from those in healthy controls, particularly in SIBO (+) patients, suggesting a role of gut microbiota in the pathogenesis of FABD.

Background/aims: The negative effects on the eradication success of Helicobacter pylori infection after previous exposure to macrolides, including clarithromycin on clarithromycin-based first-line therapy have been demonstrated. However, whether this is true for metronidazole-based second-line quadruple therapy remains unclear. We investigated the relationship between past administration of metronidazole and the failure of metronidazole-based second-line quadruple therapy in patients with H. pylori infection., Methods: Patients over 20 years of age who were diagnosed with H. pylori infection between January 1998 and March 2016 were enrolled in this study. The relationship between the clinical parameters and the results of a C13-urea breath test after metronidazole-based second-line quadruple therapy was analyzed in patients for whom clarithromycin-based triple therapy failed to eradicate H. pylori., Results: The H. pylori eradication failure rate was significantly higher in patients with a history of metronidazole use than in patients without a history of metronidazole use (p = 0.011). Multivariable analysis showed that the odds ratio of previous metronidazole use for eradication failure was 3.468 (95% confidence interval, 1.391 to 8.649; p = 0.008). In the subgroup analysis of patients with a history of metronidazole use, the duration of metronidazole use and interval between its use and eradication therapy did not significantly affect H. pylori eradication failure., Conclusion: Previous exposure to metronidazole was a significant risk factor for treatment failure of metronidazole-based second-line quadruple therapy; therefore, this should be considered when establishing a treatment strategy for patients with H. pylori infection.

Background/aims: Adequate bowel preparation is important for successful colonoscopy. We aimed to evaluate the clinical feasibility and effectiveness of abdominal vibration stimulation in bowel preparation before therapeutic colonoscopy., Methods: A single center, prospective, randomized, investigator-blinded study was performed between January 2016 and December 2016. Patients for therapeutic colonoscopy were prospectively enrolled and assigned to either the vibrator group or walking group. Patients who refused to participate in this study as part of the experimental group consented to register in the control group instead. During the preparation period, patients assigned to the walking group walked ≥3,000 steps, whereas those assigned to the vibrator group received abdominal vibrator stimulation and restricted walking. All patients received the same colon cleansing regimen: 4-L split-dose polyethylene glycol (PEG) solution., Results: Three hundred patients who received PEG solution for therapeutic colonoscopy were finally enrolled in this study (n=100 per group). Bowel cleansing with abdominal vibration stimulation showed almost similar results to that with walking exercise (Boston Bowel Preparation Scale score for the entire colon: vibrator vs walking vs control, 7.38±1.55 vs 7.39±1.55 vs 6.17±1.15, p<0.001). There were no significant differences between the vibrator group and walking group regarding instances of diarrhea after taking PEG, time to first diarrhea after taking PEG, total procedure time, and patient satisfaction., Conclusions: This study indicates that, compared with conventional walking exercise, abdominal vibration stimulation achieved similar rates of bowel cleansing adequacy and colonoscopy success without compromising safety or patient satisfaction.

Colorectal cancer is a major cause of cancer-related deaths worldwide. Histologic diagnosis using biopsy samples of colorectal neoplasms is the most important step in determining the treatment methods, but these methods have limitations in accuracy and effectiveness. Herein, we report a dual-recognition two-photon probe and its application in the discrimination between human colorectal neoplasms. The probe is composed of two monosaccharides, d-glucosamine and β-d-galactopyranoside, in a fluorophore for the monitoring of both glucose uptake and β-gal hydrolysis. In vitro/cell imaging studies revealed the excellent selectivity and sensitivity of the probe for glucose transporter-mediated glucose uptake and β-gal activity. Cancer-specific uptake was monitored by increased fluorescence intensity, and additional screening of cancer cells was achieved by changes in emission ratio owing to the higher activity of β-gal. Using human colon tissues and two-photon microscopy, we found that the plot of intensity versus ratio can accurately discriminate between colorectal neoplasms in the order of cancer progression (normal, adenoma, and carcinoma).

