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Liu WH, Xiong M, Chen GQ, Long Z, Xu C, Zhu L, Wu JS. Laparoscopic intracorporeal anastomosis vs open anastomosis for ileostomy reversal in Crohn's disease: A single center retrospective study. World J Gastrointest Surg 2025; 17:98269. [PMID: 39872758 PMCID: PMC11757179 DOI: 10.4240/wjgs.v17.i1.98269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2024] [Revised: 10/24/2024] [Accepted: 11/12/2024] [Indexed: 12/27/2024] Open
Abstract
BACKGROUND There is an increased maturation of laparoscopic intracorporeal anastomosis techniques. However, research on its application for small bowel stoma reversal in patients with Crohn's disease (CD) is limited. Therefore, in this study, we compared the perioperative outcomes between laparoscopic intracorporeal ileostomy reversal (LIIR) and open ileostomy reversal (OIR). AIM To compare the safety, feasibility, bowel function recovery, and short- and long-term LIIR and OIR outcomes in patients with CD. METHODS This study included patients who underwent ileal reversal for CD between January 2021 and January 2023 at our institution. The baseline data, postoperative recovery, and complication indicators were retrospectively analyzed. Logistic regression analysis was conducted to explore factors that significantly influenced the development of enteral nutrition intolerance-related symptoms. RESULTS Notably, 15 of the 45 patients in this study underwent OIR, and the remaining 30 received LIIR. Notably, no statistically significant differences were found between the two groups regarding clinical baseline characteristics, operation time, intraoperative hemorrhage, anastomotic site, enterolysis range, first postoperative flatus, postoperative complications, reoperation rate, or incidence of postoperative enteral nutrition intolerance. Compared with the OIR group, the LIIR group had a shorter postoperative hospital stay (P = 0.045), lower incidence of enteral nutrition intolerance symptoms (P = 0.019), and earlier postoperative total enteral nutrition initiation (P = 0.033); however, it incurred higher total hospital costs (P = 0.038). Furthermore, multivariate logistic regression analysis revealed that the duration of surgery and anastomotic technique were independent risk factors for postoperative symptoms of enteral nutrition intolerance (P < 0.05). CONCLUSION Laparoscopic intracorporeal anastomosis for ileostomy reversal is safe and feasible. Patients who underwent this technique demonstrated improved tolerance to postoperative enteral nutrition and quicker resumption of total enteral nutrition.
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Affiliation(s)
- Wei-Hang Liu
- Department of General Surgery, Chongqing General Hospital, Chongqing 401120, China
| | - Mao Xiong
- Department of General Surgery, Chongqing General Hospital, Chongqing 401120, China
| | - Guo-Qing Chen
- Department of General Surgery, Chongqing General Hospital, Chongqing 401120, China
| | - Zhui Long
- Department of General Surgery, Chongqing General Hospital, Chongqing 401120, China
| | - Chao Xu
- Department of General Surgery, Chongqing General Hospital, Chongqing 401120, China
| | - Li Zhu
- Department of General Surgery, Chongqing General Hospital, Chongqing 401120, China
| | - Jing-Song Wu
- Department of General Surgery, Chongqing General Hospital, Chongqing 401120, China
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Duan M, Lu M, Diao Y, Cao L, Wu Q, Liu Y, Gong J, Zhu W, Li Y. Azathioprine Plus Exclusive Enteral Nutrition Versus Azathioprine Monotherapy for the Prevention of Postoperative Recurrence in Patients with Crohn's Disease: An Open-Label, Single-Centre, Randomized Controlled Trial. J Crohns Colitis 2024; 18:1113-1121. [PMID: 38253914 DOI: 10.1093/ecco-jcc/jjae015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Revised: 01/07/2024] [Accepted: 01/20/2024] [Indexed: 01/24/2024]
Abstract
BACKGROUND Azathioprine [AZA] effectively prevents postoperative endoscopic recurrence [ER] in Crohn's disease [CD]. However, the efficacy of AZA emerges after 3 months. Exclusive enteral nutrition [EEN] can maintain remission in CD. The present trial investigates whether AZA plus postoperative 3-month EEN is superior to AZA alone in preventing ER of CD. METHODS In total, 84 high-risk CD patients undergoing intestinal resection received AZA alone or AZA plus 3 months of EEN [AZA + EEN] postoperatively. The primary endpoint was the rate of ER at 12 months. Secondary endpoints included the rate of ER at 3 months, clinical recurrence [CR], CD activity index [CDAI] scores, faecal calprotectin [FC], and C-reactive protein [CRP]. Quality of life was assessed using Short Form-36 [SF-36] and the Inflammatory Bowel Disease Questionnaire [IBDQ]. RESULTS Patients in the AZA + EEN group exhibited significantly lower rates of ER compared to the AZA group at both 12 months (33.3% [13/39] vs 63.2% [24/38], P = 0.009) and 3 months (8.6% [3/35] vs 28.1% [9/32], P = 0.037) post-surgery. The rates of CR between the two groups at 3 and 12 months were similar. CDAI scores, FC, albumin level, and CRP were all comparable between the two groups. Quality of life was significantly higher in the AZA group than in the AZA + EEN group at 3 months but became comparable from 5 to 12 months postoperatively. CONCLUSION In high-risk CD patients, combining AZA with postoperative 3-month EEN reduces 1-year ER but may temporarily impact quality of life. Further large-scale, long-term studies are warranted. TRIAL NUMBER NCT05214430.
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Affiliation(s)
- Ming Duan
- Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China
| | - Mengjie Lu
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Yanqing Diao
- Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China
| | - Lei Cao
- Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China
| | - Qiong Wu
- Department of Scientific Research and Training, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing 210002, China
| | - Yuxiu Liu
- Data and Statistics Division, Department of Critical Care Medicine, Jinling Hospital, Nanjing Medical University, Nanjing 210002, China
- Department of Biostatistics, School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515, China
| | - Jianfeng Gong
- Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China
| | - Weiming Zhu
- Department of Colorectal and Proctology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Yi Li
- Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China
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Diao N, Liu X, Lin M, Yang Q, Li B, Tang J, Ding N, Gao X, Chao K. Exclusive Enteral Nutrition Orchestrates Immunological Balances as Early as Week 4 in Adult Patients of Crohn's Disease: A Pilot, Open-Lable Study. Nutrients 2023; 15:5091. [PMID: 38140350 PMCID: PMC10745958 DOI: 10.3390/nu15245091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2023] [Revised: 11/24/2023] [Accepted: 12/02/2023] [Indexed: 12/24/2023] Open
Abstract
BACKGROUND AND AIMS The efficacy and underlying mechanisms of exclusive enteral nutrition (EEN) in adult patients with Crohn's disease (CD) remain controversial. This study aimed to evaluate the role of EEN in adult patients with CD and to explore the mechanisms from the perspective of immunoregulation. METHODS This is a prospective, open-label pilot study. Active patients with CD were enrolled and prescribed an amino-acid-rich elemental diet for 12 weeks. Dynamic changes in immune cells, including neutrophils, monocytes, T cells and B cells, were detected by flow cytometry. Plasma cytokines were evaluated by ELISA. RESULTS Twenty adult patients with CD were enrolled. Among them, 1 discontinued treatment due to poor compliance, and 19 patients were included for final analysis. Clinical remission was achieved in 47.37% (9/19), 63.16% (12/19), and 73.68% (14/19) patients at weeks 4, 8, and 12, respectively. Endoscopic remission and transmural healing were achieved in 52.63% (10/19) and 15.79% (3/19) patients at week 12. Notably, there was no significant difference in clinical remission between week 4 and week 8 (p = 0.33) or week 12 (p = 0.09). Furthermore, we observed a rapid reconstitution of immunologic homeostasis as early as week 4. At week 4, both the frequency and activation of neutrophils and monocytes were decreased after EEN therapy. Significant decreases in Th17 cells and naïve B cells, increases in memory B cells, and regulatory B cells were also detected. These changes remained stable at weeks 8 and 12. CONCLUSIONS EEN with an amino-acid-rich elemental diet orchestrated immunological balances and induces clinical remission in adult CD patients as early as week 4, suggesting a 4-week EEN therapy may be feasible and practicable in clinical practice.
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Affiliation(s)
- Na Diao
- Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China; (N.D.); (X.L.); (M.L.); (Q.Y.); (B.L.); (J.T.); (N.D.)
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China
| | - Xinyu Liu
- Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China; (N.D.); (X.L.); (M.L.); (Q.Y.); (B.L.); (J.T.); (N.D.)
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China
| | - Minzhi Lin
- Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China; (N.D.); (X.L.); (M.L.); (Q.Y.); (B.L.); (J.T.); (N.D.)
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China
| | - Qingfan Yang
- Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China; (N.D.); (X.L.); (M.L.); (Q.Y.); (B.L.); (J.T.); (N.D.)
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China
| | - Bingyang Li
- Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China; (N.D.); (X.L.); (M.L.); (Q.Y.); (B.L.); (J.T.); (N.D.)
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China
| | - Jian Tang
- Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China; (N.D.); (X.L.); (M.L.); (Q.Y.); (B.L.); (J.T.); (N.D.)
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China
| | - Ni Ding
- Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China; (N.D.); (X.L.); (M.L.); (Q.Y.); (B.L.); (J.T.); (N.D.)
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China
| | - Xiang Gao
- Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China; (N.D.); (X.L.); (M.L.); (Q.Y.); (B.L.); (J.T.); (N.D.)
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China
| | - Kang Chao
- Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China; (N.D.); (X.L.); (M.L.); (Q.Y.); (B.L.); (J.T.); (N.D.)
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China
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Ferrante M, Pouillon L, Mañosa M, Savarino E, Allez M, Kapizioni C, Arebi N, Carvello M, Myrelid P, De Vries AC, Rivière P, Panis Y, Domènech E. Results of the Eighth Scientific Workshop of ECCO: Prevention and Treatment of Postoperative Recurrence in Patients With Crohn's Disease Undergoing an Ileocolonic Resection With Ileocolonic Anastomosis. J Crohns Colitis 2023; 17:1707-1722. [PMID: 37070324 DOI: 10.1093/ecco-jcc/jjad053] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Indexed: 04/19/2023]
Abstract
Despite the introduction of biological therapies, an ileocolonic resection is often required in patients with Crohn's disease [CD]. Unfortunately, surgery is not curative, as many patients will develop postoperative recurrence [POR], eventually leading to further bowel damage and a decreased quality of life. The 8th Scientific Workshop of ECCO reviewed the available scientific data on both prevention and treatment of POR in patients with CD undergoing an ileocolonic resection, dealing with conventional and biological therapies, as well as non-medical interventions, including endoscopic and surgical approaches in case of POR. Based on the available data, an algorithm for the postoperative management in daily clinical practice was developed.
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Affiliation(s)
- Marc Ferrante
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
- Translational Research in Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
| | - Lieven Pouillon
- Imelda GI Clinical Research Center, Imelda General Hospital, Bonheiden, Belgium
| | - Míriam Mañosa
- Department of Gastroenterology and Hepatology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Edoardo Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
- Gastroenterology Unit, Azienda Ospedale Università di Padova, Padua, Italy
| | - Matthieu Allez
- Gastroenterology Department, Hôpital Saint-Louis - APHP, Université Paris Cité, INSERM U1160, Paris, France
| | - Christina Kapizioni
- Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Naila Arebi
- Department of Inflammatory Bowel Disease, St Mark's Hospital, Harrow, London, UK
| | - Michele Carvello
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Pär Myrelid
- Department of Surgery, Linköping University Hospital and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Annemarie C De Vries
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, the Netherlands
| | - Pauline Rivière
- Department of Gastroenterology and Hepatology, Centre Médico-chirurgical Magellan, Hôpital Haut-Lévêque, CHU de Bordeaux, Université de Bordeaux, INSERM CIC 1401, Bordeaux, France
| | - Yves Panis
- Paris IBD Center, Groupe Hospitalier Privé Ambroise-Paré Hartmann, Neuily/Seine, France
| | - Eugeni Domènech
- Department of Gastroenterology and Hepatology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
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Limketkai BN, Godoy-Brewer G, Parian AM, Noorian S, Krishna M, Shah ND, White J, Mullin GE. Dietary Interventions for the Treatment of Inflammatory Bowel Diseases: An Updated Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2023; 21:2508-2525.e10. [PMID: 36470529 DOI: 10.1016/j.cgh.2022.11.026] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 11/17/2022] [Accepted: 11/20/2022] [Indexed: 12/29/2022]
Abstract
BACKGROUND & AIMS This study aimed (1) to systematically review controlled trials of solid food diets for the treatment of inflammatory bowel disease (IBD); and (2) to grade the overall quality of evidence. METHODS Systematic review of prospective controlled trials of solid food diets for the induction or maintenance of remission in IBD. Two authors independently performed study selection, data extraction, and assessment of certainty of evidence. Meta-analyses were performed on studies with quantitative data on response, remission, and relapse. RESULTS There were 27 studies for meta-analysis. For induction of remission in Crohn's disease (CD), low refined carbohydrate diet and symptoms-guided diet outperformed controls, but studies had serious imprecision and very low certainty of evidence. The Mediterranean diet was similar to the Specific Carbohydrate Diet (low certainty of evidence), and partial enteral nutrition (PEN) was similar to exclusive enteral nutrition (very low certainty of evidence). PEN reduced risk of relapse (very low certainty of evidence), whereas reduction of red meat or refined carbohydrates did not (low certainty of evidence). For ulcerative colitis, diets were similar to controls (very low and low certainty of evidence). CONCLUSIONS Among the most robust dietary trials in IBD currently available, certainty of evidence remains very low or low. Nonetheless, emerging data suggest potential benefit with PEN for induction and maintenance of remission in CD. Reduction of red meat and refined carbohydrates might not reduce risk of CD relapse. As more dietary studies become available, the certainty of evidence could improve, thus allowing for more meaningful recommendations for patients.
