key: cord-0847489-mm1608ul
authors: M’Koma, Amosy Ephreim
title: Inflammatory Bowel Disease: Clinical Diagnosis and Surgical Treatment-Overview
date: 2022-04-21
journal: Medicina (Kaunas)
DOI: 10.3390/medicina58050567
sha: c1b7454fb85d215a8d719336c91c0c42fe0499a1
doc_id: 847489
cord_uid: mm1608ul

This article is an overview of guidelines for the clinical diagnosis and surgical treatment of predominantly colonic inflammatory bowel diseases (IBD). This overview describes the systematically and comprehensively multidisciplinary recommendations based on the updated principles of evidence-based literature to promote the adoption of best surgical practices and research as well as patient and specialized healthcare provider education. Colonic IBD represents idiopathic, chronic, inflammatory disorders encompassing Crohn’s colitis (CC) and ulcerative colitis (UC), the two unsolved medical subtypes of this condition, which present similarity in their clinical and histopathological characteristics. The standard state-of-the-art classification diagnostic steps are disease evaluation and assessment according to the Montreal classification to enable explicit communication with professionals. The signs and symptoms on first presentation are mainly connected with the anatomical localization and severity of the disease and less with the resulting diagnosis “CC” or “UC”. This can clinically and histologically be non-definitive to interpret to establish criteria and is classified as indeterminate colitis (IC). Conservative surgical intervention varies depending on the disease phenotype and accessible avenues. The World Gastroenterology Organizations has, for this reason, recommended guidelines for clinical diagnosis and management. Surgical intervention is indicated when conservative treatment is ineffective (refractory), during intractable gastrointestinal hemorrhage, in obstructive gastrointestinal luminal stenosis (due to fibrotic scar tissue), or in the case of abscesses, peritonitis, or complicated fistula formation. The risk of colitis-associated colorectal cancer is realizable in IBD patients before and after restorative proctocolectomy with ileal pouch-anal anastomosis. Therefore, endoscopic surveillance strategies, aimed at the early detection of dysplasia, are recommended. During the COVID-19 pandemic, IBD patients continued to be admitted for IBD-related surgical interventions. Virtual and phone call follow-ups reinforcing the continuity of care are recommended. There is a need for special guidelines that explore solutions to the groundwork gap in terms of access limitations to IBD care in developing countries, and the irregular representation of socioeconomic stratification needs a strategic plan for how to address this serious emerging challenge in the global pandemic.

Colonic inflammatory bowel disease (IBD), or the colitides, encompasses Crohn's colitis (CC) and ulcerative colitis (UC), the two highly heterogeneous, debilitating, incurable, persistent, relapsing/worsening, immune-arbitrated inflammatory pathologies of the digestive system canal [1] . UC causes inflammation and ulceration of the epithelial layer and, to a lesser degree, the submucosae layer of the larger intestine (colon and rectum) only [2] . CC varies from UC in location, in that it is segmental and causes inflammation impacting the whole digestive system from the mouth to the anus and can further cause inflammation deeper within all the intestinal layers (transmural and skip lesions) that may affect other organs through fistulation [3, 4] . IBD has significant impacts on patient health quality of life (QoL), mental health, work productivity, and healthcare resources [5, 6] .

There are established guidelines for the diagnosis of IBD [7, 8] , which include international clinical practice tool recommendations that incorporate various best practices, and other evidence has widely been issued [9, 10] . Thirty percent of IBD patients with colonic IBD present with ambiguous diagnosis [11] . In the past two decades, there have been vast advances in research, i.e., molecular diagnostics and surgical technical evolution for IBD management [12, 13] . The aim of this overview is to provide disease guidance consensus for healthcare professionals managing IBD, to ensure that investigation, diagnosis, surgical treatment, and monitoring decisions are based on the best available common consent evidence, and to promote and ameliorate the best accepted practice.

Effectuates of IBD are not yet fully understood, but are believed to be multifactorial [1, 14, 15] , i.e., a susceptible host (e.g., genetic, gut barrier and the exaggerated innate/adaptive immune response) and external/exogenous factors (e.g., normal indigenous intestinal luminal flora) are important basic associates that probably induce and perpetuate the pathogenesis of IBD [16] . The mechanistic trigger processes are mediated through components of the autoimmune response to self-antigens [17, 18] . Recently, research has paid attention to the role of antibodies in downstream events and mechanisms of autoimmunity and inflammation [19, 20] . Whether the fabrication of antibodies is a serologic product of IBD or if it is a consequence of barrier dysfunction caused by inflammation remains a significant knowledge gap.

