SciELO - Scientific Electronic Library Online

vol.109 número12Can we rely on inflammatory biomarkers for the diagnosis and monitoring Crohn's disease activity?Hepatopulmonary syndrome: which blood gas analysis criteria and position should we use for diagnosis? índice de autoresíndice de materiabúsqueda de artículos
Home Pagelista alfabética de revistas  

Servicios Personalizados




Links relacionados

  • En proceso de indezaciónCitado por Google
  • No hay articulos similaresSimilares en SciELO
  • En proceso de indezaciónSimilares en Google


Revista Española de Enfermedades Digestivas

versión impresa ISSN 1130-0108

Rev. esp. enferm. dig. vol.109 no.12 Madrid dic. 2017 



Enteral nutrition is associated with a decreased risk of surgical intervention in Crohn's disease patients with spontaneous intra-abdominal abscess



Xiao-Bin Zheng1,2, Xiang Peng3, Xiao-Yu Xie4, Lei Lian1,2, Xian-Rui Wu1,2, Jian-Cong Hu1,2, Xiao-Wen He1,2, Jia Ke1,2, Yu-Feng Chen1,2, Min Zhi3, Xiao-Jian Wu1,2, Xiao-Sheng He1,2 and Ping Lan1,2

1Department of Colorectal Surgery.
2Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases.
3Department of Gastroenterology.
4Department of Medical Oncology. The Sixth Affiliated Hospital of Sun Yat-sen University. Guangzhou, Guangdong. China

Author's contribution: Xiao-bin Zheng and Xiang Peng contributed equally to this study.

This work was supported by the National Key Clinical Discipline, National Natural Science Foundation of China (No. 81400604) and Science and Technology Planning Project of Guangdong Province (No. 2015B020229001).





Background: The impact of enteral nutrition (EN) on surgical risk in Crohn's disease (CD) patients suffering from spontaneous intra-abdominal abscess (IAA) was evaluated.
Methods: CD patients diagnosed with spontaneous IAA from 2008 to 2015 were included in the study. The impact of EN on surgical risk was evaluated using both univariate and multivariate analyses.
Results: A total of 87 patients were enrolled, 66 (75.9%) were male. The mean age at the development of an abscess was 30.2 ± 10.1 years and the median duration of illness from CD diagnosis until the development of an abscess was three (2-6) years. After a median follow-up of 1.9 (1.1-2.9) years, surgical intervention was performed in 42 patients (48.3%). Patients treated with EN were less likely to require surgical intervention (26.1% vs 56.3%, p = 0.01). Multivariate analysis showed that EN was an independent protective factor for the risk of surgery with a hazard ratio of 0.27 (95% confidence interval: 0.11-0.65, p = 0.004) after adjusting for abdominal pain, history of abdominal surgery, concomitant intestinal stenosis and prior use of antibiotics within three months.
Conclusions: Surgical intervention is common for CD patients with IAA. Appropriate application of EN may help obviate the need for surgical treatment.

Key words: Crohn's disease. Intra-abdominal abscess. Enteral nutrition. Surgical intervention.



Crohn's disease (CD) is a chronic disease characterized by inflammation that involves the full thickness of the bowel wall. Consequently, the occurrence of spontaneous intra-abdominal abscess (IAA) is common in CD patients. Approximately 10% to 30% of patients with CD will spontaneously develop IAA during the course of the illness (1,2). Management of CD patients with IAA is challenging and requires the expertise of multiple specialists working together. In a previous study (3), we showed that interventional procedures such as percutaneous drainage might be helpful in the treatment of CD-related IAA. However, surgery is often required due to the failure of non-operative management.

Risk factors and the timing of surgery in CD patients with IAA are controversial. It has been reported that nutritional status may influence the timing of surgical intervention (4). However, the impact of enteral nutrition (EN) on the risk of surgery in CD patients with spontaneous IAA is rarely studied. The current literature suggests that EN therapy is effective in patients with quiescent or severe CD (5-7) and may decrease the rate of intestinal surgery in pediatric CD (8). The aim of this study was to evaluate the influence of EN on surgical risk in CD patients with spontaneous IAA.


