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Li RB, Li CQ, Zhang SY, Li KY, Zhao ZC, Liu G. Fecal calprotectin as an indicator in risk stratification of pouchitis following ileal pouch-anal anastomosis for ulcerative colitis. Ann Med 2023; 55:305-310. [PMID: 36594484 PMCID: PMC9815261 DOI: 10.1080/07853890.2022.2162115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Pouchitis is the most common complication following restorative proctocolectomy and ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). Fecal calprotectin (FC) is a noninvasive indicator of the intestinal inflammatory status. This study was conducted to evaluate the clinical value of the FC concentration for the diagnosis and risk assessment of pouchitis. PATIENTS AND METHODS This retrospective study involved patients who underwent IPAA for UC at Tianjin Medical University General Hospital from January 2015 to January 2019. The patients were categorized into pouchitis and non-pouchitis groups based on their Pouchitis Disease Activity Index (PDAI) score. Laboratory indicators, including the FC concentration, were collected from both groups. RESULTS Sixty-six patients with UC after IPAA were included in the study and divided into the non-pouchitis group (n = 40) and pouchitis group (n = 26). The correlation coefficient between the FC concentration and the PDAI score was 0.651 (p < 0.001). Receiver operating characteristic analysis showed that the FC cut-off value for predicting pouchitis was 579.60 μg/g (area under the curve, 0.938). The patients were then divided into three subgroups according to their PDAI score (0-2, 3-6, and ≥7), and significant differences in the FC concentration were found among the three subgroups. The best FC cut-off value for predicting a high risk of pouchitis (PDAI score of 3-6) was 143.25 μg/g (area under the curve, 0.876). CONCLUSIONS FC is a useful biomarker in patients with pouchitis. Patients are advised to regularly undergo FC measurement to monitor for pouchitis. An FC concentration in the range of 143.25-579.60 μg/g is predictive of a high risk for pouchitis, and further examination and preventive treatment are necessary in such patients.KEY MESSAGESFecal calprotectin can be used to quantify pouch inflammation.Fecal calprotectin can be used to predict a high risk of pouchitis.
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Affiliation(s)
- Rui-Bin Li
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
| | - Chun-Qiang Li
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
| | - Shi-Yao Zhang
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
| | - Kai-Yu Li
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
| | - Zhi-Cheng Zhao
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
| | - Gang Liu
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
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Falloon K, Cohen BL, Ottichilo R, Grove D, Rieder F, Qazi T. Biomarkers for the Evaluation of Pouch Inflammation: A Systematic Review. CROHN'S & COLITIS 360 2022; 4:otac043. [PMID: 36778511 PMCID: PMC9802421 DOI: 10.1093/crocol/otac043] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Indexed: 11/25/2022] Open
Abstract
Background Ileal pouch inflammation is a common problem following ileal pouch-anal anastomosis (IPAA). Despite its prevalence, diagnosis remains multimodal and requires endoscopy. The use of biomarkers in the prediction of and/or association with pouchitis has not been well characterized. We performed a systematic review to summarize the available evidence. Method A search of Ovid, MEDLINE, Cochrane Library, EMBASE, and Web of Science was conducted. Inclusion criteria included studies evaluating biomarkers for the evaluation and prediction of inflammation in patients with IPAA utilizing pouchoscopy as the gold standard. Exclusion criteria included studies on the role of the microbiome or genetic markers. Results A total of 28 studies, 5 case-control studies, and 23 observational cohort studies were identified. Fecal biomarkers were assessed in 23 studies, of which fecal calprotectin was the most commonly studied with sensitivities ranging from 57% to 92% and specificities from 19% to 92%. Six studies examined serum biomarkers. None of the serum biomarkers demonstrated a high sensitivity or specificity in association with pouch inflammation. Six studies described the longitudinal assessment of biomarkers. Of these studies, only three reported a predictive role of biomarkers in diagnosing endoscopic inflammation. Conclusions Biomarkers have emerged as a potential option to improve the management of pouchitis given the relative ease of sampling compared to pouchoscopy. Unfortunately, the evaluated biomarkers have not consistently demonstrated accuracy in predicting inflammation. Moreover, these biomarkers have not been reliably shown to be sensitive or specific in association with endoscopic pouch inflammation to merit their widespread use in clinical practice.
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Affiliation(s)
- Katherine Falloon
- Department of Gastroenterology, Hepatology & Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Benjamin L Cohen
- Department of Gastroenterology, Hepatology & Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Ronald Ottichilo
- Department of Inflammation and Immunity; Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - David Grove
- Department of Inflammation and Immunity; Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Florian Rieder
- Department of Gastroenterology, Hepatology & Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
- Department of Inflammation and Immunity; Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Taha Qazi
- Department of Gastroenterology, Hepatology & Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
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Kinugasa T, Mitsuyama K, Murotani K, Mizobe T, Ochi T, Yoshimura T, Kuwaki K, Isobe T, Akagi Y. Non-invasive Monitoring of Pouchitis After Total Proctocolectomy Using Fecal Calprotectin Levels. Kurume Med J 2022; 67:57-63. [PMID: 35944985 DOI: 10.2739/kurumemedj.ms6723005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
BACKGROUND Fecal calprotectin (FC) is the most widely used marker for evaluating the disease activity of ulcerative colitis (UC). However, studies on FC in pouchitis after total proctocolectomy are scarce. We aimed to examine the correlations between the FC level and clinical findings and Pouchitis Disease Activity Index (PDAI) in UC patients who underwent total proctocolectomy (TP) with ileal pouch-anal canal anastomosis (IPAA) or ileal pouch-anal canal anastomosis (IACA). METHODS Between April 2008 and March 2018, 15 patients, consisting of 8 males and 7 females, with an average age at operation of 46.5 years, participated in this study. The average observation period was 68.3 months. The subjects underwent FC level measurements and endoscopic examinations. RESULTS The mean FC level was 418.69 μg/g (range: 10-1650 μg/g). Pouchitis was found in one (6.6%) patient, as detected by endoscopy. Among the 15 cases, FC levels were positively correlated with white blood cell count as well as albumin and C-reactive protein levels. There was a significant positive correlation between the PDAI score and FC levels (p<0.05). The median FC level was 111 mg/g in those with pouchitis, which was significantly higher than the 16 mg/g in those without pouchitis (p<0.05). Moreover, a significant positive correlation was found between the endoscopic findings of inflammation and FC levels (p<0.00005). CONCLUSION FC levels were correlated with the PDAI score, blood testing data, and endoscopic findings, suggesting that the FC level could be a useful index of postoperative pouchitis and ileal pouch condition in patients undergoing TP with IPAA as UC treatment.
