Diagnostic Value of Adding Magnifying Chromoendoscopy to Magnifying Narrow-Band Imaging Endoscopy for Colorectal Polyps.

BACKGROUND & AIMS: This study examined the additional value of magnifying chromoendoscopy (MCE) on magnifying narrow-band imaging endoscopy (M-NBI) in the optical diagnosis of colorectal polyps. METHODS: A multicenter prospective study was conducted at 9 facilities in Japan and Germany. Patients with colorectal polyps scheduled for resection were included. Optical diagnosis was performed by M-NBI first, followed by MCE. Both diagnoses were made in real time. MCE was performed on all type 2B lesions classified according to the Japan NBI Expert Team classification and other lesions at the discretion of endoscopists. The diagnostic accuracy and confidence of M-NBI and MCE for colorectal cancer (CRC) with deep invasion (≥T1b) were compared on the basis of histologic findings after resection. RESULTS: In total, 1173 lesions were included between February 2018 and December 2020, with 654 (5 hyperplastic polyp/sessile serrated lesion, 162 low-grade dysplasia, 403 high-grade dysplasia, 97 T1 CRCs, and 32 ≥T2 CRCs) examined using MCE after M-NBI. In the diagnostic accuracy for predicting CRC with deep invasion, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for M-NBI were 63.1%, 94.2%, 61.6%, 94.5%, and 90.2%, respectively, and for MCE they were 77.4%, 93.2%, 62.5%, 96.5%, and 91.1%, respectively. The sensitivity was significantly higher in MCE (P < .001). However, these additional values were limited to lesions with low confidence in M-NBI or the ones diagnosed as ≥T1b CRC by M-NBI. CONCLUSIONS: In this multicenter prospective study, we demonstrated the additional value of MCE on M-NBI. We suggest that additional MCE be recommended for lesions with low confidence or the ones diagnosed as ≥T1b CRC. Trials registry number: UMIN000031129.

Accurate Evaluation of Residual Common Bile Duct Stones by Endoscopic Ultrasound: A Two-Step Check Method for Residual Stone Clearance.

BACKGROUND/AIMS: Residual common bile duct (CBD) stones occasionally become symptomatic after stone removal with endoscopic retrograde cholangiopancreatography (ERCP) upon removal of the endoscopic biliary stent (EBS). An accurate evaluation of residual stones before stent removal is necessary. This study evaluated a new two-step check method using endoscopic ultrasound (EUS) for the detection of residual stones after ERCP stone removal. METHODS: Fifty-six patients who underwent CBD stone removal and EBS placement were prospectively enrolled. Residual stones were evaluated by the check method. EBS was removed at the time of the check method or at a later time of residual stone removal. The primary outcome was to evaluate the efficacy of this check method. RESULTS: Residual CBD stone/sludge was detected in 20 of 56 patients (35.7%; stones: 28.6%, sludge: 7.1%) by the check method and removed by the ERCP procedure at a later time. After stent and final stone removal, patients were followed for an average of 211 days; cholangitis recurred in only 1.8% of patients. There were no adverse events associated with the check method. Temporary EBS prevented the recurrence of cholangitis by residual stone and caused no adverse events in the pancreatobiliary tract until the two-step check method (median, 113 days; range, 17-232 days). CONCLUSION: The new check method may be ideal and feasible for EBS removal because recurrences are very rare when a clear CBD has been verified, and an additional ERCP procedure is also possibly avoided.

Postpolypectomy bleeding of colorectal polyps in patients with continuous warfarin and short-term interruption of direct oral anticoagulants.

