Introduction

Delayed perforation remains the most dreaded complication following endoscopic mucosal resection (EMR) of large (>/-20mm) non-pedunculated colorectal polyps (LNPCP) and is reported with a frequency of 1.1-3.6% (1,2). It is associated with prolonged hospitalisation and high rates of surgery and stoma formation. The Sydney Deep Mural Injury (DMI) Classification System (3) was first published in July 2016 and we sought to evaluate its subsequent impact on the frequency of delayed perforation

Aims & Methods

A prospective cohort of consecutive patients who underwent colonic EMR in an expert tissue resection centre was evaluated. Following EMR, the standard practice included methodical defect assessment, DMI classification and clip closure of DMI Type 2 or greater. DMI type 3 or greater was defined as significant DMI. Clip closure was performed using through-the-scope clips, targeting the area of DMI rather than complete defect closure. Clinical follow-up by way of a structured telephone interview was conducted at two weeks to screen for adverse events. Routine endoscopic surveillance was performed 6 months post EMR. Data collected included patient and lesion characteristics, the rate of DMI by sub-type, rates of clip closure and the rate of delayed perforation.

Results

Between July 2016 and June 2023 (84 months), 1069 LNPCP underwent EMR (median size 35mm, IQR 20). The rates of DMI, clip closure and perforation by DMI subtype are shown in Table 1. Two (2/1069 [0.19%]) delayed perforations were recorded. Case 1 resulted after EMR of a 50mm LNPCP involving the full circumference of the ileocaecal valve; the fat component within the defect created difficulty in accurately assessing the defect for DMI. The patient was managed conservatively. Case 2 involved a 40mm LNPCP in the ascending colon. No significant DMI was identified after EMR. Clip placement to prevent delayed bleeding was performed with the colon fully distended, creating a shearing effect on the muscularis propria. The patient experienced post-procedural pain and cross-sectional imaging revealed gas and contrast leak. Right hemicolectomy with primary anastomosis was performed. One clip prong had penetrated beyond the muscularis propria. Of the cases with significant DMI, 96% (n=47/49) were discharged on the same day. Successful endoscopic closure was achieved in 48 (98%). One case of DMI type III was not closed as the defect was located in the distal rectum, distal to the peritoneal reflection; there were no adverse events.

Table 1: Rates of intraprocedural and delayed perforation by Sydney Deep Mural Injury (DMI) sub-type in 1069 LNPCP which underwent conventional EMR between July 2016 and June 2023

Conclusion

Meticulous defect interrogation, accurate DMI classification and targeted clip closure of significant DMI resulted in a low rate (<0.2%) of delayed perforation in an expert tissue resection centre. Universal application of the Sydney DMI Classification system greatly attenuates the risk of delayed perforation.

References

1. Heldwein W, Dollhopf M, Rosch T et al. The Munich Polypectomy Study (MUPS): prospective analysis of complications and risk factors in 4000 colonic snare polypectomies. Endoscopy 2005; 37: 1116-1122
2. Heresbach D, Kornhauser R, Seyrig JA et al. A national survey of endoscopic mucosal resection for superficial gastrointestinal neoplasia. Endoscopy 2010; 42: 806-813
3. Burgess NG, Bassan MS, McLeod D, Williams SJ, Byth K, Bourke MJ. Deep mural injury and perforation after colonic endoscopic mucosal resection: a new classification and analysis of risk factors. Gut. 2017 Oct;66(10):1779-1789
   

Introduction

Endoscopic mucosal resection (EMR) of large (>/-20mm) non-pedunculated colorectal polyps (LNPCP) </- 40mm is associated with an increased risk of recurrent or residual adenoma (RRA). Margin Thermal Ablation to the EMR defect margin using snare-tip soft coagulation (MTA) reduces the rate of RRA. We sought to analyse its effect in a large prospective cohort of LNPCP >/-40mm.

Aims & Methods

We retrospectively analysed a prospectively collected cohort of consecutive patients who underwent EMR in an expert tissue resection centre. MTA technique was developed in 2012. Enrolment for the MTA randomised control occurred between July 2013-May 2016 and became standard practice from mid-2017. The cohort was divided into three phases: ‘pre-MTA’; April 2008- June 2012, ‘MTA adoption’; July 2012-June 2017 and ‘standardised MTA’; July 2017-April 2023. The primary outcome was to compare the RRA rate between the three time periods.

