A mathematical simulation model to determine the optimal endoscopic screening strategy for detection of H. pylori-naïve gastric neoplasms.

BACKGROUND: The effectiveness of esophagogastroduodenoscopy (EGD) screening in cohorts with low Helicobacter pylori prevalence is unknown. This study aimed to develop an optimally efficient EGD screening strategy for detecting H. pylori-naïve gastric neoplasms (HpNGNs). METHODS: EGD data of 12 institutions from 2016 to 2022 were retrospectively analyzed. Age-related HpNGN prevalence, tumor growth rate, missing rate, and detection threshold size were calculated from the databases. Subsequently, using clinical data, a novel mathematical model that simultaneously simulated demographic changes and HpNGN detection was developed. Screening strategies using different starting ages (40/45/50 years) and intervals (2/5/10 years) were also compared. The detection rates of all tumors occurring within the virtual cohort and number-needed-to-test (NNT) were measured as outcomes. RESULTS: Data of 519,368 EGDs and 97 HpNGNs (34 pure signet ring cell carcinomas, 26 gastric adenocarcinomas of the fundic gland type, 30 foveolar gastric adenoma-Raspberry type, and seven undifferentiated-type cancer cases) were analyzed. A virtual cohort with a 70-year time horizon was used to simulate the occurrence, growth, and detection of 346,5836 people. Among the strategies with detection rate > 50%, the screening strategy with a 5-year interval starting at 45 years of age had the lowest NNT. Adopting this strategy, most HpNGNs were detected at < 20 mm in size, and the deep submucosal invasion rate was less than 30%. CONCLUSIONS: A mathematical simulation model revealed that screening every 5 years starting at 45 years of age could efficiently assist in identifying HpNGNs at an early stage.

Cost-effectiveness analysis of single colonoscopy versus single fecal test for colorectal cancer diagnosis and treatment.

BACKGROUND AND AIM: Regular endoscopy or fecal immunochemical test (FIT) is ideal for screening colorectal cancer. However, only a limited number of individuals undergo regular screening. This study aimed to compare the cost-effectiveness of a single colonoscopy with a single FIT performed for colorectal cancer screening. METHODS: A microsimulation model was constructed based on real-world observational data collected from three institutions between 2019 and 2022 that compared colonoscopy-based screening with FIT-based screening. The total costs of diagnosis and treatment of the detected lesions using the two strategies were calculated. The incremental cost-effectiveness ratio (ICER) per life year gained (LYG) of the colonoscopy-based strategy was calculated. RESULTS: Data from 11 407 patients undergoing colonoscopies and 59 176 patients undergoing FITs were used to establish a model. In the base case analysis of screening strategies, colonoscopy was more cost-effective than FIT (ICER 415 193 yen/LYG). The ICER of the colonoscopy-based strategy among 60- to 69-year-old patients was lowest at 394 200 yen/LYG, whereas that in 20- to 29-year-old patients was highest. Monte Carlo simulations showed that the colonoscopy-based strategy was more cost-effective than the FIT-based strategy (net monetary benefit [NMB]: 5 695 957 yen vs 5 348 253 yen). When the adenoma detection rate in the colonoscopy was over 30% or the positive FIT rate was lower than 8.6% in the FIT-based strategy, the NMB of the colonoscopy-based strategy exceeded that of the FIT-based strategy. CONCLUSION: In the microsimulation model, colonoscopy is recommended as a one-time screening procedure in patients aged >60 years with >30% ADR or <8.6% positive FIT rate.

An algorithm-based active cleansing protocol can reduce the bowel preparation time for screening colonoscopy: A propensity score matching study.