Patients and methods


The study was approved by the Institutional Review Board (IRB) of the Sixth Affiliated Hospital of Sun Yat-sen University. A historical cohort of eligible CD patients diagnosed with spontaneous IAA between October 2008 and December 2015 were evaluated. Both paper based and electronic medical records were carefully reviewed when necessary.

Inclusion and exclusion criteria

Patients who met the following inclusion criteria were included in the study: a) CD as an underlying diagnosis; b) regular follow-up at the hospital; and c) IAA identified by ultrasonography, computed tomography (CT) or magnetic resonance imaging (MRI). The study exclusion criteria included: a) perianal abscess without an intra-abdominal or pelvic abscess; b) abscess developed immediately after laparotomy (within three months of surgery) or caused by a silk suture; and c) < 3 months of follow-up after abscess resolution.

Patient groups

Patients were classified into the EN and non-EN group. The therapy option was determined by physicians according to their clinical experience. EN therapy was adopted mainly to improve the nutritional status of CD patients.

Definition of variables

In this study, EN therapy refers specifically to continuous feeding with elemental (Peptisorb Liquid, Nutricia, Wuxi) or polymeric formula (Fresubin, Sino-Swed Pharmaceutical Corp. Ltd, Wuxi) via a naso-intestinal tube (Flocare Bengmark Naso-Intestinal Tubes, Nutricia, Wuxi) for four weeks, during which no oral foods or fluids (except for water and weak tea) were allowed. Patients in the EN group were given a formula with 30 to 40 Kcal/kg body weight and 1.2 to 1.6 g protein/kg body weight. All patients enrolled in the EN group were fed as inpatients. Patients in the non-EN group were fed with an oral diet (liquid diet or semi-liquid diet without oral nutrition supplements) or parenteral nutrition including carbohydrates and electrolytes in order to maintain the water-electrolyte balance. Each patient was followed-up every day and the patient could contact their clinician whenever necessary.

Demographic and clinical variables were defined as follows: general information (sex, age), age at the time of CD diagnosis, age at development of an abscess, duration of CD until the development of an abscess (the time interval from the date of CD diagnosis to the date of IAA formation), Montreal classification L (including L1 [ileal], L2 [colonic], L3 [ileocolonic] and L4 [upper GI tract modifier]), body mass index (BMI) before treatment, fever, abdominal pain, simplified Crohn's disease activity index (simplified CDAI) before treatment, history of abdominal surgery, comorbidities (perianal abscess, intestinal fistula or intestinal stenosis), abscess location (peritoneal cavity, abdominal wall, pelvic cavity or multiple abscesses), maximum abscess diameter. Biologic variables before treatment included albumin (< 35 g/l vs ≥ 35 g/l), low hemoglobin (< 120 g/l for male, < 110 g/l for female), elevated platelet count (> 300*10^9/l), elevated white blood cell count (> 10*10^9/l), elevated erythrocyte sedimentation rate (ESR, > 15 mm/h for male, > 20 mm/h for female) and elevated C-reactive protein (CRP, > 10 mg/l).

Outcome measurement

The primary outcome was the need for surgical intervention to treat CD patients with IAA. Other outcomes including recurrence of an abscess and the time to recurrence were also examined. Patient follow-up started from the date of the first hospitalization due to IAA complicating CD until the date of the most recent contact.

Statistical analysis

Descriptive statistics were computed for all variables. Continuous data are expressed as mean ± standard deviation of the mean (mean ± SD) or medians (interquartile range, IQR) (M [Q25, Q75]), and categorical data are expressed as frequencies. Comparisons of the distribution of clinical characteristics between the EN and non-EN patients were performed using the 2-tail t-test (or Wilcoxon rank sum test as appropriate) for continuous variables and the Chi-squared test (or the Fisher's exact test as appropriate) for categorical variables. The impact of EN on surgical risk was depicted with Kaplan-Meier curves and the log-rank test. The multivariable Cox proportional hazards model using the enter method was used to identify risk factors associated with the requirement for surgery adjusting for confounding factors. A number of different combinations among the examined variables were tested for possible interactions, in particular among the independent factors related to the need for surgical intervention in the final multivariable model. A p value less than 0.05 was considered as statistically significant.