BACKGROUND AND AIMS: Postpolypectomy bleeding (PPB) is the most common adverse event after colorectal polypectomy. Use of anticoagulants is an important risk factor for PPB. This study aimed to evaluate PPB in patients receiving treatment with warfarin and direct oral anticoagulants (DOACs). METHODS: Between August 2017 and July 2019, 5449 patients with 12,601 polyps who underwent endoscopic snare resection of colorectal polyps were enrolled. Endoscopic snare resection was performed in patients receiving continuous warfarin (C-warfarin) and in patients who experienced 1 day cessation of (O-) of DOACs in accordance with the Japanese Gastroenterological Endoscopy Society guidelines. RESULTS: The PPB rate in the group receiving anticoagulants was statistically higher than that in the group without anticoagulants (8.5% [33/387] vs 1.2% [63/5,062], respectively; P < .001). By multivariate logistic regression analysis, male gender (odds ratio [OR], 2.17; P = .007), warfarin (OR, 4.64; P < .001), DOACs (OR, 6.59; P < .001), and multipolyp removal (OR, 1.77; P = .007) were significant risk factors for PPB. PPB was observed in 9 and 21 patients in the C-warfarin and O-DOACs groups, respectively: C-warfarin (8.0% [9/113]), O-dabigatran (6.1% [2/33]), O-rivaroxaban (14.8% [9/61]), O-apixaban (9.8% [9/92]), and O-edoxaban (1.8% [1/56]). The PPB rate with the O-edoxaban group was significantly lower than that with the O-rivaroxaban group (P < .05). CONCLUSIONS: Use of anticoagulant therapy was an independent risk factor for PPB. The rates of PPB in patients receiving C-warfarin and O-DOACs were also higher than those in patients not receiving anticoagulants. Edoxaban may be safe through short-term withdrawal in patients undergoing endoscopic snare resection of colorectal polyps.

Water-assisted colonoscopy: an international modified Delphi review on definitions and practice recommendations.

BACKGROUND AND AIMS: Since 2008, a plethora of research studies has compared the efficacy of water-assisted (aided) colonoscopy (WAC) and underwater resection (UWR) of colorectal lesions with standard colonoscopy. We reviewed and graded the research evidence with potential clinical application. We conducted a modified Delphi consensus among experienced colonoscopists on definitions and practice of water immersion (WI), water exchange (WE), and UWR. METHODS: Major databases were searched to obtain research reports that could potentially shape clinical practice related to WAC and UWR. Pertinent references were graded (Grading of Recommendations, Assessment, Development and Evaluation). Extracted data supporting evidence-based statements were tabulated and provided to respondents. We received responses from 55 (85% surveyed) experienced colonoscopists (37 experts and 18 nonexperts in WAC) from 16 countries in 3 rounds. Voting was conducted anonymously in the second and third round, with ≥80% agreement defined as consensus. We aimed to obtain consensus in all statements. RESULTS: In the first and the second modified Delphi rounds, 20 proposed statements were decreased to 14 and then 11 statements. After the third round, the combined responses from all respondents depicted the consensus in 11 statements (S): definitions of WI (S1) and WE (S2), procedural features (S3-S5), impact on bowel cleanliness (S6), adenoma detection (S7), pain score (S8), and UWR (S9-S11). CONCLUSIONS: The most important consensus statements are that WI and WE are not the same in implementation and outcomes. Because studies that could potentially shape clinical practice of WAC and UWR were chosen for review, this modified Delphi consensus supports recommendations for the use of WAC in clinical practice.

Relationship between colonic diverticulosis and colon neoplasms in Japanese patients.

BACKGROUND AND AIM: Colonic diverticulosis (CD) has been reported to be associated with presence of colon neoplasms (CNs) in Western patients, since most of the associated risk factors are common between them. However, such correlation has not been fully investigated in Asian patients. In this study, the association of CNs with CD was evaluated in a multicenter investigation. METHODS: We enrolled 5633 patients who underwent both colonoscopy and esophagogastroduodenoscopy due to annual follow-up, screening for positive occult blood testing and abdominal symptoms between January 2016 and December 2017 at three institutions. The relationship between the presence of CNs and CD was investigated, and predictors for presence of CNs were determined by multivariate logistic analysis. RESULTS: The enrolled patients consisted of 1799 (31.9%) with CD (average age 70.0 years, male 64.0%) and 3834 without CD (66.0 years, male 52.9%), with the prevalence of CNs in those groups 46.6% and 44.2%, respectively (P = 0.090). Predictors for early colon cancer were shown to be age (OR 1.02, 95% CI 1.01-1.04, P = 0.010), laxatives use (OR 1.76, 95% CI 1.17-2.64, P = 0.007), gastric neoplasms (OR 2.16, 95% CI 1.23-3.81, P = 0.008), and CD (OR 1.64, 95% CI 1.16-2.31, P = 0.005). Early colon cancer in the distal colon was most frequently detected in patients with right-sided CD (RR 2.50, P = 0.001). CONCLUSION: In Japanese patients, early colon cancer was more frequently found in those with as compared to those without CD. The presence of CD may be an important indicator for an index colonoscopy examination to detect colon cancer. (Clinical-trial-registry: UMIN000038985).

The effect of anticoagulants on delayed bleeding after colorectal endoscopic submucosal dissection.