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Affiliation(s)
- Tetsushi Kinugasa
- Department of Surgery, Department of Medicine, Kurume University School of Medicine
| | - Keiichi Mitsuyama
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine
| | - Kenta Murotani
- Biostatistics Center, Kurume University Graduate School of Medicine
| | - Tomoaki Mizobe
- Department of Surgery, Department of Medicine, Kurume University School of Medicine
| | - Takafumi Ochi
- Department of Surgery, Department of Medicine, Kurume University School of Medicine
| | - Tetsuhiro Yoshimura
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine
| | - Koutarou Kuwaki
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine
| | - Taro Isobe
- Department of Surgery, Department of Medicine, Kurume University School of Medicine
| | - Yoshito Akagi
- Department of Surgery, Department of Medicine, Kurume University School of Medicine
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Ollech JE, Bannon L, Maharshak N, Bar N, Goren I, Tulchinsky H, Yanai H, Dotan I. Fecal Calprotectin Is Increased in Pouchitis and Progressively Increases With More Severe Endoscopic and Histologic Disease. Clin Gastroenterol Hepatol 2022; 20:1839-1846.e2. [PMID: 34798336 DOI: 10.1016/j.cgh.2021.11.012] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 10/22/2021] [Accepted: 11/10/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Data regarding fecal calprotectin (FC), commonly used for noninvasive monitoring in inflammatory bowel diseases, are scarce in patients with ileal pouch-anal anastomosis (IPAA). We aimed to assess the association between FC levels and pouch inflammation in patients with ulcerative colitis who underwent IPAA. METHODS A cross-sectional study of adults with ulcerative colitis who underwent IPAA with J-pouch formation prospectively followed in a dedicated pouch clinic. Patients had clinical, endoscopic, and histologic assessments within 90 days of FC sampling. Each patient encounter was evaluated separately. Pouchitis was defined as a Pouchitis Disease Activity Score of ≥7 (maximum score: 18). RESULTS Overall, 156 patients had 296 encounters that met inclusion criteria. A total of 52% of patients were male, median age at evaluation was 43 (IQR, 35-58) years, and median pouch age was 10 (interquartile range [IQR], 2.5-15) years. Median FC values were significantly lower in patients without compared with those with pouchitis (208 [IQR, 96-478] μg/g vs 550 [IQR, 250-1051] μg/g; P < .0001). Mean FC values increased among patients with higher endoscopic and histologic scores. FC performed better than C-reactive protein as a predictor of pouchitis. FC of >460 μg/g had >80% specificity for predicting significant endoscopic disease (Pouchitis Disease Activity Score endoscopic subscore ≥5), while an FC of <125 μg/g had over 80% specificity in predicting endoscopic remission. CONCLUSIONS FC levels are increased in patients with endoscopic and histologic inflammation of the pouch. FC may be a useful tool in the management of patients following IPAA.
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Affiliation(s)
- Jacob E Ollech
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
| | - Lian Bannon
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Internal Medicine Division, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Nitsan Maharshak
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; IBD Unit, Department of Gastroenterology and Hepatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Nir Bar
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; IBD Unit, Department of Gastroenterology and Hepatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Idan Goren
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Hagit Tulchinsky
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Colorectal Unit, Division of Surgery, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Henit Yanai
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Iris Dotan
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
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D'Amico F, Nancey S, Danese S, Peyrin-Biroulet L. A Practical Guide for Faecal Calprotectin Measurement: Myths and Realities. J Crohns Colitis 2021; 15:152-161. [PMID: 32392336 DOI: 10.1093/ecco-jcc/jjaa093] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS Faecal calprotectin [FC] is a valid and non-invasive marker of mucosal inflammation. It is widely used both in clinical trials and in daily clinical practice for patients with inflammatory bowel diseases, but currently no accepted standardization for FC testing is available. Our primary aim here was to provide a clinician's guide containing all the practical information on FC measurement in order to avoid any confounding factors, to minimize intra- and inter-individual variability in dosage, and to ensure a better and adequate interpretation of the results. METHODS We conducted a detailed search of the scientific literature in the PubMed/MEDLINE, EMBASE and Cochrane databases up to January 2020 to find all relevant and available articles on pre-analytical and analytical phases of FC measurement. RESULTS FC testing is a multi-step procedure consisting of a pre-analytical phase aimed to collect and process the stool sample and a subsequent analytical phase of FC measurement. Several factors can influence test results determining false positives or false negatives. Importantly, this faecal marker is mostly used for patient follow-up and as a predictor of treatment response. For this reason, any altered data may affect the physicians' decisions, negatively impacting on patient management. CONCLUSIONS This review provides for the first time practical advice to minimize dosage variability, although further dedicated studies are needed to compare commercially available tests and identify the best tools for the most precise and accurate FC measurement.
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Affiliation(s)
- Ferdinando D'Amico
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,Department of Gastroenterology and Inserm NGERE U1256, University Hospital of Nancy, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - Stéphane Nancey
- Department of Gastroenterology, Hospices Civils de Lyon, Lyon-Sud Hospital, Pierre Benite, and Inserm U1111, CIRI, Lyon, France
| | - Silvio Danese
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,IBD Center, Department of Gastroenterology, Humanitas Research Hospital, Rozzano -IRCCS-, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm NGERE U1256, University Hospital of Nancy, University of Lorraine, Vandoeuvre-lès-Nancy, France
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Fecal calprotectin: current and future perspectives for inflammatory bowel disease treatment. Eur J Gastroenterol Hepatol 2020; 32:1091-1098. [PMID: 32282400 DOI: 10.1097/meg.0000000000001731] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Fecal calprotectin has been widely studied in inflammatory bowel disease (IBD) under clinical and therapeutic settings. It showed a good correlation with clinical, endoscopic, and histologic findings. For these reasons, fecal calprotectin is currently one of the most useful tools in IBD care, both in diagnosis and in clinical management. The development of biologic drugs allowed a deeper control of disease, which sometimes reaches histological healing; this is associated with a reduced risk of relapses and complications. The management of IBD treatment is currently carried out with a treat-to-target approach, and mucosal healing is considered at present to be the optimal therapeutic target, but the future is going through histologic remission. Fecal calprotectin is probably the best marker of mucosal healing, but it is correlated also with histologic remission: moreover, it has been recently studied as a possible therapeutic target in the CALM study. We carried out a comprehensive literature review in order to evaluate the role of fecal calprotectin at present and in the future in the management of IBD therapies.
