Introduction

Colorectal endoscopic submucosal dissection (ESD) allows high rate of en bloc resection of colorectal neoplasm. It is still not widely used; however, the factors that limit its diffusion are its technical difficulty, its duration and the risk of complications. Due to the long duration and the high risk of intra-procedural discomfort, colorectal ESD is usually performed under deep sedation or in narcosis. The aim of the study is to determine the factors associated with intra-procedural discomfort.

Aims & Methods

We retrospectively analyzed colorectal ESD performed in our centre between November 2018 March 2023. Procedures performed in narcosis with anaesthesiologist assistance were excluded. We collected data of sedation, in particularly the presence of pain during the procedure was measured with the Gloucester scale from nursing records. The patients were divided into two groups: the first with no/mild discomfort (Gloucester 1-2), the second group with moderate/severe discomfort (Gloucester 3-4). Univariate and multivariate analyses were performed to examine factors that may have influenced intra-procedural discomfort.

Results

		UNIVARIATE ANALYSIS			MULTIVARIATE ANALYSIS
VARIABLE	OR	95% CI	p	OR	CI	p
Size lesion < 40 mm	2.30	1.11 - 4.77	0.0237	2.78	1.29 - 5.99	0.0092
Underwater-ESD	2.26	1.03 - 4.92	0.0357	2.76	1.21 - 6.28	0.0154
Rectum	1.81	0.79 - 4.13	0.1501
Right colon	0.72	0.35 - 1.47	0.3632
Left colon	0.82	0.35 - 1.90	0.6391
Non granular	0.74	0.35 - 1.55	0.4214
Granular	0.93	0.46 - 1.91	0.8531
Sessile	2.55	0.69 - 9.36	0.1293

A total of 154 colorectal ESD for superficial neoplasms were considered. 18 colorectal ESD were excluded because performed in narcosis. The remaining 136 colorectal ESD (male 59,6% with a median age of 68.4 ± 10.1) achived en bloc resection and complete resection in 124 (91 %) and 121 (89 %) cases respectively; mean major diameter’s neoplasms was 3.8 cm (±1.81cm), in 79 cases the size was < 40 mm (42%). 65 neoplasms were located in the right colon (48%), 30 in the left colon (22%) and 41 in the rectum (30%). 53 colorectal ESD (39%) were performed using underwater technique. 92 patients (67 %) were included in the first group (Goucester 1-2), the other 45 patients (33 %) in the second group (Goucester 3-4). On univariate analysis, underwater-ESD (OR 2.2; 95% CI 1.03 – 4.92) and small size of the neoplasms (< 4 cm) (OR2.3; 95% CI 1.11 – 4.78) were significantly associated with lower intra-procedural discomfort during the procedure. The morphology (non granular, granular or sessile) and the localization were not associated with intra-procedural discomfort. The multivariate analysis confirmed the significantly correlation of underwater-ESD and small neoplasms size with lower discomfort during procedures.

Conclusion

Underwater-ESD and lesion size < 40 mm are associated to less discomfort during colorectal ESD. These findings should be taken into consideration approaching colorectal ESD.

Introduction

Colorectal endoscopic submucosal dissection (ESD) is not widely performed in western countries due to technical complexity, risk of adverse events, and procedure time. Hybrid ESD (H-ESD) - partial submucosal dissection followed by snare-assisted resection – may be useful to achieved endoscopic resection in difficult situations. In our center we use H-ESD as rescue therapy during conventional ESD in case of unstable position, inability to achieving appropriate and safe knife angle, advanced submucosal fibrosis or thin submucosal layer and patient instability.

Aims & Methods

We retrospectively analyzed colorectal ESD performed in our centre between January 2014 and March 2023, colorectal lesions in inflammatory bowel diseases were excluded. Univariate and multivariate analyses were conducted to examine factors that may have influenced switch to H-ESD.

Results

A total of 281 colorectal ESDs for superficial neoplasms in 276 patients were considered. 160 patients (58%) were male with an average age of 68,9 years. In 55 (19,6%) cases ESD was switch to H-ESD.. 171 lesions were located in the colon (60.8 %) and 110 (39.1%) in the rectum; mean maximum diameter of the neoplasms was 35,9 mm (SD 18,4 mm). En bloc resection and complete resection (en bloc resection and R0) were achieved in 259 (92 %) and 245 (86 %) cases respectively.
On univariate analysis, the use of waterjet system-assisted knife (OR 0,3; 95% CI 0,17-0,57), underwater-ESD (OR 0,24; 95% CI 0,09-0,63), rectal localization (OR 0,17; 95% CI 0,07-0,40) and granular laterally spreading morphology (OR 0,40; 95% CI 0,21-0,75) were significantly associated to the achievement of complete ESD. Proximal colon localization (OR 3,9; 95% CI 2,08-7,30), severe submucosal fibrosis (OR 4,9; 95% CI 2,51-9,63), non-granular laterally spreading morphology (OR 2,31; 95% CI 1,27-4,21) and maximum diameter < 40 mm (OR 3,91; 95% CI 1,83-8,38) were related to the switch to H-ESD. On multivariate analysis only waterjet system-assisted knife use and U-ESD were significantly correlated with achievement of complete ESD; severe submucosal fibrosis and proximal colon localization resulted significantly related to the switch to H-ESD.

