Efficacy of prophylactic clip closure in reducing the risk of delayed bleeding after colorectal endoscopic submucosal dissection in patients on anticoagulant therapy: Multicenter prospective study.

OBJECTIVES: The high rate of delayed bleeding after colorectal endoscopic submucosal dissection (ESD) in patients undergoing anticoagulant therapy remains a problem. Whether prophylactic clip closure reduces the rate of delayed bleeding in these patients is unclear. This study aimed to evaluate the efficacy of prophylactic clip closure in patients receiving anticoagulants. METHODS: This multicenter prospective interventional trial was conducted at nine referral centers in Japan. Patients regularly taking anticoagulants, including warfarin potassium or direct oral anticoagulants, and undergoing ESD for colorectal neoplasms were enrolled. The discontinuation of anticoagulants was minimized according to recent guidelines. After the ESD, post-ESD ulcers were prophylactically closed using endoclips. The primary end-point was the incidence of delayed bleeding. The sample size was 45 lesions, and prophylactic clip closure was considered effective when the upper limit of the 90% confidence interval (CI) for delayed bleeding did not exceed 20%. RESULTS: Forty-five lesions were used, and three were excluded. Complete closure was achieved in 41/42 lesions (97.6%). The overall delayed bleeding rate was low, at 4.9% (2/41; 90% [CI] 0.8-14.5), which was significantly lower than that at the prespecified threshold of 20% (P = 0.007). The median closure procedure time was 17 min, and the median number of clips was nine. No massive delayed bleeding requiring transfusion, interventional radiology, or surgery was observed, and no thromboembolic events were observed. CONCLUSION: Prophylactic clip closure may reduce the risk of delayed bleeding following colorectal ESD in patients receiving anticoagulants. TRIAL REGISTRATION: UMIN Clinical Trial Registry (UMIN000036734).

Diagnostic value of endoscopic ultrasonography for the depth of gastric cancer suspected of submucosal invasion: a multicenter prospective study.

BACKGROUND: Although the combination of conventional endoscopy (CE) and endoscopic ultrasonography (EUS) is useful for predicting the depth of early gastric cancer (EGC), the diagnostic value of EUS for submucosal (SM) invasive cancer has not been fully investigated. METHODS: We conducted a multicenter prospective study from May 2017 to January 2021 to evaluate the validity of a diagnostic strategy combining CE and EUS and to clarify the additional value of EUS for EGC suspected of SM invasion. In each case, the diagnosis was first made using CE, followed by EUS, and finally confirmed using a combination algorithm. RESULTS: A total of 180 patients with EGC were enrolled from 10 institutions, of which 175 were analyzed. The histopathological depths were M, SM1, SM2, and ≥ MP in 72, 16, 64, and 23 lesions, respectively. Treatment included 92 endoscopic submucosal dissection cases and 83 surgical cases. The overall diagnostic accuracy classified by M-SM1 or SM2-MP was 58.3% for CE, 75.7% for EUS, and 78.9% for the combination of CE and EUS; the latter two were significantly higher than that of CE alone (P < 0.001). The CE, EUS, and combination accuracy rates in 108 differentiated-type lesions were 51.9%, 77.4%, and 79.6%, respectively; the latter two were significantly higher than CE alone (P < 0.001). A significant additive effect of EUS was observed in CE-SM2 low-confidence lesions but not in CE-M-SM1 lesions or in CE-SM2 high-confidence lesions. Among the nine CE findings, irregular surface, submucosal tumor-like elevation, and non-extension signs were significant independent markers of pSM2-MP. Poorly delineated EUS lesions were misdiagnosed. CONCLUSIONS: EUS provides additional value for differentiated-type and CE-SM2 low-confidence EGCs in diagnosing invasion depth. CLINICAL REGISTRATION NUMBER: UMIN000025862.

Local recurrence after endoscopic resection of sessile serrated lesions: A multicenter prospective study by the Osaka Gut Forum.

