Does Surgical Intervention Within 48 Hours Improve Postoperative Outcomes in Ulcerative Colitis Complicated by Megacolon?

Abstract

Background

Intravenous glucocorticoids have been suggested as first-line therapy for patients with ulcerative colitis (UC) and megacolon. However, there is no definite consensus regarding the timing of surgical intervention when medical therapy fails.

Methods

Data were collected from 56 consecutive patients diagnosed with megacolon UC who underwent surgery between January 2000 and September 2024. Patients who underwent surgery within 48 h of the diagnosis were defined as the early group, and those who underwent surgery after 48 h were defined as the delayed group. The short-term surgical outcomes were compared between the 2 groups, and the factors associated with postoperative complications were investigated.

Results

Among the 56 patients with megacolon, 37 were categorized into the early group and 19 into the delayed group. There was a tendency toward a lower incidence of severe postoperative complications (Clavien-Dindo grade ≥3) in the early group than in the delayed group with statistical significance (P = .043). Furthermore, the risk of colonic perforation significantly increased when more than 48 h had passed since diagnosis (P = .0015). A multivariate analysis identified colonic perforation as a significant risk factor for severe postoperative complications.

Discussion

We suggest that surgical intervention within 48 h may reduce the incidence of colonic perforation in the treatment of UC complicated by megacolon, thereby potentially decreasing the risk of severe postoperative complications.

Keywords

ulcerative colitis timing of surgery megacolon

Key Takeaways

• Surgical intervention within 48 h of megacolon diagnosis in ulcerative colitis may reduce the incidence of colonic perforation.

• Delayed surgery is associated with an increased risk of severe postoperative complications.

• Colonic perforation is a significant predictor of adverse postoperative outcomes in UC with megacolon.

Introduction

Ulcerative colitis (UC) with megacolon is caused by the inflammation of all layers of the intestinal tract and destruction of the muscularis propria, including toxic megacolon with toxic symptoms. Patients with UC-associated megacolon have a high risk of colonic perforation, and those with perforation have a high mortality rate. Therefore, surgical intervention should be performed immediately after the diagnosis, regardless of the presence of toxic symptoms.^1,2 However, several new medical therapies are now available, and surgery can still be avoided even in some cases of severe UC, including toxic megacolon.³ Intravenous corticosteroids are recommended as the first-choice treatment for severe UC in evidence-based guidelines from the World Society of Emergency Surgery and the European Crohn’s and Colitis Organization.^4,5 Surgical intervention is considered if there is no clinical improvement or if biological signs of deterioration are observed after 24-72 h.^4-6 However, there is currently no consensus or strong evidence regarding the optimal timing of surgery for megacolon-treated UC. Establishing the optimal timing for surgical intervention in cases of complicated megacolon, which carries a high risk for colonic perforation, is therefore highly recommended. We conducted this retrospective study to investigate whether early surgery for the treatment of UC-complicated megacolon affects short-term surgical outcomes. We also investigated the factors associated with the development of postoperative complications. Our findings may serve as useful clinical indicators for determining the indications and optimal timing of surgery in patients with UC and megacolon.

Methods

Study Design and Patients

A single-arm retrospective observational design was used in this study. Data from consecutive patients diagnosed with megacolon UC between January 2000 and September 2024 were obtained from the hospital database. Of these patients, those who underwent surgery were selected for the analysis. Fifty-six patients were ultimately enrolled in the study.

Patient data, preoperative medical treatment, and surgical outcomes were obtained. Surgical outcomes included the surgical procedure, operation time, blood loss, postoperative complications, and length of postoperative hospital stay. Postoperative complications were graded according to the Clavien-Dindo classification and cases classified as Grade 3 or higher in the Clavien-Dindo classification were defined as severe postoperative complications.⁷ Toxic megacolon was defined according to the criteria reported by Jalan. Jalan et al reported that they considered a patient “toxic” if the patient met 3 of the 4 criteria in group A (pyrexia >38.6°C, tachycardia >120 beats/min, leukocytosis >10 500/mm³, hemoglobin <60%) plus at least 1 of the 4 criteria in group B (dehydration, mental changes, electrolyte imbalance, hypotension). A diagnosis of “megacolon” was made if abdominal X-ray or CT scan findings showed a maximum transverse colon dilation of 6 cm or more.⁸

