Effects of early diet resumption on the incidence of complications following polypectomy: A randomized controlled trial

Abstract

BACKGROUND

Patients with early oral intake after intestinal surgery achieve better nutritional status and fewer postoperative complications. However, no guidelines or expert consensus have established the optimal timing for diet resumption following colorectal polypectomy.

AIM

To determine the timing, feasibility, and clinical benefits of early diet resumption following colorectal polypectomy.

METHODS

In the Second Affiliated Hospital of Zhejiang University School of Medicine, a total of 1502 patients with polyps under 3 cm were recruited and randomly assigned to an experimental group (n = 751) and a control group (n = 751). Following polypectomy, the experimental group consumed rice soup at 2 hours, while the control group received rice soup at 6 hours. The study focused on delayed post-polypectomy bleeding (DPPB), with secondary evaluation of post-polypectomy perforation, hypoglycemia, fever, and length of stay (LOS).

RESULTS

The comparison between the two groups revealed no significant differences in DPPB rates (4.7% vs 5.5%, P = 0.480) and major bleeding rates (1.5% vs 2.1%, P = 0.332). Both groups displayed median bleeding times of 2 days. No notable differences in perforation (0.0% vs 0.3%, P = 0.479) and fever rates (2.1% vs 2.9%, P = 0.324) were observed between the two groups. However, the experimental group showed significantly lower incidence of hypoglycemia (0.4% vs 1.5%, P < 0.05) and shorter LOS [1 (1, 2) day vs 2 (1, 2) days, P < 0.001] following polypectomy. Subgroup analyses further confirmed that early diet resumption had no adverse effects on patients, irrespective of polyp count, size, pathology, or polypectomy modalities.

CONCLUSION

Early diet resumption following colorectal polypectomy for polyps not exceeding 3 cm is advisable as it does not significantly increase the risk of complications.

Key Words: Colorectal polyps; Polypectomy; Early diet resumption; Post-polypectomy complications; Randomized controlled trial

Core Tip: This randomized controlled trial included 1502 patients with colorectal polyps under 3 cm at the Second Affiliated Hospital of Zhejiang University School of Medicine. The participants were randomly assigned to an experimental group and a control group. The experimental and control groups resumed oral intake at 2 hours and 6 hours post-polypectomy, respectively. Throughout the 14-day follow-up, the post-polypectomy complications of the two groups were evaluated. The results revealed that early diet resumption does not increase the risk of post-polypectomy complications; conversely, a lower incidence of hypoglycemia and a shorter length of stay were found post-polypectomy.

INTRODUCTION

Colorectal polyps are commonly described as elevated lesions that protrude into the intestinal cavity from the mucosal layer. Among these, adenomatous polyps are the most prevalent and well-known precancerous lesions, involving a carcinogenesis rate between 1.2% and 4.5%[1,2]. Early identification, accurate diagnosis, and timely treatment of colorectal polyps can effectively decrease the prevalence and fatality of colorectal cancer[3]. Colonoscopy stands as the “gold standard” in detecting colorectal polyps, and colonoscopic polypectomy is widely regarded as the preferred treatment for these lesions. The procedure involves potential complications such as bleeding, perforation, and the post-polypectomy coagulation syndrome (PPCS). Despite the relatively low incidence of complications, their occurrence may be life-threatening and significantly increase the economic burden. Bleeding is the most frequently encountered complication, with a reported incidence spanning from 0.2% to 6.1%[4-7]. Bleeding can be further categorized into immediate bleeding (intraoperative) and delayed bleeding (postoperative)[3,7,8]. The European Society of Gastrointestinal Endoscopy (ESGE) defines delayed post-polypectomy bleeding (DPPB) as bleeding that occurs within 30 days following polypectomy that requires an emergency visit, hospitalization, or re-intervention (repeated endoscopy, angiography, or surgery)[3,8]. Previous literature has shown that the incidence of DPPB ranges from 0.2% to 1.9%[4,5,8], with the majority of cases presenting between one to three days following the procedure[4,9]. The management of intraoperative bleeding is relatively straightforward and has a relatively small impact on patients; in contrast, DPPB is unpredictable and often involves delayed detection and treatment. In addition, the incidence of colorectal perforation and coagulation syndrome associated with polypectomy are estimated to be within the ranges of 0.037% to 1.1% and 0.07% to 2.9%, respectively[10-12].

The incidence of post-polypectomy complications is influenced by various factors, encompassing patient gender, underlying disease, the use of anticoagulants or antiplatelet agents, as well as the size, morphology, and location of polyps, modality of polypectomy, endoscopist’s experience, etc. Currently, no guidelines or expert consensus have established the optimal timing for diet resumption following colorectal polypectomy. Furthermore, whether the early consumption of food may elevate the frequency of post-polypectomy complications remains undetermined. At present, the majority of hospitals in China require patients to fast for 6-24 hours following polypectomy. However, prolonged fasting throughout the perioperative period increases the risk of water and electrolyte disturbance, hypotension, hypoglycemia, and other adverse reactions. A meta-analysis reported that patients who resumed early oral feeding following intestinal surgery showed decreased catabolism, improved nutritional status, reduced postoperative complications, and an overall improvement in their post-surgical recovery, thereby reducing medical resource consumption[13]. Therefore, this clinical randomized controlled study aims to evaluate the timing, feasibility, and clinical benefits of early diet resumption following polypectomy, providing evidence to guide clinical practice.

