|
1
|
Khan F, Abdulla N, du Plessis TL, Karlsson K, Barrow P, Bebington B, Gu L, Kaur M. Identification and Validation of Biomarkers to Predict Early Diagnosis of Inflammatory Bowel Disease and Its Progression to Colorectal Cancer. Biochem Genet 2024:10.1007/s10528-024-10917-z. [PMID: 39325241 DOI: 10.1007/s10528-024-10917-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 09/13/2024] [Indexed: 09/27/2024]
Abstract
Inflammatory bowel disease (IBD) has become a common global health problem as prevalence continues to rise. It is often associated with increased risk of colorectal cancer (CRC) development. Limitations in current IBD biomarker-based diagnosis hinder the accuracy of early detection of CRC progression. Therefore, in this study, we proposed the use of transcription factor (TF)-based biomarkers that can potentially detect the transition of IBD to CRC. Various bioinformatic analysis and online database validations, and RT-qPCR validations were performed to identify possible diagnostic TFs. RUNX1 was identified as a promising TF that regulates 106 IBD/CRC-related genes. The incorporation of RUNX1 in combination with currently known IBD biomarkers, FEV + NFKB1 + RELA, achieved a comparable sensitivity and specificity scores of 99% and 87%, respectively, while RUNX1 in combination with known CRC markers, CEA + TIMP1 + CA724 + CA199, achieved a sensitivity and specificity score of 97% and 99%, respectively. Furthermore, a small pilot RT-qPCR-based analysis confirmed a demarcated shift in expression profiles in CA724, CEA, RUNX1 and TIMP1 in IBD patients compared to CRC patients' tissue samples. Specifically, CA724 is noticeably elevated in IBD, while the levels of CEA, RUNX1 with TIMP1 are probable genes that may be employed in discerning IBD progression to CRC. Therefore, these preliminary results once validated in large patient cohorts could potentially have a significant impact on CRC disease stratification, resulting in a more precise prediction for treatment and treatment outcomes, especially in South African patients.
Collapse
Affiliation(s)
- Farhat Khan
- School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Johannesburg, WITS-2050, South Africa
| | - Naaziyah Abdulla
- School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Johannesburg, WITS-2050, South Africa
| | - Thea-Leonie du Plessis
- School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Johannesburg, WITS-2050, South Africa
| | - Kay Karlsson
- Wits Donald Gordon Medical Centre, Park Town, Johannesburg, 2193, South Africa
| | - Peter Barrow
- Wits Donald Gordon Medical Centre, Park Town, Johannesburg, 2193, South Africa
| | - Brendan Bebington
- Wits Donald Gordon Medical Centre, Park Town, Johannesburg, 2193, South Africa
| | - Liang Gu
- School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Johannesburg, WITS-2050, South Africa
| | - Mandeep Kaur
- School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Johannesburg, WITS-2050, South Africa.
| |
Collapse
|
|
2
|
Angriman I, Degasperi S, Mescoli C, Lacognata C, Armellin C, Caruso A, Scognamiglio F, Fassan M, D'Incà R, Savarino E, Zingone F, Spolverato G, Pucciarelli S, Bardini R, Ruffolo C, Scarpa M. Leaving behind a diseased small bowel during surgery for Crohn's disease: Long-term outcomes. Surg Today 2024; 54:523-533. [PMID: 37882838 DOI: 10.1007/s00595-023-02759-w] [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: 05/29/2023] [Accepted: 09/04/2023] [Indexed: 10/27/2023]
Abstract
PURPOSES Stricture is a common complication of Crohn's disease (CD) and may be treated with bowel-sparing procedures. Our study analyzed what happens in terms of intestinal and systemic inflammation when the diseased bowel is left behind following surgery. METHODS In this retrospective study, we enrolled 42 consecutive patients who underwent strictureplasty (alone or with resection) for stricturing CD. Control patients who underwent complete diseased bowel resection were identified and propensity score-matched for the sex, age, and history of abdominal surgery. Biohumoral values were collected at follow-up examinations at 1, 6, and 12 months after surgery. Magnetic resonance imaging (MRI) was performed before and after strictureplasty in 19 patients. RESULTS In the strictureplasty group, fecal calprotectin levels were decreased at 12 months (p = 0.03), whereas in the resectiongroup, they were decreased at 6 months (p = 0.02). On MRI, the ADC [apparent diffusion coefficient] (p < 0.001), wall thickness (p = 0.046) and Magnetic Resonance Index of Activity (MaRIA) (p < 0.001) and Clermont (p < 0.001) scores were improved after strictureplasty. Surgical recurrence was more frequent in the strictureplasty group than in the resection group (p = 0.003). CONCLUSIONS Our retrospective study showed that even if the diseased bowel was left behind after surgery, the intestinal inflammatory activity still decreased. However, the permanence of the diseased bowel still increased the risk of reoperation, probably because of the fibrotic nature of the stenosis and the multifocality of CD.
Collapse
Affiliation(s)
- Imerio Angriman
- Chirurgia Generale 3 Unit, Azienda Ospedale Università di Padova, Via Giustiniani 2, 35128, Padua, Italy
| | | | - Claudia Mescoli
- Pathology Unit, Azienda Ospedale Università di Padova, Padua, Italy
| | | | - Claudia Armellin
- Chirurgia Generale 3 Unit, Azienda Ospedale Università di Padova, Via Giustiniani 2, 35128, Padua, Italy
| | - Antonino Caruso
- Gastroenterology Unit, Azienda Ospedale Università di Padova, Padua, Italy
| | - Federico Scognamiglio
- Chirurgia Generale 3 Unit, Azienda Ospedale Università di Padova, Via Giustiniani 2, 35128, Padua, Italy
| | - Matteo Fassan
- Pathology Unit, Azienda Ospedale Università di Padova, Padua, Italy
| | - Renata D'Incà
- Gastroenterology Unit, Azienda Ospedale Università di Padova, Padua, Italy
| | - Edoardo Savarino
- Gastroenterology Unit, Azienda Ospedale Università di Padova, Padua, Italy
| | - Fabiana Zingone
- Gastroenterology Unit, Azienda Ospedale Università di Padova, Padua, Italy
| | - Gaya Spolverato
- Chirurgia Generale 3 Unit, Azienda Ospedale Università di Padova, Via Giustiniani 2, 35128, Padua, Italy
| | - Salvatore Pucciarelli
- Chirurgia Generale 3 Unit, Azienda Ospedale Università di Padova, Via Giustiniani 2, 35128, Padua, Italy
| | - Romeo Bardini
- Chirurgia Generale Unit, Azienda Ospedale Università di Padova, Padua, Italy
| | - Cesare Ruffolo
- Chirurgia Generale 3 Unit, Azienda Ospedale Università di Padova, Via Giustiniani 2, 35128, Padua, Italy
| | - Marco Scarpa
- Chirurgia Generale 3 Unit, Azienda Ospedale Università di Padova, Via Giustiniani 2, 35128, Padua, Italy.
| |
Collapse
|
|
3
|
Padoan A, Musso G, Contran N, Basso D. Inflammation, Autoinflammation and Autoimmunity in Inflammatory Bowel Diseases. Curr Issues Mol Biol 2023; 45:5534-5557. [PMID: 37504266 PMCID: PMC10378236 DOI: 10.3390/cimb45070350] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 06/28/2023] [Accepted: 06/28/2023] [Indexed: 07/29/2023] Open
Abstract
In this review, the role of innate and adaptive immunity in the pathogenesis of inflammatory bowel diseases (IBD) is reported. In IBD, an altered innate immunity is often found, with increased Th17 and decreased Treg cells infiltrating the intestinal mucosa. An associated increase in inflammatory cytokines, such as IL-1 and TNF-α, and a decrease in anti-inflammatory cytokines, such as IL-10, concur in favoring the persistent inflammation of the gut mucosa. Autoinflammation is highlighted with insights in the role of inflammasomes, which activation by exogenous or endogenous triggers might be favored by mutations of NOD and NLRP proteins. Autoimmunity mechanisms also take place in IBD pathogenesis and in this context of a persistent immune stimulation by bacterial antigens and antigens derived from intestinal cells degradation, the adaptive immune response takes place and results in antibodies and autoantibodies production, a frequent finding in these diseases. Inflammation, autoinflammation and autoimmunity concur in altering the mucus layer and enhancing intestinal permeability, which sustains the vicious cycle of further mucosal inflammation.
Collapse
Affiliation(s)
- Andrea Padoan
- Department of Medicine-DIMED, University of Padova, Via Giustiniani 2, 35128 Padova, Italy
| | - Giulia Musso
- Department of Medicine-DIMED, University of Padova, Via Giustiniani 2, 35128 Padova, Italy
| | - Nicole Contran
- Department of Medicine-DIMED, University of Padova, Via Giustiniani 2, 35128 Padova, Italy
| | - Daniela Basso
- Department of Medicine-DIMED, University of Padova, Via Giustiniani 2, 35128 Padova, Italy
| |
Collapse
|
|
4
|
Macedo CP, Sarmento Costa M, Gravito-Soares E, Gravito-Soares M, Ferreira AM, Portela F, Figueiredo P. Role of Intestinal Ultrasound in the Evaluation of Postsurgical Recurrence in Crohn's Disease: Correlation with Endoscopic Findings. GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2022; 29:178-186. [PMID: 35702171 PMCID: PMC9149544 DOI: 10.1159/000517999] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Accepted: 05/10/2021] [Indexed: 05/31/2025]
Abstract
INTRODUCTION Endoscopy remains the exam of choice in the evaluation of activity in Crohn's disease (CD) after surgery (ACD-AS). However, intestinal ultrasound (IUS) may represent a noninvasive alternative. The objective of this study is to determine the diagnostic accuracy of this modality compared to endoscopy. MATERIAL AND METHODS This is a cross-sectional study, comprising a period of 14 months, carried out in patients with established CD and ileocecal resection due to the disease. IUS (HI-VISION Avius®, Tokyo, Japan) was performed with linear probe B-mode/Doppler prior to ileocolonoscopy. IUS and ileocolonoscopy were performed on the same day by 2 specialists in Gastroenterology dedicated to ultrasound and inflammatory bowel disease, in a double-blind mode. Collected demographic and clinical data (Harvey-Bradshaw Index [HBI]; remission ≤4), serological/fecal inflammatory parameters (leukocytes [4-10 × 109 cells/L], C-reactive protein [≤0.5 mg/dL], and fecal calprotectin [<50 mg/kg]), endoscopy (Rutgeerts score: remission RESULTS Thirty-nine patients (female: 64.1%, mean age: 43.5 ± 15.3 years) were included. The median post-surgery follow-up was 9 years (IQR 3-12). The Montreal classification was as follows: L1, 61.5% (n = 24); L3, 38.5% (n = 15); B1 and B2, 28.2% (n = 11); and B3, 43.6% (n = 17). Most patients were in clinical remission (87.2%; n = 34), with a mean HBI of 2.1 ± 2.2. Twenty-two patients (56.4%) had normal inflammatory markers. IUS (intestinal wall thickening >3 mm and/or Limberg score >1) was abnormal in 61.5% (n = 24) of the cases. Endoscopic remission (Rutgeerts score CONCLUSIONS Ultrasound evaluation of the digestive wall is a noninvasive technique that shows a good diagnostic accuracy and a moderate concordance with endoscopy, being superior to clinical and serological/fecal inflammatory parameters.
