The effectiveness of two-stage surgical treatment of children with complicated Crohn’s disease

Introduction. Crohn’s disease (CD) is an inflammatory disease of the digestive tract of unknown etiology with segmental transmural inflammation of various parts of the gastrointestinal tract. The annual increase in the number of children with newly diagnosed CD, late diagnosis and untimely surgical treatment is one of the urgent problems due to the lack of a single algorithm of surgical treatment.

The aim: to determine the effectiveness of surgical treatment of CD in children.

Materials and methods. The study included thirty six patients with complicated CD Over the period from 2018 to 2022, a retrospective and prospective analysis of children who received medical care for CD with two-stage surgical treatment (resection of the affected area with enterostomy and subsequent restoration of gastrointestinal continuity) was carried out.

Results. Clinical activity according to Pediatric Crohn’s Disease Activity Index (PCDAI) in 23 (63.8%) children before treatment was recorded as high (30.0–75.2 points), in 15 (36.2%) children had average activity (11–29 points). After the staged surgical treatment, there was a change in the indicators — the onset of remission in 2 (5.5%) children and in 34 (94.5%) mild course (p < 0.05). Statistical analysis of anthropometric indicators revealed positive changes (HAZ p < 0.05 and BAZ p < 0.001) with increase in weight and height criteria. Assessment of laboratory dynamics revealed positive changes (p < 0.001) — the absence of anemia, hypoalbuminemia and relief of bacterial inflammation. CD debuted before the age of 10 years in 7 children (19.4%), aged 10 to 16 years — in 29 (80.5%). In 24 (66.7%) children, genetic engineering biological therapy (GEBT) at the time of the development of surgical complications was not performed, from them 15 (62.5%) received hormonal and immunomodulatory therapy while it was not effective, while for 9 (37.5%) patients the timely verification was diagnosed at the stage of development of CD complications. However, the development of surgical complications was noted in 12 (33.3%) children, despite the timely verification and appointment of treatment for genetic engineering biologic therapy (GEBT). Biological therapy was continued for 7 (58.3%) children who received GEBT before surgery, and in 5 (41.7%) patients, treatment was continued with a change of GEBT. The period of stay with a stoma was found to be  from 7 to 31 months (Me = 8).

Conclusions. In complicated forms of CD in children, despite drug therapy, including GEBT, the development of complications requiring surgical treatment was noted, which indicates an aggressive and progressive course of CD. However, the use of stage-by-stage surgical treatment showed efficiency due to the positive dynamics of anthropometric indicators, laboratory markers, the potency of surgical treatment, and made it possible to achieve stable remission against the background of specific therapy and improve the quality of life in CD children.

Contribution:
Dyakonova E.Yu., Gusev A.A. — concept and design of the study;
Bekin A.S., Potapov A.S., Lokhmatov M.M., Zvonareva A.V., Golberg M.A. — collection and processing of medical data;
Dyakonova E.Yu., Golberg M.A. — writing the text;
Yatsyk S.P. — editing the text.
All co-authors — approval of the final version of the article, responsibility for the integrity of all parts of the article.

Acknowledgment. The study had no sponsorship.

Conflict of interest. The authors declare no conflict of interest.

Received: February 16, 2023
Accepted: March 21, 2023
Published: April 28, 2023

1. Van Rheenen P.F., Aloi M., Assa A., Bronsky J., Escher J.C., Fagerberg U.L., et al. The medical management of pediatric Crohn’s disease: an ECCO-ESPGHAN guideline update. J. Crohns. Colitis. 2021; 15(2): 171–94. https://doi.org/10.1093/ecco-jcc/jjaa161

2. Snyder E.F., Davis S., Aldrich K., Veerabagu M., Larussa T., Abenavoli L., et al. Crohn disease: Identification, diagnosis, and clinical management. Nurse. Pract. 2021; 46(12): 22–30. https://doi.org/10.1097/01.npr.0000798212.61425.4f