Treatment Strategy and Surgical Indication

At our institution, our standard treatment strategy for UC with megacolon is to perform surgery in principle. However, medical treatment may be considered for patients without toxic symptoms and in good general condition. In some patients who were transferred to our hospital for surgery, medical treatment was initiated after megacolon was diagnosed at another hospital. As a result, there have been cases in which surgery was performed several days after the diagnosis of megacolon. Patients who underwent surgery within 48 h of the diagnosis were defined as the early group, while those who underwent surgery beyond 48 h were defined as the delayed group. In this study, the time of diagnosis of megacolon was defined as the time when an abdominal X-ray or CT scan first revealed a maximum transverse colon dilation of 6 cm or more. This 48 h threshold is supported by several key factors. First, existing literature indicates that the assessment of the efficacy of medical treatment for toxic megacolon typically occurs within 24 to 72 h. Specifically, 48 h is often recognized as a critical timeframe for observing the effects of corticosteroids and other medical interventions.^9,10 Second, from a clinical practicality perspective, the 48 h timeframe allows for a clear assessment of patient status without the risks associated with premature surgical intervention. If surgery is performed too early, there is a risk that medical therapies may not have been adequately trialed, potentially leading to unnecessary operations. Conversely, delaying surgery beyond 48 h can significantly increase the risk of serious complications, such as colonic perforation or sepsis. Thus, the choice of a 48 h cutoff is both evidence-based and reflective of clinical practices that balance the need for effective medical management with the urgency of surgical intervention.

Statistical Analysis and Ethics

Binary and categorical variables were presented as counts and percentages, and continuous variables were presented as medians and interquartile ranges (IQRs). Univariate analyses were performed to compare variables between the 2 groups. Binary and categorical variables were compared using Fisher’s exact test, and continuous variables were compared using the Mann-Whitney U test. A multivariate analysis was conducted using a logistic regression model to assess the relationship between severe postoperative complications (Clavien-Dindo grade ≥3) and various independent variables, including the age, colonic perforation, and time from the diagnosis to surgery.

Statistical significance was set at P < .05. All statistical analyses were performed using EZR, which is for R.¹¹ It is a modified version of the R commander designed to add statistical functions frequently used in biostatistics.

This study was conducted in accordance with the principles of the Declaration of Helsinki, and all applicable local laws and regulations. The protocol was approved by the institutional review board of Yokohama Municipal Citizen’s Hospital. In addition, written informed consent was obtained from participants prior to the study.

Results

A total of 56 patients underwent surgery for megacolon during the study period. Of these, 37 were categorized into the early group and 19 into the delayed group. The patient characteristics and medical history are presented in Table 1. There were no significant differences in patient background between the 2 groups, except for preexisting diabetes mellitus (DM). In addition, there were no significant differences in the preoperative treatment or preoperative blood test results between the 2 groups. The percentage of patients presenting with toxic symptoms was significantly higher in the early group than that in the delayed group (91.9% vs 42.1%, P < .001). Conversely, the percentage of patients who experienced colonic perforation between the megacolon diagnosis and surgery was significantly higher in the delayed group (5.4% vs 42.1%, P = .0015).

Table 1.

Characteristics of all Patients

Characteristic^a	Early	Delayed	P-value
Characteristic^a	N = 37	N = 19	P-value
Age at surgery, year, median (range)	47.0 (35.0-60.0)	51.0 (32.5-60.0)	0.72
Age at diagnosis of UC, year, median (range)	40.8 (25.3-53.4)	44.8 (22.3-56.4)	0.63
Age at surgery (≥65)	6 (16.2%)	3 (15.8%)	1.0
Sex
Male	28 (75.7%)	15 (78.9%)	1.0
Female	9 (24.3%)	4 (21.1%)
ASA score
I-II	35 (94.6%)	16 (84.2%)	0.32
III	2 (5.4%)	3 (15.8%)
Comorbidity
Heart disease	2 (5.4%)	3 (15.8%)	0.33
Diabetes mellitus	2 (5.4%)	5 (26.3%)	0.041
Cerebral vascular diseases	2 (5.4%)	3 (15.8%)	0.33
The duration from diagnosis of UC to surgery, month, median (range)	18.0 (1.0-124.0)	4.0 (1.0-49.0)	0.22
Disease extent
Total	37 (100%)	19 (100%)	1.0
Left	0 (0.0%)	0 (0.0%)
Medical therapy
Steroid (total amount of prednisolone) mg	840.0 (590.0-1320.0)	800.0 (305.0-1360.0)	0.54
Steroid (1 month preoperatively) mg	600.0 (300.0-900.0)	700.0 (180.0-865.0)	0.98
Anti TNF-α (1 year preoperatively)	9 (24.3%)	5 (26.3%)	1.0
Tacrolimus (1 year preoperatively)	6 (16.2%)	0 (0.0%)	0.083
Thiopurine (1 year preoperatively)	2 (5.6%)	1 (5.3%)	1.0
Laboratory data
WBC (/mm³)	10 000 (7505-12593)	10 150 (8465-16475)	0.44
Hb (g/dL)	9.5 (8.0-11.2)	10.0 (9.1-11.3)	0.16
CRP (mg/L)	9.8 (5.1-13.5)	11.6 (4.6-19.7)	0.53
ESR (mm/h)	52.0 (35.0-69.0)	56.0 (44.5-74.5)	0.69
TP (g/dL)	5.2 (4.9-5.6)	5.3 (5.1-5.4)	0.47
Alb (g/dL)	1.9 (1.6-2.0)	2.1 (1.7-2.4)	0.15
PNI	20.5 (18.1-23.8)	25.8 (21.0-28.2)	0.057
Toxic megacolon	34 (91.9%)	8 (42.1%)	<0.001
Colonic perforation	2 (5.4%)	8 (42.1%)	0.0015