Collapse
Affiliation(s)
- Cláudia Patricia Macedo
- Gastroenterology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - Mara Sarmento Costa
- Gastroenterology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - Elisa Gravito-Soares
- Gastroenterology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
- University of Coimbra, Faculty of Medicine, Coimbra, Portugal
| | - Marta Gravito-Soares
- Gastroenterology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
- University of Coimbra, Faculty of Medicine, Coimbra, Portugal
| | - Ana Margarida Ferreira
- Gastroenterology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - Francisco Portela
- Gastroenterology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
- University of Coimbra, Faculty of Medicine, Coimbra, Portugal
| | - Pedro Figueiredo
- Gastroenterology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
- University of Coimbra, Faculty of Medicine, Coimbra, Portugal
| |
Collapse
|
|
5
|
Vernia F, Viscido A, Di Ruscio M, Stefanelli G, Valvano M, Latella G. Fecal Lactoferrin and Other Putative Fecal Biomarkers in Crohn's Disease: Do They Still Have a Potential Clinical Role? Digestion 2021; 102:833-844. [PMID: 34518458 DOI: 10.1159/000518419] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Accepted: 07/11/2021] [Indexed: 02/04/2023]
Abstract
INTRODUCTION The need for noninvasive markers of disease activity is mandatory in the assessment of Crohn's disease (CD). The most widely fecal biomarker in CD, despite several limits, is fecal calprotectin. This review aims to elucidate the role, if any, of all other fecal biomarkers, as alternative tools for assessing clinical and endoscopic disease activity, and predict capsule endoscopy findings, response to therapy, disease relapse, and postoperative recurrence. These fecal biomarkers included lactoferrin, S100A12, high mobility group box 1, neopterin, polymorphonuclear neutrophil elastase, fecal hemoglobin, alpha1-antitrypsin, lysozyme, human beta-defensin-2, neutrophil gelatinase-associated lipocalin, matrix metalloproteinase-9, chitinase 3-like-1, M2-pyruvate kinase, myeloperoxidase, and eosinophil proteins. METHODS A systematic electronic search in the medical literature was performed up to April 2020. Seventy eligible studies were identified out of 859 citations. Data were grouped according to the assessment of clinical and endoscopic disease activity, capsule endoscopy findings, response to therapy, prediction of relapse, and postoperative recurrence. RESULTS The overall correlation between lactoferrin and clinical indexes is poor, while performance is good with endoscopic scores. Lactoferrin seems to represent a reasonably good surrogate marker of response to therapy and to be potentially useful in identifying patients at high risk for endoscopic relapse or postoperative recurrence. The evaluation of the performance of all other fecal markers is limited by the lack of adequate data. CONCLUSIONS None of the fecal markers so far represents an acceptable alternative to calprotectin in clinical practice. Fecal lactoferrin is the only possible exception, but a more extensive investigation is still required.
Collapse
Affiliation(s)
- Filippo Vernia
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, Piazza S. Tommasi, L'Aquila, Italy
| | - Angelo Viscido
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, Piazza S. Tommasi, L'Aquila, Italy
| | - Mirko Di Ruscio
- IBD Unit of IRCCS Ospedale Sacro Cuore - Don Calabria, Verona, Italy
| | - Gianpiero Stefanelli
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, Piazza S. Tommasi, L'Aquila, Italy
| | - Marco Valvano
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, Piazza S. Tommasi, L'Aquila, Italy
| | - Giovanni Latella
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, Piazza S. Tommasi, L'Aquila, Italy
| |
Collapse
|
|
6
|
Lężyk-Ciemniak E, Tworkiewicz M, Wilczyńska D, Szaflarska-Popławska A, Krogulska A. Usefulness of Testing for Fecal Calprotectin in Pediatric Gastroenterology Clinical Practice. Med Princ Pract 2021; 30:311-319. [PMID: 33120396 PMCID: PMC8436627 DOI: 10.1159/000512631] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Accepted: 10/25/2020] [Indexed: 01/11/2023] Open
Abstract
Gastrointestinal tract symptoms such as abdominal pain, constipation, diarrhea, and fever are common reasons for which parents take children to the pediatrician. An increasing prevalence of chronic diseases of the gastrointestinal tract and a decrease in the median age of their onset indicate the need to search for new diagnostic methods for differentiating inflammatory bowel diseases (IBDs) from other gastrointestinal tract diseases. An example of a novel biomarker is fecal calprotectin (FC), which is considered a noninvasive and useful marker of intestinal inflammation. This review summarizes currently available information on the use of FC in the diagnosis and monitoring of IBD in children. Additionally, it attempts to determine the course of action depending on the concentration of FC. Application of FC determination within the framework of primary medical care can decrease the number of children unnecessarily referred either to endoscopic or radiologic examination. There is a double advantage of calprotectin screening; for patients, it reduces delays in diagnosis and unnecessary exposure to endoscopy, and for doctors, it reduces pressure on endoscopy testing and facilitates decision-making. We emphasize the role of FC as a noninvasive marker, primarily in patients with IBD, in monitoring disease activity, predicting relapse, monitoring therapy efficacy, and monitoring postoperative relapses.
Collapse
Affiliation(s)
- Eliza Lężyk-Ciemniak
- Department of Pediatrics, Allergology and Gastroenterology Collegium Medicum Bydgoszcz, NCU Toruń, Bydgoszcz, Poland
| | - Magdalena Tworkiewicz
- Department of Pediatrics, Allergology and Gastroenterology Collegium Medicum Bydgoszcz, NCU Toruń, Bydgoszcz, Poland
| | - Dominika Wilczyńska
- Department of Pediatrics, Allergology and Gastroenterology Collegium Medicum Bydgoszcz, NCU Toruń, Bydgoszcz, Poland
| | - Anna Szaflarska-Popławska
- Department of Pediatric Endoscopy and Gastrointestinal Function Testing, NCU Toruń, Bydgoszcz, Poland
| | - Aneta Krogulska
- Department of Pediatrics, Allergology and Gastroenterology Collegium Medicum Bydgoszcz, NCU Toruń, Bydgoszcz, Poland
| |
Collapse
|
|
7
|
Iacucci M, Cannatelli R, Labarile N, Mao R, Panaccione R, Danese S, Kochhar GS, Ghosh S, Shen B. Endoscopy in inflammatory bowel diseases during the COVID-19 pandemic and post-pandemic period. Lancet Gastroenterol Hepatol 2020; 5:598-606. [PMID: 32305075 PMCID: PMC7162648 DOI: 10.1016/s2468-1253(20)30119-9] [Citation(s) in RCA: 72] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 04/06/2020] [Accepted: 04/07/2020] [Indexed: 12/15/2022]
Abstract
The coronavirus disease 2019 (COVID-19) pandemic is changing the management of many chronic diseases, including that of patients with inflammatory bowel diseases (IBD). In particular, the performance of routine endoscopy is temporarily suspended, and only emergency endoscopy is allowed in many countries where severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread. We highlight different scenarios in which endoscopy should still be performed urgently in patients with IBD, as well as recommendations regarding the use of personal protective equipment. We suggest a pathway for performing safe endoscopy and discuss the potential risks of postponing endoscopy in IBD. Finally, we propose a post-pandemic plan for access to endoscopy.
Collapse
Affiliation(s)
- Marietta Iacucci
- Institute of Translational of Medicine, Institute of immunology and immunotherapy and NIHR Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, UK; Department of Gastroenterology and Hepatology, University of Calgary, Calgary, AB, Canada
| | - Rosanna Cannatelli
- Institute of Translational of Medicine, Institute of immunology and immunotherapy and NIHR Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, UK; Department of Gastroenterology, Spedali Civili of Brescia, Italy
| | - Nunzia Labarile
- Institute of Translational of Medicine, Institute of immunology and immunotherapy and NIHR Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, UK; Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Italy
| | - Ren Mao
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, OH, USA
| | - Remo Panaccione
- Department of Gastroenterology and Hepatology, University of Calgary, Calgary, AB, Canada
| | - Silvio Danese
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Center, IRCCS, Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Gursimran S Kochhar
- Department of Gastroenterology, Hepatology & Nutrition, Allegheny Health Network, Pittsburgh, PA, USA
| | - Subrata Ghosh
- Institute of Translational of Medicine, Institute of immunology and immunotherapy and NIHR Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, UK; Department of Gastroenterology and Hepatology, University of Calgary, Calgary, AB, Canada.
| | - Bo Shen
- Center for Inflammatory Bowel Disease, Columbia University Irving Medical Center/New York-Presbyterian Hospital, New York, NY, USA
| |
Collapse
|
|
8
|
Niaz B, Saeed F, Ahmed A, Imran M, Maan AA, Khan MKI, Tufail T, Anjum FM, Hussain S, Suleria HAR. Lactoferrin (LF): a natural antimicrobial protein. INTERNATIONAL JOURNAL OF FOOD PROPERTIES 2019. [DOI: 10.1080/10942912.2019.1666137] [Citation(s) in RCA: 70] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Bushra Niaz
- Institute of Home & Food Sciences, Government College University, Faisalabad, Pakistan
| | - Farhan Saeed
- Institute of Home & Food Sciences, Government College University, Faisalabad, Pakistan
| | - Awais Ahmed
- Institute of Home & Food Sciences, Government College University, Faisalabad, Pakistan
| | - Muhammad Imran
- Faculty of Allied Health Sciences, University Institute of Diet & Nutritional Sciences, University of Lahore, Lahore, Pakistan
| | - Abid Aslam Maan
- National Institute of Food Science and Technology, University of Agriculture, Faisalabad, Pakistan
| | | | - Tabussam Tufail
- Institute of Home & Food Sciences, Government College University, Faisalabad, Pakistan
| | | | - Shahzad Hussain
- College of Food and Agricultural Sciences, King Saud, University, Riyadh, Saudi Arabia
| | | |
Collapse
|
|
9
|
Cerrillo E, Moret I, Iborra M, Pamies J, Hervás D, Tortosa L, Sáez-González E, Nos P, Beltrán B. A Nomogram Combining Fecal Calprotectin Levels and Plasma Cytokine Profiles for Individual Prediction of Postoperative Crohn's Disease Recurrence. Inflamm Bowel Dis 2019; 25:1681-1691. [PMID: 30925193 DOI: 10.1093/ibd/izz053] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND The aims of this study were to characterize the immune response profile in patients with Crohn's disease (CD) and early postoperative recurrence (POR), to identify predictive biomarkers, and to develop a noninvasive predictive tool for individual estimation of POR risk. METHODS Sixty-one patients who had undergone ileocolonic resection for CD were prospectively included and followed up for 24 months. Fecal calprotectin (FC), analytical parameters, and plasma cytokines were obtained before surgery and at various time points during postoperative follow-up. Morphological recurrence was assessed by ileocolonoscopy or magnetic resonance enterography within 6-12 months after surgery. Clinical activity was scored using the Harvey-Bradshaw Index. RESULTS Twenty-seven patients (44.3%) had morphological recurrence during follow-up. Fecal calprotectin values were significantly associated with POR risk over time. The receiver operating characteristic curve for FC provided an area under the curve (AUC) of 0.88 (95% confidence interval, 0.75-0.96), and morphological recurrence was best predicted by FC ≥160 μg/g at 6 months after surgery (85% sensitivity, 70% specificity, 26% predictive positive value, 98% negative predictive value [NPV]). The plasma cytokine profile showed higher presurgery interleukin (IL)-13 plasma levels and higher IL-6 and interferon (IFN)-γ levels at 6 months after surgery in patients with POR compared with patients without recurrence. The combination of FC, IL-6, and IFN-γ values at 6 months gave an AUC of 0.90 for predicting an early recurrence. CONCLUSIONS FC values <160 μg/g at 6 months have a high NPV to rule out early lesions. Combined values of FC, IL-6, and IFN-γ levels at 6 months postsurgery constitute a prognostic index with a high predictive capacity to assess the risk of early POR.
Collapse
Affiliation(s)
- Elena Cerrillo
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain.,Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain.,Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBEREHD), Institute of Health Carlos III, Madrid, Spain
| | - Inés Moret
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain.,Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain.,Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBEREHD), Institute of Health Carlos III, Madrid, Spain
| | - Marisa Iborra
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain.,Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain.,Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBEREHD), Institute of Health Carlos III, Madrid, Spain
| | - José Pamies
- Radiology Department, La Fe University and Polytechnic Hospital, Valencia, Spain
| | - David Hervás
- Biostatistics Unit, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain
| | - Luis Tortosa
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain.,Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain
| | - Esteban Sáez-González
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain.,Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain
| | - Pilar Nos
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain.,Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain.,Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBEREHD), Institute of Health Carlos III, Madrid, Spain
| | - Belén Beltrán
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain.,Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain.,Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBEREHD), Institute of Health Carlos III, Madrid, Spain
| |
Collapse
|
|
10
|
Liu R, Guo Z, Cao L, Wang Z, Gong J, Li Y, Zhu W. Profile of Consecutive Fecal Calprotectin Levels in the Perioperative Period and Its Predictive Capacity for Early Endoscopic Recurrence in Crohn's Disease. Dis Colon Rectum 2019; 62:318-326. [PMID: 30451756 DOI: 10.1097/dcr.0000000000001263] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND The perioperative behavior of fecal calprotectin and whether it predicts early postoperative endoscopic recurrence of Crohn's disease are unknown. OBJECTIVE We aimed to compare the perioperative profiles of fecal calprotectin between patients with Crohn's disease and patients without Crohn's disease undergoing intestinal resection and to identify the association between consecutive fecal calprotectin levels and endoscopic recurrence 3 months after surgery in patients with Crohn's disease. DESIGN This was a prospective observational study. SETTINGS This study was conducted in a tertiary referral hospital. PATIENTS One hundred fourteen consecutive patients (90 Crohn's disease, 24 non-Crohn's disease) who underwent resection were recruited. MAIN OUTCOME MEASURES Univariate and multivariate analyses were performed to identify variations and risk factors. The predictive accuracy of the possible predictors was assessed by using receiver operating characteristic curves. RESULTS The fecal calprotectin levels on preoperative day 14 and postoperative days 14, 21, 28, 60, and 90 were higher in the Crohn's disease group than they were in non-Crohn's disease group (p < 0.05). Twenty patients (22.2%) developed endoscopic recurrence 3 months after resection. The trend for fecal calprotectin change (Δfecal calprotectin) from preoperative day 14 to postoperative day 14 was opposite in the recurrence and nonrecurrence groups. Multivariate analysis showed that this change was a predictive factor of early endoscopic recurrence (p < 0.05). ΔFecal calprotectin was more accurate at predicting early endoscopic recurrence than was fecal calprotectin at single time points with a cutoff value of 240 μg/g. LIMITATIONS This is a single-center trial with a limited cohort of patients. CONCLUSIONS The perioperative fecal calprotectin levels were higher in patients with Crohn's disease than they were in the control group. The change in fecal calprotectin levels from preoperative day 14 to postoperative day 14 could serve as a practical predictive index for early postoperative endoscopic recurrence. See Video Abstract at http://links.lww.com/DCR/A796.
