Surgical resection for CD patients is correlated to high ePOC risks. And some serious postoperative complications such as intra-abdominal septic complications occur more frequently in CD than other diseases 16, necessitating evaluation of the frequency and risk factors of ePOCs for CD.
In this retrospective study, 34.0% patients experienced at least one ePOC, wound infection being the most frequent complication. This incidence is comparable with the current literature, ranging from 21–37%7–13. The mortality rate was 1.0% and IASCs were recorded in 11.3% cases, in line with previous studies8–12. Numerous studies examined the incidence of ePOCs. A retrospective multi-center study(n=231) of an adult cohort in three countries (Japan, Brazil and Italy) reported an overall ePOCs of 24%. Among 55 reported complications, 12% were intra-abdominal septic complications including anastomotic leakage (8%) and intra-abdominal abscesses (4%). Blood transfusion and perforating disease were independent significant risk factors for overall complications and IASCs, respectively8. Another more recent retrospective study in Europe evaluated the risk of postoperative complications in 199 CD patients. 62 (31%) patients experienced at least some kind of ePOCs and IASCs occurred in 34 patients (17%). One patient (0.5%) died from septic shock following proctocolectomy. A bivariate analysis revealed that surgical anastomosis and preoperative hemoglobin level of < 10 g/dl were associated with an increased postoperative IASC rate11.
Due to high rates of ePOCs for CD surgeries, preoperative risk evaluation of complications seems pivotal to patient optimization for surgery 17. In our study, A diagnosis-surgery duration>6 months(odds-ratio [OR]=4.07; confidence interval [CI] 95%[1.10-15.09], P=0.036), serum platelet count <300*1000/mm3(odds-ratio [OR]=6.74; confidence interval [CI] 95%[1.58-28.71], P=0.01), serum GGT level >10U/L(odds-ratio [OR]=9.22; confidence interval [CI] 95%[1.23-68.99], P=0.031) were significantly associated with a higher risk for ePOCs in a binary regression.
As a progressive disease, CD results in cumulative bowel damage over time, leading to irreversible complications18. In a population-based study on the CD progression, about 19% of patients had already experienced penetrating or stricturing complications within the first 3 months of diagnosis, but complications occurred in 50% of patients within 20 years after diagnosis19, indicating longer disease duration is associated with increasing disease severity. Therefore, rapid and early intervention including medications and surgery may effectively prevent CD progression so as to reduce the risk of adverse complications and healthcare burden20. Shorter disease duration is related to a higher response rate to biologic agents in CD patients21. Issues regarding on the safety of early surgical intervention for CD patients, however, are still a subject to debate without a clear consensus. Recently published data from a retrospective study with 153 CD patients undergoing elective ileocolic resection in a Greek tertiary center revealed that disease duration was not an independent predictor for POCs: complication rates in those who went on surgery <5 years, in 5-10 years and >10 years after diagnosis were 16.1%, 13.9% and 36.4%, respectively, with no intergroup differences in the incidence of POCs12. Our series, however, reported a significant correlation between diagnosis-surgery duration >6 months and ePOCs, in accordance with some previous large studies. For example, a retrospective study in France, concerning 592 consecutive patients who underwent surgery for CD, reported that CD duration >2 years is significantly associated with ePOCs(P=0.01) in univariate analysis10. We believe that our findings augment the evidence for the negative effect of long diagnosis-surgery duration on the postoperative course of CD patients. Therefore, we recommend early surgery for eligible patients in order to avoid postoperative complications. Elżbieta et al. examined the relationship between CD duration and CARD15 expression, one of the susceptibility genes in CD, and found a significantly higher peripheral mRNA level of the CARD15 in patients with disease duration between 12 and 60 months, compared to patients whose disease duration was <12 months 22. We speculated that higher CARD15 expression over longer disease duration modified the disease behavior23, making it more complicated, thus leading to a higher rate of ePOCs. And further studies are needed to precisely explore the safety of early surgical intervention and its ability to prevent disease progression in CD.
