Clinical impact of diverting ileostomy and high-output stoma on adjuvant chemotherapy for rectal cancer: a retrospective cohort study

Abstract

Purpose

Diverting ileostomy (DI) may cause fluid and electrolyte loss, potentially impairing the tolerability of adjuvant chemotherapy (ACT) in patients with rectal cancer. However, its clinical impact, especially in the presence of high-output stoma (HOS), remains unclear.

This study aimed to evaluate the effects of DI and perioperative HOS on chemotherapy completion, dose intensity, and the incidence of severe adverse events (AEs).

Methods

We retrospectively analyzed 107 patients with rectal cancer who underwent curative resection and received postoperative ACT between June 2012 and December 2024 at Tottori University. Chemotherapy completion, relative dose intensity (RDI), and grade ≥ 3 AEs were compared between patients with and without DI. A subgroup analysis assessed the influence of HOS among DI patients.

Results

Chemotherapy completion rate and RDI were comparable between patients with and without DI. However, the incidence of grade ≥ 3 AEs was significantly higher in the DI group than in the non-DI group (18.2% vs. 4.1%, P = 0.015), and DI was identified as an independent risk factor in multivariate analysis (odds ratio [OR] 5.749, P = 0.022). Among patients with DI, those with HOS had a significantly lower oxaliplatin RDI than those without HOS (37.5% vs. 75.0%, P = 0.007), and HOS independently predicted failure to complete oxaliplatin-based regimens (OR 13.423, P = 0.039).

Conclusions

While DI does not impair overall chemotherapy delivery, it is associated with increased early toxicity. HOS may compromise oxaliplatin administration and should prompt early recognition and targeted supportive interventions.

Introduction

Colorectal cancer remains a leading causes of cancer-related death worldwide [1, 2]. Radical surgical resection is the mainstay of treatment for colorectal cancer, and adjuvant chemotherapy (ACT) is often recommended for pathological Stage II–III cases [3–6]. ACT typically includes fluoropyrimidine and oxaliplatin (OX), which can cause gastrointestinal adverse events (AEs), such as diarrhea and vomiting [7]. These AEs may lead to dose reductions, treatment delays, or even discontinuation of therapy.

In surgery for rectal cancer, a diverting ileostomy (DI) is often constructed to reduce the risk and clinical consequences of anastomotic leakage [8–11]. While DI effectively protects the anastomosis, high output may result in dehydration, electrolyte imbalances, and renal dysfunction, potentially impairing the tolerability of systemic chemotherapy [12–15]. Indeed, recent reports have shown that patients undergoing ACT with a DI are more likely to experience severe diarrhea and require dose modifications [16]. In particular, patients who develop a high-output stoma (HOS) perioperatively often also develop a more severe clinical condition because of dehydration, and may have an increased risk of treatment-related complications, including dose reductions and severe AEs. However, few studies have systematically evaluated the impact of a DI on ACT tolerability and treatment completion rates, and even fewer have explored the specific influence of a perioperative HOS on chemotherapy delivery.

In this study, we retrospectively evaluated the effects of DI on ACT completion, relative dose intensity (RDI), and the incidence of AEs in patients undergoing ACT after surgery for rectal cancer. Additionally, we investigated the clinical impact of an HOS on ACT delivery.

Materials and methods

Patients

Of the 504 patients who underwent radical resection for rectal cancer at Tottori University between June 2012 and December 2024, 107 patients who received ACT were included in this retrospective study. Pathological staging was determined in accordance with the Union for International Cancer Control TNM classification, 8th edition [17]. Patients who received preoperative chemoradiotherapy or chemotherapy were also included. Patients who developed recurrence during the ACT course were excluded from this study.

The present study was approved by the Certified Review Board of Tottori University Hospital (approval number: 21A075). This study was conducted using an opt-out approach approved by the institutional ethics committee, and the need to obtain individual patient consent was waived.