BACKGROUND AND AIM: Sessile serrated lesions (SSLs) act as precursors to colorectal cancer, sometimes harbor carcinomas, and are sometimes incompletely resected. We aimed to evaluate local recurrence after endoscopic resection of SSL ≥10 mm. METHODS: This prospective, single-arm, observational study was performed at eight Japanese tertiary institutions. Colorectal lesions ≥10 mm were resected endoscopically, and the pathological diagnosis was either an SSL or hyperplastic polyp (HP). Follow-up colonoscopy was performed 1 year later, and the local recurrence was evaluated by biopsy. RESULTS: From October 2018 to September 2021, 104 cases with 123 lesions were registered. Among the pathologically diagnosed 105 SSLs and 18 HPs, 95 and 7 lesions were diagnosed as SSLs and HPs, respectively, by central pathological review. Among the 104 endoscopically diagnosed SSLs, 86 were diagnosed as SSLs, whereas among the 11 endoscopically diagnosed HPs, two were diagnosed as HPs by central pathological review (the rest were SSLs). Among the 95 patients with 113 lesions who underwent follow-up colonoscopy, resection scars were identified in 95 (84%) lesions. Three (3.1%; 95% confidence interval 0.6-8.7%) local recurrences were diagnosed pathologically among 98 pathologically diagnosed SSLs. Two (6%) local recurrences were diagnosed in patients with SSLs ≥20 mm. CONCLUSIONS: The local recurrence rate after endoscopic resection of SSLs ≥10 mm was 3.1%. Careful follow-up is recommended after endoscopic resection of large SSLs. Endoscopically diagnosed HPs ≥10 mm were sometimes pathologically diagnosed as SSL and should be considered for resection.

Geriatric nutritional risk index as a prognostic indicator in elderly patients with early colorectal cancer undergoing endoscopic submucosal dissection.

OBJECTIVES: Data on the long-term outcomes of endoscopic submucosal dissection (ESD) performed in elderly patients with early colorectal cancer (CRC) are limited. We analyzed the prognosis of elderly CRC patients, not only from the viewpoint of treatment curability but also from the patients' baseline physical condition assessed by several indexes. METHODS: A retrospective analysis of 729 patients aged ≥75 years who underwent ESD for Tis/T1 CRC in 16 institutions was conducted. The patients were classified into three groups based on curability: curative ESD (Group A, n = 582), non-curative ESD with additional surgery (Group B, n = 60), and non-curative ESD without additional surgery (Group C, n = 87). Overall survival (OS) was compared among the groups, and factors associated with reduced OS were investigated. RESULTS: The median follow-up periods in Groups A, B, and C were 41, 49, and 46 months, respectively (P = 0.62), during which 92 patients died. Two patients (0.3%) in Group A, none (0%) in Group B, and three (3.4%) in Group C died of CRC. Three-year OS rates in Groups A, B, and C were 93.9%, 96.1%, and 90.1%, respectively, without a significant difference (P = 0.07). Multivariate analysis indicated low (<96.3) geriatric nutritional risk index (GNRI) as the sole independent predictor for reduced OS (hazard ratio 3.37; 95% confidence interval 2.18-5.22; P < 0.0001). CONCLUSIONS: Low GNRI, but not the curability attained by ESD, was independently associated with reduced OS in patients with early CRC aged ≥75 years.

Helicobacter pylori eradication prevents secondary gastric cancer in patients with mild-to-moderate atrophic gastritis.

BACKGROUND AND AIM: Whether Helicobacter pylori eradication prevents metachronous recurrence after endoscopic resection (ER) of early gastric cancer remains controversial. This multicenter retrospective study aimed to evaluate the long-term (> 5 years) effects of H. pylori eradication by stratifying patients' baseline degrees of atrophic gastritis. METHODS: A total of 483 H. pylori-positive patients who had undergone ER for early gastric cancer were divided into two groups-(i) those having undergone successful H. pylori eradication within 1 year after ER (eradicated group, n = 294) and (ii) those with failed or not attempted H. pylori eradication (non-eradicated group, n = 189). The cumulative incidences of metachronous gastric cancer between the two groups were compared for all patients, for patients with mild-to-moderate atrophic gastritis (n = 182), and for patients with severe atrophic gastritis (n = 301). RESULTS: During a median follow-up of 5.2 years (range 1.1-14.8), metachronous cancer developed in 52 (17.7%) patients in the eradicated group and in 35 (18.5%) patients in the non-eradicated group (P = 0.11, log-rank test). In patients with mild-to-moderate atrophic gastritis (111 and 71 in the eradicated and non-eradicated groups, respectively), the cumulative incidence of metachronous cancer was significantly lower in the eradicated group than that in the non-eradicated group (P = 0.03, log-rank test). However, no significant intergroup difference was observed in patients with severe atrophic gastritis (P = 0.69, log-rank test). CONCLUSIONS: Helicobacter pylori eradication had a preventive effect on the development of metachronous gastric cancer in patients with mild-to-moderate atrophic gastritis.