BACKGROUND AND AIMS: The withdrawal of antithrombotic therapy from patients at high risk of thromboembolism is controversial. Previously, treatment with anticoagulants, such as warfarin and dabigatran, was recommended for heparin bridge therapy (HBT) during endoscopic submucosal dissection (ESD). However, HBT is associated with a high risk of bleeding during and after ESD. This study aimed to investigate the clinical outcomes of colorectal ESD in patients treated with warfarin and direct oral anticoagulants (DOAC). METHODS: This study included 412 patients with superficial colorectal neoplasms that were resected by ESD between June 2010 and June 2018. The patients were classified into two groups: without antithrombotics (n = 286) and with anticoagulants (n = 51). The anticoagulants group was further divided into two groups: warfarin (n = 26) and DOAC (n = 25). RESULTS: Among all patients, delayed bleeding occurred in 35 (8.5% [35/412]) patients. The bleeding rate in the anticoagulants group (11.8% [6/51]) was higher than that in the group without antithrombotics (6.6% [19/286]), but the difference was not statistically significant (P = 0.240). The bleeding rate in the DOAC group (16.0% [4/25]) was higher than that in the warfarin group (7.7% [2/26]), but the difference was not statistically significant (P = 0.419). All delayed bleeding was successfully managed with endoscopic hemostasis. Thromboembolic events were not observed in any patients. CONCLUSIONS: The bleeding rate with anticoagulants was relatively high. However, all bleeding events with anticoagulants were minor and clinically controllable. Colorectal ESD with DOAC and warfarin may be feasible and acceptable.

Endoscopic transpapillary gallbladder drainage for acute cholecystitis is feasible for patients receiving antithrombotic therapy.

OBJECTIVES: Patients with acute cholecystitis receiving antithrombotic therapy (ATT) have an increased risk of bleeding complications during surgery and percutaneous drainage. Endoscopic transpapillary gallbladder drainage (ETGBD) is recommended for such cases; however, evidence is limited. To investigate this issue further, we performed a retrospective multicenter study. METHODS: One hundred thirty patients with acute cholecystitis who underwent ETGBD were enrolled. They were divided into an ATT group (continuation of ATT on the day of the procedure and/or heparin substitution) and a Non-ATT group (discontinuation or no use of ATT). The primary outcome was bleeding complication rate, and the secondary outcomes were technical success rate, clinical success rate and total complication rate. RESULTS: Eighty-three patients were enrolled in the ATT group, and 47 were enrolled in the Non-ATT group. In the ATT group, 42.2% continued multi-agent ATT. No bleeding complications occurred in either group. There were no significant differences between the ATT and Non-ATT groups in the technical success rate (84.3% vs 89.4%, P = 0.426 respectively) or the clinical success rate (97.1% vs 100%, P = 0.259, respectively). The overall early complication rate was 3.1% (4/130): mild pancreatitis (n = 3) and cholangitis (n = 1). Stent dysfunction was found in 10.9% of patients (at 196 days on average), and the 12-month stent patency rate was 69.0%. CONCLUSIONS: No significant difference was found in the bleeding complication rate between ETGBD with and without ATT. ETGBD may be an ideal drainage method for patients with acute cholecystitis receiving ATT.

Saline-pocket endoscopic submucosal dissection for superficial colorectal neoplasms: a randomized controlled trial (with video).

BACKGROUND AND AIMS: Colorectal endoscopic submucosal dissection (ESD) is a time-consuming procedure because of the technical difficulty. The newly developed saline-pocket ESD (SP-ESD) provides a clearer view and better traction of the submucosal layer compared with the standard ESD with gas insufflation (S-ESD). This study aimed to prospectively compare the efficacy and safety between S-ESD and SP-ESD in patients with superficial colorectal neoplasms (SCNs). METHODS: From April 2017 to November 2018, 95 patients with SCNs ≥20 mm in diameter were prospectively and randomly enrolled. Four patients were excluded because of an incomplete ESD procedure. Patients were finally allocated to 2 groups, S-ESD with 45 patients and SP-ESD with 46 patients. The primary outcome was dissection speed. Secondary outcomes were ESD procedure time, en bloc and complete resection rates, perforation rate, and adverse effects. RESULTS: Median dissection speed was significantly faster in the SP-ESD than the S-ESD group (20.1 mm2/min [range, 17.3-28.1] vs 16.3 mm2/min [range, 11.4-19.8]; P < .001). Median procedure time was significantly shorter in the SP-ESD than the S-ESD group (29.5 minutes [range, 22.3-44] vs 41 minutes [range, 31-55]; P < .001). The en bloc and complete resection rates were 100% in both groups. No perforations occurred among patients. The volume of saline solution used in the SP-ESD group was significantly greater than that in the S-ESD group (200 mL [range, 120-250] vs 150 mL [range, 100-200]; P = .016). CONCLUSIONS: SP-ESD improved dissection speed and procedure time compared with S-ESD. SP-ESD may be an alternative method for resection of SCNs. (Clinical trial registration number: UMIN 000026317.).

