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Treatment outcomes of endoscopic submucosal dissection and surgery for colorectal neoplasms in patients with ulcerative colitis

Abstract Objectives This study aimed to clarify the validity and long‐term outcomes of colorectal endoscopic submucosal dissection (ESD) of visible lesions (≥20 mm) in patients with ulcerative colitis (UC) and investigate the incidence of undetected lesions in surgical specimens. Methods This single‐center retrospective study included 11 lesions from nine patients with UC who underwent ESD and 19 lesions from nine patients with UC who underwent colectomy between March 2001 and January 2019. We evaluated the endoscopic findings of scarring, atrophy, and loss of haustra in the ESD group, and we determined the lesion visibility in the colectomy group. We investigated the clinicopathological features of all lesions and examined the follow‐up evaluations in the ESD group. Results The en bloc and curative resection rates of ESDs were 91% and 82%, respectively. Endoscopic findings of scarring, atrophic colitis, and loss of haustra were observed in two (18%), seven (64%), and one (9%) lesions, respectively. The two lesions with scarring showed severe submucosal fibrosis. Mortality and recurrence were not observed during the median follow‐up of 25 months. Metachronous lesions ≥20 mm were detected in two patients, which were successfully treated with ESDs. In the colectomy specimens, 21% of the lesions were undetected, 67% had multiple neoplasms, and 33% had multiple invasive cancers. Conclusions ESD is feasible and valid for large visible lesions in patients with UC; however, for lesions with endoscopic findings of scarring, technical difficulties in endoscopic resection must be considered. In addition, intensive surveillance colonoscopy is necessary to detect undetected lesions.


INTRODUCTION
In Japan, the number of patients with ulcerative colitis (UC) was 168,000 in 2016, which shows an increase of 1.8-fold compared to the number 10 years ago, and the number of treatments for UC-associated neoplasias (UCANs) are expected to increase. 1 In the clinical guidelines from Western countries and Japan, surgical interventions, including total colectomy, are recommended to improve the prognosis of patients with UC when high-grade dysplasia or invasive carcinoma is detected by surveillance colonoscopy. 2,3 However, for local lesions, such as low-grade dysplasia and sporadic epithelial neoplasia (SPEN), endoscopic treatment can be a therapeutic option.

Recently, the Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in Inflammatory Bowel Disease Patients
International Consensus Recommendations (SCENIC) announced a consensus statement that after complete endoscopic resection of endoscopically visible lesions, surveillance colonoscopy, rather than colectomy, is recommended. 4 This recommendation has been adopted by the American Society for Gastrointestinal Endoscopy 3 and the European Crohn's and Colitis Organization. 2 Several studies have reported favorable long-term outcomes of endoscopic mucosal resection and polypectomy for polypoid or small neoplastic lesions in patients with UC. [5][6][7] Although some studies on the treatment outcomes of ESD for patients with UC have been conducted, the sample size was small (i.e., 7-32 patients) and almost all reported lesion's were relatively small (i.e., <20 mm); thus, the available data are limited. [8][9][10][11][12] Furthermore, the endoscopic management of visible lesions greater than 20 mm in size remains a concern because of the technical difficulties and the possibility of other synchronous undetected lesions. Moreover, pre-ESD endoscopic findings that could predict technical difficulties during ESD procedure are unknown.
Thus, in this study, we aimed to clarify the validity and long-term outcomes of colorectal ESD of visible lesions ≥20 mm in patients with UC and investigate the incidence of undetected lesions in surgical specimens.

Study population
This study was approved by the ethical review board of our institu-

Endoscopic submucosal dissection procedure
Details of the ESD techniques have been described previously. 13 All procedures were performed using the following: an insulation-

Histopathology analysis
Endoscopically resected specimens were serially sectioned at 2-3 mm intervals, and surgically resected specimens were sectioned at 4-5 mm intervals. Histological classification was according to the World Health Organization criteria. 14 We identified low-grade dysplasia and low-grade adenoma by evaluating the proliferative zone. 12 The histopathological classifications were as follows: lowgrade dysplasia, low-grade tubular adenoma, high-grade tubular adenoma, sessile serrated lesion, traditional serrated adenoma, lowgrade adenocarcinoma, high-grade adenocarcinoma, squamous cell carcinoma. 12 Based on a previous study, low-grade dysplasia was classified as UCAN, and low-grade tubular adenoma and high-grade tubular adenoma were classified as SPEN. 12 Curative resection was confirmed when pathological findings showed R0 resection without any of the following features: submucosal deep invasion (≥1000 μm), lymphovascular involvement, or poorly differentiated adenocarcinoma component. 13 Histological classification was confirmed by a gastrointestinal pathologist (SS).