Endoscopic detection and differentiation of esophageal lesions using a deep neural network.

BACKGROUND AND AIMS: Diagnosing esophageal squamous cell carcinoma (SCC) depends on individual physician expertise and may be subject to interobserver variability. Therefore, we developed a computerized image-analysis system to detect and differentiate esophageal SCC. METHODS: A total of 9591 nonmagnified endoscopy (non-ME) and 7844 ME images of pathologically confirmed superficial esophageal SCCs and 1692 non-ME and 3435 ME images from noncancerous lesions or normal esophagus were used as training image data. Validation was performed using 255 non-ME white-light images, 268 non-ME narrow-band images/blue-laser images, and 204 ME narrow-band images/blue-laser images from 135 patients. The same validation test data were diagnosed by 15 board-certified specialists (experienced endoscopists). RESULTS: Regarding diagnosis by non-ME with narrow-band imaging/blue-laser imaging, the sensitivity, specificity, and accuracy were 100%, 63%, and 77%, respectively, for the artificial intelligence (AI) system and 92%, 69%, and 78%, respectively, for the experienced endoscopists. Regarding diagnosis by non-ME with white-light imaging, the sensitivity, specificity, and accuracy were 90%, 76%, and 81%, respectively, for the AI system and 87%, 67%, and 75%, respectively, for the experienced endoscopists. Regarding diagnosis by ME, the sensitivity, specificity, and accuracy were 98%, 56%, and 77%, respectively, for the AI system and 83%, 70%, and 76%, respectively, for the experienced endoscopists. There was no significant difference in the diagnostic performance between the AI system and the experienced endoscopists. CONCLUSIONS: Our AI system showed high sensitivity for detecting SCC by non-ME and high accuracy for differentiating SCC from noncancerous lesions by ME.

Incidence of gastric adenocarcinoma among lesions diagnosed as low-grade adenoma/dysplasia on endoscopic biopsy: A multicenter, prospective, observational study.

BACKGROUND AND AIM: Differentiation between gastric adenocarcinoma and low-grade adenoma/dysplasia (LGA) on endoscopic forceps biopsy is difficult. We aim to clarify the incidence of carcinoma in specimens, obtained by endoscopic resection (ER), from cases that had been diagnosed as LGA (Vienna category 3) on endoscopic biopsy. METHODS: In this multicenter, prospective, observational study, patients with gastric adenoma (Vienna category 3 or 4.1) diagnosed on endoscopic forceps biopsy were enrolled. All the specimens were subjected to histopathological central review. Primary endpoint was the incidence of carcinoma (Vienna category 4.2 or over) among the biopsy-proven gastric LGA. Secondary endpoints were the histological findings of resected specimens, clinicopathological features of carcinoma, and short-term outcomes of all ER cases. RESULTS: Ninety-five patients with 104 lesions diagnosed as gastric adenoma were enrolled. After central review of the biopsy specimens, 47 lesions were diagnosed as LGA and seven lesions (15%) as adenocarcinoma (95% confidence interval, 7.6-28%). Carcinoma was detected in lesions that had a minimum size of 6 mm; the incidence of carcinoma was higher in the larger lesions. There was a histological discrepancy between biopsy and ER material in more than 60% of the cases. CONCLUSIONS: A substantial proportion of biopsy-proven gastric LGA specimens were diagnosed as adenocarcinoma after ER. This indicated histological discrepancy between biopsy-proven gastric LGA and histology of the resected material.

