Can Biologics Repair Perforated Ileum
- Research article
- Open Access
- Published:
The clinical characteristics of patients with free perforation in Korean Crohn's disease: results from the CONNECT study
BMC Gastroenterology volume 15, Article number:31 (2015) Cite this article
Abstract
Background
Gratuitous perforation is the most severe and debilitating complication associated with Crohn's affliction (CD), and information technology ordinarily requires emergency surgery. The aim of this study was to evaluate the incidence of gratis perforation amongst Korean patients with CD.
Methods
The CrOhn'south illness cliNical NEtwork and CohorT (CONNECT) study was conducted nationwide in Korea, and patients who were diagnosed with CD betwixt 1982 and 2008 were included in this retrospective study. We investigated the incidence of free perforation amid these patients and their clinical characteristics.
Results
A total of 1346 patients were analyzed and 88 patients (six.v%) were identified with complimentary perforation in CD. The mean historic period of the costless perforation group was 31.8 ± thirteen.0 years, which was significantly higher than that of the not-perforated group (27.5 ± 12.1 years) (p = 0.004). Free perforation was the presenting sign of CD in 46 patients (52%). Of the 94 perforations that were present in 88 patients, 81 involved the ileum. Multivariate logistic regression assay determined that complimentary perforation was significantly associated with beingness aged ≥ 30 years at diagnosis (OR 2.082, p = 0.002) and bowel strictures (OR 1.982, p = 0.004). The mortality rate in the free perforation group was significantly college (4.5%) than that in the non-perforated group (0.half dozen%) (p < 0.001).
Conclusion
The incidence of complimentary perforation in Korean patients with CD was 6.five%. Existence aged ≥ 30 years at CD diagnosis and bowel strictures were significant gamble factors associated with complimentary perforation.
Peer Review reports
Background
Crohn's disease (CD) is a chronic and relapsing inflammatory bowel illness (IBD) that can affect the entire gastrointestinal (GI) tract. The early and accurate diagnosis of CD tin can be challenging, especially in patients in whom there is mild clinical activity that mimics symptoms associated with functional GI disorders [one].
Costless perforation is relatively rare among the major complications of CD that include stenoses, fistulae and perforations. Still, free perforation is the almost severe and debilitating complication, and information technology normally requires emergency surgery. While the incidence of CD remains lower than that in western countries, the recent increases in its incidence in Asian countries are remarkable [2,three]. The characteristics of CD have been found to differ between western countries and Asian countries with respect to its prevalence betwixt gender, the locations of the involved segments, and the frequencies of GI complications [two,4-7]. A higher incidence of free perforation has been reported in Japan (6.viii%) [8] compared with western countries (1–iii%) [ix-13]. However, no big-scale studies accept been conducted to investigate gratis perforation in patients with CD in Korea. The aim of this study is to decide the incidence of free perforation, the clinical characteristics of CD patients with costless perforation, and the risk factors associated with free perforation in patients with CD in Korea.
Methods
Report population
A full of 1382 patients who had been diagnosed with CD between July 1982 and December 2008 were included in this retrospective accomplice of the CrOhn's disease cliNical NEtwork and CohorT (CONNECT) written report [14]. Although the CONNECT study could not include all CD patients in Korea, nevertheless, 34 institutes were participated in this nationwide cohort report, therefore, we suggested that the CONNECT report could be representative of the Korean CD population. Nosotros conducted a comparative study between patients with free perforation and those without free perforation. The study was canonical by the Institutional Ethics Review Board of Seoul Paik Hospital.
Illness diagnosis and classifications
CD was diagnosed according to the diagnostic guidelines for CD in Korea [xv]. The diagnoses were systematically re-evaluated before the patients were enrolled in the written report and they were confirmed at the end of the written report. The final diagnoses were documented in accordance with the disease phenotypes within the Montreal classification [16].
Spontaneous free perforation
Free perforation in CD was divers as a spontaneous perforation of the modest or large bowel accompanied by the catamenia of the abdominal contents into the peritoneal cavity. We excluded abscess ruptures and secondary perforations that were attributable to other primary lesions and were identified from the patients' surgical and medical records.