Collapse
Affiliation(s)
- Ruiqing Liu
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, People's Republic of China
| | | | | | | | | | | | | |
Collapse
|
|
11
|
Mumolo MG, Bertani L, Ceccarelli L, Laino G, Di Fluri G, Albano E, Tapete G, Costa F. From bench to bedside: Fecal calprotectin in inflammatory bowel diseases clinical setting. World J Gastroenterol 2018; 24:3681-3694. [PMID: 30197475 PMCID: PMC6127662 DOI: 10.3748/wjg.v24.i33.3681] [Citation(s) in RCA: 122] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2018] [Revised: 06/05/2018] [Accepted: 06/27/2018] [Indexed: 02/06/2023] Open
Abstract
Fecal calprotectin (FC) has emerged as one of the most useful tools for clinical management of inflammatory bowel diseases (IBD). Many different methods of assessment have been developed and different cut-offs have been suggested for different clinical settings. We carried out a comprehensive literature review of the most relevant FC-related topics: the role of FC in discriminating between IBD and irritable bowel syndrome (IBS) and its use in managing IBD patients In patients with intestinal symptoms, due to the high negative predictive value a normal FC level reliably rules out active IBD. In IBD patients a correlation with both mucosal healing and histology was found, and there is increasing evidence that FC assessment can be helpful in monitoring disease activity and response to therapy as well as in predicting relapse, post-operative recurrence or pouchitis. Recently, its use in the context of a treat-to-target approach led to a better outcome than clinically-based therapy adjustment in patients with early Crohn’s disease. In conclusion, FC measurement represents a cheap, safe and reliable test, easy to perform and with a good reproducibility. The main concerns are still related to the choice of the optimal cut-off, both for differentiating IBD from IBS, and for the management of IBD patients.
Collapse
Affiliation(s)
- Maria Gloria Mumolo
- Department of General Surgery and Gastroenterology, Gastroenterology Unit, Azienda Ospedaliero Universitaria Pisana, Pisa 56124, Italy
| | - Lorenzo Bertani
- Department of New Technologies and Translational Research in Medicine and Surgery, University of Pisa, Pisa 56122, Italy
| | - Linda Ceccarelli
- Department of General Surgery and Gastroenterology, Gastroenterology Unit, Azienda Ospedaliero Universitaria Pisana, Pisa 56124, Italy
| | - Gabriella Laino
- Department of New Technologies and Translational Research in Medicine and Surgery, University of Pisa, Pisa 56122, Italy
| | - Giorgia Di Fluri
- Department of General Surgery and Gastroenterology, Gastroenterology Unit, Azienda Ospedaliero Universitaria Pisana, Pisa 56124, Italy
| | - Eleonora Albano
- Department of New Technologies and Translational Research in Medicine and Surgery, University of Pisa, Pisa 56122, Italy
| | - Gherardo Tapete
- Department of New Technologies and Translational Research in Medicine and Surgery, University of Pisa, Pisa 56122, Italy
| | - Francesco Costa
- Department of General Surgery and Gastroenterology, Gastroenterology Unit, Azienda Ospedaliero Universitaria Pisana, Pisa 56124, Italy
| |
Collapse
|
|
12
|
Dai C, Jiang M, Sun MJ. Fecal markers in the management of inflammatory bowel disease. Postgrad Med 2018; 130:597-606. [PMID: 30063872 DOI: 10.1080/00325481.2018.1503919] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Accepted: 07/20/2018] [Indexed: 12/13/2022]
Abstract
Inflammatory bowel disease (IBD) is characterized by periods of symptomatic remission and relapse. Diagnosis and assessment of IBD are based on clinical evaluation, serum parameters, radiology, and endoscopy. Fecal markers have emerged as new diagnostic tools to detect and monitor intestinal inflammation. Fecal calprotectin (FC) and lactoferrin (FL) were identified decades ago as potentially revolutionary markers for IBD. Following these discoveries numerous additional markers, including S100A12, M2-PK, metalloproteinases, hemoglobin, myeloperoxidase, lysozyme, polymorphonuclear elastase, neopterin, and nitric oxide, have also been suggested as novel markers of IBD. But only FC and FL are used for the management of clinical IBD patients. The objective of this review is to introduce the clinical applications of fecal markers in the diagnosis, monitoring and prediction of outcomes of inflammatory bowel disease.
Collapse
Affiliation(s)
- Cong Dai
- a Department of Gastroenterology, First Affiliated Hospital , China Medical University , Shenyang , China
| | - Min Jiang
- a Department of Gastroenterology, First Affiliated Hospital , China Medical University , Shenyang , China
| | - Ming-Jun Sun
- a Department of Gastroenterology, First Affiliated Hospital , China Medical University , Shenyang , China
| |
Collapse
|
|
13
|
Tham YS, Yung DE, Fay S, Yamamoto T, Ben-Horin S, Eliakim R, Koulaouzidis A, Kopylov U. Fecal calprotectin for detection of postoperative endoscopic recurrence in Crohn's disease: systematic review and meta-analysis. Therap Adv Gastroenterol 2018; 11:1756284818785571. [PMID: 30034529 PMCID: PMC6048608 DOI: 10.1177/1756284818785571] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Accepted: 06/06/2018] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Anastomotic recurrence is frequent in patients with Crohn's disease (CD) following ileocecal resection. The degree of endoscopic recurrence, quantified by the Rutgeerts score (RS), correlates with risk of clinical and surgical recurrence. Several studies demonstrate the accuracy of fecal calprotectin (FC) for detection of endoscopic recurrence, however the optimal threshold FC value remains to be established. The aim of our meta-analysis was to evaluate the accuracy of common FC cut-offs for detection of endoscopic recurrence. METHODS We performed a systematic literature search for studies evaluating postoperative recurrence in CD which reported RS and FC levels. Endoscopic recurrence was defined as RS = 2-4 (or RS ⩾ 2). We calculated pooled diagnostic sensitivity, specificity, diagnostic odds ratio (DOR) and constructed summary receiver operating characteristic (SROC) curves for each available FC cut-off value. RESULTS A total of 54 studies were retrieved; 9 studies were eligible for analysis. Diagnostic accuracy was calculated for FC values of 50, 100, 150 and 200 µg/g. A significant threshold effect was observed for all FC values. The optimal diagnostic accuracy was obtained for FC value of 150 µg/g, with a pooled sensitivity of 70% [95% confidence interval (CI) 59-81%], specificity 69% (95% CI 61-77%), and DOR 5.92 (95% CI 2.61-12.17). The area under the SROC curve was 0.73. CONCLUSION FC is an accurate surrogate marker of postoperative endoscopic recurrence in CD patients. The FC cut-off 150 μg/g appears to have the best overall accuracy. Serial FC evaluations may eliminate or defer the need for colonoscopic evaluation in up to 70% of postoperative CD patients.
Collapse
Affiliation(s)
- Yuen Sau Tham
- Centre for Liver & Digestive Disorders, The
Royal Infirmary of Edinburgh, Edinburgh, UK
| | - Diana E. Yung
- Centre for Liver & Digestive Disorders, The
Royal Infirmary of Edinburgh, Edinburgh, UK
| | - Shmuel Fay
- Department of Gastroenterology, Sheba Medical
Centre, Ramat Gan, Israel Sackler School of Medicine, Tel-Aviv University,
Tel-Aviv, Israel
| | - Takayuki Yamamoto
- Inflammatory Bowel Disease Centre, Yokkaichi
Social Insurance Hospital, Yokkaichi, Mie, Japan
| | - Shomron Ben-Horin
- Department of Gastroenterology, Sheba Medical
Centre, Ramat Gan, Israel Sackler School of Medicine, Tel-Aviv University,
Tel-Aviv, Israel
| | - Rami Eliakim
- Department of Gastroenterology, Sheba Medical
Centre, Ramat Gan, Israel Sackler School of Medicine, Tel-Aviv University,
Tel-Aviv, Israel
| | | | | |
Collapse
|
|
14
|
Chen JM, Liu T, Gao S, Tong XD, Deng FH, Nie B. Efficacy of noninvasive evaluations in monitoring inflammatory bowel disease activity: A prospective study in China. World J Gastroenterol 2017; 23:8235-8247. [PMID: 29290660 PMCID: PMC5739930 DOI: 10.3748/wjg.v23.i46.8235] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2017] [Revised: 09/28/2017] [Accepted: 11/01/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To optimize the efficacy of noninvasive evaluations in monitoring the endoscopic activity of inflammatory bowel disease (IBD).
METHODS Fecal calprotectin (FC), clinical activity index (CDAI or CAI), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and procalcitonin (PCT) were measured for 136 IBD patients. Also, FC was measured in 25 irritable bowel syndrome (IBS) patients that served as controls. Then, endoscopic activity was determined by other two endoscopists for colonic or ileo-colonic Crohn’s disease (CICD) with the “simple endoscopic score for Crohn’s disease” (SES-CD), CD-related surgery patients with the Rutgeerts score, and ulcerative colitis (UC) with the Mayo score. The efficacies of these evaluations to predict the endoscopic disease activity were assessed by Mann-Whitney test, χ2 test, Spearman’s correlation, and multiple linear regression analysis.
RESULTS The median FC levels in CD, UC, and IBS patients were 449.6 (IQR, 137.9-1344.8), 497.9 (IQR, 131.7-118.0), and 9.9 (IQR, 049.7) μg/g, respectively (P < 0.001). For FC, CDAI or CAI, CRP, and ESR differed significantly between endoscopic active and remission in CICD and UC patients, but not in CD-related surgery patients. The SES-CD correlated closely with levels of FC (r = 0.802), followed by CDAI (r = 0.734), CRP (r = 0.658), and ESR (r = 0.557). The Mayo score also correlated significantly with FC (r = 0.837), CAI (r = 0.776), ESR (r = 0.644), and CRP (r = 0.634). For FC, a cut-off value of 250 μg/g indicated endoscopic active inflammation with accuracies of 87.5%, 60%, and 91.1%, respectively, for CICD, CD-related surgery, and UC patients. Moreover, clinical FC activity (CFA) calculated as 0.8 × FC + 4.6 × CDAI showed higher area under the curve (AUC) of 0.962 for CICD and CFA calculated as 0.2 × FC + 50 × CAI showed higher AUC (0.980) for UC patients than the FC. Also, the diagnostic accuracy of FC in identifying patients with mucosal inflammation in clinical remission was reflected by an AUC of 0.91 for CICD and 0.96 for UC patients.
CONCLUSION FC is the most promising noninvasive evaluation for monitoring the endoscopic activity of CICD and UC. CFA might be more accurate for IBD activity evaluation.
Collapse
Affiliation(s)
- Jin-Min Chen
- Department of Gastroenterology, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang 441021, Hubei Province, China
| | - Tao Liu
- Department of Gastroenterology, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510665, Guangdong Province, China
| | - Shan Gao
- Department of Gastroenterology, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang 441021, Hubei Province, China
| | - Xu-Dong Tong
- Department of Gastroenterology, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang 441021, Hubei Province, China
| | - Fei-Hong Deng
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Biao Nie
- Department of Gastroenterology, the First Affiliated Hospital of Jinan University, Jinan University, Guangzhou 510630, Guangdong Province, China
| |
Collapse
|
|
15
|
Yamamoto T, Shimoyama T. Monitoring and detection of disease recurrence after resection for Crohn's disease: the role of non-invasive fecal biomarkers. Expert Rev Gastroenterol Hepatol 2017; 11:899-909. [PMID: 28708427 DOI: 10.1080/17474124.2017.1356226] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Ileocolonoscopy is the gold standard for the diagnosis and assessment of postoperative recurrence in Crohn's disease (CD). Nevertheless, endoscopy is time-consuming and invasive. A minimally invasive and simple screening test would improve patient adherence to examination and provide greater clinical benefit. A number of fecal biomarkers have been evaluated for their utility for the diagnosis and monitoring of inflammatory bowel disease as alternative tests to endoscopy. Area covered: In this review, we focused on the utility of fecal biomarkers in the management of postoperative CD. Our major endeavor was to present an evidence-based assessment of the results of clinical trials on the available data. A literature search was conducted using the Medline. Expert commentary: Calprotectin and lactoferrin, both neutrophil-derived proteins, are the two most frequently used fecal biomarkers in clinical trials and practice. Several studies evaluated the role of these fecal biomarkers in patients with postoperative CD. These studies suggest that fecal calprotectin, and to a lesser degree lactoferrin, are useful in assessing endoscopic severity and in predicting future clinical recurrence after resection for CD. However, large scale, well-designed studies are necessary to rigorously evaluate the role of fecal biomarkers in postoperative CD.