3. Däbritz J., Gerner P., Enninger A., Claßen M., Radke M. Inflammatory bowel disease in childhood and adolescence: diagnosis and treatment. Dtsch. Arztebl. Int. 2017; 114(19): 331–8. https://doi.org/10.3238/arztebl.2017.0331

4. Roda G., Chien Ng.S., Kotze P.G., Argollo M., Panaccione R., Spinelli A., et al. Crohn’s disease. Nat. Rev. Dis. Primers. 2020; 6(1): 22. https://doi.org/10.1038/s41572-020-0156-2

5. Kornienko E.A., Khavkin A.I., Fedulova E.N., Volynets G.V., Gabruskaya T.V., Skvortsova T.A., et al. Draft recommendations of the Russian society of pediatric gastroenterology, hepatology and nutrition on diagnosis and treatment of Crohn’s disease in children. Eksperimental’naya i klinicheskaya gastroenterologiya. 2019; (11): 100–34. https://doi.org/10.31146/1682-8658-ecg-171-11-100-134 https://elibrary.ru/cftald (in Russian)

6. Eszter Müller K., Laszlo Lakatos P., Papp M., Veres G. Incidence and Paris classification of pediatric inflammatory bowel disease. Gastroenterol. Res. Pract. 2014; 2014: 904307. https://doi.org/10.1155/2014/904307

7. Assa A., Rinawi F., Shamir R. The long-term predictive properties of the Paris classification in paediatric inflammatory bowel disease patients. J. Crohns. Colitis. 2018; 12(1): 39–47. https://doi.org/10.1093/ecco-jcc/jjx125

8. Fernandes M.A., Verstraete S.G., Phan T.G., Deng X., Stekol E., LaMere B., et al. Enteric virome and bacterial microbiota in children with ulcerative colitis and Crohn disease. J. Pediatr. Gastroenterol. Nutr. 2019; 68(1): 30–6. https://doi.org/10.1097/mpg.0000000000002140

9. Jin W., Yang D.H., Tchah H., Kwon K.A., Kim J.H., Jeong S.J., et al. Wasting condition as a marker for severe disease in pediatric Crohn’s disease. Medicine (Baltimore). 2022; 101(20): e29296. https://doi.org/10.1097/md.0000000000029296

10. Li N., Shi R.H. Updated review on immune factors in pathogenesis of Crohn’s disease. World J. Gastroenterol. 2018; 24(1): 15–22. https://doi.org/10.3748/wjg.v24.i1.15

11. Gu P., Kapur A., Li D., Haritunians T., Vasiliauskas E., Shih D.Q., et al. Serological, genetic and clinical associations with increased health-care resource utilization in inflammatory bowel disease. J. Dig. Dis. 2018; 19(1): 15–23. https://doi.org/10.1111/1751-2980.12566

12. Eder P., Adler M., Dobrowolska A., Kamhieh-Milz J., Witowski J. The role of adipose tissue in the pathogenesis and therapeutic outcomes of inflammatory bowel disease. Cells. 2019; 8(6): 628. https://doi.org/10.3390/cells8060628

13. Li X.H., Feng S.T., Cao Q.H., Coffey J.C., Baker M.E., Huang L., et al. Degree of creeping fat assessed by computed tomography enterography is associated with intestinal fibrotic stricture in patients with Crohn’s disease: A Potentially novel mesenteric creeping fat index. J. Crohns. Colitis. 2021; 15(7): 1161–73. https://doi.org/10.1093/ecco-jcc/jjab005

14. Mao R., Kurada S., Gordon I.O., Baker M.E., Gandhi N., McDonald C., et al. The mesenteric fat and intestinal muscle interface: creeping fat influencing stricture formation in Crohn’s disease. Inflamm. Bowel. Dis. 2019; 25(3): 421–6. https://doi.org/10.1093/ibd/izy331

15. Travis S.P., Stange E.F., Lémann M., Oresland T., Chowers Y., Forbes A., et al. European evidence based consensus on the diagnosis and management of Crohn’s disease: current management. Gut. 2006; 55(Suppl. 1): i16–35. https://doi.org/10.1136/gut.2005.081950b