Clinical characteristics of the patients with costless perforation and its incidence
We examined the clinical characteristics of the patients with complimentary perforation in CD, including the fourth dimension of symptom onset, the year of diagnosis, the therapeutic drug history, and the Montreal classification. We as well investigated the anatomical areas in which gratis perforation occurred and the risk factors associated with gratis perforation in patients with CD. To evaluate the clinical result, nosotros compared the groups in relation to GI complications that often require surgery, hospitalizations, and result in mortality.
Statistical analysis
The continuous variables are described as the medians and the standard deviations (SD), and the chiselled variables are presented as proportions and percentages. The differences between the groups were assessed using the χtwo examination for categorical variables and independent t-test for continuous variables. Multivariate logistic regression assay was used to examine the associations between the clinical characteristics of the patients and gratis perforation in patients with CD. Relative chance (RR) was used to evaluate the mortality rate of patients with free perforation. The data were analyzed using PASW Statistics for Windows, Version 18.0 (IBM Corporation, Armonk, NY, U.s.).
Results
Incidence of free perforation
A full of 124 patients were recorded as having whatever blazon of perforation associated with CD. Of these, 14 patients were excluded from the study, because thorough evaluations of their clinical and surgical findings adamant that their perforations did non satisfy the definition of spontaneous free perforation (viii patients had abscess ruptures, 2 patients had fistulae that mimicked perforations, two patients had peptic ulcer perforations, 1 patient had a perforation acquired by colonoscopy, and i patient had a perforation that was secondary to a GI malignancy). In add-on, 22 patients who had suspected but non confirmed free perforations, co-ordinate to their surgical records, were excluded from the study. Hence, of 1346 patients, 88 (6.5%) were identified with gratis perforation in CD. Amongst the 88 patients with gratis perforation, it was the presenting sign that was associated with a diagnosis of CD in 46 patients (52%), and free perforation adult after the diagnosis of CD in 42 patients (48%).
Clinical characteristics of CD patients with gratuitous perforation
We divided the patients with CD into the free perforation group (due north = 88) and the not-perforated grouping (northward = 1258). The mean follow-upwards periods were 125.9 ± 64.4 months for the gratuitous perforation group and 103.7 ± 50.ix months for the not-perforated group. The hateful age of the patients in the free perforation group was 31.8 ± thirteen.0 years, and this was significantly college than that in the non-perforated group, which was 27.5 ± 12.one years (p = 0.004).
The median time interval between the showtime symptom and a diagnosis of CD was 5.ane (0–276.6) months in the complimentary perforation grouping and 3.5 (0–412.4) months in non-perforated grouping, a difference that was not significant (p = 0.074).
The location of the disease at diagnosis showed significant differences betwixt the groups, and small bowel involvement was establish more than frequently in the costless perforation grouping (p = 0.032). Of the 94 perforations that were present in 88 patients, 81 (86.2%) involved the ileum, 6 (6.iv%) involved the jejunum, and 7 (seven.9%) involved the colon, and 5 patients had perforations at multiple sites (3 patients had perforations in the colon and ileum, 1 patient had perforations in the jejunum and ileum, and 1 patient had three perforations in the ileum). Surgery was performed on all of the patients, and it comprised i primary repair and 93 segmental resections. Nosotros did not identify any mortality that was attributable to the surgery. Tabular array ane shows the comparison of characteristics betwixt free perforation group and not-perforated group in our CD accomplice.
Risk factors associated with free perforation
Univariate analysis of the factors associated with costless perforation showed that bowel strictures were significantly more than frequent in the free perforation group compared with the non-perforated grouping (forty.9% vs. 25.7%, p = 0.001). Meaning differences were apparent between the free perforation group and the non-perforated group in relation to the frequencies of other fistulae (22.7% vs. fourteen.7%, p = 0.040) and intra-abdominal abscesses (23.ix% vs. 11.8%, p = 0.001), but the frequency of perianal fistulae did not differ betwixt the groups (Table 1).