MATERIALS AND METHODS

Patients

Patients diagnosed with colorectal polyps who were admitted to Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine (located in Hangzhou, Zhejiang Province, China) were prospectively recruited. Patients underwent sedated colonoscopic polypectomy between December 1, 2021, and March 28, 2023. The inclusion criteria were: (1) Age > 18 years old; (2) Hospitalized for painless colonoscopic polypectomy; (3) Polyp size ≤ 3 cm; and (4) Patients with a clear understanding of the treatment risks, voluntary participation in this experiment, and signed informed consent. The exclusion criteria were: (1) Patients with severe comorbidities, such as heart, lung, or kidney failure, and severe liver or pancreatic diseases (e.g., cirrhosis, chronic pancreatitis); (2) Patients with drug addiction or uncontrolled neuropsychiatric disorders; (3) Pregnant patients; (4) Patients with a previous history of colorectal cancer; and (5) Patients with a low educational level who could not understand our perioperative precautions and required family members to assist in describing their conditions and preparing for endoscopic treatment, and patients who could not understand the purpose of our project. All the participants were randomly divided into the experimental group and the control group using a random allocation sequence generated by a random number table. Patient data were collected, including the age, gender, body mass index (BMI), smoking and alcohol consumption history, history of hypertension, history of diabetes, history of cardiovascular and cerebrovascular diseases, history of hyperlipidemia, history of anticoagulants or antiplatelet agents use, polyp number, polyp size (estimated using the opening width of biopsy forceps), polyp morphology, polyp location, polyp pathology, modality and duration of polypectomy, post-polypectomy length of stay (LOS), post-polypectomy complications, etc. In patients who underwent multiple polyp removal and experienced DPPB, the site of active bleeding, blood vessel stumps, adhesive blood clots, or black blood scabs identified by repeat colonoscopy was considered a bleeding lesion[4]. If none of the above bleeding signs were observed or repeat endoscopy was not conducted, the largest polyp was deemed to be the default source of the bleeding lesion[4].

Study design

The study was designed as a parallel randomized controlled trial. The primary endpoint was DPPB, assessed by both incidence and time to onset. The secondary endpoints included post-polypectomy colorectal perforation, hypoglycemia, fever, and LOS. Five endoscopists with over 3 years of extensive polypectomy experience (minimum 1000 procedures performed) were selected to perform the operations using Olympus 260/290 series colonoscopes. The endoscopists received regular unified training and underwent regular blind assessments of polyp size under endoscopy. In hybrid endoscopic submucosal dissection (ESD) cases where polyp size was measured during pathological assessment, the polyp size was determined by the pathological measurement data. The criteria for colorectal polypectomy techniques, including cold forceps polypectomy (CFP)/cold snare polypectomy (CSP), hot snare polypectomy (HSP), endoscopic mucosal resection (EMR), and ESD for colorectal polypectomy, were primarily based on the ESGE Clinical Guideline[3]. Based on our center’s experience, hybrid ESD may be selected for the excision of laterally spreading tumors sized 10–30 mm with relatively superficial invasion[14]. Patients undergoing conventional ESDs were excluded. All the participants attended 7-day and 14-day follow-ups to meticulously evaluate post-polypectomy complications. This study was conducted in accordance with the ethical guidelines of the Helsinki Declaration and was approved by the Institutional Review Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine. The clinical trial had also been registered in the International Clinical Trial Registry.

Interventions

All the participants were required to withhold anticoagulant and antiplatelet agents 5-7 days before polypectomy, which were resumed 24 hours following polypectomy if no complications occurred. The experimental group consumed rice soup 2 hours post-polypectomy, semi-liquid food 24 hours post-polypectomy, and gradually transitioned to a regular diet within 2 weeks. In contrast, the control group consumed rice soup 6 hours post-polypectomy, semi-liquid food 24 hours post-polypectomy, and gradually transitioned to a regular diet within 2 weeks. The patients were advised to rest for two weeks following polypectomy, avoid drinking alcohol, and refrain from any exercises that increase abdominal pressure. The patients were informed to contact the endoscopy center or to attend the emergency room for medical treatment in case of symptoms of complications.

Definition of DPPB

In this study, DPPB was defined as more than one episode of melena or hematochezia within 14 days following polypectomy[4]. DPPB was classified into minor and major bleeding. Minor bleeding was defined as self-limiting bleeding that improved on its own without treatment. Major bleeding was defined as bleeding requiring an emergency room visit, hospitalization/transfusion, or hemoglobin levels falling ≥ 2 g/dL from baseline, further requiring treatment with hemostatic drugs, repeat endoscopy, angiography, or surgery[4].

Definition of post-polypectomy perforation, hypoglycemia, and fever

Post-polypectomy colorectal perforation was characterized by postoperative abdominal pain accompanied by imaging abnormalities (X-ray showing subphrenic free gas or computed tomography showing local or diffuse gas or intestinal fluid released into the peritoneum)[10]. Post-polypectomy hypoglycemia was defined as the occurrence of hypoglycemic symptoms such as cold sweat, hunger, palpitations during fasting following polypectomy, and a blood glucose level lower than 3.9 mmol/L as measured by a blood glucose meter. Post-polypectomy fever was defined as the absence of fever before the procedure and an ear temperature ≥ 37.4 °C following polypectomy unexplained by other causes, regardless of any abdominal symptoms.

Sample size calculation

This study adopted a randomized controlled design. The experimental group received food 2 hours post-polypectomy, whereas the control group received food 6 hours post-polypectomy. The incidence of post-polypectomy complications was the outcome index. Based on the complication incidence rate data mentioned above, the total complication rate for both groups were 6%, and the non-inferiority margin was defined for the experimental group compared to the control group as an absolute risk difference of 4% to ensure that the complication rate in the experimental group did not exceed 10%. The α-error level was set to 0.05 (two-sided), and the β-error level was set to 0.20. According to the sample size formula (Supplementary material), a sample size of 723 subjects was required in the experimental group and the control group, respectively. Anticipating a 10% loss to follow-up and refusal, at least 804 subjects were needed in each group. In total, at least 1608 participants should be included.

Statistical analysis

Continuous data were expressed as mean and SD or median and interquartile range. Categorical data were presented as numbers and percentages. For statistical analysis of categorical data, such as the primary endpoint, Pearson’s χ² test or two-tailed Fisher’s exact test was used to compare differences in rates between the two groups. For statistical analysis of continuous data, a t test or a rank-sum test of two independent samples was performed. In addition, binary logistic regression was conducted to evaluate the risk factors of DPPB, and the odds ratio and associated 95%CI were calculated. All tests for significance were two-tailed, and P < 0.05 were considered statistically significant. All analyses were performed using Statistical Product and Service Solutions 26.0.