Stoma creation

The decision to create a diverting stoma was made at the surgeon’s discretion, on the basis of a comprehensive assessment of factors, such as bowel obstruction, nutritional status, tumor location, preoperative therapy, and intraoperative findings. In most cases, a DI was constructed using the terminal ileum, approximately 40 cm proximal to the ileocecal valve. However, in three patients, a diverting colostomy was selected instead of a DI, also at the surgeon’s discretion. In all cases, stoma closure was performed after ACT completion or discontinuation.

Adjuvant chemotherapy

The choice of ACT regimen and the initial dose were determined by the treating physician, while considering the patient’s age, performance status, and comorbidities. ACT was generally initiated within 8 weeks after surgery, in line with standard clinical practice. In this study, the median interval from surgery to ACT initiation was 36 days (range: 20–106 days), as determined by the treating physician based on the patient’s recovery status and clinical condition.

Among the 107 patients, 54 received capecitabine plus oxaliplatin (CAPOX), 5 received 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX), 30 received tegafur-uracil (UFT), 14 received capecitabine monotherapy, and 4 received S-1.

The standard treatment duration was 6 months. However, in the 18 patients who received OX combination therapy, treatment duration was reduced to 3 months, on the basis of clinical trial evidence and physician judgment [18].

HOS

HOS was defined as stoma output > 1500 mL on any single day during the perioperative period, as in previous studies [19, 20]. We adopted this single-day cutoff in line with existing clinical practice and supported by prior work from our group [21], although we acknowledge the potential variability in stoma output due to factors such as oral intake or transient diarrhea. Stoma output was routinely measured and documented by medical staff during the postoperative course in-hospital. When patients developed an HOS, we often prescribed probiotics and/or antidiarrheal agents.

Endpoints and data collection

The endpoints of this study were as follows: ACT completion rate, RDI of each chemotherapeutic agent, and the incidence of grade ≥ 3 AEs as defined by the Common Terminology Criteria for Adverse Events, version 5.0. These endpoints were compared between patients with and without a DI. Additionally, among patients with a DI, a subgroup analysis was performed to evaluate the impact of an HOS, comparing patients with and without an HOS.

Data on patient demographics; tumor characteristics; surgical details; chemotherapy regimens; treatment duration; dose reductions, delays, and discontinuation; and AEs were retrospectively collected from electronic medical records. The RDI was calculated as the ratio of the actual delivered dose to the planned dose, adjusted for treatment duration.

Statistical analyses

The chi-squared test and Mann–Whitney U test were used to compare the clinicopathological characteristics between groups. The cumulative incidence of grade ≥ 2 and 3 AEs were estimated using the Kaplan–Meier method and compared using the log-rank test. Univariate and multivariate logistic regression analyses were performed to identify independent predictors of grade ≥ 3 AEs and failure to complete OX-based ACT. P < 0.05 was considered statistically significant. Variables with a p-value < 0.1 in the univariate analysis were included in the multivariate model. SPSS software (SPSS for Mac, Version 25; IBM Corp., Armonk, NY, USA) was used for the statistical analyses.

Results

A patient flowchart is provided in Fig. 1; 107 patients who received ACT following radical rectal cancer surgery were included in this study. Among them, 33 patients underwent DI creation (DI group), while 74 did not (non-DI group).

Fig. 1.

Patient flowchart. Of the 504 patients who underwent curative rectal cancer surgery, 107 who received adjuvant chemotherapy were included in this study. Patients were divided on the basis of the presence or absence of a diverting ileostomy, and subgroup analysis was performed on the basis of the presence of a high-output stoma. ACT, adjuvant chemotherapy; DI, diverting ileostomy; HOS, high-output stoma

The patients’ characteristics are summarized in Table 1. The DI group included significantly more male patients compared with the non-DI group (P = 0.025). Furthermore, low anterior resection and intersphincteric resection were more common in the DI vs. non-DI groups, reflecting surgical decisions to protect low anastomoses with a diverting stoma. OX-based combination regimens were selected more frequently in the DI vs. non-DI groups (P = 0.043). No significant differences were observed in other baseline characteristics, including age, performance status, comorbidities, or neoadjuvant therapy.