	Univariate Logistic Regression			Multivariate Logistic Regression
VARIABLE	OR	CI	P	OR	CI	P
Proximal colon	3,90	2,08-7,30	<0,0001	3,0481	1,21-7,68	0,0181
Rectum	0,17	0,07-0,40	<0,0001	0,3956	0,13- 1,21	0,1048
LST NG	2,31	1,27-4,21	0,0061	0,6277	0,22-1,78	0,3812
LST G	0,40	0,21-0,75	0,0039	0,4494	0,15-1,32	0,1452
Maximum diameter < 40 mm	3,91	1,83-8,38	0,0004	1,9589	0,81-4,76	0,1378
Severe submucosal fibrosis (F2)	4,91	2,52-9,63	<0,0001	4,6588	2,10-9,88	0,0001
Waterjet system-assisted knife	0,30	0,17-0,57	0,0002	0,4297	0,21-0,88	0,0219
Underwater ESD	0,24	0,09-0,64	0,0039	0,1612	0,06-0,47	0,0008

Conclusion

The use of waterjet system-assisted knife and underwater technique reduce the need to switch to H-ESD during endoscopic submucosal dissection of superficial colorectal lesions. Severe submucosal fibrosis and proximal location are risk factors for the need for the H-ESD switch.

Introduction

A positive resection margin after endoscopic submucosal dissection (ESD) of a colorectal neoplasm is associated with an increased risk of recurrence. However, it may be caused by cauterization or tangential specimen cutting. We aimed to identify the clinical significance of positive resection margins in colorectal neoplasms after ESD.

Aims & Methods

We reviewed 1010 patients who underwent colorectal ESD at two hospitals between 2015 and 2020. The inclusion criteria were that the patient 1) had an en bloc resection, 2) had at least one follow-up colonoscopy. The recurrence rates and presence of residual tumors in the surgical specimens were evaluated.

Results

A total of 632 patients were enrolled. Among them, 557 patients had complete resections, and 75 had incomplete resections with positive resection margins in vertical and/or horizontal margin. The rate of additional surgery after ESD and recurrence was significantly higher in patients with incomplete resection compared to patients with complete resection. However, in patients with non-invasive colorectal neoplasm, all 411 patients, including those with complete and incomplete resection, had no recurrence. Among 221 patients with invasive lesions, 39 underwent additional surgery due to non-curative resection. Positive vertical margin and lymphovascular invasion were associated with remnant tumors in the surgical specimen. Lymphovascular invasion was associated with lymph node metastasis. However, no remnant tumor nor lymph node metastases were found in patients with only one unfavorable histological factor, including 1) positive vertical margin, 2) a submucosal invasion depth > 1000 µm, 3) lymphovascular invasion, 4) poorly differentiated cancer, and 5) high tumor-budding grade.

Conclusion

A positive resection margin after en bloc colorectal ESD for noninvasive lesions was not associated with recurrence. In T1 colorectal cancer with a positive vertical resection margin, salvage surgery can be considered in selected patients with additional risk factors.

Introduction

Endoscopic submucosal dissection (ESD) is emerging as the standard treatment for suspected superficial submucosal invasion lesions. Considering the global population ageing, understating the feasibility of this approach in elderly patients is of the utmost importance. Studies in this field have shown a tendency towards reduced resection rates and higher rates of complications.

Aims & Methods

We sought to assess the effectiveness and safety of colorectal ESD for patients aged ≥ 80 yo compared to 65-79 yo patients. We prospectively enrolled consecutive patients aged >64 years undergoing colorectal ESD between January 2019 and December 2023 from ten Italian Tertiary Referral Centres. Patients were classified as Elderly Group (E-Group, age >80 yo) and non-elderly group (NE-Group, 65-79 yo). Procedure outcomes and adverse events were compared between E-Group and NE-Group and between patients with comorbidities and healthy (1-CM-Group and H-Group).

Results

A total of 980 patients were included [269 (27.5%) in the E-Group and 711 (72.5%) in the NE-Group]. Table 1 summarises the principal data and outcomes.