Background/aims: Barcelona Clinic Liver Cancer (BCLC) C stage demonstrates considerable heterogeneity because it includes patients with either symptomatic tumors (performance status [PS], 1-2) or with an invasive tumoral pattern reflected by the presence of vascular invasion (VI) or extrahepatic spread (EHS). This study aimed to derive a more relevant staging system by modification of the BCLC system considering the prognostic implication of PS., Methods: A total of 7,501 subjects who were registered in the Korean multicenter hepatocellular carcinoma (HCC) registry database from 2008 to 2013 were analyzed. The relative goodness-of-fit between staging systems was compared using the Akaike information criterion (AIC) and integrated area under the curve (IAUC). Three modified BCLC (m-BCLC) systems (#1, #2, and #3) were devised by reducing the role of PS., Results: As a result, the BCLC C stage, which includes patients with PS 1-2 without VI/EHS, was reassigned to stage 0, A, or B according to their tumor burden in the m-BCLC #2 model. This model was identified as the most explanatory and desirable model for HCC staging by demonstrating the smallest AIC (AIC=70,088.01) and the largest IAUC (IAUC=0.722), while the original BCLC showed the largest AIC (AIC=70,697.17) and the smallest IAUC (IAUC=0.705). The m-BCLC #2 stage C was further subclassified into C1, C2, C3, and C4 according to the Child-Pugh score, PS, presence of EHS, and tumor extent. The C1 to C4 subgroups showed significantly different overall survival distribution between groups (p<0.001)., Conclusions: An accurate and relevant staging system for patients with HCC was derived though modification of the BCLC system based on PS.

γ-Glutamyltransferase (GGT) plays a role in cleaving the γ-glutamyl bond of glutathione. The GGT is known to be overexpressed in some tumors and has been recognized as a potential biomarker for malignant tumors. Colon cancer is one of the most common cancers worldwide; however, there is no quantitative method for detecting cancer cells in human colon tissues. In this study, we report a ratiometric two-photon probe for GGT that can be applied in human colon tissues. The probe (Probe 2) showed high fluorescence efficiency, marked fluorescence changes, excellent kinetics, and selectivity for the GGT in live colon cells. Additionally, we obtained ratiometric two-photon microscopy images of GGT activity in human colon tissue. We used this method to compare normal and cancer tissues based on their ratio values; the ratio value was higher in cancer tissue than in normal tissue. This study provides a method for quantitative analysis of GGT, particularly in human colon cancer, which will be useful for studying GGT-related diseases and diagnosing colon cancer.

Background/aim: Fibroblast growth factor (FGF), vascular endothelial growth factor, and hepatocyte growth factor play a critical role in the pathogenesis of hepatocellular carcinoma (HCC)., Materials and Methods: We assessed nine single nucleotide polymorphisms (SNPs) in the FGF1, FGF2, FGF receptor (FGFR)-2, Flt-1, and c-MET genes in 245 HCC patients and 483 chronic hepatitis B virus (HBV) carriers without HCC., Results: Kaplan-Meier analysis showed that patients with the FGF2 rs308447 TT genotype had shorter overall survival than patients with the CC or CT genotype (p=0.016) and that FGF2 rs308379 A allele carriers had shorter overall survival than patients with the TT genotype (p=0.020)., Conclusion: Multivariate Cox proportional analysis revealed that the FGF2 rs308379 A allele (hazard ratio(HR)=1.663, p=0.004) and advanced tumor stage (HR=3.430, p<0.001) were independent prognostic factors for overall survival in patients with HCC., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aims: The mucosal healing process after endoscopic submucosal dissection (ESD) is mostly scarring change (flat type), but a protruded lesion is occasionally found. We investigated the factors influencing the mucosal healing process, such as the flat and protruded types., Methods: A total of 2,096 ESD cases were performed from February 2005 to December 2013, and 1,757 underwent follow-up endoscopy after 3 months to check the healing type of the ulceration. We retrospectively reviewed the medical charts to analyze demographic, endoscopic, and pathological findings between the 2 groups., Results: Forty-eight cases were of the protruded type and 1,709 were of the flat type. In univariate analysis, the protruded type was found more in the antrum, anterior wall, and greater curvature (p < 0.001). In protruded types, the Helicobacter pylori (H. pylori) infection rate was lower (p < 0.017), the mean length of ESD specimen was shorter (p < 0.012), the fibrosis rate was lower (p < 0.033), and the mean number of hot biopsy and clips during ESD were less (p < 0.008 and p < 0.001 respectively)., Conclusions: The healing type of mucosal ulceration after ESD seemed to be influenced by location, specimen size, and the presence of an H. pylori infection., (© 2019 S. Karger AG, Basel.)

