Introduction

Aims & Methods

Results

Conclusion

Introduction

Endoscopic resection techniques, such as Endoscopic Mucosal Resection (EMR) and Endoscopic Submucosal Dissection (ESD), are used to remove precancerous and early-stage cancerous lesions in the gastrointestinal tract. While ESD is the gold standard due to its en-bloc and R0 resection capability, Underwater Endoscopic Mucosal Resection (UEMR) has emerged as an alternative. UEMR uses water buoyancy to aid lesion resection, potentially improving safety and reducing procedure time. However, its comparative effectiveness remains unclear.

Aims & Methods

The primary aim of this systematic review and meta-analysis is to compare the efficacy, safety, and procedural efficiency of Underwater Endoscopic Mucosal Resection (UEMR) versus Endoscopic Submucosal Dissection (ESD) in the treatment of gastrointestinal lesions.
A systematic search was conducted in PubMed, Embase, Google Scholar, Scopus, and Cochrane Library. Eligible studies compared UEMR and ESD in gastrointestinal lesions, providing data on en-bloc resection, R0 resections, adverse events, and procedure time. Randomized controlled trials (RCTs), cohort studies, and comparative studies were included.
Two reviewers independently extracted data, resolving discrepancies by discussion. Study quality was assessed using the Cochrane Risk of Bias Tool. Random-effects models were used for pooled analyses, calculating odds ratios (OR) and mean differences with 95% confidence intervals (CI). Heterogeneity was evaluated via the I² statistic.

Results

The analysis included four studies (three RCTs and one cohort study), with a total of 651 patients. Regarding efficacy, UEMR showed significantly lower en-bloc resection rates compared to ESD (OR = 0.01, 95% CI [0.01–0.06], Z = 6.85, p < 0.00001), suggesting a reduced ability to achieve complete lesion removal in a single piece. Similarly, R0 resection rates were also lower in the UEMR group (OR = 0.16, 95% CI [0.09–0.22], Z = 9.09, p < 0.0001), although with high heterogeneity (I² = 83%), possibly reflecting variations in patient selection, operator expertise, and technical differences among studies. In terms of safety, no significant difference was observed in adverse event rates between UEMR and ESD (OR = 0.48, 95% CI [0.10–2.34], Z = 0.90, p = 0.37), indicating comparable safety profiles. However, UEMR demonstrated an advantage in procedural time, being 5.89 times faster than ESD (p < 0.0001). This suggests that while UEMR may offer time efficiency, it comes at the cost of lower en-bloc and R0 resection rates, raising questions about its suitability for lesions requiring complete and margin-free excision. Further studies are needed to clarify the impact of these differences on long-term patient outcomes and to determine the optimal indications for UEMR in clinical practice.

Conclusion

UEMR offers a quicker alternative to ESD but lacks its high resection quality, making ESD preferable for lesions requiring en-bloc or R0 resection. Gastroenterologists must weigh UEMR’s speed against ESD’s superior efficacy. Standardizing UEMR techniques may improve its resection quality and expand its role in clinical practice. Future research should optimize UEMR and address variability in resection outcomes.

References

1. Nett A, Binmoeller K. Underwater Endoscopic Mucosal Resection. Gastrointest Endosc Clin N Am. 2019 Oct;29(4):659-673. doi: 10.1016/j.giec.2019.05.004.
2. Ferlitsch M et al. Colorectal polypectomy and endoscopic mucosal resection: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2024. Endoscopy. 2024;56(1):1-20. doi: 10.1055/a-2304-3219.
3. de Souza MHG, Ribeiro IB, de Moura DTH, et al. Underwater versus conventional endoscopic mucosal resection for colorectal lesions: a systematic review and meta-analysis of randomized clinical trials. Surg Endosc. 2023;37(5):3456-3465. doi: 10.1007/s00464-022-09456-7
4. Chandan S, Mohan BP, Khan SR, et al. Safety and efficacy of underwater versus conventional endoscopic mucosal resection for colorectal polyps: Systematic review and meta-analysis of RCTs. Gastrointest Endosc. 2023;97(6):1087-1095.e3. doi: 10.1016/j.gie.2023.01.012.
5. Inoue T, Nishida T, Maekawa A, et al. Underwater endoscopic mucosal resection versus endoscopic submucosal dissection for 20–30 mm colorectal polyps: a prospective randomized study. Endoscopy. 2022;54(5):456-464. doi: 10.1055/a-1500-1234.
6. Park SS, Lee IS, Lee SH, et al. Comparison of underwater endoscopic mucosal resection and endoscopic submucosal dissection of rectal neuroendocrine tumors (with videos). Gastrointest Endosc. 2021;93(3):637-646.e2. doi: 10.1016/j.gie.2020.08.030.
7. Takeuchi Y, Uedo N, Hotta K, et al. Underwater endoscopic mucosal resection for colorectal lesions: Can it be an “Underwater” revolution? World J Gastroenterol. 2020;26(20):2545-2553. doi: 10.3748/wjg.v26.i20.2545.