Patient characteristics

A total of 87 eligible patients were identified from our registry, including 66 (75.9%) males and 19 (24.1%) females. The mean age at CD diagnosis and the development of an abscess was 28.3 ± 9.3 years and 30.2 ± 10.1 years, respectively. The median duration of illness from the diagnosis of CD until the development of an abscess was three (2-6) years. Among the 87 eligible patients, comorbidities included perianal abscess (n = 28, 32.2%), intestinal fistula (n = 67, 77.0%) and intestinal stenosis (n = 48, 55.2%). There were 27 patients (31.0%) who had a history of abdominal surgery (Table 1). After a median follow-up of 1.9 (1.1-2.9) years, surgical intervention was required in 42 patients (48.3%). Patients treated with EN were less likely to require surgical intervention (26.1% vs 56.3%, p = 0.01) (Table 1). There was no significant difference with regard to clinical characteristics between EN and non-EN patients such as prior medical therapy within three months, characteristics of IAA and laboratory values before treatment.



EN is associated with a lower risk for surgical intervention

Kaplan-Meier analysis was used to investigate the impact of EN on the risk of surgical intervention and showed that patients treated with EN had a lower surgical risk in comparison to patients without (log-rank test, p = 0.014) (Fig. 1). The univariate Cox proportional hazard regression model also showed that EN was significantly associated with a lower risk for surgical intervention, with a hazard ratio (HR) of 0.36 (95% confidence interval [CI]: 0.15-0.85, p = 0.019) (Table 2).




Other potential risk factors for surgical intervention identified by univariate analysis included history of abdominal surgery (p = 0.002) and concomitant intestinal stenosis (p = 0.025). Abdominal pain (p = 0.021) and prior use of antibiotics within three months (p = 0.043) were both potential protective factors for surgical risk. Other variables such as simplified CDAI before treatment, concomitant perianal abscess or intestinal fistula, percutaneous drainage, characteristics of IAA and laboratory values had no relationship with the risk of requiring surgery (Table 2). A multivariate Cox proportional hazard regression model was constructed to identify the risk factors related to the need for surgical intervention in this patient population. EN was shown to be an independent protective factor for the risk of surgery with a HR of 0.27 (95% CI: 0.11-0.65, p = 0.004) after adjusting for abdominal pain, history of abdominal surgery, concomitant intestinal stenosis and prior use of antibiotics within three months (Table 3).



Assessment of nutritional and inflammatory parameters in EN groups

A rising trend was observed when the BMI values before and after EN treatment of patients in the EN group were compared, although the difference did not reach statistical significance (before EN 17.8 ± 2.7 vs after EN 18.4 ± 2.6, p = 0.17). Other parameters of nutritional status such as albumin (p = 0.016) and hemoglobin (p = 0.002) significantly increased after four weeks of EN treatment (Table 4). Rapid declines were observed in the inflammatory index including ESR (p < 0.001), CRP (p = 0.002) and platelet count (p < 0.001). Simplified CDAI also decreased significantly after EN treatment (before EN 5.5 ± 1.1 vs after EN 2.3 ± 0.9, p < 0.001) (Table 4).



