Crohn's disease (CD) is a chronic, relapsing disease whose symptoms interfere with the daily activities of patients, especially in young patients who have a long life expectancy (1, 2). The incidence of pediatric CD, particularly in children 10–19 years of age, is increasing and the phenotype is often characterized by an aggressive disease course, higher risk of surgery (because of stenosis), and more extensive phenotypes compared with adults (1, 3). Quality of life (QoL) is considered the most important outcome for chronic conditions such as CD. In general, QoL is the feeling of overall life satisfaction, as determined by the mentally alert individual whose life is being evaluated. In health care, health-related QoL (HRQoL) is the assessment of how the individual's well-being may be affected by a disease, disability, or disorder (4, 5). Numerous physical and psychological factors contribute to the poor HRQoL in pediatric patients with CD, such as its relatively young age of onset, associated extraintestinal complications, disability, and debilitating symptoms (diarrhea, abdominal pain, gastrointestinal bleeding) that have the potential to cause significant psychosocial stress (1, 6). Even in the era of routine immunomodulator and biological therapies for moderate to severe CD, modifying the natural history of the disease remains a challenge, and about 20–30% of children require surgery within 10 years of diagnosis (1, 7, 8). Indications for surgery in CD include complications such as stricture, perforation, abscess, fistula, or severe perianal disease (1). Patients being referred for surgery experience a more aggressive disease and a poorer HRQoL (1, 9). Literature data mainly coming from adult studies showed that HRQoL in these patients seems to improve following resectional surgery (6, 10, 11). In pediatric patients with CD, the effects of small bowel resection on HRQoL have not been systematically studied. The aim of the present study was to evaluate the long-term health outcomes of children with CD and undergone ileocolonic resection and to compare preoperative and postoperative HRQoL with a disease-specific questionnaire.

Data were obtained in 10 patients (9 males), who underwent surgery at a median age of 13.5 years (range 13–18). The median amount of time that had elapsed after the operation was 4 years (range 1–9). The majority of patients underwent surgery because of active disease despite optimal medical therapy (4 with anti-TNF alpha). Table 1 presents the background data of the patients.

HRQoL median scores were 43.2 and 34.5, 12 and 6 months before surgery, respectively. There was a significant improvement seen at 12 months postoperatively (median 65.4, p < 0.001). This improvement was observed in all dimensions of HRQoL. About systemic and gastrointestinal symptoms (Table 2), a highly significant reduction (p < 0.001) of stool blood, abdominal pain, and fatigue was reported at 12 months after surgery. A significant improvement (p < 0.001) of appetite and weight was also reported, with less difficulty to perform the general activity of daily living (p < 0.001). Nonetheless, despite a slight reduction, stool frequency improvement was not significant in comparison to baseline.

Nearly all patients reported frequent school absences before surgery, with low scores both at 12 (median score 2.60 ± 1.26) and 6 months (1.60 ± 0.97). The most reported IBD-related problems which had caused an absence from school were abdominal pain, fatigue and diarrhea in 5, 3, and 2 patients both 12 and 6 months before surgery. School absences significantly reduced at 12 months after surgery (4.60 ± 0.84, p < 0.001).

Preoperatively, the scores showed markedly impaired social functioning (Table 3), including the ability to play and/or go out with friends, perform a sport, travel and/or go on holiday, with a significant recovery at 12 months from surgery (p < 0.001, p < 0.008, p < 0.002, respectively).

About the emotional functioning (Table 4), CD patients reported a significant reduction of feelings of anger, injustice and embarrassment due to their disease at 12-month follow-up (p < 0.036 and p < 0.039, respectively). On the contrary, surgery did not affect their concerns for future health problems (p = 0.202). Overall, nearly all patients were completely satisfied (score 5) with the outcome of the surgery at 12-month follow-up, with absolute score values of 75.

There were no operation-related mortality and complications. Two patients were started on biologics (adalimumab) for preventing postoperative recurrence. By the end of the follow-up, all patients were in clinical remission (PCDAI <10), and none of them experienced surgical complications and/or recurrences (Rutgeerts score <i2).