It is important to understand how modifiable factors, especially pre-operative lab parameters, affect outcomes after surgical interventions, so that we can identify high-risk CD population for preoperative optimization. Current data concerning these aspects are, however, relatively scarce, focusing mainly on hemoglobin, CRP and albumin level9,10,12. Therefore, one of the unique aspects of our study is the evaluation of numerous possible preoperative lab data. In multivariate analysis, serum platelet count <300*1000/mm3 and serum GGT level >10U/L were found to be independent risk factors of ePOCs. Low platelet counts can serve as an indicator for active CD24, which also helps to explain the correlation between low serum platelet count and a higher risk of ePOCs. On the other hand, Jessika et al.25 determined that the presence of liver test abnormalities, including gamma-glutamyl transpeptidase, was identified as an indicator for complicated CD(HR 2.6, p < 0.0001). And elevated gamma-glutamyl transpeptidase itself suggests abnormal liver function, which might account for a higher risk of ePOCs. Therefore, according to our study, CD patients who are going to be operated but with serum platelet count <300*1000/mm3 or gamma-glutamyl transpeptidase level >10U/L can be better prepared. Abnormal lab values need to be corrected in these patients to improve postoperative safety.
Anti-TNF-alpha agents have been used in the treatment of CD, and their efficacy on CD progression has been well demonstrated3–5. Early initiation of infliximab within the first 2 years of diagnosis reduces the rate of surgery26. However, given its potential impact on wound healing and immunosuppressive properties, a crucial concern is whether patients undergoing major abdominal surgery after anti-TNF drug exposure are at increased risk of early postoperative complications27. In our series, previous exposure to anti-TNF agents in CD patients was not a risk factor for ePOCs, in line with most studies. A Mayo Clinic study28 supported this idea by illustrating no association between infliximab use and early complications after abdominal surgery for CD. A Los Angeles study27 revealed a higher but statistically insignificant rate of adverse outcomes in anti-TNF detectable versus undetectable group. Another Canadian retrospective case-control study 29 compared postoperative outcomes of CD patients with or without exposure to anti-TNF agents within 180 days of abdominal surgery, but no intergroup difference was found. The most recent, prospective multicentric literature that included serum drug level measures at time of surgery found no association between preoperative exposure to anti-TNF and postoperative complications30. Some studies, however, reached contrary conclusions. Antoine et al. 10 in 2018 found that preoperative anti-TNF therapy was a predictor of morbidity after surgery for ileocolonic CD. Some meta-analyses indicated that preoperative anti-TNF exposure was a risk factor of POCs in CD patients31–34. Most of the studies have been criticized for not being able to control crucial confounding factors, such as disease severity, nutritional status as well as preoperative corticosteroid use, which make conclusions less convincing: elevated postoperative complication rates may just be a reflection of disease severity and a higher likelihood of poor nutritional status, but not a direct effect of preoperative anti-TNF exposure. More valid data are needed to confirm our results.
Our study presents certain limitations. First, the retrospective design indicates that data can only be passively retrieved from patients’ medical records. Therefore, some data are incomplete or even not collected at all, including procalcitonin levels, configuration of anastomosis (end-to-end vs. side- to-side), patients’ smoking status, BMI values, which are presumable risk factors for ePOCs. Secondly, the sample size(n=97) is not big enough due to the single-center design, which may lead to insufficient size of some subgroups (such as patients with anti-TNF preoperative exposure). Thus, detection of differences may be more difficult and some risk factors for ePOCs might be precluded. Finally, we choose patients from a high-level center that managed CD patients with complicated and severe conditions, suggesting poorer prognosis than other patients despite well-trained and experienced surgeons and multidisciplinary teams. However, we believe that our study adds more new and convincing evidence of risk factors of ePOCs in CD patients.
In conclusion, the incidence of ePOCs was 34.0% among CD patients undergoing surgical resection. Diagnosis-surgery duration exceeding 6 months, serum platelet count <300*1000/mm3 and serum GGT level >10U/L were identified as independent risk factors for the ePOCs. And preoperative anti-TNF exposure was not associated with an elevated ePOC rate.