Predictors of the efficacy of vedolizumab in patients with ulcerative colitis.

Vedolizumab is a treatment option for ulcerative colitis but data on predictors of treatment response remain insufficient to establish personalized treatment strategies. We aimed to investigate the real-world effectiveness of vedolizumab in adult patients with ulcerative colitis and explore factors involved in predicting treatment response. This single-center, single-arm, prospective observational study included 26 patients with clinically active ulcerative colitis patients' characteristics at baseline, epidemiological information, existing treatment, clinical activity index score, endoscopic score, and blood test data were collected. Serum levels of tumor necrosis factors alpha, interferon gamma, interleukin-4, interleukin-6, interleukin-10, interleukin-17, soluble mucosal addressin cell adhesion molecule 1, and soluble vascular cell adhesion molecule 1 were measured. Patient characteristics in the remission and non-remission groups were compared based on these parameters. Clinical remission at 6 weeks of treatment occurred in 9 (35%) of the 26 patients. At 14 weeks, clinical remission was observed in 11 patients (42%). There were no significant differences pertaining to age, sex, duration of disease, extent of disease, steroid resistance, or prior treatment with biological agents among the two groups after 14 weeks of treatment. Hemoglobin ≥ 11.5 g/dL (odds ratio, 15.0; 95% confidence interval, 1.50-149; P=0.014) and soluble mucosal addressin cell adhesion molecule 1 ≥ 765 pg/mL (odds ratio, 17.3; 95% confidence interval, 2.36-127; P=0.004) were significant factors. In conclusion, hemoglobin and serum soluble mucosal addressin cell adhesion molecule 1 levels are factors correlated with the therapeutic efficacy of vedolizumab.

Endoscopic Papillectomy for Ampullary Gangliocytic Paraganglioma: A Case Series and Literature Review.

Background Gangliocytic paraganglioma (GP) significantly affects patients' quality of life. However, studies on endoscopic papillectomy (EP) for ampullary GP are limited. We therefore evaluated the safety and efficacy of EP for treating ampullary GP. Methods We retrospectively reviewed the clinicopathological characteristics of patients with GP who underwent EP at Nagoya University Hospital and conducted a literature survey. Results We enrolled six patients with a median tumor diameter of 17 mm. Complications related to EP were observed in three patients: two experienced bleeding, one had mild acute pancreatitis, and one had perforation (duplicate patients included), all of whom improved conservatively. Five resected specimens were confined to the submucosal layer, and one was beyond the submucosal layer. All patients were monitored without surgery, and no disease recurrence was observed after a median follow-up of 73 months. A literature review identified 14 patients, and additional surgery due to a positive vertical margin after EP revealed lymph node metastasis in 2 patients. There was no disease recurrence or death. Conclusion EP led to good long-term outcomes and effectively treated ampullary GP. Considering the potential for lymph node metastasis, additional surgery is recommended if the tumor exceeds the submucosal layer.

Initial Tumor Size and Narrow-Band Image Findings Estimate Growth Speed in Duodenal Tumors.

INTRODUCTION: Recently, the detection of superficial non-ampullary duodenal epithelial tumors (SNADETs) including adenomas and superficial duodenal carcinomas has increased. Various endoscopic treatment methods have also been reported for SNADETs, but there are few reports on the natural history. The aim of this study was to analyze factors related to tumor growth and determine the characteristics of SNADETs which need early therapeutic intervention. METHODS: A single-center, retrospective study was performed on the medical records of 309 patients with SNADETs who underwent endoscopic or surgical resection between January 2010 and May 2021. Of these, 41 patients who were followed up for more than 1 year by endoscopy were analyzed. The primary outcome was an analysis of the tumor growth speed. Secondary outcomes were the relationship between the tumor growth speed and mucin phenotype, tumor size and findings of magnifying endoscopy with narrow-band imaging (M-NBI). RESULTS: The observation period was 24 months (13-182). Tumor growth speed was 1.1 mm/year (0-21.6). Tumor diameter ≥10 mm at first detection (p = 0.004; odds ratio 19.5 [2.03-186.96]) and mixed type by M-NBI (p = 0.036; odds ratio 9.69 [1.05-89.88]) were identified as risk factors of tumors growing at a rate of ≥3 mm/year. There was no statistically significant difference in the speed of tumor growth between the different mucin immunohistochemical phenotypes. CONCLUSION: Initial tumor size and findings of M-NBI are useful to predict tumor growth and consider early intervention.