Results

Over 15 years until April 2023, 973 LNPCP >/-40mm in 973 patients underwent EMR (median lesion size 50mm, IQR 20mm) of which 893 (92%) were successful. 824 patients (median lesion size 50mm, IQR 20) underwent SC1 (median of 6 months [IQR 4]). The rates of RRA in the pre-MTA, MTA-adoption and standardised-MTA phases were 20.3% (n=45/221), 19.1% (n=59/309) and 4.4% (n=13/294) respectively (p=<0.001). The rates of complete MTA in the pre-MTA, MTA adoption and standardised-MTA phases were 0, 38.2% (n=118/309) and 93.9% (n=276/294). 18 (6.1%) of cases within the standardised-MTA did not receive MTA due to difficult access (n=7), concern for stricture formation in fully circumferential LNPCP (n=9) or sedation-related issues (n=2). The rate of RRA in this group was 22.2% (n=4/18).

Conclusion

MTA post-EMR of LNPCP >/-40mm (median size 50mm) significantly reduced the rate of RRA in a large, prospective cohort. When MTA was not applied, RRA was similar across the three time periods (p=0.1), indicating that the main impact on RRA reduction was the use of MTA with snare-tip soft coagulation, rather than a factor of EMR technique improvement over time.

Introduction

Endoscopic mucosal resection (EMR) is standard of care for the management of large (≥20mm) non-pedunculated colonic polyps (LNPCPs). Its efficacy and cost effectiveness were limited by recurrence. Margin thermal ablation (MTA) to the post-EMR defect, has greatly mitigated this problem. However, electrocautery-related complications of delayed bleeding and perforation incur significant morbidity.
Cold snare polypectomy is effective and safe for the resection of small polyps with negligible recurrence rates. Application of cold snare resection to LNPCPs, while an attractive alternative, lacks high-quality evidence. We conducted a randomized trial to compare the efficacy and safety of cold EMR (C-EMR) to conventional (H-EMR).

Aims & Methods

A prospective single-centre randomized controlled trial was conducted at an Australian tertiary referral centre for flat, 15-50mm adenomatous LNPCPs referred for endoscopic resection. Prior to resection, eligible LNPCPs were randomly assigned to EMR using a dedicated cold snare or conventional H-EMR with margin thermal ablation (control). First surveillance colonoscopy (SC1) was conducted 6 months following resection. Scars were evaluated with high-definition white-light, narrow-band imaging and biopsy. The primary outcome was endoscopically visible and/or histologically confirmed recurrence at SC1. Secondary outcomes were clinically significant post-EMR bleeding (CSPEB), delayed perforation and technical success.

Results

931 LNPCPs were referred for endoscopic resection between November 2019-September 2023. 177 LNPCPs in 177 patients were randomized to either the C-EMR arm (n=87) or H-EMR arm (n=90). Treatment groups were equivalent with no significant difference in lesion size or technical success (86/87 (98.9%) vs 90/90 (100%); p=0.31). One C-EMR required conversion to H-EMR due to unexpected submucosal fibrosis. Following exclusions, 146 LNPCPs undertook SC1 (76 C-EMR, 70 H-EMR). 5 patients await surveillance. On intention to treat and per protocol analysis, recurrence was significantly greater in C-EMR (16/87, 18.4% vs 1/90, 1.1%; p<0.001 and 16/76, 21.1% vs 1/70, 1.4%; p<0.001 respectively). Significant deep mural injury (27/90 (30%) vs 0; p<0.001) and delayed perforation (1/90 (1.1%) vs 0; p=0.32) only occurred in the H-EMR group. CSPEB and intraprocedural bleeding were significantly greater in the H-EMR arm (7/90 (7.8%) vs 1/87 (1.1%); p = 0.034 and 12/90 (13.3%) vs C-EMR arm 1/87 (1.1%); p=0.002 respectively).

Conclusion

Compared to conventional H-EMR, C-EMR for flat, adenomatous LNPCPs, demonstrates superior safety with equivalent technical success. However, endoscopic recurrence is significantly greater for cold snare resection and is currently a limitation of the technique.

Disclosure

Michael Bourke: Research Support: Olympus Medical, Cook Medical, Boston Scientific
The remaining authors have no financial, professional, or personal conflicts of interest to disclose

Introduction

Endoscopic submucosal dissection (ESD) is increasingly promoted as the optimal treatment strategy for all large non-pedunculated colorectal polyps (LNPCP). The effect of a universal en bloc strategy on oncological outcomes for the treatment of LNPCP in the right colon is unknown. We evaluated this in a large Western population.

Aims & Methods

We retrospectively analysed prospectively collected data from major tertiary centres where patients were referred for endoscopic resection (ER) of LNPCP (N=5084). Patients found to have cancer after ER and those referred directly to surgery were included. The primary outcome was to determine the proportion of right colon LNPCP with low-risk cancer.