En-bloc resection and R0 rate did not statistically differ (p=0.30; p=0.05) between E and NE-Groups. Oncological curative resection was achieved in the two groups without significant differences (p=0.41). Histological outcomes were comparable between the two groups, except for lymphovascular invasion [E:14 (5.2%) vs NE:14 (2.0%); p=0.007 – OR:2.9 (CI:1.3-6-6)]. Regarding clinical course, intraprocedural and 14 days-adverse events (AEs), no statistically significant differences were found between the two groups, except for a higher rate of post-procedure delirium in the E-Group [6 (2.2%) vs 1 (0.1%); p=0.001–OR:16.2 (CI:1.9-135.2)]. 1-CM-Group showed a higher rate of intraprocedural bleeding (p=0.001), fever onset (p<0.001), C-reactive protein (p=0.006) and procalcitonin increase (p=0.02), delayed perforation (p=0.03) and systemic infections (p=0.02) compared to the H-Group. The presence of one or more comorbidity, but not the age, was associated with a poorer clinical course [p<0.001; OR:2.3 (CI:1.5-3.6)] and poor overall course (poor clinical course combined with 14 days AEs) [p=<0.001; OR:2.1 (CI:1.4-3.0)]. ASA classification (OR: 1.36; CI:1.01-1.83), the presence of one comorbidity (OR: 1.73; CI:1.14-2.63), and procedure time (OR: 1.01; CI:1.00-1.01) were poor outcome predictors. After excluding patients with at least one comorbidity, still no differences in terms of poor overall course (p=0.21) were registered between E and NE-Group.

Conclusion

Colorectal ESD is an effective and safe procedure in elderly patients. Physicians should ackowledge delirium as a possible AE in patients aged over 80. The presence of comorbidities should drive the execution of a comprehensive pre-procedural assessment and post-procedural care, to optimize outcomes and minimize complications.

Introduction

The technique of colorectal ESD has become increasingly standerdised, but challenges still remain for difficult cases. These include lesions occurring on the gravity side that become submerged in fluids, lesions at the colonic flexures that are difficult to approach, and lesions that face the endoscope perpendicularly. The advantages of “gel-immersion endoscopy”, include not only the easier identification of the bleeding point, but also enhancement of the visual field by clearing away the intestinal fluids and residues, aid traction of the lesion using buoyancy, and allowing to secure the visual field between the intestinal folds without needing to insufflate of the intestinal tract with gas. These advantages are favorable for colorectal ESD, and there are case reports of colorectal gel-immersion ESD (Gi-ESD), but there have been no studies of consecutive case series.

Aims & Methods

The present study aimed to clarify the indications and outcomes of Gi-ESD. This was a retrospective cohort study of consecutive patients with colorectal neoplasms who underwent ESD between July 2022 and May 2024. The inclusion criteria consisted of all colorectal ESD performed in our hospital. The exclusion criteria include (i) non-neoplastic lesion; (ii) carcinoma invading muscularis propria; (iii) underwater ESD method; and (iv) use of traction devices, (v)significant loss of clinical data. Gi-ESD was defined as mucosal incision and submucosal dissection performed partially or totally under clear gel (VISCOCLEAR, Otsuka pharmaceutical factory, Japan). Conventional ESD (c-ESD) was defined as all incisions and dissection performed without gel. The primary outcomes were en bloc resection rate and histologic R0 resection rate. Secondary outcomes were procedure time, dissection speed, intraoperative or postoperative perforation, postoperative hemorrhage, and gel-related adverse events.

Results

Among the 260 ESD, 29 were Gi-ESD group and 231 were c-ESD group. Gi-ESD group had significantly larger tumor diameters (25mm vs 18mm, p = 0.001), had a higher rate of lesions located in the cecum or ascending colon (55.2% vs 31.2%, P = 0.01), and had a higher rate of factors associated with difficult ESD (24.1% vs 9.5%, P< 0.05).
Gel was used to improve the visual field and aid traction during ESD, by lifting the lesion using buoyancy in 14 cases(48.3%) where the lesions occurred on the gravity side, to secure the visual field in cases where the lesion could not be approached without degassing such as behind the folds or colonic flexure in 9 cases(31%), and to allow ESD to be performed in a parallel direction with the muscularis propria in lesions that would otherwise have faced the endoscope perpendicularly under CO₂ insufflation in 6 cases(20.7%). Procedure time was significantly longer in the Gi-ESD group (50min vs 32min; P<0.001), but there was no significant difference in the dissection speed (14mm2/min vs 16.1mm2/min, p=0.45). There were no significant differences in the incidences of intraoperative perforation (0% vs 0.4%), delayed perforation (0% vs 0%), or post operative hemorrhage (3.4% vs 0.4%, p=0.21). There were no significant differences in both the en bloc resection rate (100% vs 99.1%) and the pathologic complete resection rate (96.6% vs 88.7%, p=0.33).

