Clinical meaning of sarcopenia in patients undergoing endoscopic treatment.

With increasing global life expectancy, the significance of geriatric assessment parameters has increased. Sarcopenia is a crucial assessment parameter and is defined as the age-related loss of muscle mass and strength. Sarcopenia is widely acknowledged as a risk factor for postoperative complications in diverse advanced malignancies and has a detrimental effect on the long-term prognosis. While most studies have primarily concentrated on the correlation between sarcopenia and advanced cancer, more recent investigations have focused on the relationship between sarcopenia and early-stage cancer. Endoscopic submucosal dissection (ESD), which is less invasive than surgical intervention, is extensively employed in the management of early-stage cancer, although it is associated with complications such as bleeding and perforation. In recent years, several reports have revealed the adverse consequences of sarcopenia in patients with early-stage cancer undergoing ESD. This literature review briefly summarizes the recent studies on the association between sarcopenia and ESD.

Verification of the increase in concomitant dysplasia and cancer with the size of sessile serrated lesions.

Background and study aims This study aimed to evaluate the relationship between sessile serrated lesion (SSL) size and the comorbidity rate of SSL with dysplasia (SSLD) and cancer in SSL (SSL-cancer). Patients and methods This retrospective, single-center analysis identified SSL cases that underwent endoscopic resection between January 2015 and December 2022. The prevalence of SSL, SSLD, and SSL-cancer and their annual trends were assessed. The tumor diameter was stratified as 0 to 5 mm, 6 to 9 mm, 10 to 19 mm, and ≥ 20 mm in size. Furthermore, the frequency of SSL-D/SSL-cancer was determined in each group. Results The prevalence of SSL was 2.9% (1328/45799). This prevalence was 1.8% (112/6192) in 2015 and 4.2% (230/5500) in 2022, indicating an increasing trend over time. A total of 1825 lesions were assessed: 1751 (96.0%), 55 (3.0%), 14 (0.8%), and 5 (0.3%) of lesions were SSL, SSL with low-grade dysplasia, SSL with high-grade dysplasia and SSL-cancer, respectively. Stratifying the SSLs by size: 0 to 5 mm, 5 to 9 mm, 10 to 19 mm, and ≥ 20 mm, SSLD and SSL-cancer rates were 2.3% (10/429), 2.4% (16/674), 5.3% (31/584), and 11.8% (16/136), respectively. SSLD and SSL-cancer were observed in 2.4% (26/1103) of small SSLs < 10 mm. Conclusions In cases of SSL, the rate of SSLD and SSL-cancer increased as the lesion diameter increased. A certain rate of SSLD and SSL-cancer was observed even in small SSLs less than 5mm.

Characteristics of microbiomes of the saliva, duodenal bulb, and descending portion of superficial nonampullary duodenal epithelial tumors.

INTRODUCTION: Nonampullary duodenal epithelial tumors are rare, but their prevalence is increasing. Various gastrointestinal cancers have been associated with microbiomes. We evaluated the characteristics of the salivary and duodenal microbiomes of patients with nonampullary duodenal epithelial tumors. METHODS: Saliva and biopsy samples from the duodenal bulb and descending portion were obtained from 15 patients with nonampullary duodenal epithelial tumors and 10 controls. Next-generation sequencing was performed to identify bacteria for comparison. RESULTS: Saliva samples had higher Amplicon Sequence Variants (ASVs) and more observed species than duodenal samples. Saliva samples from patients with nonampullary duodenal epithelial tumor were dominated by Bacteroidetes and Prevotella, whereas Proteobacteria and Neisseria were dominant in the control samples. The relative abundance of bacteria was higher in patients with nonampullary duodenal epithelial tumors. Most bacteria were classified as bacteria of oral origin. Oribacterium and Stomatobaculum were significantly higher in the saliva, duodenal bulb, and descending portion of patients with nonampullary duodenal epithelial tumors. CONCLUSION: Patients with nonampullary duodenal epithelial tumors had different salivary and duodenal microbiomes than controls. Bacteria types differed between groups at each site, and most bacteria of oral origin were more abundant in patients with nonampullary duodenal epithelial tumors.

Feasibility of colorectal endoscopic submucosal dissection in elderly patients: the impact of sarcopenia.