RESULTS

Recruitment and participant flow

A total of 1623 patients were recruited in this study and underwent polypectomy. Among them, 806 patients were randomly assigned to the experimental group, and 817 patients were randomly assigned to the control group. However, during the experiment, 121 patients withdrew due to severe comorbidities, anal diseases, cancer indicated by polyp pathology, poor compliance, and loss to follow-up. Therefore, 1502 patients were ultimately included in the analysis, with 751 patients in each of the experimental and control groups (Figure 1).

Figure 1  Flowchart of patient recruitment.

Baseline characteristics

The mean age of the patients in the experimental group was 57.6 years ± 10.7 years (23-82 years), with a BMI of 24.0 kg/m² ± 3.1 kg/m², and slightly more males (455/751, 60.6%). In the experimental group, the median polyp size was 0.9 cm (0.3-3.0 cm), and the median polyp number was 2 (range: 1-16). Overall, there were 244 cases (32.5%) of single polyps and 507 cases (67.5%) of multiple polyps. Pedunculated polyps accounted for 26.2% (197/751), with the left colon (LC) being the most common location of polyps (360/751, 47.9%). In the experimental group, 86 cases (11.5%) were treated with CFP and CSP, 650 cases (86.6%) were treated with HSP and EMR, and 15 cases (2.0%) were treated with hybrid ESD. The median duration of polypectomy was 21 minutes. In the control group, the mean age of the patients was 57.2 years ± 11.3 years (18-83 years). Similarly, a larger proportion of males (484/751, 64.4%) was found in this group, with an average BMI of 24.0 kg/m² ± 3.1 kg/m². The median polyp size in the control group was 1.0 cm (0.3-3.0 cm), and the median polyp number was 2 (1-32). A total of 247 cases (32.9%) of single polyps and 504 cases (67.1%) of multiple polyps were found. Pedunculated polyps accounted for 26.5% (199/751), with the polyps most commonly being located in the LC (375/751, 49.9%). In the control group, 87 cases (11.6%) were treated with CFP and CSP, 644 cases (85.8%) with HSP and EMR, and 20 cases (2.7%) with hybrid ESD. The median duration of polypectomy was also 21 minutes. No statistically significant differences in age, gender, smoking and drinking history, BMI, history of hypertension, and other underlying diseases were observed between the two groups. Additionally, no significant differences in the size, number, morphology, and location of polyps, as well as the modality and duration of polypectomy, were found between the two groups. The baseline data of the two groups were comparable (Table 1).

Table 1 Characteristics of patients who underwent polypectomy in experimental group and control group, n (%).

Characteristic	Experimental group (n = 751)	Control group (n = 751)	P value
Age (year) (mean ± SD)	57.6 ± 10.7	57.2 ± 11.3	0.387
Sex			0.122
Male	455 (60.6)	484 (64.4)
Female	296 (39.4)	267 (35.6)
Smoking history	205 (27.3)	204 (27.2)	0.954
Drinking history	111 (14.8)	133 (17.7)	0.124
Hypertension	267 (35.6)	283 (37.7)	0.391
Diabetes	89 (11.9)	75 (10.0)	0.247
Cardio-cerebral vascular disease	59 (7.9)	58 (7.7)	0.923
Body mass index (kg/m2) (mean ± SD)	24.0 ± 3.1	24.0 ± 3.1	0.708
Polyp number [median (P25, P75)]	2 (1, 4)	2 (1, 4)	0.910
Polyp size (cm) [median (P25, P75)]	0.9 (0.8, 1.0)	1.0 (0.8, 1.1)	0.307
Pedunculated polyp	197 (26.2)	199 (26.5)	0.907
Polyp location			0.332
Right colon (caecum, ascending colon)	157 (20.9)	168 (22.4)
Transverse colon (liver flexure, transverse colon, spleen flexure)	234 (31.2)	208 (27.7)
Left colon (descending colon, sigmoid colon, rectum)	360 (47.9)	375 (49.9)
Duration of polypectomy (minutes) [median (P25, P75)]	21 (15, 30)	21 (16, 31)	0.131
Polypectomy modality			0.688
Cold forceps polypectomy and cold snare polypectomy	86 (11.5)	87 (11.6)
Hot snare polypectomy and endoscopic mucosal resection	650 (86.6)	644 (85.8)
Hybrid endoscopic submucosal dissection	15 (2.0)	20 (2.7)

Overall outcomes

The overall incidence of DPPB was 5.1% (n = 76), among which the total incidence of major bleeding was 1.8% (n = 27) (Table 2). The experimental group comprised 35 cases of DPPB and 11 cases of major bleeding, whereas 41 cases of DPPB and 16 cases of major bleeding were recorded in the control group. The comparison of the incidence of DPPB (4.7% vs 5.5%, P = 0.480) and major bleeding (1.5% vs 2.1%, P = 0.332) between the two groups demonstrated no statistically significant difference. The median timing of DPPB and major bleeding in both groups was 2 days. In the experimental group, 82.9% (n = 29) of DPPB occurred within 3 days following polypectomy, and similar findings were observed in the control group (Figure 2). Notably, the timing of DPPB [2 (1, 3) days vs 2 (1, 3) days, P = 0.294] and major bleeding [2 (1, 3) days vs 2 (2, 3) days, P = 0.939] showed no statistically significant differences between the two groups. The total incidences of post-polypectomy fever and colorectal perforation were 2.5% (n = 38) and 0.1% (n = 2), respectively. Fever occurred in 16 patients in the experimental group and 22 patients in the control group. All cases of perforation occurred in the control group. The incidence of post-polypectomy fever (2.1% vs 2.9%, P = 0.324) and perforation (0.0% vs 0.3%, P = 0.479) showed no significant differences between the two groups. The total incidence of post-polypectomy hypoglycemia was 0.9% (n = 14), among which 3 cases occurred in the experimental group and 11 cases occurred in the control group. Our data revealed that the incidence of post-polypectomy hypoglycemia in the experimental group was lower than that in the control group (0.4% vs 1.5%, P = 0.032). Moreover, the post-polypectomy LOS of the experimental group was significantly shorter than that of the control group [1 (1, 2) day vs 2 (1, 2) days, P < 0.001].