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Affiliation(s)
- Berkeley N Limketkai
- Center for Inflammatory Bowel Diseases, Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA School of Medicine, Los Angeles, California; Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
| | | | - Alyssa M Parian
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Shaya Noorian
- Center for Human Nutrition, Division of Clinical Nutrition, UCLA School of Medicine, Los Angeles, California
| | - Mahesh Krishna
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Neha D Shah
- Colitis and Crohn's Disease Center, Division of Gastroenterology, UCSF School of Medicine, San Francisco, California
| | - Jacob White
- Welch Library, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Gerard E Mullin
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
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Wu EH, Guo Z, Zhu WM. Postoperative diarrhea in Crohn’s disease: Pathogenesis, diagnosis, and therapy. World J Clin Cases 2023; 11:7-16. [PMID: 36687182 PMCID: PMC9846968 DOI: 10.12998/wjcc.v11.i1.7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2022] [Revised: 12/08/2022] [Accepted: 12/23/2022] [Indexed: 01/04/2023] Open
Abstract
Diarrhea is a frequent symptom in postoperative patients with Crohn’s diseases (CD), and several different mechanisms likely account for postoperative diarrhea in CD. A targeted strategy based on a comprehensive understanding of postoperative diarrhea is helpful for better postoperative recovery.
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Affiliation(s)
- En-Hao Wu
- Department of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, Jiangsu Province, China
| | - Zhen Guo
- Department of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, Jiangsu Province, China
| | - Wei-Ming Zhu
- Department of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, Jiangsu Province, China
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Otley A, Day AS, Zachos M. Nutritional Management of Inflammatory Bowel Disease. PEDIATRIC INFLAMMATORY BOWEL DISEASE 2023:355-383. [DOI: 10.1007/978-3-031-14744-9_27] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Harada K, Ferdous T, Fujiwara R, Watanabe K, Mizukami Y, Mishima K. An elemental diet protects mouse salivary glands from 5‑fluorouracil‑induced atrophy. Oncol Lett 2022; 23:178. [PMID: 35464303 PMCID: PMC9025579 DOI: 10.3892/ol.2022.13298] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2021] [Accepted: 02/14/2022] [Indexed: 11/18/2022] Open
Abstract
An elemental diet (ED) reduces adverse effects of chemotherapy, including oral mucositis, in patients with cancer. However, the detailed mechanism(s) of the healing effects of an ED remains unclear. In the present study, the protective effects of the ED, Elental®, were examined against 5-fluorouracil (5-FU)-induced oral mucositis and salivary gland atrophy in mice. Mucositis was induced in female ICR mice by injection of 5-FU. The mice were orally administered Elental® (ED group) or saline (control group). After treatment, the mice body weight, salivary gland weight and the histological changes in the salivary gland granular duct area were monitored. The mice body weight remained stable in the ED group, but was significantly decreased in the control group. Moreover, the salivary gland weight was higher in the ED group compared with the control group. In addition, the salivary gland granular duct area cells were larger in the ED group compared with the control group. Whole transcriptome analysis and network analysis were conducted to understand the mechanisms of action of Elental® against oral mucositis. Whole transcriptome analysis and Ingenuity Pathways Analysis data suggested that Elental® contributed to the recovery of mitochondrial function in 5-FU-damaged salivary glands. Immunohistochemical analysis of salivary gland tissue demonstrated that the expression of cytochrome c oxidase subunit 4 and epidermal growth factor were higher in the ED group compared with the control group. Next, the rate of apoptosis in the salivary glands was examined using terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assays. The number of TUNEL-positive cells in the salivary glands was lower in the ED group compared with the control group. These findings suggested that Elental® may protect mouse salivary glands from 5-FU-induced atrophic changes, which suggests that ED treatment may improve xerostomia and alleviate oral mucositis in patients with cancer receiving 5-FU-based chemotherapy.
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Affiliation(s)
- Koji Harada
- Department of Oral and Maxillofacial Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755‑8505, Japan
| | - Tarannum Ferdous
- Department of Oral and Maxillofacial Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755‑8505, Japan
| | - Rieko Fujiwara
- Department of Oral and Maxillofacial Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755‑8505, Japan
| | - Kenji Watanabe
- Center for Gene Research, Yamaguchi University, Ube, Yamaguchi 755‑8505, Japan
| | - Yoichi Mizukami
- Center for Gene Research, Yamaguchi University, Ube, Yamaguchi 755‑8505, Japan
| | - Katsuaki Mishima
- Department of Oral and Maxillofacial Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755‑8505, Japan
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Fujiwara R, Harada K, Ferdous T, Mishima K. Amino Acids May Have Protective Effects on Salivary Glands of 5-FU-administered Mice. In Vivo 2022; 36:198-205. [PMID: 34972715 DOI: 10.21873/invivo.12691] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 11/25/2021] [Accepted: 11/29/2021] [Indexed: 12/22/2022]
Abstract
BACKGROUND/AIM This study aimed to identify the most useful components of Elental® in the treatment of 5-fluorouracil (FU)-induced mucositis and salivary gland atrophy in mice. MATERIALS AND METHODS Mice (except the control group) were intraperitoneally injected with 5-FU. The mice received saline (control group and 5-FU group), dextrin (Dextrin group), amino acids (17AA group), or Elental® (Elental® group). RESULTS The volume and weight of salivary glands was higher in 17AA and Elental® groups compared to 5-FU group. The number of mucous glands was higher, whereas the number of damaged granular ductal epithelial cells was lower in the salivary glands of all groups except the 5-FU group. Salivation was also decreased in the 5-FU group compared to the other groups. CONCLUSION Amino acids could be the most effective components of Elental® for protecting mouse salivary glands from 5-FU-induced atrophic changes, and might be useful in the treatment of oral mucositis in cancer patients.
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Affiliation(s)
- Rieko Fujiwara
- Department of Oral and Maxillofacial Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Koji Harada
- Department of Oral and Maxillofacial Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Tarannum Ferdous
- Department of Oral and Maxillofacial Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Katsuaki Mishima
- Department of Oral and Maxillofacial Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan
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Ceballos D, Hernández-Camba A, Ramos L. Diet and microbiome in the beginning of the sequence of gut inflammation. World J Clin Cases 2021; 9:11122-11147. [PMID: 35071544 PMCID: PMC8717522 DOI: 10.12998/wjcc.v9.i36.11122] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Revised: 08/26/2021] [Accepted: 11/18/2021] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract due, at least partially, to an aberrant and excessive mucosal immune response to gut bacteria in genetically-predisposed individuals under certain environmental factors. The incidence of IBD is rising in western and newly industrialized countries, paralleling the increase of westernized dietary patterns, through new antigens, epithelial function and permeability, epigenetic mechanisms (e.g., DNA methylation), and alteration of the gut microbiome. Alteration in the composition and functionality of the gut microbiome (including bacteria, viruses and fungi) seems to be a nuclear pathogenic factor. The microbiome itself is dynamic, and the changes in food quality, dietary habits, living conditions and hygiene of these western societies, could interact in a complex manner as modulators of dysbiosis, thereby influencing the activation of immune cells' promoting inflammation. The microbiome produces diverse small molecules via several metabolic ways, with the fiber-derived short-chain fatty acids (i.e., butyrate) as main elements and having anti-inflammatory effects. These metabolites and some micronutrients of the diet (i.e., vitamins, folic acid, beta carotene and trace elements) are regulators of innate and adaptive intestinal immune homeostasis. An excessive and unhealthy consumption of sugar, animal fat and a low-vegetable and -fiber diet are risk factors for IBD appearance. Furthermore, metabolism of nutrients in intestinal epithelium and in gut microbiota is altered by inflammation, changing the demand for nutrients needed for homeostasis. This role of food and a reduced gut microbial diversity in causing IBD might also have a prophylactic or therapeutic role for IBD. The relationship between dietary intake, symptoms, and bowel inflammation could lead to dietary and lifestyle recommendations, including diets with abundant fruits, vegetables, olive oil and oily fish, which have anti-inflammatory effects and could prevent dysbiosis and IBD. Dietary modulation and appropriate exclusion diets might be a new complementary management for treatment at disease flares and in refractory patients, even reducing complications, hospitalizations and surgery, through modifying the luminal intestinal environment.
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Affiliation(s)
- Daniel Ceballos
- Department of Gastroenterology, Hospital Universitario de Gran Canaria Doctor Negrin, Las Palmas 35019, Canarias, Spain
| | - A Hernández-Camba
- Department of Gastroenterology, Hospital Universitario Nuestra Señora de La Candelaria, Santa Cruz de Tenerife 38010, Canarias, Spain
| | - Laura Ramos
- Department of Gastroenterology, Hospital Universitario de Canarias, San Cristóbal de La Laguna 38320, Canarias, Spain
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11
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Mitrev N, Huang H, Hannah B, Kariyawasam VC. Review of exclusive enteral therapy in adult Crohn's disease. BMJ Open Gastroenterol 2021; 8:bmjgast-2021-000745. [PMID: 34580154 PMCID: PMC8477235 DOI: 10.1136/bmjgast-2021-000745] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 09/07/2021] [Indexed: 12/14/2022] Open
Abstract
Background Exclusive enteral nutrition (EEN) is a potentially effective but underused therapy for Crohn’s disease (CD) in adults. It is first-line induction treatment for paediatric patients but remains a second-line or third-line therapy in adults. Objective To analyse the evidence for EEN in adult patients with CD, and summarise this in a narrative review. Methods In April/May 2020 and July 2021, a literature search was performed using the Medical Subject Headings (MeSH) terms: ‘Crohn’s disease’, ‘CD’, ‘inflammatory bowel disease’, ‘IBD’, ‘exclusive enteral nutrition’, ‘enteral nutrition’, ‘EEN’, in PubMed, Scopus, Cochrane. Additional studies were obtained from references of search result articles as well as general reading. Studies with adult patients with CD treated with EEN were selected. 79 articles of relevance were found. Where data in adults were lacking, data from paediatric studies as extrapolated with care. Results EEN in adult patients been shown to improve clinical, biomarker, endoscopic and radiologic measures of disease activity. EEN avoids the potential adverse effects of recurrent corticosteroids for induction such as metabolic derangements and opportunistic infections. EEN has also demonstrated benefits among adult patients with fistulising and stricturing CD. It may avoid surgery in such patients. Preoperative EEN has also been shown to reduce postoperative complications and recurrence. There appears to be benefits in combing EEN with antitumour necrosis factor agents, however, benefits of combination therapy with other biologics are less clear. A major drawback of EEN therapy in adults has been poor compliance. More palatable polymeric formulations improved patient education and dietitian support may overcome this. Evidence in adults is limited to small studies, often with suboptimal control arms and lack of blinding. Larger scale studies with improved study design are needed to confirm these beneficial effects. Conclusion Despite limitations in evidence EEN should be considered in treating adults with CD.
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Affiliation(s)
- Nikola Mitrev
- Department of Gastroenterology, Blacktown Hospital, Blacktown, New South Wales, Australia.,Western Sydney University Blacktown Mount Druitt Medical School, Blacktown, New South Wales, Australia
| | - Hin Huang
- Western Sydney University Blacktown Mount Druitt Medical School, Blacktown, New South Wales, Australia
| | - Barbara Hannah
- Department of Gastroenterology, Blacktown Hospital, Blacktown, New South Wales, Australia
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12
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Wellens J, Vermeire S, Sabino J. Let Food Be Thy Medicine-Its Role in Crohn's Disease. Nutrients 2021; 13:832. [PMID: 33802429 PMCID: PMC8001864 DOI: 10.3390/nu13030832] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Revised: 02/26/2021] [Accepted: 02/27/2021] [Indexed: 12/16/2022] Open
Abstract
The food we eat is thought to play a role in both the increasing incidence as well as the course of Crohn's disease. What to eat and what to avoid is an increasingly important question for both patients and physicians. Restrictive diets are widely adopted by patients and carry the risk of inducing or worsening malnutrition, without any guarantees on anti-inflammatory potential. Nevertheless, exploration of novel therapies to improve long-term management of the disease is desperately needed and the widespread use of exclusive enteral nutrition in the induction of paediatric Crohn's disease makes us wonder if a similar approach would be beneficial in adult patients. This narrative review discusses the current clinical evidence on whole food diets in achieving symptomatic and inflammatory control in Crohn's disease and identifies knowledge gaps with areas for future research.
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Affiliation(s)
| | | | - João Sabino
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, 3000 Leuven, Belgium; (J.W.); (S.V.)
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13
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Abstract
The purpose of this article is to provide an updated review of the definition, prevalence, causes, and clinical management of malnutrition in inflammatory bowel disease (IBD). Prevalence of malnutrition in IBD is estimated to be between 6.1% and 69.7% depending on the definition used, the type of IBD, the clinical setting, and whether the IBD is active or in remission. Whereas older definitions of malnutrition have been found to be correlated with mortality and length of hospital stay, the more recent European Society for Clinical Nutrition and Metabolism (ESPEN) 2015 and the Global Leadership Initiative on Malnutrition (GLIM) definitions provide significantly different prevalence estimates of malnutrition when applied to the same patient population, and further work is needed to validate these two definitions against clinical outcomes. In patients with IBD with identified malnutrition, oral nutrition supplementation, enteral nutrition, or parenteral nutrition should be started. In malnourished patients with Crohn's disease undergoing surgery, preoperative enteral nutrition has been demonstrated to reduce the rate of postoperative complications. Overall, patients with IBD are at significant risk for malnutrition and should be screened for malnutrition by using a validated screening tool. The management of malnutrition in IBD is complex, and studies are often limited in their size or their ability to demonstrate an improvement in clinical outcomes based on specific nutrition-related interventions. Future studies particularly regarding the validation of new screening tools and perioperative management of malnutrition may provide insight into the standardization of diagnosis and management of malnutrition in IBD.