^aThe median interquartile range is presented as a continuous variable, and numbers and percentages are shown for categorical variables.

The surgical outcomes are summarized in Table 2. There were no significant differences between the 2 groups in terms of operative time, blood loss, or surgical procedures. The incidence of severe postoperative complications was significantly higher in the delayed group than in the early group (9 cases [24.3%] vs 10 cases [52.6%]; P = .043). Postoperative complications included paralytic ileus, small bowel obstruction, pelvic abscess, surgical site infection, and thrombus formation. Notably, the incidence of pelvic abscesses was significantly higher in the delayed group than in the early group (P = .016). One death occurred in each group. In both cases, the cause of death was Acute Respiratory Distress Syndrome (ARDS) resulting from pneumonia and sepsis. The median postoperative hospital stay was 27.0 days in the early group and 26.0 days in the delayed group; however, the difference was not significant (P = .85). In addition, within the delayed surgery group, severe postoperative complications occurred in both toxic and nontoxic subgroups at similarly high rates (50% [4/8] and 54.5% [6/11], respectively).

Table 2.

Surgical Outcomes of all Patients

Surgical outcomes^a	Early	Delayed	P-value
Surgical outcomes^a	N = 37	N = 19	P-value
Operation time, min, median (range)	199.0 (176.0-225.0)	212.0 (173.0-244.5)	.35
Blood loss, g, median (range)	150.0 (80.0-450.0)	165.0 (55.0-546.0)	.93
Surgical procedure
Subtotal colectomy with ileostomy and suprapubic mucous fistula	31 (83.8%)	16 (84.2%)	1
Total colectomy and ileal J-pouch anal canal anastomosis without ileostomy	5 (13.5%)	3 (15.8%)
Total colectomy and ileal J-pouch anal canal anastomosis with ileostomy	1 (2.7%)	0 (0.0%)
Early postoperative outcome
Severe complications (Clavien-Dindo classification system grade 3 or higher)	9 (24.3%)	10 (52.6%)	.043
Ileus / small bowel obstruction	3 (8.1%)	1 (5.3%)	1
Anastomotic leakage	0 (0.0%)	1 (5.3%)	.34
Intraabdominal/pelvic abscess	2 (5.4%)	6 (31.6%)	.016
Surgical site infection	2 (5.4%)	1 (5.3%)	1
Postoperative bleeding	3 (8.1%)	2 (10.5%)	1
Pneumonia	1 (2.7%)	1 (5.3%)	1
Others	2 (5.4%)	0 (0.0%)	1
Mortality	1 (2.7%)	1 (5.3%)	1
Postoperative hospital stay, days, median (range)	27.0 (19.0-41.0)	26.0 (17.0-35.0)	.85

^aThe median interquartile range is presented as a continuous variable, and numbers and percentages are shown for categorical variables.

In Table 3, we compared patient backgrounds according to the occurrence of severe postoperative complications. The percentage of patients ≥65 years old, the incidence of colonic perforation, and the proportion of cases where more than 48 h had elapsed between the diagnosis of megacolon and surgery were significantly higher in patients who developed severe complications than in those who did not.

Table 3.