Non-Hypervascular Hypointense Hepatic Nodules during the Hepatobiliary Phase of Gadolinium-Ethoxybenzyl-Diethylenetriamine Pentaacetic Acid-Enhanced MRI as a Risk Factor of Intrahepatic Distant Recurrence after Radiofrequency Ablation of Hepatocellular Carcinoma.

BACKGROUND: Non-hypervascular hypointense hepatic nodules during the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI have been reported to be associated with intrahepatic distant recurrence (IDR) after hepatectomy or radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). IDR is categorized into hypervascular transformation of non-hypervascular hypointense hepatic nodules and new intrahepatic recurrence. The aim of this study was to evaluate the relationship between non-hypervascular hypointense hepatic nodules on Gd-EOB-DTPA-enhanced MRI and IDR after RFA, focusing on new intrahepatic recurrence. METHODS: Ninety-one consecutive patients with 115 HCCs undergoing pretreatment Gd-EOB-DTPA-enhanced MRI and RFA for treatment of HCC were enrolled. RESULTS: Of the 91 patients who underwent RFA for HCC, 24 had non-hypervascular hypointense hepatic nodules on pretreatment Gd-EOB-DTPA-enhanced MRI. Recurrences were observed in 15 and 19 patients with and without non-hypervascular hypointense hepatic nodules, respectively. Of the 15 recurrences in patients with non-hypervascular hypointense hepatic nodules, 10 patients had new intrahepatic recurrences. The cumulative incidence of new intrahepatic recurrence was significantly higher in patients with non-hypervascular hypointense hepatic nodules than in those without non-hypervascular hypointense hepatic nodules (p < 0.0001). Multivariate analysis revealed that the presence of non-hypervascular hypointense hepatic nodules and Child-Pugh score were independent risk factors for new intrahepatic recurrence. CONCLUSIONS: Non-hypervascular hypointense hepatic nodules during the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI were a useful predictive factor for IDR, particularly for new intrahepatic recurrence, after RFA.

Comparison of Contrast-Enhanced Ultrasound and Gadolinium-Ethoxybenzyl-Diethylenetriamine Pentaacetic Acid-Enhanced MRI for the Diagnosis of Macroscopic Type of Hepatocellular Carcinoma.

OBJECTIVE: We compared the efficacy of contrast-enhanced ultrasound sonography (CEUS) with sonazoid and gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI for the assessment of macroscopic classification of nodular hepatocellular carcinoma (HCC). METHODS: Seventy-seven consecutive patients with 79 surgically resected HCCs who underwent both preoperative CEUS and Gd-EOB-DTPA-enhanced MRI were enrolled in this retrospective study. Based on the macroscopic diagnosis of resected specimens, nodules were categorized into the simple nodular (SN) and non-SN type HCC. Two hepatologists independently assessed image datasets of the post-vascular phase of CEUS and hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI to compare their diagnostic performance. RESULTS: Gd-EOB-DTPA-enhanced MRI enabled the evaluation of macroscopic classification in a significantly larger number of nodules than CEUS (78/79 (98.7%) vs. 70/79 (88.6%), p < 0.05). Of 70 nodules that could be evaluated by both modalities, 41 and 29 nodules were pathologically categorized as SN and non-SN, respectively. The areas under the receiver operating characteristic curve (AUC) for non-SN did not differ between CEUS and Gd-EOB-DTPA-enhanced MRI (reader 1: 0.748 for CEUS, 0.808 for MRI; reader 2: 0.759 for CEUS, 0.787 for MRI). The AUC of combined CEUS and Gd-EOB-DTPA-enhanced MRI for SN HCC was 0.855 (reader 1) and 0.824 (reader 2), indicating higher AUC values for the combined modalities. CONCLUSIONS: The diagnostic performance for macroscopic classification of nodular HCC of CEUS was comparable with that of Gd-EOB-DTPA-enhanced MRI, although some HCCs could not be evaluated by CEUS owing to lower detectability. The combination of the 2 modalities had a more accurate diagnostic performance.

Clinical outcomes of endoscopic submucosal dissection for superficial esophageal neoplasms: a multicenter retrospective cohort study.