Multivariate logistic regression assay determined that free perforation was significantly associated with being over 30 years of age when CD was diagnosed (odds ratio [OR] 2.082, 95% confidence interval [CI] 1.311–3.307, p = 0.002) and having bowel strictures (OR 1.982, 95% CI 1.243–3.160, p = 0.004). Nonetheless, the location of the disease in the ileum (p = 0.194), the presence of other fistulae (p = 0.268), and the presence of intra-intestinal abscesses (p = 0.098) were not significantly associated with complimentary perforation (Tabular array 2).
Prognosis of CD patients with free perforation
Twelve patients died during the study, and the mortality of the perforation group (4.6%, 4/88) was significantly college compared with that of the non-perforated group (0.6%, 8/1258) (RR = vii.72, 95% CI two.28–26.15, p = 0.001). 8 deaths were attributed to CD, with 3/88 patients (three.4%) died in the perforation group and five/1258 patients (0.39%) died in the non-perforated group.
Discussion
It is difficult to accurately determine the incidence of free perforation considering of its rarity. The CONNECT retrospective cohort study has enabled us to report that the incidence of free perforation amidst Korean patients who were diagnosed with CD between 1982 and 2008 is relatively high at half dozen.5% compared with the incidence of 1–3% in western countries [9-xiii]. However, our result is similar to the incidence of free perforation in Japanese patients with CD that was reported from a Japanese meta-analysis (6.eight%) [8]. To the all-time of our knowledge, this is the first report of the incidence of gratuitous perforation in patients with CD using data from a big-scale multicenter accomplice study undertaken in Eastern asia.
It is widely accepted that the IBD phenotypes differ between Asian and Caucasian populations [2,four,5,xiv]. With regard to the location of gratis perforation, Greenstein et al. reported that 50.0% of perforations occur in the ileum and 50.0% of perforations occur in the colon [eleven]. However, in our study we found that ileal perforations had a dramatically higher incidence (86.2%) and that colonic perforations occurred in simply 7.4% of the patients. The Japanese study also reported that 80.0% of perforations occur in the ileum, which is similar to our results [viii]. These findings may reverberate the different characteristics of these patients and the fact that involvement of the small bowel is more frequent in Asia [iv]. Although multivariate logistic regression analysis did not make up one's mind an association betwixt the location of the affliction in the ileum and free perforation, nosotros think that the perforation hazard might exist associated with diagnostic difficulties that relate to the location of the initial lesion.
Multivariate logistic regression analysis adamant that being over xxx years of age when CD was diagnosed was significantly associated with gratis perforation (OR ii.082, p = 0.002). In the current study cohort, the mean age at which CD was diagnosed was 31.viii years in the complimentary perforation group. These results had led the states to consider that the high rate of free perforation in our study might be owing to diagnostic delays and subsequent handling delays, which can lead to poor prognoses [1,17,xviii]. This concept is supported past the finding that the time interval between symptom onset and diagnosis was a piffling longer in the perforation group compared with the not-perforated group, but this difference was non statistically significant (p = 0.074). In add-on, free perforation was the presenting sign that was associated with a diagnosis of CD in 52% of the patients in the perforation grouping, while it has been reported as 23–thirty% in other studies [xi]. Nosotros consider that the high proportion of free perforation as the presenting sign of CD is indicative of failures to reach early diagnoses of CD that resulted in an increase in the perforation rate among patients with CD.
Reports from previous studies accept suggested that steroids increase the take chances of gratuitous perforation by obscuring clinical signs and past preventing the closure of perforations [9-12,19-21]. Some studies have reported that anti-tumor necrosis cistron (TNF) agents are adventure factors for free perforation [22,23]. However, our analysis could not accurately make up one's mind the influence of anti-TNF agents, because many of the patients with complimentary perforation were diagnosed before infliximab had been introduced into clinical practice in Korea. Recently, Korean retrospective study including 721 subjects reported that the cumulative probabilities of operation (P = 0.905) and reoperation (P = 0.418) showed no differences between the ii groups which divided by the introduction of biologic agents (two groups depending on the appointment of CD diagnosis; 1987 to 2005 vs. 2006 to 2022) [24]. The authors of this study suggested that a considerable proportion (36.8%) of the second group may have been given anti-TNF agents simply after developing a pregnant level of bowel harm. Therefore, a farther prospective study with "early use of biologic agents" would be needed to appraise accurately the influence of anti-TNF agents on costless perforation [25].