BACKGROUND: Methods that minimize the time for on-site bowel preparation before colonoscopy are needed. We prospectively validated that a novel algorithm-based active cleansing (ABAC) protocol could reduce the time for preparation compared with the conventional method. METHODS: This was an open-label, multicenter, prospective comparative study from April to October 2021. The study compared the bowel preparation time for colonoscopy between patients instructed with the ABAC protocol and control groups. Patients in the ABAC protocol group as well as the control group were administered 2000 mL of polyethylene glycol (PEG) within 2 hours. After the first two hours, patients in the protocol group voluntarily took 300 ml of the solution without the instruction of nursing staff depending on the number of defecations in the first 2 hours. The intervention and control groups were adjusted for background characteristics by propensity score matching (PSM). RESULTS: After adjustment by PSM, 174 patients in each of the two groups were included in the final analysis. In the intention-to-treat analysis, the preparation time was significantly shorter in the intervention group than that in the control group (126.3 ± 32.7 min vs. 144.9 ± 39.9 min, P = 0.018). The proportion of additional PEG intake was significantly higher in the intervention group (16 [9.2%] vs. 6 [3.4%], P = 0.047). The number of defecations was also higher in the intervention group than in the control group (7.8 ± 2.5 vs. 6.3 ± 2.2, P = 0.001). CONCLUSIONS: Simple active instruction protocol is effective to reduce on-site bowel preparation time and nursing staff labor for colonoscopy.

Dietary restriction after cold snare polypectomy of colorectal polyp for prevention of delayed bleeding.

Background and Aim: Cold snare polypectomy (CSP) for small colorectal polyps is a safe technique; however, there is little evidence on whether dietary restriction after CSP is essential. This study aimed to determine whether dietary restriction after CSP is necessary to prevent delayed bleeding. Methods: This is a randomized, controlled, non-inferiority trial conducted between November 2021 and March 2022. Patients with non-pedunculated small colorectal polyps (<10 mm) and who did not take anticoagulants were randomly allocated to two groups: (i) the normal diet (ND) group, and (ii) the low-residue diet (LRD) group. The ND group was instructed to eat anything after CSP, whereas the LRD group was advised to take LRD for 3 days after CSP. The primary endpoint was the occurrence of delayed major bleeding that needed endoscopic hemostasis. Results: A total of 193 patients (average 57.5 years old, 51.9% male) were enrolled in the study. Subsequently, 97 and 96 patients were allocated to the ND and LRD group, respectively. The occurrence of delayed major bleeding was 1.0% in the ND group and 2.1% in the LRD group (95% confidence interval [CI]: -4.4% to 2.4%; difference: -1.1%), which showed the non-inferiority of the ND group. In addition, there was no difference between the two groups with respect to the occurrence of minor delayed bleeding (3.1% and 4.2%, respectively; difference: -1.1% [95% CI: -6.4% to 4.2%]). Conclusion: Dietary restriction after CSP for low-bleeding-risk colorectal polyps is not necessary for the prevention of delayed bleeding (Registration number: UMIN000045669).

Pre-administration of super-low volume polyethylene glycol is as effective as senna laxative as bowel preparation for colonoscopy: a randomized controlled phase 2 trial.

BACKGROUND AND PURPOSE: Senna laxatives are commonly used for bowel preparation before colonoscopies in Japan. However, this laxative frequently causes complications such as abdominal pain. This study aimed to establish a novel method of bowel preparation, which involved the pre-administration of super-low volume polyethylene glycol (PEG) for three days followed by the same-day administration of low volume PEG. METHODS: This study was a prospective, multicenter, investigator-blinded, phase 2, randomized control trial. The intake of 13.9 g (120 mL) of PEG or 1 g of a senna laxative for 3 days before the examination was indicated for each group, and 2 L of PEG solution was used for preparation on the examination day. The primary endpoint was the efficacy of bowel cleansing, as assessed by the Boston bowel preparation scale. The secondary endpoints were the adenoma detection rate and occurrence of complications. RESULTS: A total of 250 patients were initially enrolled. A total of 122 patients from each group were included in the intention-to-treat analysis. In the intention-to-treat analysis, the responder rates were the same for the two groups (56.6% vs 50.8%). Additionally, the adenoma detection rate did not differ between the two groups (34.9% vs 41.8%, P = 0.3795). In contrast, adherence was higher in the PEG group (93.4% vs 82.8%, P = 0.0101), and the occurrence of complications was lower in the PEG group (1.7% vs 16.4%, P = 0.0001). CONCLUSION: The novel super-low volume PEG method for bowel preparation was as effective as the conventional method with senna laxatives.