Univariate Analysis of Independent Predictors of Severe Postoperative Complications

Characteristic^a	Without severe complications	With severe complications	P-value
Characteristic^a	N = 37	N = 19	P-value
Age at surgery
<65	34 (91.9%)	13 (68.4%)	.049
≥65	3 (8.1%)	6 (31.6%)
Sex
Male	27 (73.0%)	16 (84.2%)	.51
Female	10 (27.0%)	3 (15.8%)
ASA score
I-II	35 (94.6%)	16 (84.2%)	.32
III	2 (5.4%)	3 (15.8%)
Diabetes mellitus
Absence	34 (91.9%)	15 (78.9%)	.22
Presence	3 (8.1%)	4 (21.1%)
Preoperative albumin (g/dl)
≥3.0	2 (5.4%)	0 (0.0%)	.54
<3.0	35 (94.6%)	19 (100.0%)
Steroid (total amount of prednisolone) mg
<10 000	35 (94.6%)	18 (94.7%)	1
≥10 000	2 (5.4%)	1 (5.3%)
Steroid (1 month preoperatively) mg/day
<20	16 (43.2%)	8 (42.1%)	1
≥20	21 (56.8%)	11 (57.9%)
Immunosuppressant administration (1 year preoperatively)
Absence	26 (70.3%)	11 (57.9%)	.37
Presence	11 (29.7%)	8 (42.1%)
Toxic megacolon
Absence	7 (18.9%)	7 (36.8%)	.20
Presence	30 (81.1%)	12 (63.2%)
Colonic perforation
Absence	35 (94.6%)	11 (57.9%)	.0015
Presence	2 (5.4%)	8 (42.1%)
Preoperative medical therapy
>48 hrs	9 (24.3%)	10 (52.6%)	.043
≤48 hrs	28 (75.7%)	9 (47.4%)

^aNumbers and percentages are shown for categorical variables.

Finally, we conducted a multivariate analysis to identify factors predictive of severe postoperative complications. The analysis revealed one significant factor: colonic perforation (Table 4).

Table 4.

Multivariate Analysis of Independent Predictors of Severe Postoperative Complications

Factor	OR^a	P-value	95% CI^b
Age at surgery (≥65)	4.25	.11	0.72-25.20
Colonic perforation	6.74	.047	1.01-44.40
Preoperative medical therapy (>48 h)	2.17	.30	0.50-9.36

^aOdds Ratio.

^bConfidence interval.

Discussion

The present study revealed 3 important findings. First, early surgical intervention within 48 h of the diagnosis tended to reduce the incidence of severe postoperative complications in patients with UC with megacolon. Second, the risk of colonic perforation was significantly increased when more than 48 h had elapsed after the diagnosis of UC with megacolon. Third, colonic perforation was identified as a risk factor for the development of severe postoperative complications, even though the number of patients with colonic perforation in this study is small.

Intravenous glucocorticoids have been suggested as the first-line therapy for patients with UC-related megacolon. If there was no evidence of improvement, urgent surgery was indicated.⁵ In a case-control study by Katzka et al, surgery was avoided in approximately 50% of patients after 7 days of intravenous antimicrobial and steroid therapy.¹² In contrast, a case-control study by Carmelo et al reported that approximately 15% of patients died despite undergoing surgical intervention immediately after the megacolon diagnosis.¹³ There is no definite consensus regarding the timing of surgery, and decisions regarding the timing of surgical intervention are currently left to the discretion of each institution and treating physician. A previous report on severe ulcerative colitis found that severe postoperative complications in the early surgical intervention group and the non-early surgical intervention group were approximately 20% and 50%, respectively, which were similar to the respective rates of 24.3% and 52.6% found in the present study, despite differences in the criteria for the timing of surgical intervention.¹⁴ In the present study, although there was no marked difference in the mortality between the 2 groups, the incidence of severe postoperative complications was significantly higher in the delayed group than in the early group. This highlights the increased risk of complications associated with delayed surgical intervention.

One of the most important problems associated with megacolon is the risk of colonic perforation. In a previous report, Norland et al noted that the risk of gastrointestinal perforation did not worsen with prolonged medical therapy.¹⁵ However, another report stated that the risk of perforation increased to 50% in patients who received treatment more than 72 h after the diagnosis of UC with megacolon.¹⁶ Thus, the relationship between the course of UC with megacolon and the risk of perforation remains controversial. In this study, the proportion of colonic perforation was significantly increased when more than 48 h had elapsed after the diagnosis of UC complicated with megacolon. Although only 10 cases of colonic perforation developed, a small number of cases were studied, suggesting that early surgical intervention will have possibility to reduce the risk of colonic perforation. The mortality rate of patients with UC complicated by perforation has improved since the 27% reported by Heppell et al in 1986; however, prognosis remains poor.¹⁷ Recent studies indicate that mortality in perforated cases is 3 to 5 times higher than in non-perforated cases.¹⁸ In the present study, the mortality was low in both groups, but the incidence of intra-abdominal abscesses of grade ≥3, according to the Clavien-Dindo classification, was significantly higher in the delayed group than in the early group. This may be associated with intra-abdominal infections resulting from colonic perforations. We believe that surgical intervention before colonic perforation improves the prognosis.