Collapse
Affiliation(s)
- Takayuki Yamamoto
- a Inflammatory Bowel Disease Center , Yokkaichi Hazu Medical Center , Yokkaichi , Japan.,b Department of Surgery , Yokkaichi Hazu Medical Center , Yokkaichi , Japan
| | - Takahiro Shimoyama
- a Inflammatory Bowel Disease Center , Yokkaichi Hazu Medical Center , Yokkaichi , Japan.,b Department of Surgery , Yokkaichi Hazu Medical Center , Yokkaichi , Japan
| |
Collapse
|
|
16
|
Turvill J, Rook L, Rawle M, Robins G, Smale S, Kant P, Phillips A. Validation of a care pathway for the use of faecal calprotectin in monitoring patients with Crohn's disease. Frontline Gastroenterol 2017; 8:183-188. [PMID: 28839907 PMCID: PMC5558279 DOI: 10.1136/flgastro-2016-100780] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2016] [Revised: 01/09/2017] [Accepted: 01/10/2017] [Indexed: 02/04/2023] Open
Abstract
INTRODUCTION We have previously published an evidence-based care pathway for the use of faecal calprotectin (FC) to monitor patients with Crohn's disease established on therapy. Patients are treated as low, intermediate or high risk of continuing Crohn's disease activity based on their FC, whatever their phenotype and surgical status are. Low-risk patients (FC <100 µg/g) are offered 12 monthly follow-ups or step down of therapy if asymptomatic or initial expectant symptomatic treatment. Intermediate-risk patients (FC 100-250 µg/g) are reviewed at 6 months with a repeat FC. High-risk patients (two consecutive FCs >250 µg/g) are flagged up to the responsible clinician as likely having an active Crohn's disease. METHODS To validate this care pathway over a 2-year period, by determining its negative predictive value (NPV) and positive predictive value (PPV). RESULTS 123 patients were managed by means of the care pathway for a mean of 24.4 months. The NPV and PPV were 0.97 (CI 0.93 to 0.98) and 0.85 (CI 0.80 to 0.94), respectively (sensitivity: 0.92 (0.83 to 0.96) and specificity: 0.95 (0.92 to 0.98)). Importantly 69% of patients with FC >250 µg/g were in clinical remission, the care pathway identifying patients who would benefit from presymptomatic disease modification. CONCLUSIONS This validation of a pragmatic clinical care pathway demonstrates a safe and effective mechanism by which to use FC to monitor risk of disease activity in patients with Crohn's disease established on therapy. It provides a framework for prioritising follow-up and for identifying patients at risk of continuing disease activity or those in whom therapy could be stepped down.
Collapse
Affiliation(s)
- James Turvill
- Department of Gastroenterology, York Hospital, York Teaching Hospital NHS Foundation Trust, York, UK
| | - Lisa Rook
- Department of Gastroenterology, York Hospital, York Teaching Hospital NHS Foundation Trust, York, UK
| | - Maxine Rawle
- Department of Gastroenterology, York Hospital, York Teaching Hospital NHS Foundation Trust, York, UK
| | - Gerry Robins
- Department of Gastroenterology, York Hospital, York Teaching Hospital NHS Foundation Trust, York, UK
| | - Simon Smale
- Department of Gastroenterology, York Hospital, York Teaching Hospital NHS Foundation Trust, York, UK
| | - Prashant Kant
- Department of Gastroenterology, York Hospital, York Teaching Hospital NHS Foundation Trust, York, UK
| | - Anne Phillips
- Department of Gastroenterology, York Hospital, York Teaching Hospital NHS Foundation Trust, York, UK
| |
Collapse
|
|
17
|
Abstract
Despite advances in our understanding of the pathophysiology underlying inflammatory bowel disease, there remains a significant need for biomarkers that can differentiate between Crohn's disease and ulcerative colitis with high sensitivity and specificity, in a cost-efficient manner. As the focus on personalized approaches to the delivery of medical treatment increases, new biomarkers are being developed to predict an individual's response to therapy and their overall disease course. In this review, we will outline many of the existing and recently developed biomarkers, detailing their role in the assessment of patients with inflammatory bowel disease. We will identify opportunities for improvement in our biomarkers, including better differentiation between the subtypes of inflammatory bowel disease. We will also discuss new targets and strategies in biomarker development, including combining modalities to create biomarker signatures to improve the ability to predict disease courses and response to therapy among individual patients.
Collapse
|
|
18
|
Herranz Bachiller MT, Barrio Andres J, Fernandez Salazar L, Ruiz-Zorrilla R, Sancho Del Val L, Atienza Sanchez R. The utility of faecal calprotectin to predict post-operative recurrence in Crohńs disease. Scand J Gastroenterol 2016; 51:720-6. [PMID: 26758472 DOI: 10.3109/00365521.2015.1130164] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Endoscopic recurrence in Crohńs disease occurs in up to 80% of patients during the first year after surgery. Due to this, these patients need close monitoring. Faecal calprotectin has been proposed to be used as a non-invasive marker to monitor inflammatory activity. Up to now the use of faecal markers in endoscopic recurrence has been scarcely studied and with contradictory results. MATERIAL AND METHODS This was a cross-sectional observational study of diagnostic validity. It included all patients with Crohńs disease (CD) and ileocolic resection retrospectively who had had an ileocolonoscopy and a determination of faecal calprotectin before this colonoscopy, from 2007 to 2015. RESULTS Ninety-seven patients were included. We observed that the mean value of faecal calprotectin increased as the Rutgeerts score increased. The variable of that most statistical significance obtained in bivariate analysis was faecal calprotectin (p < 0.0001). Area under curve (AUC) of faecal calprotectin in endoscopic recurrence was 0.74 (95% CI: 0.644-0.842), and an optimal cut-off of 60 mcrgr/gr, obtained a score of 0.45 using Youden test. This indicated that calprotectin would have 88% Sensitivity and 58% Specificity in detecting any recurrence, the NPV was approximately 83,9%. None of the other variables studied had a significant correlation. CONCLUSION Faecal calprotectin predicts endoscopic recurrence in CD patients who have gone through surgery, however the cut-off point is still a problem so we cannot recommend calprotectin as a substitute of colonoscopy for CD monitoring and treatment adjustment.
Collapse
Affiliation(s)
| | - Jesus Barrio Andres
- a Department of Gastroenterology , Rio Hortega Hospital, Valladolid , Calle Dulzaina, 2 , Valladolid , Spain
| | - Luis Fernandez Salazar
- b Department of Gastroenterology, Universitary Clinic Hospital, Valladolid , Calle Ramón Y Cajal, S/N , Valladolid , Spain
| | - Rafael Ruiz-Zorrilla
- a Department of Gastroenterology , Rio Hortega Hospital, Valladolid , Calle Dulzaina, 2 , Valladolid , Spain
| | - Lorena Sancho Del Val
- a Department of Gastroenterology , Rio Hortega Hospital, Valladolid , Calle Dulzaina, 2 , Valladolid , Spain
| | - Ramon Atienza Sanchez
- a Department of Gastroenterology , Rio Hortega Hospital, Valladolid , Calle Dulzaina, 2 , Valladolid , Spain
| |
Collapse
|
|
19
|
Abstract
BACKGROUND Endoscopic recurrence after surgery for Crohn's disease (CD) is high, and it has important prognostic value. Crohn's disease will recur in the majority of patients after surgery. Fecal calprotectin (FC) and lactoferrin (FL) have attracted interest in the postoperative setting for predicting relapse. We have evaluated the accuracy of FC and FL in diagnosing endoscopic recurrence (ER) using the modified Rutgeerts score (MRS) compared with the Rutgeerts score (RS). METHODS A series of consecutive patients who underwent ileocolonic resection for Crohn's disease were evaluated. Biomarkers, clinical indexes, and fecal markers were recorded on the day of ileocolonoscopy. ER was defined as a MRS ≥ i2b or a RS ≥ i2. RESULTS Ninety-nine patients were included in this prospective cohort. The median time between surgery and colonoscopy was 87.5 months (IQR, 31-137). FC and FL levels were higher in patients with ER than in those in remission (Median FC, 196.5 μg/g [IQR, 96-634 μg/g] versus 42.1 μg/g [IQR 19-91.60 μg/g; P < 0.001]; Median FL, 23.27 μg/g [IQR 8.9-47.8 μg/g] versus 2 μg/g [IQR 0.9-7.26 μg/g; P < 0.001]). Using the MRS, 34% of patients presented with ER compared with 76% if the RS was used. The RS performed worse than the MRS with a decrease in sensitivity (74% versus 48% for FC and 85% versus 55% for FL) and in NPV (91% versus 33% for FC, and 90% versus 37% for FL). Furthermore, the accuracy of the MRS was higher than that of the RS (75% versus 55%). CONCLUSIONS Both FC and FL proved to correlate well with endoscopic findings in the evaluation of Crohn's disease after surgery. Both markers predicted recurrence with greater accuracy when the MRS was used. Fecal markers can be used to monitor disease recurrence after intestinal resection, with patients being selected to undergo further endoscopic evaluation.
Collapse
|
|
20
|
Ikhtaire S, Shajib MS, Reinisch W, Khan WI. Fecal calprotectin: its scope and utility in the management of inflammatory bowel disease. J Gastroenterol 2016; 51:434-46. [PMID: 26897740 DOI: 10.1007/s00535-016-1182-4] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2015] [Accepted: 02/04/2016] [Indexed: 02/07/2023]
Abstract
Gastrointestinal symptoms such as abdominal pain, dyspepsia, and diarrhea are relatively nonspecific and a common cause for seeking medical attention. To date, it is challenging for physicians to differentiate between functional and organic gastrointestinal conditions and it involves the use of serological and endoscopic techniques. Therefore, a simple, noninvasive, inexpensive, and effective test would be of utmost importance in clinical practice. Fecal calprotectin (FC) is considered to be a reliable biomarker that fulfills these criteria. FC can detect intestinal inflammation, and its level correlates well with macroscopic and histological inflammation as detected by colonoscopy and biopsies, respectively. FC has a decent diagnostic accuracy for differentiating organic diseases and functional disorders because of its excellent negative predictive value in ruling out inflammatory bowel disease (IBD) in symptomatic undiagnosed patients. There is accumulating evidence that FC has been effectively used to monitor the natural course of IBD, to predict relapse, and to see the response to treatment. This novel biomarker has the ability to assess mucosal healing (MH), which is a therapeutic goal in IBD management. A literature search was carried out using PubMed with the keywords FC, IBD, intestinal inflammation, and MH. In our review, we provide an overview of the utility and scope of FC as a biomarker in patients with IBD as well as undiagnosed patients with lower gastrointestinal symptoms.
Collapse
Affiliation(s)
- Shapur Ikhtaire
- Department of Pathology and Molecular Medicine, McMaster University, Room 3N7, HSC, 1280 Main Street West, Hamilton, ON, L8S 1R7, Canada
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Mohammad Sharif Shajib
- Department of Pathology and Molecular Medicine, McMaster University, Room 3N7, HSC, 1280 Main Street West, Hamilton, ON, L8S 1R7, Canada
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Walter Reinisch
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
- Division of Gastroenterology, Department of Medicine, McMaster University, Hamilton, ON, Canada
| | - Waliul Islam Khan
- Department of Pathology and Molecular Medicine, McMaster University, Room 3N7, HSC, 1280 Main Street West, Hamilton, ON, L8S 1R7, Canada.