INTRODUCTION: Colorectal cancer (CRC) is a public health concern associated with high incidence rates. Sarcopenia is a known risk factor for postoperative complications, although an association between increased complications after colorectal endoscopic submucosal dissection (ESD) and sarcopenia remains undocumented. Herein, we aimed to explore the feasibility of colorectal ESD in patients with sarcopenia. METHODS: This retrospective study included 499 patients (69 with and 430 without sarcopenia). We evaluated the short- and long-term outcomes of colorectal ESD. RESULTS: There were no significant differences between the two groups regarding en bloc, R0, or curative resection rates. However, poor bowel preparation was significantly more common in the sarcopenia group. Moreover, patients with sarcopenia exhibited a significant increase in complications (37.7% vs. 10.5%). Multivariate analysis revealed that sarcopenia (odds ratio [OR] 3.78, 95% confidence interval [Cl] 1.85-7.73, p < 0.001), anticoagulation therapy (OR 3.59, 95% Cl 1.86-6.92, p < 0.001), procedure time (OR 1.28, 95% Cl 1.11-1.47, p < 0.001), and resection size (OR 1.25, 95% Cl 1.03-1.52, p = 0.02) were significantly correlated with Common Terminology Criteria for Adverse Events (CTCAE) ≥ grade 2. The correlation between sarcopenia and CTCAE ≥ grade 2 was maintained after matching, resulting in more extended hospital stays in patients with sarcopenia. However, we detected no association between sarcopenia and overall survival and ESD-related death. CONCLUSION: Sarcopenia is a risk factor for complications in colorectal ESD, suggesting that colorectal ESD could be performed for patients with sarcopenia, although much caution should be taken.

Risk factors for rebleeding in gastroduodenal ulcers.

BACKGROUND: Rebleeding after hemostasis of the gastroduodenal ulcer (GDU) is one of the indicators associated with death among GDU patients. However, there are few studies on risk score that contribute to rebleeding after endoscopic hemostasis of bleeding peptic ulcers. AIMS: The aim of this study was to identify factors associated with rebleeding, including patient factors, after endoscopic hemostasis of bleeding gastroduodenal ulcers and to stratify the risk of rebleeding. METHODS: We retrospectively enrolled 587 consecutive patients who were treated for Forrest Ia to IIa bleeding gastroduodenal ulcers with endoscopic hemostasis at three institutions. Risk factors associated with rebleeding were assessed using univariate and multivariate logistic regression analyses. The Rebleeding Nagoya University (Rebleeding-N) scoring system was developed based on the extracted factors. The Rebleeding-N score was internally validated using bootstrap resampling methods. RESULTS: Sixty-four patients (11%) had rebleeding after hemostasis of gastroduodenal ulcers. Multivariate logistic regression analysis revealed four independent rebleeding risk factors: blood transfusion, albumin <2.5, duodenal ulcer, and diameter of the exposed vessel ≧2 mm. Patients with 4 risk factors in the Rebleeding-N score had a 54% rebleeding rate, and patients with 3 risk factors had 44% and 25% rebleeding rates. In the internal validation, the mean area under the curve of the Rebleeding-N score was 0.830 (95% CI = 0.786-0.870). CONCLUSIONS: Rebleeding after clip hemostasis of bleeding gastroduodenal ulcers was associated with blood transfusion, albumin <2.5, diameter of the exposed vessel ≧2 mm, and duodenal ulcer. The Rebleeding-N score was able to stratify the risk of rebleeding.

Monoclonal Antibody Against Mature Interleukin-18 Ameliorates Colitis in Mice and Improves Epithelial Barrier Function.

BACKGROUND: Antitumor necrosis factor (TNF)-α antibodies have improved the outcome of inflammatory bowel disease (IBD); but half of patients remain unresponsive to treatment. Interleukin-18 (IL-18) gene polymorphism is associated with resistance to anti-TNF-α antibodies, but therapies targeting IL-18 have not been clinically applied. Only the mature protein is biologically active, and we aimed to investigate whether specific inhibition of mature IL-18 using a monoclonal antibody (mAb) against a neoepitope of caspase-cleaved mature IL-18 could be an innovative treatment for IBD. METHODS: The expression of precursor and mature IL-18 in patients with UC was examined. Colitis was induced in C57/BL6 mice by administering dextran sulfate sodium (DSS), followed by injection with anti-IL-18 neoepitope mAb. Colon tissues were collected and subjected to histological analysis, immunohistochemistry, immunoblotting, and quantitative polymerase chain reaction. Colon epithelial permeability and microbiota composition were analyzed. RESULTS: Mature IL-18 expression was elevated in colon tissues of patients with active ulcerative colitis. Administration of anti-IL-18 neoepitope mAb ameliorated acute and chronic DSS-induced colitis; reduced interferon-γ, TNF-α, and chemokine (CXC motif) ligand-2 production and epithelial cell permeability; promoted goblet cell function; and altered the intestinal microbiome composition. The suppressive effect of anti-IL-18 neoepitope mAb was superior to that of anti-whole IL-18 mAb. Furthermore, combination therapy with anti-TNF-α Ab suppressed acute and chronic colitis additively by suppressing cytokine expressions and reducing cell permeability by upregulating claudin1 and occludin expression. CONCLUSIONS: Anti-IL-18 neoepitope mAb ameliorates acute and chronic colitis, suggesting that this mAb will be an innovative therapeutic option for IBD.