Quality management system for screening esophagogastroduodenoscopy improves detection of Helicobacter pylori -negative interval gastric cancer.

Background and study aims Double-checking the findings of examinations is necessary for endoscopy quality control in gastric cancer screening; however, there have been no reports showing its effectiveness. We prospectively analyzed the effectiveness of a quality management system (QMS) in endoscopy for gastric cancer screening. Patients and methods QMS was defined as having images and reports checked by a second endoscopist on the same day and reporting inconsistencies to the examining endoscopist. Patients diagnosed with early gastric cancer (EGC) in the 2 years before and after the introduction of QMS were divided into two groups: the interval cancer group, which included those for whom cancer was detected within 1 year of the last endoscopy and the noninterval cancer group. Changes in detection rates were compared. Results Before the introduction of QMS, 11 interval EGC cases were diagnosed among 36,189 endoscopies, whereas after the introduction, 32 interval ECG cases were diagnosed among 38,290 endoscopies ( P  = 0.004). Fifteen noninterval EGC cases were diagnosed before the introduction, while 12 noninterval EGC cases were diagnosed after the introduction; no significant difference was observed. Subanalyses by Helicobacter pylori (HP) infection status revealed no difference in the detection rate among HP-positive EGC patients, but the detection rates among HP-eradicated and HP-naïve EGC patients were improved ( P  = 0.005 and P  = 0.011). Logistic regression analysis showed that QMS was an independent predictor for detection of HP-negative interval EGC ( P  = 0.017, OR = 4.4, 95 % CI: 2.0-9.7). Conclusions QMS improved the detection rate for HP-negative interval early gastric cancer. (UMIN000042991).

Erratum: Quality management system for screening esophagogastroduodenoscopy improves detection of Helicobacter pylori -negative interval gastric cancer.

[This corrects the article DOI: 10.1055/a-1594-1833.].

Individual feedback and monitoring of endoscopist performance improves the adenoma detection rate in screening colonoscopy: a prospective case-control study.

BACKGROUND AND PURPOSE: Previous reports have suggested that a longer withdrawal time (WT) during colonoscopy led to an improved adenoma detection rate (ADR); however, there are few controlled studies that substantiated monitoring WT as an educational method. We aimed to validate a feedback and monitoring system to improve the ADR in screening colonoscopy in a prospective case-control setting. METHODS: After collecting data in the pre-feedback period (3.5 months), the individual performance and the average ADR and WT values of the facility were provided to 6 endoscopists in the intervention group, while 3 endoscopists were isolated as the control group during the feedback period (2 weeks). The intervention group consisted of two subgroups, the Fast and Slow WT groups, according to the results from the pre-feedback period. The endoscopists in the intervention group were instructed to be aware of their own WT in each examination during the post-feedback period (4 months). The performances of all endoscopists in the post-feedback period were analyzed and compared with those in the pre-feedback period. RESULTS: Among the initial analyses, the correlation analysis and multivariate analysis revealed that WT was an independent predictor for the ADR (P = 0.0101). After providing individual performance feedback and instruction regarding real-time WT monitoring, the WT was significantly prolonged in the Fast WT group (P = 0.0346) but did not change in the Slow WT and control groups. In addition, the ADR of the Fast WT group significantly improved after the intervention (P = 0.024), whereas the ADR of the Slow WT and control groups did not change. CONCLUSION: Providing individual feedback on ADR and WT and monitoring WT helped improve the endoscopists' ADRs.

Tight Chemomechanical Coupling of the F1 Motor Relies on Structural Stability.

The F1 motor is a rotating molecular motor that ensures a tight chemomechanical coupling between ATP hydrolysis/synthesis reactions and rotation steps. However, the mechanism underlying this tight coupling remains to be elucidated. In this study, we used electrorotation in single-molecule experiments using an F1ßE190D mutant to demonstrate that the stall torque was significantly smaller than the wild-type F1, indicating a loose coupling of this mutant, despite showing similar stepping torque as the wild-type. Experiments on the ATPase activity after heat treatment and gel filtration of the α3ß3-subcomplex revealed the unstable structure of the ßE190D mutant. Our results suggest that the tight chemomechanical coupling of the F1 motor relies on the structural stability of F1. We also discuss the difference between the stepping torque and the stall torque.