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada.
| |
Collapse
|
|
21
|
Wright EK, Kamm MA, De Cruz P, Hamilton AL, Ritchie KJ, Keenan JI, Leach S, Burgess L, Aitchison A, Gorelik A, Liew D, Day AS, Gearry RB. Comparison of Fecal Inflammatory Markers in Crohn's Disease. Inflamm Bowel Dis 2016; 22:1086-1094. [PMID: 26818420 DOI: 10.1097/mib.0000000000000671] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Fecal biomarkers are used increasingly to monitor Crohn's disease (CD). However, the relative accuracy of different markers in identifying inflammation has been poorly evaluated. We evaluated fecal calprotectin (FC), lactoferrin (FL), and S100A12 (FS) using endoscopic validation in a prospective study of the progression of CD after intestinal resection. METHODS Data were collected from 135 participants in a prospective, randomized, controlled trial aimed at preventing postoperative CD recurrence. Three hundred nineteen stool samples were tested for FC, FL, and FS preoperatively and 6, 12, and 18 months after resection. Colonoscopy was performed at 6 and/or 18 months. Endoscopic recurrence was assessed blindly using the Rutgeerts score. C-reactive protein (CRP) and Crohn's Disease Activity Index (CDAI) were assessed. RESULTS FC, FL, and FS concentrations were elevated preoperatively (median: 1347, 40.9, and 8.4 μg/g, respectively). At 6 months postoperatively, marker concentrations decreased (166, 3.0, 0.9 μg/g) and were higher in recurrent disease than remission (275 versus 72 μg/g, P < 0.001; 5.7 versus 1.6 μg/g, P = 0.007; 2.0 versus 0.8 μg/g, P = 0.188). FC > 135 μg/g, FL > 3.4 μg/g, and FS > 10.5 μg/g indicated endoscopic recurrence (score ≥ i2) with a sensitivity, specificity, and negative predictive value (NPV) of 0.87, 0.66, and 91%; 0.70, 0.68, and 81%; 0.91, 0.12, and 71%, respectively. FC and FL correlated significantly with the presence and severity of endoscopic recurrence, whereas FS, CRP and CDAI did not. CONCLUSIONS FC was the optimal fecal marker for monitoring disease activity in postoperative CD and was superior to CRP and CDAI. FL offered modest sensitivity for detecting recurrent disease, whereas S100A12 was sensitive but had low specificity and NPV.
Collapse
Affiliation(s)
- Emily K Wright
- *Department of Gastroenterology, St Vincent's Hospital and University of Melbourne, Melbourne, Australia; †Imperial College London, London, United Kingdom; ‡Department of Surgery, University of Otago, Christchurch, New Zealand; §School of Women's and Children's Health, University of NSW, Sydney, Australia; ‖Department of Paediatrics, University of Otago, Christchurch, New Zealand; ¶Melbourne EpiCentre, University of Melbourne and Melbourne Health, Melbourne, Australia; and **Department of Medicine, University of Otago, Christchurch, New Zealand
| | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
22
|
Low Fecal Calprotectin Correlates with Histological Remission and Mucosal Healing in Ulcerative Colitis and Colonic Crohn's Disease. Inflamm Bowel Dis 2016; 22:623-30. [PMID: 26829408 DOI: 10.1097/mib.0000000000000652] [Citation(s) in RCA: 125] [Impact Index Per Article: 13.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Data regarding the correlation of histologic and endoscopic healing with fecal calprotectin (FC) are conflicting. We examined how FC levels correlate with histological and endoscopic remission in colonic inflammatory bowel disease. METHODS Fifty-eight patients (23 with colonic Crohn's disease [CD] and 35 with ulcerative colitis [UC]) were included. Clinical activity was assessed by Harvey-Bradshaw index (CD) and Mayo score (UC). Inflammatory activity was assessed by ileocolonoscopy, C-reactive protein, and FC. Clinical remission was defined as Harvey-Bradshaw index ≤ 4 or Mayo score ≤ 2 and mucosal healing as Mayo endoscopic subscore = 0 (UC), and Simple Endoscopic Score-CD <3 (CD). Histologic activity was assessed in 27 patients (15 CD, 12 UC). Histological remission was defined as absence of active inflammation (Geboes score <3.1) and absence of basal plasmacytosis. RESULTS In UC, FC correlated with clinical Mayo score (r = 0.63, P < 0.0001). This correlation was strengthened by adding the endoscopic subscore (r = 0.90, P < 0.0001). The endoscopic subscore also independently correlated with FC (r = 0.96, P < 0.0001). In Crohn's colitis, endoscopic activity correlated with FC (r = 0.61, P < 0.001). FC levels were lower overall for patients with endoscopic remission compared with active endoscopic disease (median 100 versus 1180 μg/g, P < 0.0001). FC also correlated with histological remission (Geboes score < 3.1) and absence of basal plasmacytosis in CD (r = 0.77, r = 0.80, respectively; P < 0.01). Area under the curve for FC as a predictor of histological remission (Geboes score <3.1) was 0.95 (95% CI, 0.82-1). CONCLUSIONS Low FC correlates well with histological remission and mucosal healing in colonic inflammatory bowel disease and is thus a clinically useful surrogate for inflammatory activity.
Collapse
|
|
23
|
Chang S, Malter L, Hudesman D. Disease monitoring in inflammatory bowel disease. World J Gastroenterol 2015; 21:11246-11259. [PMID: 26523100 PMCID: PMC4616202 DOI: 10.3748/wjg.v21.i40.11246] [Citation(s) in RCA: 128] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2015] [Revised: 07/26/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023] Open
Abstract
The optimal method for monitoring quiescent disease in patients with Crohn’s disease (CD) and ulcerative colitis is yet to be determined. Endoscopic evaluation with ileocolonoscopy is the gold standard but is invasive, costly, and time-consuming. There are many commercially available biomarkers that may be used in clinical practice to evaluate disease status in patients with inflammatory bowel disease (IBD), but the most widely adopted biomarkers are C-reactive protein (CRP) and fecal calprotectin (FC). This review summarizes the evidence for utilizing CRP and FC for monitoring IBD during clinical remission and after surgical resection. Endoscopic correlation with CRP and FC is evaluated in each disease state. Advantages and drawbacks of each biomarker are discussed with special consideration of isolated ileal CD. Fecal immunochemical testing, traditionally used for colorectal cancer screening, is mentioned as a potential new alternative assay in the evaluation of IBD. Based on a mixture of information gleaned from biomarkers, clinical status, and endoscopic evaluation, the best treatment decisions can be made for the patient with IBD.
Collapse
|
|
24
|
Clinicians' guide to the use of fecal calprotectin to identify and monitor disease activity in inflammatory bowel disease. Can J Gastroenterol Hepatol 2015; 29:369-72. [PMID: 26125109 PMCID: PMC4610647 DOI: 10.1155/2015/852723] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Objective monitoring of the severity of inflammation in patients with inflammatory bowel disease (IBD) is an essential part of disease management. However, repeat endoscopy to define extent and severity of inflammation is not practical. Fecal calprotectin (FC) is a biomarker that can be used as a surrogate test to distinguish inflammatory from noninflammatory gastrointestinal disease. METHODS A targeted search of the literature regarding FC, focusing primarily on the past three years, was conducted to develop practical clinical guidance on the current utility of FC in the routine management of IBD patients. RESULTS It is recommended that samples for FC testing be obtained from the first bowel excretion of the day. FC testing should be used as standard of care to accurately confirm inflammation and 'real-time' disease activity when a clinician suspects an IBD flare. Although FC is a reliable marker of inflammation, its role in routine monitoring in improving long-term outcomes has not yet been fully assessed. Based on available evidence, the authors suggest the following cut-off values and management strategies: when FC levels are <50 µg⁄g to 100 µg⁄g, quiescent disease is likely and therapy should be continued; when FC levels are >100 µg⁄g to 250 µg⁄g, inflammation is possible and further testing (eg, colonoscopy) is required to confirm inflammation; and when FC levels are >250 µg⁄g, active inflammation is likely and strategies to control inflammation should be initiated (eg, optimizing current therapies or switching to an alternative therapy). DISCUSSION FC is a useful biomarker to accurately assess the degree of inflammation and should be incorporated into the management of patients with IBD.
Collapse
|
|
25
|
Sands BE. Biomarkers of Inflammation in Inflammatory Bowel Disease. Gastroenterology 2015; 149:1275-1285.e2. [PMID: 26166315 DOI: 10.1053/j.gastro.2015.07.003] [Citation(s) in RCA: 282] [Impact Index Per Article: 28.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2015] [Revised: 07/02/2015] [Accepted: 07/06/2015] [Indexed: 02/07/2023]
Abstract
Recent observations suggest that subjective measures of disease activity in inflammatory bowel disease (IBD) are often misleading. Objective measures of inflammation are more closely associated with important long-term outcomes, but often depend upon invasive and costly procedures such as ileocolonoscopy and cross-sectional imaging by computed tomography or magnetic resonance imaging. Noninvasive, accurate, and inexpensive measures of intestinal inflammation would allow clinicians to adopt widely the paradigm of adjusting therapies with a goal of controlling inflammation. Blood, stool, and urine markers have all been explored as indicators of intestinal inflammation in IBD, and although none has been universally adopted, some have been well-characterized, and others hold great promise. Serum C-reactive protein and fecal calprotectin are among the best-studied noninvasive biomarkers of inflammation in IBD, and their test characteristics have been described in the setting of differentiating IBD from irritable bowel syndrome, for grading inflammation, to describe the response to therapy, and in demonstrating recurrent inflammation after medical or surgically induced remission. High-throughput research platforms, including gene expression arrays, metabolomics and proteomics, are also being applied to the discovery of novel biomarkers of inflammation. It is certain that biomarkers of inflammation will attain growing importance in the clinic as we strive for more effective and cost-effective strategies to treat patients with IBD.
Collapse
Affiliation(s)
- Bruce E Sands
- Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.
| |
Collapse
|
|
26
|
Klimczak K, Lykowska-Szuber L, Eder P, Krela-Kazmierczak I, Stawczyk-Eder K, Szymczak A, Michalak M, Studniarek A, Linke K. The diagnostic usefulness of fecal lactoferrin in the assessment of Crohn's disease activity. Eur J Intern Med 2015. [PMID: 26198785 DOI: 10.1016/j.ejim.2015.06.015] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND Diagnosis and monitoring of Crohn's disease (CD) is difficult and time-consuming. In recent years, diagnostic usefulness of fecal calprotectin has been proven. However, data on the utility of other fecal markers are scarce. AIMS To evaluate the usefulness of fecal lactoferrin (FL) in the assessment of CD activity. METHODS The group consisted of 101 CD patients (median age: 30 years, IQR: 24-37). FL was measured in a single stool sample by using the immunoenzymatic methods. The clinical activity of the disease was evaluated by using the Crohn's Disease Activity Index (CDAI). Depending on the location of the disease, either a colonoscopy or magnetic resonance enterography was performed or both in order to evaluate the disease activity by using appropriate endoscopic and enterographic scores. RESULTS Median FL concentration was 84.14 (IQR: 36.4-302.9) μg/ml and it correlated with C-reactive protein concentration (p=0.0000001, r=0.5), CDAI (p=0.002, r=0.3) and colonic Simple Endoscopic Score for Crohn's Disease (SES-CD) (p=0.000004, r=0.5). Assuming endoscopic remission in the large intestine with colonic SES-CD≤3 points, a ROC curve showed that FL concentration of 145.82 μg/ml had 84.6% sensitivity and 60.5% specificity in discriminating CD patients with endoscopically active and inactive disease [AUC: 0.676 (95% CI: 0.531-0.8), (p=0.0347)]. The positive predictive value for this concentration was 42% and negative predictive value -92%. CONCLUSIONS FL is a sensitive marker of CD activity and it reliably reflects the mucosal inflammatory lesions in large intestine. Thus, it can be helpful in diagnostics and monitoring of CD.