Analysis of Neuropeptides in the Intestinal Mucus of Patients with Ulcerative Colitis Using RNA Sequencing.

INTRODUCTION: Inflammation in ulcerative colitis (UC) originates in the colorectal mucosa. Transcriptome sequencing analysis of the colorectal mucosa allows the identification of potential neuropeptides related to local neurotransmission. The intestinal mucus lining the surface of the mucosa may harbor biomarkers of mucosal inflammation; however, this has not been sufficiently investigated, given the difficulty in obtaining human samples. We previously reported the feasibility of obtaining mucin samples for proteomic analysis by brushing during colonoscopy. Herein, we aimed to investigate the composition of the intestinal mucus and detect neuropeptides characteristic of UC. METHODS: Mucus and mucosal samples were collected from patients with UC from the colorectum in areas showing remission or active UC using a brush catheter and biopsy forceps during colonoscopy. RNA sequencing findings of mucus samples of active and remission areas were compared. RNA and protein expression levels of significantly upregulated neuropeptides were analyzed. RESULTS: Of the neuropeptides associated with UC, somatostatin (SST) was significantly elevated in areas of remission, according to RNA sequencing results of mucus and expression levels in mucus RNA and proteins. Conversely, SST expression in the mucosa was increased in the inflamed areas. Flow cytometry revealed that the fluorescence intensity of SST-positive cells in the remission zone was higher in the mucus than in the mucosa. CONCLUSION: SST expression in the mucus is considered to be an important factor associated with UC activity.

Outcomes of surgical treatment for enterovesical fistula in Crohn's disease.

Enterovesical fistula (EVF) in Crohn's disease (CD) often does not improve with medical treatment and requires surgical treatment. The surgical treatment strategy for EVF in CD is definitive resection of the intestinal tract side, and performing a leak test using dye injection into the bladder after EVF dissection to determine the appropriate surgical procedure for the bladder side. This study aimed to evaluate the outcomes of surgical treatment for EVF in CD. Twenty-one patients who underwent surgery for EVF between 2006 and 2021 were included and retrospectively evaluated for clinical background, surgical procedures, and postoperative complications. The most common origin of EVF was the ileum (17 cases; 81%), and the most common site of EVF formation was the apex (12; 57%). Surgical approaches were laparotomy in 11 (52%) cases and laparoscopy in 10 (48%). Surgical procedures on the bladder side were fistula dissection in 13 (62%) cases and sutured closure of fistula in 8 (38%). A comparison of approaches revealed no significant difference in operative time, but the amount of blood loss was significantly less in the laparoscopy (p < 0.01). There was no significant difference in the occurrence of postoperative complications between approaches. Postoperative anti-TNF-α antibody agents were used in 17 (81%) cases, and there were no cases of recurrent EVF. In conclusion, definitive resection of the intestinal tract and minimal treatment on the bladder side were sufficient to achieve satisfactory outcomes for EVF in CD.

Sessile serrated lesion prevalence and factors associated with their detection: a post-hoc analysis of a multinational randomized controlled trial from Asia.

BACKGROUND: Sessile serrated lesions (SSLs) are associated with an increased risk of colorectal cancer. Data on the prevalence of SSLs in Asia are limited. We performed this study to estimate the prevalence of SSLs in Asia and to explore endoscopic factors that are associated with SSL detection. METHODS: This is a post-hoc analysis of a multicenter randomized controlled trial from four Asian countries/regions that compared adenoma detection rates using linked-color imaging (LCI) and white-light imaging. Colonoscopies were performed in an average-risk population for screening, diagnostic examination, or polyp surveillance. Patients with SSLs were compared against those without SSLs to evaluate for possible predictors of SSL detection using Firth's logistic regression. RESULTS: 2898 participants (mean age 64.5 years) were included in the analysis. The estimated prevalence of SSLs was 4.0% (95%CI 3.4%-4.8%), with no sex or age group differences. On multivariable analysis, use of LCI (adjusted odds ratio [aOR] 1.63, 95%CI 1.10-2.41), experienced endoscopists (aOR 1.94, 95%CI 1.25-3.00), use of transparent cap (aOR 1.75, 95%CI 1.09-2.81), and longer withdrawal time (aOR 1.06, 95%CI 1.03-1.10) were independently associated with SSL detection. Synchronous adenoma detection (aOR 1.89, 95%CI 1.20-2.99) was also predictive of SSL detection. CONCLUSION: The prevalence of SSLs in Asia is 4.0%. Use of LCI or a transparent cap, greater endoscopist experience, and longer withdrawal time were all associated with increased SSL detection.