16. Rusova T.V., Ratmanova G.A. Regular medical examination of children with ulcerative colitis and Crohn’s disease. Eksperimental’naya i klinicheskaya gastroenterologiya. 2019; (11): 51–8. https://doi.org/10.31146/1682-8658-ecg-171-11-51-58 https://elibrary.ru/zzrbdw (in Russian)

17. Foster A.J., Smyth M., Lakhani A., Jung B., Brant R.F., Jacobson K. Consecutive fecal calprotectin measurements for predicting relapse in pediatric Crohn’s disease patients. World J. Gastroenterol. 2019; 25(10): 1266–77. https://doi.org/10.3748/wjg.v25.i10.1266

18. Pykov M.I., Vrublevskaya A.M. Echography in the diagnostics of inflammatory bowel diseases in children. Detskaya khirurgiya. 2020; 24(2): 101–7. https://doi.org/10.18821/1560-9510-2020-24-2-101-107 https://elibrary.ru/fobdkg (in Russian)

19. Habernig S., Malle P., Hausegger K.A. Inflammatory gastrointestinal diseases in children: Radiological diagnosis. Radiologe. 2018; 58(4): 326–33. https://doi.org/10.1007/s00117-018-0370-z

20. Neville J.J., Macdonald A., Fell J., Choudhry M., Haddad M. Therapeutic strategies for stricturing Crohn’s disease in childhood: a systematic review. Pediatr. Surg. Int. 2021; 37(5): 569–77. https://doi.org/10.1007/s00383-020-04848-0

21. Kerur B., Machan J.T., Shapiro J.M., Cerezo C.S., Markowitz J., Mack D.R., et al. Biologics delay progression of Crohn’s disease, but not early surgery, in children. Clin. Gastroenterol. Hepatol. 2018; 16(9): 1467–73. https://doi.org/10.1016/j.cgh.2018.02.027

22. Berger T.D., Lee H.M., Padmanaban L.R., Wine E., Yerushalmy-Feler A., Hojsak I., et al. Clinical features and outcomes of paediatric patients with isolated colonic Crohn disease. J. Pediatr. Gastroenterol. Nutr. 2022; 74(2): 258–66. https://doi.org/10.1097/mpg.0000000000003335

23. Penagini F., Cococcioni L., Pozzi E., Dilillo D., Rendo G., Mantegazza C., et al. Biological therapy in pediatric age. Pharmacol. Res. 2020; 161: 105120. https://doi.org/10.1016/j.phrs.2020.105120

24. Zimmerman L., Bousvaros A. The pharmacotherapeutic management of pediatric Crohn’s disease. Expert. Opin. Pharmacother. 2019; 20(17): 2161–8. https://doi.org/10.1080/14656566.2019.1659778

25. Kang B., Choe Y.H. Early biologic treatment in pediatric Crohn’s disease: Catching the therapeutic window of opportunity in early disease by treat-to-target. Pediatr. Gastroenterol. Hepatol. Nutr. 2018; 21(1): 1–11. https://doi.org/10.5223/pghn.2018.21.1.1

26. Burgess C.J., Gillett P., Mitchell D., Hammond P., Henderson P., Wilson D.C. Incidence of paediatric stricturing duodenal Crohn disease: a 19-year population-based cohort study. J. Pediatr. Gastroenterol. Nutr. 2019; 69(5): 539–43. https://doi.org/10.1097/mpg.0000000000002444

27. Gupta N., Cohen S.A., Bostrom A.G., Kirschner B.S., Baldassano R.N., Winter H.S., et al. Risk factors for initial surgery in pediatric patients with Crohn’s disease. Gastroenterology. 2006; 130(4): 1069–77. https://doi.org/10.1053/j.gastro.2006.02.003

28. Ponorac S., Dahmane Gošnak R., Urlep D., Ključevšek D. Diagnostic value of quantitative contrast-enhanced ultrasound in comparison to endoscopy in children with Crohn’s disease. J. Ultrasound. Med. 2023; 42(1): 193–200. https://doi.org/10.1002/jum.1604