Introduction

ESD (endoscopic submucosal dissection) and EFTR (endoscopic full-thickness resection) are treatments of choice in the endoscopic resection of small and superficially submucosal invasive GI lesions. It is often challenging to assess the best curative option in this setting. ESD is currently thought to be the gold standard technique.

Aims & Methods

We retrospectively analyzed all gastrointestinal pT1 lesions < 30 mm resected by either ESD or EFTR in our Unit from 2016 and December 2022. As primary endpoints we assessed en bloc resection, R0 resection (clear margins) and curative resection (no further need for surgery) rate. As secondary endpoints we analyzed mean procedural time, cost and adverse events that occurred within or after both procedures. Statistical analysis was performed with Pearson chi-square test.

Results

35 ESD and 32 EFTR were enrolled. En bloc resection was achieved in, respectively, 90 % (32/35) and 96% (30/32), with no statistical difference (RR 0.93, p= 0.9), likewise R0 resection (29/35, 83% vs 30/32, 96%, RR 0.86, p=0.7) and curative resection (23/35, 66% vs 20/32, 64%, RR 1.03, p= 0.7). Mean procedural time was lower in EFTR, although not significantly (67 ± 37 min vs 50 ± 15.6 min, p=0.7), while adverse events rate was similar (5/35, 13% vs 3/32, 10%). Eventually, mean procedural cost per hospitalization day was lower in ESD than EFTR (1503 ± 360 € vs 2260 ± 210€), considering a medium hospitalization time of 2.4 days and 2 days, respectively.

Conclusion

ESD and EFTR turned out to be equally successful in achieving R0 and curative resection in pT1 small lesions, so that ESD should remain gold standard in an experienced setting, even though EFTR could allow easier and faster en bloc resection in most challenging ESD, albeit more expensive.

Introduction

Endoscopic submucosal dissection (ESD) is widely recognized as the preferred technique for removing large benign colorectal lesions and those with a risk of submucosal invasive cancer (SMIC), with the goal of achieving en-bloc resection. R0 resection is crucial for enabling organ-preservation strategies, particularly in endoscopically resected T1-colorectal cancer (T1-CRC).

Aims & Methods

This study aims to evaluate R0 resection rates in a large cohort of colorectal ESDs by assessing vertical and lateral margins and identifying predictive factors for vertical margin involvement. Furthermore, the presence of other prognostic risk factors for lymph node metastasis (LNM) will be analyzed in this large cohort of T1-CRC. This is a multicenter prospective cohort study in 13 centers, including all colorectal ESDs between 09/2019 and 09/2024. Procedural and histological outcomes were analyzed using univariate and multivariate analysis.

Results

7495 large colorectal polyps were included, of which 781 were T1-CRCs with a median size of 45 [35-65] mm. En bloc resection occurred in 96.7% and R0 resection in 74.9%. Lateral resection margins were free in 92.5%, with positive margins for adenocarcinoma in only 0.8% (low grade dysplasia in 2.6%, high grade in 1.2%, missing data in 2.6%). Vertical margins were free in 80.3%, and decreased significantly when deep SMIC was present to 75.0%, compared to 95.7% for superficial SMIC. However deep SMIC with up to 2000 µm invasion depth, demonstrated free vertical resection margins in still 80.7%, after which it gradually decreased to 73.1% and 67.7% at an infiltration depth of 2000-3000 µm and >3000 µm respectively. Predictive factors for free vertical resection margins include lesion size >50mm (OR=1.66, [1.01;2.71], p=0.045) and rectal location (OR=1.86, [1.04;3.3], p=0.035). Significant difference was observed in the presence of prognostic risk factors for LNM between superficial and deep SMIC, with lympho-vascular invasion (LVI) being present in 9.6% and high-grade tumor budding (Bd) in 17.1% in superficial SMIC, compared to 25.0% and 30.0% respectively, in deep SMIC. However, absence of LVI, Bd or poor differentiation was noted in 75.9% of superficial and 61.7% of deep T1-CRC. Concerning deep SMIC, no relation was observed in the presence of these risk factors with respect to the depth of infiltration.

