Efficacy of texture and color enhancement imaging for the visibility and diagnostic accuracy of non-polypoid colorectal lesions.

Objective: A newly launched endoscopy system (EVIS X1, CV-1500; Olympus) is equipped with texture and color enhancement imaging (TXI). We aimed to investigate the efficacy of TXI for the visibility and diagnostic accuracy of non-polypoid colorectal lesions. Methods: We examined 100 non-polypoid lesions in 42 patients from the same position, angle, and distance of the view in three modes: white light imaging (WLI), narrow-band imaging (NBI), and TXI. The primary outcome was to compare polyp visibility in the three modes using subjective polyp visibility score and objective color difference values. The secondary outcome was to compare the diagnostic accuracy without magnification. Results: Overall, the visibility score of TXI was significantly higher than that of WLI (3.7 ± 1.1 vs. 3.6 ± 1.1; p = 0.008) and lower than that of NBI (3.7 ± 1.1 vs. 3.8 ± 1.1; p = 0.013). Color difference values of TXI were higher than those of WLI (11.5 ± 6.9 vs. 9.1 ± 5.4; p < 0.001) and lower than those of NBI (11.5 ± 6.9 vs. 13.1 ± 7.7; p = 0.002). No significant differences in TXI and NBI (visibility score: 3.7 ± 1.0 vs. 3.8 ± 1.1; p = 0.833, color difference values: 11.6 ± 7.1 vs. 12.9 ± 8.3; p = 0.099) were observed for neoplastic lesions. Moreover, the diagnostic accuracy of TXI was significantly higher than that of NBI (65.5% vs. 57.6%, p = 0.012) for neoplastic lesions. Conclusions: TXI demonstrated higher visibility than that of WLI and lower than that of NBI. Further investigations are warranted to validate the performance of the TXI mode comprehensively.

Comparison of remimazolam and midazolam for sedation during colonoscopy in Japanese patients: A propensity score matching analysis.

Objectives: To compare the efficacy and safety of sedation with midazolam and remimazolam for colorectal endoscopy. Methods: This single-center, two-arm, post-hoc analysis of the REM-IICTJP01 study investigated the efficacy and safety of remimazolam for gastrointestinal endoscopic sedation. We enrolled 40 and 208 patients who underwent colonoscopy under remimazolam and midazolam sedation, respectively, during the same period. The primary outcome was the time from the end of the colonoscopy until discharge. The secondary outcomes included the time from the end of the colonoscopy until awakening, dosage, and adverse events. Propensity score matching was employed to eliminate the effect of confounding factors. Results: Thirty-seven patients in each group were matched. After propensity matching, the time to awakening after colonoscopy was 28.0 (13.0-37.0) min in the midazolam group and 0 (0-0) min in the remimazolam group; moreover, the time till discharge was 40.0 (35.0-46.5) min in the midazolam group and 0 (0-5.0) min in the remimazolam group, both of which were significantly shorter in the remimazolam group (p < 0.01). The number of additional doses was 0 (0-0) and 2 (1-3) in the midazolam and remimazolam groups, respectively. The total dose was 2.0 (2.0-3.5) and 6.0 (5.0-7.0) mg in the midazolam and remimazolam groups, respectively. Conclusions: Remimazolam yielded significantly faster times to awakening and discharge safely compared to midazolam.

Safety and efficacy of underwater endoscopic mucosal resection for 10-20 mm colorectal serrated lesions (SEA CLEAR study).