Follow-up
Patients who underwent ESD and curative resection were followed up with colonoscopy within 1 year after the ESD and at 1-to 2-year intervals thereafter. Abdominal computed tomography (CT) was performed as needed.

Data collection
Long-term clinical outcome data between May and November 2020 were obtained. Information on age, sex, Mayo endoscopic subscore, UC disease duration, histopathological type, and tumor invasion depth were obtained from medical records. The cecum, ascending colon, and transverse colon were classified as right-sided colon; the descending colon and sigmoid colon, as left-sided colon. The rectosigmoid colon was classified as the rectum.

Endoscopic submucosal dissection data
Clinicopathological and treatment outcome data were analyzed using our prospectively stored database. To examine the clinicopathological characteristics of the lesions resected by ESD, we evaluated the following: UC disease extent, endoscopic lesion size, lesion location, endoscopic macroscopic type based on the Paris classification, Japan NBI Expert Team classification, pit pattern, en bloc resection rate, R0 resection rate, curative resection rate, excision time, perforation, postoperative bleeding, local recurrence, metachronous dysplasia, and additional surgery. 15 The extent of UC disease was estimated from endoscopic findings.

Colectomy
To examine the clinicopathological characteristics of the lesions in the colectomy specimen, we evaluated the following: the lesion visibility, UC disease extent, endoscopic macroscopic type based on the Paris classification, surgical procedure, histopathological lesion size, lesion location, number of synchronous lesions, histopathological diagnosis of synchronous lesions, and tumor-node-metastasis (TNM) staging.
Preoperative colonoscopy was performed with white-light and, if necessary, using Indigo carmine to improve visualization of epithelial surface detail. We defined visible dysplasia as dysplasia identified on targeted biopsies from a lesion visualized at preoperative colonoscopy, 4 and we defined undetected dysplasia as dysplasia identified on resected surgical specimen without a visible lesion at preoperative colonoscopy. The extent of UC disease was estimated from both endoscopic and pathological findings. The macroscopic type of endoscopically undetected lesions was evaluated using the resected specimen. TNM staging was classified according to the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma (3d English Edition). 18 For synchronous multiple lesions, TNM staging was performed for the lesion with the highest tumor stage.

Patient characteristics
ESD was performed in 11 lesions from nine patients, including two patients with metachronous lesions detected by surveillance colonoscopy. Nine patients underwent colectomy, including one patient who had noncurative resection and total colectomy as additional surgeries ( Figure 2).
The characteristics of the patients who underwent ESD or colectomy are shown in Table 1. There were eight men and 10 women. The median age at treatment was higher in ESD patients

Treatment outcome of ESD
The treatment outcomes of ESD are shown in Table 3. En bloc resection, R0 resection, and curative resection rates were 91% (10 lesions No perforation occurred during the procedure.
Moreover, noncurative resection was performed in two lesions.
One was a piecemeal resection that was accompanied by scarring and atrophy, and the other noncurative resection did not exhibit such endoscopic findings but required additional surgery because of superficial tumor invasion (500 μm from the muscularis mucosa) associated with lymphatic invasion. 19 In addition, two lesions showed severe submucosal fibrosis, and these lesions had endoscopic findings of scarring and atrophic colitis.
In the remaining nine lesions, severe submucosal fibrosis was not observed; of the nine lesions, one had endoscopic findings of loss of haustra and five had endoscopic findings of atrophic colitis.

Follow-up
The median follow-up period of nine patients whose lesions were Both patients underwent ESD, and curative resection was performed.
Subsequent surveillance colonoscopy revealed no local recurrence.
None of the patients died of colorectal cancer associated with ESD.

Clinicopathological characteristics of colectomy
The characteristics of the 19 lesions detected in the nine resected colectomy specimens are shown in Table 4  The colonoscope could not be inserted into the proximal lesion because of distal stenosis.