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Affiliation(s)
- Austin Lin
- Department of Internal Medicine, University of Chicago Medicine, Chicago, Illinois, USA
| | - Dejan Micic
- Department of Internal Medicine, Section of Gastroenterology, Hepatology and Nutrition, University of Chicago Medicine, Chicago, Illinois, USA
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14
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Shah RS, Click BH. Medical therapies for postoperative Crohn's disease. Therap Adv Gastroenterol 2021; 14:1756284821993581. [PMID: 33643440 PMCID: PMC7890708 DOI: 10.1177/1756284821993581] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Accepted: 01/19/2021] [Indexed: 02/04/2023] Open
Abstract
Postoperative recurrence of Crohn's disease is common and requires a multidisciplinary approach between surgeons and gastroenterologists in the perioperative and postoperative period to improve outcomes in this patient population. Endoscopic recurrence precedes clinical and surgical recurrence and endoscopic monitoring is crucial to guide postoperative management. Risk stratification of patients is recommended to guide early prophylactic management, and follow-up endoscopic monitoring can guide intensification of therapy. This review summarizes evidence behind postoperative recurrence rates, disease monitoring techniques, nonbiologic and biologic therapies available to prevent and treat postoperative recurrence, risk factors associated with recurrence, and postoperative management strategies guided by endoscopic monitoring.
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Affiliation(s)
- Ravi S. Shah
- Cleveland Clinic - Internal Medicine, 9500 Euclid Ave, Cleveland, OH 44195, USA
| | - Benjamin H. Click
- Cleveland Clinic - Gastroenterology, Hepatology, and Nutrition, Cleveland, OH, USA
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15
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Ogasawara H, Hayasaka M, Maemoto A, Furukawa S, Ito T, Kimura O, Endo T. Levels of major and trace metals in the scalp hair of Crohn's disease patients: correlations among transition metals. Biometals 2021; 34:197-210. [PMID: 33387116 DOI: 10.1007/s10534-020-00272-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Accepted: 11/13/2020] [Indexed: 12/16/2022]
Abstract
Concentrations of 16 metals in the scalp hair of male Crohn's disease (CD) patients (n = 28) were compared to those of male control subjects (n = 25). The majority of patients (n = 20) took an anti-inflammatory agent (mesalazine), and several patients underwent colectomy. A low concentration of serum ferritin was observed in approximately 50% of CD patients due to Fe-deficiency anemia. The concentrations of Fe, Cr, and Co in the hair of CD patients were significantly higher than those of control subjects, and particularly high concentrations were found in CD patients with low serum ferritin. Significant correlations were found among the concentrations of Fe, Cr, and Co in the hair of CD patients, but not in control subjects. In agreement with previous reports, a significant negative correlation was found between ferritin and transferrin concentrations in serum, although the available data in this study was limited (n = 8). Transferrin not only binds to Fe3+ but also to Cr3+ and Co3+, and the amount of transferrin is increased in Fe-deficiency anemia. Thus, the majority of the Fe3+, Cr3+, and Co3+ in the serum of CD patients is likely to bind to transferrin, which may be associated with the higher concentrations of those metals, as well as the significant correlations among those metals in the scalp hair of CD patients. In addition, colectomy may alter the intestinal absorption rate of some metals, while mesalazine may increase the concentrations of Mn and some metals in the scalp hair by chelate formation.
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Affiliation(s)
- Hideki Ogasawara
- Kashiwaba Neurosurgical Hospital, E1-15-20, Tsukisamu, Toyohira-Ku, Sapporo, Hokkaido, 062-8513, Japan
| | - Moriaki Hayasaka
- School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 1757, Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan
| | - Atsuo Maemoto
- Sapporo Higashi Tokushukai Hospital, N33-E14, Higashi-Ku, Sapporo, Hokkaido, 065-0033, Japan
| | - Shigeru Furukawa
- Sapporo Higashi Tokushukai Hospital, N33-E14, Higashi-Ku, Sapporo, Hokkaido, 065-0033, Japan
| | - Takahiro Ito
- Sapporo Higashi Tokushukai Hospital, N33-E14, Higashi-Ku, Sapporo, Hokkaido, 065-0033, Japan
| | - Osamu Kimura
- School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 1757, Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan
| | - Tetsuya Endo
- School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 1757, Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan.
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16
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Kusunoki K, Toiyama Y, Okugawa Y, Yamamoto A, Omura Y, Kusunoki Y, Yin C, Kondo S, Okita Y, Ohi M, Sasaki H, Bando T, Uchino M, Ikeuchi H, Kusunoki M. The advanced lung cancer inflammation index predicts outcomes in patients with Crohn's disease after surgical resection. Colorectal Dis 2021; 23:84-93. [PMID: 32644245 DOI: 10.1111/codi.15248] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Accepted: 06/25/2020] [Indexed: 12/13/2022]
Abstract
AIM Precise biomarkers for predicting prognosis could help to identify high-risk Crohn's disease (CD) patients to facilitate better follow-up during the postoperative course. In this study, the primary aim is the identification of the most reliable nutrition marker that predicts surgical relapse in CD patients. METHOD We first evaluated the predictive value of various nutrition markers for postoperative surgical relapse in CD patients and identified the advanced lung cancer inflammation index (ALI) as a promising biomarker. Then, we assessed the clinical significance of preoperative ALI in CD patients using two cohorts. RESULTS Preoperative ALI showed the highest correlation with reoperation rate compared with other nutritional parameters in CD patients receiving surgical resection (sensitivity 53%, specificity 86%, area under the curve 0.71). Lower levels of preoperative ALI were significantly correlated with the presence of perianal disease. A lower level of preoperative ALI was an independent prognostic factor for reoperation rate after an intestinal resection (hazard ratio 3.37, 95% CI 1.38-10.12, P = 0.006), and the prognostic impact of preoperative ALI was successfully validated in an independent cohort using the same cut-off value. CONCLUSION Preoperative ALI might be useful for postoperative management of CD patients.
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Affiliation(s)
- K Kusunoki
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Japan.,Department of Inflammatory Bowel Disease, Division of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - Y Toiyama
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Japan
| | - Y Okugawa
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Japan.,Department of Genomic Medicine, Mie University Hospital, Tsu, Japan
| | - A Yamamoto
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Japan
| | - Y Omura
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Japan
| | - Y Kusunoki
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Japan
| | - C Yin
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Japan
| | - S Kondo
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Japan
| | - Y Okita
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Japan
| | - M Ohi
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Japan
| | - H Sasaki
- Department of Inflammatory Bowel Disease, Division of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - T Bando
- Department of Inflammatory Bowel Disease, Division of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - M Uchino
- Department of Inflammatory Bowel Disease, Division of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - H Ikeuchi
- Department of Inflammatory Bowel Disease, Division of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - M Kusunoki
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Japan
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17
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The Role of Inflammation in Crohn's Disease Recurrence after Surgical Treatment. J Immunol Res 2020; 2020:8846982. [PMID: 33426097 PMCID: PMC7781709 DOI: 10.1155/2020/8846982] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Revised: 12/04/2020] [Accepted: 12/08/2020] [Indexed: 02/08/2023] Open
Abstract
Introduction Postoperative recurrence after surgery for Crohn's disease (CD) is virtually inevitable, and its mechanism is poorly known. Aim To review the numerous factors involved in CD postoperative recurrence (POR) pathogenesis, focusing on single immune system components as well as the immune system as a whole and highlighting the clinical significance in terms of preventive strategies and future perspectives. Methods A systematic literature search on CD POR, followed by a review of the main findings. Results The immune system plays a pivotal role in CD POR, with many different factors involved. Memory T-lymphocytes retained in mesenteric lymph nodes seem to represent the main driving force. New pathophysiology-based preventive strategies in the medical and surgical fields may help reduce POR rates. In particular, surgical strategies have already been developed and are currently under investigation. Conclusions POR is a complex phenomenon, whose driving mechanisms are gradually being unraveled. New preventive strategies addressing these mechanisms seem promising.
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18
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van Rheenen PF, Aloi M, Assa A, Bronsky J, Escher JC, Fagerberg UL, Gasparetto M, Gerasimidis K, Griffiths A, Henderson P, Koletzko S, Kolho KL, Levine A, van Limbergen J, Martin de Carpi FJ, Navas-López VM, Oliva S, de Ridder L, Russell RK, Shouval D, Spinelli A, Turner D, Wilson D, Wine E, Ruemmele FM. The Medical Management of Paediatric Crohn's Disease: an ECCO-ESPGHAN Guideline Update. J Crohns Colitis 2020; 15:jjaa161. [PMID: 33026087 DOI: 10.1093/ecco-jcc/jjaa161] [Citation(s) in RCA: 308] [Impact Index Per Article: 61.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
OBJECTIVE We aimed to provide an evidence-supported update of the ECCO-ESPGHAN guideline on the medical management of paediatric Crohn's disease [CD]. METHODS We formed 10 working groups and formulated 17 PICO-structured clinical questions [Patients, Intervention, Comparator, and Outcome]. A systematic literature search from January 1, 1991 to March 19, 2019 was conducted by a medical librarian using MEDLINE, EMBASE, and Cochrane Central databases. A shortlist of 30 provisional statements were further refined during a consensus meeting in Barcelona in October 2019 and subjected to a vote. In total 22 statements reached ≥ 80% agreement and were retained. RESULTS We established that it was key to identify patients at high risk of a complicated disease course at the earliest opportunity, to reduce bowel damage. Patients with perianal disease, stricturing or penetrating behaviour, or severe growth retardation should be considered for up-front anti-tumour necrosis factor [TNF] agents in combination with an immunomodulator. Therapeutic drug monitoring to guide treatment changes is recommended over empirically escalating anti-TNF dose or switching therapies. Patients with low-risk luminal CD should be induced with exclusive enteral nutrition [EEN], or with corticosteroids when EEN is not an option, and require immunomodulator-based maintenance therapy. Favourable outcomes rely on close monitoring of treatment response, with timely adjustments in therapy when treatment targets are not met. Serial faecal calprotectin measurements or small bowel imaging [ultrasound or magnetic resonance enterography] are more reliable markers of treatment response than clinical scores alone. CONCLUSIONS We present state-of-the-art guidance on the medical treatment and long-term management of children and adolescents with CD.
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Affiliation(s)
- Patrick F van Rheenen
- Department of Paediatric Gastroenterology, University of Groningen, University Medical Centre Groningen, Beatrix Children's Hospital, Groningen, The Netherlands
| | - Marina Aloi
- Pediatric Gastroenterology and Liver Unit, Maternal and Child Health Department, Sapienza - University of Rome, Rome, Italy
| | - Amit Assa
- Department of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center, Petach Tikvah, Affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Israel
| | - Jiri Bronsky
- Paediatric Gastroenterology Unit, Department of Paediatrics, University Hospital Motol, Prague, Czech Republic
| | - Johanna C Escher
- Department of Paediatric Gastroenterology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands
| | - Ulrika L Fagerberg
- Department of Pediatrics/Centre for Clinical Research, Västmanland Hospital, Västeras and Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden
| | - Marco Gasparetto
- Department of Paediatric Gastroenterology, Barts Health Trust, The Royal London Children's Hospital, London, UK
| | | | - Anne Griffiths
- Department of Paediatrics, Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, University of Toronto, Toronto, Canada
| | - Paul Henderson
- Child Life and Health, University Of Edinburgh, Edinburgh, UK
| | - Sibylle Koletzko
- Department of Pediatrics, Division of Gastroenterology and Hepatology, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany
- Department of Pediatrics, Gastroenterology and Nutrition, School of Medicine Collegium Medicum University of Warmia and Mazury, Olsztyn, Poland
| | - Kaija-Leena Kolho
- Department of Paediatrics, Children´s Hospital, University of Helsinki and Tampere University, Tampere, Finland
| | - Arie Levine
- Pediatric Gastroenterology and Nutrition Unit, Wolfson Medical Center, Tel Aviv University, Israel
| | - Johan van Limbergen
- Division of Pediatric Gastroenterology and Nutrition, Amsterdam UMC - location AMC, Amsterdam, The Netherlands
| | | | - Víctor Manuel Navas-López
- Pediatric Gastroenterology and Nutrition Unit, IBIMA, Hospital Regional Universitario de Málaga, Málaga, Spain
| | - Salvatore Oliva
- Pediatric Gastroenterology and Liver Unit, Maternal and Child Health Department, Sapienza - University of Rome, Rome, Italy
| | - Lissy de Ridder
- Department of Paediatric Gastroenterology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands
| | - Richard K Russell
- Department of Paediatric Gastroenterology and Nutrition, Royal Hospital for Sick Children, Edinburgh, UK
| | - Dror Shouval
- Pediatric Gastroenterology Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Antonino Spinelli
- Department of Colon and Rectal Surgery, Humanitas Clinical and Research Center - IRCCS, Rozzano Milano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Dan Turner
- Paediatric Gastroenterology, Shaare Zedek Medical Centre, the Hebrew University of Jerusalem, Israel
| | - David Wilson
- Child Life and Health, University Of Edinburgh, Edinburgh, UK
| | - Eytan Wine
- Division of Pediatric Gastroenterology, Edmonton Pediatric IBD Clinic (EPIC), Departments of Pediatrics & Physiology, University of Alberta, Edmonton, Canada
| | - Frank M Ruemmele
- Assistance Publique- Hôpitaux de Paris, Hôpital Necker Enfants Malades, Pediatric Gastroenterology, Paris, France
- Faculté de Médecine, Université Sorbonne Paris Cité, Paris Descartes, Paris, France
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19
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Kim ES, Heo YA. Prevent postoperative recurrence of paediatric Crohn’s disease by risk-based treatment and early monitoring. DRUGS & THERAPY PERSPECTIVES 2020. [DOI: 10.1007/s40267-020-00758-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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20
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Wolford DD, Fichera A. Prophylaxis of Crohn's disease recurrence: A surgeon's perspective. Ann Gastroenterol Surg 2020; 4:514-520. [PMID: 33005846 PMCID: PMC7511563 DOI: 10.1002/ags3.12368] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 05/10/2020] [Accepted: 05/26/2020] [Indexed: 12/23/2022] Open
Abstract
Management of inflammatory bowel disease has evolved extensively in the last three decades. We have learnt a lot about the pathophysiology and natural history of the disease. New effective classes of drugs with the associated potential morbidity have been introduced. New surgical techniques have been popularized leading to a better understanding of the optimal timing of surgery. The result is a very complex subspecialty of gastroenterology and colorectal surgery called the "IBDologist." Only if we manage these complex patients in the context of a multi-disciplinary team will we be able to obtain outstanding outcomes, specifically with high and sustained remission rates for these patients.