The verbal mechanism that underlies free perforation in CD is unknown, just 2 hypotheses take been proposed. The first and nearly plausible hypothesis suggests that an increase in the intraluminal pressure proximal to a stenosis causes a bowel distension to perforate the sparse layer overlying a deep ulcer [8-12,21,26]. In this study, nosotros identified that bowel strictures are an independent gamble factor associated with free perforation (OR 1.982, p = 0.004). The 2d hypothesis suggests that in some patients who do not take dilatations and strictures, bowel ischemia may exist attributed to the inflammation of the small vessels [27]. We could not investigate the histopathologic findings in detail nor could nosotros evaluate bowel ischemia in the current retrospective study.
In add-on to bowel strictures, complications such as fistulae and intra-intestinal abscesses, adult frequently and hospitalizations were more frequent in the perforation grouping. The mortality charge per unit was college in the free perforation group (4.v%) compared with the non-perforated group (0.half dozen%) (RR = seven.72, p < 0.001). Given that there were no deaths from surgical complications, nosotros considered that perforation might be indicative of a poor prognosis, considering it is an acute and severe complexity that requires emergency surgery, and it is an integral part of the natural course of the disease. Similis et al. similarly reported a college rate of operative recurrences among patients with CD and perforations compared with those who did non have perforations [28]. Still, with improvement in surgical procedures [29-31] and the availability of newer medication including biologics, this may pb to the successful treatment of patients [32].
This report is limited by its retrospective pattern. First, some of the surgical records did non contain complete descriptions of the patients. Second, we could not accurately evaluate the effects of the medications on the perforations or the complications associated with the perforations, considering the dates on which the medications were initiated and the timings of the onset of complications were non accurately recorded. We propose that future studies should be undertaken that use data from a prospective cohort of the CONNECT study [14].
Decision
The incidence of costless perforation in Korean patients with CD was 6.v%, and this is higher than the incidence in western countries, which reflects the specific phenotype of Asian patients with CD. The diagnosis of CD at an older age (≥ 30 years) and bowel strictures were significant risk factors associated with costless perforation.
Abbreviations
- CD:
-
Crohn'due south disease
- IBD:
-
Inflammatory bowel disease
- GI:
-
Gastrointestinal
- CONNECT report:
-
The CrOhn's illness cliNical NEtwork and Cohort report
- SD:
-
Standard deviations
- TNF:
-
Tumor necrosis factor
References
-
Vavricka SR, Spigaglia SM, Rogler M, Pittet V, Michetti P, Felley C, et al. Systematic evaluation of take a chance factors for diagnostic delay in inflammatory bowel illness. Inflamm Bowel Dis. 2022;18:496–505.
-
Ng SC, Tang West, Ching JY, Wong M, Chow CM, Hui AJ, et al. Incidence and phenotype of inflammatory bowel affliction based on results from the Asia-pacific Crohn'due south and colitis epidemiology study. Gastroenterology. 2022;145:158–65.
-
Yang SK, Yun S, Kim JH, Park JY, Kim HY, Kim YH, et al. Epidemiology of inflammatory bowel illness in the Songpa-Kangdong commune, Seoul, Korea, 1986–2005: a KASID study. Inflamm Bowel Dis. 2008;14:542–9.
-
Kim ES, Kim WH. Inflammatory bowel disease in Korea: epidemiological, genomic, clinical, and therapeutic characteristics. Gut Liver. 2010;iv:i–14.
-
Cheon JH. Genetics of inflammatory bowel diseases: a comparing between Western and Eastern perspectives. J Gastroenterol Hepatol. 2022;28:220–half dozen.
