Adverse events of endoscopic full-thickness resection:results from the German and Dutch nationwide colorectal FTRD registry

Background and Aims: Endoscopic full-thickness resection (eFTR) is emerging as a minimally invasive alternative to surgery for complex colorectal lesions. Previous studies have demonstrated favorable safety results; however, large studies representing a generalizable estimation of adverse events (AEs) are lacking. Our aim was to provide further insight in AEs after eFTR.Methods: Data from all registered eFTR procedures in the German and Dutch colorectal full-thickness resection device registries between July 2015 and March 2021 were collected. Safety outcomes included immediate and late AEs.Results: Of 1892 procedures, the overall AE rate was 11.3% (213/1892). No AE-related mortality occurred. Perforations occurred in 2.5% (47/1892) of all AEs, 57.4% (27/47) of immediate AEs, and 42.6% (20/47) of delayed AEs. Successful endoscopic closure was achieved in 29.8% of cases (13 immediate and 1 delayed), and antibiotic treatment was sufficient in 4.3% (2 delayed). The appendicitis rate for appendiceal lesions was 9.9% (13/131), and 46.2% (6/13) could be treated conservatively. The severe AE rate requiring surgery was 2.2% (42/1892), including delayed perforations in .9% (17/1892) and immediate perforations in .7% (13/1892). Delayed perforations occurred between days 1 and 10 (median, 2) after eFTR, and 58.8% (10/17) were located on the left side. Other severe AEs were appendicitis (.4%, 7/1892), luminal stenosis (.1%, 2/1892), delayed bleeding (.1%, 1/1892), pain after eFTR close to the dentate line (.1%, 1/1892), and grasper entrapment in the clip (.1%, 1/1892).Conclusions: Colorectal eFTR is a safe procedure with a low risk for severe AEs in everyday practice and without AE-related mortality. These results further support the position of eFTR as an established minimally invasive technique for complex colorectal lesions.</p

Consensus molecular subtype transition during progression of colorectal cancer

The consensus molecular subtype (CMS) classification divides colorectal cancer (CRC) into four distinct subtypes based on RNA expression profiles. The biological differences between CMSs are already present in CRC precursor lesions, but not all CMSs pose the same risk of malignant transformation. To fully understand the path to malignant transformation and to determine whether CMS is a fixed entity during progression, genomic and transcriptomic data from two regions of the same CRC lesion were compared: the precursor region and the carcinoma region. In total, 24 patients who underwent endoscopic removal of T1–2 CRC were included. Regions were subtyped for CMS and DNA mutation analysis was performed. Additionally, a set of 85 benign adenomas was CMS-subtyped. This analysis revealed that almost all benign adenomas were classified as CMS3 (91.8%). In contrast, CMS2 was the most prevalent subtype in precursor regions (66.7%), followed by CMS3 (29.2%). CMS4 was absent in precursor lesions and originated at the carcinoma stage. Importantly, CMS switching occurred in a substantial number of cases and almost all (six out of seven) CMS3 precursor regions showed a shift to a different subtype in the carcinoma part of the lesion, which in four cases was classified as CMS4. In conclusion, our data indicate that CMS3 is related to a more indolent type of precursor lesion that less likely progresses to CRC and when this occurs, it is often associated with a subtype change that includes the more aggressive mesenchymal CMS4. In contrast, an acquired CMS2 signature appeared to be rather fixed during early CRC development. Combined, our data show that subtype changes occur during progression and that CMS3 switching is related to changes in the genomic background through acquisition of a novel driver mutation (TP53) or selective expansion of a clone, but also occurred independently of such genetic changes

Extracolonic cancer risk in Dutch patients with APC (adenomatous polyposis coli)-associated polyposis

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Efficacy and safety of peroral endoscopic myotomy for esophageal diverticula