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7
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The role of fecal calprotectin in the diagnosis of acute pouchitis following IPAA for ulcerative colitis: a systematic clinical review. Int J Colorectal Dis 2020; 35:1619-1628. [PMID: 32617664 DOI: 10.1007/s00384-020-03669-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/10/2020] [Indexed: 02/07/2023]
Abstract
PURPOSE Total proctocolectomy (TPC) with ileal pouch anal anastomosis (IPAA) is commonly performed for patients with refractory ulcerative colitis (UC). Pouchitis occurs in 20-50% of these patients. Fecal calprotectin is a biomarker that correlates well with the pouchitis disease activity index. However, its role in the diagnosis and management of acute pouchitis has not been thoroughly defined. The aim of this study is to review previously established cut-off values and contextualize the clinical utility of fecal calprotectin. METHODS Search of Medline, EMBASE, CENTRAL, and PubMed was performed. Articles were eligible if they measured fecal calprotectin in the setting of pouchitis in patients who underwent TPC with IPAA for UC. Risk of bias of the included studies was evaluated with the QUADAS-2. RESULTS From 117 relevant citations, seven studies with 256 patients (44.8% female, 39.88 years) met inclusion criteria. The pooled prevalence of pouchitis was 42%. The derived fecal calprotectin cut-off values ranged from 56 to 494 μg/g. The corresponding sensitivities and specificities ranged from 57 to 100% and 38 to 92%, respectively. The area under the curve was reported in three studies and ranged from 0.832 to 0.840. CONCLUSION Fecal calprotectin may be a reliable diagnostic tool for acute pouchitis in patients following TPC with IPAA for UC. The high sensitivity of fecal calprotectin for detection of pouchitis makes it a valuable test for ruling out pouchitis. When used in conjunction with other biomarkers, the high specificity offers value in ruling in pouchitis. However, given the complexity of this disease process, relying solely on biomarkers for diagnosis is currently unreasonable.
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Bengtsson J, Adlerberth I, Östblom A, Saksena P, Öresland T, Börjesson L. Effect of probiotics (Lactobacillus plantarum 299 plus Bifidobacterium Cure21) in patients with poor ileal pouch function: a randomised controlled trial. Scand J Gastroenterol 2016; 51:1087-92. [PMID: 27150635 DOI: 10.3109/00365521.2016.1161067] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Poor pouch function after restorative proctocolectomy for ulcerative colitis is a considerable problem. Pouchitis and functional disorders are the most common reasons. Probiotics seem to have a beneficial effect in pouchitis but have not been assessed in functional pouch disorders. The aim was to analyse the effects of probiotics in patients with poor pouch function. METHODS Thirty-three patients were randomized to probiotics (Lactobacillus plantarum 299 and Bifidobacterium infantis Cure 21) or placebo in a double blinded, 1:1 fashion. The treatment effect was assessed by the pouch functional score (PFS; 0-15, 15 worst), pouchitis disease activity index (PDAI; 0-18, 18 worst), and levels of four faecal biomarkers of inflammation (calprotectin, lactoferrin, myeloperoxidase [MPO] and eosinophilic cationic protein [ECP]). RESULTS Thirty-two patients were included (probiotics = 17, placebo = 16). There was no difference in change in the PFS from before to after treatment between the groups (median difference: -1.00, 95% C.I. -3.00 to 0.00, p = 0.119). Furthermore, probiotics had no effect on PDAI (median difference: 0.00, 95% C.I. 0.00-1.00, p = 0.786), or on faecal biomarkers. Significant correlations were observed between PDAI and each of the faecal biomarkers at study start. There were no correlations between PFS or PDAI symptom subscore and the biomarkers. PDAI endoscopic and histologic subscores correlated significantly to each of the biomarkers. CONCLUSION The hypothesis that probiotics improves pouch-related dysfunction was not confirmed. Faecal biomarkers could play a future role in the management of pouch patients.
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Affiliation(s)
- J Bengtsson
- a Department of Surgery , Sahlgrenska University Hospital , Gothenburg , Sweden
| | - I Adlerberth
- b Department of Infectious Diseases , Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
| | - A Östblom
- b Department of Infectious Diseases , Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
| | - P Saksena
- c Department of Pathology , Sahlgrenska University Hospital , Gothenburg , Sweden
| | - T Öresland
- d Akershus University Hospital, University of Oslo , Oslo , Norway
| | - L Börjesson
- a Department of Surgery , Sahlgrenska University Hospital , Gothenburg , Sweden
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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: 48] [Impact Index Per Article: 5.3] [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.
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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.
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Abstract
Inflammatory bowel disease (IBD) and irritable bowel syndrome share many symptoms. While irritable bowel syndrome is a functional bowel disorder for which no specific treatment is available, the range of effective therapies for IBD is evolving rapidly. Accurate diagnosis of IBD is therefore essential. Clinical assessment, together with various imaging modalities and endoscopy, has been the mainstay of diagnosis for many years. Fecal biomarkers of gastrointestinal inflammation have appeared in the past decade, of which calprotectin, a neutrophil cytosolic protein, has been studied the most. Crohn’s disease and ulcerative colitis are chronic remitting and relapsing diseases, and objective assessment of disease activity and response to treatment are important. This review focuses on the use of fecal calprotectin measurements in the diagnosis and monitoring of patients with IBD.