Collapse
Affiliation(s)
- Katarzyna Klimczak
- Department of Gastroenterology, Human Nutrition and Internal Diseases, Poznan University of Medical Sciences, Heliodor Swiecicki Clinical Hospital, Przybyszewskiego Street 49, 60-355 Poznan, Poland
| | - Liliana Lykowska-Szuber
- Department of Gastroenterology, Human Nutrition and Internal Diseases, Poznan University of Medical Sciences, Heliodor Swiecicki Clinical Hospital, Przybyszewskiego Street 49, 60-355 Poznan, Poland
| | - Piotr Eder
- Department of Gastroenterology, Human Nutrition and Internal Diseases, Poznan University of Medical Sciences, Heliodor Swiecicki Clinical Hospital, Przybyszewskiego Street 49, 60-355 Poznan, Poland.
| | - Iwona Krela-Kazmierczak
- Department of Gastroenterology, Human Nutrition and Internal Diseases, Poznan University of Medical Sciences, Heliodor Swiecicki Clinical Hospital, Przybyszewskiego Street 49, 60-355 Poznan, Poland
| | - Kamila Stawczyk-Eder
- Department of Gastroenterology, Human Nutrition and Internal Diseases, Poznan University of Medical Sciences, Heliodor Swiecicki Clinical Hospital, Przybyszewskiego Street 49, 60-355 Poznan, Poland
| | - Aleksandra Szymczak
- Department of Gastroenterology, Human Nutrition and Internal Diseases, Poznan University of Medical Sciences, Heliodor Swiecicki Clinical Hospital, Przybyszewskiego Street 49, 60-355 Poznan, Poland
| | - Michal Michalak
- Department of Computer Science and Statistics, Poznan University of Medical Sciences, Dabrowskiego Street 79, 60-529, Poland
| | - Adam Studniarek
- Department of Gastroenterology, Human Nutrition and Internal Diseases, Poznan University of Medical Sciences, Heliodor Swiecicki Clinical Hospital, Przybyszewskiego Street 49, 60-355 Poznan, Poland
| | - Krzysztof Linke
- Department of Gastroenterology, Human Nutrition and Internal Diseases, Poznan University of Medical Sciences, Heliodor Swiecicki Clinical Hospital, Przybyszewskiego Street 49, 60-355 Poznan, Poland
| |
Collapse
|
|
27
|
Boschetti G, Laidet M, Moussata D, Stefanescu C, Roblin X, Phelip G, Cotte E, Passot G, Francois Y, Drai J, Del Tedesco E, Bouhnik Y, Flourie B, Nancey S. Levels of Fecal Calprotectin Are Associated With the Severity of Postoperative Endoscopic Recurrence in Asymptomatic Patients With Crohn's Disease. Am J Gastroenterol 2015; 110:865-72. [PMID: 25781366 DOI: 10.1038/ajg.2015.30] [Citation(s) in RCA: 110] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2014] [Revised: 12/01/2014] [Accepted: 01/01/2015] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Fecal calprotectin (fCal) is widely used as marker of gut inflammation and is strongly associated with the severity of endoscopic lesions in Crohn's disease (CD). We analyzed the relationships between levels of fCal and high-sensitivity C-reactive protein (hsCRP) and the presence and severity of postoperative endoscopic recurrence in asymptomatic CD patients (Harvey-Bradshaw index≤3). METHODS Blood and fecal samples were collected in consecutive asymptomatic CD patients (Harvey-Bradshaw index 0.85 ± 0.19, mean ± s.e.m.) who had undergone an ileocolonic resection. hsCRP and fCal were measured and a routine ileocolonoscopy was performed within 18 months (median 7 months) from resection, to detect endoscopic recurrence according to the Rutgeerts score. RESULTS Eighty-six patients were included in this prospective multicenter observational cohort. fCal concentrations differed significantly in patients with endoscopic recurrence when compared with those in endoscopic remission (mean ± s.e.m.: 473 ± 78 μg/g vs. 115 ± 18 μg/g; P<0.0001). The area under the receiver operating characteristic (ROC) curve to discriminate between patients in endoscopic remission and recurrence was 0.86 for fCal and lower for hsCRP (0.70). The best cutoff point for fCal to distinguish between endoscopic remission and recurrence was 100 μg/g as determined by the ROC curve, and its sensitivity, specificity, positive and negative predictive values (NPVs), as well as overall accuracy were 95%, 54%, 69%, 93%, and 77%, respectively. CONCLUSION Measurement of fCal concentrations is a promising and useful tool for monitoring asymptomatic CD patients after ileocolonic resection. Taking into account the high NPV of fCal, a threshold below 100 μg/g could avoid systematic ileocolonoscopies in 30% of patients from this population.
Collapse
Affiliation(s)
- Gilles Boschetti
- 1] Hospices Civils de Lyon, Department of Gastroenterology, Hopital Lyon-Sud, Pierre-Bénite, France [2] INSERM U1111, International Center for Research in Infectiology, Lyon, France
| | - Marc'harid Laidet
- Hospices Civils de Lyon, Department of Gastroenterology, Hopital Lyon-Sud, Pierre-Bénite, France
| | - Driffa Moussata
- Hospices Civils de Lyon, Department of Gastroenterology, Hopital Lyon-Sud, Pierre-Bénite, France
| | - Carmen Stefanescu
- Assistance Publique-Hôpitaux de Paris, Department of Gastroenterology, Hopital Beaujon, Paris 7 Université, Clichy, France
| | - Xavier Roblin
- Department of Gastroenterology, Hopital Nord, Saint-Etienne, France
| | - Gildas Phelip
- Hospices Civils de Lyon, Department of Gastroenterology, Hopital Lyon-Sud, Pierre-Bénite, France
| | - Eddy Cotte
- Hospices Civils de Lyon, Department of Digestive Surgery, Hopital Lyon-Sud, Pierre-Bénite, France
| | - Guillaume Passot
- Hospices Civils de Lyon, Department of Digestive Surgery, Hopital Lyon-Sud, Pierre-Bénite, France
| | - Yves Francois
- Hospices Civils de Lyon, Department of Digestive Surgery, Hopital Lyon-Sud, Pierre-Bénite, France
| | - Jocelyne Drai
- Laboratory of Biochemistry, Hospices Civils de Lyon, Hopital Lyon-Sud, Pierre-Bénite, France
| | | | - Yoram Bouhnik
- Assistance Publique-Hôpitaux de Paris, Department of Gastroenterology, Hopital Beaujon, Paris 7 Université, Clichy, France
| | - Bernard Flourie
- 1] Hospices Civils de Lyon, Department of Gastroenterology, Hopital Lyon-Sud, Pierre-Bénite, France [2] INSERM U1111, International Center for Research in Infectiology, Lyon, France
| | - Stephane Nancey
- 1] Hospices Civils de Lyon, Department of Gastroenterology, Hopital Lyon-Sud, Pierre-Bénite, France [2] INSERM U1111, International Center for Research in Infectiology, Lyon, France
| |
Collapse
|
|
28
|
Furderer T, Mantion G, Heyd B. Emergency surgery for intestinal obstruction revealing ileal Crohn's disease (CD) during pregnancy. BMJ Case Rep 2015; 2015:bcr-2013-009468. [PMID: 25969480 DOI: 10.1136/bcr-2013-009468] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Few data are available regarding emergency surgery for Crohn's disease (CD) during pregnancy. A 22-year -old woman, at 26 weeks of pregnancy, was admitted for premature labour, intestinal obstruction and systemic inflammation. Biology and ultrasonography were not helpful; imaging was completed with a CT scan, which confirmed the mechanical ileal obstruction. The intestinal obstruction worsened and led to emergency surgery. An inflammatory stenosis of the terminal ileum with two fistulas was found. An ileal resection and ileostomy were performed. The pathological analysis of the resected specimen confirmed CD. The postoperative course was uneventful. The delivery of a baby with normal weight and status occurred at term (40 weeks of amenorrhoea). There have been only 10 case reports of intestinal complications revealing CD during pregnancy. The delay in diagnosis and adequate treatment led to significant maternal and fetal morbidity and mortality. This case suggests that intestinal surgery for CD is feasible during pregnancy and may be associated with a favourable outcome for the baby as well as for the mother.
Collapse
Affiliation(s)
| | | | - Bruno Heyd
- University Hospital Besançon, Besançon, France
| |
Collapse
|
|
29
|
Reply to can fecal calprotection identify postoperative recurrence of Crohn's disease? Inflamm Bowel Dis 2015; 21:E7. [PMID: 25856771 DOI: 10.1097/mib.0000000000000416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
|
|
30
|
Wright EK, Kamm MA, De Cruz P, Hamilton AL, Ritchie KJ, Krejany EO, Leach S, Gorelik A, Liew D, Prideaux L, Lawrance IC, Andrews JM, Bampton PA, Jakobovits SL, Florin TH, Gibson PR, Debinski H, Macrae FA, Samuel D, Kronborg I, Radford-Smith G, Selby W, Johnston MJ, Woods R, Elliott PR, Bell SJ, Brown SJ, Connell WR, Day AS, Desmond PV, Gearry RB. Measurement of fecal calprotectin improves monitoring and detection of recurrence of Crohn's disease after surgery. Gastroenterology 2015; 148:938-947.e1. [PMID: 25620670 DOI: 10.1053/j.gastro.2015.01.026] [Citation(s) in RCA: 222] [Impact Index Per Article: 22.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2014] [Revised: 01/13/2015] [Accepted: 01/17/2015] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS Crohn's disease (CD) usually recurs after intestinal resection; postoperative endoscopic monitoring and tailored treatment can reduce the chance of recurrence. We investigated whether monitoring levels of fecal calprotectin (FC) can substitute for endoscopic analysis of the mucosa. METHODS We analyzed data collected from 135 participants in a prospective, randomized, controlled trial, performed at 17 hospitals in Australia and 1 hospital in New Zealand, that assessed the ability of endoscopic evaluations and step-up treatment to prevent CD recurrence after surgery. Levels of FC, serum levels of C-reactive protein (CRP), and Crohn's disease activity index (CDAI) scores were measured before surgery and then at 6, 12, and 18 months after resection of all macroscopic Crohn's disease. Ileocolonoscopies were performed at 6 months after surgery in 90 patients and at 18 months after surgery in all patients. RESULTS Levels of FC were measured in 319 samples from 135 patients. The median FC level decreased from 1347 μg/g before surgery to 166 μg/g at 6 months after surgery, but was higher in patients with disease recurrence (based on endoscopic analysis; Rutgeerts score, ≥i2) than in patients in remission (275 vs 72 μg/g, respectively; P < .001). Combined 6- and 18-month levels of FC correlated with the presence (r = 0.42; P < .001) and severity (r = 0.44; P < .001) of CD recurrence, but the CRP level and CDAI score did not. Levels of FC greater than 100 μg/g indicated endoscopic recurrence with 89% sensitivity and 58% specificity, and a negative predictive value (NPV) of 91%; this means that colonoscopy could have been avoided in 47% of patients. Six months after surgery, FC levels less than 51 μg/g in patients in endoscopic remission predicted maintenance of remission (NPV, 79%). In patients with endoscopic recurrence at 6 months who stepped-up treatment, FC levels decreased from 324 μg/g at 6 months to 180 μg/g at 12 months and 109 μg/g at 18 months. CONCLUSIONS In this analysis of data from a prospective clinical trial, FC measurement has sufficient sensitivity and NPV values to monitor for CD recurrence after intestinal resection. Its predictive value might be used to identify patients most likely to relapse. After treatment for recurrence, the FC level can be used to monitor response to treatment. It predicts which patients will have disease recurrence with greater accuracy than CRP level or CDAI score.
Collapse
Affiliation(s)
- Emily K Wright
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia; University of Melbourne, Melbourne, Australia
| | - Michael A Kamm
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia; University of Melbourne, Melbourne, Australia.
| | - Peter De Cruz
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia; University of Melbourne, Melbourne, Australia
| | - Amy L Hamilton
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia; University of Melbourne, Melbourne, Australia
| | - Kathryn J Ritchie
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia
| | | | - Steven Leach
- School of Women's and Children's Health, University of New South Wales, Sydney, Australia
| | | | - Danny Liew
- Melbourne EpiCentre, University of Melbourne, Melbourne, Australia
| | - Lani Prideaux
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia; University of Melbourne, Melbourne, Australia
| | - Ian C Lawrance
- Centre for Inflammatory Bowel Diseases, Fremantle Hospital, Freemantle, Australia; The University of Western Australia, Fremantle, Australia
| | - Jane M Andrews
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, Australia; University of Adelaide, Adelaide, Australia
| | - Peter A Bampton
- Department of Gastroenterology and Hepatology, Flinders Medical Centre, Adelaide, Australia; Flinders University, Adelaide, Australia
| | - Simon L Jakobovits
- Department of Gastroenterology, Alfred Health, Melbourne, Australia; Monash University, Melbourne, Australia
| | - Timothy H Florin
- Department of Gastroenterology, Mater Health Services, Brisbane, Australia
| | - Peter R Gibson
- Department of Gastroenterology, Alfred Health, Melbourne, Australia; Monash University, Melbourne, Australia
| | - Henry Debinski
- Melbourne Gastrointestinal Investigation Unit, Cabrini Hospital, Melbourne, Australia
| | - Finlay A Macrae
- University of Melbourne, Melbourne, Australia; Department of Colorectal Medicine and Genetics, and Department of Medicine, Royal Melbourne Hospital, Melbourne, Australia
| | - Douglas Samuel
- Department of Gastroenterology, Bankstown Hospital, Sydney, Australia
| | - Ian Kronborg
- Department of Gastroenterology, Western Hospital, Melbourne, Australia
| | - Graeme Radford-Smith
- IBD Group Queensland Institute of Medical Research, University of Queensland, Brisbane, Australia; Department of Gastroenterology, Royal Brisbane and Womens Hospital, Brisbane, Australia
| | - Warwick Selby
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, Australia
| | - Michael J Johnston
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia
| | - Rodney Woods
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia
| | - P Ross Elliott
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia
| | - Sally J Bell
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia
| | - Steven J Brown
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia
| | - William R Connell
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia
| | - Andrew S Day
- Department of Paediatrics, University of Otago, Christchurch, New Zealand
| | - Paul V Desmond
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia; University of Melbourne, Melbourne, Australia
| | - Richard B Gearry
- Department of Medicine, University of Otago, Christchurch, New Zealand
| |
Collapse
|
|
31
|
Yamamoto T. The clinical value of faecal calprotectin and lactoferrin measurement in postoperative Crohn's disease. United European Gastroenterol J 2015; 3:5-10. [PMID: 25653853 DOI: 10.1177/2050640614558106] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2014] [Accepted: 10/09/2014] [Indexed: 12/13/2022] Open
Abstract
Most patients with Crohn's disease (CD) ultimately require one or more operations over their lifetime. Nevertheless, surgery is not a cure and postoperative CD recurrence is common. Ileocolonoscopy has been considered to be the gold standard in the diagnosis and monitoring of postoperative recurrence in patients with CD. However, endoscopy is a time-consuming and invasive procedure. Simple and non-invasive methods for the detection of postoperative recurrence are desirable. Faecal inflammatory biomarkers such as calprotectin and lactoferrin provide an accurate and non-invasive diagnostic and monitoring modality for inflammatory bowel disease. However, there have been limited data on the role of faecal biomarkers in the postoperative setting. Recently, several studies evaluated the value of faecal calprotectin and lactoferrin measurement after surgery for CD. This review was conducted to assess the role of faecal calprotectin and lactoferrin measurements in patients with postoperative CD.