BACKGROUND AND AIMS: Colorectal serrated lesions (SLs) are precursors of colorectal carcinoma via the serrated neoplasia pathway. However, the success rate of endoscopic resection of large SLs is low. Therefore, this study aimed to determine the safety and efficacy of underwater endoscopic mucosal resection (UEMR) for SLs sized 10-20 mm. METHODS: This two-center prospective observational study included patients with at least one SL sized 10-20 mm. We resected the SLs by UEMR and performed tattooing at the resection site. Surveillance colonoscopy was performed 12 months postoperatively to evaluate local recurrence. The primary outcome was the complete resection rate of UEMR, which was defined as en bloc resection with no serrated tissue in the four marginal biopsies and histologically negative margins. RESULTS: UEMR was performed for 65 SLs in 58 patients, with a median lesion size of 14 mm. The en bloc, R0 resection, and complete resection rates were 87.7% (57/65), 61.5% (40/65), and 60.0% (39/65), respectively. Adverse events included 1 (1.5%) immediate bleeding and 1 (1.5%) delayed perforation. Surveillance colonoscopy was performed in 50 patients with 57 scars, and the rates of identification for tattoos and scars were 94.7% (54/57) and 100% (57/57), respectively. The recurrence rate was 5.3% (3/57), and all three recurrent lesions were completely resected endoscopically. CONCLUSIONS: This two-center prospective study demonstrated that UEMR for SLs sized 10-20 mm was comparable to previous conventional endoscopic mucosal resection outcomes.

Evaluation of intra- and inter-individual variations in plasma belimumab concentrations in adult patients with systemic lupus erythematosus.

In this study, plasma belimumab concentrations were measured over the course of treatment in systemic lupus erythematosus (SLE) patients on belimumab therapy, and intra- and interindividual variations in plasma belimumab concentration were evaluated. A single-center prospective study was conducted at Oita University Hospital to evaluate trough plasma concentrations over the course of treatment in 13 SLE patients treated with intravenous belimumab. Plasma belimumab concentrations were measured by a validated ultra-high performance liquid chromatography with tandem mass spectrometry method. The median age of the patients was 40 (interquartile range: 35-51) years and the median weight was 51.8 (47.0-58.1) kg. A mean of 9.4 (range: 1-13) blood samples was collected per patient at routine visits. The mean (± SD) plasma belimumab concentration was 33.4 ± 11.9 µg/mL in the patient with the lowest concentration and 170.0 ± 16.6 µg/mL in the patient with the highest concentration, indicating a 5-fold difference between patients. On the other hand, the within-patient coefficient of variation ranged from 7.1% to 35.7%, showing no large variations. No significant correlation was observed between plasma belimumab concentration and belimumab dose (mg/kg) (Spearman's rank correlation coefficient = 0.22, p = .54). Examinations of trough plasma belimumab concentrations over the course of treatment in patients with SLE showed small intraindividual variation but large interindividual variation. Plasma belimumab trough concentration varied widely among patients administered the approved dose.

Endoscopic hand suturing has the potential to reduce bleeding after gastric endoscopic submucosal dissection in patients on antithrombotic agents: Multicenter phase II study.

OBJECTIVES: The risk of postoperative bleeding is high after gastric endoscopic submucosal dissection (ESD) in patients continuously treated with antithrombotic agents (ATAs). The effectiveness of endoscopic hand suturing (EHS) on bleeding after gastric ESD was investigated in patients at high risk of delayed bleeding. METHODS: Patients with neoplasms ≤2 cm who underwent gastric ESD and continued to receive perioperative ATAs were enrolled in this multicenter phase II study. The mucosal defect was closed with EHS after removing the lesion. Postoperative bleeding rate was assessed for 3-4 postoperative weeks as a primary outcome measure. The technical success of EHS and adverse events were also assessed. Based on expected and threshold postoperative bleeding rates of 10% and 25%, respectively, we aimed to include 48 patients in the study. RESULTS: A total of 49 patients were enrolled in the study, and 43 patients were finally registered as the per-protocol set. The postoperative bleeding rate was 7.0% (3/43 patients; the upper limit of one-sided 95% confidence interval [CI], 17.1% and 97.5% CI, 19.1%). The upper limits of the CI were below the threshold value (25%), and the postoperative bleeding rate was below the expected value (10%). The technical EHS success rate, closure maintenance rate on postoperative day 3, and postoperative subclinical bleeding rate were 100%, 83%, and 2%, respectively. No severe adverse events related to EHS were observed. CONCLUSIONS: Endoscopic hand suturing may prevent postoperative bleeding in patients undergoing gastric ESD while being treated continuously with ATAs (UMIN000038140).