While the Western world including US, Canada and Europe continues to advance and improve ambulatory regimens care delivery [21, 22] to meet high-quality, safety, efficacy, coordination of care, and recommended precision evidenced-based care in IBD patients [23, 24] , developing nations at large have healthcare service constraints and limitations to meet the required standard of care [25] due to limited resources and healthcare personnel not being trained and having no knowledge about treating these diseases [26] . Furthermore, regarding cost-effectiveness considerations and recommendations by the World Health Organization (WHO) and the World Gastroenterology Organization (WGO) [27, 28] , developing countries struggle the most. The economic implications of IBD are enormous [29] . Hospital admission rates and costs for IBD show an increasing trend [30, 31] . In the US alone, the estimated annual direct treatment costs are greater than USD 6.8 billion, and indirect costs amount to an additional USD 5.5 billion [32, 33] . The healthcare systems, both at the level of primary care and referral hospitals in developing nations, face significant infrastructural limitations as they lack the regular clinical supervision and laboratory assessments needed for evaluating, diagnosing, treating, and monitoring IBD patients [5, 6] , and will increasingly have difficulty affording the surgical treatment need of these patients as per the herewith presented approval guidelines compared to developed wealthy societies.

A literature search for the diagnosis and treatment recommendation guidelines for IBD was performed using predetermined protocols from PubMed, Cumulative Index of Nursing and Allied Health Literature (CINAHL), the Google search engine, Cochrane Database and IBD-associated society organizations, i.e., the American Gastroenterological Association [34, 35] , MEDLINE and EMBASE were searched between 1980 and 2021.

Currently, there is no standardized diagnostic test tool for IBD [36, 37] . The standard state-of-the-art diagnosis of IBD relies on amassing of clinical, radiologic, endoscopic, and histopathologic clarification [38, 39] . This inexact compilation technique is not always accurate, and about 15% of colonic IBD patients cannot be delineated as UC or CC and are labeled as having "indeterminate colitis" (IC). This is because the clarification criteria for UC and CC are indefinite [40, 41] . In addition, another 15% of the colonic IBD cases that undergo pouch surgery, i.e., restorative proctocolectomy with ileal pouch-anal anastomosis (RPC-IPAA) for their definitive UC diagnosis based on the pathologist's final designation of endoscopic biopsies, will have their initial UC diagnosis reciprocated to ileal Crohn's disease (CD) based on the postoperative follow-up when clinical and histopathology changes indicate the evolution of CD in the ileal reservoir and/or because authentic CC was not evident prior to colectomy [42, 43] . Half of these patients with pouch ileal CD will require reservoir/pouch excision or diversion [44, 45] .

Ulcerative colitis' (UC) peak onset is mostly in early adulthood [46] . A consequence of untreated UC is chronic inflammation and ulcerations in the mucosal and to a lesser degree submucosal linings confined to the large intestine (colon and rectum) [39, 46] . Approximately 15% of patients may encounter hostile development, and these patients may require hospital admission for fulminant disease [46, 47] . To establish the diagnosis and disease state of a patient sample, gastrointestinal pathologists depend most on nanoscopic visual examination and the elucidation of marked and/or colored tissue sections [48, 49] . These procedures are endowed with a significant degree of discourse [50] , and are surfeited with expostulations [50, 51] . Careful professional tutoring in pathology subspecialties has helped to achieve the benchmark of care and abolish exorbitant oversights [52, 53] . Notwithstanding these eminently thorough benchmarks, ineludible scenes arise in which impartiality cannot be formally assured and where significant variance of opinion occurs amongst consultant specialists [54] . Further to the fundamental guidelines and associated specialized reviews, moderate to severe UC is circumscribed based on the Truelove and Witts criteria and Mayo Clinic score, as presented in Table 1 [55] [56] [57] . Mayo Clinic scores of 6-12 with an endoscopic subscore of 2 or 3 are viewed as moderate to severe disease. These guidelines are explicated as hospital-admitted patients with the following Truelove and Witts criteria: six or more hematochezia (bloody diarrhea) movements/day with at least one marker of inseparable toxicity, including heartbeat/rate > 90 beats/min, body temperature > 37.8 • C, blood hemoglobin < 10.5 g/dL, and/or an erythrocyte sedimentation rate (ESR) of −30 mm/h [56] . 