Long-Term Monitoring and Clinical Implications of Small Bowel Capsule Endoscopy in Patients with Crohn's Disease with Small Bowel Lesions: A Retrospective Analysis.

INTRODUCTION: Crohn's disease (CD) induces persistent inflammation throughout the gastrointestinal (GI) tract, potentially resulting in complications such as intestinal stenosis and fistulas, particularly in the small bowel. Small bowel capsule endoscopy (SBCE) is recommended for monitoring CD, especially when GI tract patency is maintained. This study aimed to retrospectively assess patients with CD who underwent SBCE to determine the timing of clinical changes and address the current lack of evidence regarding GI tract patency loss during CD treatment. METHODS: Of the 166 consecutive patients who underwent SBCE at our institution, 120 were followed up and included in this study. Forty-six patients were excluded due to colitis type or immediate treatment changes post-SBCE. This study focused on the primary and secondary endpoints, including the cumulative stricture-free rate of the GI tract, emergency hospitalization post-SBCE, and post-SBCE treatment strategies, at the discretion of the attending physicians. RESULTS: Demographic data revealed that the mean age of the study population was 43 years and that there was a male predominance (75%). The median disease duration was 12 years and the mean Crohn's Disease Activity Index was 98. During a 1,486-day observation period, 37% of patients experienced treatment changes. A Lewis score of >264 and perianal lesions were identified as independent risk factors for additional treatment needs. Emergency hospitalization occurred in 6% of patients and GI patency failure in 11%. Female sex and Lewis score>264 were associated with higher risks. GI patency rate declined 2 years after SBCE. CONCLUSIONS: For patients who experienced no treatment changes based on SBCE results, it is recommended to undergo SBCE monitoring at intervals of no longer than 2 years.

A prospective study on the histological evaluation of type 1 autoimmune pancreatitis using endoscopic ultrasound-guided fine needle biopsy with a 19-gauge Franseen needle.

BACKGROUND/PURPOSE: To assess the diagnostic efficacy and safety of endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) using a 19-gauge Franseen needle for autoimmune pancreatitis (AIP). METHODS: Twenty patients suspected of having type 1 AIP were prospectively enrolled and underwent EUS-FNB with a 19-gauge Franseen needle. Their data were compared with those of historical controls: a total of 29 type 1 AIP patients had EUS-FNB with a 22-gauge Franseen needle. RESULTS: Specimens suitable for histological evaluation were obtained from 19 of the 20 patients (95%), and the median total tissue area was 11.9 mm2. The histological diagnosis rate of AIP was 65% (95% CI: 43.2%-82%). Adverse events were observed in three patients (15%), and a switch to 22-gauge needles occurred during transduodenal puncture in two patients. Compared to those punctured with 22-gauge needles, patients punctured with 19-gauge needles had greater prevalence of each characteristic feature of lymphoplasmacytic sclerosing pancreatitis, but the difference was not statistically significant. CONCLUSIONS: EUS-FNB using a 19-gauge Franseen needle demonstrated favorable performance for the histological diagnosis of AIP and allowed for large tissue samples, potentially facilitating pathological diagnosis. However, during transduodenal puncture, maneuverability is reduced; therefore, the needle may need to be selected according to the puncture site.

What is the appropriate method of pathological specimen collection for cholangiocarcinoma detection in primary sclerosing cholangitis?