We investigate a novel monoclonal antibody that specifically recognizes a neoepitope of caspase-cleaved IL-18 and alleviates dextran sulfate sodium-induced colitis by suppressing the secretion of inflammatory cytokines, improving intestinal epithelial permeability, promoting goblet cell function, and regulating intestinal microbiota.

Low Expectancy of Conversion Surgery with R0 Resection in Patients with CEA > 5.0 ng/mL at the Initial RECIST Evaluation for Metastatic Gastric Cancer.

This retrospective study examined early the predictive factors for successful conversion surgery (CS) with R0 resection in patients with metastatic gastric cancer (MGC) who underwent systemic chemotherapy. This study included 204 patients diagnosed with metastatic gastric adenocarcinoma, who received chemotherapy between 2009 and 2019. Of these patients, 31 (15%) underwent CS with R0 resection. The incidence of CS with R0 resection was not affected by the volume of metastatic lesions or the presence of peritoneal metastasis. The overall survival time of the CS with R0 resection group was significantly longer than that of the non-CS group (hazard ratio, 0.12; 95% confidence interval, 0.07-0.23; p < 0.0001), with a 5 year overall survival rate of 50.2%. Multivariate analysis of 150 patients, excluding those with disease progression until the initial Response Evaluation Criteria in Solid Tumors (RECIST) evaluation, showed that carcinoembryonic antigen > 5.0 ng/mL at the initial RECIST evaluation was an independent, significant, and unfavorable predictor of CS with R0 resection (odds ratio, 0.21; p = 0.0108), whereas systemic chemotherapy with trastuzumab for HER2-positive cancer was a favorable factor (odds ratio, 4.20; p = 0.0119). Monitoring serum carcinoembryonic antigen levels during chemotherapy may be a useful predictor of the CS implementation in patients with MGC.

Reduced DEFA5 Expression and STAT3 Activation Underlie the Submucosal Invasion of Early Gastric Cancers.

INTRODUCTION: Submucosal invasion is a core hallmark of early gastric cancer (EGC) with poor prognosis. However, the molecular mechanism of the progression from intramucosal gastric cancer (IMGC) to early submucosal-invasive gastric cancer (SMGC) is not fully understood. The objective of this study was to identify genes and pathways involved in the submucosal invasion in EGC using comprehensive gene expression analysis. METHODS: Gene expression profiling was performed for eight cases of IMGC and eight cases of early SMGC with submucosal invasion ≥500 µm. To validate the findings of gene expression analysis and to examine the gene expression pattern in tissues, immunohistochemical (IHC) staining was performed for 50 cases of IMGC and SMGC each. RESULTS: Gene expression analysis demonstrated that the expression levels of small intestine-specific genes were significantly decreased in SMGC. Among them, defensin alpha 5 (DEFA5) was the most downregulated gene in SMGC, which was further validated in SMGC tissues by IHC staining. Gene set enrichment analysis showed a strong association between SMGC, the JAK-STAT signaling pathway, and the upregulation of STAT3-activating cytokines. The expression of phosphorylated STAT3 was significant in the nucleus of tumor cells in SMGC tissues but not in areas expressing DEFA5. CONCLUSION: The results of this study strongly suggest that the downregulation of DEFA5 and the activation of STAT3 play a significant role in the submucosal invasion of EGC.

Repeated steroid injection and polyglycolic acid shielding for prevention of refractory esophageal stricture.