Quality Indicators for the Detection of Helicobacter pylori-Negative Early Gastric Cancer: A Retrospective Observational Study.

BACKGROUND/AIMS: While Helicobacter pylori (HP)-negative gastric cancer is frequently reported, little is known about the predictors for detecting HP-negative early gastric cancer (EGC). We aimed to evaluate the predictors for the detection of HP-negative EGC. METHODS: We retrospectively reviewed 13,477 consecutive asymptomatic cases where upper endoscopy was performed by nine physicians from April 2017 to March 2019 and analyzed the detection rate of high-risk lesions (HRLs), including EGC, tubular adenoma, and lymphoma, according to the status of HP infection. The observation time was corrected for multiple regression analyses. RESULTS: For all physicians, the average observation time for screening HP-eradicated and -naïve patients was shorter than that for screening HP-positive patients (p<0.05). Multiple regression analyses revealed that the observation time in the three groups was an independent predictor for detecting HRLs in HP-eradicated patients (p=0.03106, 0.01263, and 0.02485, respectively), while experience of endoscopy was an independent predictor for detecting HRLs in HP-naïve patients (p=0.02638). CONCLUSION: While observation time during screening endoscopy was a quality indicator for detecting HRLs in HP-eradicated patients, experience of endoscopy was a quality indicator for detecting HRLs in HP-naïve patients.

Association Between Inflammatory Bowel Disease and Pruritus.

Background: Inflammatory bowel disease (IBD) is often complicated by extraintestinal manifestations. We frequently encounter IBD patients with pruritus; however, clinical evidence for the association of these conditions is lacking. Therefore, the present study investigated the incidence of pruritus in IBD patients. Methods: Seventy-one IBD outpatients, including 55 with ulcerative colitis (UC) and 16 with Crohn disease, and 39 healthy volunteers (HVs) were surveyed about their pruritus symptoms using a visual analogue scale (VAS). Disease activities in UC and Crohn disease patients were classified according to partial Mayo and IOIBD (International Organization for the Study of inflammatory Bowel Disease) scores, respectively. Skin barrier condition was examined by measuring transepidermal water loss and stratum corneum hydration. The distribution of intraepidermal nerve fibers in skin samples from 9 UC patients was examined immunohistochemically using an antiprotein gene product (PGP) 9.5 antibody. Results: Visual analogue scale scores were higher in IBD patients than in HV (P < 0.001). Active stage IBD patients had more severe pruritus VAS scores than those in the remission stage (P = 0.036). Transepidermal water loss was higher in IBD patients (P < 0.001) and active stage IBD patients (P = 0.004), while stratum corneum hydration was lower in IBD patients (P = 0.019) and active stage IBD patients than in HV (P = 0.019). A relationship was observed between the degree of pruritus and number of PGP9.5-immunoreactive intraepidermal nerve fibers in UC patients. Conclusions: Inflammatory bowel disease patients, particularly active stage patients, frequently exhibit symptoms of pruritus and dry skin. This result may have predictive and therapeutic implications for the treatment of IBD symptoms.

Evaluation of interactive effects on the ionic conduction properties of polymer gel electrolytes.