-
Kim JY, Yang S-K, Byeon J-South, Myung Southward-J, Choe J-W, Jo J-Y, et al. The incidence and natural history of perianal fistulas in Korean patients with Crohn's disease. Intest Res. 2006;4:22–31.
-
Song SM, Kim Y, Oh SH, Kim KM. Nutritional status and growth in Korean children with Crohn'southward disease: a unmarried-center report. Gut Liver. 2022;8:500–7.
-
Ikeuchi H, Yamamura T. Free perforation in Crohn's affliction: review of the Japanese literature. J Gastroenterol. 2002;37:1020–7.
-
Steinberg DM, Cooke WT, Alexander-Williams J. Costless perforation in Crohn's affliction. Gut. 1973;14:187–90.
-
Greenstein AJ, Mann D, Sachar DB, Aufses Jr AH. Complimentary perforation in Crohn'due south disease: I. A survey of 99 cases. Am J Gastroenterol. 1985;lxxx:682–9.
-
Greenstein AJ, Sachar DB, Mann D, Lachman P, Heimann T, Aufses Jr AH. Spontaneous free perforation and perforated abscess in 30 patients with Crohn's disease. Ann Surg. 1987;205:72–half dozen.
-
Katz S, Schulman N, Levin 50. Free perforation in Crohn's disease: a report of 33 cases and review of literature. Am J Gastroenterol. 1986;81:38–43.
-
Freeman HJ. Spontaneous free perforation of the pocket-sized intestine in Crohn's disease. Can J Gastroenterol. 2002;16:23–7.
-
Cheon JH, Kim YS, Ye BD, Lee KM, Kim YH, Kim JS, et al. Crohn'south Disease Clinical Network and Cohort (CONNECT) study: the first pace toward nationwide multicenter inquiry of Crohn'south disease in Korea. Intest Res. 2022;12:173–v.
-
Ye BD, Jang BI, Jeen YT, Lee KM, Kim JS, Yang SK. Diagnostic guideline of Crohn'south disease. Korean J Gastroenterol. 2009;53:161–76.
-
Satsangi J, Silverberg MS, Vermeire S, Colombel JF. The Montreal nomenclature of inflammatory bowel disease: controversies, consensus, and implications. Gut. 2006;55:749–53.
-
Nahon S, Lahmek P, Lesgourgues B, Poupardin C, Chaussade S, Peyrin-Biroulet L, et al. Diagnostic delay in a French cohort of Crohn'due south disease patients. J Crohns Colitis. 2022;8:964–9.
-
Schoepfer AM, Dehlavi MA, Fournier N, Safroneeva Due east, Straumann A, Pittet 5, et al. Diagnostic delay in Crohn's illness is associated with a complicated affliction course and increased operation charge per unit. Am J Gastroenterol. 2022;108:1744–53. quiz 1754.
-
Cooke WT, Fielding JF. Corticosteroid or corticotrophin therapy in Crohn's affliction (regional enteritis). Gut. 1970;11:921–7.
-
Sparberg 1000, Kirsner JB. Long-term corticosteroid therapy for regional enteritis: an assay of 58 courses in 54 patients. Am J Dig Dis. 1966;11:865–80.
-
Abascal J, Diaz-Rojas F, Jorge J, Sanchez-Vegazo I, Escartin P, Abreu L, et al. Costless perforation of the pocket-size bowel in Crohn's disease. Earth J Surg. 1982;6:216–xx.
-
Eshuis EJ, Griffioen GH, Stokkers PC, Ubbink DT, Bemelman WA. Anti tumour necrosis factor every bit risk factor for free perforations in Crohn'south disease? A case–control written report. Colorectal Dis. 2022;xiv:578–84.
-
Lim CS, Moon Westward, Park SJ, Park MI, Kim HH, Kim JB, et al. A rare example of free bowel perforation associated with infliximab treatment for structuring Crohn's disease. Korean J Gastroenterol. 2022;62:169–73.