Figure 2 Comparison of the timing between the experimental and control groups. A: Major bleeding event; B: Minor bleeding event.

Table 2 Clinical outcomes of patients in experimental group and control group following polypectomy, n (%).

Characteristic	Total (n = 1502)	Experimental group (n = 751)	Control group (n = 751)	P value
DPPB	76 (5.1)	35 (4.7)	41 (5.5)	0.480
Major bleeding	27 (1.8)	11 (1.5)	16 (2.1)	0.332
The timing of DPPB (day) [median (P25, P75)]	2 (1, 3)	2 (1, 3)	2 (1, 3)	0.294
The timing of major bleeding (day) [median (P25, P75)]	2 (2, 3)	2 (1, 3)	2 (2, 3)	0.939
Post-polypectomy perforation	2 (0.1)	0 (0.0)	2 (0.3)	0.479
Post-polypectomy hypoglycemia	14 (0.9)	3 (0.4)	11 (1.5)	0.032a
Post-polypectomy fever	38 (2.5)	16 (2.1)	22 (2.9)	0.324
post-polypectomy length of stay (day) [median (P25, P75)]	1 (1, 2)	1 (1, 2)	2 (1, 2)	< 0.001b

^aP < 0.05.

^bP < 0.01.

DPPB: Delayed post-polypectomy bleeding.

Subgroup analysis

Subgroup analysis of patients who underwent polypectomy of a single polyp revealed no significant differences in the incidence of DPPB (2.5% vs 2.8%, P = 0.796), major bleeding (0.8% vs 1.2%, P = 1.000), post-polypectomy hypoglycemia (0.0% vs 1.2%, P = 0.251), and post-polypectomy fever (2% vs 4%, P = 0.198) between the two groups. Similarly, the timing of DPPB [2.5 (1.0, 4.8) days vs 3.0 (1.0, 4.0) days, P = 0.942] and major bleeding [4.0 (1.0, 7.0) days vs 3.0 (2.0, 4.0) days, P = 1.000) between the two groups also showed no statistically significant differences. However, the post-polypectomy LOS in the experimental group was significantly shorter than that in the control group [1 (1, 1) day vs 1 (1, 2) day, P < 0.001]. In this subgroup, no perforation was reported in either group during the 14-day follow-up. Additionally, the subgroup analysis of patients who underwent polypectomy of multiple polyps revealed no difference in the incidence of post-polypectomy complications between the two groups. Conversely, the post-polypectomy LOS of the experimental group was significantly shorter. The data are shown in Table 3.

Table 3 Subgroup analysis of patients with single polyp or multiple polyps in experimental group and control group, n (%).

Characteristic	Single polyp (n = 491)			Multiple polyps (n = 1011)
	Experimental group (n = 244)	Control group (n = 247)	P value	Experimental group (n = 507)	Control group (n = 504)	P value
Age (years) (mean ± SD)	54.3 ± 12.0	52.9 ± 11.9	0.193	59.2 ± 9.7	59.2 ± 10.4	0.979
Sex			0.498			0.134
Male	117 (48.0)	126 (51.0)		338 (66.7)	358 (71.0)
Female	127 (52.0)	121 (49.0)		169 (33.3)	146 (29.0)
Duration of polypectomy (minute) [median (P25, P75)]	15 (12, 21)	17 (13, 21)	0.018a	25 (18, 33)	25 (19, 33)	0.479
Polyp size (cm) [median (P25, P75)]	0.8 (0.7, 1.0)	0.8 (0.8, 1.0)	0.392	1.0 (0.8, 1.1)	1.0 (0.8, 1.2)	0.457
Polypectomy modality			0.121			0.456
Cold forceps polypectomy and cold snare polypectomy	24 (9.8)	13 (5.3)		62 (12.2)	74 (14.7)
Hot snare polypectomy and endoscopic mucosal resection	215 (88.1)	226 (91.5)		435 (85.8)	418 (82.9)
Hybrid endoscopic submucosal dissection	5 (2.0)	8 (3.2)		10 (2.0)	12 (2.4)
DPPB	6 (2.5)	7 (2.8)	0.796	29 (5.7)	34 (6.7)	0.500
Major bleeding	2 (0.8)	3 (1.2)	1.000	9 (1.8)	13 (2.6)	0.381
The timing of DPPB (day) [median (P25, P75)]	2.5 (1.0, 4.8)	3.0 (1.0,4.0)	0.942	2.0 (1.0, 3.0)	2.0 (1.0, 3.0)	0.198
The timing of major bleeding (day) [median (P25, P75)]	4.0 (1.0, 7.0)	3.0 (2.0, 4.0)	1.000	2.0 (1.5, 3.0)	2 (1.5, 3.5)	0.889
Post-polypectomy perforation	0 (0.0)	0 (0.0)	-	0 (0.0)	2 (0.4)	0.476
Post-polypectomy hypoglycemia	0 (0)	3 (1.2)	0.251	3 (0.6)	8 (1.6)	0.127
Post-polypectomy fever	5 (2)	10 (4)	0.198	11 (2.2)	12 (2.4)	0.822
post-polypectomy length of stay (day) [median (P25, P75)]	1 (1, 1)	1 (1, 2)	< 0.001b	1 (1, 2)	2 (1, 2)	< 0.001b

^aP < 0.05.

^bP < 0.01.

DPPB: Delayed post-polypectomy bleeding.

Subgroup analysis was also performed based on the size of polyps (Table 4). In the subgroup with polyp size < 1 cm, the post-polypectomy LOS was significantly shorter [1 (1, 2) day vs 1 (1, 2) day, P < 0.001] in the experimental group. No differences in the incidence of DPPB (3% vs 3.1%, P = 0.970), major bleeding (0.5% vs 1.0%, P = 0.668), post-polypectomy perforation (0.0% vs 0.5%, P = 0.246), post-polypectomy hypoglycemia (0.3% vs 1.8%, P = 0.072), and post-polypectomy fever (1.8% vs 2.6%, P = 0.443) were observed between the two groups, as well as in the timing of DPPB [2.0 (1.3, 3.8) days vs 2.5 (1.0, 4.0) days, P = 1.000] and major bleeding [1.0 (1.0, 1.0) day vs 3.5 (1.5, 4.0) days, P = 0.134]. In the 14-day follow-up of the subgroup with polyp size ≥ 1 cm, no perforation was observed. Notably, in the subgroup with a polyp size ≥ 1 cm, the post-polypectomy LOS in the experimental group was shorter than that in the control group [1 (1, 2) day vs 2 (1, 2) days, P < 0.001], while the incidence of post-polypectomy complications and the timing of DPPB in the two groups showed no statistically significant differences.