Collapse
Affiliation(s)
- Takayuki Yamamoto
- Inflammatory Bowel Disease Centre and Department of Surgery, Yokkaichi Hazu Medical Centre, Yokkaichi, Japan
| |
Collapse
|
|
32
|
Fecal calprotectin for evaluating postoperative recurrence of Crohn's disease: a meta-analysis of prospective studies. Inflamm Bowel Dis 2015; 21:315-22. [PMID: 25569739 DOI: 10.1097/mib.0000000000000262] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Fecal calprotectin (FC) levels have been extensively reported to correlate with clinical and endoscopic activities in Crohn's disease (CD); however, the utility of FC levels in the postoperative setting remains to be determined. Using meta-analysis, we aimed to evaluate the utility of FC as a noninvasive marker of recurrence in patients with CD who had undergone previous surgical resection. METHODS An electronic search using keywords related to CD and FC was performed in multiple electronic resources from 1966 to March 2014. The extracted data were pooled using a hierarchical summary receiver operating curve model. RESULTS Ten articles met the inclusion criteria, and methodological quality was determined in detail for each study. The 10 studies presented FC levels in 613 postoperative CD patients. The pooled sensitivity and specificity values for assessing suspected endoscopic recurrence were 0.82 (95% confidence interval (CI), 0.73-0.89, 8 studies, n = 391) and 0.61 (95% CI, 0.51-0.71), respectively. The overall positive and negative likelihood ratios were 2.11 (95% CI, 1.68-2.66) and 0.29 (95% CI, 0.197-0.44), respectively. The pooled sensitivity and specificity values for evaluating clinical relapse were 0.59 (95% CI, 0.47-0.71; 3 studies, n = 183) and 0.88 (95% CI, 0.80-0.93), respectively. The overall positive and negative likelihood ratios were 5.10 and 0.47, respectively. CONCLUSIONS As a simple and noninvasive marker, FC is useful in evaluating recurrence of postoperative patients with CD.
Collapse
|
|
33
|
Sipponen T, Kolho KL. Fecal calprotectin in diagnosis and clinical assessment of inflammatory bowel disease. Scand J Gastroenterol 2015; 50:74-80. [PMID: 25523558 DOI: 10.3109/00365521.2014.987809] [Citation(s) in RCA: 96] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
The fecal neutrophil-derived biomarker calprotectin has several features of an ideal noninvasive test for detecting intestinal inflammation: it is simple, reliable, and low in cost. Its utility in differentiating inflammatory bowel diseases (IBDs) from functional conditions such as irritable bowel syndrome is well documented. Fecal calprotectin (FC) correlates closely with endoscopic activity of IBD. Emerging evidence suggest its usefulness in serial monitoring of disease activity and of therapy success in IBD. A low FC concentration predicts persistence of clinical remission especially in non-symptomatic ulcerative colitis and Crohn's colitis. Here, an overview is given to the current role of FC in diagnosis and clinical assessment of IBD.
Collapse
Affiliation(s)
- Taina Sipponen
- Department of Medicine, Division of Gastroenterology, Helsinki University Central Hospital , Helsinki , Finland
| | | |
Collapse
|
|
34
|
Lehmann FS, Burri E, Beglinger C. The role and utility of faecal markers in inflammatory bowel disease. Therap Adv Gastroenterol 2015; 8:23-36. [PMID: 25553077 PMCID: PMC4265086 DOI: 10.1177/1756283x14553384] [Citation(s) in RCA: 109] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Crohn's disease and ulcerative colitis are characterized by periods of symptomatic relapse and remission. Diagnosis and assessment of inflammatory bowel disease has so far been based on clinical evaluation, serum parameters, radiology and endoscopy. Faecal markers such as calprotectin or lactoferrin have emerged as new diagnostic tools to detect and monitor intestinal inflammation. This review focuses on their potential clinical applications and limitations in the management of inflammatory bowel disease.
Collapse
Affiliation(s)
- Frank S. Lehmann
- Division of Gastroenterology and Hepatology, University Hospital of Basel, Switzerland
| | - Emanuel Burri
- Division of Gastroenterology and Hepatology, University Hospital of Basel, Switzerland
| | - Christoph Beglinger
- Division of Gastroenterology and Hepatology, University Hospital of Basel, 4031 Basel, Switzerland
| |
Collapse
|
|
35
|
Role of biomarkers in the study and management of inflammatory bowel disease: a "nonsystematic" review. Inflamm Bowel Dis 2014; 20:2511-8. [PMID: 25222663 DOI: 10.1097/mib.0000000000000135] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
|
|
36
|
Wright EK, De Cruz P, Gearry R, Day AS, Kamm MA. Fecal biomarkers in the diagnosis and monitoring of Crohn's disease. Inflamm Bowel Dis 2014; 20:1668-1677. [PMID: 24918319 DOI: 10.1097/mib.0000000000000087] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The diagnosis and monitoring of Crohn's disease has traditionally relied on clinical assessment, serum markers of inflammation, and endoscopic examination. Fecal biomarkers such as calprotectin, lactoferrin, and S100A12 are predominantly derived from neutrophils, are easily detectable in the feces, and are emerging as valuable markers of intestinal inflammation. This review focuses on the role of fecal biomarkers in the diagnosis and monitoring of Crohn's disease, in particular how these biomarkers change with disease activity and remission, how they can be used to monitor the response to medical therapy, their value in predicting clinical relapse, and their role in monitoring the postoperative state.
Collapse
Affiliation(s)
- Emily K Wright
- *St. Vincent's Hospital and University of Melbourne, Melbourne, Australia; and †Christchurch Hospital and University of Otago, Christchurch, New Zealand
| | | | | | | | | |
Collapse
|
|
37
|
Abstract
Surgical treatment does not cure Crohn's disease, and postoperative recurrence is a feature of the clinical course of the disease. Ileocolonoscopy remains the gold standard for the surveillance of recurrent Crohn's disease and should be performed 6-12 months after an operation. Many other non-invasive techniques are also useful and complement endoscopy for the early diagnosis of postoperative recurrence. Anti-TNF agents show great efficacy for the prevention of postoperative recurrence, and long-term use can maintain remission. It remains undetermined whether early treatment after postoperative endoscopic recurrence is ultimately as efficacious as prophylactic therapy.
Collapse
Affiliation(s)
- Zhiping Yang
- Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, 127 West Changle Road, Xi'an, China
| | | | | | | |
Collapse
|
|
38
|
Lasson A, Strid H, Ohman L, Isaksson S, Olsson M, Rydström B, Ung KA, Stotzer PO. Fecal calprotectin one year after ileocaecal resection for Crohn's disease--a comparison with findings at ileocolonoscopy. J Crohns Colitis 2014; 8:789-95. [PMID: 24418661 DOI: 10.1016/j.crohns.2013.12.015] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2013] [Revised: 12/18/2013] [Accepted: 12/18/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Ileocaecal resection for Crohn's disease is commonly performed. The severity of endoscopic lesions in the anastomotic area one year postoperatively is considered to reflect the subsequent clinical course. Fecal calprotectin (FC) has been shown to correlate with the findings at ileocolonoscopy in Crohn's disease. The objectives of this study were to assess whether the concentration of FC reflects the endoscopic findings one year after ileocaecal resection and to evaluate the variation of FC in individual patients during 6months prior to the ileocolonoscopy. METHODS Thirty patients with Crohn's disease and ileocaecal resection performed within one year were included. Stool samples were delivered monthly until an ileocolonoscopy was performed one year postoperatively. RESULTS One year after surgery the median values of FC were not significantly different between the patients in endoscopic remission (n=17) and the patients with an endoscopic recurrence (189 (75-364) vs 227 (120-1066)μg/g; p=0.25). However, most patients with low values were in remission and all patients with high (>600μg/g) calprotectin values had recurrent disease. The variability of the FC concentration was most pronounced in patients with diarrhea. CONCLUSIONS We found no statistical difference in the concentrations of calprotectin between patients in endoscopic remission and patients with a recurrent disease one year after ileocaecal resection for Crohn's disease. However, among the minority of patients with low or high values, FC indicated remission and recurrence, respectively. There was significant variation of the fecal calprotectin concentrations over time, which affects the utility of calprotectin in clinical practice.
Collapse
Affiliation(s)
- Anders Lasson
- Department of Internal Medicine, Södra Älvsborgs Hospital, Borås, Sweden.
| | - Hans Strid
- Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
| | - Lena Ohman
- Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Sweden.
| | - Stefan Isaksson
- Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Sweden.
| | - Mikael Olsson
- Department of Internal Medicine, Norra Älvsborgs Hospital, Trollhättan, Sweden.
| | - Britt Rydström
- Department of Internal Medicine, Södra Älvsborgs Hospital, Borås, Sweden.
| | - Kjell-Arne Ung
- Department of Internal Medicine, Skaraborgs Hospital, Skövde, Sweden.
| | - Per-Ove Stotzer
- Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
| |
Collapse
|
|
39
|
Yamamoto T, Shiraki M, Bamba T, Umegae S, Matsumoto K. Faecal calprotectin and lactoferrin as markers for monitoring disease activity and predicting clinical recurrence in patients with Crohn's disease after ileocolonic resection: A prospective pilot study. United European Gastroenterol J 2014; 1:368-74. [PMID: 24917985 DOI: 10.1177/2050640613501818] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2013] [Accepted: 07/23/2013] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Several studies have reported that faecal calprotectin and lactoferrin showed a close correlation with endoscopic inflammation in patients with inflammatory bowel disease. However, the clinical significance of faecal calprotectin or lactoferrin in postoperative Crohn's disease (CD) is not fully evaluated. This prospective study was to investigate the relationship between endoscopic activity, and faecal calprotectin and lactoferrin, and assess the predictive value of these markers for future recurrence. METHODS Twenty patients who remained in remission during 6-12 months after ileocolonic resection for CD were included. All patients underwent ileocolonoscopy for assessing endoscopic activity (Rutgeerts score) in the neo-terminal ileum. A stool sample was collected for measurement of calprotectin and lactoferrin. All patients were then followed up for 12 months, and clinical recurrence was defined as a CDAI >150 with an increase of ≥70 points. RESULTS The mean time between surgery and the endoscopic examination at entry was 7.2 months. The endoscopic scores were i0 or i1 in 10 patients, i2 in six patients, i3 in three patients, and i4 in one patient. Both calprotectin and lactoferrin positively correlated with the endoscopic scores (p = 0.0001 and p = 0.038, respectively). Six patients developed clinical recurrence during the 12-month follow-up. Both calprotectin and lactoferrin levels were significantly higher in patients with clinical recurrence than those in remission (p = 0.0007 and p = 0.025, respectively). A cutoff value of 170 µg/g for calprotectin had a sensitivity of 83% and a specificity of 93% to predict a risk of clinical recurrence, while a cutoff value of 140 µg/g for lactoferrin had a sensitivity of 67% and a specificity of 71%. CONCLUSIONS Both calprotectin and lactoferrin levels correlate well with endoscopic activity after ileocolonic resection for CD. Calprotectin and lactoferrin could be clinically relevant biomarkers for predicting postoperative recurrence. Further well-designed large trials should strengthen the findings of the present investigation.