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Affiliation(s)
- Natalie E Walsham
- Department of Clinical Biochemistry, University Hospital Lewisham, Lewisham, London, UK
| | - Roy A Sherwood
- Department of Clinical Biochemistry, Viapath at King's College Hospital NHS Foundation Trust, London, UK
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Yamamoto T, Shimoyama T, Bamba T, Matsumoto K. Consecutive Monitoring of Fecal Calprotectin and Lactoferrin for the Early Diagnosis and Prediction of Pouchitis after Restorative Proctocolectomy for Ulcerative Colitis. Am J Gastroenterol 2015; 110:881-7. [PMID: 25916224 DOI: 10.1038/ajg.2015.129] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2014] [Accepted: 03/03/2015] [Indexed: 12/11/2022]
Abstract
OBJECTIVES This prospective study was conducted to evaluate the significance of consecutive monitoring of fecal calprotectin and lactoferrin for the early diagnosis and prediction of pouchitis after restorative proctocolectomy for ulcerative colitis (UC). METHODS Sixty patients who had ileostomy closure following total proctocolectomy and ileal pouch-anal anastomosis for UC were included. Stool samples were collected for the measurement of calprotectin and lactoferrin every 2 months up to 12 months after the ileostomy closure. When patients had symptoms suggestive of pouchitis, endoscopic examination was immediately undertaken. All asymptomatic patients underwent endoscopy at 12 months. Pouchitis was defined as a pouchitis disease activity index score of ≥7. RESULTS During the 12 months, 10 patients (17%) developed pouchitis. In patients with pouchitis, fecal calprotectin and lactoferrin levels were elevated already 2 months before the diagnosis of pouchitis. In contrast, these fecal biomarkers remained at low levels, and they did not change significantly in patients without pouchitis. A cutoff value of 56 μg/g for calprotectin had a sensitivity of 100% and a specificity of 84% to predict pouchitis, whereas a cutoff value of 50 μg/g for lactoferrin had a sensitivity of 90% and a specificity of 86%. At the time of endoscopy, the median calprotectin and lactoferrin levels were significantly higher in patients with pouchitis than those without pouchitis. CONCLUSIONS Elevated fecal calprotectin and lactoferrin levels appeared to be significant predictors of pouchitis after restorative proctocolectomy for UC. Consecutive monitoring of these fecal biomarkers is useful for the early diagnosis of pouchitis.
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Affiliation(s)
- Takayuki Yamamoto
- Inflammatory Bowel Disease Center, Yokkaichi Hazu Medical Center, Yokkaichi, Mie, Japan
| | - Takahiro Shimoyama
- Inflammatory Bowel Disease Center, Yokkaichi Hazu Medical Center, Yokkaichi, Mie, Japan
| | - Takuya Bamba
- Inflammatory Bowel Disease Center, Yokkaichi Hazu Medical Center, Yokkaichi, Mie, Japan
| | - Koichi Matsumoto
- Inflammatory Bowel Disease Center, Yokkaichi Hazu Medical Center, Yokkaichi, Mie, Japan
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Farkas K, Bálint A, Bor R, Földesi I, Szűcs M, Nagy F, Szepes Z, Annaházi A, Róka R, Molnár T. Faecal matrix metalloprotease-9 is a more sensitive marker for diagnosing pouchitis than faecal calprotectin: results from a pilot study. Expert Rev Gastroenterol Hepatol 2015; 9:387-92. [PMID: 25264031 DOI: 10.1586/17474124.2015.965144] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Potential non-invasive markers of pouchitis would have a great deal of significance within clinical practice. AIM This study is aimed at assessing the diagnostic accuracy of fecal calprotectin and matrix metalloprotease-9 as potential markers in patients both with and without pouchitis. PATIENTS AND METHODS Stool and blood samples were collected from 33 ileal pouch-anal anastomosis patients before a follow-up pouchoscopy. Biopsy samples were taken for histological purposes. The presence of cuffitis and stenosis was evaluated with an endoscopy. Calprotectin and matrix metalloprotease-9 were quantified with an enzyme-linked immunosorbent assay. RESULTS Pouchitis was detected in 30.3% of the patients. The levels of fecal calprotectin and matrix metalloprotease-9 increased significantly in patients with pouchitis. The sensitivity and specificity of matrix metalloprotease-9 was higher than that of fecal calprotectin. Only matrix metalloprotease-9 correlated significantly with the severity of pouchitis. DISCUSSION Fecal matrix metalloprotease-9 has a high specificity in the diagnosis of pouchitis.
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Affiliation(s)
- Klaudia Farkas
- First Department of Medicine, University of Szeged H-6720, Korányi fasor 8, Szeged, Hungary
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Abstract
BACKGROUND Patients with ulcerative colitis undergoing total proctocolectomy with ileal pouch-anal anastomosis may develop pouchitis. Alpha-1-antitrypsin (AAT) is an acute phase reactant produced mainly by hepatocytes, but also locally in the gut. Data on noninvasive biomarkers of pouchitis are scarce. METHODS To identify biomarkers that correlate with pouch inflammation, ulcerative colitis pouch patients were prospectively recruited and underwent clinical, endoscopic, and histologic evaluations. The Pouchitis Disease Activity Index (PDAI) was calculated, and pouchitis was defined by a score ≥7. Serum and fecal AAT, C-reactive protein (CRP), fecal calprotectin, ferritin and albumin levels were measured. RESULTS Seventy-one ulcerative colitis pouch patients (mean age 43.8 ± 8.3 yr, 50.7% males) were included. The main indication for ileal pouch-anal anastomosis was intractable colitis (83.1%). Median serum AAT level (183.0 mg/dL, 155.1-232.0) was significantly higher in patients with a PDAI ≥7 compared with those with a PDAI <7 (167.6 mg/dL, 151.0-181.0) (P = 0.03). Serum AAT, CRP, and fecal calprotectin levels significantly correlated with PDAI scores: r = 0.583, P < 0.001; r = 0.584, P < 0.001; and r = 0.606, P = 0.001, respectively. Serum AAT and CRP levels correlated significantly (r = 0.650, P < 0.001), as did serum AAT and fecal calprotectin levels (r = 0.663, P < 0.001). Fecal AAT levels did not correlate with any tested biomarker. Receiver operating characteristic analysis demonstrated sensitivity, specificity, and positive predictive value of 55.6%, 100%, and 100%, respectively, for diagnosing pouchitis at a serum AAT cutoff level of 189 mg/dL. CONCLUSIONS Serum AAT is a specific noninvasive biomarker of pouchitis. AAT levels correlate with disease activity and CRP and calprotectin levels.
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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.
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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
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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.
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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.
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Affiliation(s)
- Taina Sipponen
- Department of Medicine, Clinic of Gastroenterology, Helsinki University Central Hospital, Helsinki, Finland
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Biomarkers in management of inflammatory bowel disease. GASTROENTEROLOGY REVIEW 2013; 8:275-83. [PMID: 24868269 PMCID: PMC4027818 DOI: 10.5114/pg.2013.38728] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/01/2013] [Revised: 10/08/2013] [Accepted: 10/12/2013] [Indexed: 12/21/2022]
Abstract
In recent years the use of faecal and serologic biomarkers has been evaluated in the diagnosis and management of inflammatory bowel disease (IBD). Faecal calprotectin (FC) has been proposed as a surrogate marker for intestinal inflammation; elevated concentrations in IBD patients have been confirmed in numerous studies. Already available rapid calprotectin tests help to differentiate between IBD and irritable bowel syndrome. Faecal calprotectin greatly correlates with endoscopic activity scales and reflects the mucosal healing; thus in patients in clinical remission high levels of it correlate with increased risk of disease relapse in the following 12 months. Adapting the calprotectin assay as a screening test before colonoscopy enables a significant reduction in endoscopic procedures. ANCA/ASCA antibodies have been used in IBD diagnosis and to distinguish CD from ulcerative colitis (UC). Lactoferrin and S100A12 protein were also used to assess the disease activity. This review aims to present the actual potential of biomarker assays for faster diagnosis of IBD and their ability to monitor the disease course, predict exacerbations and improve the way IBD is managed.