Table 4 Subgroup analysis of patients with polyps’ size < 1 cm or polyps’ size ≥ 1 cm in experimental group and control group, n (%).

Characteristic	Polyp size < 1 cm (n = 784)			Polyp size ≥ 1 cm (n = 718)
	Experimental group (n = 395)	Control group (n = 389)	P value	Experimental group (n = 356)	Control group (n = 362)	P value
Age (years) (mean ± SD)	57.2 ± 10.6	56.2 ± 11.5	0.224	58.2 ± 10.8	58.2 ± 11.0	0.997
Sex			0.245			0.307
Male	239 (60.5)	251 (64.5)		216 (60.7)	233 (64.4)
Female	156 (39.5)	138 (35.5)		140 (39.3)	129 (35.6)
Duration of polypectomy (minute) [median (P25, P75)]	19 (14, 27)	19 (15, 28)	0.335	24 (17, 33)	25 (18, 33)	0.278
Polyp number [median (P25, P75)]	2 (1, 3)	2 (1, 3)	0.798	3 (1, 4)	3 (1, 4)	0.664
Polypectomy modality			0.824			0.829
Cold forceps polypectomy and cold snare polypectomy	68 (17.2)	68 (17.5)		18 (5.1)	19 (5.2)
Hot snare polypectomy and endoscopic mucosal resection	322 (81.5)	314 (80.7)		328 (92.1)	330 (91.2)
Hybrid endoscopic submucosal dissection	5 (1.3)	7 (1.8)		10 (2.8)	13 (3.6)
DPPB	12 (3)	12 (3.1)	0.970	23 (6.5)	29 (8.0)	0.423
Major bleeding	2 (0.5)	4 (1.0)	0.668	9 (2.5)	12 (3.3)	0.532
The timing of DPPB (day) [median (P25, P75)]	2.0 (1.3, 3.8)	2.5 (1.0, 4.0)	1.000	2.0 (1.0, 3.0)	2.0 (1.0, 2.5)	0.205
The timing of major bleeding (day) [median (P25, P75)]	1.0 (1.0, 1.0)	3.5 (1.5, 4.0)	0.134	3.0 (2.0, 3.5)	2.0 (2.0, 2.8)	0.273
Post-polypectomy perforation	0 (0.0)	2 (0.5)	0.246	0 (0.0)	0 (0.0)	-
Post-polypectomy hypoglycemia	1 (0.3)	7 (1.8)	0.072	2 (0.6)	4 (1.1)	0.697
Post-polypectomy fever	7 (1.8)	10 (2.6)	0.443	9 (2.5)	12 (3.3)	0.532
Post-polypectomy length of stay (day) [median (P25, P75)]	1.0 (1.0, 2.0)	1.0 (1.0, 2.0)	< 0.001b	1.0 (1.0, 2.0)	2.0 (1.0, 2.0)	< 0.001b

^aP < 0.05.

^bP < 0.01.

DPPB: Delayed post-polypectomy bleeding.

Subgroup analysis of patients who underwent neoplastic or non-neoplastic polyp removal yielded similar conclusions. No significant differences were observed in the incidence of post-polypectomy complications, as well as the timing of DPPB and major bleeding between the two groups. However, the post-polypectomy LOS was significantly shorter in the experimental group compared to the control group. The data are shown in Table 5.

Table 5 Subgroup analysis of patients with neoplastic polyp or non-neoplastic polyp in experimental group and control group, n (%).

Characteristic	Neoplastic polyp (n = 1200)			Non-neoplastic polyp (n = 302)
	Experimental group (n = 581)	Control group (n = 619)	P value	Experimental group (n = 170)	Control group (n = 132)	P value
Age (years) (mean ± SD)	57.6 ± 10.7	57.2 ± 11.3	0.387	54.9 ± 12.4	53.8 ± 12.1	0.463
Sex			0.251			0.248
Male	354 (60.9)	397 (64.1)		101 (59.4)	87 (65.9)
Female	227 (39.1)	222 (35.9)		69 (40.6)	45 (34.1)
Duration of polypectomy (minute) [median (P25, P75)]	22 (16, 31)	22 (16, 31)	0.480	20 (14, 28)	21 (16, 31)	0.101
Polyp size (cm) [median (P25, P75)]	1.0 (0.8, 1.1)	1.0 (0.8, 1.1)	0.928	0.8 (0.7, 1.0)	0.8 (0.7, 1.0)	0.191
Polypectomy modality			0.537			0.872
Cold forceps polypectomy and cold snare polypectomy	59 (10.2)	69 (11.1)		27 (15.9)	18 (13.6)
Hot snare polypectomy and endoscopic mucosal resection	510 (87.8)	532 (85.9)		140 (82.4)	112 (84.8)
Hybrid endoscopic submucosal dissection	12 (2.1)	18 (2.9)		3 (1.8)	2 (1.5)
DPPB	27 (4.6)	32 (5.2)	0.676	8 (4.7)	9 (6.8)	0.430
Major bleeding	10 (1.7)	12 (1.9)	0.779	1 (0.6)	4 (3.0)	0.232
The timing of DPPB (day) [median (P25, P75)]	2.0 (1.0, 3.0)	2.0 (1.0, 3.0)	0.367	2.0 (2.0, 2.8)	2.0 (1.0, 4.0)	0.724
The timing of major bleeding (day) [median (P25, P75)]	2.5 (1.0, 3.3)	2.0 (2.0, 3.0)	0.864	2.0	3.0 (1.3, 4.0)	0.709
Post-polypectomy perforation	0 (0.0)	2 (0.3)	0.500	0 (0.0)	0 (0.0)	-
Post-polypectomy hypoglycemia	3 (0.5)	7 (1.1)	0.394	0 (0.0)	4 (3.0)	0.075
Post-polypectomy fever	10 (1.7)	18 (2.9)	0.174	6 (3.5)	4 (3.0)	1.000
Post-polypectomy length of stay (day) [median (P25, P75)]	1.0 (1.0, 2.0)	2.0 (1.0, 2.0)	< 0.001b	1.0 (1.0, 2.0)	2.0 (1.0, 2.0)	< 0.001b

^bP < 0.01.