Predominantly colonic Crohn's disease, or Crohn's colitis, is an IBD diagnosed in at least four patients per 100,000 live births in the United States and Canada, and the incidence and prevalence are rising internationally [58] [59] [60] , specifically in developing nations [26, 58] . Clinically, CC differs from UC in that it may result in inflammation deeper within the entire colonic walls (mucosa, submucosa, muscularis and serosa, (trammeller) (colon, and rectum) [39] . Furthermore, CC may also affect other systemic organs outside the colon tract through fistulation [3, 4, 61] . The conciliate features for diagnosing CC comprise an inexact combination of classification systems discussed above in Section 3 for IBD clinical diagnosis, and histopathological findings demonstrating focal, asymmetric, transmural, or granulomatous features [62, 63] . Abdominal computed tomography (CT) colonography is the most widely recommended and preferred first-line radiologic study used in the evaluation/assessment of CC. The diagnostic accuracy of magnetic resonance colonography is equivalent to that of CT scans and prevents liability exposure to ionizing radiation. Endoscopic score metrics are the gold standard tool used to estimate the activity of CC, and they are used more often in clinical trials to compute proof of the efficacy and safety of various drugs inducing and maintaining remission and mucosal healing. There are several multipronged scoring systems, but the most used to measure clinical disease severity include the CC Activity Index (CDAI), the Harvey-Bradshaw index (HBI), the short IBD questionnaire (SIBDQ) and the Lehmann score [62, 63] .

In colonic IBD, delineation between CC from UC is often inconclusive [11, 40, 41, 64] , thereby confounding effective and appropriate surgeries [39] . Approximately 30% of patients with colonic IBD are indistinguishable, especially during the prodromal stage, and are therefore labeled as "indeterminate colitis" (IC) due to the non-definitive establishment of criteria for CC and UC [40, 65, 66] . Therefore, understanding the biomolecules and different cellular mechanisms driving IBD heterogeneity is vital to the development of future drug inhibitors to improve patient care [67] [68] [69] [70] . The distinction between UC and CC in otherwise IC is of utmost importance when determining a patient's candidacy for RPC-IPAA, the standard curative surgical procedure in the treatment for UC. The success of RPC-IPAA surgery and convalescence largely depend on correct diagnosis. To address the IBD diagnosis dilemma in clinical settings, there are published data that have shown robust evidence supporting the presence of human alpha defensin 5 (DEFA5, alias HD5) in the colon crypt mucosa with aberrant expression of Paneth cell-like cells (PCLCs) and apparent crypt-cell-like cells (CCLCs) in areas identified with an ectopic colonic ileal metaplasia that is consistent with the diagnosis of CC [11, 71] . This conceptual innovation relies on the expression of DEFA5 and the CCLCs in the colonic mucosal crypt of CC patients and its definitive discriminatory use as a biomarker to facilitate the unambiguous diagnosis of CC with a positive predictive value (PPV) of 96 percent [11, 71] .

Histopathology and clinical evaluation show that CC and UC, the two major classifications of IBD subtypes, are indeed discrete entities and have disparate causes and distinguishable mechanisms of tissue damage [72, 73] . The foundational inquiry is why the systemic innate immune process responds aggressively to indigenous innocuous inextinguishable bacteria (the commensals), deliverance complex mixes of tissue by-product signatures (cytokines, chemokine, growth factors) and other substances that cause inflammation (antibody-antigen reaction against mucosal resistance).

When diet, health coaching and lifestyle changes, conservative drug therapy, or other treatments fail and do not relieve IBD symptoms, surgery is inevitably recommended.