Table 1.

Baseline characteristics of patients on the basis of the presence or absence of a diverting ileostomy

		All patients (n = 107)	DI group (n = 33)	Non-DI group (n = 74)	P value
Age (years)	median (range)	65 (29–83)	65 (33–77)	66.5 (29–83)	0.751
Sex	M/F	64/43	25/8	39/35	0.025
BMI (kg/m2)	median (range)	22.7 (15.1–36.1)	22.9 (15.1–30.6)	22.6 (15.3–36.1)	0.656
Hypertension	present/absent	29/78	10/23	19/55	0.619
Diabetes mellitus	present/absent	16/91	6/27	10/64	0.532
Heart failure	present/absent	2/105	0/33	2/72	0.34
ASA-PS	1/2/3	20/71/16	4/24/5	16/47/11	0.498
Distance from the tumor to the anal verge	≤ 5 cm/5-10 cm/10-15 cm	41/32/34	10/22/1	31/10/33	< 0.00001
Surgical procedure	HAR/LAR/ISR/APR	29/45/4/29	0/29/4/0	29/16/0/29	0.00002
Endoscopic resection	present/absent	6/101	1/32	5/69	0.439
NAC	present/absent	24/83	7/26	17/57	0.840
Neoadjuvant CRT	present/absent	37/70	12/21	25/49	0.796
Preoperative BUN (mg/dl)	median (range)	14.3 (5.3–48.6)	14.1 (9.2–19.9)	14.35 (5.3–48.6)	0.777
Preoperative Cr (mg/dl)	median (range)	0.68 (0.30–3.60)	0.71 (0.40–1.40)	0.68 (0.30–3.60)	0.566
Preoperative eGFR (ml/min/1.73m2)	median (range)	79.4 (14.2–203.6)	82.4 (40.1–124.5)	76.7 (14.2–203.6)	0.414
(y)pStage	I/II/III	3/18/86	0/3/30	3/15/56	0.582
Regimen	OX combi/FP mono	59/48	23/10	36/38	0.043
CAPOX	number	54	20	34
FOLFOX	number	5	3	2
UFT	number	30	6	24
Capecitabine	number	14	3	11
S-1	number	4	1	3
Duration from surgery to start of ACT (days)	median (range)	36 (20–106)	32 (20–63)	38 (20–106)	0.084
Pre-ACT BUN (mg/dl)	median (range)	13.6 (5.8–24.0)	14.7 (8.4–23.3)	13.5 (5.8–24.0)	0.254
Pre-ACT Cr (mg/dl)	median (range)	0.71 (0.30–1.40)	0.76 (0.40–1.40)	0.67 (0.30–1.30)	0.036
Pre-ACT eGFR (ml/min/1.73m2)	median (range)	79.0 (38.6–189.7)	78.3 (38.6–112.6)	79.7 (44.7–189.7)	0.399

BMI body mass index, ASA-PS American Society of Anesthesiologists physical status, NAC neoadjuvant chemotherapy, CRT chemoradiotherapy, BUN blood urea nitrogen, Cr serum creatinine, eGFR estimated glomerular filtration rate, CAPOX capecitabine plus oxaliplatin, FOLFOX 5-fluorouracil, leucovorin and oxaliplatin, UFT tegafur-uracil, ACT adjuvant chemotherapy, HAR high anterior resection, LAR low anterior resection, ISR intersphincteric resection, APR abdominoperineal resection, OX combi oxaliplatin combination therapy, FP mono fluoropyrimidine monotherapy

Preoperative renal function, evaluated using serum creatinine and blood urea nitrogen concentrations, and the estimated glomerular filtration rate, did not differ significantly between the groups. However, at the time of ACT initiation, serum creatinine concentrations were significantly higher in the DI vs. non-DI groups (median: 0.76 vs. 0.67 mg/dL, respectively; P = 0.036), while blood urea nitrogen concentrations and estimated glomerular filtration rates remained comparable (Table 1).