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Abstract
BACKGROUND Fecal lactoferrin is a marker of intestinal inflammation and can be assessed with a simple qualitative immunochromatographic rapid test. OBJECTIVE We aimed to assess the sensitivity and specificity of the test in the diagnosis of pouchitis and evaluate its clinical utility in the surveillance of inflammation of the pouch after antibiotic therapy. DESIGN Between October 2005 and September 2009, we recruited a consecutive series of patients who had their ileal pouch examined under a general anesthetic. Distinctions between healthy and inflamed pouches were made by the use of the Pouch Disease Activity Index. Fecal samples were taken before biopsy of the pouch, and a clinician blinded to the examination findings performed the lactoferrin test. After antimicrobial treatment, a number of patients with pouchitis had a repeat examination and lactoferrin test. RESULTS There were 85 (41 male) patients. Median age was 42 (interquartile range, 36-49) years. Twenty-four patients had pouchitis. The test was positive in all 24 patients with pouchitis and 5 patients with a healthy pouch. The sensitivity and specificity of the test for pouchitis was 100% and 92%. The positive predictive value was 82%. In 7 patients who received antibiotic treatment for their pouchitis, the test was able to accurately predict the resolution and/or persistence of pouchitis. CONCLUSION The qualitative fecal lactoferrin rapid test is a sensitive method for the diagnosis and confirmation of resolution of pouchitis. The test provides clinicians with greater confidence in the prescription of antibiotics for suspected pouchitis and its surveillance.
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Smith LA, Gaya DR. Utility of faecal calprotectin analysis in adult inflammatory bowel disease. World J Gastroenterol 2012; 18:6782-9. [PMID: 23239916 PMCID: PMC3520167 DOI: 10.3748/wjg.v18.i46.6782] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2012] [Revised: 08/23/2012] [Accepted: 09/19/2012] [Indexed: 02/06/2023] Open
Abstract
The inflammatory bowel diseases (IBD), Crohn’s disease and ulcerative colitis, are chronic relapsing, remitting disorders. Diagnosis, along with assessment of disease activity and prognosis present challenges to managing clinicians. Faecal biomarkers, such as faecal calprotectin, are a non-invasive method which can be used to aid these decisions. Calprotectin is a calcium and zinc binding protein found in the cytosol of human neutrophils and macrophages. It is released extracellularly in times of cell stress or damage and can be detected within faeces and thus can be used as a sensitive marker of intestinal inflammation. Faecal calprotectin has been shown to be useful in the diagnosis of IBD, correlates with mucosal disease activity and can help to predict response to treatment or relapse. With growing evidence supporting its use, over the last decade this faecal biomarker has significantly changed the way IBD is managed.
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Utility of fecal and serum anti-Saccharomyces cerevisiae antibodies in the diagnosis of Crohn's disease-like condition of the pouch. Int J Colorectal Dis 2012; 27:1455-63. [PMID: 22430887 DOI: 10.1007/s00384-012-1444-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/29/2012] [Indexed: 02/04/2023]
Abstract
BACKGROUND Fecal antibodies against bacterial products may directly reflect the interaction between luminal bacteria and mucosal immunity, and assays for these antibodies may be clinically useful in the diagnosis and differential diagnosis of Crohn's disease-like (CDL) condition of the pouch. AIMS This study aims to evaluate stool and serum anti-Saccharomyces cerevisiae antibodies (ASCA) in normal and diseased pouches, to assess the correlation between ASCA levels and endoscopic disease activity, and to ascertain the diagnostic utility of ASCA for CDL of the pouch. METHODS One hundred eighty-nine patients with ileal pouches were prospectively enrolled and corresponding serum and pouch aspirate samples were collected. Fecal and serum ASCA levels were measured with enzyme-linked immunosorbent assay in a blinded fashion. Statistical analysis was then conducted using the signed rank test, Spearman correlation coefficients, and analysis of variance. RESULTS Forty-three patients (22.8 %) had irritable pouch syndrome or normal pouches, 74 (39.2 %) had pouchitis/cuffitis, 52 (27.5 %) had CDL, 9 (4.8 %) had familial adenomatous polyposis, and 11 (5.8 %) had surgical complications of the pouch. Receiver operating characteristic curves to distinguish CDL from other categories of pouch dysfunction had an area under the curve (AUC) of 0.608 for fecal ASCA and an AUC of 0.517 for serum ASCA. Neither fecal nor serum ASCA correlated with endoscopic disease activity scores. There was a significant difference in the mean values of fecal ASCA between inflammatory and fistulizing CDL (0.27 vs. 0.03 ELISA units/ml, P < 0.05). CONCLUSIONS Fecal ASCA appears to be better than serum ASCA in differentiating CDL from other pouch disorders, although this distinction may be of limited clinical utility.
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Kaur M, Ippoliti AF. Ileal Pouch-Anal Anastomosis: A Gastroenterology Perspective. SEMINARS IN COLON AND RECTAL SURGERY 2012. [DOI: 10.1053/j.scrs.2012.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Abstract
Overall, fecal markers have been found to be more accurate than serum markers. However, fecal markers are not specific for IBD and may be elevated in a range of organic conditions. Fecal calprotectin and lactoferrin can still differentiate inflammatory disease from functional bowel disorders. Comparison studies have found an overall diagnostic accuracy in IBD of 80% to 100% for both calprotectin and lactoferrin. Elevated levels are found in both CD and UC making it difficult to distinguish between these 2 diagnoses from these biomarkers alone. Both markers correlated well to mucosal healing and histologic improvement. Hence, they may be useful in monitoring response to treatment and predicting endoscopic and clinical relapse. Overall, patients with elevated markers were at higher risk of postoperative recurrence than those with normal levels. Fecal markers are useful in predicting pouchitis as well. Fecal markers are helpful as an adjunctive tool in overall evaluation of patients with nonspecific symptoms and as a management tool in those with inflammatory disease to monitor disease activity and possibility of relapse. They are less invasive than colonoscopy and can help guide management in a more cost-effective manner.