BACKGROUND: Postoperative stricture and refractory stricture are severe adverse events which occur after expansive esophageal endoscopic submucosal dissection (ESD). The aim of this study was to assess the efficacy of steroid injection, polyglycolic acid (PGA) shielding, and of additional steroid injection thereafter for the prevention of refractory esophageal stricture. METHODS: This is a retrospective cohort study of 816 consecutive cases of esophageal ESD performed between 2002 and 2021 at the University of Tokyo Hospital. After 2013, all patients with a diagnosis of superficial esophageal carcinoma covering over 1/2 the esophageal circumference underwent preventive treatment immediately after ESD with either "PGA shielding", "steroid injection", or "steroid injection + PGA shielding". Additional steroid injection was performed for high-risk patients after 2019. RESULTS: The risk of refractory stricture was especially high in the cervical esophagus (OR 24.77, p = 0.002) and after total circumferential resection (OR 894.04, p < 0.001). "Steroid injection + PGA shielding" was the only method significantly effective in preventing stricture occurrence (OR 0.36; 95% CI 0.15-0.83, p = 0.012). This method also decreased the risk of refractory stricture (OR 0.38; 95% CI 0.10-1.28, p = 0.096), but additional steroid injection was the only significantly effective method for prevention of refractory stricture (OR 0.42; 95% CI 0.14-0.98, p = 0.029). CONCLUSION: Combining steroid injection and PGA shielding is effective for preventing post-ESD stricture and refractory stricture. Additional steroid injection is a viable option for patients at high-risk for refractory stricture.

Performing the ABC Method Twice for Gastric Cancer Risk Stratification: A Retrospective Study Based on Data from a Large-Scale Screening Facility.

The ABC method is a classification method used for stratifying the risk of gastric cancer. However, whether the ABC method should be performed only once or multiple times throughout an individual's lifetime remains unclear. Therefore, this study aimed to analyze whether performing ABC screening twice in a lifetime is useful. We retrospectively analyzed the data of individuals who participated in health checkups in 2010 and 2015. We collected data on patient characteristics, pepsinogen levels, anti-Helicobacter pylori antibody titers, and the presence of gastric cancer. Overall, 7129 participants without a history of H. pylori eradication were included in this study. The participants' average age in 2010 was 48.4 ± 8.3 years, and 58.1% were male. In addition, 11 and 20 cases of new H. pylori infection (0.15%) and spontaneous eradication (0.28%), respectively, were recorded. No significant difference was found in the incidence of gastric cancer between participants who underwent the ABC method once and those who underwent it twice (Group A: 0.16% vs. 0.16%; Group B: 0.47% vs. 0.39%; and Group C + D: 1.97% vs. 1.82%). Therefore, performing the ABC method twice, 5 years apart, does not significantly improve gastric cancer risk stratification.

Successful prevention of stenosis after circumferential endoscopic resection of esophageal cancer.

Circumferential resection of a >5-cm longitudinal mucosal defect following esophageal endoscopic submucosal dissection (ESD) is a risk factor for refractory stenosis. Circumferential ESD was performed in 3 patients with 64, 69, and 70 mm longitudinal mucosal defects. A local steroid injection was used to treat the postoperative ulcer, followed by an oral steroid. In all three cases, the ulcer healed without the need for endoscopic dilation. A combination of local injection and oral steroids effectively prevented esophageal stenosis in patients with high-risk stenosis after ESD.

Diagnostic Performance of Endocytoscopy for Esophageal Eosinophilia.

INTRODUCTION: Eosinophils in the esophageal epithelium are unevenly distributed in eosinophilic esophagitis (EoE). Esophageal eosinophilia (EE) may be observable by endocytoscopy (EC). This study aimed to evaluate the diagnostic performance of EC for the diagnosis of EE. METHODS: A total of 33 EoE patients underwent EC with methylene blue staining from March 2020 to April 2021. A total of 194 EC images with corresponding biopsies were obtained. Three findings of EC, increased squamous cells (item I), increased inflammatory cells (item II), and cells with bilobed nuclei (item III), were established. These findings were reviewed by two endoscopists to diagnose EE. Another four endoscopists reviewed the images for interobserver agreement. RESULTS: When all three items were met by EC, the sensitivity and the accuracy for the diagnosis of EE were 88% and 76%, respectively. The integrated diagnostic odds ratios (ORs) for the diagnosis of EE of the four endoscopists were significant (OR: 3.98, 95% CI: 2.94-5.40, p < 0.001). The results were similar when only item III was met. Interobserver agreement was good for item III to diagnose EE (kappa value = 0.653). DISCUSSION/CONCLUSION: The diagnostic performance of EC for EE is acceptable and has good interobserver agreement. It may be useful for targeted biopsy in EoE patients.