Treatment outcomes and chemotherapy intensity

The overall ACT completion rate was 44.9%, with no significant difference between the DI and non-DI groups (54.5% vs. 51.4%, respectively; P = 0.760). Similarly, the proportion of patients who completed ACT without dose reduction was not significantly different (DI vs. non-DI groups: 21.2% vs. 48.6%, respectively; P = 0.294) (Table 2). The median average RDI was 80.0% in the DI group and 81.3% in the non-DI group, with no significant difference between the two groups. There was no significant difference in the RDIs of OX and fluoropyrimidine.

Table 2.

Comparison of adjuvant chemotherapy outcomes and adverse events between the diverting ileostomy (DI) and non-DI groups

		All patients (n = 107)	DI group (n = 33)	Non-DI group (n = 74)	P value
Completion	number (%)	56 (52.3)	18 (54.5)	38 (51.4)	0.760
Completion without dose reduction	number (%)	30 (28.0)	7 (21.2)	26 (48.6)	0.294
ARDI	median (range)	80.0 (10.0–100.0)	80.0 (12.5–100.0)	81.3 (10.0–100.0)	0.665
OX RDI	median (range)	56.4 (12.5–100.0)	61.3 (12.5–100.0)	52.9 (12.5–100.0)	0.576
FP RDI	median (range)	92.5 (12.5–100.0)	89.6 (12.5–100.0)	95.5 (20.0–100.0)	0.491
Grade ≧ 2 AEs	number (%)	55 (51.4)	21 (63.6)	34 (45.9)	0.091
Grade ≧ 3 AEs	number (%)	9 (8.4)	6 (18.2)	3 (4.1)	0.015
Grade ≧ 3 AEs by type
Acute kidney injury	number	3	2	1
Diarrhea	number	3	1	2
Hand-foot syndrome	number	1	1	0
Neutropenia	number	1	1	0
Oral mucositis	number	1	1	0

ARDI average relative dose intensity, OX oxaliplatin, FP fluoropyrimidine, RDI relative dose intensity, AEs adverse events

AEs

Grade ≥ 2 AEs occurred in 51.4% of all patients, with no significant difference between the DI and non-DI groups (63.6% vs. 45.9%, respectively; P = 0.091). In contrast, the incidence of grade ≥ 3 AEs was significantly higher in the DI group (18.2%) compared with the non-DI group (4.1%) (P = 0.015) (Table 2). Kaplan–Meier analysis of grade ≥ 2 AEs showed a steady increase over time, suggesting that these events tended to accumulate with increasing chemotherapy cycles (Fig. 2a). In contrast, grade ≥ 3 AEs occurred predominantly within the first three cycles, indicating that severe toxicity developed early during ACT (Fig. 2b). Multivariate analysis confirmed the presence of an ileostomy as an independent risk factor for grade ≥ 3 AEs (odds ratio: 5.749; P = 0.022) (Table 3).

Fig. 2.

Kaplan–Meier curves for the incidences of adverse events. (a) Cumulative incidence of grade ≥ 2 adverse events during adjuvant chemotherapy. (b) Cumulative incidence of grade ≥ 3 adverse events during adjuvant chemotherapy. ACT, adjuvant chemotherapy; DI, diverting ileostomy; AEs, adverse events

Table 3.