Ionic mobility of electrolyte materials is essentially determined by the nanoscale interactions, the ion-ion interactions and ion-solvent interactions. We quantitatively evaluated the interactive situation of the lithium polymer gel electrolytes through the measurements of ionic conductivity and diffusion coefficients of the mobile species of the lithium polymer electrolytes. The interactive force between the cation and anion in the gel depended on the mixing ratio of the binary solvent, ethylene carbonate plus dimethyl carbonate (EC/DMC). The gel with the solvent (3:7 EC:DMC) showed minimal cation-anion interaction, which is the cause of the highest ionic mobility compared with those of the other gels with different solvents. This suggests that the cation-anion interaction does not simply depend on the dielectric constant of the solvent but is associated with the solvation condition of the lithium. In the case of the gel with the 3:7 EC/DMC solvent, most of the EC species strongly coordinate to a lithium ion, forming the stable solvated lithium, Li(EC)(3)(+), and there are no residual EC species for exchange with them. As a result, the solvating EC species would be a barrier that restricts the anion attack to the lithium leading to the smallest cation-anion interaction. On the other hand, interaction between the cation and polar sites, hydroxyl and oxygen groups of ether of the polyvinyl butyral (PVB) and polyethylene oxide (PEO) polymer, respectively, in the gels was another dominant factor responsible for cation mobility. It increased with increasing polar site concentration per lithium. In case of the PVB gels, cation-anion interaction increased with an increasing polymer fraction of the gel contrary to the independent feature of PEO gels with the change of the polymer fraction. This indicates that the cation-anion interaction is associated with the polymer structure of the gel characterized by the kind and configuration of polar groups, molecular weight, and network morphology of the polymer.

Divergent expression of L-type amino acid transporter 1 during uterine cervical carcinogenesis.

L-type amino acid transporter 1 (LAT1) is a Na⁺-independent neutral amino acid transporter that has an essential role in cell proliferation. Although LAT1 expression is observed in various tumor cell lines and immunohistochemical expression of LAT1 has been investigated in carcinomas of various organs, LAT1 expression in uterine cervical neoplasm has not been reported. Therefore, in the present study, we immunohistochemically analyzed LAT1 expression along with the well-known markers of cervical carcinogenesis Ki-67 and p16 in normal uterine cervical mucosa (49 specimens) as well as cervical intraepithelial neoplasia (17 mild or moderate dysplasias and 19 severe dysplasias or carcinomas in situ) and invasive carcinomas (17 squamous cell carcinomas and 9 adenocarcinomas). LAT1 expression was limited to the basal layer of normal squamous epithelium, and it was significantly decreased in cervical intraepithelial neoplasia (P < .001), generally paralleled by increased expression of Ki-67 and p16. Interestingly, in invasive squamous cell carcinoma, LAT1 expression again increased especially at the invasive fronts (P < .001), whereas Ki-67 and p16 expressions were almost unchanged relative to noninvasive neoplasia. Although virtually no LAT1 expression was demonstrated in normal uterine cervical glands, LAT1 expression was observed in some adenocarcinomas (P < .001). The present study suggests that LAT1 expression decreases because of human papillomavirus infection as reflected by p16 overexpression in cervical intraepithelial neoplasia, whereas LAT1 expression in invasive carcinoma is associated with acquired malignant potential.

Aortic aneurysms in systemic lupus erythematosus: a meta-analysis of 35 cases in the literature and two different pathogeneses.

BACKGROUND: Aortic aneurysms including dissection are uncommon complications of systemic lupus erythematosus, but the incidence has been increasing with an improved prognosis for this disease. However, the mechanisms contributing to aneurysm formation in systemic lupus erythematosus have not been fully clarified. METHODS: A meta-analysis of published cases was conducted to clarify the patient characteristics that may contribute to aneurysm formation in systemic lupus erythematosus. A search of relevant studies published over the past 40 years (1969-2008) was carried out in the publications on aortic aneurysms with systemic lupus erythematosus, and 35 cases were identified. The contributing factors to aneurysm formation as well as the patient prognosis were searched for sex, age, duration of corticosteroid treatment, aneurysm site (thoracic and/or abdominal), mortality, evidence of atherosclerotic involvement, and presence or absence of an operation, rupture, dissection, cystic medial degeneration, vasculitis, and hypertension. Each of these factors was assigned to each point score. Based on the point scores, a statistical analysis of rank correlation was thereafter performed. RESULTS: The factors correlating with the presence of thoracic or abdominal lesions differed significantly. The presence of thoracic aneurysms correlated with dissection and cystic medial degeneration, whereas abdominal lesions correlated with the finding of atherosclerosis. Thoracic lesions showed a high rate of death, while abdominal lesions were associated with a relatively favorable prognosis. Abdominal lesions were related to the duration of steroid therapy. The other correlations among the various factors were also evaluated, with the finding of cystic medial degeneration associated with vasculitis. CONCLUSION: Two principal patterns emerged from this analysis. One was the fatal nonatherosclerotic thoracic aneurysm which was associated with cystic medial degeneration and probably due to vasculitis. The other was atherosclerotic abdominal aneurysm which was complicated by long-term steroid treatment and it showed a relatively favorable prognosis.