DPPB: Delayed post-polypectomy bleeding.

Additionally, a subgroup analysis was performed based on the different modalities of polypectomy (Table 6). In the CFP and CSP subgroup, the experimental group exhibited a shorter post-polypectomy LOS [1 (1, 2) day vs 2 (1, 2) days, P < 0.001], whereas no statistically significant differences were found in the incidence of post-polypectomy complications and the timing of DPPB between the two groups. In the HSP and EMR subgroup, the experimental group had a shorter post-polypectomy LOS [1 (1, 2) day vs 2 (1, 2) days, P < 0.001) and a lower incidence of post-polypectomy hypoglycemia (0.3% vs 1.6%, P = 0.019) compared with the control group. Meanwhile, there were no differences in the incidence of other post-polypectomy complications and the timing of DPPB between the two groups. No perforation was observed in the hybrid ESD subgroup, and no statistically significant differences were found in the incidence of post-polypectomy complications and post-polypectomy LOS between the two groups.

Table 6 Subgroup analysis of patients who underwent different modalities of polypectomy in experimental group and control group, n (%).

Characteristic	Cold forceps polypectomy and cold snare polypectomy (n = 173)			Hot snare polypectomy and endoscopic mucosal resection (n = 1294)			Hybrid endoscopic submucosal dissection (n = 35)
	Experimental group (n = 86)	Control group (n = 87)	P value	Experimental group (n = 650)	Control group (n = 644)	P value	Experimental group (n = 15)	Control group (n = 20)	P value
Age (years) (mean ± SD)	58.7 ± 10.2	58.2 ± 11.2	0.758	57.6 ± 10.7	57.0 ± 11.4	0.363	55.6 ± 14.3	57.7 ± 10.1	0.613
Sex			0.377			0.215			0.506
Male	58 (67.4)	64 (73.6)		390 (60.0)	408 (63.4)		7 (46.7)	12 (60.0)
Female	28 (32.6)	23 (26.4)		260 (40.0)	236 (36.6)		8 (53.3)	8 (40.0)
Duration of polypectomy (minute) [median (P25, P75)]	20 (13, 32)	21 (16, 32)	0.230	21 (15, 29)	21 (16, 30)	0.262	37 (26, 59)	34 (29, 47)	0.677
Polyp size (cm) [median (P25, P75)]	0.8 (0.5, 0.9)	0.8 (0.6, 0.9)	0.171	1.0 (0.8, 1.1)	1.0 (0.8, 1.1)	0.412	1.2 (0.8, 2.0)	1.1 (0.8, 1.5)	0.490
Polyp number [median (P25, P75)]	3.0 (1.0, 5.3)	4.0 (2.0, 6.0)	0.144	2.0 (1.0, 4.0)	2.0 (1.0, 4.0)	0.596	2.0 (1.0, 3.0)	2.0 (1.0, 4.0)	0.904
DPPB	2 (2.3)	4 (4.6)	0.688	31 (4.8)	37 (5.7)	0.431	2 (13.3)	0 (0.0)	0.176
Major bleeding	0 (0.0)	0 (0.0)	-	9 (1.4)	16 (2.5)	0.151	2 (13.3)	0 (0.0)	0.176
The timing of DPPB (day) [median (P25, P75)]	5.0 (4.0, 6.0)	1.5 (1.0, 11.0)	0.348	2.0 (1.0, 3.0)	2.0 (1.0, 3.0)	0.410	1.5 (1.0, 2.0)	-	-
The timing of major bleeding(day) [median (P25, P75)]	-	-	-	3.0 (1.5, 3.5)	2.0 (2.0, 3.8)	0.703	1.5 (1.0, 2.0)	-	-
Post-polypectomy perforation	0 (0.0)	1 (1.1)	1.000	0 (0.0)	1 (0.2)	0.498	0 (0.0)	0 (0.0)	-
Post-polypectomy hypoglycemia	1 (1.2)	0 (0.0)	0.497	2 (0.3)	10 (1.6)	0.019a	0 (0.0)	1 (5.0)	1.000
Post-polypectomy fever	1 (1.2)	5 (5.7)	0.218	14 (2.2)	15 (2.3)	0.831	1 (6.7)	2 (10.0)	1.000
post-polypectomy length of stay(day) [median (P25, P75)]	1.0 (1.0, 2.0)	2.0 (1.0, 2.0)	< 0.001b	1.0 (1.0, 2.0)	2.0 (1.0, 2.0)	< 0.001b	2.0 (1.0, 4.0)	2.0 (2.0, 2.0)	0.790

^aP < 0.05.

^bP < 0.01.

DPPB: Delayed post-polypectomy bleeding.

Furthermore, multivariate analyses were conducted to analyze the risk factors for DPPB and major bleeding. The independent variable assignments are presented in Table 7. The results of the former showed that age < 50 years old, polyp number, and polyp size were independent risk factors for DPPB (Table 8). Patients aged < 50 years had a 1.067-fold increased risk of DPPB compared to those aged ≥ 50 years. The risk of DPPB increased 0.079 times for each additional polyp removed. For every 1 cm increase in polyp size, the risk of DPPB increased by 1.633 times. The results of the latter showed that age < 50 years old and polyp number were independent risk factors for major bleeding (Table 9). Patients aged < 50 years had a 1.824-fold increased risk of major bleeding compared to those aged ≥ 50 years. For each additional polyp removed, the risk of major bleeding increased by 0.138 times. In contrast, early diet resumption following polypectomy was not a risk factor for DPPB or major bleeding.

Table 7 Variable assignments.