Novel endoscopic approaches using the endocytoscopy for the target biopsy in esophageal eosinophilia.

BACKGROUND AND AIMS: Multiple biopsies are recommended for the diagnosis of eosinophilic esophagitis (EoE) because inflammatory changes are frequently patchy. Reports on EoE using endocytoscopy (ECS) are limited. This present study aimed to assess if diagnostic yield improves by adding ECS on conventional white light imaging (WLI) in patients with esophageal eosinophilia (EE). METHODS: A total of 284 biopsy specimens from 71 patients with a known diagnosis of EE were enrolled and divided into the WLI group (156 specimens) or the ECS group (128 specimens). Four biopsies from 5 and 10 cm proximal to the esophagogastric junction were taken from each patient. In the ECS group, the biopsy was performed where bilobed nuclei were observed. The biopsy sensitivity for EE, eosinophil count of a single specimen and the biopsy sensitivity of each endoscopic finding were evaluated between both groups. RESULTS: The sensitivity of a single biopsy specimen was higher in the ECS group than that of the WLI group (62.5 vs. 41.7%, P < 0.001). In addition, the median eosinophil count in the ECS group was significantly higher [19 vs. 6.5/high-power field (HPF), P < 0.001]. For each endoscopic finding, ECS-based biopsy had higher sensitivity than that of WLI in the diagnosis of edema (33.1 vs. 11.3%, P = 0.007) and linear furrows (75.8 vs. 52%, P = 0.005). CONCLUSION: This study showed that adding ECS to WLI improved the biopsy sensitivity and eosinophil detection in patients with EE.

Scoring system for predicting the prognosis of elderly gastric cancer patients after endoscopic submucosal dissection.

OBJECTIVES: Comprehensive assessments of the long-term outcomes of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) in the elderly are unavailable. We aimed to create a scoring system to predict the long-term prognosis after ESD for EGC among patients aged ≥75 years. METHODS: We conducted retrospective studies of two cohorts: a single-center cohort (2006-2011) for developing the scoring system, and a multicenter cohort for validating the developed system (2012-2016). In the development cohort, factors related to death after ESD were identified using multivariable Cox regression analysis, and a predictive scoring system was developed. In the validation cohort, the scoring system was validated in 295 patients. RESULTS: In the development cohort, Charlson comorbidity index (CCI) ≥3 (hazard ratio [HR] 3.017), high psoas muscle index (PMI) (HR 2.206), and age ≥80 years (HR 1.978) were significantly related to overall survival after ESD. Therefore, high CCI, low PMI, and age ≥80 years were assigned 1 point each. The patients were categorized into low (≤1 point) and high (≥2 points) score groups based on their total scores. In the validation cohort, 184 and 111 patients were assigned to the low- and high-score groups, respectively. In comparisons based on Kaplan-Meier curves, the 5-year survival rate was 91.5% in the low-score group and 57.8% in the high-score group (log-rank test; P < 0.001). CONCLUSION: Our scoring system including high CCI, low PMI, and age ≥80 years could stratify the long-term prognosis of elderly patients aged ≥75 years after ESD for EGC.

Factors Related to Delayed Adverse Events of Endoscopic Submucosal Dissection in the Duodenum.

INTRODUCTION: Endoscopic submucosal dissection for duodenal neoplasms (D-ESD) is considered a technically demanding procedure regarding the high risk of delayed adverse events. Data regarding optimal managements of ulcers after D-ESD are lacking. METHODS: A retrospective analysis was performed on consecutive 145 cases of D-ESD for superficial nonampullary duodenal epithelial tumors at a single referral center. Factors related to delayed adverse events and the healing process of ulcers after D-ESD were analyzed. RESULTS: Complete ulcer suture after D-ESD was performed in 128 cases (88%). Two delayed perforation occurred among cases with incomplete suture. Delayed bleeding occurred in 8 cases (6%) within 3 weeks. The ulcer closure rate at second-look endoscopy (SLE) was significantly low among cases with delayed bleeding (12.5% vs. 75%, p = 0.001). The bleeding rate before SLE was significantly high among patients who did not have complete ulcer closure after D-ESD (0.8% vs. 12%, p = 0.036). The ratio of lesions located in the second oral-Vater was significantly low among ulcers re-opened at SLE (38% vs. 14%, p = 0.044). Proton-pump inhibitors (PPIs) were administered for a median of 7 weeks (range 1-8 weeks). At 3 weeks, active ulcer stages were observed in a few cases, and healing or scarring was observed in most cases. CONCLUSIONS: Complete ulcer suture was related to decreased risk of delayed adverse events after D-ESD. From the bleeding period and healing process of D-ESD ulcers, the minimum required length of PPI may be 3 weeks after D-ESD.