Randomized Controlled Trial of Remimazolam Compared with Placebo in Japanese Patients Undergoing Colonoscopy: A Phase III, Investigator-Initiated Trial.

INTRODUCTION: We conducted an investigator-initiated clinical trial in which remimazolam was used to achieve sedation in patients undergoing colonoscopies. METHODS: This multicenter, double-blind, placebo-controlled, phase III investigator-initiated trial included patients who underwent colonoscopy under sedation with remimazolam (initial dose: 3 mg; additional dose: 1 mg) or normal saline (placebo). The primary endpoint of the study was the successful sedation rate during colonoscopy, defined as achieving a Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score of ≤4 before the procedure, maintaining this score throughout colonoscopy, and requiring no more than five additional drug doses per 15 min. RESULTS: The sedation success rate was 95.0% (38/40 patients) in the remimazolam group and 0.0% (0/11 patients) in the placebo group (p < 0.01). The time from the end of procedure to regaining consciousness was 0.0 (interquartile range: 0.0-0.0) min in both groups. The time from the end of the procedure to ambulation was 5.0 (interquartile range: 0.0-10.0) min in the remimazolam group and 0.0 (interquartile range: 0.0-0.0) min in the placebo group (p = 0.02). Serious adverse events were not observed. CONCLUSION: The use of remimazolam to achieve sedation in Japanese patients undergoing colonoscopy was more effective than placebo.

Clinical utility of the forward-viewing echoendoscope in patients after pancreatoduodenectomy: A prospective study.

Background and Objectives: Endoscopic treatment of obstructive jaundice and pancreatitis due to hepaticojejunostomy (H-J), pancreatojejunostomy (P-J) strictures, and tumor recurrence after pancreatoduodenectomy (PD) is technically challenging. Treatment of P-J strictures results in poor outcomes. Although conventional EUS that has an oblique view is not suitable for such patients, forward-viewing EUS (FV-EUS) may become a useful option. This study aimed to evaluate the feasibility and efficacy of FV-EUS in patients who have undergone PD. Methods: Patients with PD who were scheduled to undergo diagnosis and treatment using FV-EUS for H-J or P-J lesions were enrolled in this single-center prospective study. After observation of the P-J and H-J using FV-EUS according to a predetermined protocol, treatment using FV-EUS was performed as needed. Results: A total of 30 patients were enrolled, and FV-EUS was used to observe P-J and H-J in 24 and 28 patients, respectively. The detection rates of P-J and H-J by endoscopy were 50% (12/24) and 96.4% (27/28), respectively, and by EUS were 70.8% (17/24) and 100% (28/28), respectively. Of these, P-J and H-J were found by endoscopy only after EUS observation in 3 and 1 patient, respectively. The success rates of endoscopic treatment using FV-EUS were 66.7% (2/3), 95.2% (20/21), and 25% (1/4) for benign P-J strictures, benign H-J strictures, and tumor recurrence, respectively. Conclusions: Endoscopic treatment using FV-EUS is feasible and effective for patients after PD. Moreover, FV-EUS increases the P-J lesion detection rate by adding EUS observation.

Endoscopic hand suturing using a modified through-the-scope needle holder for mucosal closure after colorectal endoscopic submucosal dissection: Prospective multicenter study (with video).

OBJECTIVES: Endoscopic hand suturing (EHS) is a novel technique for closing a mucosal defect after endoscopic submucosal dissection (ESD). We investigated the technical feasibility of colorectal EHS using a modified flexible through-the-scope needle holder. METHODS: This was a prospective multicenter study conducted at two referral centers between June 2022 and April 2023. This study included colorectal neoplasms 20-50 mm in size located in the sigmoid colon or rectum. A modified flexible through-the-scope needle holder, with an increased jaw width to facilitate needle grasping, was used for colorectal EHS. The primary end-points were sustained closure rate on second-look endoscopy (SLE) performed on postoperative days 3-4 and suturing time for colorectal EHS. Secondary end-points included complete closure rate and delayed adverse events. RESULTS: We enrolled 20 colorectal neoplasms in 20 patients, including four patients receiving antithrombotic agents. The tumor location was as follows: lower rectum (n = 8), upper rectum (n = 2), rectosigmoid colon (n = 4), and sigmoid colon (n = 6), and the median mucosal defect size was 37 mm (range, 21-65 mm). The complete closure rate was 90% (18/20 [95% confidence interval (CI) 68.3-98.8%]), and the median suturing time was 49 min (range, 23-92 min [95% CI 35-68 min]). Sustained closure rate on SLE was 85% (17/20 [95% CI 62.1-96.8%]). No delayed adverse events were observed. CONCLUSION: EHS demonstrated a high sustained closure rate. Given the long suturing time and technical difficulty, EHS should be reserved for cases with a high risk of delayed adverse events.

