Introduction

ESD is the gold standard of treatment for large superficial colorectal lesions in Asia. In Western countries, it is struggling to establish itself as the reference treatment because of its technical difficulty. France, after publishing worrying results 10 years ago, has set up effective training allowing a wide territorial offer. Despite the results reported by expert centers, there is still a debate about the feasibility of colonic dissection compared to rectal dissection due to the greater technical difficulty and the higher risk of complications in this location. The aim of this study was to analyze 3 years after the creation of the prospective French ESD colorectal cohort (FECCO), the results of colorectal ESD, with focusing on comparison between colonic and rectal ESD.

Aims & Methods

The aim of this study was to analyze 3 years after the creation of the prospective French ESD colorectal cohort (FECCO), the results of colorectal ESD, with focusing on comparison between colonic and rectal ESD. This is a prospective cohort that included all colorectal ESD performed in 12 French centers and one Belgian center September 2019 and September 2022. The objectives of this study were to compare the results of colonic and rectal lesions and rectal lesions treated by ESD in terms of En bloc, R0, curative resection, perforation rate clinically significant delayed bleeding rates and in terms of secondary surgery.

Results

Between September 2019 and September 2022, 3901 colorectal ESD were performed in the 13 centers by 35 operators. The average age of the patients was 68 years, 65% of the cases were granular LST. The average size of the lesions were 54 mm. The lesions were located in the colon in 62% of cases. The mean procedure time was 73 min and the mean procedure speed was was 34 mm2/min. The rates of en bloc, R0 and curative resection were 95%, 88% and 84% respectively
When comparing rectal and colonic lesions:
- Rectal lesions were significantly larger: (60 mm vs 50 mm, p < 0.0001)
- the procedure time was longer in the rectum than in the colon (84 vs 64 min; p < 0.0001) but procedural speed was significantly higher in the rectum (36 mm2/min vs 32 mm2/min p<0.001).
- The rate of en bloc resection was higher in the rectum: 96% vs 94%, p=0.041
- There was no difference in terms of R0 resection: 88.3% vs 87%, p=0.231;
- curative resection was significantly more frequent in the colon: 85.6% vs 81.3%, p=0.003
- there was more per-procedural perforation in the colon: 10.6% vs 7.1%, p=0.002
- the surgical referral rate for a complication was higher in the colon: 0.7% vs O.1%, p=0.012
- there was more clinically significant delayed bleeding in the rectum: 4.5% vs 6.8%, p=0.003
- the length of hospital stay was significantly longer for colonic lesions: 1.8 vs 1.5 days.

Conclusion

The strengths of our study are the prospective design and the number of lesions included (largest worldwide series about colorectal ESD) in a short inclusion period limiting a temporal bias. Carcinologic results are equivalent to best literature on the topic.
The two principal limitations are that 75%of the lesions were included by 4 centers (13 physicians) and that several centers applied a selective strategy according to the scope manoeuvrability considering piece-meal EMR in case of very poor scope manoeuvrability.
The results of colorectal ESD in France are confirmed on a large scale and the differences between rectal and colonic lesions are negligible when the procedure is mastered leading to the use of ESD as a first line treatment for superficial colorectal lesions larger than 2 cm.

Introduction

Initial reports have described rectal endoscopic knife-assisted full-thickness resection (kFTR) as a novel technique for achieving R0 resection in deeply invasive or technically challenging rectal lesions, avoiding the significant morbidity and mortality of rectal surgery.^1,2​​​​ We aimed to evaluate the feasibility, safety, and technical outcomes of rectal kFTR.

Aims & Methods

In this retrospective international study, we included consecutive patients who underwent rectal kFTR at 15 centres across 4 continents between April 2017 and April 2025. We included patients with adenocarcinoma suspected of deep submucosal invasion, severe fibrosis, or subepithelial lesions were included. Primary outcomes were technical success, en-bloc and R0 resection rates and adverse events. Secondary outcomes included rectal preservation, length of hospital stay, and recurrence. Risk factors for adverse events were evaluated using univariate and multivariate logistic regression.

Results

A total of 94 patients (mean age 65 years [IQR 58-73]; 56.4% male; 79.8% ASA I/II) underwent rectal kFTR. Median lesion size was 35 mm [IQR 25-50]. kFTR was performed for suspected deep invasion (57; 60.6%), severe fibrosis (31; 33%), and subepithelial lesions (6; 6.4%). Of lesions included, 59 (62.8%) were in the distal rectum, and 13 (13.8%) were anterior.

Technical success was achieved in 92 procedures (97.9%). Mean procedure time was 135 minutes (IQR 100-180). Antibiotics were administered in 83 procedures (88.3%) for a median of 5 days (IQR 5-5). Median hospital stay was 1 day (IQR 1 - 3). Overall, 19 adverse events occurred in 15/94 (16%) patients: 12 (63.1%) mild, 6 (31.6%) moderate, and 1 (5.3%) severe per ASGE lexicon. Delayed bleeding occurred in 4 (4.3%) patients, and post-procedural pain in 7 patients (7.4%). Surgery was required in one case for a recto-vaginal fistula. Increasing lesion size was the only risk factor independently associated with a higher risk of adverse events (OR 1.05, 95% CI 1.02–1.09, p = 0.003).