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Affiliation(s)
- Bincy P Abraham
- Section of Gastroenterology and Hepatology, Baylor College of Medicine, 1709 Dryden Street, Suite 800, Houston, TX 77030, USA.
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Røkke O, Iversen K, Olsen T, Ristesund SM, Eide GE, Turowski GE. Long-Term Followup of Patients with Active J-Reservoirs after Restorative Proctocolectomy for Ulcerative Colitis with regard to Reservoir Function, Mucosal Changes, and Quality of Life. ISRN GASTROENTEROLOGY 2011; 2011:430171. [PMID: 21991508 PMCID: PMC3168452 DOI: 10.5402/2011/430171] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/18/2011] [Accepted: 06/15/2011] [Indexed: 12/19/2022]
Abstract
Objective. Study the functional results and mucosal changes in the ileal pouch after restorative proctocolectomy with J-reservoir for ulcerative colitis. Material and Methods. Followup study of 125 patients with J-reservoir with one disease-specific- and one general (SF-36) quality of life-questionnaire, rectoscopy with biopsies, and stool samples to evaluate inflammation, dysplasia, presence of Helicobacter pylori and calprotectin level. Results. Fourteen J-reservoirs were removed or deactivated, leaving 111 patients for followup. The followup time was 6.8 (1-15) years. 87.4% of the patients were satisfied. 93.1% had some kind of functional restriction: food- (75.5%), social- (28.9%), physical- (37%) or sexual restriction (15.3%). 18.6% had often or sometimes faecal incontinence. Low daytime faecal frequency was associated with good quality of life. 13 patients (12.6%) had a less favourable result. There was no pouch-dysplasia. Calprotectin levels were increased in patients with visible pouch inflammation or history of pouchitis. HP was diagnosed by RUT in 42.3%, but was not associated with inflammation or pouchitis. Conclusions. Most patients were satisfied with the J-reservoir in spite of a high frequency of various restrictions. 12.6% (13 patients) had a less favourable functional result, partly due to a high frequency of defecations, pain, pouchitis and inflammation.
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Affiliation(s)
- Ola Røkke
- Department of Gastrointestinal Surgery, Akershus University Hospital, 1478 Lørenskog, Norway
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Manolakis AC, Kapsoritakis AN, Tiaka EK, Potamianos SP. Calprotectin, calgranulin C, and other members of the s100 protein family in inflammatory bowel disease. Dig Dis Sci 2011; 56:1601-1611. [PMID: 21203903 DOI: 10.1007/s10620-010-1494-9] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2010] [Accepted: 11/10/2010] [Indexed: 12/18/2022]
Abstract
BACKGROUND Since their discovery, S100 proteins have been associated with diverse diseases of inflammatory, degenerative, or malignant nature. Due to their participation in inflammation, they have also been studied with regard to inflammatory bowel disease (IBD). METHOD To provide a review of available literature, a PubMed, MEDLINE, and Embase-based literature search was performed, using all available nomenclature for each member of the S100 protein family, along with the terms inflammatory bowel disease, ulcerative colitis, Crohn's disease, or indeterminate colitis. RESULT S100A8/A9, also known as calprotectin, S100A12, or calgranulin C and in a lesser extent S100P, are involved in the pathogenesis, activity, diagnosis, and therapeutic management of IBD. The majority of available literature is focused primarily on S100A8/9, although there is growing evidence on the significance of S100A12. Most studies emphasize the potential merit of S100A8/A9 and S100A12, as markers for differential diagnosis, monitoring of activity, or disease relapse, in IBD. Limitations, regarding the diagnostic utility of these markers, seem to exist and are mainly related to the publication of conflicting results, i.e., for IBD activity, and to the fact that S100A8/A9 and S100A12 are not disease-specific. CONCLUSIONS Although the existing data link specific S100 proteins with IBD, there are still several drawbacks in the use of these markers for diagnostic purposes. Thus, it seems that further research is mandatory in order to eliminate the impact of confounding factors but also to detect additional associations between S100 proteins and IBD or novel S100 proteins with a closer correlation with IBD.
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Affiliation(s)
- Anastassios C Manolakis
- Department of Gastroenterology, School of Medicine, University Hospital of Larissa, University of Thessaly, 4110 Larissa, Greece.
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Caccaro R, D'Incá R, Sturniolo GC. Clinical utility of calprotectin and lactoferrin as markers of inflammation in patients with inflammatory bowel disease. Expert Rev Clin Immunol 2010; 6:551-8. [PMID: 20594128 DOI: 10.1586/eci.10.26] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Crohn's disease and ulcerative colitis have a feature in common (i.e., chronic inflammation). Their clinical management requires repeated assessments; endoscopy with histological examination remains the gold standard for detecting and quantifying intestinal inflammation. An ideal marker should be quick and easy to obtain noninvasively, and should be inexpensive and reproducible. Several laboratory tests have been studied but, to date, a disease marker is not yet available. A combination of signs and symptoms, laboratory findings and imaging techniques is consequently still needed for assessing disease activity and prognosis. In recent years, research has drawn attention to fecal markers owing to their specificity for intestinal inflammation, ease of sample collection, availability of commercial immunoassays and convenience. Biological markers have been used to assess inflammatory bowel disease patients for the purposes of their clinical management, monitoring disease activity, predicting relapses, assessing prognosis and monitoring response to treatment.
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Affiliation(s)
- Roberta Caccaro
- Department of Surgical and Gastroenterological Sciences, University of Padua, Via Giustiniani 2, 35127 Padova, Italy
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Lu H, Lian L, Navaneethan U, Shen B. Clinical utility of C-reactive protein in patients with ileal pouch anal anastomosis. Inflamm Bowel Dis 2010; 16:1678-84. [PMID: 20186934 DOI: 10.1002/ibd.21239] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
BACKGROUND Inflammatory and noninflammatory complications of ileal pouch-anal anastomosis (IPAA) are common after restorative proctocolectomy for ulcerative colitis (UC). The clinical utility of C-reactive protein (CRP) in ileal pouch disorders has not been investigated. MATERIALS AND METHODS All IPAA patients with underlying UC who had serum CRP tested within 2 weeks of pouch endoscopy were included. The correlation between the level of serum CRP and the Pouch Disease Activity Index (PDAI) scores were evaluated. Diagnostic accuracy of CRP in assessing disease activity by PDAI endoscopy subscores was evaluated. RESULTS There were 83 patients (with a total 88 CRP tests), including normal pouches (n = 7), active pouchitis (n = 6), chronic pouchitis (n = 18), Crohn's disease of the pouch (n = 23), cuffitis (n = 13), irritable pouch syndrome (n = 10), and surgery-associated complications (n = 11). Levels of CRP did not differ significantly among healthy and diseased pouch groups. CRP levels significantly correlated with the PDAI endoscopy subscores in the pouch body (P = 0.006) and afferent limb (P = 0.03). A CRP level of greater than 0.7 mg/dL for CRP using the receiver operating characteristics curve obtained the best sensitivity of 69.7% and specificity of 63.6% to detect active pouch inflammation. CONCLUSIONS Serum CRP levels correlated with endoscopic inflammation in the pouch and afferent limb. Elevated CRP levels might be useful to monitor the degree of inflammatory activity in pouch noninvasively. However, the CRP level as a snapshot had a limited role in distinction between healthy and diseased pouch conditions diagnosed based on longitudinal clinical and endoscopic evaluation.