Results

Over 180 months until June 2023, 3294 sporadic right colon LNPCP in 2956 patients were referred for ER at 7 sites (median size 30mm [IQR 15]). 63 (2.1%) patients were referred directly to surgery and cancer was proven in 56 (88.9%). 2851/2956 (96.4%) LNPCP underwent ER (median size 35mm [IQR 20]) of which 75 (2.6%) were cancers. The overall prevalence of cancer in the right colon was 4.4% (131/2956). Detailed histopathological analysis was possible in 115/131 (88%) cancers (71 after ER, 44 direct to surgery, Table 1). 23/2940 (0.78%) sporadic right colon LNPCP were low-risk cancers.

Table 1: Final Oncologic Outcomes; comparison between histopathologic variables of cases referred directly to surgery versus following endoscopic resection

Conclusion

The proportion of right colon LNPCP referred for ER containing low-risk cancer amenable to endoscopic cure was <1%, in a large, multicentre Western cohort. A universal ESD strategy for the management of right colon LNPCP is unlikely to yield improved patient outcomes given the minimal impact on oncological outcomes, significant resource demands and increased adverse events.

Introduction

Radical resection in the rectum is associated with significant morbidity and poses a mortality risk, particularly in elderly or comorbid patients. Early or T1 rectal cancer is often curable and can be managed with local endoscopic resection techniques with reduced morbidity and negligible mortality. To establish a pathway for appropriate treatment of these early lesions through the multidisciplinary team (MDT), an early rectal cancer working party (ERCWP) was formed to evaluate management trends and outcomes within our hospital network. The ERCWP was multi-speciality comprising of gastroenterologists, colorectal surgeons and radiation oncologists.

Aims & Methods

A retrospective review was performed across four institutions that make up our network to identify all patients with a new diagnosis of localised (T1-T4,N0,M0) rectal or recto-sigmoid cancer between January 2015 and August 2023. Patients with confirmed adenocarcinoma staged as T1N0M0 or T2N0M0 were included in the analysis. Available electronic medical records from the time of index resection and all encounters for the following 12 months were reviewed. Patients were excluded if their treatment was completed at an outside institution. Patient outcomes were stratified by location of tumour (rectum / recto-sigmoid) and mode of resection (Endoscopic resection, Local surgical excision or Radical surgical resection). Major adverse events included any one of the following: ostomy, deep incisional site infection, abscess, wound dehiscence, pneumonia, sepsis, septic shock, acute renal failure, deep venous thrombosis, pulmonary embolus, stroke/cerebrovascular accident, myocardial infarction, ventilator >48 hours, still in hospital >30 days, cardiac arrest, reoperation, readmission and/or mortality.

Results

A total of 111 localized (T1/T2,N0) and 153 locally advanced (T3/T4,N0) lesions were newly diagnosed during the study period. 95/111 patients with localized disease were included (M=62/95, 65.3% F=33/95, 34.7%). Mean age was 67.8 years in the endoscopy group and 67.0 years in the radical surgical resection group. Mortality was 2.2% in the group of patients who had surgery (1/46). There was no mortality in patients who received endoscopic resection. Major adverse events were recorded in 16/46 (34.8%) of patients who underwent surgery. There were no major adverse events in patients who received endoscopic resection. Mean length of stay was 1.47 days in patients who had endoscopic resection and 10.2 days in patients who had radical resection. Mean length of stay was prolonged where there was a treatment related major adverse event (14.8 days, mean difference 9.8 days, p=<0.001). 78.5% (51/65) of the cohort with T1 cancer was low risk (well or moderately well differentiated and no lymphovascular invasion). Of the 16 patients with T1 rectal cancer who underwent definitive surgery, 15 (93.8%) were suitable for cure by en-bloc endoscopic excision. Following establishment of the ERCWP in 2020, there have been no cases of radical resection in the rectum for T1 cancer. For T1 cancer in the rectum, major adverse events were 5/34 (14.7%) pre ERCWP formation and 1/13 (7.7%) post ERCWP formation (p=<0.001).

Conclusion

Surgery carries a high risk of morbidity in patients with rectal cancer. Endoscopic resection carries a favourable risk profile and is currently being underutilised. Formation of a local expert group focusing on outcomes in T1 cancer can reduce unwarranted variation and similar groups should be formed at local institutions to optimise patient outcomes.

Introduction

EMR is the standard of care for the management of large (≥20mm) non-pedunculated colonic polyps (LNPCPs). However, its efficacy and cost effectiveness, are limited by recurrence and the necessity for scheduled surveillance. Consequently, current surveillance intervals are conservative. Margin thermal ablation (MTA) after EMR for LNPCPs has dramatically reduced the incidence of recurrence at first surveillance colonoscopy at six-months (SC1). If this effect is durable, then subsequent surveillance intervals in patients who have been cleared of synchronous polyps could be substantially lengthened. We prospectively evaluated long-term surveillance outcomes in a cohort of LNPCPs that have undergone MTA.