Accuracy of Serum Leucine-Rich Alpha-2 Glycoprotein in Evaluating Endoscopic Disease Activity in Crohn's Disease.

BACKGROUND: Mucosal healing, confirmed by endoscopic evaluation, is the long-term goal of treatment for Crohn's disease (CD). Leucine-rich alpha-2 glycoprotein (LRG) is a new serum biomarker correlated with disease activity in inflammatory bowel disease. However, studies evaluating its relationship with CD, particularly in the context of small intestinal lesions, are scarce. The aim of this study was to investigate the accuracy of LRG in assessing endoscopic activity, especially remission, in patients with CD. METHODS: Between July 2020 and March 2021, 72 patients with CD who underwent LRG testing and double-balloon endoscopy at the same time were included. Endoscopic activity was evaluated using the applied Simple Endoscopic Score for Crohn's disease, including small intestine lesions. The relationship of LRG with clinical symptoms and endoscopic activity was assessed, and its predictive accuracy was evaluated. RESULTS: Leucine-rich alpha-2 glycoprotein showed a significant positive correlation with endoscopic activity (r = 0.619, P < .001), even in patients with active lesions in the small intestine (r = 0.626, P < .001). Multivariate logistic regression revealed that LRG was the only factor associated with endoscopic remission. An LRG cutoff value of 8.9 µg/mL had a sensitivity of 93.3%; specificity of 83.3%; positive predictive value of 96.6%; negative predictive value of 71.4%; accuracy of 91.7%; and area under the curve of 0.904 for the prediction of endoscopic remission. CONCLUSIONS: Leucine-rich alpha-2 glycoprotein can be used in assessing endoscopic activity and is a reliable marker of endoscopic remission in CD patients. It can be an intermediate target in the treatment of CD.

This study investigated leucine-rich alpha-2 glycoprotein's ability to assess endoscopic activity and endoscopic remission in patients with CD. The results showed that leucine-rich alpha-2 glycoprotein can assess endoscopic activity in CD patients and is a reliable marker of endoscopic remission.

Analysis of immunologic comorbidities in ulcerative colitis patients: a tool to prevent exacerbations in ulcerative colitis cases.

There have been previous studies, especially in Western countries and even in some areas in Asia, about extra-intestinal manifestations (EIMs) and its link with the outcome of inflammatory bowel disease (IBD), which includes Crohn's disease (CD), and ulcerative colitis (UC). This link is crucial when discussing a patient's prognosis and important when dealing with UC management. The aim of this study was to clarify the most common comorbidities associated with UC, emphasizing immunologic comorbidities in Japan. This study was a retrospective analysis performed at Nagoya University Hospital. The data collection started in March, 2019, and continued for two years. We retrieved the medical records of 105 patients with UC diagnosis, from which the data of 176 EIMs were extracted and analyzed. Results showed that EIMs with UC in the active phase accounted for 43.7% of total EIMs. Twenty-six patients with immune-mediated inflammatory disease frequently had an active phase (odds ratio [OR] 3.84, 99% CI, 1.44-10.27). Comorbidities showing an active manifestation of symptoms and UC in the active phase were significantly correlated in patients with immunological comorbidities, such as peripheral arthritis (r = 0.97, p < 0.01) and rheumatoid arthritis (RA) (r = 0.99, p < 0.01), as well as in patients with primary sclerosis cholangitis (PSC) (r = 0.98, p < 0.01). In conclusion, this analysis suggests the importance of having full comprehension of how immunological comorbidities affect the natural development of UC, which is of vital importance to prevent further UC complications and properly adjust the management of the disease.

The effects of ustekinumab on small intestinal lesions and stenotic lesions.