Surgery has a definite role in CD treatment protocols, and seems to positively impact the natural history of the disease (17). Some studies have demonstrated that the early use of biologics do not reduce the risk of surgery in CD (1, 18). Surgery can be a viable option in elective cases of CD, such as stricture or fistula, growth retardation, delayed puberty or a clinical condition unresponsive to medical treatment. It is also to be considered in urgent situations, such as occlusive syndrome, abscess or fistulas unresponsive to conservative treatment, massive hemorrhage or intestinal perforation (17).

In the present retrospective cross-sectional study, the long-term HRQoL and health-outcomes after surgery in pediatric CD median 4 years after bowel resection were studied, and it was showed that children and adolescents with CD have low HRQoL score and that HRQoL significantly improves postoperatively. A very limited number of studies evaluated the HRQoL in pediatric patients before and after surgery for CD (9, 19). In 2013 Piekkala et al. (19) carried out a retrospective study on 36 pediatric CD patients who had undergone intestinal resections during childhood between 1985 and 2008. Moreover, they selected 2 controls (with no IBD) per patient with CD matched for age and sex. All patients and controls answered questionnaires about health outcomes and QoL. Most patients had undergone surgery because of active disease despite optimal medical therapy (3 with infliximab) or steroid dependency (56%), as in the present study. The median follow-up after primary resection was longer than our study, with a median of 10 years (range 2–21). The different dimensions and overall HRQoL scores were similar between the patients and their matched controls. Similarly to our study, 96% were completely or moderately satisfied with the outcomes of the surgery (19). Notably, the overall HRQoL, physical and social functioning at follow-up were significantly lower among patients who had missed school or work because of surgery compared with patients who could normally attend school or work. Two other studies performed in the same center on limited number of patients (5 in each study) reported restricted sport activities in children due to stoma formation (20, 21). Permanent stoma had no impact on HRQoL in children compared to adults with a stoma who scored lower for general health and physical activity compared to controls (19, 22). In this study, no surgical complications were registered during the follow-up period. Data coming from pediatric literature are scarce and suggest that the number of complication in pediatric patients are higher if compared with adult data, but further studies are warranted. In the study by Piekkala et al. (19), nearly all patients had at least 1 surgical complication, mostly represented by strictures in the anastomosis.

About disease reactivation after surgery, literature data consistently report that about 50–60% of pediatric patients had a clinical relapse within 1.8–5 years postoperatively (7, 19, 23–26). On the other hand, the reoperation rates are very variable, ranging from 8–18% at 2 years (7, 27) to 29–50% at 10 years (17, 27). In this study, no disease re-activation after surgery was recorded, probably due to the small number of patients. One patient was started on anti-TNFα therapy soon after the intervention, as recommended in high-risk patients (extensive disease, short disease duration from diagnosis to surgery, recurrent surgery, long resected segment, surgery for fistulizing disease, disease complications, perianal disease, smoking) (1, 28).

Any conclusions drawn from the findings of this research study must be qualified in light of the study's limitations. First, the small number of patients, which precluded reliable statistical analysis (such as the evaluation of possible predictors of HRQoL after surgery); second, the retrospective design, so recruited cases and clinical management are the confounding variables; third, the lack of a control population, in order to compare life situation (and HRQoL) with that of patients with CD. Moreover, data were obtained by phone and not during a face to face consultation. The strength of the present study is being one of the limited number of studies reporting HRQoL outcome before and after surgery for CD in pediatric patients. Collection of HRQoL data provides insight into the impact of treatment on patient health status and well-being, especially in the pediatric group of age.

In conclusion, this study confirms that HRQoL is low in children and adolescents with complicated CD who previously failed medical therapy. Ileocecal resection for CD is safe and associated with significant and sustained improvement of the physical, psychological, and social dimensions of HRQoL in affected children. CD is a model of chronic disease, whose clinical and pharmacological management is crucial to gain an optimal HRQoL. On the other hand, the impact of therapy on HRQoL should be considered an integrative, “positive” step of the management strategy. The clinician should consider these HRQoL-related aspects, in comparison with pharmacological therapies-related concerns, such as the high infection risk carried out by high dose of biological or immunosuppressant drugs. This present study adds a contribution in this area, and confirms that surgery may positively affect HRQoL in pediatric patients with CD.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by Ethics Committee of the University of Messina. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.

All authors have made substantial contributions to the design of the study, acquisition and interpretation of data, drafting the article and revising it critically for important intellectual content, and finally approved the version to be submitted.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.