Outcomes after the first hospitalization due to IAA complicating CD

During the overall median follow-up of 1.9 (1.1-2.9) years, surgical intervention was performed in 42 patients (48.3%). The indications for surgery included medicine only failure (n = 1), percutaneous drainage failure (n = 7), intestinal fistula (n = 25) and intestinal obstruction (n = 9). The median surgery interval among these patients was 0.42 (0.27-0.79) months, while the median follow-up of the remaining 45 patients was 1.65 (0.73-2.37) years (Fig. 2). Abscesses recurred in 17.8% of the patients in the conservative group and 28.6% of the surgical group, although this was not statistically significant (p = 0.23). There was a trend towards a longer interval to abscess recurrence in the surgical group than in the conservative group, although this did not reach statistical significance (1.2 [1.0-2.9] vs 0.9 [0.3-1.1] years, p = 0.053) (Fig. 2). No significant differences were observed with regard to nutritional or inflammatory parameters in patients with or without surgical intervention (Table 5).





CD is characterized by intestinal transmural inflammation, which always leads to deep ulceration, and this is sometimes followed by perforation of the bowel wall. As a result, spontaneous IAA is a common complication in CD patients with an incidence of about 10% to 30% (1). Management of these patients is a clinical challenge. Surgical intervention is integrant and frequently required for unresolved cases or those that are not amenable to or that have failed percutaneous drainage. Although surgery may treat the acute septic complication of CD, it is important to realize that surgical treatment usually does not cure CD, as recurrence after bowel resection is the rule rather than the exception. In addition, bowel resection for CD can be complicated by anastomotic septic complications and new fistula formation, which may hinder the recovery process. The advantage of surgical over nonsurgical management in reducing abscess recurrence rates and complications is controversial (9-15). As the concept of "bowel-sparing" is of paramount importance in the management of CD, factors involved in the need for surgery should be further studied. This may help to avoid unnecessary and invasive surgery.

EN serves as an adjunctive therapy and has been widely used in a variety of diseases including abdominal sepsis (16), pancreatitis (17,18) and inflammatory bowel diseases (IBD) (5,19-22). A large body of evidence (5,8,21,23-30) suggests a beneficial role of EN in the management of CD. It is well known that malnutrition is common in CD patients. The Malnutrition Universal Screening Tool was proposed to be combined with body composition to detect more CD patients at risk of malnutrition and sarcopenia in order to start EN therapy immediately (31). EN is now recommended by the pediatric committee of the European Crohn's and Colitis Organization and the European Society for Paediatric Gastroenterology Hepatology and Nutrition as a first-choice agent to induce remission in pediatric CD. The remission rates in pediatric studies are consistently > 75% (32). In addition, EN has also been reported to be effective in reducing postoperative complications (33,34) and recurrence (35) in CD patients, which may be linked with the improvement of nutritional and inflammatory status. However, the impact of EN on surgical risk in CD patients with spontaneous IAA has rarely been studied.

The role of EN in reducing surgical risk in CD patients with spontaneous IAA was investigated in the present study. No difference was observed before treatment between patients in the EN and non-EN groups with regard to patient demography, duration of CD, BMI, history of abdominal surgery, co-morbidities, prior medical therapy within three months, characteristics of IAA and laboratory values. About 48.3% of patients in this study underwent a surgical intervention after a median follow-up of 1.9 (1.1-2.9) years, which was lower than the rate of 80% reported in the study by Yamaguchi (1) in 2004. This might be due to the increasing use of interventional procedures such as percutaneous drainage over the past decade (36). Due to the benefits of EN in the management of CD patients as mentioned above, we expect that EN will serve as a protective factor for the risk of surgery after adjusting for the other factors. The results in this study support our hypothesis that EN exerts beneficial effects with regard to the avoidance of surgical intervention in CD patients with IAA.