BACKGROUND: In primary sclerosing cholangitis (PSC), it is important to understand the cholangiographic findings suggestive of malignancy, but it is difficult to determine whether cholangiocarcinoma is present due to modifications caused by inflammation. This study aimed to clarify the appropriate method of pathological specimen collection during endoscopic retrograde cholangiopancreatography for surveillance of PSC. METHODS: A retrospective observational study was performed on 59 patients with PSC. The endpoints were diagnostic performance for benign or malignant on bile cytology and transpapillary bile duct biopsy, cholangiographic findings of biopsied bile ducts, diameters of the strictures and upstream bile ducts, and their differences. RESULTS: The sensitivity (77.8% vs. 14.3%, P = 0.04), specificity (97.8% vs. 83.0%, P = 0.04), and accuracy (94.5% vs. 74.1%, P = 0.007) were all significantly greater for bile duct biopsy than for bile cytology. All patients with cholangiocarcinoma with bile duct stricture presented with dominant stricture (DS). The diameter of the upstream bile ducts (7.1 (4.2-7.2) mm vs. 2.1 (1.2-4.1) mm, P < 0.001) and the diameter differences (6.6 (3.1-7) mm vs. 1.5 (0.2-3.6) mm, P < 0.001) were significantly greater in the cholangiocarcinoma group than in the noncholangiocarcinoma group with DS. For diameter differences, the optimal cutoff value for the diagnosis of benign or malignant was 5.1 mm (area under the curve = 0.972). CONCLUSION: Transpapillary bile duct biopsy should be performed via localized DS with upstream dilation for the detection of cholangiocarcinoma in patients with PSC. Especially when the diameter differences are greater than 5 mm, the development of cholangiocarcinoma should be strongly suspected.

Monoclonal Antibodies Against Mature Interleukin-18 Ameliorate Colitis and Repair Goblet Cell Function.

BACKGROUND: Numerous biological interventions and small molecules are used to treat Crohn's disease; however, the effectiveness of these treatments varies largely. Non-responsiveness to biological therapies is associated with interleukin (IL)-18 gene polymorphisms and high IL-18 expression has been implicated in the pathogenesis of Crohn's disease. AIMS: The aim of this study was to elucidate the expression of precursor and mature IL-18 in patients with Crohn's disease who exhibited varied responses to cytokine-targeted treatments and determine whether selective inhibition of mature IL-18 offers a novel therapeutic avenue. METHODS: We generated a monoclonal antibody that specifically recognizes the neoepitope of caspase-cleaved mature IL-18. Expression of precursor and mature IL-18 was analyzed in patients with Crohn's disease. Anti-mature IL-18 monoclonal antibodies were intraperitoneally administered in an acute colitis mouse model, and the disease activity index, body weight loss, tissue pathology, proinflammatory cytokine expression, goblet cell function, and microbiota composition were assessed. RESULTS: Precursor and mature IL-18 expression was upregulated and goblet cell function was impaired in patients with Crohn's disease who were unresponsive to biological therapies. Administration of anti-mature IL-18 antibodies ameliorated induced colitis by repairing goblet cell function and restoring the mucus layer. CONCLUSIONS: The newly developed monoclonal antibody holds promise as a therapeutic alternative for Crohn's disease.

Analysis of the Characteristics of Coexisting Lesions in Colorectal Cancer Patients in an International Study: A Subgroup Analysis of the ATLAS Trial.

INTRODUCTION: We investigated coexisting lesion types in patients with invasive colorectal cancer (CRC) in a multinational study for comprehending the adenoma-carcinoma and serrated pathway about the development of CRC. METHODS: We retrospectively reviewed 3,050 patients enrolled in the international randomized controlled trial (ATLAS study) to evaluate the colorectal polyp detection performance of image-enhanced endoscopy in 11 institutions in four Asian countries/regions. In the current study, as a subgroup analysis of the ATLAS study, 92 CRC patients were extracted and compared to 2,958 patients without CRC to examine the effects of age, sex, and coexisting lesion types (high-grade adenoma [HGA], low-grade adenoma with villous component [LGAV], 10 adenomas, adenoma ≥10 mm, sessile serrated lesions [SSLs], and SSLs with dysplasia [SSLD]). Additional analyses of coexisting lesion types were performed according to sex and location of CRC (right- or left-sided). RESULTS: A multivariate analysis showed that HGA (odds ratio [95% confidence interval] 4.29 [2.16-8.18]; p < 0.01), LGAV (3.02 [1.16-7.83], p = 0.02), and age (1.04 [1.01-1.06], p = 0.01) were independently associated with CRC. According to sex, the coexisting lesion types significantly associated with CRC were LGAV (5.58 [1.94-16.0], p < 0.01) and HGA (4.46 [1.95-10.20], p < 0.01) in males and HGA (4.82 [1.47-15.80], p < 0.01) in females. Regarding the location of CRC, SSLD (21.9 [1.31-365.0], p = 0.03) was significant for right-sided CRC, and HGA (5.22 [2.39-11.4], p < 0.01) and LGAV (3.46 [1.13-10.6], p = 0.02) were significant for left-sided CRC. CONCLUSIONS: The significant coexisting lesions in CRC differed according to sex and location. These findings may contribute to comprehending the pathogenesis of CRC.