Low-power pure-cut hot snare polypectomy for colorectal polyps 10-14 mm in size: a multicenter retrospective study.

BACKGROUND AND AIM: Hot snare excision using electrocautery is widely used for large colorectal polyps (>10 mm); however, adverse events occur due to deep thermal injury. Colorectal polyps measuring 10-14 mm rarely include invasive cancer. Therefore, less invasive therapeutic options for this size category are demanding. We have developed hot snare polypectomy with low-power pure-cut current (LPPC HSP), which is expected to contribute to less deep thermal damage and lower risk of adverse events. This study aimed to evaluate the efficacy and safety of LPPC HSP for 10-14 mm colorectal polyps, compared with conventional endoscopic mucosal resection (EMR). METHODS: In this multicenter, retrospective, observational study, clinical outcomes of EMR and LPPC HSP for 10-14 mm nonpedunculated colorectal polyps between January 2021 and March 2022 were compared using propensity score matching. RESULTS: We identified 203 EMR and 208 LPPC HSP cases. After propensity score matching, the baseline characteristics between the groups were comparable, with 120 pairs. The en bloc and R0 resection rates were not significantly different between EMR and LPPC HSP groups (95.8% vs 97.5%, P = 0.72; 90.0% vs 91.7%, P = 0.82). The rates of delayed bleeding and perforation did not differ between the groups. CONCLUSIONS: Compared with conventional EMR, LPPC HSP showed a similar resection ability without an increase in adverse events. These results suggest that LPPC HSP is a safe and effective treatment for 10-14 mm nonpedunculated colorectal polyps.

Clinical outcomes and learning curve of Tip-in endoscopic mucosal resection for 15-25 mm colorectal neoplasms among non-experts.

BACKGROUND AND AIM: Tip-in endoscopic mucosal resection (EMR) has a high en bloc resection rate for large colorectal neoplasms. However, non-experts' performance in Tip-in EMR has not been investigated. We investigated whether Tip-in EMR can be achieved effectively and safely even by non-experts. METHODS: This retrospective study included consecutive patients who underwent Tip-in EMR for 15-25 mm colorectal nonpedunculated neoplasms at a Japanese tertiary cancer center between January 2014 and December 2020. Baseline characteristics, treatment outcomes, learning curve of non-experts, and risk factors of failing self-achieved en bloc resection were analyzed. RESULTS: A total of 597 lesions were analyzed (438 by experts and 159 by non-experts). The self-achieved en bloc resection (69.8% vs 88.6%, P < 0.001) and self-achieved R0 resection (58.3% vs 76.5%, P < 0.001) rates were significantly lower in non-experts with <10 cases of experience than in experts, but not in non-experts with >10 cases. Adverse event (P = 0.165) and local recurrence (P = 0.892) rates were not significantly different between experts and non-experts. Risk factors of failing self-achieved en bloc resection were non-polypoid morphology (OR 3.4, 95% CI 1.6-7.3, P = 0.001), lesions with an underlying semilunar fold (OR 3.6, 95% CI 1.6-7.3, P < 0.001), positive non-lifting sign (OR 3.1, 95% CI 1.2-8.0, P = 0.023), and non-experts with an experience of ≤10 cases (OR 3.6, 95% CI 2.1-6.3, P < 0.001). CONCLUSION: The clinical outcomes of Tip-in EMR for 15-25 mm lesions performed by non-experts were favorable.