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Affiliation(s)
- Hong Lu
- Department of Gastroenterology, Peking Union Medical College Hospital, Beijing, China
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Abstract
Inflammatory markers play a key role in the evaluation of patients with gastrointestinal symptoms. For patients presenting with nonspecific symptoms of abdominal pain and diarrhea, distinguishing inflammatory bowel disease from other disorders can be difficult, and invasive diagnostic procedures may be required. Inflammatory markers can be useful to differentiate patients who may require further workup from those who do not. Several serum, fecal, and other markers are reviewed for their use in clinical practice. Although no single ideal marker exists, a few show promise in diagnosing inflammatory disease, monitoring disease activity, and predicting relapse.
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Navaneethan U, Shen B. Laboratory tests for patients with ileal pouch-anal anastomosis: clinical utility in predicting, diagnosing, and monitoring pouch disorders. Am J Gastroenterol 2009; 104:2606-15. [PMID: 19603012 DOI: 10.1038/ajg.2009.392] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgical treatment of choice for patients with medically refractory ulcerative colitis (UC) or UC-associated dysplasia, and for the majority of patients with familial adenomatous polyposis. Pouchitis and other complications of IPAA are common. There are scant data on laboratory markers for the evaluation and diagnosis of pouch disorders. The presence of immunogenotypic markers such as genetic polymorphisms of interleukin-1 (IL-1) receptor antagonist, NOD2/CARD15, Toll-like receptor, and tumor necrosis factor-alpha has been reported to be associated with pouchitis. Immunophenotypic/serologic markers such as perinuclear antineutrophil cytoplasmic antibody and anti-CBir1 have been investigated as possible markers for predicting and diagnosing pouchitis. Fecal markers including lactoferrin and calprotectin seem to be useful in distinguishing inflammatory from noninflammatory pouch disorders. In our practice, we have encountered a large number of pouch patients with Clostridium difficile infection. Laboratory evaluation provides information on the etiology and pathogenesis of pouchitis, and it also helps practicing clinicians with accurate diagnosis, differential diagnosis, disease stratification, and management of ileal pouch disorders.
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Affiliation(s)
- Udayakumar Navaneethan
- The Pouchitis Clinic, Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
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Abstract
BACKGROUND Dimeric M2-pyruvate kinase (dM2-PK) is overexpressed in tumour cells with rapid cell turnover. Its concentrations correlate well with the staging and metastatic capability of the tumour cells. We investigated the use of faecal dM2-PK as a noninvasive marker of pouch inflammation (pouchitis) in patients having undergone restorative proctocolectomy. METHODS Stool samples were obtained from 46 patients with ulcerative colitis (UC) and eight with familial adenomatous polyposis. Pouchitis was defined using the objective pouchitis score (OPS) and the pouch disease activity index. Faecal dM2-PK was measured using a quantitative sandwich-type enzyme immunoassay (ScheBo Biotech UK) and the results compared with reciprocal faecal calprotectin concentrations. RESULTS Using the OPS, 6 of the 46 patients with UC had pouchitis and prepouch ileitis, 13 had UC pouchitis alone, and 27 had a non-inflamed UC pouch. One patient with familial adenomatous polyposis had pouchitis and prepouch ileitis and 7 had an non inflamed pouch. Respective median dM2-PK values (U/ml) for these five groups were 49.5 (4.5-110), 12 (1-192.3), 2.2 (0.1-95.2), 19.5 and 1 (0.1-3). Statistically significant differences were noted between inflamed and non inflamed pouches (P<0.0001). dM2-PK correlated significantly with the OPS, pouch disease activity index, endoscopic appearances, acute histological and neutrophil scores (<0.0001). The receiver operating characteristic analysis demonstrated a sensitivity and specificity of 80 and 70.6%, respectively. dM2-PK and faecal calprotectin concentrations correlated closely (r=0.87, P<0.0001). CONCLUSION This study demonstrates that faecal dM2-PK is a sensitive marker of pouch inflammation and that its concentration directly correlates with the objective markers of pouchitis severity.
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Abstract
While the overall incidence of pouchitis is low, extensive research continues at clinical and experimental levels in attempts to unravel its etiology. The ileal pouch and pouchitis together represent a unique in vivo opportunity to study mucosal adaptation and inflammation in depth. In the recent past, molecular data relating to pouchitis has significantly expanded. These data provide invaluable insight into intracellular and extracellular events that underpin mucosal adaptation and inflammation. Advances in classification, risk factor evaluation, and prevention have meant that a review of this data, as well as its relationship to our current understanding of pouchitis, is both timely and warranted. Therefore, the aim of this review is to summarize recent data in the context of the established literature.
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Affiliation(s)
- John Calvin Coffey
- Department of Academic Surgery, Cork University Hospital, Cork, Ireland.
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Sutherland AD, Gearry RB, Frizelle FA. Review of fecal biomarkers in inflammatory bowel disease. Dis Colon Rectum 2008; 51:1283-91. [PMID: 18543035 DOI: 10.1007/s10350-008-9310-8] [Citation(s) in RCA: 70] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2007] [Revised: 12/19/2007] [Accepted: 01/20/2008] [Indexed: 12/11/2022]
Abstract
PURPOSE We reviewed potential fecal biomarkers of inflammatory bowel disease and assessed their utility in a range of clinical applications. METHODS A literature search using PubMed, MEDLINE, and Embase database was performed, locating all language articles on fecal biomarkers, including calprotectin and lactoferrin. The references of these papers were searched manually for further references. RESULTS A wide range of fecal biomarkers have been evaluated in the research setting. Only fecal calprotectin and lactoferrin have translated into useful clinical tools. These biomarkers have demonstrated high sensitivity for organic intestinal disease and good correlation with other measures of disease activity in inflammatory bowel disease. CONCLUSIONS Fecal calprotectin and lactoferrin are useful triage tools to differentiate organic intestinal disorders from functional disorders. They also have a role in monitoring inflammatory bowel disease activity and predicting relapse.
