Effect of optical diagnosis training on recognition and treatment of submucosal invasive colorectal cancer in community hospitals: a prospective multicenter intervention study.

BACKGROUND: Recognition of submucosal invasive colorectal cancer (T1 CRC) is difficult, with sensitivities of 35 %-60 % in Western countries. We evaluated the real-life effects of training in the OPTICAL model, a recently developed structured and validated prediction model, in Dutch community hospitals. METHODS: In this prospective multicenter study (OPTICAL II), 383 endoscopists from 40 hospitals were invited to follow an e-learning program on the OPTICAL model, to increase sensitivity in detecting T1 CRC in nonpedunculated polyps. Real-life recognition of T1 CRC was then evaluated in 25 hospitals. Endoscopic and pathologic reports of T1 CRCs detected during the next year were collected retrospectively, with endoscopists unaware of this evaluation. Sensitivity for T1 CRC recognition, R0 resection rate, and treatment modality were compared for trained vs. untrained endoscopists. RESULTS: 1 year after e-learning, 528 nonpedunculated T1 CRCs were recorded for endoscopies performed by 251 endoscopists (118 [47 %] trained). Median T1 CRC size was 20 mm. Lesions were mainly located in the distal colorectum (66 %). Trained endoscopists recognized T1 CRCs more frequently than untrained endoscopists (sensitivity 74 % vs. 62 %; mixed model analysis odds ratio [OR] 2.90, 95 %CI 1.54-5.45). R0 resection rate was higher for T1 CRCs detected by trained endoscopists (69 % vs. 56 %; OR 1.73, 95 %CI 1.03-2.91). CONCLUSION: Training in optical recognition of T1 CRCs in community hospitals was associated with increased recognition of T1 CRCs, leading to higher en bloc and R0 resection rates. This may be an important step toward more organ-preserving strategies.

Oncologic outcomes of screen-detected and non-screen-detected T1 colorectal cancers.

BACKGROUND: The incidence of T1 colorectal cancer (CRC) has increased with the implementation of CRC screening programs. It is unknown whether the outcomes and risk models for T1 CRC based on non-screen-detected patients can be extrapolated to screen-detected T1 CRC. This study aimed to compare the stage distribution and oncologic outcomes of T1 CRC patients within and outside the screening program. METHODS: Data from T1 CRC patients diagnosed between 2014 and 2017 were collected from 12 hospitals in the Netherlands. The presence of lymph node metastasis (LNM) at diagnosis was compared between screen-detected and non-screen-detected patients using multivariable logistic regression. Cox proportional hazard regression was used to analyze differences in the time to recurrence (TTR), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival. Additionally, the performance of conventional risk factors for LNM was evaluated across the groups. RESULTS: 1803 patients were included (1114 [62%] screen-detected), with median follow-up of 51 months (interquartile range 30). The proportion of LNM did not significantly differ between screen- and non-screen-detected patients (12.6% vs. 8.9%; odds ratio 1.41; 95%CI 0.89-2.23); a prediction model for LNM performed equally in both groups. The 3- and 5-year TTR, MFS, and CSS were similar for patients within and outside the screening program. However, overall survival was significantly longer in screen-detected T1 CRC patients (adjusted hazard ratio 0.51; 95%CI 0.38-0.68). CONCLUSIONS: Screen-detected and non-screen-detected T1 CRCs have similar stage distributions and oncologic outcomes and can therefore be treated equally. However, screen-detected T1 CRC patients exhibit a lower rate of non-CRC-related mortality, resulting in longer overall survival.

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.

Limited wedge resection for T1 colon cancer (LIMERIC-II trial) - rationale and study protocol of a prospective multicenter clinical trial.