Linked color imaging improves colorectal lesion detection especially for low performance endoscopists: An international trial in Asia.

BACKGROUND AND AIM: Linked color imaging (LCI) is an image-enhanced endoscopy technique that accentuates the color difference between red and white, potentially improving the adenoma detection rate (ADR). However, it remains unclear whether LCI performance in detecting colorectal lesions differs based on endoscopists' experience levels. We aimed to evaluate the differences in LCI efficacy based on the experience levels of endoscopists by conducting an exploratory analysis. METHODS: In this post hoc analysis of an international randomized controlled trial comparing the detection of adenoma and other lesions using colonoscopy with LCI and high-definition white light imaging (WLI), we included patients from 11 institutions across four countries/regions: Japan, Thailand, Taiwan, and Singapore. We retrospectively reviewed differences in the lesion detection of LCI according to endoscopists' colonoscopy history or ADR. RESULTS: We included 1692 and 1138 patients who underwent colonoscopies performed by 54 experts (experience of ≥ 5000 colonoscopies) and by 43 non-experts (experience of < 5000 colonoscopies), respectively. Both expert and non-expert groups showed a significant improvement in ADR with LCI compared to WLI (expert, 61.7% vs 46.4%; P < 0.001; non-expert, 56.6% vs 46.4%; P < 0.001). LCI had no effect on sessile serrated lesion detection rate in non-experts (3.1% vs 2.5%; P = 0.518). LCI significantly improved detection rates in endoscopists with relatively low detection performance, defined as an ADR < 50%. CONCLUSIONS: This exploratory study analyzed data from a previous trial and revealed that LCI is useful for both experts and non-experts and is even more beneficial for endoscopists with relatively low detection performance using WLI.

Efficacy of endoscopic submucosal resection with a ligation device for small rectal neuroendocrine tumor: study protocol of a multicenter open-label randomized control trial (BANDIT trial).

BACKGROUND: Endoscopic resection is widely accepted as a local treatment for rectal neuroendocrine tumors sized ≤ 10 mm. However, there is no consensus on the best method for the endoscopic resection of rectal neuroendocrine tumors. As a simplified endoscopic procedure, endoscopic submucosal resection with a ligation device (ESMR-L) indicates a histologically complete resection rate comparable to that of endoscopic submucosal dissection (ESD). We hypothesized that ESMR-L than ESD would be preferred for rectal neuroendocrine tumors. Hence, this trial aimed to verify whether ESMR-L is non-inferior to ESD in terms of histologically complete resection rate. METHODS: This is a prospective, open-label, multicenter, non-inferiority, randomized controlled trial of two parallel groups, conducted at the Shizuoka Cancer Center and 31 other institutions in Japan. Patients with a lesion endoscopically diagnosed as a rectal neuroendocrine tumor ≤ 10 mm are eligible for inclusion. A total of 266 patients will be recruited and randomized to undergo either ESD or ESMR-L. The primary endpoint is the rate of en bloc resection with histologically tumor-free margins (R0 resection). Secondary endpoints include en bloc resection rate, procedure time, adverse events, hospitalization days, total devices and agents cost, adverse event rate between groups with and without resection site closure, outcomes between expert and non-expert endoscopists, and factors associated with R0 resection failure. The sample size is determined based on the assumption that the R0 resection rate will be 95.2% in the ESD group and 95.3% in the ESMR-L group, with a non-inferiority margin of 8%. With a one-sided significance level of 0.05 and a power of 80%, 226 participants are required. Assuming a dropout rate of 15%, 266 patients will be included in this study. DISCUSSION: This is the first multicenter randomized controlled trial comparing ESD and ESMR-L for the R0 resection of rectal neuroendocrine tumors ≤ 10 mm. This will provide valuable information for standardizing endoscopic resection methods for rectal neuroendocrine tumors. TRIAL REGISTRATION: Japan Registry of Clinical Trials, jRCTs042210124. Registered on Jan 6, 2022.