Background and Aim: The histologic discrepancies between preoperative endoscopic forceps biopsy (EFB) and endoscopic submucosal dissection (ESD) specimens sometimes confuse the endoscope operator. This study aimed to analyze the limitation of the biopsy-based diagnosis before ESD and to evaluate which factors affect the discordant pathologic results between EFB and ESD., Methods: A total of 1427 patients, who were diagnosed with gastric adenoma by EFB, were enrolled. Cancer confirmed on EFB was excluded (n = 513). We retrospectively reviewed cases and compared histologic diagnoses in the biopsy sample with the final diagnosis in the endoscopically resected specimen., Results: The diagnosis was upgraded (from low-grade dysplasia to high-grade dysplasia or adenocarcinoma, or from high-grade dysplasia to adenocarcinoma) in 328 cases (23.0%), concordant in 944 (66.1%), and downgraded (from high-grade dysplasia to low-grade dysplasia or non-neoplasia, or from low-grade dysplasia to non-neoplasia) in 155 (10.9%). Multivariate logistic regression analysis showed that surface ulceration and depressed lesions were associated with significant risk factors for upgrading. Age younger than 60 years and size <1 cm were associated with significant factors for downgrading., Conclusions: Careful endoscopic observation should consider size, ulceration, and depression to ensure accurate diagnosis when a gastric neoplasm is suspected., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background/aims: Probiotics are expected to modify the composition of gut microbiota. We aimed to investigate the changes in the composition and diversity of gut microbiota by the administration of probiotics in healthy individuals., Methods: Twelve healthy volunteers with age range of 30-42 years provided baseline fecal samples. Subsequently, they took commercially available probiotic capsules (a mixture for Bifidobacterium , Lactobacillus , and Enterococcus ) for 4 weeks. Fecal samples were collected at 4 weeks of administration and 2 weeks after the stop of administration. Fecal microbiota was analyzed via 16S ribosomal RNA gene sequencing., Results: The mean Shannon index was not significantly altered by the 4-week administration of probiotics (4.365 vs 4.556, P ＞ 0.05). The proportion of Bacteroidetes , Actinobacteria , Firmicutes , and Proteobacteria was not significantly changed by the 4-week administration of probiotics. At the genus level, the proportions of Lactobacillus (2.138% vs 2.773%, P = 0.028) and Enterococcus (0.022% vs 2.758%, P = 0.004) significantly increased 4 weeks after the administration of probiotics, but reduced 2 weeks after the stop of administration (2.773% vs 3.292%, P = 0.064 and 2.758% vs 0.001%, P = 0.001)., Conclusions: The diversity of fecal microbiota is not significantly affected by 4 weeks of probiotics administration. The proportion of fecal microbiota at the genus level is significantly altered by the administration of probiotics. However, this effect does not seem to last long, probably because of homeostasis or dietary influence.

Acidified extracellular pH (pHe) is directly related to various disorders such as tumor invasion and the resistance to drugs. In this study, we developed two-photon-excitable emission ratiometric probes (XBH1-3) for the in situ measurement of pHe. These probes, based on benzimidazole and polar solubilizing groups, exhibited a strong two-photon-induced fluorescence and sensitive blue-to-green emission color changes with p K a values of 5.1-5.7. XBH1, containing a carboxylic acid, stained the extracellular region in neutral media; it entered the cell under acidic media, thereby allowing a precise measurement of the extra- and intra-cellular pH values in the acidified tissue. XBH2, containing the sulfonate peripheral unit, facilitated the monitoring of the pHe value only. Ratiometric two-photon microscopy imaging revealed that XBH1 can directly monitor the pH values both inside and outside the cells in colon cancer tissue; there is also the morphological aspect. This could be useful for cancer analyses and drug development.