Impact of a new dedicated sheath device for tissue sampling of biliary stricture on pathological diagnostic yield: Retrospective study.

Background and study aims Endoscopic transpapillary biliary forceps biopsy (TBFB) is a common method for obtaining specimens from biliary lesions. Its diagnostic yield is unsatisfactory; to overcome this disadvantage, a dedicated sheath has been developed. This study aimed to evaluate the outcomes of conventional TBFB and TBFB with a novel sheath device. Patients and methods Consecutive patients who underwent TBFB between January 2020 and December 2021 were retrospectively evaluated. The rate of obtaining adequate samples, failed attempts at forceps insertion into the bile duct, and sensitivity were compared between the two groups. Results Ninety-two patients who underwent 115 endoscopic retrograde cholangiopancreatographies (76 in the conventional group vs. 39 in the dedicated sheath group) were included. The rates of obtaining adequate samples, failed attempts of the forceps into the bile duct, and sensitivity were 72.4% vs. 89.7% ( P = 0.03), 28.3% vs. 0% ( P < 0.01), and 66.7% vs. 88.9% ( P = 0.02), respectively. Conclusions TBFB with the novel sheath device contributed to improved sensitivity for diagnosis of biliary stricture without insertion of forceps outside the bile duct.

Risk factors for intraoperative and delayed perforation related with gastric endoscopic submucosal dissection.

BACKGROUND AND AIM: Perforation is one of the most important complications of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). Several studies have examined risk factors for intraoperative and delayed perforations, but most were retrospective analyses with small numbers of patients. METHODS: This study represents a secondary analysis of a Japanese multicenter prospective cohort study. We investigated the factors associated with each type of perforation using 9015 patients with 9975 EGCs undergoing ESD between July 2010 and June 2012. RESULTS: Intraoperative perforation occurred in 198 patients (2.2%) with 203 lesions (2.0%), necessitating emergency surgery for four lesions (0.04% [2.0%, 4/203]). Delayed perforation occurred in another 37 patients (0.4%) with 42 lesions (0.4%), requiring emergency surgery for 12 lesions (0.12% [28.6%, 12/42]). Factors showing significant independent correlations with intraoperative perforation were upper or middle third of the stomach; remnant stomach or gastric tube; procedure time ≥100 min; tumor size >35 mm; body mass index (BMI) < 18.5 kg/m2; and ≥72 years. Factors showing significant independent correlations with delayed perforation were procedure time ≥60 min; BMI < 18.5 kg/m2; ≥75 years; ulceration; and tumor size >20 mm. Intraoperative perforation occurred most frequently at the greater curvature in the upper third of the stomach (7.9%), whereas delayed perforation occurred most frequently at the greater curvature in the middle third (1.2%). CONCLUSION: This multicenter prospective cohort study clarified the risk and risk factors of intraoperative and delayed perforation related to ESD for EGCs, providing information to help endoscopists reduce perforation.

Relationship of plasma 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid concentration with OATP1B activity in patients with chronic kidney disease.

Organic anion-transporting polypeptides (OATP)1B are drug transporters mainly expressed in the sinusoidal membrane. Many studies have suggested that OATP1B activity is affected by genetic factor, the uremic toxin 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), and inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Coproporphyrin-I (CP-I) is spotlighted as a highly accurate endogenous substrate of OATP1B. We previously reported a positive correlation between plasma CMPF and CP-I concentrations in patients with chronic kidney disease (CKD). The present study evaluated the impact of genetic polymorphisms, CMPF, IL-6, TNF-α, and estimated glomerular filtration rate (eGFR) on individual differences in OATP1B activity in patients with CKD. Seventy-three patients with CKD who received kidney transplant at least 3 months earlier were analyzed. Plasma CP-I concentration was higher in OATP1B1*15 carriers than in non-carriers. In all patients, CP-I did not correlate significantly with CMPF, IL-6, TNF-α, or eGFR. However, when the dataset was cut off at CMPF concentration of 8 and 7 µg/mL, 4 µg/mL, 3 µg/mL or 2 µg/mL, CMPF correlated positively with CP-I, and correlation coefficient tended to be higher as plasma CMPF concentration was lower. In conclusion, OATP1B1*15 impacted OATP1B activity in patients with CKD, but IL-6 and TNF-α did not. However, the impact of CMPF on OATP1B activity was limited to low CMPF concentrations, and the effect could be saturated at high concentrations. When prescribing an OATP1B substrate drug for patients with CKD, the OATP1B1*15 carrier status and plasma CMPF concentration may need to be considered to decide the dose regimen.