Independent variable	Assignment
Delayed post-polypectomy bleeding	“No” = 0, “yes” = 1
Major bleeding	“No” = 0, “yes” = 1
Age (year)	“≥ 50” = 0, “<50” = 1
Polyp number	Continuous variable
Polyp size	Continuous variable
Pedunculated polyp	“No” = 0, “yes” = 1
Polypectomy modality	Hybrid endoscopic submucosal dissection as a reference
Polyp location	Right colon as a reference
Early diet resumption following polypectomy	“No” = 0, “yes” = 1

Table 8 Multivariate analysis of risk factors for delayed post-polypectomy bleeding.

Variable	B	SE	Wald	P value	OR	95%CI of OR value
						Lower	Upper
Age (< 50 years)	0.726	0.263	7.619	0.006b	2.067	1.234	3.461
Polyp number	0.076	0.035	4.823	0.028a	1.079	1.008	1.155
Polyp size (cm)	0.968	0.306	9.988	0.002b	2.633	1.444	4.800
Pedunculated polyp	0.190	0.276	0.476	0.490	1.209	0.705	2.075
Early diet resumption following polypectomy	-0.106	0.240	0.196	0.658	0.899	0.562	1.439

^aP < 0.05.

^bP < 0.01.

OR: Odds ratio.

Table 9 Multivariate analysis of risk factors for major bleeding.

Variable	B	SE	Wald	P value	OR	95%CI of OR value
						Lower	Upper
Age (< 50 years)	1.038	0.419	6.133	0.013a	2.824	1.242	6.422
Hybrid endoscopic submucosal dissection			2.364	0.307
Cold forceps polypectomy and cold snare polypectomy	-18.239	2869.280	0.000	0.995	0.000	0.000
Hot snare polypectomy and endoscopic mucosal resection	-1.222	0.795	2.364	0.124	0.294	0.062	1.399
Right colon			6.738	0.034
Left colon	0.944	0.572	2.725	0.099	2.570	0.838	7.879
Transverse colon	-0.716	0.881	0.660	0.417	0.489	0.087	2.749
Polyp number	0.129	0.050	6.567	0.010a	1.138	1.031	1.256
Polyp size (cm)	0.718	0.480	2.243	0.134	2.051	0.801	5.250
Pedunculated polyp	0.333	0.454	0.540	0.462	1.396	0.574	3.395
Early diet resumption following polypectomy	-0.305	0.404	0.567	0.451	0.737	0.334	1.629

^aP < 0.05.

OR: Odds ratio.

DISCUSSION

According to the 2019 guidelines for colonoscopy intestinal preparation issued by the ESGE, patients are required to take polyethylene glycol electrolyte solutions for intestinal preparation from the night preceding the polypectomy and to refrain from consuming any other food[15]. The traditional postoperative fasting approach is based on the hypothesis that consuming food too soon can irritate the wound mucosa. Additionally, the abrasive nature of certain food residue, coupled with increased intestinal motility, may hinder the wound’s natural healing process or result in premature detachment of eschar and titanium clips, ultimately leading to bleeding. Therefore, most doctors require patients to abstain from food for a period of time following polypectomy. However, definitive and reliable research data are lacking, and the optimal duration of post-polypectomy fasting remains controversial. Extended fasting throughout the perioperative period can lead to the depletion of protein, fat, and energy reserves, thereby elevating the risk of postoperative malnutrition. In addition, the operative trauma and the loss of essential water and electrolytes increase the risk of adverse events such as hypotension and hypoglycemia. These factors collectively hinder the patient’s postoperative recovery and impact clinical outcomes. With the development of enhanced recovery after surgery (ERAS), early postoperative oral feeding has been widely adopted in clinical practice in developed countries. A meticulously conducted meta-analysis of randomized clinical trials revealed that early postoperative oral feeding in patients who underwent colorectal surgery significantly decreased the incidence of postoperative complications, effectively reduced LOS, and accelerated postoperative recovery[16]. Toledano et al’s research also demonstrated that early feeding following intestinal surgery can promote early recovery of intestinal function and shorten LOS compared to traditional postoperative fasting[17]. In accordance with the concept of ERAS, early diet resumption promotes the rapid recovery of patients following polypectomy. Therefore, this study was conducted to evaluate the influence and clinical benefits of early diet resumption following polypectomy on patients.

This study conducted a thorough comparison of the experimental and control groups, revealing that early diet resumption following polypectomy did not elevate the incidence of DPPB, major bleeding, post-polypectomy perforation, or post-polypectomy fever. Moreover, early diet resumption also had no effect on the timing of DPPB and major bleeding. Conversely, the incidence of post-polypectomy hypoglycemia was reduced, and the post-polypectomy LOS was shortened. Various subgroup analyses revealed that early diet resumption did not negatively impact patients with different numbers of polyps, size, pathology, or modalities of polypectomy. These findings are in accordance with a previous randomized controlled trial, which reported that an unrestricted diet following polypectomy does not increase the incidence of post-polypectomy complications but can shorten LOS and decrease cost[18]. Furthermore, multivariate analyses were conducted to explore the risk factors of DPPB and major bleeding, ultimately proving that early diet resumption was not a significant independent risk factor for these conditions. According to previous reports, the important predictors of DPPB include hypertension, polyp size, proximal colon location, modality of polypectomy, and the use of anticoagulants[8,19,20]. On the other hand, factors that are known to increase the risk of post-polypectomy perforation include en bloc snare excision for lesions ≥ 25 mm, high-grade dysplasia/early cancer, and location in the transverse colon[3]. Concerning PPCS, independent risk factors include hypertension, larger polyps, and non-polypoid lesion morphology[21]. So far, no study has reported that early diet resumption may elevate the incidence of complications following polypectomy.