Fascin expression in dendritic cells and tumor epithelium in thymoma and thymic carcinoma.

The majority of thymomas are histologically characterized by tumor-infiltrating lymphocytes. Mature dendritic cells (DCs) are known to assemble lymphocytes through antigen presentation to T lymphocytes. Fascin, a 55-kDa actin-binding protein and a known marker for mature DCs, regulates filaments necessary for the formation of filopodia in cell migration. Moreover, fascin expression in various epithelial neoplasms has recently been reported to be associated with invasion of tumor cells and clinically aggressive manifestations. In the present study, we investigated fascin expression immunohistochemically in tissues of thymomas and thymic carcinomas surgically resected at our institute. A total of 34 thymomas and 5 thymic carcinomas were included. The amount and immunohistochemical intensity of both fascin(+) DCs and tumor epithelium were counted and assessed, and the clinicopathological data were also scored. Statistical analyses revealed that the amount of fascin(+) DCs with the formation of clusters was associated with lymphocyte-rich variants (p=0.002) and cortical differentiation (p=0.037) of thymoma with complication from myasthenia gravis (p=0.002). The quantity of fascin(+) epithelium was associated with a strong intensity of fascin in infiltrating DCs (p=0.002) with the formation of clusters (p=0.002) and favorable prognosis, as assessed by the Masaoka staging system (p=0.001). The amount of infiltrating DCs (p=0.024) and fascin(+) epithelium were lower in thymic carcinoma. It was concluded that fascin(+) epithelium may induce tumor immunity through the surveillance activity of fascin(+) DCs in thymic neoplasms, thus improving prognosis.

Ammonium induced expression of the red algal chloroplast gene Ycf18, a putative homolog of the cyanobacterial NblA gene involved in nitrogen deficiency-induced phycobilisome degradation.

In cyanobacteria, nutrient deficiency-induced phycobilisome degradation is controlled by the NblA gene. Red algae also have an NblA-related gene, Ycf18, in their chloroplast genomes. To elucidate the role of Ycf18, the expression pattern of Ycf18 in a red alga, Porphyra yezoensis, was investigated. Ycf18 expression was low in nitrate medium, but was greatly promoted in ammonium medium. Nitrogen starvation caused bleaching, but did not affect the expression of Ycf18. The responses of Ycf18 to nitrogen-starvation and the supply of ammonium were distinct from those of NblA, suggesting that Ycf18 has a role other than the regulation of phycobilisome degradation.

Multiple aortic aneurysms complicated by a rupture in the systemic lupus erythematosus: a case report.

We report the case of a 61-year-old female who suffered from systemic lupus erythematosus (SLE) and died of a ruptured abdominal aortic aneurysm (AA). She was diagnosed to have SLE at 39 years of age, and was administrated steroids and prostaglandin E(2). From 52 years of age, AA, peripheral arterial occlusion, and multiple organ infarctions appeared repeatedly. At 59 years of age, she was found to be affected by antiphospholipid antibody syndrome (APS). In the following year, expansion of an abdominal AA was identified, but she was given only conservative treatment. In the next year, sudden epigastralgia and dyspnea occurred, and she died. An autopsy revealed multiple AAs up to 11 cm in diameter, one of which showed ruptures, forming a retroperitoneal hematoma. Marked atherosclerosis of the aorta was noted, and she also had aortic dissection accompanied by cystic medial necrosis (CMN). An old myocardial infarction and brain infarction were also confirmed. Although SLE with APS is common, a complication of the disease by CMN, multiple AAs, or ruptured AA has been described in several cases to date. Regarding the etiology of this complicated presentation, we presume synergistic involvement of various factors, such as atherosclerosis and CMN associated with SLE, thrombosis due to APS, and prolonged steroid therapy.