Current status of preoperative endoscopic biliary drainage for distal and hilar biliary obstruction.

The purpose of preoperative biliary drainage (PBD) is to reduce complications during the perioperative period. The extrahepatic bile duct comprises distal and hilar bile ducts and assessing the need for PBD must be considered separately for each duct, as surgical procedures and morbidities vary. The representative disease-causing distal bile duct obstruction is pancreatic cancer. A randomized controlled trial has revealed that PBD carries the risk of recurrent cholangitis and pancreatitis before surgery, thus eliminating the need for PBD when early surgery is feasible. However, neoadjuvant therapy has seen a rise in recent years, resulting in longer preoperative waiting periods and an increased demand for PBD. In such cases, metal stents are preferable to plastic stents due to their lower stent occlusion rates. When endoscopic transpapillary biliary drainage (EBD) is not viable, endoscopic ultrasound-guided biliary drainage may be a suitable substitute. In the hilar bile duct, the representative disease-causing obstruction is hilar cholangiocarcinoma. PBD's necessity has long been a subject of contention. In spite of earlier criticisms of routine PBD, recent views have emerged recommending PBD, particularly when major hepatectomy is required, to prevent postoperative liver failure. Given the risk of tumor seeding associated with percutaneous transhepatic biliary drainage, EBD is preferable. Nevertheless, as its shortcomings involve recurrent cholangitis until surgery due to stent or tube obstruction, it is necessary to seek out novel approaches to circumvent complications. In this review we summarize the current evidence for PBD in patients with distal and hilar biliary obstruction.

Usefulness of Belimumab in Adult Patients With Systemic Lupus Erythematosus Evaluated Using Single Indexes: A Meta-Analysis and Systematic Review.

Background: Belimumab is the first antibody drug approved for systemic lupus erythematosus (SLE), and is a fully human monoclonal antibody that inhibits soluble B lymphocyte stimulator protein. In clinical trials, a composite index was used to assess efficacy of belimumab. However, clinical guidelines on SLE treatment currently use single efficacy indexes. Objective: The main objective of this study was to perform a meta-analysis to evaluate the efficacy of belimumab utilizing single indexes used in routine clinical practice, rather than the composite efficacy index used in clinical trials during the development phase. As a secondary endpoint, safety was also evaluated. Methods: Several databases were searched to identify reports published up to December 1, 2021 on randomized controlled trials examining the efficacy of belimumab in adult patients with SLE. From the clinical trial data, efficacy was evaluated using single indexes including the SLE Disease Activity Index (SLEDAI), British Isles Lupus Assessment Group Index, and Physician Global Assessment. Safety was also assessed. Data were synthesized and analyzed using Review Manager 5.4. This study protocol was registered in the UMIN Clinical Trials Registry (Registration number: UMIN000052846). Results: The search identified 12 reports that met the inclusion criteria. Five reports were included in efficacy evaluation and 9 in safety evaluation. The primary endpoint was SLEDAI. Significantly more belimumab-treated patients achieved a ≥4-point reduction in SLEDAI (relative risk 1.28; 95% confidence interval, 1.16-1.40; P < 0.00001) compared with placebo. Other efficacy endpoints were also improved significantly in the belimumab group. No difference in safety was found between belimumab and placebo. Conclusions: The present meta-analysis evaluating clinical trial data using various single indexes recommended by clinical guidelines for SLE verifies that addition of belimumab to standard of care is efficacious for moderate-to-severe SLE.