Next, we identified risk factors for surgical complications. A previous study reported that the American Society of Anesthesiologists score, preoperative anemia, and use of immunosuppressants, among others, were risk factors.^19,20 In contrast to previous reports, the present study was conducted only in patients with megacolon as a complication, and most of the patients shared the same risk factors as previously reported. Among these, colonic perforation was identified as a predictor of severe postoperative complications in the multivariate analysis. Therefore, in the treatment of UC with megacolon, surgery within 48 h of the diagnosis may reduce the risk of colonic perforation and subsequently lower the incidence of severe postoperative complications.

It is important to note that this study specifically analyzed patients with megacolon who ultimately required surgical intervention, regardless of whether they were initially classified as toxic or nontoxic. In our cohort, even patients initially considered nontoxic progressed to surgery, indicating failure of medical management. Within the delayed surgery group, both toxic and nontoxic patients demonstrated similarly high rates of severe postoperative complications. Therefore, our recommendation for surgery within 48 h applies specifically to this surgical population. Clinically, toxic megacolon requires intensive medical therapy with corticosteroids, close monitoring, and early surgical consultation; surgery is mandatory if there is no improvement after 24-72 h or if perforation occurs.^4,5 Currently, no standardized guideline exists for nontoxic megacolon, and while some reports suggest that selected patients may avoid surgery with medical management, evidence is limited.^3,21,22 These distinctions should inform clinical decision-making.

Our findings are consistent with existing guidelines and prior studies that recommend early surgical intervention for patients with megacolon to reduce the risk of perforation and other severe complications.^4,5 By specifically examining the impact of a 48-h threshold in our cohort, this study provides additional real-world evidence supporting the importance of timely operative management.

Several limitations associated with the present study should be acknowledged. First, the sample size was relatively small. However, no previous study has specifically focused on cases of megacolon disease, and the findings of this study may still have a potentially significant impact on clinical practice. Second, this study was limited to patients with UC and megacolon who had undergone surgery. Consequently, we were unable to evaluate the response rate to medical therapy among patients with UC complicated by megacolon, nor could we assess the proportion of patients who might have avoided surgery due to recent advancements in pharmacotherapy for ulcerative colitis. This exclusion represents a selection bias, as patients with less severe disease may have been successfully managed medically within the initial 48-h period and therefore were not captured in this analysis. Third, treatment approaches, including biologic agents, have evolved over the study period (2000-2024). These advances may have influenced treatment decisions and timing of surgery, representing a source of temporal bias. Fourth, as this was a retrospective study, patient allocation to the early and delayed groups was performed post hoc, which inherently introduces potential selection bias. In our cohort, patients in the early surgery group presented with more severe or toxic symptoms, while the delayed group exhibited a higher rate of colonic perforation. These findings reflect inherent selection bias based on clinical assessment and decision-making. Additionally, interhospital transfers may have introduced delays in diagnosis and surgical intervention, representing another source of potential selection bias in our cohort. In contrast, a prospective study design, wherein patients are pre-allocated to intervention groups based on predetermined criteria, would minimize such bias and yield more robust evidence. However, conducting a prospective study on this topic poses significant practical challenges due to the rarity of toxic megacolon in ulcerative colitis. To overcome this limitation, future multicenter prospective studies are warranted to validate the findings and further establish optimal surgical timing. Finally, the choice of surgical procedure, including performing total colectomy and ileal J-pouch anal canal anastomosis in some emergency cases, may have contributed to postoperative complications and represents an additional limitation of this study.

In conclusion, based on the results of this study, we suggest that surgical intervention within 48 h may reduce the incidence of colonic perforation in the treatment of UC complicated by megacolon, thereby potentially decreasing the risk of severe postoperative complications.

Footnotes

Acknowledgments

The authors would like to thank all medical staff involved in patient care and data collection.

ORCID iD

Eiichi Nakao

Ethical Considerations

The protocol for this research project has been approved by a suitably constituted Ethics Committee of the institution and it conforms to the provisions of the Declaration of Helsinki. Committee of the institutional review boards of Yokohama Municipal Citizen’s Hospital, Approval No. 20-12-11.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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