Surgery for ulcerative colitis: One of the greatest achievements in surgery of the colon and rectum over the past four decades has been the development and reconstruction of the sphincter-preserving pelvic pouch operation, the RPC-IPAA (Figure 1 ), in patients with refractory UC [74, 75] . The development and refinement of pelvic pouch surgery requires the excision and removal of the entire diseased colon while maintaining gut continuity, trans-anal fecal continence/defecation, deferral, discrimination, and fertility. The success of RPC-IPAA surgery is largely dependent on careful patient selection, in particular the correct diagnosis combined with meticulous surgical technique [12, 76, 77] . Pelvic pouch reconstruction surgery, RPC-IPAA, is the criterion standard surgical procedure for patients with UC [74, 75] . The 5-and 10-year cumulative risk of colectomy (emergence or elective) is 10-15%, primarily limited to patients with moderate to severe disease activity; a subset of hospitalized patients with acute severe UC (ASUC), also called fulminant UC, have short-term colectomy rates of 25-30% [47, [78] [79] [80] [81] . In some cases, it is not possible to maintain a pouch due to subsequent complications; in this case, a permanent terminal ileostomy may be required [44, [82] [83] [84] [85] [86] [87] [88] . 

In CD, there is inflammatory mechanical stress p that plays a critical role in intestinal fibrosis and smooth muscle hyperplasia, causi minal continuity to be impaired and/or blocked [91, 92] . Due to bowel strictures a obstructions, containing various degrees of inflammation, fibrosis, and hyperplas mation, up to two-thirds of people with CC will require at least one surgery in the time. However, surgery does not cure CC. Currently, fibrotic strictures require endo balloon dilatation and/or surgical resection. Surgical resection seeks to remove d stream blockages or constriction and keeps the upstream distended bowel to mainta Lumina continuity, but recurrences after surgical resection occur at a rate of 100% patients still suffer long-term bowel symptoms, i.e., abdominal discomfort, pain, an stipation. The benefits of surgery for CC are usually temporary, and the disease oft curs, frequently at the anastomosis site. Postoperatively, it is recommended to pre 

In CD, there is inflammatory mechanical stress process that plays a critical role in intestinal fibrosis and smooth muscle hyperplasia, causing luminal continuity to be impaired and/or blocked [91, 92] . Due to bowel strictures and/or obstructions, containing various degrees of inflammation, fibrosis, and hyperplasia formation, up to two-thirds of people with CC will require at least one surgery in their lifetime. However, surgery does not cure CC. Currently, fibrotic strictures require endoscopic balloon dilatation and/or surgical resection. Surgical resection seeks to remove downstream blockages or constriction and keeps the upstream distended bowel to maintain the Lumina continuity, but recurrences after surgical resection occur at a rate of 100% and patients still suffer long-term bowel symptoms, i.e., abdominal discomfort, pain, and constipation. The benefits of surgery for CC are usually temporary, and the disease often recurs, frequently at the anastomosis site. Postoperatively, it is recommended to prescribe adjuvant medication to minimize and/or delay the risk of recurrence, which occurs at a rate of 100%, given sufficient time after resection, and many patients will still suffer long-term bowel symptoms, i.e., constipation and abdominal pain.

Surgery for indeterminate colitis: The inability to distinguish between CC and UC leads to the diagnosis of IC [11] . Here, dispersal favors UC, but focal transmural inflammation or inflammation in the ileum is anticipated in blackwash ileitis and no fistulation [11] . IC is seen in about 15% of patients suffering from IBD when features attributable to both UC and CD are inconclusive [11, 71] . Dysplasia on a background of IC warrants surgical resection based on the same principles of management for either CD-or UC-associated dysplasia. The specific surgical approach is based on whether UC or CC is more likely. In such a circumstance, human alpha defensin 5 (DEFA5) testing is found to be an accurate candidate biomarker to assist in delineating between CC and UC in the IC patient cohort [11, 71] . When the disease is more severe, completing the total abdominal colectomy (TAC) first to assist in making a pathological diagnosis may be effective. This can be followed by a proctectomy (in the case of CC) or IPAA (in the case of UC). In cases where UC is suggested, and in a highly select group of patients with a CC-like phenotype without ileal or anal disease, an RPC-IPAA may be considered. Overall, treatment is often based on the likely phenotype and patients should be advised that if ileal-pouch CD manifests itself after an RPC-IPAA, conversion to an end ileostomy is likely [42, 44] .