-
Kim NH, Jung YS, Moon CM, Lee SY, Kim ER, Kim YH, et al. Long-term clinical outcomes of Korean patient with Crohn'due south disease following early on use of infliximab. Intest Res. 2022;12:281–6.
-
Ye BD. Could early anti-tumor necrosis gene therapy change the prognosis of Crohn's illness? Intest Res. 2022;12:263–5.
-
Menguy R. Surgical management of costless perforation of the small intestine complicating regional enteritis. Ann Surg. 1972;175:178–89.
-
Kyle J, Caridis T, Duncan T, Ewen SW. Costless perforation in regional enteritis. Am J Dig Dis. 1968;13:275–83.
-
Simillis C, Yamamoto T, Reese GE, Umegae South, Matsumoto Grand, Darzi AW, et al. A meta-analysis comparing incidence of recurrence and indication for reoperation later on surgery for perforating versus nonperforating Crohn's disease. Am J Gastroenterol. 2008;103:196–205.
-
Alves A, Panis Y, Bouhnik Y, Pocard Grand, Vicaut E, Valleur P. Risk factors for intra-abdominal septic complications after a showtime ileocecal resection for Crohn's disease: a multivariate analysis in 161 sequent patients. Dis Colon Rectum. 2007;50:331–six.
-
Iesalnieks I, Kilger A, Glass H, Muller-Wille R, Klebl F, Ott C, et al. Intraabdominal septic complications following bowel resection for Crohn's disease: detrimental influence on long-term outcome. Int J Colour Dis. 2008;23:1167–74.
-
Goyer P, Alves A, Bretagnol F, Bouhnik Y, Valleur P, Panis Y. Touch on of complex Crohn's disease on the outcome of laparoscopic ileocecal resection: a comparative clinical study in 124 patients. Dis Colon Rectum. 2009;52:205–10.
-
Jeong SY, Moon JS, Park KJ, Kim YS. Successful handling of postoperative fistula with infliximab in a patient with Crohn'due south affliction. Intest Res. 2022;12:74–7.
Acknowledgements
This work was supported by the Inquiry Program funded by the Korea Centers for Illness Control and Prevention. (2013-E63004-01).
Author information
Affiliations
Corresponding author
Additional information
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
YSD performed the statistical analysis and drafted the manuscript. YSK conceived of the study, and participated in its design and coordination and helped to draft the manuscript. JSK conceived of the study and participated in its blueprint and coordination. JPI participated in the design of the written report and interpretation of the data. JHC participated in the design of the study. BDY participated in the pattern of the study and interpretation of the data. SIB performed the statistical analysis and interpreted the data. JWK participated in its blueprint and coordination. YSP participated in its design and coordination and interpretation of the data. JHL participated in its design and coordination and estimation of the data. YHK conceived of the report and participated in its blueprint and coordination. DSH participated in its blueprint and coordination. WHK conceived of the report and participated in its design and coordination. All authors read and approved the final manuscript.
Rights and permissions
Open up Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits apply, sharing, adaptation, distribution and reproduction in any medium or format, equally long as you requite appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and point if changes were made.
The images or other third political party material in this commodity are included in the article'southward Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted utilize, you volition need to obtain permission direct from the copyright holder.
To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.
The Creative Commons Public Domain Dedication waiver (https://creativecommons.org/publicdomain/cipher/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Reprints and Permissions
About this article
Cite this article
Doh, Y.South., Kim, Y.Due south., Bae, S.I. et al. The clinical characteristics of patients with free perforation in Korean Crohn's disease: results from the CONNECT study. BMC Gastroenterol 15, 31 (2015). https://doi.org/10.1186/s12876-015-0262-x
-
Received:
-
Accepted:
-
Published:
-
DOI : https://doi.org/10.1186/s12876-015-0262-10
Keywords
- Crohn's illness
- Intestinal perforation
- Adventure factors
- Delayed diagnosis
- Cohort study
Can Biologics Repair Perforated Ileum,
Source: https://bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-015-0262-x
Posted by: blytheshesed.blogspot.com
0 Response to "Can Biologics Repair Perforated Ileum"
Post a Comment