Water-pocket endoscopic submucosal dissection for superficial gastric neoplasms (with video).

BACKGROUND AND AIMS: During endoscopic submucosal dissection (ESD), a clear view is essential for precise dissection of the appropriate submucosal layer. Some advantages have been reported for underwater techniques of endoscopic resection in comparison with the gas insufflation method. We have developed a new ESD method with the creation of a local water pocket (WP) that provides a clear view in the dissection field. Therefore, we aimed to investigate the feasibility and safety of WP-ESD for superficial gastric neoplasms. METHODS: We prospectively recruited 50 patients with gastric neoplasms (early gastric cancer or gastric adenomas) between April 2017 and December 2017. Among them, 48 patients were treated with the WP-ESD technique. The patients undergoing WP-ESD were compared with 48 patients treated with standard ESD (S-ESD) who were selected by propensity score matching. The primary outcome was the ESD procedure time. RESULTS: Total procedure time was significantly shorter in the WP-ESD group than in the S-ESD group (median [interquartile range], 27.5 [19-45] minutes vs 41 [29.8-69] minutes; P < .001). Similarly, the dissection speed was significantly greater in the WP-ESD group than in the S-ESD group (median [interquartile range], 22.5 [16.8-35.3] mm2/min vs 17.3 [12.7-22.1] mm2/min; P < .001). The rates of complete en bloc resection in the WP-ESD group and the S-ESD group were 97.9% and 95.8%, respectively (P > .99). There were no perforations in either group. CONCLUSION: WP-ESD was associated with a shorter procedure time than S-ESD. WP-ESD may provide an alternative method for resection of superficial gastric neoplasms. (Clinical trial registration number: UMIN 000030266.).

Role of EUS combined with a newly modified scoring system to detect pancreatic high-grade precancerous lesions.

Backgrounds and Objectives: Although pancreatic cancer (PC) has an extremely poor prognosis, the 5-year survival rate of patients with pancreatic high-grade precancerous lesion without invasive carcinoma (PHP) is favorable. PHP diagnosis and identification of patients requiring intervention are needed. We aimed to validate a modified PC detection scoring system regarding its detection ability for PHP and PC in the general population. Subjects and Methods: We modified an existing PC detection scoring system that incorporates low-grade risk (LGR) factors (family history, presence of diabetes mellitus [DM] or worsening DM, heavy drinking, smoking, stomach symptoms, weight loss, and pancreatic enzyme) and high-grade risk (HGR) factors (new-onset DM, familial PC, jaundice, tumor biomarkers, chronic pancreatitis, intraductal papillary mucinous neoplasm, cysts, hereditary PC syndrome, and hereditary pancreatitis). Each factor was scored as one point; LGR score ≥3 points and/or HGR score ≥1 point (positive scores) were indicative of PC. The newly modified scoring system incorporated main pancreatic duct dilation as an HGR factor. The PHP diagnosis rate using this scoring system combined with EUS was prospectively analyzed. Results: Among 544 patients with positive scores, 10 had PHP. The diagnosis rates were 1.8% for PHP and 4.2% for invasive PC. Although the number of LGR and HGR factors tended to increase with PC progression, none of the individual factors were significantly different between patients with PHP and those without lesions. Conclusion: The newly modified scoring system evaluating multiple factors associated with PC could potentially identify patients with higher risk of PHP or PC.

Randomized, sham-controlled, clinical trial of repetitive transcranial magnetic stimulation for patients with Alzheimer's dementia in Japan.

