Evaluation of pathological findings in predicting postoperative endoscopic recurrence in Crohn’s disease: A retrospective cohort study

Abstract

BACKGROUND

Crohn’s disease (CD) patients with intestinal involvement often require surgical intervention due to resistance to medical therapy. Postoperative recurrence remains a significant challenge, with the Rutgeerts score commonly used to predict endoscopic recurrence.

AIM

To evaluate the relationship between microscopic and macroscopic pathological findings in resected intestinal specimens and the Rutgeerts score to predict endoscopic recurrence in CD patients.

METHODS

This retrospective cohort study included 32 patients over 18 years of age with intestinal CD who underwent surgery at General Surgery Clinic of Ankara Bilkent City Hospital between November 2019 and October 2023. Resection specimens were histopathologically re-examined, and postoperative colonoscopy reports were classified according to the Rutgeerts score. The association between pathological findings and endoscopic recurrence was analyzed statistically.

RESULTS

No significant association was found between macroscopic findings and Rutgeerts scores or endoscopic recurrence (P > 0.05). However, the presence and severity of neutrophilic cryptitis (P = 0.035) and crypt abscesses (P = 0.010) in microscopic findings were significantly associated with higher Rutgeerts scores, indicating a parallel increase with endoscopic recurrence. Other microscopic findings showed no significant correlation with Rutgeerts scores or endoscopic recurrence (P > 0.05).

CONCLUSION

The presence of neutrophilic cryptitis and crypt abscesses in resected intestinal specimens of CD patients increases the likelihood of endoscopic recurrence. Early postoperative medical treatment and close endoscopic follow-up may benefit high-risk patients to prevent recurrence, with treatment decisions made by a weekly multidisciplinary council involving General Surgery, Gastroenterology, and Radiology.

Key Words: Crohn’s disease; Endoscopic recurrence; Pathological findings; Rutgeerts score; Predicting

Core Tip: This study highlights the predictive role of histological findings in postoperative Crohn’s disease management. Specifically, neutrophilic cryptitis and crypt abscesses in resected specimens are significantly associated with endoscopic recurrence, as measured by the Rutgeerts score. These findings can guide clinicians in identifying high-risk Crohn’s disease patients for early intervention and intensified endoscopic monitoring to mitigate recurrence risks, with decisions supported by a weekly multidisciplinary council.

INTRODUCTION

Crohn’s disease (CD) is a chronic inflammatory bowel disease characterized by periods of remission and flare-ups, often requiring surgical intervention when medical therapies fail. Despite advances in biotherapies, nearly all surgically treated CD patients experience endoscopic and clinical recurrence over time. Reported rates of clinical recurrence after surgery range from 17%-55% at 5 years, 32%-76% at 10 years, and 72%-73% at 20 years, with reoperation rates increasing steadily over time[1]. The Rutgeerts score, based on endoscopic findings, is widely used to predict postoperative recurrence in CD[2]. However, identifying predictors of recurrence before endoscopic signs manifest could enable earlier intervention and improve outcomes. Pathological findings in resected specimens may offer insights into the likelihood of recurrence, yet their predictive value remains understudied[3].

This study aimed to assess the relationship between microscopic and macroscopic pathological findings in resected intestinal specimens and the Rutgeerts score in CD patients with intestinal involvement to predict postoperative endoscopic recurrence. The decision-making process for surgical intervention and postoperative management was guided by a weekly multidisciplinary council involving General Surgery, Gastroenterology, and Radiology, ensuring a consensus-based approach tailored to individual patient needs.

MATERIALS AND METHODS

Study design and population

This retrospective cohort study was conducted at the General Surgery Clinic of Ankara Bilkent City Hospital between November 2019 and October 2023. A total of 56 patients aged 18 years and older, diagnosed with CD involving the intestine and undergoing surgical resection, were initially identified. After applying exclusion criteria, 32 patients were included in the final analysis. Exclusion criteria included death during the postoperative period (n = 1), inability to confirm a definitive CD diagnosis upon re-examination of pathology specimens (n = 1), permanent end ileostomy at surgery (n = 4), unclosed diverting ileostomies (n = 9), and failure to attend follow-up colonoscopy (n = 10).

