Patients
This study included 178 lesions in 165 consecutive patients that were resected by ESD in Hiroshima University Hospital between December 2008 and December 2018. All enrolled patients aged over 80 years underwent ESD at the time. Patients who had undergone colectomy or who presented with inflammatory bowel disease, familial adenomatous polyposis, and Lynch syndrome were excluded.
Compliance with ethical standards
This study was performed in accordance with the Declaration of Helsinki and its later amendments. All patients were informed of the risks and benefits of ESD, and each patient provided written informed consent for the use of their data for publication. This study was approved by the Institutional Review Board of Hiroshima University Hospital (No. 932, registration date: April 25, 2014).
Indications of ESD
The indications for ESD were as reported previously [7.8]: (1) lesions for which application of en bloc resection with snare EMR was difficult, such as nongranular laterally spreading tumors (particularly the pseudo-depressed type), lesions exhibiting a VI-type pit pattern, carcinoma with shallow submucosal invasion, large depressed type tumors, and large protruding type lesions suspected to be carcinoma; (2) mucosal tumors with submucosal fibrosis; (3) sporadic localized tumors in conditions of chronic inflammation such as ulcerative colitis; and (4) local residual or recurrent early carcinomas after endoscopic resection. Before endoscopic therapy, we examined all lesions primarily with magnifying endoscopy [11,21-24] and determined the indications for ESD or EMR in accordance with the indications provided in the strategy. We performed ESD for lesions that we had diagnosed as deep and submucosally invasive if the patients requested ESD for palliative local cure owing to the severity of their chronic concomitant diseases or malignant diseases. In this study, we only evaluated patients who could be prepared for colonoscopy with more than 1-L bowel cleansing agent; Niflec® (Ajinomoto Co., Inc. Tokyo, Japan).
ESD procedures
ESD was performed by four endoscopists (S.T., S.O., Y.N., and H.T.). We predominantly used a DualKnife J (Olympus Medical Systems Co., Ltd, Tokyo, Japan), IT knife nano (Olympus Medical Systems Co., Ltd, Tokyo, Japan), or Flex knife (Olympus Medical Systems Co. Ltd, Tokyo, Japan). Depending on the situation, we also used an SB knife Jr. (Sumitomo Bakelite Co., Ltd, Tokyo, Japan). Carbon dioxide (CO2) insufflation was used instead of room air insufflation. ESD procedures were performed with a high-resolution magnifying video endoscope (CF-H260AZI, CF-Q260JI, or PCF-H290TI; Olympus Optical Co., Ltd, Tokyo, Japan) or upper gastrointestinal endoscope (GIF- Q260J; Olympus Optical Co. Ltd, Tokyo, Japan). Undiluted 0.4% sodium hyaluronate (MucoUp®; Johnson & Johnson K.K., Tokyo, Japan) was used as the injection solution. After injection of the solution into the submucosal layer, a circumferential incision was made using a single ESD knife. The submucosal layer was then dissected using one or two ESD knives. Visible vessels or arteries in the ulcers were grasped precisely with hemostatic forceps.
Histologic assessment
The excised specimens were stretched and pinned, fixed in 10% buffered formalin, sliced into 2 mm sections, and assessed microscopically. The depth of submucosal invasion was determined according to the General Rules for Clinical and Pathological Studies on Cancer of the Colon, Rectum, and Anus outlined by the Japanese Society for the Colon and Rectum (JSCCR) [25-27]. Lesions were classified as adenoma (including tubular adenoma, tubulovillous adenoma, and serrated adenoma), Tis carcinoma (carcinoma in situ), T1a carcinoma (adenocarcinoma with shallow submucosal invasion [< 1000 μm]), or T1b carcinoma (adenocarcinoma with deep submucosal invasion [≧ 1000 μm]).
A curative resection was determined using the JSCCR guideline criteria, which involved satisfying all four of the following characteristics: a well/moderately differentiated or papillary carcinoma, no lymphovascular invasion, a submucosal invasion depth < 1000 mm, and grade 1 budding. The inclusion of an additional colectomy with lymph node dissection was considered based on the current guidelines at the time [25-27].
Variables investigated
The following variables for clinical outcomes of ESD were investigated: complete en bloc resection, abandoned cases, median procedure time, and complications (delayed bleeding and perforation). Poor scope operability was defined as situations in which paradoxical movement of the endoscope, poor control with adhesions, and lesion motion with heart beats or breathing occurred, as reported previously [28]. A complete en bloc resection was defined as a one-piece resection of the entire lesion, as observed endoscopically, and negative margins were defined through histopathological diagnosis.
We compared the prognosis among three groups; curative resection, non-curative resection with additional surgical resection of lymph nodes, and non-curative resection followed up without additional surgical resection. Curative resection, according to the JSCCR Guidelines for the Treatment of Colorectal Cancer [25-27], was defined by histopathological confirmation of well/moderately differentiated or papillary histologic grade lesion-free deep and lateral margins, no vascular invasion, a submucosal invasion depth of < 1000 μm, and grade 1 budding (low grade). Tumor locations were divided into the right colon, left colon, and rectum. Based on their growth patterns, the growth types of the tumors were classified into either superficial or protruding type [29]. We classified the degree of submucosal fibrosis into three groups (F0, F1, and F2) as described previously [16], which were further subdivided into two groups: F0 and F1 were non or mild, and F2 was severe. We used The American Society of Anesthesiologists classification of physical status (ASA-PS) [30,31] for categorizing the preoperative status of patients before ESD. (ASA-PS class 1; a normal healthy patients, ASA-PS class 2; a patient with a mild systemic disease, ASA-PS class 3; a patient with a severe systemic disease that is not life-threatening.) We also compared overall survival rates between ASA-PS class 1 or 2 and class 3.
Surveillance after ESD
Follow-up colonoscopy for recurrence was generally scheduled according to the type of resection (curative vs. non-curative). According to the JSCCR guidelines, in cases of curative resection, follow-up colonoscopy for local recurrence was performed once every 12 months. Cases of non-curative resection, which did not undergo additional surgery, were followed up with abdominal ultrasonography and computed tomography in addition to colonoscopy. However, we occasionally changed the period of surveillance according to the patient's physical condition. Confirmation of recurrence was based on imaging and/or pathological findings. Local recurrence was defined as recurrence at the site of resected colorectal tumors. Distant recurrence was defined as the occurrence of metastasis of colorectal origin associated with the initial tumor.
Statistical analysis
Quantitative data are presented as mean ± standard deviation or percentage. Differences in categorical variables were analyzed with the chi-square test with Yates correction or Fisher’s exact test. A p-value < 0.05 was considered statistically significant. The overall survival, disease-free survival, and disease-specific survival rates were calculated using the Kaplan-Meier method. JMP statistical software version 12.2.0 (SAS Institute, Cary, NC, USA) was used for all statistical analyses.