Conclusion

Following ESD for T1-CRC, the likelihood of achieving free vertical resection margins decreases significantly when invasion depth exceeds 2000 µm. Careful lesion selection through optical diagnosis is therefore critical. To push organ preservation, intermuscular dissection should be considered for T1-CRC with deeper invasion in the rectum. Achieving R0 resection remains paramount, as additional prognostic factors are present in approximately 38% of cases, irrespective of invasion depth.

Introduction

In contrast to mucosal rectal T1 adeno-CA with an R0 rate of up to 92% at centers, the R0 RR in studies drops to 62-64% in case of deep sm infiltration.[1,2] Traditionally total mesorectal excision (TME) follows as completion surgery. Deep sm infiltration as isolated risk factor excluding L+, V+, G3 and Bd2-3 seems associated with a low risk of LN metastases of only 2.6%. [3] MRI and even EUS often lead to a significant T and N overstaging.[4] A min.-invasive diagn.-ther. resection procedure providing a clear histo-pathologic staging without potentially destroying parts of the meso-rectum as it has been reported for full thickness resection techniques would be desirable for potential later surgical resection (TME).[5] Endoscopic Intermuscular Dissection (EID), similar to PAEM uses a new flexible endoscopic dissection technique with separation of the circumferential and longitudinal muscular layer providing a specimen ideally including the entire mucosa, submucosa and the inner circumferential muscle layer.[6,7] The new technique achieved in a first prospective MC study including 67 patients a technical success rate of 96% and a histologic R0 resection rate of 85%.[5] In the following we report on our first experiences using EID as referral center for ESD.

Aims & Methods

To evaluate EID in lesions with biopsy proven ADC of the rectum without endoscopic, EUS or clinical signs of local infiltration. Rectal polyps with biopsy proven HGIEN and/or suspicious for local malignant infiltration. Additionally 2 patients were included who had undergone neo-adjuvant RT/Ch therapy 24 and 26 months before refusing definitive surgery (TME). Both presented with local flat polyps with histopathologically SSA (1) / hyperplastic polyp with focal LGIEN adenoma (2) for diagn.-therapeutic resection. After endoscopic, EUS, MRI, abd/th CT-staging and rectal digital examination without suspicion of local malignant infiltration pts were offered to prospectively undergo EID after extensive informed consent within a prospective protocol. All procedures were carried out under gen. anesthesia by an exp. interv. endoscopist with >1000 ESDs. Post-Op all pts. were hospitalized and closely monitored.

Results

From 11-2023 to 4-2024, 8 EIDs in 8 pts (3 f/ 5 m) were carried out (mean 63 y; 34-83y). 6/8 lesions lower rectum, 1/8 middle, 1/8 upper rectum. 'En bloc' resection was achieved in 100%. Histopathology showed 3x ADC G2, 3 x HGIEN and in both cases with neodajuvant RT/Ch LGIEN adenoma. R0 resection was achieved in 2 of the 3 ADCs, with deep sm T1 infiltration in both but without any other risk factors. Tumor board recommendation was close clinical & imaging FU. In the 3rd ADC tumor infiltration reached the inner muscular layer (T2) and the pat. underwent uneventful TME 10 d after EID. All other cases were follow clinically. Mean length of hosp. stay was 7.1 days. Serious major complications did not occur. All pts. are closely followed with uneventful FU.

Conclusion

EID seems a new perspective for the endosc. resection of T1 ADC and high-risk polyps in the rectum. Two cases after potentially curative neo-adjuvant treatment for rectal cancer and refusal of TME show EID as potential diagnostic tool but have to be regard with caution due to a remaining risk of scattered tumor cells in the mesorectum with TME remaining the gold standard. More experience in multicenter prospective studies with matched pair analysis or a comparison to surgical local procedures (TAMIS etc.) is necessary for the final assessment of EID as new promising endoscopic technique.