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Affiliation(s)
- Dallas D. Wolford
- Division of Colorectal SurgeryDepartment of SurgeryBaylor University Medical CenterDallasTexasUSA
| | - Alessandro Fichera
- Division of Colorectal SurgeryDepartment of SurgeryBaylor University Medical CenterDallasTexasUSA
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21
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Argollo M, Kotze PG, Lamonaca L, Gilardi D, Furfaro F, Yamamoto T, Danese S. Prevention of Postoperative Recurrence in CD: Tailoring Treatment to Patient Profile. Curr Drug Targets 2020; 20:1327-1338. [PMID: 30894106 DOI: 10.2174/1389450120666190320110809] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Revised: 02/08/2019] [Accepted: 03/08/2019] [Indexed: 12/11/2022]
Abstract
Crohn's disease (CD) is an immune-mediated condition characterized by the transmural inflammation of the gut tissue, associated with progressive bowel damage often leading to surgical intervention. As operative resection of the damaged segment is not curative, a majority of patients undergoing intestinal resections for complicated CD present disease recurrence within 3 years after the intervention. Postoperative recurrence can be defined as endoscopic, clinical, radiological or surgical. Endoscopic recurrence rates within 1 year exceed 60% and the severity, according to the Rutgeerts' score, is associated with worse prognosis and can predict clinical recurrence (in up to 1/3 of the patients). Most importantly, about 50% of patients will undergo a reoperation after 10 years of their first intestinal resection. Therefore, the prevention of postoperative recurrence in CD remains a challenge in clinical practice and should be properly managed. We aim to summarize the most recent data on the definition, risk factors, assessment and treatment of postoperative CD recurrence.
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Affiliation(s)
- Marjorie Argollo
- Department of Gastroenterology, Universidade Federal de São Paulo, São Paulo, Brazil.,IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Institute, Milan, Italy
| | - Paulo Gustavo Kotze
- IBD outpatient clinics, Catholic University of Parana (PUCPR), Curitiba, Brazil
| | - Laura Lamonaca
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Institute, Milan, Italy
| | - Daniela Gilardi
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Institute, Milan, Italy
| | - Federica Furfaro
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Institute, Milan, Italy
| | - Takayuki Yamamoto
- Department of Surgery and IBD Centre, Yokkaichi Hazu Medical Centre, Yokkaichi, Japan
| | - Silvio Danese
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Institute, Milan, Italy.,Department of Biomedical Sciences, Humanitas University, Milan, Italy
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Yang H, Feng R, Li T, Xu S, Hao X, Qiu Y, Chen M. Systematic review with meta-analysis of partial enteral nutrition for the maintenance of remission in Crohn's disease. Nutr Res 2020; 81:7-18. [PMID: 32798791 DOI: 10.1016/j.nutres.2020.06.006] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Revised: 04/30/2020] [Accepted: 06/03/2020] [Indexed: 12/28/2022]
Abstract
Although enteral nutrition (EN) is effective for induction therapy in Crohn's disease (CD), it remains unclear whether partial enteral nutrition (PEN), i.e., EN, along with a daily diet, is effective for maintenance therapy in CD. It was hypothesized that PEN would be effective as a maintenance therapy in CD. This meta-analysis aimed to evaluate the efficacy and safety of PEN for maintenance therapy in CD. PubMed, EMBASE, Web of Science, and Cochrane Library were searched up to January 2019 for eligible prospective controlled trials, and then a meta-analysis was conducted. The primary outcome was clinical relapse, as defined in the primary studies. Eight studies with 429 patients were included in the meta-analysis. The rate of clinical relapse at 0.5 to 2 years was significantly lower in patients receiving PEN (420-1800 kcal/d) than in those not receiving nutrition therapy (RR: 0.67, 95% CI: 0.54-0.82, P < .01; number needed to treat = 5, P < .01). Patients receiving PEN exhibited a higher frequency of clinical remission maintenance at 0.5 to 1 year (67%) than did those not receiving nutrition therapy (48%; RR: 1.32, 95% CI: 1.07-1.64, P = .01). The total adverse event rate was comparable in the two groups (RR: 3.60, 95% CI: 0.70-18.66, P = .13). PEN may be more effective than the absence of EN therapy for the maintenance of remission in CD with a good safety profile.
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Affiliation(s)
- Hongsheng Yang
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan Road II, Yuexiu district, Guangzhou 510000, P.R. China; Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-Sen University, No. 26 Yuancun Road II, Tianhe district, Guangzhou 510000, P.R. China
| | - Rui Feng
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan Road II, Yuexiu district, Guangzhou 510000, P.R. China
| | - Tong Li
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan Road II, Yuexiu district, Guangzhou 510000, P.R. China
| | - Shu Xu
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan Road II, Yuexiu district, Guangzhou 510000, P.R. China
| | - Xiuxue Hao
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan Road II, Yuexiu district, Guangzhou 510000, P.R. China
| | - Yun Qiu
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan Road II, Yuexiu district, Guangzhou 510000, P.R. China.
| | - Minhu Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan Road II, Yuexiu district, Guangzhou 510000, P.R. China.
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23
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Harada K, Takenawa T, Ferdous T, Mizukami Y, Mishima K. Elemental diet directly affects chemotherapy-induced dermatitis and raw wound areas. Mol Clin Oncol 2020; 13:209-215. [PMID: 32699632 DOI: 10.3892/mco.2020.2050] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2019] [Accepted: 02/21/2020] [Indexed: 11/05/2022] Open
Abstract
Elental® is an L-glutamine-rich elemental diet (ED) that has been widely used in Japan as a nutritional supplement for malnourished patients. In addition, Elental® has been successfully used in the management of chemotherapy-induced mucositis in cancer patients. Recently, it was also reported that Elental® can effectively reduce chemotherapy-induced oral mucositis in patients with oral squamous cell carcinoma, and can also reduce mucositis and dermatitis in animal models. However, it is unclear whether oral intake or topical application of Elental® can act directly on chemotherapy-induced oral mucositis or dermatitis. The aim of the present study was to investigate the possible direct healing effect of Elental® on chemotherapy-induced dermatitis and raw wound areas in a mouse model. Dermatitis and raw wounds were induced in nude mice by administration of 5-fluorouracil (5-FU) (via gastric tube) and mechanical injury (using a metal brush or a surgical knife). We then compared the outcome following oral or topical application of Elental® in these mice. The effect of Elental® on the growth and migration ability of the human oral keratinocyte cell line, HOK, was also examined using MTT and migration assays, respectively. In the mouse model, both oral administration and topical application of Elental® reduced 5-FU-induced dermatitis and healed raw wound areas more effectively compared with the topical application of saline. The MTT assay revealed that Elental® exerted a growth-promoting effect on HOKs. In addition, Elental® enhanced the ability of HOKs to migrate, as demonstrated by the migration assay. These findings demonstrated that the topical application as well as the oral intake of Elental® exerted a direct healing effect on chemotherapy-induced dermatitis or raw wound areas. The data also indicated that oral intake of an ED may exert a direct healing effect on chemotherapy-induced oral mucositis.
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Affiliation(s)
- Koji Harada
- Department of Oral and Maxillofacial Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan
| | - Takanori Takenawa
- Department of Oral and Maxillofacial Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan
| | - Tarannum Ferdous
- Department of Oral and Maxillofacial Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan
| | - Yoichi Mizukami
- Center for Gene Research, Yamaguchi University, Ube, Yamaguchi 755-8505, Japan
| | - Katsuaki Mishima
- Department of Oral and Maxillofacial Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan
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24
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Gkikas K, Gerasimidis K, Milling S, Ijaz UZ, Hansen R, Russell RK. Dietary Strategies for Maintenance of Clinical Remission in Inflammatory Bowel Diseases: Are We There Yet? Nutrients 2020; 12:E2018. [PMID: 32645980 PMCID: PMC7400838 DOI: 10.3390/nu12072018] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 07/01/2020] [Accepted: 07/06/2020] [Indexed: 12/15/2022] Open
Abstract
The etiopathogenesis of Inflammatory bowel disease (IBD) is a result of a complex interaction between host immune response, the gut microbiome and environmental factors, such as diet. Although scientific advances, with the use of biological medications, have revolutionized IBD treatment, the challenge for maintaining clinical remission and delaying clinical relapse is still present. As exclusive enteral nutrition has become a well-established treatment for the induction of remission in pediatric Crohn's disease, the scientific interest regarding diet in IBD is now focused on the development of follow-on dietary strategies, which aim to suppress colonic inflammation and delay a disease flare. The objective of this review is to present an extensive overview of the dietary strategies, which have been used in the literature to maintain clinical remission in both Crohn's disease and Ulcerative colitis, and the evidence surrounding the association of dietary components with clinical relapse. We also aim to provide study-related recommendations to be encompassed in future research studies aiming to investigate the role of diet during remission periods in IBD.
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Affiliation(s)
- Konstantinos Gkikas
- Human Nutrition, School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow Royal Infirmary, Glasgow G31 2ER, UK; (K.G.); (K.G.)
| | - Konstantinos Gerasimidis
- Human Nutrition, School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow Royal Infirmary, Glasgow G31 2ER, UK; (K.G.); (K.G.)
| | - Simon Milling
- Institute for Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8QQ, UK;
| | - Umer Z. Ijaz
- Civil Engineering, School of Engineering, University of Glasgow, Glasgow G12 8QQ, UK;
| | - Richard Hansen
- Department of Paediatric Gastroenterology, Royal Hospital for Children, Glasgow G51 4TF, UK;
| | - Richard K. Russell
- Department of Paediatric Gastroenterology, Royal Hospital for Sick Children, Edinburgh EH9 1LF, UK
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25
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Adamina M, Gerasimidis K, Sigall-Boneh R, Zmora O, de Buck van Overstraeten A, Campmans-Kuijpers M, Ellul P, Katsanos K, Kotze PG, Noor N, Schäfli-Thurnherr J, Vavricka S, Wall C, Wierdsma N, Yassin N, Lomer M. Perioperative Dietary Therapy in Inflammatory Bowel Disease. J Crohns Colitis 2020; 14:431-444. [PMID: 31550347 DOI: 10.1093/ecco-jcc/jjz160] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS The incidence of inflammatory bowel disease [IBD] is rising worldwide and no cure is available. Many patients require surgery and they often present with nutritional deficiencies. Although randomised controlled trials of dietary therapy are lacking, expert IBD centres have long-established interdisciplinary care, including tailored nutritional therapy, to optimise clinical outcomes and resource utilisation. This topical review aims to share expertise and offers current practice recommendations to optimise outcomes of IBD patients who undergo surgery. METHODS A consensus expert panel consisting of dietitians, surgeons, and gastroenterologists, convened by the European Crohn's and Colitis Organisation, performed a systematic literature review. Nutritional evaluation and dietary needs, perioperative optimis ation, surgical complications, long-term needs, and special situations were critically appraised. Statements were developed using a Delphi methodology incorporating three successive rounds. Current practice positions were set when ≥80% of participants agreed on a recommendation. RESULTS A total of 26 current practice positions were formulated which address the needs of IBD patients perioperatively and in the long term following surgery. Routine screening, perioperative optimisation by oral, enteral, or parenteral nutrition, dietary fibre, and supplements were reviewed. IBD-specific situations, including management of patients with a restorative proctocolectomy, an ostomy, strictures, or short-bowel syndrome, were addressed. CONCLUSIONS Perioperative dietary therapy improves the outcomes of IBD patients who undergo a surgical procedure. This topical review shares interdisciplinary expertise and provides guidance to optimise the outcomes of patients with Crohn's disease and ulcerative colitis. taking advantage of contemporary nutrition science.
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Affiliation(s)
- Michel Adamina
- Department of Surgery, Cantonal Hospital Winterthur, Winterthur, Switzerland.,University of Basel, Basel, Switzerland
| | - Konstantinos Gerasimidis
- Human Nutrition, School of Medicine, Dentistry and Nursing, Glasgow Royal Infirmary, Glasgow, UK
| | - Rotem Sigall-Boneh
- PIBD Research Center, Pediatric Gastroenterology and Nutrition Unit, Wolfson Medical Center, Holon, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Oded Zmora
- Department of Surgery, Assaf Harofeh Medical Center, Tel Aviv, Israel
| | | | - Marjo Campmans-Kuijpers
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen, Groningen, The Netherlands
| | - Pierre Ellul
- Department of Medicine, Division of Gastroenterology, Mater Dei Hospital, Msida, Malta
| | | | - Paulo Gustavo Kotze
- Colorectal Surgery Unit, Catholic University of Paraná [PUCPR], Curitiba, Brazil
| | - Nurulamin Noor
- Department of Gastroenterology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Trust, Cambridge, UK
| | | | - Stephan Vavricka
- Department of Surgery, Kantonsspital Winterthur, Winerthur, Switzerland
| | - Catherine Wall
- Department of Nutritional Sciences, King's College London, London, UK
| | - Nicolette Wierdsma
- Department of Nutrition and Dietetics, Amsterdam UMC, VU University Medical Centre, Amsterdam, The Netherlands
| | - Nuha Yassin
- Department of Colorectal Surgery, Wolverhampton Hospital, Wolverhampton, UK
| | - Miranda Lomer
- Department of Nutritional Sciences, King's College London, London, UK.,Department of Nutrition and Dietetics, Guy's and St Thomas' NHS Foundation Trust, London, UK
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26
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Two Cases of Atraumatic Chylous Ascites Characterized by Hypotriglyceridemia and Partially Managed with an Oral Fat-Free Elemental Diet. Case Rep Gastrointest Med 2020; 2020:7641476. [PMID: 31970002 PMCID: PMC6969991 DOI: 10.1155/2020/7641476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2019] [Revised: 08/01/2019] [Accepted: 08/13/2019] [Indexed: 11/19/2022] Open
Abstract
Most cases of chylous ascites occur after surgery, but it also develops in nonoperative cases, although rarely. Such cases are often difficult to treat. In this study, we treated 2 cases of atraumatic chylous ascites, which were controlled by combining diuretic treatment with an oral fat-free elemental diet (Elental®, EA Pharma Co., Ltd., Tokyo, Japan). Elental can provide oral nutrition compatible with a lipid-restricted diet, which may be useful for control of chylous ascites. We report on these cases, including literature review-based considerations.