BACKGROUND AND STUDY AIMS: The safety and efficacy of endoscopic submucosal dissection (ESD) for superficial esophageal neoplasms (SENs) have not been evaluated in a multicenter survey. The aim of this study was to investigate the clinical outcomes in a multicenter study that included municipal hospitals. PATIENTS AND METHODS: Of 312 consecutive patients with 373 esophageal lesions treated by ESD at 11 hospitals from May 2005 to December 2012, a total of 368 SENs in 307 patients were retrospectively analyzed. RESULTS: The median tumor size was 18 mm (range 2 - 85 mm). The median procedure time was 90 minutes (range 12 - 450 minutes). The en bloc resection and complete resection rates were 96.7 % (95 % confidence interval [CI] 94.4 % - 98.1 %) and 84.5 % (95 %CI 80.5 % - 87.8 %), respectively. Perforation (including mediastinal emphysema), postoperative pneumonia, bleeding, and esophageal stricture, occurred in 5.2 % (95 %CI 3.3 % - 7.9 %), 1.6 % (95 %CI 0.7 % - 3.5 %), 0 %, and 7.1 % (95 %CI 4.9 % - 10.2 %) of patients, respectively. All of these complications were cured conservatively. No procedure-related mortality occurred. Early treatment periods (odds ratio [OR] = 4.04; P < 0.01) and low volume institutions (OR = 3.03; P  = 0.045) were significantly independent risk factors for perforation. The circumference of the lesion was significantly associated with postoperative stricture (OR = 32.3; P < 0.01). The procedure times significantly decreased in the later period of the study (P < 0.01). Follow-up data (median 35 months; range 4 - 98 months) showed significant differences in overall survival (P = 0.03) and recurrence-free survival (P < 0.01) rates between patients with curative and noncurative resections. CONCLUSIONS: Esophageal ESD has become feasible with acceptable complication risks and favorable long term outcomes.

Outcomes of ESD for patients with early gastric cancer and comorbid liver cirrhosis: a propensity score analysis.

BACKGROUND: Gastric cancer and liver cirrhosis (LC) are often comorbid. However, little is known about the clinical outcomes of gastric endoscopic submucosal dissection (ESD) in patients with comorbid LC. METHODS: This case-control study used a multicentre retrospective cohort. We identified 69 LC patients from the cohort of patients with early gastric cancer, who underwent gastric ESD at 12 hospitals from March 2003 to November 2010. Using the propensity score matching method, 69 patients without LC were used to compare the short- and long-term outcomes of ESD. RESULTS: Among the 69 LC patients, 53 (77 %) were Child-Pugh grade A (CP-A) and 16 (28 %) had past or present histories of hepatocellular carcinoma (HCC). Short-term outcomes did not differ between the LC patients and controls or between the CP-A and CP-B/C patients. Although the LC patients had significantly worse long-term outcomes than the controls (the 5-year overall survival rates were 60 vs. 91 %, respectively), patients with CP-A liver function without HCC histories had an overall survival almost equivalent to that of patients without LC (controls). CONCLUSIONS: LC patients appear to be good candidates for ESD if they have CP-A liver function and no history of HCC. Although their short-term outcomes were not inferior, the patients with Child-Pugh grades B/C or with histories of HCC benefited less from ESD.

Renal impairment during the treatment of telaprevir with peginterferon and ribavirin in patients with chronic hepatitis C.

AIM: Renal damage has been reported as an important complication during combination treatment of peginterferon (PEG IFN), ribavirin (RBV) and telaprevir (TVR) for chronic hepatitis C. However, very little is known about this complication. We investigated the role TVR plays in renal damage during this triple therapy. METHODS: Twenty-five chronic hepatitis C patients with genotype 1 and high viral load received TVR in combination with PEG IFN and RBV for 12 weeks followed by treatment with PEG IFN and RBV. Renal function of these patients was prospectively evaluated for 16 weeks. RESULTS: Creatinine clearance decreased significantly during PEG IFN/RBV/TVR treatment. Consequently, serum creatinine and cystatin C significantly rose during PEG IFN/RBV/TVR treatment. Serum creatinine returned to pretreatment levels after the termination of TVR. The increase of serum creatinine and cystatin C from baseline significantly correlated with serum TVR level at day 7, which was determined by starting dose of TVR per bodyweight . When the patients were classified according to the starting dose of TVR per bodyweight, renal impairment was observed only in the high-dose (TVR ≥33 mg/kg per day) group, not in the low-dose (TVR <33 mg/kg per day) group. CONCLUSION: These results suggest that TVR dose per bodyweight is important for the occurrence of renal impairment in PEG IFN/RBV/TVR treatment.