References

1. Watanabe D, Toyonaga T, Ooi M et al. Clinical outcomes of deep invasive submucosal colorectal cancer after ESD. Surg Endosc 2018; 32: 2123-30
2. Yamada M, Saito Y, Takamaru H et al. Long-term clinical outcomes of en- doscopic submucosal dissection for colorectal neoplasms in 423 cases: a retrospective study. Endoscopy 2017;49: 233-42
3. Zwager LW, Bastiaansen BAJ, Montazeri NSM et al. Deep Submucosal Invasion Is Not an Independent Risk Factor for Lymph Node Metastasis in T1 Colorectal Cancer: A Meta-Analysis. Gastroenterology 2022;163:174-89
4. Detering R, van Oostendorp SE et al. MRI cT1-2 rectal cancer staging accuracy: a population-based study. Br J Surg 2020;107:1372-82
5. Eid Y, Alves A et al. Does previous transanal excision for early rectal cancer impair surgical outcomes and pathologic findings of completion total mesorectal excision? Results of a systematic review of the literature. J Visc Surg 2018; 155: 445–52
6. Moons LMG, Bastiaansen BAJ, Richir MC et al. Endoscopic intermuscular dissection for deep submucosal invasive cancer in the rectum: a new en- doscopic approach. Endoscopy 2022;54: 993-8
7. Toyonaga T, Ohara Y et al. Peranal endoscopic myectomy (PAEM) for rectal lesions with severe fibrosis and exhibiting the muscle-retracting sign. Endoscopy 2018; 50: 813–7

Introduction

The standard treatment for pT1 colorectal cancer classified as high risk (poor differentiation, deep submucosal invasion, intense tumor budding, resection margins that are positive or lymphovascular invasion) is surgery [1]. However, some studies have revealed that patients who undergo surgery and endoscopic treatment have similar disease progression outcomes, and it is also controversial which histological factors influence disease progression [2,3].

Aims & Methods

The aim of this study was to analyze the characteristics and evolution of patients undergoing surgery or endoscopic treatment after the resection of pT1 colorectal adenocarcinoma with histological findings considered high risk for lymph node metastasis.
We conducted an observational study of historical cohorts. We included patients with pT1 Adenocarcinoma and histological criteria of poor prognosis with at least six months of follow-up, and who were diagnosed between 2018 and 2024. The therapeutic approach was determined by a multidisciplinary committee.

Results

We included 54 patients (74.1% male) with a mean age of 65.3 years and mean follow-up time of 3.07 years; no significant differences in both groups. The indications for colonoscopy were screening (42.6%), alarm symptoms (38.9%), radiological findings (3.7%), prior polypectomy (9.3%), history of colorectal cancer (1.9%), and family history (3.7%). The rate of patients with endoscopic complications was 2.9% intraprocedural bleeding and 2.9% delayed bleeding.
The mean lesion size was 23.48 mm, and the most common location was the rectum.
Regarding the therapeutic approach, 63.0% of patients underwent surgery and 29.6% underwent endoscopic surveillance. Among the surgical patients, complications included suture dehiscence (6%), and hemorrhage (2%). In the surgical specimen analysis, residual lesion was found in 6 patients, and metastatic lymph nodes in 2. 5.55% required adjuvant therapy due to lymph node involvement, and 1.85% were stage IV at diagnosis, excluded from the comparative analysis.
Comparing both study groups, the surgical group had a significantly higher rate of submucosal invasion, with no differences in the remaining characteristics studied. During the study period, progression with lymph node involvement was observed in one patient who underwent surgery and two patients who underwent endoscopy treatment (average time 11 and 24.5 months, respectively). No patient has developed distant metastases to date.

Conclusion

In our study, patients who underwent endoscopic treatment did not present significant differences with respect to those who received surgery in terms of long-term tumor progression, despite having a higher rate of submucosal invasion. Further studies with larger sample sizes are needed to determine which factors and to what extent influence lymphatic and distant dissemination of pT1 adenocarcinoma.

References

1. Hassan C, Wysocki PT, Fuccio L, Seufferlein T, Dinis-Ribeiro M, Brandão C, et al. Endoscopic surveillance after surgical or endoscopic resection for colorectal cancer: European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Digestive Oncology (ESDO) Guideline. Endoscopy 2019;51:266–77. https://doi.org/10.1055/a-0831-2522.
2. Ozeki T, Shimura T, Ozeki T, Ebi M, Iwasaki H, Kato H, et al. The risk analyses of lymph node metastasis and recurrence for submucosal invasive colorectal cancer: Novel criteria to skip completion surgery. Cancers (Basel) 2022;14:822. https://doi.org/10.3390/cancers14030822.
3. Zwager LW, Bastiaansen BAJ, Montazeri NSM, Hompes R, Barresi V, Ichimasa K, et al. Deep submucosal invasion is not an independent risk factor for lymph node metastasis in T1 colorectal cancer: A meta-analysis. Gastroenterology 2022;163:174–89. https://doi.org/10.1053/j.gastro.2022.04.010.