Data collection

Data were retrospectively collected from the hospital’s electronic records, including demographic characteristics (age at surgery, gender, smoking status), clinical features (age at symptom onset, disease localization, medical treatments, radiological methods for diagnosis), and surgical details (indication for surgery, type of anastomosis, stoma status, and need for reoperation). Indications for surgery, such as strictures, fistulas, or abscesses, were determined by the weekly multidisciplinary council involving General Surgery, Gastroenterology, and Radiology, based on resistance to medical therapy or progressive disease. Postoperative colonoscopy reports were reviewed to determine the Rutgeerts score, and the timing of colonoscopy (months after surgery) was recorded. Resection specimens were retrieved from the pathology archives and re-evaluated by two experienced pathologists. Macroscopic findings (adhesions, fistulas, strictures, aphthous lesions, cobblestone appearance, ulcers, intestinal wall thickness) and microscopic findings (aphthous ulcers, crypt distortion, increased lymphocytes, increased plasma cells, neutrophilic cryptitis, crypt abscesses, pseudopyloric metaplasia, submucosal fibrosis, neuronal hyperplasia, muscular hypertrophy, neuritis, ganglionitis, surgical margin involvement, non-caseating granulomas, fissured ulcers, transmural lymphoid aggregates, vasculitis, eosinophil count per high-power field) were systematically recorded.

Outcome measures

The primary outcome was the presence of endoscopic recurrence, defined as a Rutgeerts score of i2a or higher (i2a, i2b, i3, i4), assessed via postoperative colonoscopy. Patients with scores of i0 or i1 were classified as being in endoscopic remission. The secondary outcome was the association between pathological findings and the severity of endoscopic recurrence, as indicated by the Rutgeerts score.

Statistical analysis

Descriptive statistics were presented as n (%) for categorical variables and as mean ± SD or median (minimum-maximum) for continuous variables, depending on normality, assessed using the Shapiro-Wilk test and graphical methods. Categorical variables were compared using χ² tests or Fisher’s exact test, as appropriate. The Kruskal-Wallis test was used to compare intestinal wall thickness across Rutgeerts score groups, and the Mann-Whitney U test was used to compare wall thickness between patients with and without endoscopic recurrence. A P value < 0.05 was considered statistically significant. Analyses were performed using IBM SPSS Statistics 21.0 (IBM Corp., Armonk, NY, United States) and Microsoft Excel 2007.

RESULTS

Demographic and clinical characteristics

Of the 56 patients initially screened, 32 met the inclusion criteria. The cohort consisted of 18 females (32.1%) and 38 males (67.9%). The mean age at surgery was 39.07 ± 14.17 years, with 50.0% of patients aged 18-35 years, 26.8% aged 36-49 years, and 23.2% aged 50-70 years. Smoking status revealed 54.5% active smokers, 33.3% never smokers, and 12.2% former smokers. The mean age at symptom onset was 33.93 ± 13.46 years, with 63.0% of patients experiencing symptom onset between 16-35 years. Disease localization was ileal in 17.8%, ileocolonic in 71.4%, and colonic in 10.7% of patients. Preoperative medical treatments included various combinations of adalimumab, azathioprine, infliximab, mesalazine, prednisolone, indomethacin, sulfasalazine, budesonide, and vedolizumab. Diagnosis was confirmed using computed tomography in 44 patients and magnetic resonance enterography in 36 patients (Table 1).

Table 1 Demographic and clinical characteristics of the study population, mean ± SD/n (%).

Characteristic	Value
Total patients	56 (32 analyzed)
Gender
Female	18 (32.1)
Male	38 (67.9)
Age at surgery, years	39.07 ± 14.17
Smoking status
Active smoker	18 (54.5)
Never smoker	11 (33.3)
Former smoker	4 (12.2)
Age at symptom onset, years	33.93 ± 13.46
Disease localization
Ileal	10 (17.8)
Ileocolonic	40 (71.4)
Colonic	6 (10.7)

Surgical findings

Indications for surgery included strictures in 80.0% of patients, fistulas in 39.3%, abscesses in 19.6%, and perforation in 1.8%. Anastomosis without ileostomy was performed in 35.7% of patients, anastomosis with a diverting loop ileostomy in 60.7%, and end ileostomy in 7.1%. The choice of surgical procedure was determined by the weekly multidisciplinary council, considering the severity of complications (e.g., end ileostomy for severe cases) and patient condition. A second surgery during the lifetime was required in 17.9% of patients. The mean time to postoperative colonoscopy was 11.66 ± 7.35 months.

Endoscopic recurrence

Postoperative colonoscopy revealed no patients with a Rutgeerts score of i0. The distribution of Rutgeerts scores was as follows: I1 in 15.6% (n = 5), i2a in 15.6% (n = 5), i2b in 28.1% (n = 9), i3 in 18.7% (n = 6), and i4 in 21.8% (n = 7). Endoscopic recurrence (Rutgeerts score ≥ i2a) was observed in 84.3% of patients.

Pathological findings

Macroscopic findings: Macroscopic examination revealed adhesions in 40.6% of patients, fistulas in 31.2%, strictures in 71.9%, aphthous lesions in 87.5%, cobblestone appearance in 75.0%, and ulcers in 93.7%. The mean intestinal wall thickness was 13.72 ± 3.60 mm. No statistically significant association was found between macroscopic findings and Rutgeerts scores (P > 0.05) or endoscopic recurrence (P > 0.05).