The underlying mechanisms that constitute the association between EN and surgical risk in IAA complicating CD are not clear. Defects in intestinal epithelial tight junction barrier function have been shown to lead to increased intestinal permeation to toxic luminal substances (e.g., bacteria, bacterial by-products, antigens and enzymes). Altered permeability has been reported in those suffering from CD (37-38). It has been reported that EN was able to maintain normal transepithelial electrical resistance, short circuit current, paracellular permeability and the morphological distribution of tight junction proteins (39), and therefore maintain a normal permeability and gut barrier function. This restoration of gut barrier morphology and function is closely related with a mechanism involving the inhibition of long myosin light chain kinase (MLCK) (39). Moreover, previous studies (23,25,29,40,41) have indicated that EN modulates the gut microbiota which is linked with CD disease activity and thus exerts a beneficial effect on the recovery of bowel function. Interestingly, it was suggested that ileal enterocytes might experience nutrient stress during EN treatment as the amino acid requirements of enterocytes were primarily provided by first pass catabolism of a lumen-supplied dietary amino acids and enterocytes were limited in their ability to utilize arterial supplied amino acids (42). Amino acid limitation and other nutrient stress might inhibit the serine/threonine protein kinase, which are mammalian targets of rapamycin (mTOR), resulting in the activation of autophagy (43,44). Thus, EN might further support mucosal healing by limiting the growth and functional activity of potentially antagonistic microbes while simultaneously inducing autophagy to repair damaged host cells. In addition, Hu et al. (45) have reported that EN therapy was effective to relieve inflammatory bowel stricture. Interestingly, they also observed a dramatic decrease in the inflammatory index including CRP, ESR and CDAI after EN treatment. This is consistent with the finding of this study. Given that mural inflammation could cause bowel wall edema and thus lead to stricture in CD patients, we assumed that EN might reduce the thickness of the bowel wall and relieve inflammatory bowel stricture by effectively reversing the inflammatory component and alleviating mural inflammation. This could also help to eliminate the need for surgical treatment.

Our study also indicated that a history of abdominal surgery and concomitant intestinal stenosis were both potential risk factors for surgical intervention, which was consistent with previous studies (11,36). Therefore, it is also important that surgical history and concomitant diseases are considered when determining whether surgery is indicated for an IAA case. In line with several previous studies (10-12,15), we found no significant differences in the rate of abscess recurrence between the conservative group and the surgical group. These data suggest that it would be advantageous to use EN therapy in CD patients with IAA in order to avoid invasive operations according to the concept of damage control (46).

The findings of this study have several clinical implications. To the best of our knowledge, our study is the first to show that EN was associated with a decreased risk of surgical intervention in CD patients with spontaneous IAA. This information is valuable to patients as well as clinicians as it may help to evaluate the risk of surgical intervention and determine the individual treatment schedule. Moreover, efforts could be made in the future to decrease the surgery rate by the appropriate use of EN therapy in patients.

There are several limitations in our study, particularly relating to its retrospective design. For example, the heterogeneity with regard to patient characteristics is inevitable. In particular, the clinical decision making with regard to surgery was subjective and dependent on a variety of specific clinical circumstances. Given that this research was conducted in one single center with a relatively small sample size, a careful interpretation of our data and further studies including more examples are definitely required to overcome this limitation.

In conclusion, our findings imply that EN was an independent protective factor for the risk of surgical intervention in CD patients with spontaneous IAA. Appropriate application of EN should be encouraged to help patients recover from the disease and obviate the need for surgical intervention.



Author contributions: XBZ, XP and XSH contributed to the study concept and design, acquisition, analysis and interpretation of data and drafting of the manuscript. XYX, LL, XRW, JCH and XWH contributed the data collection and manuscript review. JK, YFC, MZ and XJW contributed to the study concept and design, analysis and interpretation of data and critical revision of the manuscript for important intellectual content. XSH and PL supervised the study. All authors read and approved the final manuscript.



1. Yamaguchi A, Matsui T, Sakurai T, et al. The clinical characteristics and outcome of intraabdominal abscess in Crohn's disease. J Gastroenterol 2004;39:441-8. DOI: 10.1007/s00535-003-1317-2.         [ Links ]

2. Richards RJ. Management of abdominal and pelvic abscess in Crohn's disease. World J Gastrointest Endosc 2011;3:209-12. DOI: 10.4253/wjge.v3.i11.209.         [ Links ]

3. He X, Lin X, Lian L, et al. Preoperative percutaneous drainage of spontaneous intra-abdominal abscess in patients with Crohn's disease: A meta-Analysis. J Clin Gastroenterol 2015;49:e82-90.         [ Links ]

