Training in optical diagnosis in community hospitals is associated with improved recognition and treatment of T1 CRC: a prospective multicenter intervention study (OPTICAL II).

BACKGROUND AND STUDY AIMS: Recognition of T1 colorectal cancer (CRC) is difficult, with sensitivities of 35-60% in Western countries. We evaluated the real-life effects of the implementation of the OPTICAL model, a recently developed structured and validated prediction model, in Dutch community hospitals. PATIENTS AND METHODS: In this prospective multicenter study, 383 endoscopists from 40 hospitals were invited to follow an e-learning on the OPTICAL-model, to increase sensitivity for detecting T1CRC in non-pedunculated polyps. Next, real-life recognition of T1CRC was evaluated in 25 hospitals. Endoscopic and pathologic reports of T1CRCs detected during the next year were collected retrospectively while endoscopists were unaware of this evaluation. Sensitivity for recognition of T1CRC, R0 resection rate, and treatment modality were compared for trained vs. untrained endoscopists and for recognised vs. unrecognised T1CRCs. RESULTS: Within 1 year after the e-learning 251 endoscopists detected 528 non-pedunculated T1CRCs, 118 (47%) of the endoscopist were trained. T1CRCs had a median size of 20mm and were mainly located in the distal colorectum (66%). Trained endoscopists recognised T1CRCs more frequently than untrained endoscopists (sensitivity 74% vs. 62%; mixed model analysis OR 2.90; 95%CI 1.54-5.45. A higher rate of R0 resection was seen for T1CRCs detected by trained endoscopists (69% vs. 56%, OR 1.73; 95%CI 1.03-2.91). CONCLUSION: Training in optical recognition of T1CRCs in community hospitals was associated with an increase in sensitivity for T1CRCs. Recognition led to a higher rate of en bloc local excision, resulting in higher R0-resection rates. This may be an important step towards more organ-preserving strategies.

Standardised training for endoscopic mucosal resection of large non-pedunculated colorectal polyps to reduce recurrence (*STAR-LNPCP study): a multicentre cluster randomised trial.

OBJECTIVE: Endoscopic mucosal resection (EMR) is the preferred treatment for non-invasive large (≥20 mm) non-pedunculated colorectal polyps (LNPCPs) but is associated with an early recurrence rate of up to 30%. We evaluated whether standardised EMR training could reduce recurrence rates in Dutch community hospitals. DESIGN: In this multicentre cluster randomised trial, 59 endoscopists from 30 hospitals were randomly assigned to the intervention group (e-learning and 2-day training including hands-on session) or control group. From April 2019 to August 2021, all consecutive EMR-treated LNPCPs were included. Primary endpoint was recurrence rate after 6 months. RESULTS: A total of 1412 LNPCPs were included; 699 in the intervention group and 713 in the control group (median size 30 mm vs 30 mm, 45% vs 52% size, morphology, site and access (SMSA) score IV, 64% vs 64% proximal location). Recurrence rates were lower in the intervention group compared with controls (13% vs 25%, OR 0.43; 95% CI 0.23 to 0.78; p=0.005) with similar complication rates (8% vs 9%, OR 0.93; 95% CI 0.64 to 1.36; p=0.720). Recurrences were more often unifocal in the intervention group (92% vs 76%; p=0.006). In sensitivity analysis, the benefit of the intervention on recurrence rate was only observed in the 20-40 mm LNPCPs (5% vs 20% in 20-29 mm, p=0.001; 10% vs 21% in 30-39 mm, p=0.013) but less evident in ≥40 mm LNPCPs (24% vs 31%; p=0.151). In a post hoc analysis, the training effect was maintained in the study group, while in the control group the recurrence rate remained high. CONCLUSION: A compact standardised EMR training for LNPCPs significantly reduced recurrences in community hospitals. This strongly argues for a national dedicated training programme for endoscopists performing EMR of ≥20 mm LNPCPs. Interestingly, in sensitivity analysis, this benefit was limited for LNPCPs ≥40 mm. TRIAL REGISTRATION NUMBER: NTR7477.

Clip placement to prevent delayed bleeding after colonic endoscopic mucosal resection (CLIPPER): study protocol for a randomized controlled trial.