Univariate and multivariate logistic regression analysis of the predictors of grade ≥ 3 adverse events

		Univariate analysis			Multivariate analysis
		Odds ratio	95% CI	P value	Odds ratio	95% CI	P value
Age (years)	≥ 70 vs. < 70	1.160	0.293—4.588	0.832
ASA-PS	≥ 3 vs. 1, 2	1.446	0.168—12.416	0.737
NAC	present vs. absent	3.120	0.767—12.697	0.096	3.575	0.815—15.688	0.091
Neoadjuvant CRT	present vs. absent	1.576	0.396—6.263	0.518
(y)pStage	III vs. I, II	2.051	0.242—17.367	0.510
Pre-ACT BUN (mg/dl)	≥ 20 vs. < 20	1.625	0.177—14.909	0.668
Pre-ACT Cr (mg/dl)	≥ 0.79 vs. < 0.79	1.813	0.455—7.231	0.399
Pre-ACT eGFR (ml/min/1.73m2)	≤ 60 vs. > 60	1.714	0.323—9.109	0.527
Regimen	OX combi vs. FP mono	3.096	0.612—15.657	0.172
Ileostomy	present vs. absent	5.259	1.227—22.534	0.025	5.749	1.292—25.574	0.022

ASA-PS American Society of Anesthesiologists physical status, NAC neoadjuvant chemotherapy, CRT chemoradiotherapy, BUN blood urea nitrogen, Cr serum creatinine, eGFR estimated glomerular filtration rate, OX combi oxaliplatin combination therapy, FP mono fluoropyrimidine monotherapy

Impact of an HOS

In Table 4, among the 33 patients with a DI, 12 (36.4%) developed an HOS (Fig. 1). None of the patients with a colostomy in the non-DI group met the criteria for HOS. There were no statistically significant differences in ACT completion rates (33.3% vs. 66.7%; P = 0.064), completion without dose reduction (16.7% vs. 23.8%; P = 0.629), or average RDI (median 69.8 vs. 84.0; P = 0.082) between patients with and without an HOS, respectively. However, the median OX RDI was significantly lower in the HOS group than that in the non-HOS group (37.5% vs. 75.0%, respectively; P = 0.007). The incidence of grade ≥ 3 AEs was numerically higher in the HOS group than that in the non-HOS group (33.3% vs. 9.5%, respectively; P = 0.088); however, this difference was not statistically significant.

Table 4.

Comparison of chemotherapy outcomes and adverse events between patients with and without a high-output stoma in the ileostomy group

		All ileostomy patients (n = 33)	HOS (n = 12)	Non-HOS (n = 21)	P value
Completion	number (%)	18 (54.5)	4 (33.3)	14 (66.7)	0.064
Completion without dose reduction	number (%)	7 (21.2)	2 (16.7)	5 (23.8)	0.629
ARDI	median (range)	80.0 (12.5–100.0)	69.8 (25.0–100.0)	84.0 (12.5–100.0)	0.082
OX RDI	median (range)	61.3 (12.5–100.0)	37.5 (12.5–100.0)	75.0 (42.5–100.0)	0.007
FP RDI	median (range)	89.6 (12.5–100.0)	81.6 (25.0–100.0)	91.7 (12.5–100.0)	0.246
Grade ≧ 2 AEs	number (%)	21 (63.6)	9 (75.0)	12 (57.1)	0.305
Grade ≧ 3 AEs	number (%)	6 (18.2)	4 (33.3)	2 (9.5)	0.088

HOS high-output stoma, ARDI average relative dose intensity, OX oxaliplatin, FP fluoropyrimidine, RDI relative dose intensity, AEs adverse events

Among 23 patients in the DI group who received OX-combined ACT, multivariate analysis identified HOS as a significant independent predictor of non-completion (odds ratio: 13.423; P = 0.039) (Table 5). Other clinical variables, including age, neoadjuvant therapy, and renal function parameters, were not significantly associated with treatment completion.

Table 5.