The data in our study were carefully analyzed, revealing an overall incidence of DPPB of 5.1%, which is higher than reported in previous studies. However, the incidence of major bleeding was 1.8%, which is comparable to prior research findings[4,5,8,22,23]. The ESGE defines DPPB as bleeding that occurs following polypectomy and requires an emergency visit, hospitalization, or re-intervention, which is similar to the definition of major bleeding in this study. Numerous published studies have employed a retrospective approach, focusing solely on cases of patients with significant bleeding requiring another visit to the hospital. In contrast, this study adopted a prospective design that encompasses not just the clinically evident major bleeding events but also the self-limiting minor bleeding events. Therefore, in this study, DPPB was divided into minor and major bleeding to evaluate the broader postoperative situation. Notably, minor amounts of melena or hematochezia may have been caused by delayed discharge of intraoperative bleeding; hence, the actual incidence of minor bleeding may be lower than the data of our study. Furthermore, according to the 2017 ESGE guidelines, the incidence of delayed bleeding after EMR is about 6%-7%[5,24]. In the present study, the majority of patients were treated with EMR, which may have led to a higher overall incidence of DPPB. Our research data showed that approximately 80% of DPPB events occur within the first three days following polypectomy, which was similar to the results observed in previous studies[4,9]. Additionally, multivariate analyses demonstrated that age < 50 years old, polyp number, and polyp size were independent risk factors for DPPB, while age < 50 years old and polyp number were independent risk factors for major bleeding. Both Park et al’s and Lu et al's studies revealed that low age is a risk factor for DPPB, which is consistent with our conclusion[4,20]. This may be attributed to the fact that most young patients return to work or daily life as soon as possible following polypectomy. Previous reports have shown that polyp size is a recognized risk factor[8,20,25-27], with a correlation between the removal of multiple polyps and DPPB[28-30]. In the course of the 14-day follow-up, the cases of DPPB were primarily induced by factors such as rough diet, drinking, heavy lifting, climbing stairs, and fatigue. These behaviors can result in the premature dislodgement of stump eschars or hemostatic devices (such as titanium clips or nylon ropes), ultimately causing bleeding. Early consumption of rice soup following polypectomy does not result in the peeling of eschar or the detachment of hemostatic devices and does not increase the incidence of DPPB.

Considering factors such as anesthesia recovery and return to the ward, the earliest time for patients to receive food is 2 hours following polypectomy. Our hospital currently regularly requires patients to fast for 4-6 hours following polypectomy. For patient safety and to ensure comparability, the control group resumed their diet at 6 hours post-polypectomy. Additionally, considering that the extended follow-up time may lead to an increase in the loss to follow-up rate, only complications that occurred within 14 days following polypectomy were analyzed. In this study, all post-polypectomy complications were effectively managed by conservative management, re-endoscopy, and surgical interventions. The findings revealed that patients did not benefit from prolonged fasting. In contrast, eating light and easy-to-digest food as soon as possible can supplement the necessary nutrition for the patient’s body, reduce the incidence of hypoglycemia, and improve clinical outcomes. This study has demonstrated the high level of safety and feasibility of diet resumption 2 hours following polypectomy, also providing nutritional and economic benefits. Our findings challenge conventional views and practices, unveiling fresh perspectives for the future clinical management of patients who have undergone polypectomy. Therefore, patients should be encouraged to consume an early, clear liquid diet following polypectomy and gradually increase food intake and food texture. Additionally, our data confirm a relatively low incidence of post-polypectomy complications, so outpatient polypectomy can be performed on a subset of patients (CFP, CSP, HSP, or EMR of single or few polyps).

Nevertheless, the limitations of the present study should be acknowledged. This study is only a single-center clinical trial. Hence, multicenter clinical trials should be conducted to confirm the findings. Moreover, data collection for the primary endpoint mainly relied on telephone follow-up. Some cases of minor bleeding may have involved recall bias, and a minor amount of melena or hematochezia might be caused by delayed discharge of intraoperative bleeding, thereby affecting the accuracy of the conclusion. To reduce the above biases, a major bleeding group was set up to include patients who had significant post-polypectomy bleeding and sought medical treatment. Due to the limitations of clinical trials, a comprehensive fecal occult blood test or repeat colonoscopy could not be completed on every patient presenting with bleeding symptoms to ascertain the presence of DPPB. Furthermore, a positive fecal occult blood test cannot distinguish between intraoperative bleeding and post-polypectomy bleeding. In patients with minor bleeding, a repeat colonoscopy is unnecessary and can increase the financial burden. Consequently, our data collection and statistical analysis were limited to minimizing potential biases as far as possible. Regarding the incidence of post-polypectomy hypoglycemia, routine blood glucose monitoring was not conducted for every patient following polypectomy due to the ambiguity of the timing of postoperative blood glucose monitoring. Therefore, blood glucose was only monitored for patients who exhibited symptoms of hypoglycemia following polypectomy, which might lead to biased results. Based on the collected data, early diet resumption seemed to be related to a reduction in the incidence of post-polypectomy hypoglycemia. However, these findings should be interpreted with caution. Furthermore, only colorectal polyps with a size of ≤ 3 cm were included, and the limited number of the hybrid ESD cases in the sample might diminish the effectiveness of the conclusions derived from the hybrid ESD subgroup analysis. Simultaneously, to ensure patient safety during the trial process, a narrow time frame for the grouping setting might result in insignificant differences among the groups due to insufficient time for any meaningful changes to occur. The conclusions of our research were partially influenced by the skill of the endoscopist, introducing a degree of subjectivity in assessing observation indicators such as the size and location of the polyps. To minimize bias, we have specified the estimation method for polyp size, selection criteria and training methods for endoscopists, as detailed in the study design section. Despite its limitations, this study represents the largest randomized controlled trial investigating the effects of early diet resumption following polypectomy. Notably, the risk factors for DPPB and major bleeding were prospectively explored.

CONCLUSION

In summary, post-polypectomy patients should resume oral intake early instead of prolonged fasting. Early diet resumption does not elevate the risk of complications such as DPPB, major bleeding, post-polypectomy perforation, or post-polypectomy fever, and has no effect on the timing of DPPB and major bleeding. Conversely, early diet resumption can help reduce the incidence of post-polypectomy hypoglycemia and shorten post-polypectomy LOS. Early diet resumption was not a risk factor for DPPB or major bleeding. Age < 50 years, polyp number, and polyp size are independent risk factors for DPPB, while age < 50 years and polyp number are independent risk factors for major bleeding.