An Analysis of Delayed Bleeding in Cases of Colorectal Endoscopic Submucosal Dissection Due to Types of Direct Oral Anticoagulants in Japan.

BACKGROUND & AIMS: Reported rates of delayed bleeding (DB) after endoscopic resection using direct oral anticoagulants (DOACs) are high and heterogeneous. This large-scale multicenter study analyzed cases of DB after colorectal endoscopic submucosal dissection related to various types of DOACs in Japan (the ABCD-J study) with those associated with warfarin. METHODS: We retrospectively reviewed 1019 lesions in patients treated with DOACs and 459 lesions in patients treated with warfarin among 34,455 endoscopic submucosal dissection cases from 47 Japanese institutions between 2012 and 2021. The DB rate (DBR) with each DOAC was compared with that with warfarin. Risk factors for DB in patients treated with DOACs or warfarin were also investigated. RESULTS: The mean tumor sizes in the DOAC and warfarin groups were 29.6 ± 14.0 and 30.3 ± 16.4 mm, respectively. In the DOAC group, the DBR with dabigatran (18.26%) was significantly higher than that with apixaban (10.08%, P = .029), edoxaban (7.73%, P = .001), and rivaroxaban (7.21%, P < .001). Only rivaroxaban showed a significantly lower DBR than warfarin (11.76%, P = .033). In the multivariate analysis, heparin bridging therapy (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.27-3.73, P = .005), rectal location (2.01, 1.28-3.16, P = .002), and procedure time ≥55 minutes (2.43, 1.49-3.95, P < .001) were significant risk factors for DB in the DOAC group. The DB risk in the DOAC group (OR, (95% CI)) was 2.13 (1.30-3.50) and 4.53 (2.52-8.15) for 1 and 2 significant risk factors, respectively. CONCLUSIONS: Dabigatran was associated with a higher DBR than other DOACs, and only rivaroxaban was associated with a significantly lower DBR than warfarin.

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.

Current status of and future issues related to endoscopic papillectomy.

Endoscopic papillectomy is widely performed to treat duodenal papillary tumors, particularly at high-volume centers. It is indicated for adenomas without intraductal extension of the bile or pancreatic ducts. However, despite numerous reports of carcinomas that expand the indications to include well-differentiated adenocarcinomas that do not invade the sphincter of Oddi, the low agreement between biopsy and final pathological diagnosis, as well as the current inability of imaging modalities to diagnose sphincter of Oddi invasion, makes it difficult to consider expanding indications. Although complications can be prevented by certain methods, such as pancreatic duct stenting, and the frequency of severe complications has decreased, the safety of the procedure remains unconfirmed. In the future, this technology is expected to progress and enable wider applications, including those in tumors with extensive horizontal spread and those with intraductal extension of the bile and pancreatic ducts. Such technology may also improve the safety and accuracy of diagnosis.

Real-world effectiveness of ustekinumab for patients with ulcerative colitis: a systematic review and meta-analysis.

Ustekinumab has recently been approved for the treatment of ulcerative colitis (UC) based on data from clinical trials. However, the effectiveness of ustekinumab in patients with UC in a real-world setting remains unclear. Hence, in this meta-analysis, we aimed to evaluate the effectiveness of ustekinumab in a real-world setting and to investigate the predictors of its effectiveness. A comprehensive literature search was performed to examine the effectiveness of ustekinumab in UC patients admitted between January 2019 and December 2021. Data on clinical remission, response, and corticosteroid-free clinical remission rates were extracted, pooled, and analyzed. Meta-regression analysis was performed to investigate the source of heterogeneity and the impact of moderators on the outcomes of interest. A total of 14 eligible studies were identified. The pooled clinical remission rate was 55.0% at week 8, 36.1% at week 16, 46.6% at month 6, and 38.6% at month 12. The meta-regression analysis showed that prior use of anti-tumor necrosis factor (TNF) agents and vedolizumab and the publication style were significant moderators. Additionally, out of 258 patients, there were 28 adverse events (AEs) (10.9%). The effectiveness of ustekinumab in real-world patients with UC was consistent with the results clinical trials. Moreover, previous treatment with anti-TNF agents and vedolizumab might have affected the effectiveness of ustekinumab.