Univariate and multivariate logistic regression analysis of the predictors of failure to complete oxaliplatin-based chemotherapy in the ileostomy group

		Univariate analysis			Multivariate analysis
		Odds ratio	95% CI	P value	Odds ratio	95% CI	P value
Age (years)	≥ 70 vs. < 70	1.167	0.224—6.081	0.855
ASA-PS	≥ 3 vs. 1, 2	1.636	0.127—21.104	0.706
NAC	present vs. absent	5.250	0.874—31.553	0.07	4.773	0.601—37.937	0.139
Neoadjuvant CRT	present vs. absent	0.964	0.160—5.795	0.968
(y)pStage	III vs. I, II	1.067	0.116—8.964	0.302
Pre-ACT BUN (mg/dl)	≥ 20 vs. < 20	3.667	0.513—26.224	0.196
Pre-ACT Cr (mg/dl)	≥ 0.79 vs. < 0.79	1.458	0.252—8.429	0.673
Pre-ACT eGFR (ml/min/1.73m2)	≤ 60 vs. > 60	3.000	0.232—38.875	0.401
HOS	present vs. absent	14.400	1.375—150.808	0.026	13.423	1.142—157.723	0.039

ASA-PS American Society of Anesthesiologists physical status, NAC neoadjuvant chemotherapy, CRT chemoradiotherapy, BUN blood urea nitrogen, Cr serum creatinine, eGFR estimated glomerular filtration rate, HOS high-output stoma

Discussion

In this study, we found that the incidence of grade ≥ 3 AEs was higher in the DI vs. non-DI groups, especially within the first three cycles of ACT. In contrast, there were no significant differences in completion rates or RDI values between patients with and without a DI. This suggests that ACT can be continued even in patients with a DI, with appropriate management, and highlights the importance of close monitoring in the early phase of treatment in clinical practice. This early clustering of severe AEs may be explained by initial intolerance to chemotherapy in patients with a DI. Among the 6 patients who developed grade ≥ 3 AEs, 3 discontinued ACT, and 3 required dose modification or discontinuation of OX. These timely clinical interventions likely mitigated further toxicity, contributing to the stabilization of AE incidence beyond the first three cycle.

The high incidence of serious AEs in the DI group might be partially explained by the frequent use of OX combination regimens; however, OX was not an independent risk factor for grade ≥ 3 AEs. In other words, the increased toxicity observed in this study may not be solely attributable to the chemotherapy regimen and could be independently associated with the presence of a DI. Subclinical dehydration, electrolyte abnormalities, and renal dysfunction associated with a DI may have increased the toxicity of systemic chemotherapy. In the present study, serum creatinine concentrations at ACT initiation were high in the DI group even though preoperative renal function did not differ between the DI and non-DI groups. This finding is consistent with those in previous reports indicating that DI construction is closely associated with decreased renal function [22, 23]. Additionally, recent studies have reported that administering ACT to patients with a DI may exacerbate chemotherapy-induced diarrhea and renal dysfunction, further supporting our findings [16, 24]. Notably, the frequent selection of oxaliplatin-based regimens in the DI group may reflect the treating physicians’ assessment that those patients, despite undergoing DI, had sufficient overall physical condition and tolerance for intensive chemotherapy. Given that disease stage distribution was not significantly different between the groups, we consider that this treatment choice was more likely influenced by patient fitness than by tumor progression.

Notably, a DI was created with a clinically justified decision to protect the anastomosis, and the results of this study do not negate the usefulness of a DI. Postoperative complications, including anastomotic leakage, have been associated with delayed or omitted ACT in colorectal cancer patients, leading to a poor prognosis [25, 26]. In fact, the presence of a DI had no significant effect on treatment completion rates or RDI values in the present study, indicating that adequate supportive care is sufficient to perform ACT. However, this result should be interpreted with caution, given the relatively small sample size of this study, which may have limited the ability to detect modest differences in treatment outcomes. The proportion of patients completing treatment without dose reduction was 21.2% in the DI group versus 48.6% in the non-DI group—a numerically meaningful difference that did not reach statistical significance. Nevertheless, our findings are consistent with a large-scale study that used the National Database of Health Insurance Claims and Specific Health Checkups in Japan, which reported that a diverting stoma does not affect the ACT dose [15]. Therefore, creating a DI should remain a valid surgical option when anastomotic protection is clinically indicated, even in patients requiring ACT. Additionally, appropriate postoperative follow-up and early intervention should be ensured after DI creation.