Background and study aims Epiphrenic diverticula are rare and mainly occur in patients with underlying esophageal motility disorders. The current standard treatment is surgical diverticulectomy often combined by myotomy and is associated with significant adverse event (AE) rates. The aim of this study was to examine the efficacy and safety of peroral endoscopic myotomy in reducing esophageal symptoms in patients with esophageal diverticula. Patients and methods We performed a retrospective cohort study including patients with an esophageal diverticulum who underwent POEM between October 2014 and December 2022. After informed consent, data were extracted from medical records and patients completed a survey by telephone. The primary outcome was treatment success, defined as Eckardt score below 4 with a minimal reduction of 2 points. Results Seventeen patients (mean age 71 years, 41.2 % female) were included. Achalasia was confirmed in 13 patients (13 /17, 76.5 %), Jackhammer esophagus in two patients (2 /17, 11.8 %), diffuse esophageal spasm in one patient (1 /17, 5.9 %) and in one patient no esophageal motility disorder was found (1 /17, 5.9 %). Treatment success was 68.8 % and only one patient (6.3 %) underwent retreatment (pneumatic dilatation). Median Eckardt scores decreased from 7 to 1 after POEM (p < 0.001). Mean size of the diverticula decreased from 3.6 cm to 2.9 cm after POEM (p < 0.001). Clinical admission was one night for all patients. AEs occurred in two patients (11.8 %) which were classified as grade II and IIIa (AGREE classification). Conclusions POEM is effective and safe to treat patients with esophageal diverticula and an underlying esophageal motility disorder

Gastric and duodenal cancer in individuals with Lynch syndrome:a nationwide cohort study

Background:Lynch syndrome increases the risk of gastric cancer (GC) and duodenal cancer (DC), particularly in individuals with MLH1 and MSH2 pathogenic variants (PVs). To provide further insight into whether, and from what age, esophagogastroduodenoscopy (EGD) surveillance may be beneficial, we evaluated the cumulative incidence and tumour characteristics of GC and DC in a large nationwide cohort of Dutch individuals with LS. Methods: For this retrospective nationwide cohort study, clinical data of individuals with LS registered at the Dutch Hereditary Cancer Registry were matched with pathology reports filed by the Dutch Pathology registry. All individuals registered between Jan 1, 1989 and Dec 31, 2021 with proven or putative PVs in one of the mismatch repair genes were included. Cumulative incidences of GC and DC were estimated for high-risk (MLH1, MSH2 and EpCAM) and low-risk (MSH6 and PMS2) PVs using competing risk methodology (Fine and Gray method) with death due to other causes as competing risk. Findings: Among 1002 individuals with high-risk and 765 individuals with low-risk PVs, 29 GCs (1.6%) and 39 DCs (2.2%) were diagnosed. Cumulative incidence of GC and DC under the age of 50 was very low (≤1%) for all individuals. At age 70 and 75, cumulative incidence of GC was 3% [95% CI 1%–5%] and 5% [3%–8%] for high-risk PVs and 1% [0%–2%] and 1% [0%–2%] for low-risk PVs (p = 0.006). For DC, cumulative incidence at age 70 and 75 was 5% [3%–7%] and 6% [3%–8%] in high-risk, 1% [0%–1%] and 2% [0%–4%] in low-risk PVs, respectively (p = 0.01). Primary tumour resection was performed in 62% (18/29) of GCs and 77% (30/39) of DC cases. Early-stage GC, defined as TNM stage I, was found in 32% (9/28) of GCs. Early-stage DC, defined as TNM stage I-IIa, was found in 39% (14/36) of DCs. Interpretation: Individuals with MLH1, MSH2, and EpCAM PVs have an increased risk of developing GC and DC at the age of 70 years, but this risk is very low before the age of 50 years. The age of onset of surveillance, the yield of GC and DC during EGD surveillance, and its cost-effectiveness should be subject of future studies. </p

Adverse events of endoscopic full-thickness resection: results from the German and Dutch nationwide colorectal FTRD registry