Surgical management of patients with IBD during the COVID-19 pandemic: The coronavirus disease 2019 (COVID-19) pandemic has been a global tragedy that changed the traditional pharmacologic and surgical management plan of patients with IBD [10, [93] [94] [95] . The main clinical outcomes were maintained during the COVID-19 pandemic period largely because scheduled visits were replaced by phone calls and virtual consultations [96] [97] [98] . Virtual clinic follow-ups used the contact center service (CCS) based on the reorganization of high-volume IBD centers and on the continuity of care during the COVID-19 pandemic. This approach could be implemented after the pandemic to optimize the resources of IBD centers [96, 99] . This has led to substantial changes, causing the interruption of non-essential endoscopic procedures and outpatient visits, particularly impacting the assessment of disease activity by increasing the risk of relapse, disease complications, delays of new diagnosis and the detection of early post-operative recurrence of CD [100] . The interventional performance of routine endoscopy was largely suspended in many IBD clinics and centers worldwide where severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had spread [93] . Experts highlight different scenarios in which endoscopy should still be performed imperatively in unique circumstances in patients with IBD, as well as suggested instructions regarding the use of personal protective equipment [93, 101] for carrying out safe procedures and the possible risks of postponing endoscopy in IBD and a post-pandemic plan for access to endoscopy as summarized by Iacucci et al. [93] . The Clinical Practice Update (CPU) from experts presented evidence that provides timely council on the surgical treatment of patients with IBD during the COVID-19 pandemic. Admittedly, the comments herewith provide perspective on a topic of high surgical importance that underwent internal peer review by the Clinical Practice Updates Committees and external peer review through standard procedures of gastroenterology [10, 93] , which are highlighted in Figure 2 . We are reminded, however, that as the understanding of the novel coronavirus progresses, IBD-specific issues and guidance may change beyond reasonable doubt [10, 102] .

Management of patients with IBD during the COVID-19 pandemic. 5-ASA, 5-aminosalicylic acid medication; CRP, C-reactive protein; mAb, monoclonal antibodies. * Symptoms and consequences of COVID-19: fever (83-99%); cough (59-82%); fatigue (44-70%); anorexia (40-84%); shortness of breath (31-40%); sputum production (28-33%); myalgias (11-35%); headache, confusion, rhinorrhea, sore throat, hemoptysis, vomiting, and diarrhea (<10%); lymphopenia (83%); computed tomography chest: bilateral, peripheral, ground-glass opacities [103] . ** Clearance of SARS-CoV-2 may enable the resumption of IBD therapy; the role of serologic antibody testing is unclear at the current time. *** Indicating new a sentence. Viral clearance testing may or may not be possible or appropriate, given local testing capabilities and health system-approved epidemiological testing strategies during the COIVD-19 pandemic. Treatments for COVID-19 are under investigation, considering therapies that have safety and efficacy in IBD. Reprint /Doneadapted with permission from Rubin et al. Ref. [10] . shortness of breath (31-40%); sputum production (28-33%); myalgias (11-35%); headache, confusion, rhinorrhea, sore throat, hemoptysis, vomiting, and diarrhea (<10%); lymphopenia (83%); computed tomography chest: bilateral, peripheral, ground-glass opacities [103] . ** Clearance of SARS-CoV-2 may enable the resumption of IBD therapy; the role of serologic antibody testing is unclear at the current time. *** Indicating new a sentence. Viral clearance testing may or may not be possible or appropriate, given local testing capabilities and health system-approved epidemiological testing strategies during the COIVD-19 pandemic. Treatments for COVID-19 are under investigation, considering therapies that have safety and efficacy in IBD. Reprint /Doneadapted with permission from Rubin et al. Ref. [10] . Informed Consent Statement: Informed consent was obtained, and patient participation in the study was voluntary.

Data Availability Statement: All data analyzed during this study are included in this published article.

The authors declare conflicts of interests to disclose, Amosy Ephreim M'Koma, has previously received Honoraria fees for Educational Presentation from Lipscomb University Health Sciences and from The International Colorectal Research summit (Korean society of coloproctology), Seoul, Korea. Furthermore, he is the inventor of two patents: (i) assay methods for diagnosing and treating inflammatory bowel disease with human alpha-defensin 5 (US Patent 16/571,034, 2020); and (ii) targeted DEFA5 antibody and assay methods for diagnosing and treating inflammatory bowel disease (US Patent 16/622,259, 2021). This does not alter our adherence to the MDPI journal's policies on sharing educational data and materials in science.