Conclusion

Using gel, en bloc resection was obtained without reducing the dissection speed, even for larger lesions associated with factors that make ESD difficult. Gi-ESD for colorectal lesions may be an alternative approach for lesions occurring on the gravity side and for lesions that are difficult to approach under CO₂ insufflation.

References

Yano T et al. Gel immersion endoscopy: A novel method to secure the visual field during endoscopy in bleeding patients. Gastrointestinal endoscopy 2016; 83: 809-11.
Nakano Y et al. Colorectal gel immersion endoscopic submucosal dissection using the tunneling method. Endoscopy 2023; 55: E864-e5.

Introduction

Piecemeal endoscopic mucosal resection (EMR) vs endoscopic submucosal dissection (ESD) has been a long standing debate in the endoscopic community worldwide with multiple studies done to evaluate the preferred method to manage large colorectal neoplasms. Piecemeal EMR with thermal ablation of the margin has been strongly advocated and reported by certain groups to be a simple, inexpensive and effective technique and this has been preferred widely due to its perceived ease of performance and shorter learning curve.¹ However, close, repeated surveillance colonoscopy is recommended even when the lesion is thought to have been completely resected² as residual tumors can cause interval cancers.³ Some groups, mainly from east Asian countries, have recommended en bloc resection by ESD due to significantly lower risk of local recurrence and precise pathological diagnosis.⁴ But its usage is limited due to concerns about risk of serious adverse events. With improvement in training and devices, colorectal ESD is now being performed by various centers globally. This study aims to report the outcomes of an international, multicenter study on colorectal ESD.

Aims & Methods

Patients who underwent colorectal ESD for lesions greater than 20mm between January 2022 to April 2024 from centers in USA, Japan, and India respectively were included in this study. Recurrent lesions after endoscopic therapy, neoplasms identified in patients with ulcerative colitis, and non-epithelial lesions were included. Primary outcomes were en bloc and R0 resection rate, delayed adverse events (bleeding/perforation), and local recurrence rate. Secondary outcomes were procedure time, lesion size, and pathology. Univariate and multivariate analysis were done to identify the risk factors for primary outcomes.

Results

309 patients (median size, 40(27.5-60)mm; location rectum 52.4%, left colon 26.2%, right colon 21.4%) were involved in this study. The en bloc resection rate was 96.1% and R0 resection rate was 90.3%. 3 patients experienced delayed bleeding which was managed endoscopically. 2 patients underwent surgery for delayed perforation. 6 patients had a local recurrence. 67(23%) patients had intramucosal carcinoma on pathology. Univariate analysis showed lesser procedure time (median(IQR) 145(80-236.25) vs 270(180-300) minutes, P= 0.005) and smaller lesion size (median(IQR) 40(26-56.25) vs 60(40-90) mm, P= 0.004) were significant factors for successful en bloc resection. However, lesser procedure time (median(IQR) 74(29.5-97.5) vs 150(82.5-240) minutes, P= 0.034) led to an increased delayed adverse event rate. Multivariate analysis using Cox regression showed en bloc resection (odds ratio 0.038; 95% confidence interval 0.003-0.421; P= 0.008) was an independent factor preventing local recurrence.

	Factors	Variables		P value
En bloc resection rate		En bloc resection (n=297)	Piecemeal resection (n=12)
	Procedure Time (median (IQR) minutes)	145 (80 – 236.25)	270 (180 – 300)	0.005
	Lesion Size (median (IQR) mm)	40 (26 – 56.25)	60 (40 – 90)	0.004
Recurrence rate		Recurrence (n=6)	No recurrence (n=257)
	En Bloc resection n (%)	4 (66.7)	246 (98)	0.009
Adverse events		Delayed adverse events (n=5)	No delayed adverse events (n=304)
	Procedure Time (median (IQR) minutes)	74 (29.5 – 97.5)	150 (82.5 – 240)	0.034

Conclusion

This international, multicenter study with data from three countries shows favorable outcomes for colorectal ESD for large lesions. The high en bloc and R0 resection rate, and low adverse event rate show increased global adaptation to this procedure. Reduced local recurrence is an added benefit. Data from a more centers globally will be valuable to establish ESD as the standard for large colorectal neoplasms.