BACKGROUND AND AIMS: Endoscopic full-thickness resection (eFTR) is emerging as a minimally invasive alternative to surgery for complex colorectal lesions. Previous studies have demonstrated favorable safety results; however, large studies representing a generalizable estimation of adverse events (AEs) are lacking. Our aim was to provide further insight in AEs after eFTR. METHODS: Data from all registered eFTR procedures in the German and Dutch colorectal full-thickness resection device registries between July 2015 and March 2021 were collected. Safety outcomes included immediate and late AEs. RESULTS: Of 1892 procedures, the overall AE rate was 11.3% (213/1892). No AE-related mortality occurred. Perforations occurred in 2.5% (47/1892) of all AEs, 57.4% (27/47) of immediate AEs, and 42.6% (20/47) of delayed AEs. Successful endoscopic closure was achieved in 29.8% of cases (13 immediate and 1 delayed), and antibiotic treatment was sufficient in 4.3% (2 delayed). The appendicitis rate for appendiceal lesions was 9.9% (13/131), and 46.2% (6/13) could be treated conservatively. The severe AE rate requiring surgery was 2.2% (42/1892), including delayed perforations in .9% (17/1892) and immediate perforations in .7% (13/1892). Delayed perforations occurred between days 1 and 10 (median, 2) after eFTR, and 58.8% (10/17) were located on the left side. Other severe AEs were appendicitis (.4%, 7/1892), luminal stenosis (.1%, 2/1892), delayed bleeding (.1%, 1/1892), pain after eFTR close to the dentate line (.1%, 1/1892), and grasper entrapment in the clip (.1%, 1/1892). CONCLUSIONS: Colorectal eFTR is a safe procedure with a low risk for severe AEs in everyday practice and without AE-related mortality. These results further support the position of eFTR as an established minimally invasive technique for complex colorectal lesions

Personalized endoscopic surveillance and intervention protocols for patients with familial adenomatous polyposis: the European FAP Consortium strategy

Background and study aims Patients with familial adenomatous polyposis (FAP) undergo colectomy and lifelong endoscopic surveillance to prevent colorectal, duodenal and gastric cancer. Endoscopy has advanced significantly in recent years, including both detection technology as well as treatment options. For the lower gastrointestinal tract, current guidelines do not provide clear recommendations for surveillance intervals. Furthermore, the Spigelman staging system for duodenal polyposis has its limitations. We present a newly developed personalized endoscopic surveillance strategy for the lower and upper gastrointestinal tract, aiming to improve the care for patients with FAP. We aim to inform centers caring for FAP patients and encourage the discussion on optimizing endoscopic surveillance and treatment in this high-risk population. Methods The European FAP Consortium, consisting of endoscopists with expertise in FAP, collaboratively developed new surveillance protocols. The proposed strategy was consensus-based and a result of several consortium meetings, discussing current evidence and limitations of existing systems. This strategy provides clear indications for endoscopic polypectomy in the rectum, pouch, duodenum and stomach and defines new criteria for surveillance intervals. This strategy will be evaluated in a 5-year prospective study in nine FAP expert centers in Europe. Results We present a newly developed personalized endoscopic surveillance and endoscopic treatment strategy for patients with FAP aiming to prevent cancer, optimize endoscopic resources and limit the number of surgical interventions. Following this new strategy, prospectively collected data in a large cohort of patients will inform us on the efficacy and safety of the proposed approaches

Cold snare polypectomy for duodenal adenomas in familial adenomatous polyposis: a prospective international cohort study

Background In patients with familial adenomatous polyposis (FAP), endoscopic resection of duodenal adenomas is commonly performed to prevent cancer and prevent or defer duodenal surgery. However, based on studies using different resection techniques, adverse events (AEs) of polypectomy in the duodenum can be significant. We hypothesized that cold snare polypectomy (CSP) is a safe technique for duodenal adenomas in FAP and evaluated its outcomes in our centers. Methods We performed a prospective international cohort study including FAP patients who underwent CSP for one or more superficial non-ampullary duodenal adenomas of any size, between 2020 and 2022. At that time, this technique was common practice in our centers for superficial duodenal adenomas. The primary outcome was the occurrence of intra- and post-procedural AEs. Results In total, 133 CSPs were performed in 39 patients with FAP (1-18 per session). Median adenoma size was 10mm (IQR 8-15mm), ranging from 5-40mm; 27 adenomas were ≥20mm (20%). Of the 133 polypectomies, 109 (82%) were performed after submucosal injection. Sixty-one adenomas (46%) were resected en bloc and 72 (54%) piecemeal. Macroscopic radical resection was achieved for 129 polypectomies (97%). Deep mural injury type II occurred in 3 polyps (2%) with no delayed perforation after prophylactic clipping. There were no clinically significant bleedings, perforations or other post-procedural AEs. Histopathology showed low-grade dysplasia in all 133 adenomas. Conclusions Cold snare polypectomy for (multiple) superficial non-ampullary duodenal adenomas in FAP seems feasible and safe. Long-term prospective research is needed to evaluate whether protocolized duodenal polypectomies prevent cancer and surgery