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27
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Yerushalmy-Feler A, Assa A. Pharmacological Prevention and Management of Postoperative Relapse in Pediatric Crohn's Disease. Paediatr Drugs 2019; 21:451-460. [PMID: 31628665 DOI: 10.1007/s40272-019-00361-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Pediatric Crohn's disease (CD) is characterized by an aggressive course that commonly requires more intensive pharmacological and surgical treatments. In spite of the therapeutic advances in monitoring and management, including the widespread use of biologic therapy, the cumulative incidence of surgery in children with CD is still high. However, surgery is usually not curative and disease recurrence after small bowel resection is common. Gastrointestinal endoscopy is currently the gold standard to evaluate disease progression after surgery, but other non-invasive methods have been suggested. Although the efficacy of several drugs as medical prophylaxis to reduce the rate of disease recurrence following intestinal resection has been evaluated, selecting the most appropriate preventive therapeutic intervention remains a challenge. The current recommendations, mostly based on adult studies due to limited pediatric data, state that treatment should be guided by risk for recurrence. Low-risk patients may be given no prophylaxis or only 5-ASA. Maintenance enteral nutrition may also be considered. Thiopurines may be used in moderate risk of CD recurrence. In high risk patients for postoperative recurrence (extensive disease, short disease duration from diagnosis to surgery, recurrent surgery, long resected segment, surgery for fistulizing disease, disease complications, perianal disease, smoking), prophylactic treatment with anti-TNFα is recommended. subsequently, therapy should be guided by repeated measurement of objective measures including endoscopic re-evaluation at 6-12 months following surgery.
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Affiliation(s)
- Anat Yerushalmy-Feler
- Pediatric Gastroenterology Unit, 'Dana-Dwek' Children's Hospital, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel.,The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Amit Assa
- Institute of Gastroenterology, Nutrition and Liver Disease, Schneider Children's Medical Center of Israel, 14 Kaplan Street, 4920235, Petach-Tikva, Israel. .,The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
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28
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Comeche JM, Caballero P, Gutierrez-Hervas A, García-Sanjuan S, Comino I, Altavilla C, Tuells J. Enteral Nutrition in Patients with Inflammatory Bowel Disease. Systematic Review, Meta-Analysis, and Meta-Regression. Nutrients 2019; 11:nu11112657. [PMID: 31689999 PMCID: PMC6893586 DOI: 10.3390/nu11112657] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Revised: 10/23/2019] [Accepted: 10/25/2019] [Indexed: 02/07/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic disease mediated by the immune system and is characterized by inflammation of the gastrointestinal tract. One of the possible treatments for this pathology is a change in the type of diet, of which enteral nutrition (EN) is one. This study is to understand how the use of EN can affect the adult population diagnosed with IBD. We conducted a systematic review, meta-analysis, and a meta-regression. On the different databases (MEDLINE, Scopus, Cochrane, LILACS, CINAHL, WOS), we found 363 registers with an accuracy of 12% (44 registers). After a full-text review, only 30 research studies were selected for qualitative synthesis and 11 for meta-analysis and meta-regression. The variables used were Crohn's disease activity index (CDAI), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). EN has been shown to have efficacy for the treatment of Crohn's disease and is compatible with other medicines. As for the CDAI or rates of remission, there were no differences between enteral and parenteral nutrition. Polymeric formulas have shown better results with respect to the CRP. The long-term treatment could dilute the good CDAI results that are obtained at the start of the EN treatment.
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Affiliation(s)
- Jose M Comeche
- Department of Community Nursing, Preventive Medicine and Public Health and History of Science (SPAIN), University of Alicante, San Vicente del Raspeig, 03690 Alicante, Spain.
| | - Pablo Caballero
- Department of Community Nursing, Preventive Medicine and Public Health and History of Science (SPAIN), University of Alicante, San Vicente del Raspeig, 03690 Alicante, Spain.
| | - Ana Gutierrez-Hervas
- Department of Nursing (SPAIN), University of Alicante, San Vicente del Raspeig, 03690 Alicante, Spain.
| | - Sofia García-Sanjuan
- Department of Nursing (SPAIN), University of Alicante, San Vicente del Raspeig, 03690 Alicante, Spain.
| | - Iris Comino
- Department of Community Nursing, Preventive Medicine and Public Health and History of Science (SPAIN), University of Alicante, San Vicente del Raspeig, 03690 Alicante, Spain.
| | - Cesare Altavilla
- Department of Community Nursing, Preventive Medicine and Public Health and History of Science (SPAIN), University of Alicante, San Vicente del Raspeig, 03690 Alicante, Spain.
| | - Jose Tuells
- Department of Community Nursing, Preventive Medicine and Public Health and History of Science (SPAIN), University of Alicante, San Vicente del Raspeig, 03690 Alicante, Spain.
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29
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Di Caro S, Fragkos KC, Keetarut K, Koo HF, Sebepos-Rogers G, Saravanapavan H, Barragry J, Rogers J, Mehta SJ, Rahman F. Enteral Nutrition in Adult Crohn's Disease: Toward a Paradigm Shift. Nutrients 2019; 11:E2222. [PMID: 31540038 PMCID: PMC6770416 DOI: 10.3390/nu11092222] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Revised: 09/05/2019] [Accepted: 09/08/2019] [Indexed: 02/06/2023] Open
Abstract
Medical and surgical treatments for Crohn's disease are associated with toxic effects. Medical therapy aims for mucosal healing and is achievable with biologics, immunosuppressive therapy, and specialised enteral nutrition, but not with corticosteroids. Sustained remission remains a therapeutic challenge. Enteral nutrition, containing macro- and micro-nutrients, is nutritionally complete, and is provided in powder or liquid form. Enteral nutrition is a low-risk and minimally invasive therapy. It is well-established and recommended as first line induction therapy in paediatric Crohn's disease with remission rates of up to 80%. Other than in Japan, enteral nutrition is not routinely used in the adult population among Western countries, mainly due to unpalatable formulations which lead to poor compliance. This study aims to offer a comprehensive review of available enteral nutrition formulations and the literature supporting the use and mechanisms of action of enteral nutrition in adult Crohn's disease patients, in order to support clinicians in real world decision-making when offering/accepting treatment. The mechanisms of actions of enteral feed, including their impact on the gut microbiome, were explored. Barriers to the use of enteral nutrition, such as compliance and the route of administration, were considered. All available enteral preparations have been comprehensively described as a practical guide for clinical use. Likewise, guidelines are reported and discussed.
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Affiliation(s)
- Simona Di Caro
- Intestinal Failure Service, GI Services, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PG, UK.
| | - Konstantinos C Fragkos
- Intestinal Failure Service, GI Services, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PG, UK.
| | - Katie Keetarut
- Department of Dietetics, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PG, UK.
| | - Hui Fen Koo
- UCL Medical School, 74 Huntley Street, Bloomsbury, London WC1E 6DE, UK.
| | - Gregory Sebepos-Rogers
- Intestinal Failure Service, GI Services, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PG, UK.
| | - Hajeena Saravanapavan
- Intestinal Failure Service, GI Services, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PG, UK.
| | - John Barragry
- Intestinal Failure Service, GI Services, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PG, UK.
| | - Jennifer Rogers
- Intestinal Failure Service, GI Services, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PG, UK.
| | - Shameer J Mehta
- Intestinal Failure Service, GI Services, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PG, UK.
| | - Farooq Rahman
- Intestinal Failure Service, GI Services, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PG, UK.
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30
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Logan M, Clark CM, Ijaz UZ, Gervais L, Duncan H, Garrick V, Curtis L, Buchanan E, Cardigan T, Armstrong L, Delahunty C, Flynn DM, Barclay AR, Tayler R, McDonald E, Milling S, Hansen RK, Gerasimidis K, Russell RK. The reduction of faecal calprotectin during exclusive enteral nutrition is lost rapidly after food re-introduction. Aliment Pharmacol Ther 2019; 50:664-674. [PMID: 31342536 PMCID: PMC6772069 DOI: 10.1111/apt.15425] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Revised: 06/10/2019] [Accepted: 06/27/2019] [Indexed: 12/18/2022]
Abstract
BACKGROUND Faecal calprotectin decreases during exclusive enteral nutrition in children with active Crohn's disease. It is unknown how faecal calprotectin changes during food re-introduction and the influence of maintenance enteral nutrition. AIMS To study changes to faecal calprotectin during exclusive enteral nutrition and at food reintroduction, and explore associations with maintenance enteral nutrition. METHODS Children with Crohn's disease were followed during exclusive enteral nutrition and during food-reintroduction. Faecal calprotectin was measured before, at 33 and 54 days of exclusive enteral nutrition, and at 17, 52 and 72 days after food-reintroduction. Maintenance enteral nutrition use was recorded with estimated weight food diaries. Data are presented with medians and Q1:Q3. RESULTS Sixty-six patients started exclusive enteral nutrition and 41 (62%) achieved clinical remission (weighted paediatric Crohn's disease activity index <12.5). Baseline faecal calprotectin (mg/kg) decreased after 4 and 8 weeks of exclusive enteral nutrition (Start: 1433 [Q1: 946, Q3: 1820] vs 33 days: 844 [314, 1438] vs 54 days: 453 [165, 1100]; P < .001). Within 17 days of food reintroduction, faecal calprotectin increased to 953 [Q1: 519, Q3: 1611] and by 52 days to 1094 [660, 1625] (both P < .02). Fifteen of 41 (37%) children in remission used maintenance enteral nutrition (333 kcal or 18% of energy intake). At 17 days of food reintroduction, faecal calprotectin was lower in maintenance enteral nutrition users than non-users (651 [Q1: 271, Q3: 1781] vs 1238 [749, 2102], P = .049) and correlated inversely with maintenance enteral nutrition volume (rho: -0.573, P = .041), kcals (rho: -0.584, P = .036) and % energy intake (rho: -0.649, P = .016). Maintenance enteral nutrition use was not associated with longer periods of remission (P = .7). Faecal calprotectin at the end of exclusive enteral nutrition did not predict length of remission. CONCLUSIONS The effect of exclusive enteral nutrition on faecal calprotectin is diminished early during food reintroduction. Maintenance enteral nutrition at ~18% of energy intake is associated with a lower faecal calprotectin at the early phase of food reintroduction but is ineffective in maintaining longer term remission.
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Affiliation(s)
- Michael Logan
- Civil Engineering, School of EngineeringUniversity of GlasgowGlasgowUK,Human Nutrition, School of Medicine, Dentistry and NursingUniversity of Glasgow, Glasgow Royal InfirmaryGlasgowUK
| | - Clare M. Clark
- Human Nutrition, School of Medicine, Dentistry and NursingUniversity of Glasgow, Glasgow Royal InfirmaryGlasgowUK
| | - Umer Zeeshan Ijaz
- Civil Engineering, School of EngineeringUniversity of GlasgowGlasgowUK
| | - Lisa Gervais
- Department of Paediatric GastroenterologyRoyal Hospital for ChildrenGlasgowUK
| | - Hazel Duncan
- Department of Paediatric GastroenterologyRoyal Hospital for ChildrenGlasgowUK
| | - Vikki Garrick
- Department of Paediatric GastroenterologyRoyal Hospital for ChildrenGlasgowUK
| | - Lee Curtis
- Department of Paediatric GastroenterologyRoyal Hospital for ChildrenGlasgowUK
| | - Elaine Buchanan
- Department of Paediatric GastroenterologyRoyal Hospital for ChildrenGlasgowUK
| | - Tracey Cardigan
- Department of Paediatric GastroenterologyRoyal Hospital for ChildrenGlasgowUK
| | | | | | - Diana M. Flynn
- Department of Paediatric GastroenterologyRoyal Hospital for ChildrenGlasgowUK
| | - Andrew R. Barclay
- Department of Paediatric GastroenterologyRoyal Hospital for ChildrenGlasgowUK
| | - Rachel Tayler
- Department of Paediatric GastroenterologyRoyal Hospital for ChildrenGlasgowUK
| | - Elizabeth McDonald
- Institute for Infection, Immunity and InflammationUniversity of GlasgowGlasgowUK
| | - Simon Milling
- Institute for Infection, Immunity and InflammationUniversity of GlasgowGlasgowUK
| | - Richard K. Hansen
- Department of Paediatric GastroenterologyRoyal Hospital for ChildrenGlasgowUK
| | - Konstantinos Gerasimidis
- Human Nutrition, School of Medicine, Dentistry and NursingUniversity of Glasgow, Glasgow Royal InfirmaryGlasgowUK
| | - Richard K. Russell
- Department of Paediatric GastroenterologyRoyal Hospital for ChildrenGlasgowUK
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31
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Sáez-González E, Mateos B, López-Muñoz P, Iborra M, Moret I, Nos P, Beltrán B. Bases for the Adequate Development of Nutritional Recommendations for Patients with Inflammatory Bowel Disease. Nutrients 2019; 11:E1062. [PMID: 31083616 PMCID: PMC6567870 DOI: 10.3390/nu11051062] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Revised: 05/07/2019] [Accepted: 05/10/2019] [Indexed: 12/13/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory condition of the gastrointestinal tract; it is a heterogeneous and multifactorial disorder resulting from a complex interplay between genetic variation, intestinal microbiota, the host immune system and environmental factors such as diet, drugs, breastfeeding and smoking. The interactions between dietary nutrients and intestinal immunity are complex. There is a compelling argument for environmental factors such as diet playing a role in the cause and course of IBD, given that three important factors in the pathogenesis of IBD can be modulated and controlled by diet: intestinal microbiota, the immune system and epithelial barrier function. The aim of this review is to summarize the epidemiological findings regarding diet and to focus on the effects that nutrients exert on the intestinal mucosa-microbiota-permeability interaction. The nature of these interactions in IBD is influenced by alterations in the nutritional metabolism of the gut microbiota and host cells that can influence the outcome of nutritional intervention. A better understanding of diet-host-microbiota interactions is essential for unravelling the complex molecular basis of epigenetic, genetic and environmental interactions underlying IBD pathogenesis as well as for offering new therapeutic approaches for the treatment of IBD.