4. Fleshman JW. Pyogenic complications of Crohn's disease, evaluation, and management. J Gastrointest Surg 2008;12:2160-3. DOI: 10.1007/s11605-008-0673-x.         [ Links ]

5. Nakahigashi M, Yamamoto T, Sacco R, et al. Enteral nutrition for maintaining remission in patients with quiescent Crohn's disease: Current status and future perspectives. Int J Colorectal Dis 2016;31:1-7. DOI: 10.1007/s00384-015-2348-x.         [ Links ]

6. Zhao J, Dong JN, Gong JF, et al. Impact of enteral nutrition on energy metabolism in patients with Crohn's disease. World J Gastroenterol 2015;21:1299-304. DOI: 10.3748/wjg.v21.i4.1299.         [ Links ]

7. Li Y, Zuo L, Zhu W, et al. Role of exclusive enteral nutrition in the preoperative optimization of patients with Crohn's disease following immunosuppressive therapy. Medicine (Baltimore) 2015;94:e478. DOI: 10.1097/MD.0000000000000478.         [ Links ]

8. Konno M, Takahashi M, Toita N, et al. Long-term therapeutic effectiveness of maintenance enteral nutrition for Crohn's disease. Pediatr Int 2015;57:276-80. DOI: 10.1111/ped.12494.         [ Links ]

9. Clancy C, Boland T, Deasy J, et al. A meta-analysis of percutaneous drainage versus surgery as the initial treatment of Crohn's disease-related intra-abdominal abscess. J Crohns Colitis 2016;10:202-8. DOI: 10.1093/ecco-jcc/jjv198.         [ Links ]

10. Liu S, Ren J, Gu G, et al. Comparative outcomes of trocar puncture with sump drain, percutaneous drainage, and surgical drainage in the management of intra-abdominal abscesses in Crohn's disease. Surg Innov 2014;21:580-9. DOI: 10.1177/1553350614526787.         [ Links ]

11. Xie Y, Zhu W, Li N, et al. The outcome of initial percutaneous drainage versus surgical drainage for intra-abdominal abscesses in Crohn's disease. Int J Colorectal Dis 2012;27:199-206. DOI: 10.1007/s00384-011-1338-x.         [ Links ]

12. Nguyen DL, Sandborn WJ, Loftus EV Jr, et al. Similar outcomes of surgical and medical treatment of intra-abdominal abscesses in patients with Crohn's disease. Clin Gastroenterol Hepatol 2012;10:400-4. DOI: 10.1016/j.cgh.2011.11.023.         [ Links ]

13. Lightner AL, Shen B. Perioperative use of immunosuppressive medications in patients with Crohn's disease in the new biological era. Gastroenterol Rep (Oxf) 2017;5:165-77. DOI: 10.1093/gastro/gow046.         [ Links ]

14. Nguyen DL, Nguyen ET, Bechtold ML. Outcomes of initial medical compared with surgical strategies in the management of intra-abdominal abscesses in patients with Crohn's disease: A meta-analysis. Eur J Gastroenterol Hepatol 2015;27:235-41. DOI: 10.1097/MEG.0000000000000273.         [ Links ]

15. Kim DH, Cheon JH, Moon CM, et al. Clinical efficacy of nonsurgical treatment of Crohn's disease-related intraabdominal abscess. Korean J Gastroenterol 2009;53:29-35.         [ Links ]

16. Leppaniemi A, Kimball EJ, De Laet I, et al. Management of abdominal sepsis - A paradigm shift? Anaesthesiol Intensive Ther 2015;47:400-8.         [ Links ]

17. Lodewijkx PJ, Besselink MG, Witteman BJ, et al. Nutrition in acute pancreatitis: A critical review. Expert Rev Gastroenterol Hepatol 2016;10:571-80. DOI: 10.1586/17474124.2016.1141048.         [ Links ]

18. Dupont B, Musikas M, Dao MT, et al. Timing and route of enteral nutrition in severe acute pancreatitis? Pancreas 2016;45:e20. DOI: 10.1097/MPA.0000000000000560.         [ Links ]

