Early Feeding Versus Delayed Feeding After Colorectal Endoscopic Submucosal Dissection

● Sample Size Calculation: This study was designed as a non-inferiority trial. The expected incidence of post-procedural adverse events was assumed to be 1.5% in both groups. Sample size estimation was performed using PASS version 11, assuming a non-inferiority margin of 5%, a one-sided alpha level of 0.025, and 80% power. Based on these assumptions, 96 patients were required per group. After allowing for a 5% dropout rate, the final target enrollment was set at 102 patients per group, resulting in a total sample size of 204 patients.

● Randomization and Blinding: This clinical study employs block randomization to allocate participants to the experimental group (early diet resumption, EDR) and the control group (delayed diet resumption, DDR) in a 1:1 ratio. Blinding will not be applied. A randomization table will be generated independently by a statistician from the Medical Statistics Department of Pusan National University Hospital, using the blockrand package in R (version 4.3.3; R Core Team, 2024, http://cran.r-project.org). The block size will remain blinded.

● Research Participation Procedure: After signing the consent form, the admission process is initiated. Basic tests such as blood tests, ECG, and chest/abdominal X-rays are conducted. Fasting and bowel preparation are performed the day before the procedure.

● Procedure and Initial Management: On the day of the procedure, both groups undergo standard colorectal ESD. Two hours after the procedure, a physical examination, CBC, and chest/abdominal X-rays are performed.

● Dietary Group Classification: Early Feeding Group: If no abnormalities are found during the examination 2 hours after the procedure, water intake begins, followed by a liquid diet and then a porridge diet if no complications occur.

Late Feeding Group: Patients remain fasting on the day of the procedure. A liquid diet begins 24 hours after the procedure, followed by a porridge diet if no complications occur.

● Survey: Patient satisfaction is evaluated through a survey. Patients visit the outpatient clinic after discharge to review procedural outcomes and assess for delayed complications.

● Observation Items: Age, sex, height, weight, BMI, underlying diseases (hypertension, diabetes, cerebrovascular disease, ischemic heart disease, other heart diseases, atrial fibrillation (or atrial flutter), other arrhythmias, chronic kidney disease, dialysis status, liver cirrhosis, other vascular diseases), history of previous abdominal surgery, smoking history, alcohol consumption history, medication history (aspirin, clopidogrel, other antithrombotic agents, warfarin, direct oral anticoagulants (DOACs), nonsteroidal anti-inflammatory drugs (NSAIDs), steroids), type of bowel preparation used, pre-procedure serum white blood cell count, pre-procedure serum hemoglobin, pre-procedure serum platelet count, pre-procedure absolute neutrophil count, pre-procedure prothrombin time (PT) (including INR), pre-procedure activated partial thromboplastin time (aPTT), post-procedure serum white blood cell count, post-procedure serum hemoglobin, post-procedure serum platelet count, post-procedure absolute neutrophil count, location of the lesion, size of the lesion (long axis, short axis), macroscopic morphology of the lesion, degree of submucosal fibrosis, resection method, resection time, post-resection management time, total procedure time, type of post-resection management performed, en bloc resection status, occurrence of complications during the procedure, measures taken for intra-procedural complications and their outcomes, occurrence of complications within 24 hours post-procedure, measures taken for complications within 24 hours post-procedure and their outcomes, occurrence of complications beyond 24 hours post-procedure, measures taken for complications beyond 24 hours post-procedure and their outcomes, length of hospital stay (days), pathology results (histology, differentiation grade, invasion depth, horizontal resection margin, vertical resection margin, lymphatic invasion, vascular invasion, perineural invasion), number of days until outpatient follow-up after discharge, patient satisfaction (Likert scale).

● Data Analysis and Statistical Methods: All statistical analyses were conducted using R software, version 4.5.3 (R Foundation for Statistical Computing, Vienna, Austria). The fmsb package was used to estimate risk differences and mean differences (MDs). Continuous data were summarized as mean ± standard deviation or median with interquartile range, depending on their distribution. Categorical data were summarized as number and percentage. Comparisons between the two groups were made using the independent t-test or Wilcoxon rank-sum test for continuous variables and the chi-square test or Fisher's exact test for categorical variables, as appropriate.

In the non-inferiority analysis, the treatment effect was expressed as the difference between the EDR and DDR groups, defined as EDR minus DDR. Two-sided 95% confidence intervals (CIs) were calculated for the risk differences. EDR was considered non-inferior to DDR for post-procedural adverse events when the upper limit of the 95% CI was below the prespecified non-inferiority margin of 5%. To evaluate potential factors associated with post-procedural adverse events, logistic regression analyses were performed. Variables considered clinically relevant and showing an association with adverse events in univariable analysis at p < 0.20 were selected for inclusion in the multivariable model.

A one-sided alpha level of 0.025 was applied for the non-inferiority test. For all other analyses, two-sided p values < 0.05 were considered statistically significant. Missing data were not imputed.

Inclusion criteria

Patients undergoing colorectal endoscopic submucosal dissection for the following lesions:

• Differentiated early colorectal cancer confined to the mucosa, without ulcers, and measuring ≤5 cm
• Laterally spreading tumors measuring ≥2 cm
• Sessile polyps measuring ≥2 cm
• Adenomas accompanied by fibrosis
• Differentiated early cancer of the colon or rectum without lymph node metastasis, aside from those covered by partial self-payment insurance (Korean National Health insurance)
• Submucosal tumors of the colon or rectum
• Patients who have signed the consent form to participate in this study

Exclusion criteria

• Under 18 years of age
• Patients with unresolved colorectal cancer
• Patients with non-remissive inflammatory bowel disease (IBD)
• Patients with blood coagulation disorders
• Patients with a prothrombin time (PT) INR ≥ 1.5 despite medical correction
• Pregnant patients
• Patients who refuse to participate in this study