BACKGROUND: Endoscopic mucosal resection (EMR) for large colorectal polyps is in most cases the preferred treatment to prevent progression to colorectal carcinoma. The most common complication after EMR is delayed bleeding, occurring in 7% overall and in approximately 10% of polyps ≥ 2 cm in the proximal colon. Previous research has suggested that prophylactic clipping of the mucosal defect after EMR may reduce the incidence of delayed bleeding in polyps with a high bleeding risk. METHODS: The CLIPPER trial is a multicenter, parallel-group, single blinded, randomized controlled superiority study. A total of 356 patients undergoing EMR for large (≥ 2 cm) non-pedunculated polyps in the proximal colon will be included and randomized to the clip group or the control group. Prophylactic clipping will be performed in the intervention group to close the resection defect after the EMR with a distance of < 1 cm between the clips. Primary outcome is delayed bleeding within 30 days after EMR. Secondary outcomes are recurrent or residual polyps and clip artifacts during surveillance colonoscopy after 6 months, as well as cost-effectiveness of prophylactic clipping and severity of delayed bleeding. DISCUSSION: The CLIPPER trial is a pragmatic study performed in the Netherlands and is powered to determine the real-time efficacy and cost-effectiveness of prophylactic clipping after EMR of proximal colon polyps ≥ 2 cm in the Netherlands. This study will also generate new data on the achievability of complete closure and the effects of clip placement on scar surveillance after EMR, in order to further promote the debate on the role of prophylactic clipping in everyday clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT03309683 . Registered on 13 October 2017. Start recruitment: 05 March 2018. Planned completion of recruitment: 31 August 2021.

Successful endoscopic treatment of a large impacted gallstone in the duodenum using laser lithotripsy, Bouveret's syndrome: A case report.

BACKGROUND: Bouveret´s syndrome is defined as a gastric outlet obstruction after passage of a gallstone through a fistula into the duodenum. Due to its rarity, the diagnosis of Bouveret's syndrome is often delayed and causes a high morbidity and mortality rate. CASE SUMMARY: A 93-year-old female presented with worsening pain in the right upper abdomen and vomiting. A gastroscopy revealed fluid retention caused by a massive obstructive stone in the bulbus. Endoscopic laser lithotripsy of the impacted stone was planned after multidisciplinary consultation. A Dornier Medilas H Solvo lithotripsy 350 µm laser fiber (10 Hz, 2 Joules) was used to disintegrate the stone into smaller pieces. The patient recovered completely. CONCLUSION: A mechanical obstruction due to a gallstone that has entered the gastrointestinal tract is a complication that appears in 0.3%-0.5% of patients who have cholelithiasis. Stones larger than 2 cm can become impacted in the digestive tract, which occurs mostly in the terminal ileum. In approximately 1%-3% of cases, the stones cause obstruction in the duodenum. This phenomenon is called Bouveret's syndrome. As this condition is mostly observed in elderly individuals with multiple comorbidities, treatment by an open surgical approach is unsuitable. Endoscopic removal is the preferred technique. The benefit of using laser lithotripsy is the precise targeting of energy onto the stone with minimal tissue injury. Endoscopic laser lithotripsy is a safe and feasible treatment option for Bouveret's syndrome.

Erythropoietin administration suppresses human monocyte function in vitro and during therapy-induced anemia in HCV patients.

Erythropoietin (EPO) is a hormone that controls red blood cell production. Binding of EPO to the EPO-receptor results in increased numbers of red blood cells in the circulation, which makes EPO a potent molecule to treat anemia in various groups of patients. Although numerous studies have examined the clinical effects of EPO, its immunological effects have received less attention. In this study, we examined the immunological effects of EPO on human monocytes. We show that human monocytes express EPO receptor mRNA, and are responsive to EPO in cell culture. In vitro exposure of PBMC from individuals to EPO and the TLR4 ligand LPS showed a significant reduction of monocytes producing IL-6 and TNF, while the frequencies of IL-12p40, IL-10, MIP-1ß and IL-8-producing cells did not change upon incubation with EPO. In addition, EPO did increase the phagocytic activity but did not affect the ability to produce ROS by monocytes. Moreover, we studied eight chronic HCV patients undergoing treatment with peg-IFN and ribavirin, who were administered EPO for treatment-induced anemia. Blood was collected before and 7 days after EPO injection. In 7 patients, we observed a significant decline at day 7 after EPO administration of the frequency of monocytes producing various pro-inflammatory cytokines following stimulation with the TLR4 ligand LPS and the TLR7/8 ligand R848, which is in line with our in vitro findings. Our findings demonstrate an inhibitory effect of EPO on the secretion of effector molecules by monocytes and a stimulatory effect on the phagocytic activity by monocytes.