Aims & Methods

Consecutive patients with LNPCPs undergoing EMR and MTA from four academic endoscopy centres were prospectively recruited. All patients that underwent successful endoscopic resection received SC1 six months post resection. EMR scars were carefully evaluated with high-definition white light, narrow band imaging with near focus and biopsy. In the absence of recurrence, second surveillance (SC2) colonoscopy was conducted at a subsequent interval of 12 months with the scar evaluation process repeated. The primary outcome was recurrence at SC2 in all LNPCPs with a recurrence-free scar at SC1.

Results

1324 LNPCPs referred for EMR were enrolled over 90 months until October 2022. Following exclusions, 1163 LNPCPs underwent EMR with complete MTA. 856 LNPCPs underwent SC1. 32 additional synchronous LNPCPs were cleared at this procedure. 25/856 (2.9%) (95%CI 1.9-4.3%) LNPCPs demonstrated recurrence. 469 LNPCPs free of recurrence at SC1 (median size 35mm) underwent SC2 at a mean interval of 22.9 months (95%CI 21.9-23.95) after the index EMR. 468 demonstrated a bland scar without recurrence. Only one recurrence occurred (0.2% 95%CI 0-1.2%), related to a 0-IIa+Is 20mm granular TVA located on the ileocaecal valve.

Conclusion

LNPCPs that have undergone successful EMR with MTA and are free of recurrence at SC1 are very unlikely to develop recurrence in subsequent surveillance out to 2 years. Following EMR of LNPCPs with MTA, patients who are cleared of synchronous neoplasia and demonstrate no recurrence after careful scar examination, can potentially undergo next surveillance in 3-5 years. Such an approach would reduce costs and enhance patient compliance.

Disclosure

Michael Bourke: Research Support: Olympus Medical, Cook Medical, Boston Scientific
The remaining authors have no financial, professional, or personal conflicts of interest to disclose

Introduction

Although delayed perforation is a rare complication of endoscopic resection of colonic lesions, the potentially fatal outcomes make this a significant risk. Using a rat model in which delayed colon perforation occurs 48 hours after thermal injury, we have demonstrated that the mechanism of delayed colonic perforation resembles the Jackson’s burn model, which is a well-established model of skin thermal injury. Based on our further discovery that bacterial infection played a role in delayed colonic perforation, we hypothesized that delayed colonic perforation would not occur in pseudo-germ-free rats.

Aims & Methods

The aim of this study is to evaluate the effect of pseudo-sterilization of the colon on delayed colonic perforation after thermal injury.
Eight rats were administered antibiotics (metronidazole, ampicillin, vancomycin, and neomycin) from day 1–5 to create a pseudo-germ-free group (n = 8). Eight further rats were administered sterilized water as a control group (n = 8). Fecal samples were collected on days 7–9 for spectrophotometric analysis of enzyme activity (β-glucuronidase, β-galactosidase, β-xylosidase). Thermal injury was induced in the colon on day 7 in nine of the pseudo-germ-free group and nine of the control group using a hemostatic forceps through an endoscope. The colon was removed on day 9 and histological evaluation performed.

Results

The activity levels of β-glucuronidase, β-galactosidase, and β-xylosidase on day 7 were significantly reduced in the pseudo-germ-free group compared with the control group (0.012 vs. 0.090, p = 0.003; 0.045 vs. 0.168, p = 0.001; and 0.008 vs. 0.047, p = 0.002, respectively). On day 9, activity levels of β-glucuronidase and β-xylosidase were significantly reduced in the pseudo-germ-free group compared with the control group (0.007 vs. 0.054, p = 0.000 and 0.015 vs. 0.042, p = 0.000, respectively). These findings clearly demonstrate the successful achievement of pseudo-sterilization. The rate of delayed perforation and number of MPO-positive cells in the serosa were significantly lower in the pseudo-germ-free group than the control group (11.1% vs. 100%, p = 0.000 and 986.985 /mm² vs. 2303.782 /mm², p = 0.023, respectively). Infiltration of Escherichia coli into the submucosal layer was only observed in the control group. Summary of results, tissue degeneration extending to the muscularis propria was observed in both groups after thermal injury; however, delayed colonic perforation was observed only in the control group, while it was significantly reduced in the pseudo-germ-free group.

Conclusion

Pseudo-germ-free conditions in the colon suppressed the occurrence of delayed colonic perforation. Bacterial infection may play a significant role in the expansion of the necrotic zone to the muscularis propria.