Collapse
Affiliation(s)
- Takayuki Yamamoto
- Inflammatory Bowel Disease Centre, Yokkaichi Social Insurance Hospital, Yokkaichi, Mie, Japan
| | - Manabu Shiraki
- Inflammatory Bowel Disease Centre, Yokkaichi Social Insurance Hospital, Yokkaichi, Mie, Japan
| | - Takuya Bamba
- Inflammatory Bowel Disease Centre, Yokkaichi Social Insurance Hospital, Yokkaichi, Mie, Japan
| | - Satoru Umegae
- Inflammatory Bowel Disease Centre, Yokkaichi Social Insurance Hospital, Yokkaichi, Mie, Japan
| | - Koichi Matsumoto
- Inflammatory Bowel Disease Centre, Yokkaichi Social Insurance Hospital, Yokkaichi, Mie, Japan
| |
Collapse
|
|
40
|
Abstract
Diagnosis and monitoring of inflammatory bowel diseases rely on clinical, endoscopic, and radiologic parameters. Inflammatory biomarkers have been investigated as a surrogate marker for endoscopic diagnosis of inflammatory activity. Fecal inflammatory biomarkers such as calprotectin and lactoferrin are direct products of bowel inflammation and provide an accurate and noninvasive diagnostic and monitoring modality for Crohn's disease and ulcerative colitis. This report contains an overview of the currently existing literature pertaining to clinical implications of fecal biomarkers for diagnosis, monitoring, and prediction of outcomes of inflammatory bowel disease.
Collapse
|
|
41
|
Burri E, Beglinger C. The use of fecal calprotectin as a biomarker in gastrointestinal disease. Expert Rev Gastroenterol Hepatol 2014; 8:197-210. [PMID: 24345070 DOI: 10.1586/17474124.2014.869476] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Abdominal discomfort including pain, bloating and diarrhea is common. It often arises from functional gastrointestinal disorders but may indicate inflammatory bowel disease (IBD). Calprotectin is an abundant neutrophil protein that is released during inflammation. When measured in feces, it can be used to differentiate between non-organic and inflammatory intestinal disorders, especially to identify IBD. Fecal calprotectin might also be useful to monitor patients with IBD under treatment and to predict the risk of recurrence of active disease prior to clinical relapse. The use of fecal calprotectin has been investigated in a number of gastrointestinal disorders other than IBD, for example, as screening test for colorectal cancer but the available data are limited. This article summarizes the current literature on the use of fecal calprotectin in clinical practice.
Collapse
Affiliation(s)
- Emanuel Burri
- Department of Gastroenterology and Hepatology, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland
| | | |
Collapse
|
|
42
|
Basso D, Zambon CF, Plebani M. Inflammatory bowel diseases: from pathogenesis to laboratory testing. Clin Chem Lab Med 2014; 52:471-81. [DOI: 10.1515/cclm-2013-0588] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2013] [Accepted: 09/10/2013] [Indexed: 02/07/2023]
|
|
43
|
A new rapid test for fecal calprotectin predicts endoscopic remission and postoperative recurrence in Crohn's disease. J Crohns Colitis 2013; 7:e641-51. [PMID: 23810085 DOI: 10.1016/j.crohns.2013.05.005] [Citation(s) in RCA: 122] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2013] [Revised: 05/20/2013] [Accepted: 05/20/2013] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Fecal calprotectin (FC), as determined by the enzyme-linked immunoassay (ELISA) test, has been proposed as a promising biomarker of endoscopic activity in Crohn's disease (CD). However data on its accuracy in predicting endoscopic remission according to location and postoperative recurrence (POR) is scarce. Our objective was to evaluate the ability of FC determined by a new quantitative point-of-care test (FC-QPOCT) to predict endoscopic remission and POR in CD patients. METHODS FC was determined simultaneously by an enzyme-linked immunoassay test (FC-ELISA) and a FC-QPOCT in CD patients undergoing colonoscopy. Clinical disease activity was assessed according to the Crohn's Disease Activity Index (CDAI). Endoscopic results were assessed according to the Crohn's Disease Endoscopic Activity Index of Severity (CDEIS) and postoperative recurrence according to the Rutgeerts' score. RESULTS A total of 115 ileocolonoscopies were performed (29 on patients with ileocolonic resection). FC levels correlated more closely with the CDEIS than leucocytes, platelets or CRP. The prediction of "endoscopic remission" (CDEIS<3), using FC-QPOCT (cut-off 272 μg/g) and FC-ELISA (cut-off 274 μg/g) presented an AUC of 0.933 and 0.935 respectively. FC-QPOCT results correlated better with endoscopic activity in the ileocolonic location (Pearson's correlation, r=0.879; P<0.001), than the colonic (r=0.725; P<0.001) or the ileal location (r=0.437; P=0.016). Median FC-QPOCT levels discriminated Rutgeerts' score i0-i1 from i2-i4 (98 (range 30-306) μg/g vs. 234.5 (range 100-612) μg/g respectively, P=0.012). CONCLUSIONS FC determined by rapid quantitative test predicts "endoscopic remission" and endoscopic postoperative recurrence in CD patients.
Collapse
|
|
44
|
Yamamoto T, Watanabe T. Strategies for the prevention of postoperative recurrence of Crohn's disease. Colorectal Dis 2013; 15:1471-80. [PMID: 23809911 DOI: 10.1111/codi.12326] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2013] [Accepted: 03/22/2013] [Indexed: 12/13/2022]
Abstract
AIM To review the optimal strategy to prevent recurrence of Crohn's disease (CD) after surgery, with particular emphasis on the risk factors that predict postoperative recurrence, methods of monitoring for recurrence and medications used to prevent postoperative recurrence. METHOD MEDLINE and the Cochrane Library were searched for clinical trials and meta-analyses that studied postoperative recurrence and prophylactic medications in CD. RESULTS The most significant factor that predicted postoperative recurrence was patient smoking status. Smokers had an increased risk of recurrence (odds ratio = 2.15; 95% confidence interval (CI) = 1.42-3.27). Similarly, perforating CD appeared to be associated with a higher recurrence rate compared with nonperforating CD (hazard ratio = 1.50; 95% CI = 1.16-1.93). The optimal monitoring strategy for postoperative recurrence has yet to be established. Nonetheless, ileocolonoscopy is considered to be the gold standard. Noninvasive imaging techniques including contrast ultrasonography and capsule endoscopy appear to be useful for postoperative monitoring. A number of meta-analyses found that mesalazine, nitroimidazole antibiotics and purine analogues (azathioprine/6-mercaptopurine) significantly reduced the risk of postoperative recurrence when compared with placebo. Additionally, recent randomized controlled trials have suggested that an early intervention with infliximab is likely to prevent recurrence after ileocolonic resection. Likewise, in prospective studies, biological therapy (infliximab/adalimumab) reduced clinical and endoscopic CD activity in patients with early endoscopic recurrence after surgery. CONCLUSION Although additional evidence is necessary, endoscopic monitoring and treatment step-up should be used to prevent postoperative recurrence of CD.
Collapse
Affiliation(s)
- T Yamamoto
- Inflammatory Bowel Disease Centre and Department of Surgery, Yokkaichi Social Insurance Hospital, Yokkaichi, Mie, Japan
| | | |
Collapse
|
|
45
|
Papamichael K, Karatzas P, Mantzaris GJ. Faecal calprotectin but not C-reactive protein (CRP) or Crohn's Disease Activity Index (CDAI) may predict post-operative endoscopic recurrence of Crohn's disease. J Crohns Colitis 2013; 7:e700-1. [PMID: 23953238 DOI: 10.1016/j.crohns.2013.07.008] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2013] [Accepted: 07/18/2013] [Indexed: 12/13/2022]
|
|
46
|
Sipponen T. Diagnostics and prognostics of inflammatory bowel disease with fecal neutrophil-derived biomarkers calprotectin and lactoferrin. Dig Dis 2013; 31:336-44. [PMID: 24246984 DOI: 10.1159/000354689] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Crohn's disease (CD), ulcerative colitis (UC), and colitis unclassified, collectively defined as inflammatory bowel disease (IBD), are the consequence of chronic inflammatory reactions in the gastrointestinal tissue. Endoscopy with biopsies is the mainstay in the diagnosis of this inflammation and is also important in the assessment of disease activity and monitoring of treatment. Furthermore, mucosal healing is increasingly becoming a therapeutic target for treatment of IBD and the golden standard of assessing it is endoscopy. However, due to the costs, invasiveness, and to limited endoscopic capacity, the need is strong for reliable surrogate markers of intestinal inflammation. Bowel contents, being in close contact with intestinal mucosa, can take up molecules that are measurable from stool samples and thus can serve as markers of inflammation. The fecal neutrophil-derived biomarkers, especially calprotectin and lactoferrin, have several features of an ideal test for detecting intestinal inflammation: they are noninvasive, simple, and low in cost. The utility of these biomarkers in distinguishing IBD from noninflammatory conditions such as irritable bowel syndrome is well documented. They correlate closely with endoscopic activity both in CD and UC. They allow serial monitoring of disease activity and of treatment success, and can even serve in predicting clinical relapse in unsymptomatic patients or sustained remission after induction with TNF-α-blocking agents. In this review an overview will be given to the role of fecal neutrophil-derived biomarkers calprotectin and lactoferrin in diagnostics and prognostics of IBD.
Collapse
Affiliation(s)
- Taina Sipponen
- Department of Medicine, Clinic of Gastroenterology, Helsinki University Central Hospital, Helsinki, Finland
| |
Collapse
|
|
47
|
Optimising monitoring in the management of Crohn's disease: a physician's perspective. J Crohns Colitis 2013; 7:653-69. [PMID: 23562672 DOI: 10.1016/j.crohns.2013.02.005] [Citation(s) in RCA: 80] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2013] [Accepted: 02/05/2013] [Indexed: 02/08/2023]
Abstract
Management of Crohn's disease has traditionally placed high value on subjective symptom assessment; however, it is increasingly appreciated that patient symptoms and objective parameters of inflammation can be disconnected. Therefore, strategies that objectively monitor inflammatory activity should be utilised throughout the disease course to optimise patient management. Initially, a thorough assessment of the severity, location and extent of disease is needed to ensure a correct diagnosis, identify any complications, help assess prognosis and select appropriate therapy. During follow-up, clinical decision-making should be driven by disease activity monitoring, with the aim of optimising treatment for tight disease control. However, few data exist to guide the choice of monitoring tools and the frequency of their use. Furthermore, adaption of monitoring strategies for symptomatic, asymptomatic and post-operative patients has not been well defined. The Annual excHangE on the ADvances in Inflammatory Bowel Disease (IBD Ahead) 2011 educational programme, which included approximately 600 gastroenterologists from 36 countries, has developed practice recommendations for the optimal monitoring of Crohn's disease based on evidence and/or expert opinion. These recommendations address the need to incorporate different modalities of disease assessment (symptom and endoscopic assessment, measurement of biomarkers of inflammatory activity and cross-sectional imaging) into robust monitoring. Furthermore, the importance of measuring and recording parameters in a standardised fashion to enable longitudinal evaluation of disease activity is highlighted.
Collapse
|
|
48
|
Rodríguez-Moranta F, Lobatón T, Rodríguez-Alonso L, Guardiola J. Calprotectina fecal en el diagnóstico de enfermedades inflamatorias. GASTROENTEROLOGIA Y HEPATOLOGIA 2013; 36:400-6. [DOI: 10.1016/j.gastrohep.2012.10.008] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/28/2012] [Accepted: 10/29/2012] [Indexed: 12/20/2022]
|
|
49
|
De Cruz P, Kamm MA, Prideaux L, Allen PB, Moore G. Mucosal healing in Crohn's disease: a systematic review. Inflamm Bowel Dis 2013; 19:429-44. [PMID: 22539420 DOI: 10.1002/ibd.22977] [Citation(s) in RCA: 120] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The traditional goals of Crohn's disease therapy, to induce and maintain clinical remission, have not clearly changed its natural history. In contrast, emerging evidence suggests that achieving and maintaining mucosal healing may alter the natural history of Crohn's disease, as it has been associated with more sustained clinical remission and reduced rates of hospitalization and surgical resection. Induction and maintenance of mucosal healing should therefore be a goal toward which therapy is now directed. Unresolved issues pertain to the benefit of achieving mucosal healing at different stages of the disease, the relationship between mucosal healing and transmural inflammation, the intensity of treatment needed to achieve mucosal healing when it has not been obtained using standard therapy, and the means by which mucosal healing is defined using current endoscopic disease activity indices. The main clinical challenge relates to defining the means of achieving high rates of mucosal healing in clinical practice.
Collapse
Affiliation(s)
- Peter De Cruz
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia
| | | | | | | | | |
Collapse
|
|
50
|
|