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Abstract
INTRODUCTION In pouchitis, the mucosa is infiltrated by activated polymorphonuclear neutrophils capable of producing calprotectin, a stable antimicrobial myelomonocytic protein. AIM The aim is to assess the ability of faecal calprotectin to differentiate between inflamed and noninflamed ileal pouches, and to correlate this with inflammation severity using the newly developed Objective Pouchitis Score. METHOD Fifty-four stool samples were collected from patients who had undergone restorative proctocolectomy; 46 from patients with ulcerative colitis and eight from those with familial adenomatous polyposis coli. Faecal calprotectin concentrations were determined by quantitative enzyme-linked immunosorbant assay. RESULTS Of the ulcerative colitis patients, six were diagnosed with pouchitis and pre-pouch ileitis (median faecal calprotectin: 865 microg/g, with a range of 95-2350 microg/g); 13 had pouchitis alone (145, 33-3350 microg/g) and 27 were uninflamed (56, 4-705 microg/g). Of the familial adenomatous polyposis patients, one had pouchitis and pre-pouch ileitis (305 microg/g), and seven had noninflamed pouches (9, 6-26 microg/g). Stool samples obtained from pouchitis patients had significantly higher calprotectin concentrations compared with those obtained from uninflamed pouches (Mann-Whitney: P<0.0001). Faecal calprotectin concentrations correlated closely with the Objective Pouchitis Score, the Pouch Disease Activity Index and endoscopic and histological inflammatory scores (Spearman rank test: P values <0.0001). Using a faecal calprotectin threshold of >or=92.5 microg/g to define a positive result, Receiver Operating Characteristic analysis demonstrated a sensitivity of 90% and a specificity of 76.5%. CONCLUSION Faecal calprotectin measurement is a useful noninvasive tool in the diagnosis of acutely inflamed ileal pouches and correlates well with the severity of pouchitis.
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Konikoff MR, Denson LA. Role of fecal calprotectin as a biomarker of intestinal inflammation in inflammatory bowel disease. Inflamm Bowel Dis 2006; 12:524-34. [PMID: 16775498 DOI: 10.1097/00054725-200606000-00013] [Citation(s) in RCA: 300] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Calprotectin is an abundant neutrophil protein found in both plasma and stool that is markedly elevated in infectious and inflammatory conditions, including inflammatory bowel disease (IBD). We conducted a systematic review of the published literature regarding fecal calprotectin to evaluate its potential as a noninvasive marker of neutrophilic intestinal inflammation. Reference ranges for fecal calprotectin have been established in healthy adults and children, and elevated concentrations of fecal calprotectin have been demonstrated in numerous studies of patients with IBD. Fecal calprotectin correlates well with histological inflammation as detected by colonoscopy with biopsies and has been shown successfully to predict relapses and detect pouchitis in patients with IBD. Fecal calprotectin has been shown to consistently differentiate IBD from irritable bowel syndrome because it has excellent negative predictive value in ruling out IBD in undiagnosed, symptomatic patients. Fecal calprotectin also may be useful in determining whether clinical symptoms in patients with known IBD are caused by disease flares or noninflammatory complications/underlying irritable bowel syndrome and in providing objective evidence of response to treatment. Although more studies are needed to define fully the role of fecal calprotectin, convincing studies and growing clinical experience point to an expanded role in the diagnosis and management of IBD.
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Affiliation(s)
- Michael R Konikoff
- Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA
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Johnson MW, Dewar DH, Ciclitira P, Forbes A, Nicholls RJ, Bjarnason I. Use of fecal lactoferrin to diagnose irritable pouch syndrome: a word of caution. Gastroenterology 2004; 127:1647-1648. [PMID: 15521043 DOI: 10.1053/j.gastro.2004.09.069] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/02/2022]
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Affiliation(s)
- I Bjarnason
- Dept. of Medicine, Guy's, King's, St Thomas's Medical School, Bessemer Road, London SE5 9PJ, UK.
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Abstract
Pouchitis is one of the commonest and most debilitating complications of a restorative proctocolectomy. The cause remains elusive, though a number of approaches have been shown to alleviate the condition. This review outlines current evidence relating to pouchitis, obtained from randomised and nonrandomised studies. Medline, the Bath Information Data Service (BIDS) and PubMed were searched using the keywords 'pouchitis' and 'inflammatory bowel disease'. In addition, articles were cross-referenced, and the abstracts of recent colorectal meetings studied.
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Affiliation(s)
- D A L Macafee
- Division of GI Surgery, Queens Medical Centre, Nottingham, UK.
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Abstract
Calprotectin is a calcium and zinc binding protein of the S100 family derived predominantly from neutrophils and monocytes. It is detectable in body fluids and tissue samples and is emerging as a valuable marker in the diagnosis, and the monitoring and determining of the prognosis of commonly encountered gastroenterological conditions. Fecal calprotectin, in particular, has for a long time been regarded as a promising marker of gastrointestinal pathology and has now been established as a routine test in Norway and at several centers in the UK.
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Affiliation(s)
- Andrew Poullis
- Gastroenterology, Endocrinology and Metabolism Division, St George's Hospital Medical School, London and Mayday University Hospital, Surrey, UK.
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Pouchitis. J Wound Ostomy Continence Nurs 2002. [DOI: 10.1097/00152192-200203000-00005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Prabhudesai A, Kumar D. Surgery of the small bowel. Curr Opin Gastroenterol 2001; 17:127-131. [PMID: 11224667 DOI: 10.1097/00001574-200103000-00005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
This review deals with various developments in the field of small-bowel surgery, including the role of ileal pouch-anal anastomosis and ileorectal anastomosis in the treatment of ulcerative colitis and familial adenomatous polyposis. We discuss modern trends in the surgical management of Crohn disease, and the increasing use of laparoscopy in the management of inflammatory bowel disease and small-bowel obstruction. In addition to looking at small-bowel tumors, this review deals with the current status of small-bowel transplantation.
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Affiliation(s)
- Ashish Prabhudesai
- Department of Colorectal Surgery, St. George's Hospital, Tooting, London, UK
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