BACKGROUND: The sole presence of deep submucosal invasion is shown to be associated with a limited risk of lymph node metastasis. This justifies a local excision of suspected deep submucosal invasive colon carcinomas (T1 CCs) as a first step treatment strategy. Recently Colonoscopy-Assisted Laparoscopic Wedge Resection (CAL-WR) has been shown to be able to resect pT1 CRCs with a high R0 resection rate, but the long term outcomes are lacking. The aim of this study is to evaluate the safety, effectiveness and long-term oncological outcomes of CAL-WR as primary treatment for patients with suspected superficial and also deeply-invasive T1 CCs. METHODS: In this prospective multicenter clinical trial, patients with a macroscopic and/or histologically suspected T1 CCs will receive CAL-WR as primary treatment in order to prevent unnecessary major surgery for low-risk T1 CCs. To make a CAL-WR technically feasible, the tumor may not include > 50% of the circumference and has to be localized at least 25 cm proximal from the anus. Also, there should be sufficient distance to the ileocecal valve to place a linear stapler. Before inclusion, all eligible patients will be assessed by an expert panel to confirm suspicion of T1 CC, estimate invasion depth and subsequent advise which local resection techniques are possible for removal of the lesion. The primary outcome of this study is the proportion of patients with pT1 CC that is curatively treated with CAL-WR only and in whom thus organ-preservation could be achieved. Secondary outcomes are 1) CAL-WR's technical success and R0 resection rate for T1 CC, 2) procedure-related morbidity and mortality, 3) 5-year overall and disease free survival, 4) 3-year metastasis free survival, 5) procedure-related costs and 6) impact on quality of life. A sample size of 143 patients was calculated. DISCUSSION: CAL-WR is a full-thickness local resection technique that could also be effective in removing pT1 colon cancer. With the lack of current endoscopic local resection techniques for > 15 mm pT1 CCs with deep submucosal invasion, CAL-WR could fill the gap between endoscopy and major oncologic surgery. The present study is the first to provide insight in the long-term oncological outcomes of CAL-WR. TRIAL REGISTRATION: CCMO register (ToetsingOnline), NL81497.075.22, protocol version 2.3 (October 2022).

Colonoscopic-Assisted Laparoscopic Wedge Resection for Colonic Lesions: A Prospective Multicenter Cohort Study (LIMERIC-Study).

OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of a modified CAL-WR. SUMMARY BACKGROUND DATA: The use of segmental colectomy in patients with endoscopically unresectable colonic lesions results in significant morbidity and mortality. CAL-WR is an alternative procedure that may reduce morbidity. METHODS: This prospective multicenter study was performed in 13 Dutch hospitals between January 2017 and December 2019. Inclusion criteria were (1) colonic lesions inaccessible using current endoscopic resection techniques (judged by an expert panel), (2) non-lifting residual/recurrent adenomatous tissue after previous polypectomy or (3) an undetermined resection margin after endoscopic removal of a low-risk pathological T1 (pT1) colon carcinoma. Thirty-day morbidity, technical success rate and radicality were evaluated. RESULTS: Of the 118 patients included (56% male, mean age 66 years, standard deviation ± 8 years), 66 (56%) had complex lesions unsuitable for endoscopic removal, 34 (29%) had non-lifting residual/recurrent adenoma after previous polypectomy and 18 (15%) had uncertain resection margins after polypectomy of a pT1 colon carcinoma. CAL-WR was technically successful in 93% and R0 resection was achieved in 91% of patients. Minor complications (Clavien-Dindo i-ii) were noted in 7 patients (6%) and an additional oncologic segmental resection was performed in 12 cases (11%). Residual tissue at the scar was observed in 5% of patients during endoscopic follow-up. CONCLUSIONS: CAL-WR is an effective, organ-preserving approach that results in minor complications and circumvents the need for major surgery. CAL-WR, therefore, deserves consideration when endoscopic excision of circumscribed lesions is impossible or incomplete.

Automatic optical diagnosis of small colorectal lesions by laser-induced autofluorescence.

BACKGROUND AND STUDY AIMS: Endoscopic optical diagnosis can potentially replace histopathological evaluation of small colorectal lesions. The aim of this study was to evaluate diagnostic performance of WavSTAT, a novel system for automatic optical diagnosis based on laser-induced autofluorescence spectroscopy. PATIENTS AND METHODS: Consecutive patients who were scheduled for colonoscopy were included in the study. Each detected lesion with a size of ≤ 9 mm was differentiated using high resolution endoscopy (HRE) by the endoscopist, who then reported this as a low or high confidence call. Thereafter, all lesions were analyzed using WavSTAT. Histopathology was used as the reference standard. The primary outcome measures were the accuracy of WavSTAT to differentiate between adenomatous and nonadenomatous lesions, and the accuracy of an algorithm combining HRE (lesions differentiated with high confidence) and WavSTAT (all remaining lesions). The secondary outcome measure was the accuracy of on-site recommended surveillance intervals. RESULTS: At total of 87 patients with 207 small colorectal lesions were evaluated. Accuracy and negative predictive value of WavSTAT were 74.4 % and 73.5 %, respectively. The corresponding figures for the algorithm were 79.2 % and 73.9 %, respectively. Accuracy of on-site recommended surveillance interval was 73.7 % for WavSTAT alone and 77.2 % for the algorithm of HRE and WavSTAT. CONCLUSIONS: Both accuracy of WavSTAT alone and the algorithm combining HRE with WavSTAT proved to be insufficient for the in vivo differentiation of small colorectal lesions, and do not fulfill American Society for Gastrointestinal Endoscopy performance thresholds for assessment of diminutive lesions. Future studies should assess whether combining WavSTAT with more advanced imaging techniques could result in a higher accuracy.Netherlands Trial Registry (NTR 3235).