Background/aim: Epithelial cell adhesion molecule (EpCAM) is expressed in hepatic progenitor cells and hepatocellular carcinoma (HCC), and is considered a marker of liver cancer stem cells., Materials and Methods: A total of 262 patients were enrolled who had undergone surgical resection for HCC, with immunohistochemical staining results for EpCAM. The immunohistochemical expression of EpCAM and other stemness-related markers was evaluated as prognosticators of tumor recurrence and survival in patients who underwent surgical resection for HCC., Results: A multivariate Cox regression analysis showed that tumor size [hazard ratio (HR)=2.26, p=0.005], intrahepatic metastasis (HR=2.31, p=0.011), and EpCAM positivity (HR=1.74, p=0.038) were associated with tumor recurrence. In a Kaplan-Meier survival analysis, patients with EpCAM-positive tumors had a significantly higher tumor recurrence rate and a reduced overall survival compared to those with EpCAM-negative tumors., Conclusion: Immunohistochemical expression of EpCAM was identified as a poor prognosticator of recurrence and survival after surgical resection in patients with HCC., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives: Recurrence of primary common bile duct (CBD) stone commonly occurs after complete removal of CBD stones in patients with cholecystectomy. This study aimed to investigate potential risk factors for the recurrence of primary CBD stones after endoscopic treatment., Materials and Methods: Between January 2005 and December 2015, the endoscopic retrograde cholangiopancreatography (ERCP) database of our medical center was retrospectively reviewed; information regarding eligible patients who had recurrent CBD stones with a history of previous cholecystectomy was collected. The characteristics of the patients, CBD stone, CBD and ERCP-related factors were analyzed., Results: The recurrence rate of CBD stone was 18.5% (115/622) after endoscopic treatment in patients with cholecystectomy. In univariate analysis, the number of CBD stones (≥2), CBD stone diameter (≥10 mm), stone composition, stone consistency, CBD diameter (≥15 mm), bile duct dilatation pattern, sharp bile duct angulation (<145°), balloon dilatation, large balloon (>12 mm) dilatation, endoscopic mechanical lithotripsy, endoscopic sphincterotomy, and endoscopic papillary balloon dilatation alone method were significant between the non-recurrence and recurrence groups. However, in multivariate analysis (based on the binary logistic regression method), the number of CBD stones (≥2) (adjusted odds ratio [AOR] 3.232; 95% confidence interval [CI] 1.344-7.773; p = .009), cholesterol stone (AOR 2.824; 95% CI 1.175-6.786; p =.02) and sharp bile duct angulation (<145°) (AOR 2.462; 95% CI 1.062-5.711; p = .036) were independent risk factors of CBD stone recurrence after cholecystectomy., Conclusions: CBD stone number (≥2), cholesterol stone and sharp bile duct angulation (<145°) are associated with recurrent common bile duct stones after cholecystectomy.

Background: Wire-guided cannulation has been widely accepted as a useful technique for achieving selective biliary access because it has significantly increased the success rate of biliary cannulation compared with conventional contrast-assisted cannulation. Unlike conventional guidewires with a straight tip, a loop-tip guidewire (LGW) has a closed distal loop that may facilitate less traumatic access through the epithelial folds of the intra-duodenal biliary segments. The aim of this study was to compare the performance of a LGW with a straight-tip guidewire (SGW) in achieving successful selective biliary cannulation., Methods: From December 2014 to December 2015, we performed 192 wire-guided biliary cannulations for a naïve papilla in a randomized controlled trial. Patients were randomly assigned to the LGW group (n = 96) or the SGW group (n = 96). Our study protocol did not include crossover to the other guidewire arm if randomized wire-guided cannulation proved unsuccessful within the first 10 min., Results: There was no significant difference in primary successful biliary cannulation between the two groups (LGW group: 86.5%; SGW group: 77.1%; p = 0.134). The rate and the mean number of unintentional pancreatic duct cannulations during wire-guided biliary cannulation were significantly lower in the LGW group than in the SGW group (LGW group: 14.6%; SGW group: 28.1%; p = 0.034; LGW group: 0.2 ± 0.5; SGW group: 0.6 ± 1.3; p = 0.007). Post-ERCP pancreatitis developed in 5.2% of patients in the LGW group and 8.3% of patients in the SGW group (p = 0.567)., Conclusions: The biliary cannulation rate of the LGW was not significantly different from those of conventional guidewires. Use of the LGW was associated with a lower rate of unintentional pancreatic duct cannulation during wire-guided biliary cannulation than use of the SGW.