Crohn's disease patients suffer from symptoms originating from small bowel lesions, including strictures. As many of these patients also have a potential risk of surgery, it is important to consider various therapeutic strategies for small bowel lesions. We retrospectively analyzed the therapeutic effects of ustekinumab, interleukin-12 and -23 blocker, for small intestinal lesions and intestinal stenosis in order to contribute to the optimal management of Crohn's disease. Patients who underwent total colonoscopy or small bowel endoscopy before and after the introduction of ustekinumab were enrolled in this study. The colonoscopy findings were evaluated by the simple endoscopic score for Crohn's disease, and small bowel endoscopy findings were evaluated using the modified simple endoscopic score for Crohn's disease. Endoscopic scores were compared before and after the introduction of ustekinumab and between the responders and non-responders to ustekinumab. Responders were defined as those whose Crohn's disease activity index score at 24 weeks fell below 150 points, or those whose score decreased by more than 100 points from the pre-induction level. A total of 50 patients were enrolled in the study, and the number of responders was 35. Pre-induction simple endoscopic scores were lower for responders, but no significant difference was observed in the modified simple endoscopic scores. The total decrease in the endoscopic score was significantly higher in the responders for both the small and large intestine. Use of ustekinumab as a first-line treatment for patients with small bowel lesions or stricture-prone lesions may be a new treatment consideration in the future.

Gender-specific factors contributing to visceral obesity including the sleep-obesity relationship: a large-scale cross-sectional study from East Asia.

Our study aimed to evaluate the relationship between visceral obesity and its associated factors, especially sleep duration in East Asia. We conducted univariate and multivariate analyses using the data of 2538 participants (mean age 56.4 ± 10.8 years) who underwent medical checkups and computed tomography of the abdomen to calculate the visceral fat area from 2008 to 2020. We additionally performed logistic regression analyses using each sleep-duration group (< 5, 5-6, 6-7, 7-8, and ≥ 8 h) and their respective propensity scores as covariates. According to the criteria of visceral obesity(a visceral fat area ≥ 100 cm2), 1147 of 1918 men (59.8%) and 131 of 620 women (21.1%) had visceral obesity. In multivariate analyses, visceral obesity was significantly associated with age, body mass index and triglyceride in both genders, high-density lipoproteins, uric acid levels, and daily alcohol consumption in men; and glycated hemoglobin (HbA1c) in women. In both multivariate and propensity score matching analyses, sleep duration of > 8 h and visceral obestiy showed a positive association in men but a negative association in women with statistical significance. In conclusion, our large-scale cross-sectional study in East Asia identified various gender-specific factors associated with visceral obesity including the long sleep duration.

Network Analysis of Gut Microbiota Including Fusobacterium and Oral Origin Bacteria and Their Distribution on Tumor Surface, Normal Mucosa, and in Feces in Patients with Colorectal Cancer.

INTRODUCTION: Fusobacterium and several bacteria are reported to be associated with colorectal cancer (CRC). However, their relationship and whether they cause CRC or are just adapted to the cancerous environment is not known. We approached this subject by investigating the correlation and distribution of the bacteria throughout the colon in patients with CRC and elucidated the relationship between microbiota and CRC. METHODS: Twenty-five patients with CRC who underwent colonoscopy for endoscopic submucosal dissection or surgery were prospectively enrolled. Fecal samples were taken before bowel preparation, and mucosal samples were collected from three sites (tumor surface, tumor-adjacent mucosa, and cecum) during colonoscopy using a cytology brush. The microbiota was identified and analyzed by sequencing of the 16S rRNA gene of the V3-V4 region. We evaluated the correlation between the bacteria based on network analysis and the distribution of Fusobacterium in the colon. RESULTS: A network consisting of many bacteria was found in all sites; especially, oral origin bacteria including Fusobacterium formed a positively correlated network on tumor surface. Streptococcus showed a significantly higher relative abundance on tumor surface than in feces. The relative abundance of Fusobacterium had significant positive correlations between tumor surface and feces, tumor-adjacent mucosa, and cecum. CONCLUSION: In patients with CRC, many bacteria were correlated with each other, and Fusobacterium and oral origin bacteria formed a positively correlated network on tumor surface. Fusobacterium was equally distributed on tumor surface and throughout the lumen and mucus in the colon. In the colon where Fusobacterium is widely distributed, Fusobacterium would adhere to the tumor surface and be correlated with oral origin bacteria to make a microenvironment that is favorable for CRC.