Microscopic findings: Microscopic findings included aphthous ulcers in 75.0% of patients (21.9% severe), crypt distortion in 78.1% (21.9% severe), increased lymphocytes in 65.6% (34.4% severe), increased plasma cells in 68.8% (31.2% severe), neutrophilic cryptitis in 68.8% (31.2% severe), and crypt abscesses in 62.5% (28.1% severe). Other findings included pseudopyloric metaplasia in 65.6% (18.8% severe), submucosal fibrosis in 81.2% (18.8% severe), neuronal hyperplasia in 56.2% (37.5% severe), non-caseating granulomas in 31.2%, fissured ulcers in 59.4%, transmural lymphoid aggregates in 78.1%, and vasculitis in 9.4%. Eosinophil counts per high-power field were ≤ 30 in 9.4%, 31-50 in 18.8%, 51-100 in 40.6%, and > 100 in 31.2% of patients. The presence and severity of neutrophilic cryptitis (χ² = 9.954, P = 0.035) and crypt abscesses (χ² = 19.172, P = 0.010) were significantly associated with higher Rutgeerts scores, indicating a parallel increase with endoscopic recurrence. Other microscopic findings showed no significant association with Rutgeerts scores or endoscopic recurrence (P > 0.05; Table 2).

Table 2 Association between microscopic findings and Rutgeerts score.

Microscopic finding	Rutgeerts score distribution	P value
Neutrophilic cryptitis	Significant increase with higher scores	0.035
Crypt abscesses	Significant increase with higher scores	0.010
Other findings (e.g., granulomas, ganglionitis)	No significant association	> 0.05

DISCUSSION

This retrospective cohort study evaluated the relationship between pathological findings in resected intestinal specimens and postoperative endoscopic recurrence in CD patients, as assessed by the Rutgeerts score[1]. Our findings highlight the predictive value of specific microscopic features, particularly neutrophilic cryptitis and crypt abscesses, in identifying patients at higher risk of endoscopic recurrence. The high rate of endoscopic recurrence (84.3%) in our cohort aligns with previous reports, which estimate endoscopic recurrence in up to 70% of CD patients within the first year post-surgery[2]. The absence of a significant association between macroscopic findings and endoscopic recurrence suggests that gross pathological features may not be reliable predictors of recurrence, consistent with prior studies[3].

In contrast, the significant association between neutrophilic cryptitis and crypt abscesses and higher Rutgeerts scores (P = 0.035 and P = 0.010, respectively) underscores the importance of histological assessment in predicting recurrence. These findings are supported by Brennan et al[4], who identified active histological inflammation, including cryptitis and crypt abscesses, as predictors of flare-ups in CD patients in remission. The presence of these features may reflect ongoing inflammatory activity at a microscopic level, predisposing patients to recurrence. Given this, the weekly multidisciplinary council recommended early medical therapy and intensified endoscopic monitoring for patients with these histological findings to prevent recurrence. Other microscopic findings, such as granulomas and ganglionitis, showed no significant association with endoscopic recurrence in our study, despite their previously reported prognostic relevance[3]. This discrepancy may be attributed to the small sample size or the impact of preoperative anti-tumor necrosis factor therapies, which have been shown to reduce histological inflammation and granuloma formation[5]. The predominance of male patients (67.9%) in our cohort contrasts with the traditionally higher prevalence of CD in females but aligns with recent studies in Western populations and Türkiye, where male-to-female ratios have become more balanced[6]. The high proportion of active smokers (54.5%) in our study is notable, as smoking is a well-established risk factor for postoperative recurrence in CD[7].

Our findings suggest that histological evaluation of resection specimens could guide postoperative management. Patients with neutrophilic cryptitis and crypt abscesses were identified by the weekly multidisciplinary council as candidates for tailored postoperative strategies, including early medical therapy and more frequent endoscopic monitoring. However, the retrospective design and relatively small sample size limit the generalizability of our results. Future prospective studies with larger cohorts are needed to validate these findings and establish standardized histological criteria for predicting recurrence in CD.

CONCLUSION

The presence of neutrophilic cryptitis and crypt abscesses in resected intestinal specimens is significantly associated with an increased likelihood of postoperative endoscopic recurrence in CD patients. These histological findings can serve as early predictors of recurrence, enabling tailored postoperative management strategies, such as early medical therapy and close endoscopic follow-up, as determined by the weekly multidisciplinary council involving General Surgery, Gastroenterology, and Radiology, to improve outcomes in high-risk patients. Further research is warranted to refine the role of histopathology in the management of CD.