Background: Several medications have been applied to Alzheimer's dementia patients (AD) but their efficacies have been insufficient. The efficacy and safety of 4 weeks of repetitive transcranial magnetic stimulation (rTMS) in Japanese AD were evaluated in this exploratory clinical trial. Methods: Forty-two patients, aged 60-93 years (average, 76.4 years), who were taking medication (> 6 months) and had Mini-Mental State Examination (MMSE) scores ≤ 25 and Clinical Dementia Rating Scale scores (CDR-J) of 1 or 2, were enrolled in this single-center, prospective, randomized, three-arm study [i.e., 120% resting motor threshold (120% RMT), 90% RMT for the bilateral dorsolateral prefrontal cortex, and Sham]. Alzheimer's Disease Assessment Scale-Japanese Cognitive (ADAS-J cog), Montreal Cognitive Assessment (MoCA-J), Clinical Global Impression of Change (CGIC), Neuropsychiatric inventory (NPI), and EuroQOL 5 Dimensions 5-Level (EQ-5D-5L) were administered. The primary endpoint was the mean change from baseline in the MMSE score (week 4). An active rTMS session involved applying 15 trains bilaterally (40 pulses/train at 10 Hz; intertrain interval, 26 s). Participants received ≥ 8 interventions within the first 2 weeks and at least one intervention weekly in the 3rd and 4th weeks. Full Analysis set (FAS) included 40 patients [120% RMT (n = 15), 90% RMT (n = 13), and Sham (n = 12)]. Results: In the FAS, MMSE, ADAS-J cog, MoCA-J, CDR-J, CGIC, NPI, and EQ-5D-5L scores between the three groups were not significantly different. Two patients were erroneously switched between the 120% RMT and 90% RMT groups, therefore, "as treated" patients were mainly analyzed. Post hoc analysis revealed significant treatment efficacy in participants with MMSE scores ≥ 15, favoring the 120% RMT group over the Sham group. Responder analysis revealed 41.7% of the 120% RMT group had a ≥ 3-point improvement in the ADAS-J cog versus 0% in the Sham group (Fisher's exact test, p = 0.045). The MoCA-J showed the same tendency but was not significant. Efficacy disappeared in week 20, based on the ADAS-cog and MoCA-J. No intervention-related serious adverse events occurred. Conclusion: This paper is the first report of using rTMS in Japanese AD patients. The treatment seems safe and moderate-mild stage AD should be target population of pivotal clinical trial with 120% RMT rTMS.

Cytomegalovirus-associated esophagitis on early esophageal cancer in immunocompetent host: a case report.

BACKGROUND: Cytomegalovirus (CMV)-associated gastrointestinal diseases usually occur in immunocompromised patients; however, few cases has also been described in healthy hosts despite still unclear pathological mechanisms. CMV esophagitis causes various lesions, such as erythematous mucosa, erosions, and ulcers, although such inflammatory changes can appear in superficial esophageal cancers or in surrounding areas. CMV-associated esophagitis has been also reported in cancer patients, but typically in those with advanced and/or terminal stage cancers secondary to chemoradiotherapy-induced immunosuppression or the physiologic demands of the malignancy itself. To our best knowledge, we firstly report on an immunocompetent patient subject to endoscopic submucosal dissection (ESD) for early esophageal cancer complicated with CMV infection. CASE PRESENTATION: A 77-year-old man underwent esophagogastroduodenoscopy (EGD) at a local clinic. EGD revealed a lugol-unstained reddish lesion with whitish exudates in the middle-distal esophagus. Histological evaluation of lesion biopsy revealed atypical squamous epithelium with CMV-positive granulation tissue and aggregates of macrophages, prompting referral for further examination and treatment. Magnifying endoscopy with narrow-band imaging showed an erosive lesion with white moss in a well-demarcated brownish area with irregular mesh-like microvessels. ESD was performed for diagnosis and treatment. Histopathological examination of the resected specimen revealed superficial, moderately differentiated squamous cell carcinoma (SCC) with multiple lymphatic infiltration, and few CMV-positive cells were found in the erosive part of the SCC. Interestingly, he had no underlying conditions to predispose to CMV infection and no risk factors for esophageal cancer, other than gender and age. He received neither steroids for stricture prevention nor antiviral agents post-EGD and 4-month follow-up was negative for esophagitis. CONCLUSIONS: This is the first report of a case of CMV esophagitis superimposed on early esophageal cancer in an immunocompetent host and might provide valuable information for possible adverse effects of steroid administration during ESD procedures, despite their common use for prevention of post-ESD stricture.

An unexpected cause of lower gastrointestinal bleeding.

Although appendiceal bleeding is rare, physicians should keep this finding in mind as a possible cause of bleeding from the right colon because the colonoscopic diagnosis may be essential in determining the need for surgical intervention.