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Affiliation(s)
- Esteban Sáez-González
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, 46026 Valencia, Spain.
- Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), 46026 Valencia, Spain.
| | - Beatriz Mateos
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, 46026 Valencia, Spain.
- Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), 46026 Valencia, Spain.
| | - Pedro López-Muñoz
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, 46026 Valencia, Spain.
| | - Marisa Iborra
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, 46026 Valencia, Spain.
- Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), 46026 Valencia, Spain.
- Biomedical Research Network Center for Liver and Digestive Diseases (CIBEREHD), 28029 Madrid, Spain.
| | - Inés Moret
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, 46026 Valencia, Spain.
- Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), 46026 Valencia, Spain.
- Biomedical Research Network Center for Liver and Digestive Diseases (CIBEREHD), 28029 Madrid, Spain.
| | - Pilar Nos
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, 46026 Valencia, Spain.
- Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), 46026 Valencia, Spain.
- Biomedical Research Network Center for Liver and Digestive Diseases (CIBEREHD), 28029 Madrid, Spain.
| | - Belén Beltrán
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, 46026 Valencia, Spain.
- Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), 46026 Valencia, Spain.
- Biomedical Research Network Center for Liver and Digestive Diseases (CIBEREHD), 28029 Madrid, Spain.
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Ogasawara H, Hayasaka M, Maemoto A, Furukawa S, Ito T, Kimura O, Endo T. Stable isotope ratios of carbon, nitrogen and selenium concentration in the scalp hair of Crohn's disease patients who ingested the elemental diet Elental ®. RAPID COMMUNICATIONS IN MASS SPECTROMETRY : RCM 2019; 33:41-48. [PMID: 30280438 DOI: 10.1002/rcm.8296] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/07/2018] [Revised: 09/14/2018] [Accepted: 09/15/2018] [Indexed: 06/08/2023]
Abstract
RATIONALE Elental® is an elemental diet widely used as a nutritional supplement for Crohn's disease (CD) patients in Japan. Elental® contains amino acids as nitrogen sources and does not contain selenium (Se), and the δ13 C and δ15 N values of Elental® are markedly higher and lower, respectively, than those of a normal diet. METHODS We compared the δ13 C and δ15 N values and Se concentration in the scalp hair of CD patients with those of control subjects who ate a regular diet, and estimated the amount of Elental® ingested as a supplement. The δ13 C and δ15 N values and the Se concentrations were quantified using isotope ratio mass spectrometry (IRMS) and inductively coupled plasma mass spectrometry (ICP-MS), respectively. RESULTS An increase in Elental® ingestion increased the δ13 C value in the hair of CD patients (p <0.05), while it reduced the δ15 N value (p <0.05) and tended to reduce the Se concentration in female patients. CONCLUSIONS The amount of Elental® ingested could be estimated by the δ13 C and δ15 N values in the hair of CD patients. Furthermore, the Se deficiency in female patients may be predicted from the δ13 C and δ15 N values.
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Affiliation(s)
- Hideki Ogasawara
- Kashiwaba Neurosurgical Hospital, E1-15-20, Tsukisamu, Toyohira-Ku, Sapporo, Hokkaido, 062-8513, Japan
| | - Moriaki Hayasaka
- Sapporo Higashi Tokushukai Hospital, N33-E14, Higashi-Ku, Sapporo, Hokkaido, 065-0033, Japan
| | - Atsuo Maemoto
- Sapporo Higashi Tokushukai Hospital, N33-E14, Higashi-Ku, Sapporo, Hokkaido, 065-0033, Japan
| | - Shigeru Furukawa
- Sapporo Higashi Tokushukai Hospital, N33-E14, Higashi-Ku, Sapporo, Hokkaido, 065-0033, Japan
| | - Takahiro Ito
- Sapporo Higashi Tokushukai Hospital, N33-E14, Higashi-Ku, Sapporo, Hokkaido, 065-0033, Japan
| | - Osamu Kimura
- School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 1757, Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan
| | - Tetsuya Endo
- School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 1757, Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan
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Day AS. Exclusive Enteral Nutrition in Children With Crohn’s Disease. DIETARY INTERVENTIONS IN GASTROINTESTINAL DISEASES 2019:107-116. [DOI: 10.1016/b978-0-12-814468-8.00009-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Xu Y, Guo Z, Cao L, Xie T, Shen W, Li Y, Gong J, Zhu W. Isolated colonic Crohn's disease is associated with a reduced response to exclusive enteral nutrition compared to ileal or ileocolonic disease. Clin Nutr 2018; 38:1629-1635. [PMID: 30193873 DOI: 10.1016/j.clnu.2018.08.022] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2018] [Revised: 08/12/2018] [Accepted: 08/17/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Exclusive enteral nutrition (EEN) as a primary therapy is safe and effective for inducing the clinical remission of active luminal Crohn's disease (CD). Whether isolated colonic involvement affects the efficacy of EEN is controversial. We aimed to identify the influence of isolated colonic CD on the efficacy of EEN and to determine other potential predictors of the response to induction therapy with EEN in adult patients with CD. METHODS Data for adult CD patients treated with EEN as an induction therapy at our centre from January 1, 2014, to May 31, 2017, were reviewed. Eligible patients were divided into an isolated colonic Crohn's disease (cCD) group and a non-isolated colonic Crohn's disease (non-cCD) group according to the disease location. The rates of clinical remission and inflammatory and nutritional serum markers were compared between the groups. Possible relationships between isolated colonic involvement or other potential factors and the efficacy of EEN were assessed by univariate and multivariate analyses. The propensity score matching method was used to confirm the results. RESULTS Overall, 241 patients were included in the analysis: 52 patients in the cCD group and 189 patients in the non-cCD group. The rates of clinical remission differed between the two groups (cCD group: 51.9% versus non-cCD group: 68.3%, P = 0.029). Multivariate analyses indicated that isolated colonic involvement was associated with a reduced response to EEN (OR = 2.74; [CI] 95% = [1.2-6.23], P = 0.016). Additionally, the lean body mass index (LBMI) before treatment was associated with the efficacy of EEN (OR = 0.636; [CI] 95% = [0.444-0.912], P = 0.014). These associations were confirmed using the propensity score model. For patients with isolated colonic CD, multivariate analysis showed that pancolitis (OR = 16.7; [CI] 95% = [1.074-260.5], P = 0.044) was another independent factor for the efficacy of EEN. Further analysis showed that even in patients who achieved clinical remission after EEN, inflammatory serum markers declined more slowly in the cCD group than in the non-cCD group, and the time to remission was longer in the cCD group. CONCLUSIONS Isolated colonic CD showed a reduced response to induction therapy with EEN compared with ileal or ileocolonic disease in adult patients. Patients with isolated colonic CD required more time to benefit from EEN therapy compared with patients with non-colonic CD. Additionally, LBMI before treatment was associated with the efficacy of EEN.
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Affiliation(s)
- Yihan Xu
- Research Institute of General Surgery, Jinling Hospital, Nanjing, China; Nanjing Medical University, Nanjing, China
| | - Zhen Guo
- Research Institute of General Surgery, Jinling Hospital, Nanjing, China
| | - Lei Cao
- Research Institute of General Surgery, Jinling Hospital, Nanjing, China
| | - Tingbin Xie
- Research Institute of General Surgery, Jinling Hospital, Nanjing, China
| | - Weisong Shen
- Research Institute of General Surgery, Jinling Hospital, Nanjing, China
| | - Yi Li
- Research Institute of General Surgery, Jinling Hospital, Nanjing, China
| | - Jianfeng Gong
- Research Institute of General Surgery, Jinling Hospital, Nanjing, China
| | - Weiming Zhu
- Research Institute of General Surgery, Jinling Hospital, Nanjing, China.
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Akobeng AK, Zhang D, Gordon M, MacDonald JK. Enteral nutrition for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev 2018; 8:CD005984. [PMID: 30098021 PMCID: PMC6513617 DOI: 10.1002/14651858.cd005984.pub3] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Prevention of relapse is a major issue in the management of quiescent Crohn's disease (CD). Current therapies (e.g. methotrexate, biologics, 6-mercaptopurine and azathioprine) may be effective for maintaining remission in CD, but these drugs may cause significant adverse events. Interventions that are effective and safe for maintenance of remission in CD are desirable. OBJECTIVES The primary objectives were to evaluate the efficacy and safety of enteral nutrition for the maintenance of remission in CD and to assess the impact of formula composition on effectiveness. SEARCH METHODS We searched MEDLINE, Embase, CENTRAL, the Cochrane IBD Group Specialized Register and clinicaltrials.gov from inception to 27 July 2018. We also searched references of retrieved studies and reviews. SELECTION CRITERIA Randomised controlled trials (RCTs) including participants of any age with quiescent CD were considered for inclusion. Studies that compared enteral nutrition with no intervention, placebo or any other intervention were selected for review. DATA COLLECTION AND ANALYSIS Two authors independently screened studies for inclusion, extracted data and assessed methodological quality using the Cochrane risk of bias tool. The primary outcome was clinical or endoscopic relapse as defined by the primary studies. Secondary outcomes included anthropometric measures (i.e. height and weight), quality of life (QoL), adverse events, serious adverse events and withdrawal due to adverse events. We calculated the risk ratio and 95% confidence interval (CI) for dichotomous outcomes. For continuous outcomes, we calculated the mean difference and 95% CI. A random-effects model was used for the statistical analysis. We used the GRADE criteria to assess the overall certainty of the evidence supporting the primary outcome and selected secondary outcomes. MAIN RESULTS Four RCTs (262 adult participants) met the inclusion criteria. One study (N = 33) compared an elemental diet to a non-elemental (polymeric) diet. One study (N = 51) compared a half elemental diet to a regular free diet. Another study (N = 95) compared an elemental diet to 6-mercaptopurine (6-MP) or a no treatment control group. One study (N= 83) compared a polymeric diet to mesalamine. Two studies were rated as high risk of bias due to lack of blinding or incomplete outcome data. The other two studies were judged to have an unclear risk of bias. The studies were not pooled due to differences in control interventions and the way outcomes were assessed.The effect of an elemental diet compared to a polymeric diet on remission rates or withdrawal due to adverse events is uncertain. Fifty-eight per cent (11/19) of participants in the elemental diet group relapsed at 12 months compared to 57% (8/14) of participants in the polymeric diet group (RR 1.01, 95% CI 0.56 to 1.84; very low certainty evidence). Thirty-two per cent (6/19) of participants in the elemental diet group were intolerant to the enteral nutritional formula because of taste or smell and were withdrawn from the study in the first 2 weeks compared to zero participants (0/14) in the polymeric diet group (RR 9.75, 95% CI 0.59 to 159.93; low certainty evidence). Anthropometric measures, QoL, adverse events and serious adverse events were not reported as outcomes.The effect of an elemental diet (half of total daily calorie requirements) compared to a normal free diet on relapse rates is uncertain. Thirty-five per cent (9/26) of participants in the elemental diet group relapsed at 12 months compared to 64% (16/25) of participants in the free diet group (RR 0.54, 95% CI 0.30 to 0.99; very low certainty evidence). No adverse events were reported. This study reported no differences in weight change between the two diet groups. Height and QoL were not reported as outcomes.The effect of an elemental diet compared to 6-MP on relapse rates or adverse events is uncertain. Thirty-eight per cent (12/32) of participants in the elemental diet group relapsed at 12 months compared to 23% (7/30) of participants in the 6-MP group (RR 1.61; 95% CI 0.73 to 3.53; very low certainty evidence). Three per cent (1/32) of participants in the elemental diet group had an adverse event compared to 13% (4/30) of participants in the 6-MP group (RR 0.23, 95% CI 0.03 to 1.98; low certainty evidence). Adverse events in the elemental diet group included surgery due to worsening CD. Adverse events in the 6-MP group included liver injury (n = 2), hair loss (n = 1) and surgery due to an abscess (n = 1). No serious adverse events or withdrawals due to adverse events were reported. Weight, height and QoL were not reported as outcomesThe effect of a polymeric diet compared to mesalamine on relapse rates and weight is uncertain. Forty-two per cent (18/43) of participants in the polymeric diet group relapsed at 6 months compared to 55% (22/40) of participants in the mesalamine group (RR 0.76; 95% CI 0.49 to 1.19; low certainty evidence). The mean difference in weight gain over the study period was 1.9 kg higher in the polymeric diet group compared to mesalamine (95% CI -4.62 to 8.42; low certainty evidence). Two participants in the polymeric diet group experienced nausea and four had diarrhoea. It is unclear if any participants in the mesalamine group had an adverse event. Height, QoL, serious adverse events and withdrawal due to adverse events were not reported as outcomes. AUTHORS' CONCLUSIONS The results for the outcomes assessed in this review are uncertain and no firm conclusions regarding the efficacy and safety of enteral nutrition in quiescent CD can be drawn. More research is needed to determine the efficacy and safety of using enteral nutrition as maintenance therapy in CD. Currently, there are four ongoing studies (estimated enrolment of 280 participants). This review will be updated when the results of these studies are available.