"High rate of recurrent adenomatosis during endoscopic surveillance after duodenectomy in patients with familial adenomatous polyposis".

Advanced duodenal adenomatosis in patients with familial adenomatous polyposis (FAP) is associated with a significant risk of duodenal carcinoma. Duodenectomy is sometimes indicated to prevent malignant transformation or to resect established carcinomas. Advanced recurrent adenomatosis and cancer formation in the neo-duodenum after duodenectomy in FAP have been reported. The aim of this study was to describe findings during endoscopic follow-up in a cohort of FAP patients after duodenectomy, to assess the indication and whether recommendations can be made for endoscopic surveillance. All FAP patients with a history of duodenectomy performed at a single tertiary referral centre between January 2000 and July 2011 were identified. Patient characteristics and postoperative upper endoscopic procedures were reviewed retrospectively. 19 patients, with a mean age of 49 years at the time of duodenectomy were identified. One patient was lost to follow-up. The majority of patients underwent prophylactic pancreas preserving duodenectomy (95%). Mean duration of postoperative follow-up in 18 patients was 78 months with 4 postoperative endoscopies on average. An increase in neo-Spigelman stage was seen in 9 patients, after an average interval of 35 months. Overall, newly formed adenomas in the neo-duodenum were found in 14 of 18 patients (78%), after a mean of 46 months after duodenectomy. Recurrent adenomas were mostly located in close proximity to the neo-papilla. This included advanced adenomas in 7 patients, warranting enteric re-resection in 2 patients. Continued intensive endoscopic surveillance is indicated after duodenectomy in FAP, especially of the area around the bilio- and pancreatico-enteric anastomoses.

Jejunal cancer in patients with familial adenomatous polyposis.

BACKGROUND & AIMS: Familial adenomatous polyposis (FAP) is an inherited disease affecting approximately 1:10,000 newborns, characterized by the formation of numerous adenomas in the digestive tract. Surveillance and prophylactic treatment of colonic and duodenal manifestations of this disease have much influenced disease course and survival. In more recent years, it has become clear that adenoma formation in FAP patients is not restricted to the colon and duodenum. Accordingly, these adenomas might have malignant potential, although the actual risk is unknown. METHODS: We report 3 cases of jejunal carcinoma in FAP patients and review data on incidence, prognosis, and risk factors of jejunoileal adenoma and carcinoma development in FAP. RESULTS: Three patients with FAP aged 71, 57, and 59 years developed advanced duodenal adenomatosis and a jejunal carcinoma, which was associated with poor prognosis in 2 patients. CONCLUSIONS: Jejunal adenomas in FAP patients are reported occasionally and can progress into adenocarcinoma with a poor prognosis. In the future a subset of FAP patients benefitting from jejunal surveillance should be identified.

Immunoglobulin G4-associated cholangitis: one variant of immunoglobulin G4-related systemic disease.

IgG4-associated cholangitis (IAC) is a recently defined disease entity which shares a number of clinical, biochemical, and radiological features with primary sclerosing cholangitis (PSC). In contrast to PSC, IAC responds to immunosuppressive treatment, is not associated with inflammatory bowel disease, and mainly affects elderly men above the age of 60 years. Today, IAC is regarded as one variant of IgG4-related systemic disease (ISD) of which autoimmune pancreatitis (AIP) is the best studied organ manifestation. The diagnosis of IAC is based on biochemical, radiological and histologic features, among which elevated serum levels of IgG4, extra- and intrahepatic biliary strictures as visualized by cholangiography, multifocal IgG4-rich lymphoplasmacytic sclerosing infiltrations in liver and bile duct tissue, and association with AIP are of key importance. This review aims at summarizing clinical features, diagnostic criteria, therapeutic strategies and most recent insights in the pathophysiology of IAC and other organ manifestations of ISD.