Gordon IO¹, Bettenworth D², Bokemeyer A², Srivastava A³, Rosty C⁴, Hertogh GE⁵, Robert ME⁶, Valasek MA⁷, Mao R⁸, Kurada S⁹, Harpaz N¹⁰, Borralho P¹¹, Pai RK¹², Pai RK¹³, Odze R¹⁴, Feakins R¹⁵, Parker CE¹⁶, Nguyen T¹⁶, Jairath V¹⁷, Baker ME¹⁸, Bruining DH¹⁹, Fletcher JG²⁰, Feagan BG¹⁷, Rieder F²¹; Stenosis Therapy and Anti-Fibrotic Research (STAR) Consortium. Gastroenterology. 2019 Aug 30. pii: S0016-5085(19)41258-4. doi: 10.1053/j.gastro.2019.08.033. [Epub ahead of print]

Author information

1 Department of Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic Foundation, Cleveland, USA.

2 Department of Medicine B, Gastroenterology and Hepatology, University Hospital Münster, Münster, Germany.

3 Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.

4 Department of Clinical Pathology, The University of Melbourne, Parville, VIC, Australia; Envoi Specialist Pathologists, Brisbane, QLD, Australia; Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.

5 Department of Pathology, University Hospital Leuven, Leuven, Belgium.

6 Department of Pathology, Yale University School of Medicine, New Haven, USA.

7 Department of Pathology, University of California San Diego, La Jolla, California, USA.

8 Department of Gastroenterology, First Affiliated Hospital of Sun Yat-sen University, China; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.

9 Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA; Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute; Cleveland Clinic Foundation, Cleveland, USA.

10 Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.

11 Faculdade de Medicina da Universidade de Lisboa, Instituto de Anatomia Patológica, Lisbon, Portugal.

12 Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

13 Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, AZ, USA.

14 Pathology Department, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

15 Department of Cellular Pathology, Royal London Hospital, Barts Health NHS Trust, London, United Kingdom.

16 Robarts Clinical Trials, Inc., London, ON, Canada.

17 Robarts Clinical Trials, Inc., London, ON, Canada; Department of Medicine, Western University, London, ON, Canada; Department of Biostatistics and Epidemiology, Western University, London, ON, Canada.

18 Department of Diagnostic Radiology, Imaging Institute, Digestive Diseases and Surgery Institute, and Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, USA.

19 Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota.

20 Department of Radiology, Mayo Clinic, Rochester, USA.

21 Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA; Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute; Cleveland Clinic Foundation, Cleveland, USA. Electronic address: riederf@ccf.org.

Abstract

BACKGROUND & AIMS: Stenosis is a common complication of Crohn's disease (CD) that has no effective medical therapy. Development of anti-fibrotic agents will require testing in randomized controlled trials. Computed tomography enterography- and magnetic resonance enterography-based technologies might be used to measure outcomes in these trials. These approaches have been validated in studies of patients with symptomatic strictures who underwent imaging evaluations, followed by resection with histopathologic grading of the intestinal tissue for inflammation and/or fibrosis (the reference standard). Imaging findings have correlated with findings from quantitative or semi-quantitative histologic evaluation of the degree of fibromuscular stenosis and/or inflammation on the resection specimen. However, it is not clear whether histologic findings are an accurate reference standard. We performed a systematic review of all published histologic scoring systems used to assess stenosing CD.

METHODS: We performed a comprehensive search of the Embase and Medline of studies through March 13, 2019 that used a histologic scoring system to characterize small bowel CD and assessed inflammatory and fibrotic alterations within the same adult subject. All scores fitting the criteria were included in our analysis, independently of the presence of stricturing disease, as long as inflammation and fibrosis were evaluated separately but in the same scoring system.

RESULTS: We observed substantial heterogeneity among scoring systems, which were not derived using modern principles for evaluative index development. None had undergone formal validity or reliability testing. None of the existing indices had been constructed according to accepted methods for development of evaluative indices. Basic knowledge regarding their operating properties were lacking. Specific indices to evaluate the important pathological component of myofibroblast hypertrophy or hyperplasia have not been proposed.

CONCLUSIONS: In a systematic review of publications, we found a lack of validated histopathologic scoring systems for assessment of fibromuscular stenosis. Data that describe the operating properties of existing cross-sectional imaging techniques for stenosing CD should be questioned. Development and validation of a histopathology index is an important research priority.