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Affiliation(s)
| | - Dongni Zhang
- University of Western OntarioSchulich School of Medicine & DentistryLondonONCanada
| | - Morris Gordon
- University of Central LancashireSchool of MedicinePrestonLancashireUK
| | - John K MacDonald
- Robarts Clinical TrialsCochrane IBD Group100 Dundas Street, Suite 200LondonONCanadaN6A 5B6
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Araki T, Okita Y, Kondo S, Hiro J, Toiyama Y, Inoue M, Ohi M, Inoue Y, Uchida K, Mohri Y, Kusunoki M. Risk factors for recurrence of Crohn's disease requiring surgery in patients receiving post-operative anti-tumor necrosis factor maintenance therapy. JOURNAL OF THE ANUS RECTUM AND COLON 2018; 1:15-21. [PMID: 31583295 PMCID: PMC6768679 DOI: 10.23922/jarc.2016-004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/31/2016] [Accepted: 12/28/2016] [Indexed: 12/22/2022]
Abstract
OBJECTIVES Anti-tumor necrosis factor (TNF) antibodies have shown efficacy in the prevention of recurrence of Crohn's disease after intestinal resection. However, some patients develop surgical recurrence despite this therapy. We aimed to evaluate the risk factors for recurrence of Crohn's disease requiring surgery while receiving post-operative anti-TNF therapy. METHODS We performed a retrospective evaluation of 164 patients who had received post-operative anti-TNF maintenance therapy between 2002 and 2016. We classified Crohn's disease-related re-operation as surgical recurrence and analyzed its risk factors using the Cox proportional hazard model. RESULTS Of the 164 participants, 128 had received infliximab and 36 had received adalimumab maintenance therapy. We obtained follow-up data over a mean of 60.2 months. The proportion of patients with surgical recurrence at 5 years was 14.9%. The only independent risk factor for surgical recurrence, which we identified was post-operative smoking habit (odds ratio, 5.03; 95% CI, 1.14-12.8; P=0.033). CONCLUSIONS Post-operative smoking may be a significant risk factor for post-operative surgical recurrence of Crohn's disease while receiving anti-TNF maintenance therapy.
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Affiliation(s)
- Toshimitsu Araki
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan
| | - Yoshiki Okita
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan
| | - Satoru Kondo
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan
| | - Junichiro Hiro
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan
| | - Yuji Toiyama
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan
| | - Mikihiro Inoue
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan
| | - Masaki Ohi
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan
| | - Yasuhiro Inoue
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan
| | - Keiichi Uchida
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan
| | - Yasuhiko Mohri
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan
| | - Masato Kusunoki
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan
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Sugita N, Watanabe K, Kamata N, Yukawa T, Otani K, Hosomi S, Nagami Y, Tanaka F, Taira K, Yamagami H, Tanigawa T, Shiba M, Watanabe T, Tominaga K, Kabata D, Shintani A, Arakawa T, Fujiwara Y. Efficacy of a concomitant elemental diet to reduce the loss of response to adalimumab in patients with intractable Crohn's disease. J Gastroenterol Hepatol 2018; 33:631-637. [PMID: 28857255 DOI: 10.1111/jgh.13969] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2017] [Revised: 08/24/2017] [Accepted: 08/27/2017] [Indexed: 12/27/2022]
Abstract
BACKGROUND AND AIM Secondary loss of response to adalimumab (ADA-LOR) commonly occurs in patients with Crohn's disease (CD) treated with adalimumab (ADA). We evaluated the efficacy of concomitant elemental diet (ED) therapy to reduce ADA-LOR in adult CD patients. METHODS Patients were divided into either an ED (≥900 kcal/day) or a non-ED group (<900 kcal/day). Cumulative non-ADA-LOR rates were compared between groups. The effects of ED intake to reduce ADA-LOR were also assessed in antitumor necrosis factor-alpha (TNF-α)-naïve and infliximab (IFX)-intolerant or refractory CD patients. Serum ADA and TNF-α levels were measured. RESULTS We enrolled 117 CD patients into the ED (n = 25) or non-ED (n = 92) groups. Although the cumulative non-ADA-LOR rate was higher in the ED group than in the non-ED group, ED intake was not an independent reducing factor for ADA-LOR (adjusted hazard ratio = 0.725; 95% confidence interval: 0.448-1.180; P = 0.196) in all patients. ED intake was significantly more effective in reducing ADA-LOR in IFX-intolerant or refractory patients than in anti-TNF-α-naïve patients in a dose-related manner (P for interaction <0.20). Serum ADA levels did not differ between the groups. Serum TNF-α levels were significantly lower in the ED group than in the non-ED group at week 28 (P = 0.044) and week 52 (P = 0.043). CONCLUSIONS Concomitant ED therapy reduced ADA-LOR in IFX-intolerant or refractory patients in a dose-related manner. Reductions in the TNF-α levels by concomitant ED intake may contribute to reduce ADA-LOR in CD patients.
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Affiliation(s)
- Naoko Sugita
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Kenji Watanabe
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.,Department of Intestinal Inflammation Research, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Noriko Kamata
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Tomomi Yukawa
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Koji Otani
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Shuhei Hosomi
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Yasuaki Nagami
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Fumio Tanaka
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Koichi Taira
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Hirokazu Yamagami
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Tetsuya Tanigawa
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Masatsugu Shiba
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Toshio Watanabe
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Kazunari Tominaga
- Premier Developmental Research of Medicine, Osaka Medical College, Osaka, Japan
| | - Daijiro Kabata
- Department of Medical Statistics, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Ayumi Shintani
- Department of Medical Statistics, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Tetsuo Arakawa
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Yasuhiro Fujiwara
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
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Alhagamhmad MH. Enteral Nutrition in the Management of Crohn's Disease: Reviewing Mechanisms of Actions and Highlighting Potential Venues for Enhancing the Efficacy. Nutr Clin Pract 2018; 33:483-492. [PMID: 29323428 DOI: 10.1002/ncp.10004] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2017] [Revised: 09/12/2017] [Accepted: 10/10/2017] [Indexed: 12/16/2022] Open
Abstract
Crohn's disease (CD) is a chronic condition that affects the gut and has adverse effects on growth and development. There is a global increase in the incidence and prevalence rates, and several factors are believed to contribute to this rise, including dietary habits. In contrast, the use of enteral nutrition (EN) as an exclusive source of nutrition is increasingly becoming the preferred induction treatment of pediatric CD patients in part to address the nutrition complications. However, EN therapy is considered less effective in adults with CD. A better understanding of the molecular mechanisms of enteral therapy will help improve the clinical management of CD. It is increasingly becoming evident that the therapeutic utility of EN is in part due to the reversal of the microbial changes and the direct immunomodulatory effects. Moreover, there is a potential tendency for enhancing the efficacy of EN therapy by improving the palatability of the given formulas and, more important, by magnifying the anti-inflammatory properties. Recent observations have shown that the immunomodulatory effects of EN are mediated at least in part by blocking nuclear factor-κB. Furthermore, it is likely that several ingredients of EN contribute to this activity, in particular glutamine and arginine amino acids. In addition, manipulating the composition of EN therapy by altering concentrations of the key ingredients is found to have the potential for more efficient therapy. In this review, the underlying mechanisms of EN actions will be discussed further with a focus on the potential methods for enhancing the efficacy.
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Affiliation(s)
- Moftah H Alhagamhmad
- Faculty of Medicine, University of Benghazi (Al-Arab Medical University), Benghazi, Libya
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Sigall-Boneh R, Levine A, Lomer M, Wierdsma N, Allan P, Fiorino G, Gatti S, Jonkers D, Kierkus J, Katsanos KH, Melgar S, Yuksel ES, Whelan K, Wine E, Gerasimidis K. Research Gaps in Diet and Nutrition in Inflammatory Bowel Disease. A Topical Review by D-ECCO Working Group [Dietitians of ECCO]. J Crohns Colitis 2017; 11:1407-1419. [PMID: 28961811 DOI: 10.1093/ecco-jcc/jjx109] [Citation(s) in RCA: 70] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2017] [Accepted: 08/04/2017] [Indexed: 02/06/2023]
Abstract
Although the current doctrine of IBD pathogenesis proposes an interaction between environmental factors and gut microbiota in genetically susceptible individuals, dietary exposures have attracted recent interest and are, at least in part, likely to explain the rapid rise in disease incidence and prevalence. The D-ECCO working group along with other ECCO experts with expertise in nutrition, microbiology, physiology, and medicine reviewed the evidence investigating the role of diet and nutritional therapy in the onset, perpetuation, and management of IBD. A narrative topical review is presented where evidence pertinent to the topic is summarised collectively under three main thematic domains: i] the role of diet as an environmental factor in IBD aetiology; ii] the role of diet as induction and maintenance therapy in IBD; and iii] assessment of nutritional status and supportive nutritional therapy in IBD. A summary of research gaps for each of these thematic domains is proposed, which is anticipated to be agenda-setting for future research in the area of diet and nutrition in IBD.
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Affiliation(s)
- Rotem Sigall-Boneh
- PIBD Research Center, Pediatric Gastroenterology and Nutrition Unit, Edith Wolfson Medical Center, Israel
| | - Arie Levine
- Paediatric Gastroenterology & Nutrition Unit, Wolfson Medical Center, Tel Aviv University, Israel
| | - Miranda Lomer
- Department of Nutrition and Dietetics, Guy's and St Thomas' NHS Foundation Trust and King's College London, UK
| | - Nicolette Wierdsma
- Department of Nutrition and Dietetics, VU University Medical Centre, The Netherlands
| | - Philip Allan
- Department of Translational Gastroenterology, John Radcliffe Hospital, UK
| | - Gionata Fiorino
- Department of Gastroenterology, IBD Center, Humanitas Research Hospital, Italy
| | - Simona Gatti
- Department of Paediatrics, Polytechnic University of Marche, Italy
| | - Daisy Jonkers
- Division Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School for Nutrition and Translational Research in Metabolism, The Netherlands
| | - Jaroslaw Kierkus
- Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, Children's Memorial Health Institute, Poland
| | - Konstantinos H Katsanos
- Department of Gastroenterology and Hepatology, University and Medical School of Ioannina, Greece
| | - Silvia Melgar
- APC Microbiome Institute, University College Cork, Ireland
| | - Elif Saritas Yuksel
- Department of Gastroenterology, Izmir Katip Celebi University Ataturk Teaching and Research Hospital, Turkey
| | - Kevin Whelan
- King's College London, Division of Diabetes and Nutritional Sciences, UK
| | - Eytan Wine
- Division of Paediatric Gastroenterology and Nutrition, Departments of Paediatrics and Physiology, University of Alberta, Canada
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Impact of Preoperative Exclusive Enteral Nutrition on Postoperative Complications and Recurrence After Bowel Resection in Patients with Active Crohn's Disease. World J Surg 2017; 40:1993-2000. [PMID: 26940580 DOI: 10.1007/s00268-016-3488-z] [Citation(s) in RCA: 52] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND The impact of preoperative enteral nutrition (EN) on postoperative complications and recurrence in Crohn's disease (CD) has not been investigated to date. The purpose of the present study was to determine the effect of preoperative exclusive EN on postoperative complications and recurrence after bowel resection in patients with active CD. METHODS Patient data were obtained from a prospectively maintained database. 81 patients who received bowel resection for ileal or ileocolonic CD were studied. Before operation, 42 CD patients received exclusive EN for 4 weeks, and the other patients had no nutritional therapy. All patients were followed up regularly for 2 years after surgery, and ileocolonoscopy was performed every 6 months after bowel resection. RESULTS Patients receiving exclusive EN had a dramatic improvement of nutritional (BMI, albumin, pre-albumin, and Hb) and inflammatory (CRP and CDAI) status compared with baseline after the EN therapy for 4 weeks (P < 0.05). Furthermore, significantly lower incidence of both infectious and non-infectious complications was observed in patients receiving exclusive EN compared with those received no nutritional therapy (P < 0.05). Exclusive EN therapy for 4 weeks significantly reduced endoscopic recurrence rates after resection for CD 6 months after operation. However, during the 2-year follow-up, incidence of clinical recurrence was similar in both groups (P > 0.05). CONCLUSIONS Preoperative exclusive EN therapy for 4 weeks reduced postoperative complications, which may be associated with improvement of nutritional and inflammatory status in patients with active CD.
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Abstract
Pediatric Crohn disease is characterized by clinical and endoscopic relapses. The inflammatory process is considered to be progressive and may lead to strictures, fistulas, and penetrating disease that may require surgery. In addition, medically refractory disease may be treated by surgical resection of inflamed bowel in an effort to reverse growth failure. The need for surgery in childhood suggests severe disease and these patients have an increased risk for recurrent disease and potentially more surgery. Data show that up to 55% of patients had clinical recurrence in the first 2 years after initial surgery. The current clinical report on postoperative recurrence in pediatric Crohn disease reviews the risk factors for early surgery and postoperative recurrence, operative risk factors for recurrence, and prevention and monitoring strategies for postoperative recurrence. We also propose an algorithm for postoperative management in pediatric Crohn disease.
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Harada K, Ferdous T, Kobayashi H, Ueyama Y. Elemental Diet Accelerates the Recovery From Oral Mucositis and Dermatitis Induced by 5-Fluorouracil Through the Induction of Fibroblast Growth Factor 2. Integr Cancer Ther 2017; 17:423-430. [PMID: 28745083 PMCID: PMC6041898 DOI: 10.1177/1534735417721014] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
Mucositis and dermatitis induced by anticancer agents are common complications of anticancer therapies. In this study, we evaluated the efficacy of Elental (Ajinomoto Pharmaceutical Ltd, Tokyo, Japan), an elemental diet with glutamine in the treatment of 5-fluorouracil (5-FU)-induced oral mucositis and dermatitis in vivo and tried to clarify the underlying mechanisms of its action. Oral mucositis and dermatitis was induced through a combination of 5-FU treatment and mild abrasion of the cheek pouch in hamsters and the dorsal skin in nude mice respectively. These animals received saline, dextrin or Elental suspension (18 kcal/100 g) by a gastric tube daily until sacrifice. Elental reduced oral mucositis and dermatitis more effectively than dextrin in the animal model. Moreover, growth facilitating effects of Elental on HaCaT cells were examined in vitro. MTT assay, wound healing assay, and migration assay revealed that Elental could enhance the growth, invasion, and migration ability of HaCaT. ELISA and Western blotting showed upregulated FGF2 in Elental-treated HaCaT. These findings suggest that Elental is effective for the treatment of mucositis and dermatitis, and may accelerate mucosal and skin recovery through FGF2 induction and reepithelization.