Early post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) prediction may allow safe same-day outpatients discharge after ERCP and earlier proper management. This study aimed to assess the usefulness of the 4-hour post-ERCP serum amylase and lipase levels for PEP early prediction and to investigate predictive cut-off values for 4-hour post-ERCP serum amylase and lipase levels for safe discharge and urgent initiation of resuscitation. The data of 516 consecutive patients with native papilla who underwent ERCP between January 2013 and August 2014 were retrospectively reviewed. Serum amylase and lipase levels were measured before, and 4 and 24 hours after ERCP. PEP occurred in 16 (3.1%) patients. The receiver-operator characteristic curve for 4-hour post-ERCP serum amylase and lipase levels showed that the areas under the curve were 0.919 and 0.933, respectively, demonstrating good test performances as predictors for PEP (both P values < 0.001). The amylase level > 1.5 × the upper limit of reference (ULR) was found useful for PEP exclusion with a sensitivity of 93.8%, while 4 × ULR was found useful to guide preventive therapy with the best specificity of 93.2%. Similarly, the lipase level 2 × ULR showed best sensitivity, while 8 × ULR had the best specificity. Logistic regression analysis showed that 4-hour post-ERCP amylase level > 4 × ULR, lipase level > 8 × ULR, precut sphincterotomy, and pancreatic sphincterotomy were significant predictors for PEP. In conclusion, 4-hour post-ERCP amylase and lipase levels are useful early predictors of PEP that can ensure safe discharge or prompt resuscitation after ERCP., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2017 The Korean Academy of Medical Sciences.)

Non-steroidal anti-inflammatory drugs (NSAIDs) are well known to be associated with serious upper gastrointestinal complications, such as peptic ulcer, bleeding, perforation, and obstruction. Recently, attention has been mainly focused on the small bowel injuries caused by NSAIDs, and new endoscopic techniques such as capsule endoscopy and double balloon endoscopy can help in detecting such injuries. This article reviewed the epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of small bowel injuries caused by NSAIDs. Small bowel injures by NSAIDs might occur with a similar frequency and extent as those observed in the upper gastrointestinal tract. The pathogenesis of NSAID-induced enteropathy is complex and not clearly understood. The various lesions observed in the small bowel, including petechiae, reddened folds, loss of villi, erosions, and ulcers can be detected by capsule endoscopy. A drug that could prevent or treat NSAID-induced enteropathy has not yet been developed. Therefore, further investigations should be performed to elucidate the pathogenesis of such enteropathy and develop suitable preventive and treatment strategies., Competing Interests: Conflict of interest: None.