19. Triantafillidis JK, Vagianos C, Papalois AE. The role of enteral nutrition in patients with inflammatory bowel disease: Current aspects. Biomed Res Int 2015;2015:197-67. DOI: 10.1155/2015/197167.         [ Links ]

20. Altomare R, Damiano G, Abruzzo A, et al. Enteral nutrition support to treat malnutrition in inflammatory bowel disease. Nutrients 2015;7:2125-33. DOI: 10.3390/nu7042125.         [ Links ]

21. Cuív PO, Begun J, Keely S, et al. Towards an integrated understanding of the therapeutic utility of exclusive enteral nutrition in the treatment of Crohn's disease. Food Funct 2016;7:1741-51. DOI: 10.1039/C5FO01196E.         [ Links ]

22. Nahidi L, Day AS, Lemberg DA, et al. Paediatric inflammatory bowel disease: A mechanistic approach to investigate exclusive enteral nutrition treatment. Scientifica (Cairo) 2014;2014:423817. DOI: 10.1155/2014/423817.         [ Links ]

23. Schwerdt T, Frivolt K, Clavel T, et al. Exclusive enteral nutrition in active pediatric Crohn disease: Effects on intestinal microbiota and immune regulation. J Allergy Clin Immunol 2016;138:592-6. DOI: 10.1016/j.jaci.2015.12.1331.         [ Links ]

24. Kang Y, Kim S, Kim SY, et al. Effect of short-term partial enteral nutrition on the treatment of younger patients with severe Crohn's disease. Gut Liver 2015;9:87-93. DOI: 10.5009/gnl13345.         [ Links ]

25. Kaakoush NO, Day AS, Leach ST, et al. Effect of exclusive enteral nutrition on the microbiota of children with newly diagnosed Crohn's disease. Clin Transl Gastroenterol 2015;6:e71. DOI: 10.1038/ctg.2014.21.         [ Links ]

26. Lomer MC, Gourgey R, Whelan K. Current practice in relation to nutritional assessment and dietary management of enteral nutrition in adults with Crohn's disease. J Hum Nutr Diet 2014;27(Suppl 2):28-35. DOI: 10.1111/jhn.12133.         [ Links ]

27. Soo J, Malik BA, Turner JM, et al. Use of exclusive enteral nutrition is just as effective as corticosteroids in newly diagnosed pediatric Crohn's disease. Dig Dis Sci 2013;58:3584-91. DOI: 10.1007/s10620-013-2855-y.         [ Links ]

28. Levine A, Wine E. Effects of enteral nutrition on Crohn's disease: Clues to the impact of diet on disease pathogenesis. Inflamm Bowel Dis 2013;19:1322-9. DOI: 10.1097/MIB.0b013e3182802acc.         [ Links ]

29. Tjellstrom B, Hogberg L, Stenhammar L, et al. Effect of exclusive enteral nutrition on gut microflora function in children with Crohn's disease. Scand J Gastroenterol 2012;47:1454-9. DOI: 10.3109/00365521.2012.703234.         [ Links ]

30. Yamamoto T, Nakahigashi M, Umegae S, et al. Enteral nutrition for the maintenance of remission in Crohn's disease: A systematic review. Eur J Gastroenterol Hepatol 2010;22:1-8. DOI: 10.1097/MEG.0b013e32832c788c.         [ Links ]

31. Csontos ÁA, Molnár A, Piri Z, et al. Malnutrition risk questionnaire combined with body composition measurement in malnutrition screening in inflammatory bowel disease. Rev Esp Enferm Dig 2017;109(1):26-32.         [ Links ]

32. Van Limbergen J, Haskett J, Griffiths AM, et al. Toward enteral nutrition for the treatment of pediatric Crohn disease in Canada: A workshop to identify barriers and enablers. Can J Gastroenterol Hepatol 2015;29:351-6. DOI: 10.1155/2015/509497.         [ Links ]