Scheduled endoscopic surveillance controls secondary cancer after curative endoscopic resection for early gastric cancer: a multicentre retrospective cohort study by Osaka University ESD study group.

BACKGROUND: After endoscopic submucosal dissection (ESD) of early gastric cancer (EGC), patients are at high risk for synchronous or metachronous multiple gastric cancers. OBJECTIVE: To elucidate the time at which multiple cancers develop and to determine whether scheduled endoscopic surveillance might control their development. DESIGN: A multicentre retrospective cohort study from 12 hospitals was conducted. Patients with EGC who underwent ESD with en bloc margin-negative curative resection were included. Synchronous cancer was classified as concomitant cancer or missed cancer. The cumulative incidence of metachronous cancers and overall survival rate were calculated using the Kaplan-Meier method. RESULTS: From April 1999 to December 2010, 1258 patients met the inclusion criteria. Synchronous or metachronous multiple cancers were detected in 175 patients (13.9%) during a mean of 26.8 months. Among the 110 synchronous cancers, 21 were missed at the time of the initial ESD. Many of the missed lesions existed in the upper third of the stomach and the miss rate was associated with the endoscopist's inexperience (<500 oesophagogastroduodenoscopy cases). The cumulative incidence of metachronous cancers increased linearly and the mean annual incidence rate was 3.5%. The incidence rate did not differ between patients with or without Helicobacter pylori eradication. Four lesions (0.32%) were detected as massively invading cancers during the follow-up. CONCLUSIONS: Nineteen per cent of synchronous cancers were not detected until the initial ESD. The incidence rate of metachronous cancer after ESD was constant. Scheduled endoscopic surveillance showed that almost all recurrent lesions were treatable by endoscopic resection.

Utility of computed tomography fusion imaging for the evaluation of the ablative margin of radiofrequency ablation for hepatocellular carcinoma and the correlation to local tumor progression.

AIM: To demonstrate the usefulness of the computed tomography (CT) fusion imaging for the evaluation of treatment effect of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). METHODS: Eighty-five patients with 94 HCC with complete ablation judged on conventional side-by-side interpretation of pre-RFA and post-RFA CT at the time of RFA were included in this retrospective study. CT data was retrospectively used to create fusion images of pre-RFA and post-RFA CT using automatic rigid registration and manual correction referring to intrahepatic structures and hepatic contours around a tumor. Clinical factors including a minimal ablative margin (MAM) measured on fusion images were examined to prove risk factors for local tumor progression (LTP). RESULTS: LTP was observed in 13 (13.8%) tumors with a median follow up of 21.0 months (range, 2-75). The mean MAM on the fusion image was 1.4 ± 3.1 mm and 23 tumors (24.5%) were judged to be protruding from the ablation zone. Multivariate analysis revealed that protruding from the ablation zone was the only significant factor for LTP (hazard ratio, 7.09; 95% confidential interval, 2.26-22.3; P < 0.001). CONCLUSION: Some HCC were assessed as incomplete ablation on the CT fusion images, although considered completely ablated on side-by-side images at the time of treatment, and incomplete ablation was revealed to be the only independent risk factor for LTP. The CT fusion imaging enables quantitative and accurate evaluation of treatment effect of RFA.

Elderly onset age is associated with low efficacy of first anti-tumor necrosis factor treatment in patients with inflammatory bowel disease.