To the best of our knowledge, few studies have examined the association of a perioperative HOS with ACT in as much depth as that in the present study. In a subgroup analysis of the DI group in our study, 36% of the patients developed an HOS, and although the presence of an HOS was not directly associated with treatment completion rates or AE rates, its presence significantly decreased the RDI of OX. Furthermore, the presence of an HOS was an independent predictor of failure to complete the OX combination regimen, in the multivariate analysis. These results indicate that an HOS may hinder adequate administration of highly toxic drugs, such as OX, and could therefore affect the prognosis. Indeed, several studies in colon cancer have suggested that reduced RDI of ACT is associated with poorer survival outcomes [27, 28]. Although this relationship remains to be fully validated in rectal cancer, the observed reduction in RDI due to HOS may have meaningful oncological implications. Previous studies have demonstrated that early stoma closure, even during ACT, does not negatively impact long-term oncologic outcomes compared with closure after ACT completion [29, 30]. Our novel results regarding the relationship between HOS and poor completion rates for the OX regimen, together with previous findings, suggest that in patients with an HOS, early closure could be considered to help ensure adequate chemotherapy delivery and achieve cancer control. A retrospective study reporting that early stoma closure was associated with fewer OX dose modifications supports this hypothesis [31]. However, further validation with prospective studies is needed to clarify the usefulness of this strategy.

This study has several limitations. First, the retrospective and single-center design may limit the generalizability of the findings. In addition, the relatively small sample size may have limited the statistical power to detect certain differences, particularly in treatment completion without dose reduction and subgroup comparisons. Second, the choice of DI construction and regimen depends on the discretion of the surgeon and the physician in charge, and may include the influence of decisions made on the basis of the patient’s background characteristics. Third, the definition of HOS varies in the literature, and in this study, we defined an HOS as stoma output > 1500 mL on any single day, on the basis of previous studies. However, this threshold may be affected by transient factors such as diarrhea or increased oral intake, and the generalizability of our results may vary depending on the definition used. Finally, HOS assessment was limited to the inpatient period, and post-discharge output could not be monitored, potentially underestimating its clinical impact.

In conclusion, ACT can be administered with acceptable safety and efficacy in patients with a DI, provided appropriate supportive measures are in place. However, these patients have an increased risk of early severe AEs and may require enhanced peri-treatment monitoring. In cases of an HOS, reduced OX exposure may compromise treatment intensity. Further investigation into optimal treatment strategies—including the potential role of early stoma closure—are necessary to improve chemotherapy delivery in this subgroup.

Abbreviations

ACT

Adjuvant chemotherapy

OX

Oxaliplatin

AEs

Adverse events

DI

Diverting ileostomy

HOS

High-output stoma

RDI

Relative dose intensity

Authors' contributions

Conception and design: T.Y. Acquisition of the data: T.Y, M.Y, K.U, K.O, C.Y, Y.K, K.K, T.M, N.T, T.S. Drafting and critical revision of the article: T.Y, M.Y. Final approval: Y.F. All authors have read and approved the manuscript.

Funding

The Authors confirm that no funding was received for this study.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. The present study was approved by the Certified Review Board of Tottori University Hospital (approval number: 21A075).

Ethics approval and consent to participate

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional review board of ethics committee and national research committee with the 1964 Helsinki declaration and its later amendments.

Disclosure

Authors declare no Conflict of Interests for this article.

Competing interests

The authors declare no competing interests.