A rapid, simple, and accurate procedure was developed and validated for the simultaneous quantification of two anticancer agents, volitinib and gefitinib in rat plasma by high-performance liquid chromatography with tandem mass spectrometry. The samples were separated by gradient elution from a cyano column within five minutes, using 0.1% formic acid in acetonitrile and 10 mM ammonium formate solution (pH 3.0) as mobile phase. When plasma samples were deproteinated by adding methanol, the analytes in the extract were detected in the positive ionization mode with the tracer ion mass of 346.1 → 145.1 for volitinib and 446.8 → 128.1 for gefitinib. The assay was determined to be valid in the concentration ranges of 2 to 1000 ng/mL for volitinib, and of 1 to 500 ng/mL for gefitinib. Intra- and interday accuracies ranged from 88.0 to 104.7% for volitinib and from 90.3 to 101%, for gefitinib. The precision of the assay ranged from 2.1 to 9.71% for volitinib and 2.31 to 12.1% for gefitinib. This method was successfully applied to a pharmacokinetic study of volitinib and gefitinib after the administration of an intravenous or oral dose, indicating that the developed assay can be used to simultaneously determine the concentrations of volitinib and gefitinib in rat plasma., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The objective of the current study was to determine the minimum permeability coefficient, P, needed for perfusion-limited distribution in PBPK. Two expanded kinetic models, containing both permeability and perfusion terms for the rate of tissue distribution, were considered: The resulting equations could be simplified to perfusion-limited distribution depending on tissue permeability. Integration plot analyses were carried out with theophylline in 11 typical tissues to determine their apparent distributional clearances and the model-dependent permeabilities of the tissues. Effective surface areas were calculated for 11 tissues from the tissue permeabilities of theophylline and its PAMPA P. Tissue permeabilities of other drugs were then estimated from their PAMPA P and the effective surface area of the tissues. The differences between the observed and predicted concentrations, as expressed by the sum of squared log differences with the present models were at least comparable to or less than the values obtained using the traditional perfusion-limited distribution model for 24 compounds with diverse PAMPA P values. These observations suggest that the use of a combination of the proposed models, PAMPA P and the effective surface area can be used to reasonably predict the pharmacokinetics of 22 out of 24 model compounds, and is potentially applicable to calculating the kinetics for other drugs. Assuming that the fractional distribution parameter of 80% of the perfusion rate is a reasonable threshold for perfusion-limited distribution in PBPK, our theoretical prediction indicates that the pharmacokinetics of drugs having an apparent PAMPA P of 1×10 -6 cm/s or more will follow the traditional perfusion-limited distribution in PBPK for major tissues in the body., (Copyright © 2017 Elsevier B.V. All rights reserved.)

We analyzed the causes leading to total hip arthroplasty (THA), aimed to clarify the incidence of femoroacetabular impingement (FAI) among the causes, and compared the incidence in Korea with those in other countries. From January 2000 to December 2014, 1,206 hips of 818 patients who underwent primary THA at our institute were reviewed retrospectively in terms of radiographs and electronic charts. The radiographs and radiographic parameters were reviewed and measured by 2 of the authors, who are orthopedic surgeons. Patients were categorized in terms of the causes leading to THA as primary osteoarthritis (OA), rheumatoid arthritis (RA), posttraumatic arthritis, post infectious arthritis, avascular necrosis (AVN) of the femoral head, fracture of the femoral head or neck, ankylosing spondylitis (AS), developmental dysplasia of the hip (DDH), Legg-Calvé-Perthes disease (LCPD), FAI, and others. There were 32 patients (3.91%) in the primary OA group, 41 (5.01%) in the RA group, 84 (10.27%) in the posttraumatic arthritis group, 39 (4.77%) in the post infectious arthritis group, 365 (44.62%) in the AVN group, 39 (4.77%) in the fracture group, 21 (2.57%) in the AS group, 52 (6.36%) in the DDH group, 71 (8.68%) in the LCPD group, 52 (6.36%) in the FAI group, and 22 (2.69%) in the 'other' group. The causes leading to THA in Korea differ from those in Western countries. FAI could be causes of severe secondary OA that requires THA in Korea, therefore symptomatic FAI should not be neglected., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2017 The Korean Academy of Medical Sciences.)

Hip arthroscopy is currently being leveraged in the diagnosis and treatment of a wide range of hip joint problems. In fact, great advancements in hip arthroscopy have resulted in an ever-expanding number of indications to which it is being applied. Minimally invasive hip arthroscopy allows for quicker initiation of rehabilitation and has attracted much attention as the field becomes increasingly focused on surgeries designed to preserve joints. This review aims to summarize the recent advances, applications, and impact of hip arthroscopy., Competing Interests: CONFLICT OF INTEREST: The authors declare that there is no potential conflict of interest relevant to this article.