The outcomes of patients with elderly onset (EO) inflammatory bowel disease (IBD) treated with anti-tumor necrosis factor (TNF) remains uncertain. The present study evaluated the efficacy and safety of anti-TNF treatment for bio-naïve EO-IBD. Elderly patients were defined as those 60 years and older, and further divided into those with EO (Elderly-EO) and those with non-elderly onset (Elderly-NEO). A total of 432 bio-naïve patients were enrolled in this multicenter observational study, comprising 55 with Elderly-EO (12.7%), 25 with Elderly-NEO (5.8%), and 352 under age 60 (Non-elderly, 81.5%). After 52 weeks of anti-TNF treatment, clinical and steroid-free remission rates were significantly lower in Elderly-EO than in Non-elderly (37.7% and 60.8%; P = 0.001, and 35.9% and 57.8%; P = 0.003, respectively), and comparable between Elderly-NEO and Non-elderly. Multivariate analysis revealed that elderly onset was a significant factor for both clinical remission (OR, 0.49, 95% CI 0.25-0.96) and steroid-free remission (OR, 0.51, 95% CI 0.26-0.99) after 52 weeks of anti-TNF treatment. The rate of cumulative severe adverse events was significantly higher in Elderly-EO than in Non-elderly (P = 0.007), and comparable between Elderly-NEO and Non-elderly. In conclusion, anti-TNF treatment for bio-naïve EO-IBD may be less effective and raise safety concerns.

Primary adenosquamous carcinoma of the liver detected during cancer surveillance in a patient with primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is associated with significant risk for hepatobiliary cancers. Primary hepatic adenosquamous carcinoma (ASC), a rare subtype of cholangiocarcinoma, is composed of both adenocarcinoma and squamous cell carcinoma components. We herein report the case of a patient with PSC who was diagnosed with ASC of the liver during cancer surveillance. A 74-year-old male patient was diagnosed with PSC based on blood chemistry and magnetic resonance cholangiopancreatography findings, and regular surveillance for hepatobiliary cancers was initiated. Four years later, the level of carbohydrate antigen 19-9 rapidly increased, and abdominal imaging studies revealed a cystic mass, 40 mm in diameter, containing a solid component in the right liver lobe. Right lobectomy was performed with a pre-operative diagnosis of cholangiocarcinoma; however, the definitive diagnosis was ASC based on the presence of adenocarcinoma and squamous cell carcinoma components in the resected tumor. The patient did not receive post-operative chemotherapy, but was alive for more than 4 years without recurrence at last follow-up. The present case illustrates that regular surveillance and curative resection might achieve long-term survival in hepatic ASC, which has a poor prognosis.

Efficacy of vonoprazan for the prevention of bleeding after gastric endoscopic submucosal dissection with continuous use of antiplatelet agents.

Background Post-procedural bleeding, after gastric endoscopic submucosal dissection (ESD) for high risk thromboembolic cases that require continuous antiplatelet therapy, is challenging. Its incidence rate is > 20 % among those using conventional antacids. We evaluated the efficacy of perioperative management with vonoprazan to prevent post-ESD bleeding. Materials and methods This was a multicenter prospective interventional trial conducted at 10 Japanese referral centers. Patients who regularly used antiplatelet agents (aspirin or thienopyridine derivatives, etc.) and who required continuous antithrombotic medication due to high thromboembolic risk were enrolled. They underwent gastric ESD with continuous aspirin therapy. Oral administration of vonoprazan (20 mg daily) was started from the day of ESD and continued for 28 days. The primary end point was the incidence of post-ESD bleeding. The sample size was 50 patients, and vonoprazan was considered to be effective when the upper threshold of the 95 % confidence interval (CI) for post-ESD bleeding did not exceed 20 %. Results Although 50 patients were enrolled, one patient withdrew consent. Therefore, 49 patients were included in the analysis. One patient who used aspirin and clopidogrel experienced bleeding 11 days after ESD. The overall post-ESD bleeding rate was 2.0 % (1/49; 95 %CI 0.4-10.7 %). Thromboembolic events were not observed. One case of ESD-associated adverse events (perforation) and one case of drug-associated adverse events (drug eruption, possibly due to vonoprazan) were observed. Conclusions Vonoprazan may be efficacious for preventing post-ESD bleeding in patients using continuous antiplatelet therapy, warranting further comparative study to definitively test the effectiveness of the drug.

Real-time assessment of video images for esophageal squamous cell carcinoma invasion depth using artificial intelligence.