References

1. Sidhu M, Shahidi N, Gupta S et al. Outcomes of thermal ablation of the mucosal defect margin after endoscopic mucosal resection: a prospective, international, multicenter trial of 1000 large nonpedunculated colorectal polyps. Gastroenterology. 2021 Jul 1;161(1):163-70.
2. Gupta S, Lieberman D, Anderson JC et al. Recommendations for Follow-Up After Colonoscopy and Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colorectal Cancer. Gastrointest Endosc 2020;91:463-485.e5.
3. Rutter MD, Beintaris I, Valori R et al. World Endoscopy Organization Consensus Statements on Post-Colonoscopy and Post-Imaging Colorectal Cancer. Gastroenterology 2018;155:909-925.e3.
4. Ohata K, Kobayashi N, Sakai E et al. Long-term outcomes after endoscopic submucosal dissection for large colorectal epithelial neoplasms: a prospective, multicenter, cohort trial from Japan. Gastroenterology. 2022 Nov 1;163(5):1423-34.

Introduction

Prophylactic clip closure is known to avoid delayed adverse events post colorectal endoscopic submucosal dissection (ESD).¹ It may also improve reduce the duration of hospitalization.² However, endoscopic clips have limitation of defect size that can be completely closed due to their limited opening width. Other studies have suggested methods to completely close a mucosal defect using special devices^{3, 4} which have limitations of availability, learning curve, scope removal and reinsertion, and negotiation in narrow spaces. An ideal closure technique has been described as a technique which is technically easy, requiring no special accessories or endoscopes, managed through accessory channel without endoscope removal, possible in narrow space, creating no dead space, and being economical.⁵ We recently developed a Clip with Line Pulley Securing (CLiPS) technique to completely close large mucosal defect which fulfils the criteria for an ideal closure technique.⁶

Aims & Methods

The aim of this study was to report the feasibility and efficacy of CLiPS technique for closure of large mucosal defects following colorectal ESD. This study retrospectively evaluated 53 consecutive patients who underwent closure using CLiPS technique post colorectal ESD. CLiPS technique involves deployment of a clip with nylon line on the edges of the ulcer which are approximated using external counter traction. An endoloop is deployed to fix the line. The principle is supporting the clip line with an endoloop and creating a pulley system by giving external countertraction to the line, to facilitate a strong, stable approximation of edges, thereby making the defect more linear. The line is cut and final closure is completed with conventional clips. The primary outcomes were complete closure rate and adverse events. The secondary outcomes were closure time and defect size.

Results

The lesion characteristics are given in the 'table'. Complete closure was achieved in 94.3%(50/53) of cases. The mean defect size was 48.2­+18.8 mm and median closure time was 14(5-58) minutes. There was one case each of delayed bleeding and perforation which were managed by endoscopic clipping.

Characteristic		n(%)
Paris classification	Is	3(5.7)
	IIa	45(84.9)
	IIc	5(9.4)
Location	Right colon	25(47.1)
	Left colon	18(34)
	Rectum	10(18.9)
Histopathology	Adenoma	27(50.9)
	Carcinoma	25(47.2)
	Others	1(1.9)

Conclusion

CLiPS technique has reasonable outcomes and can be considered to be a safe and effective closure method for large post ESD colorectal defects. Further prospective study may be undertaken to establish wider acceptability of this method.

References

1. Liu M, Zhang Y, Wang Y, et al. Effect of prophylactic closure on adverse events after colorectal endoscopic submucosal dissection: A meta‐analysis. Journal of Gastroenterology and Hepatology. 2020 Nov;35(11):1869-77.
2. Abe S, Saito Y, Tanaka Y, et al. A novel endoscopic hand-suturing technique for defect closure after colorectal endoscopic submucosal dissection: a pilot study. Endoscopy. 2020 Sep;52(09):780-5.
3. Farha J, Ramberan H, Aihara H, et al. A novel through-the-scope helix tack-and-suture device for mucosal defect closure following colorectal endoscopic submucosal dissection: a multicenter study. Endoscopy. 2023 Jun;55(06):571-7.
4. Keihanian T, Zabad N, Khalaf M, et al. Safety and efficacy of a novel suturing device for closure of large defects after endoscopic submucosal dissection (with video). Gastrointestinal Endoscopy. 2023 Sep 1;98(3):381-91.
5. Nomura T, Sugimoto S, Temma T, et al. Suturing techniques with endoscopic clips and special devices after endoscopic resection. Digestive Endoscopy. 2023 Mar;35(3):287-301.
6. Minato Y, Ohata K, Kimoto Y, et al. A modified approach for closing endoscopic submucosal dissection defects using clip with line pulley securing technique and endoloop. VideoGIE. 2024 Mar 27.