Clinical characteristics of Dieulafoy's lesion in the small bowel diagnosed and treated by double-balloon endoscopy.

BACKGROUND: Obscure gastrointestinal bleeding refers to bleeding for which the source cannot be ascertained even through balloon-assisted endoscopy. In certain instances, Dieulafoy's lesion in the small bowel is presumed to be the underlying cause. AIM: This retrospective study aimed to elucidate the clinical characteristics of Dieulafoy's lesion in the small bowel as diagnosed via double-balloon endoscopy while also exploring the feasibility of predicting bleeding from Dieulafoy's lesion prior to endoscopy in cases of obscure gastrointestinal bleeding. METHODS: A comprehensive analysis of our database was conducted, identifying 38 patients who received a diagnosis of Dieulafoy's lesion and subsequently underwent treatment via double-balloon endoscopy. The clinical background, diagnosis, and treatment details of patients with Dieulafoy's lesion were carefully examined. RESULTS: The median age of the 38 patients was 72 years, and 50% of the patients were male. A total of 26 (68%) patients exhibited a high comorbidity index. The upper jejunum and lower ileum were the most frequently reported locations for the occurrence of Dieulafoy's lesion in the small bowel. The detected Dieulafoy's lesions exhibited active bleeding (n = 33) and an exposed vessel with plaque on the surface (n = 5). Rebleeding after endoscopic treatment occurred in 8 patients (21%, median period: 7 days, range: 1-366 days). We conducted an analysis to determine the definitive nature of the initial double-balloon endoscopy diagnosis. Multivariate analysis revealed that hematochezia of ≥ 2 episodes constituted the independent factor associated with ≥ 2 double-balloon endoscopy diagnoses. Additionally, we explored factors associated with rebleeding following endoscopic treatment. Although the number of hemoclips utilized displayed a likely association, multivariate analysis did not identify any independent factor associated with rebleeding. CONCLUSION: If a patient encounters multiple instances of hematochezia, promptly scheduling balloon-assisted endoscopy, equipped with optional instruments without delay is advised, after standard endoscopic evaluation with esophagogastroduodenoscopy and colonoscopy is unrevealing.

Multicenter prospective registration study of efficacy and safety of capsule endoscopy in Crohn's disease in Japan (SPREAD-J study).

BACKGROUND: Evidence of small-bowel capsule endoscopy (SBCE) for evaluating lesions in Crohn's disease (CD) is lacking. We aimed to clarify the effectiveness and safety of SBCE in a large sample of patients with CD. METHODS: This multicenter prospective registration study recorded the clinical information and SBCE results of patients with definitive CD (d-CD) or suspected CD (s-CD). The primary outcomes were the rates of successful assessment of disease activity using SBCE, definitive diagnosis of CD, and adverse events. Secondary outcomes were the assessment of SBCE findings in patients with d-CD and s-CD and factors affecting SBCE incompletion and retention; and tertiary outcomes included the association between clinical disease activity or blood examination, endoscopic disease activity, ileal CD, and the questionnaire assessment of patient acceptance of SBCE. RESULTS: Of 544 patients analyzed, 541 underwent SBCE with 7 (1.3%) retention cases. Of 468 patients with d-CD, 97.6% could be evaluated for endoscopic activity. Of 76 patients with s-CD, 15.8% were diagnosed with 'confirmed CD'. CD lesions were more frequently observed in the ileum and were only seen in the jejunum in 3.4% of the patients. Male sex and stenosis were risk factors for incomplete SBCE, and high C-reactive protein levels and stenosis were risk factors for capsule retention. In L1 (Montreal classification) patients, clinical remission was associated with endoscopic remission but showed low specificity and accuracy. The answers to the acceptability questionnaire showed the minimal invasiveness and tolerability of SBCE. CONCLUSION: SBCE is practical and safe in patients with CD.