BACKGROUND: Although optimal treatment of superficial esophageal squamous cell carcinoma (SCC) requires accurate evaluation of cancer invasion depth, the current process is rather subjective and may vary by observer. We, therefore, aimed to develop an AI system to calculate cancer invasion depth. METHODS: We gathered and selected 23,977 images (6857 WLI and 17,120 NBI/BLI images) of pathologically proven superficial esophageal SCC from endoscopic videos and still images of superficial esophageal SCC taken in our facility, to use as a learning dataset. We annotated the images with information [such as magnified endoscopy (ME) or non-ME, pEP-LPM, pMM, pSM1, and pSM2-3 cancers] based on pathologic diagnosis of the resected specimens. We created a model using a convolutional neural network. Performance of the AI system was compared with that of invited experts who used the same validation video set, independent of the learning dataset. RESULTS: Accuracy, sensitivity, and specificity with non-magnified endoscopy (ME) were 87%, 50%, and 99% for the AI system and 85%, 45%, 97% for the experts. Accuracy, sensitivity, and specificity with ME were 89%, 71%, and 95% for the AI system and 84%, 42%, 97% for the experts. CONCLUSIONS: Most diagnostic parameters were higher when done by the AI system than by the experts. These results suggest that our AI system could potentially provide useful support during endoscopies.

A prospective multicenter observational study evaluating the risk of periendoscopic events in patients using anticoagulants: the Osaka GIANT Study.

Background and study aims An increasing number of patients have been using anticoagulants including anti-vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs); however, in patients using anticoagulants, limited data are available with regard to the risks of gastrointestinal bleeding and thromboembolic events during the peri-endoscopic period. We aimed to evaluate the peri-endoscopic bleeding and thrombotic risks in patients administered VKAs or DOACs. Patients and methods Consecutive patients using anticoagulants who underwent endoscopic biopsy, mucosal resection, or submucosal dissection were prospectively enrolled across 11 hospitals. The primary outcome assessed was difference in incidence of post-procedural gastrointestinal bleeding in patients using VKAs and DOACs. Duration of hospitalization and peri-procedural thromboembolic events were also compared. Results We enrolled 174 patients using VKAs and 37 using DOACs. In total, 16 patients using VKA were excluded from the analysis because of cancellation of endoscopic procedures and contraindications to the use of DOACs; 128 (81 %) patients using VKAs and 17 (46 %) using DOACs received heparin-bridging therapy (HB). The rate of post-procedural gastrointestinal bleeding in DOAC users was similar to that in VKA users (16.2 % vs. 16.4 %, P  = 1.000). Duration of hospitalization was significantly longer in patients using VKAs than in those using DOACs (median 15 vs. 7 days, P  < 0.0001). Myocardial infarction occurred during pre-endoscopic HB in one patient using VKAs. Conclusion DOAC administration showed similar post-procedural gastrointestinal bleeding risk to VKA administration in patients undergoing endoscopic procedures, but it shortened the hospital stay.

Disturbed gastrointestinal motility and decreased interstitial cells of Cajal in diabetic db/db mice.

BACKGROUND AND AIM: Diabetes mellitus (DM) often causes gastrointestinal dysmotility. Interstitial cells of Cajal (ICC), which express c-kit receptor tyrosine kinase (KIT), are considered the pacemaker cells for gastrointestinal movement. The present study was designed to determine the role of ICC in the pathogenesis of gastroenteropathy in type 2 DM. METHODS: We examined C57BL/KsJ-db/db mice as a model for type 2 DM. Gastrointestinal motility was evaluated by measuring gastric emptying, whole gut transit time, and isometric tension of the isolated small intestine. The area of KIT-positive cells in the gastrointestinal tract was examined by image analysis of fluorescent immunohistochemistry. The mRNA expression of KIT ligand, stem cell factor (SCF), in the gastrointestinal tract was quantified by real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Compared with 12-week-old db/+m control mice, diabetic db/db mice of the same age exhibited delayed gastric emptying, prolonged whole gut transit time, irregular frequency of isometric tension in the small intestine, smaller areas of KIT-positive cells in the antrum, small intestine, and colon, and lower mRNA expression levels of SCF in the small intestine and colon. CONCLUSIONS: We demonstrated disturbed gastrointestinal motility in db/db mice with reduced areas of ICC and expression of SCF. Our results suggest the involvement of ICC in the gastroenteropathy of type 2 DM.