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Affiliation(s)
- Koji Harada
- 1 Yamaguchi University Graduate School of Medicine, Ube, Japan
| | | | | | - Yoshiya Ueyama
- 1 Yamaguchi University Graduate School of Medicine, Ube, Japan
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Elental® amino acid component has protective effects on primary cultured hepatocytes and a rat model of acute liver injury. Nutr Res 2017. [PMID: 28633873 DOI: 10.1016/j.nutres.2017.04.010] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Amino acids can exert protective effects on the liver either when administered as a medication or following an operation. In this study, we examined the protective effects of amino acids on the liver using in vitro and in vivo models by studying their influence on the induction of inducible nitric oxide synthase (iNOS) and nitric oxide production as a liver injury marker in cultured hepatocytes and liver-protective effects in d-galactosamine and lipopolysaccharide (GalN/LPS)-treated rats, respectively. Primary cultured rat hepatocytes were treated with interleukin (IL)-1β in the presence or absence of Elental® amino acid component (EleAA; 17 amino acids). Rats were pretreated with either EleAA or a diet containing selected amino acids followed by GalN/LPS injection. Survival rate and mRNA expression were analyzed. EleAA inhibited iNOS induction through reduction of mRNA synthesis and stability in cultured hepatocytes, indicating prevention of liver injury, but did not show a liver-protective effect in GalN/LPS rats. Among EleAA, Lys, Trp, His, and Arg (4AA) markedly decreased nitric oxide production and inhibited nuclear factor-κB (NF-κB) activation. In GalN/LPS rats, 4AA (3% of each amino acid in diet) increased survival rate by 50% and decreased mRNA expression of iNOS, tumor necrosis factor-α, and cytokine-induced neutrophil chemoattractant-1 in the liver. 4AA reduced NF-κB activation induced by GalN/LPS. 4AA inhibited the expression of inflammatory mediators, in part through inhibition of NF-κB activation in cultured hepatocytes and GalN/LPS-treated rats. The results suggest that EleAA has therapeutic potential for organ injuries including liver.
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Ohara N, Mizushima T, Iijima H, Takahashi H, Hiyama S, Haraguchi N, Inoue T, Nishimura J, Shinzaki S, Hata T, Matsuda C, Yamamoto H, Doki Y, Mori M. Adherence to an elemental diet for preventing postoperative recurrence of Crohn’s disease. Surg Today 2017; 47:1519-1525. [DOI: 10.1007/s00595-017-1543-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2016] [Accepted: 05/07/2017] [Indexed: 12/15/2022]
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Amil-Dias J, Kolacek S, Turner D, Pærregaard A, Rintala R, Afzal NA, Karolewska-Bochenek K, Bronsky J, Chong S, Fell J, Hojsak I, Hugot JP, Koletzko S, Kumar D, Lazowska-Przeorek I, Lillehei C, Lionetti P, Martin-de-Carpi J, Pakarinen M, Ruemmele FM, Shaoul R, Spray C, Staiano A, Sugarman I, Wilson DC, Winter H, Kolho KL. Surgical Management of Crohn Disease in Children: Guidelines From the Paediatric IBD Porto Group of ESPGHAN. J Pediatr Gastroenterol Nutr 2017; 64:818-835. [PMID: 28267075 DOI: 10.1097/mpg.0000000000001562] [Citation(s) in RCA: 71] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The incidence of Crohn disease (CD) has been increasing and surgery needs to be contemplated in a substantial number of cases. The relevant advent of biological treatment has changed but not eliminated the need for surgery in many patients. Despite previous publications on the indications for surgery in CD, there was a need for a comprehensive review of existing evidence on the role of elective surgery and options in pediatric patients affected with CD. We present an expert opinion and critical review of the literature to provide evidence-based guidance to manage these patients. Indications, surgical options, risk factors, and medications in pre- and perioperative period are reviewed in the light of available evidence. Risks and benefits of surgical options are addressed. An algorithm is proposed for the management of postsurgery monitoring, timing for follow-up endoscopy, and treatment options.
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Affiliation(s)
- Jorge Amil-Dias
- *Department of Pediatrics, Centro Hospitalar, S. João, Porto, Portugal †Children's Hospital Zagreb, Faculty of Medicine, Zagreb, Croatia ‡The Juliet Keidan Institute of Pediatric Gastroenterology & Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel §Department of Pediatrics, Hvidovre University Hospital, Hvidovre, Denmark ||Pediatric Surgery, Children's Hospital, University of Helsinki, Helsinki, Finland ¶Department of Pediatric Gastroenterology, University Hospital Southampton, Southampton, UK #Department of Pediatric Gastroenterology and Nutrition, Medical University of Warsaw, Warsaw, Poland **Department of Pediatrics, University Hospital Motol, Prague, Czech Republic ††Queen Mary's Hospital for Children, Epsom and St Helier NHS Trust, Surrey ‡‡Chelsea and Westminster Hospital, London, UK §§Paris-Diderot Sorbonne-Paris-Cité University and Robert Debré Hospital, Paris, France ||||Pediatric Gastroenterology and Hepatology, Dr. von Hauner Children's Hospital, Ludwig Maximilians-University, Munich, Germany ¶¶St George's, University of London, London, UK ##Boston Children's Hospital and Harvard Medical School, Boston, MA ***Department NEUROFARBA, University of Florence - Meyer Hospital, Florence, Italy †††Unit for the Comprehensive Care of Pediatric Inflammatory Bowel Disease, Hospital Sant Joan de Déu, Barcelona, Spain ‡‡‡Department of Pediatric Gastroenterology, Necker Enfants Malades University Hospital, Sorbonne Paris Cité University, Paris Descartes University, Institut IMAGINE - INSERM U1163, Paris, France §§§Pediatric Gastroenterology Institute, Ruth Children's Hospital, Rambam Medical Center, Haifa, Israel ||||||Department of Pediatric Gastroenterology, Bristol Royal Hospital for Children, Bristol, UK ¶¶¶Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II," Naples, Italy ###Department of Pediatric Surgery, Leeds Children's Hospital, Leeds General Infirmary, Leeds, UK ****Child Life and Health, University of Edinburgh, Scotland, UK ††††MassGeneral Hospital for Children, Harvard Medical School, Boston, MA ‡‡‡‡Children's Hospital, University of Helsinki, Helsinki, Finland
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Cuív PÓ, Begun J, Keely S, Lewindon PJ, Morrison M. Towards an integrated understanding of the therapeutic utility of exclusive enteral nutrition in the treatment of Crohn's disease. Food Funct 2017; 7:1741-51. [PMID: 26948398 DOI: 10.1039/c5fo01196e] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Crohn's disease (CD) is a chronic disease characterized by episodic and disabling inflammation of the gastrointestinal tract in genetically susceptible individuals. The incidence and prevalence of CD is rising rapidly across the world emphasising that disease risk is also influenced by environmental and lifestyle factors, as well as the microbial community resident in the gut. Childhood-onset CD is associated with an aggressive disease course that can adversely impact patient growth and development. There is no cure for CD however new onset and recurrent cases of paediatric CD are often responsive to exclusive enteral nutrition (EEN) treatment. EEN treatment involves the exclusive consumption of an elemental or polymeric formula for several weeks and it is well established as a primary intervention strategy. EEN treatments typically achieve remission rates of over 80% and importantly they are associated with a high rate of mucosal healing, far superior to steroids, which is prognostic of improved long-term health outcomes. Furthermore, they are safe, have few side effects, and improve nutritional status and linear growth. Surprisingly, despite the utility of EEN our understanding of the host-microbe-diet interactions that underpin clinical remission and mucosal healing are limited. Here, we review the current state of knowledge and propose that the induction of autophagy, in addition to modulation of the microbiota and coordinated effects on inflammation and epithelial cell biology, may be critical for the therapeutic effects associated with EEN. A better understanding of EEN treatment will provide new opportunities to restore gut homeostasis and prolong periods of remission, as well as provide new insights into the factors that trigger and perhaps prevent CD.
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Affiliation(s)
- Páraic Ó Cuív
- The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Brisbane, QLD 4102, Australia.
| | - Jakob Begun
- Mater Research Institute, The University of Queensland, Brisbane, QLD 4102, Australia and School of Medicine, The University of Queensland, Brisbane, QLD 4102, Australia and Department of Gastroenterology, Mater Health Services, Brisbane, Australia
| | - Simon Keely
- School of Biomedical Science and Pharmacy, The University of Newcastle, University Drive, Callaghan, NSW 2308, Australia and Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia
| | - Peter J Lewindon
- The University of Queensland, Department of Paediatrics and Child Health, Lady Cilento Children's Hospital, QLD 4101, Australia
| | - Mark Morrison
- The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Brisbane, QLD 4102, Australia.
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47
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Otley AR, Day AS, Zachos M. Nutritional Management of Inflammatory Bowel Disease. PEDIATRIC INFLAMMATORY BOWEL DISEASE 2017:333-356. [DOI: 10.1007/978-3-319-49215-5_27] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Maintenance of Remission with Partial Enteral Nutrition Therapy in Pediatric Crohn's Disease: A Retrospective Study. Can J Gastroenterol Hepatol 2017; 2017:5873158. [PMID: 28567370 PMCID: PMC5439067 DOI: 10.1155/2017/5873158] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2016] [Accepted: 04/11/2017] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Partial enteral nutrition (PEN) may be helpful for the maintenance of remission in pediatric Crohn's disease patients. AIMS To evaluate the efficacy of PEN treatment for preventing clinical relapse. METHODS We retrospectively assessed 42 pediatric Crohn's disease patients who entered clinical remission on 4-12 weeks of exclusive enteral nutrition (EEN) and were maintained on PEN as a supplementary diet. We evaluated the efficacy of the treatment at different time points using the weighted Pediatric Crohn Disease Activity Index (wPCDAI), Physician Global Assessment, laboratory parameters, and growth of each patient. Additionally, we assessed the use of concomitant medications. RESULTS The median length of remission with PEN was 6 (0-36) months. Patients' remission was maintained on PEN without concomitant medications for a median time of zero months (0-16). The mean body mass index in the PEN group increased from 18.1 to 18.8 after six months of PEN. The median wPCDAI decreased from 30 at diagnosis to 5.0 after EEN and increased to 7.5 after three months of PEN. Overall, the median wPCDAI decreased by 26.2. CONCLUSIONS PEN treatment was partially effective in maintaining remission and was able to increase BMI and lower wPCDAI. Most patients required concomitant medication after PEN initiation.
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Yamamoto T, Shimoyama T, Kuriyama M. Dietary and enteral interventions for Crohn's disease. Curr Opin Biotechnol 2016; 44:69-73. [PMID: 27940405 DOI: 10.1016/j.copbio.2016.11.011] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2016] [Revised: 11/14/2016] [Accepted: 11/17/2016] [Indexed: 01/18/2023]
Abstract
It is now widely acknowledged that the intestinal bacterial flora together with genetic predisposing factors significantly contribute to the immunopathogenesis of inflammatory bowel disease (IBD) as reflected by mucosal immune dysregulation. Recently, there has been an increased interest in nutraceutical therapies, including probiotics, prebiotics and synbiotics. Other dietary interventions with low carbohydrate diet, omega-3 polyunsaturated fatty acids and glutamine have been attempted to downregulate the gut inflammatory response and thereby alleviate gastrointestinal symptoms. Enteral nutrition has been widely used as induction and maintenance therapies in the management of Crohn's disease (CD). In this review, a critical assessment of the results of clinical trial outcomes and meta-analyses was conducted to evaluate the efficacy of dietary and enteral interventions for CD.
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Affiliation(s)
- Takayuki Yamamoto
- Inflammatory Bowel Disease Center, Yokkaichi Hazu Medical Center, Yokkaichi, Mie, Japan.
| | - Takahiro Shimoyama
- Inflammatory Bowel Disease Center, Yokkaichi Hazu Medical Center, Yokkaichi, Mie, Japan
| | - Moeko Kuriyama
- Inflammatory Bowel Disease Center, Yokkaichi Hazu Medical Center, Yokkaichi, Mie, Japan
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Nguyen DL, Limketkai B, Medici V, Saire Mendoza M, Palmer L, Bechtold M. Nutritional Strategies in the Management of Adult Patients with Inflammatory Bowel Disease: Dietary Considerations from Active Disease to Disease Remission. Curr Gastroenterol Rep 2016; 18:55. [PMID: 27637649 DOI: 10.1007/s11894-016-0527-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
Inflammatory bowel disease (IBD) is a group of chronic, lifelong, and relapsing illnesses, such as ulcerative colitis and Crohn's disease, which involve the gastrointestinal tract. There is no cure for these diseases, but combined pharmacological and nutritional therapy can induce remission and maintain clinical remission. Malnutrition and nutritional deficiencies among IBD patients result in poor clinical outcomes such as growth failure, reduced response to pharmacotherapy, increased risk for sepsis, and mortality. The aim of this review is to highlight the consequences of malnutrition in the management of IBD and describe nutritional interventions to facilitate induction of remission as well as maintenance; we will also discuss alternative delivery methods to improve nutritional status preoperatively.
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Affiliation(s)
- Douglas L Nguyen
- Division of Gastroenterology & Hepatology, Department of Medicine, University of California-Irvine Medical Center, 101 The City Drive, Orange, CA, 92868, USA.
| | - Berkeley Limketkai
- Department of Medicine, Stanford University, 300 Pasteur Dr, Palo Alto, CA, 94304, USA
| | - Valentina Medici
- Department of Medicine, University of California-Davis, 2315 Stockton Blvd, Sacramento, CA, 95817, USA
| | - Mardeli Saire Mendoza
- Department of Medicine, Ochsner Clinic, 1514 Jefferson Hwy, New Orleans, LA, 70121, USA
| | - Lena Palmer
- Department of Medicine, Loyola University, 2160 S First Ave, Maywood, IL, 60153, USA
| | - Matthew Bechtold
- Department of Medicine, University of Missouri-Columbia, 1 Hospital Dr, Columbia, MO, 65201, USA
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