En-bloc and R0 resections were achieved in 91/94 (96.8%) and 74 (78.7%) procedures, respectively. Rectal preservation was achieved in 68 patients (72.3%) while, 25 (26.6%) underwent completion surgery for non-curative cancer resections, with no residual tumor in the surgical specimen in 11/25 cases (44%).

Among 59 patients with adenocarcinoma and available follow-up (median 12 months (IQR 6 - 23.5)), 3 (5.1%) experienced loco-regional recurrences, 1 (1.7%) had distant metastasis from a pT2 adenocarcinoma with surgery after kFTR, and 1 died of non-cancer-related causes.

Conclusion

kFTR appeared to be a feasible and safe technique for excising deeply invasive adenocarcinomas and complex fibrotic or subepithelial rectal lesions in expert centres. The high rate of R0 resections enabled accurate histopathological risk stratification, supporting individualised post-procedural management and rectal preservation in most patients. Rectal kFTR may serve as an alternative to device-assisted endoscopic full-thickness resection and local surgical excision, potentially avoiding radical surgery in highly selected patients. Further prospective research is needed to confirm these findings.

References

1. Argenziano ME*, Sorge A*, Poortmans PJ, Montori M, Balducci D, Hoorens A, Maroni L, Tate DJ, Knife-Assisted Full-Thickness Resection Guided by Pocket Detection Method for Detection and Complete Excision of Deeply Invasive Rectal Cancer, VideoGIE (2024), doi: https://doi.org/10.1016/j.vgie.2024.11.004.
2. Argenziano, M.E.*, Sorge, A.*, Hoorens, A., Montori, M., Poortmans, P.J., Smeets, S., Tornai, T., Debels, L.K., Desomer, L. and Tate, D.J. (2025), Knife-assisted full-thickness resection guided by the pocket-detection method for posterior deeply invasive rectal cancer: A novel endoscopic approach (with video). DEN Open, 5: e70116. https://doi.org/10.1002/deo2.70116

Introduction

Intraductal Papillary Mucinous Neoplasias (IPMN) are cystic neoplasias of the ducts of the pancreas. They usually occur at advanced age and can progress to invasive adenocarcinomas. While there are morphological and spatial features to assess the progression risk, a mutational footprint defining the progression risk remains to be identified. IPMNs often harbor an activating mutation of either GNAS or KRAS or both, but neither interaction nor signaling crosstalk is well understood.

Aims & Methods

Here, we use a patient-derived induced pluripotent stem cell (iPSC) model system, harboring either a wildtype or mutant GNAS with an inducible oncogenic KRAS^G12D cassette. Various iPSC genotypes were differentiated towards the pancreatic lineage including pancreatic duct-like organoids, followed by subsequent transplantation onto the porcine urinary bladder (PUB) for long-term culture. Dysplasia, mucin expression and cyst size were subsequently analysed.

Results

Already 2 weeks post transplantation, a substantial amount of CK7/CK19 positive pancreatic ductal structures were found in all grafts with a strong cystic phenotype driven by a GNAS^R201C background. The phenotype was still present 8 weeks after transplantation. The induction of KRAS^G12D for 6 weeks resulted in an increased ductal lumen, which was further boosted by GNAS^R201C. In addition, a strong GNAS^R201C dependent expression of Mucin 2, a marker for the intestinal IPMN subtype was documented. Quantification of dysplastic ductal structures revealed an increase in low grade dysplasia driven either by KRAS^G12D or GNAS^R201C. Combination of both mutations was associated with a strong increase in the amount of high grade dysplastic ductal structures. In ductal structures a pro-proliferative phenotype driven by GNAS^R201C background was observed. The amount of p21 positive nuclei was highly increased by KRAS^G12D, while it was significantly attenuated in ductal cells with a double mutated KRAS^G12D GNAS^R201C background, showing a decreased amount of oncogene induced senescence. This was recapitulated in vitro in pancreatic ductal organoids.

Conclusion

The first results show an effect of GNAS^R201C on early dysplasia formation and a further boost of KRAS^G12D driven dysplasia and high-grade dysplasia formation. Additionally, the increased proliferative and decreased senescent phenotype hints at a GNAS^R201C driven bypass of oncogene induced senescence. Our genuine patient-derived iPSC model featuring an endogenous GNAS^R201C locus will allow us to closely investigate the early formation of IPMNs and timewise resolve their transition towards an invasive phenotype to further unravel the mechanisms of IPMN formation and the collaborative pro-oncogenic signaling of KRAS^G12D with GNAS^R201C.