33. Wang H, Zuo L, Zhao J, et al. Impact of preoperative exclusive enteral nutrition on postoperative complications and recurrence after bowel resection in patients with active Crohn's disease. World J Surg 2016;40:1993-2000. DOI: 10.1007/s00268-016-3488-z.         [ Links ]

34. Li G, Ren J, Wang G, et al. Preoperative exclusive enteral nutrition reduces the postoperative septic complications of fistulizing Crohn's disease. Eur J Clin Nutr 2014;68:441-6. DOI: 10.1038/ejcn.2014.16.         [ Links ]

35. Yamamoto T, Shiraki M, Nakahigashi M, et al. Enteral nutrition to suppress postoperative Crohn's disease recurrence: A five-year prospective cohort study. Int J Colorectal Dis 2013;28:335-40. DOI: 10.1007/s00384-012-1587-3.         [ Links ]

36. Ananthakrishnan AN, McGinley EL. Treatment of intra-abdominal abscesses in Crohn's disease: A nationwide analysis of patterns and outcomes of care. Dig Dis Sci 2013;58:2013-8. DOI: 10.1007/s10620-013-2579-z.         [ Links ]

37. Edelblum KL, Turner JR. The tight junction in inflammatory disease: Communication breakdown. Curr Opin Pharmacol 2009;9:715-20. DOI: 10.1016/j.coph.2009.06.022.         [ Links ]

38. Laukoetter MG, Nava P, Nusrat A. Role of the intestinal barrier in inflammatory bowel disease. World J Gastroenterol 2008;14:401-7. DOI: 10.3748/wjg.14.401.         [ Links ]

39. Du L, Kim JJ, Shen J, et al. Crosstalk between inflammation and ROCK/MLCK signaling pathways in gastrointestinal disorders with intestinal hyperpermeability. Gastroenterol Res Pract 2016;2016:7374197. DOI: 10.1155/2016/7374197.         [ Links ]

40. Gerasimidis K, Bertz M, Hanske L, et al. Decline in presumptively protective gut bacterial species and metabolites are paradoxically associated with disease improvement in pediatric Crohn's disease during enteral nutrition. Inflamm Bowel Dis 2014;20:861-71. DOI: 10.1097/MIB.0000000000000023.         [ Links ]

41. Shah R, Kellermayer R. Microbiome associations of therapeutic enteral nutrition. Nutrients 2014;6:5298-311. DOI: 10.3390/nu6115298.         [ Links ]

42. Wu G. Dietary requirements of synthesizable amino acids by animals: A paradigm shift in protein nutrition. J Anim Sci Biotechnol 2014;5:34. DOI: 10.1186/2049-1891-5-34.         [ Links ]

43. Marion-Letellier R, Raman M, Savoye G, et al. Nutrient modulation of autophagy: Implications for inflammatory bowel diseases. Inflamm Bowel Dis 2013;19:205-12. DOI: 10.1002/ibd.23001.         [ Links ]

44. Chen R, Zou Y, Mao D, et al. The general amino acid control pathway regulates mTOR and autophagy during serum/glutamine starvation. J Cell Biol 2014;206:173-82. DOI: 10.1083/jcb.201403009.         [ Links ]

45. Hu D, Ren J, Wang G, et al. Exclusive enteral nutritional therapy can relieve inflammatory bowel stricture in Crohn's disease. J Clin Gastroenterol 2014;48:790-5. DOI: 10.1097/MCG.0000000000000041.         [ Links ]

46. Burch JM, Ortiz VB, Richardson RJ, et al. Abbreviated laparotomy and planned reoperation for critically injured patients. Ann Surg 1992;215:476-83. DOI: 10.1097/00000658-199205000-00010.         [ Links ]



Xiao-Sheng He and Ping Lan.
The Sixth Affiliated Hospital.
Sun Yat-sen University.
26 Yuancun Erheng Road.
510655 Guangzhou, Guangdong. China

Received: 16-06-2017
Accepted: 31-07-2017