The Multifactorial Etiopathogeneses Interplay of Inflammatory Bowel Disease: An Overview

Diagnosis and classification of ulcerative colitis

Surgical repair of rectovaginal fistulas in patients with Crohn's disease

Diagnosis and management of fistulizing Crohn's disease

Quality of life, work productivity impairment and healthcare resources in inflammatory bowel diseases in Brazil

Evidence-based clinical practice guidelines for inflammatory bowel disease

Consensus standards of healthcare for adults and children with inflammatory bowel disease in the UK. Front

Clinical guidelines for the management of inflammatory bowel disease: Update of a French national consensus

AGA Clinical Practice Update on Management of Inflammatory Bowel Disease during the COVID-19 Pandemic: Expert Commentary

Human alpha defensin 5 is a candidate biomarker to delineate inflammatory bowel disease

Evolution of the restorative proctocolectomy and its effects on gastrointestinal hormones

Practical guidelines on endoscopic treatment for Crohn's disease strictures: A consensus statement from the Global Interventional Inflammatory Bowel Disease Group

A meta-analysis of antibiotic therapy for active ulcerative colitis

Oxazolone colitis, a Th2 colitis model resembling ulcerative colitis, is mediated by IL-13-producing NK-T cells

Autoantibodies and an immune-based rat model of inflammatory bowel disease

The immunology of mucosal models of inflammation

Statins-Treatment option for central nervous system autoimmune disease

New insights into T cell biology and T cell-directed therapy for autoimmunity, inflammation, and immunosuppression

Utilization of health care resources by individuals with inflammatory bowel disease in the United States: A profile of time since diagnosis

The quality of health care delivered to adults in the United States

Quality of care for gastrointestinal conditions: A primer for gastroenterologists

Improved Outcomes in a Quality Improvement Collaborative for Pediatric Inflammatory Bowel Disease

Role of biological therapy for inflammatory bowel disease in developing countries

Inflammatory Bowel Disease On-Line Web-Based Guide to Health Professionals and Patients in Developing and African Nations

Threshold Values for Intervention Cost-Effectiveness by Region

Cost effectiveness of treatments for inflammatory bowel disease

Costs in inflammatory bowel diseases

Direct hospital costs for patients with inflammatory bowel disease in a Canadian tertiary care university hospital

The Impact of Inflammatory Bowel Disease in Canada 2018: Direct Costs and Health Services Utilization

Societal costs attributable to Crohn's disease and ulcerative colitis within the first 5 years after diagnosis: A Danish nationwide cost-of-illness study 2002-2016

Meta-analysis of observational studies in epidemiology: A proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group

Quantitative methods in the review of epidemiologic literature

Crohn's disease. The problem of early diagnosis

Challenging question: Can we diagnose Crohn's disease without histology?

Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 3: Special situations

Diagnosis of inflammatory bowel disease: Potential role of molecular biometrics

Indeterminate colitis: Clinical spectrum of disease

Is indeterminate colitis determinable?

The MYTHS of de novo Crohn's Disease after Restorative Proctocolectomy with Ileal Pouch-anal Anastomosis for Ulcerative Colitis

De Novo Crohn's Disease of the Pouch in Children Undergoing Ileal Pouch-Anal Anastomosis for Ulcerative Colitis

Adenocarcinoma at the Ileostomy Site after a Proctocolectomy for Ulcerative Colitis and/or Familial Adenomatous Polyposis: An Overview

Crohn's disease and indeterminate colitis and the ileal pouch-anal anastomosis: Outcomes and patterns of failure

Natural History of Adult Ulcerative Colitis in Population-based Cohorts: A Systematic Review

A proactive outreach intervention that decreases readmission after hepatectomy

Observer variation and discriminatory value of biopsy features in inflammatory bowel disease

Histopathological evaluation of colonic mucosal biopsy specimens in chronic inflammatory bowel disease: Diagnostic implications

Quantitative comparison of immunohistochemical staining measured by digital image analysis versus pathologist visual scoring

Observer variability in the interpretation of HER2/neu immunohistochemical expression with unaided and computer-aided digital microscopy

Host engulfment pathway controls inflammation in inflammatory bowel disease

Risk Stratification of Patients with Crohn's Disease: A Retrospective Analysis of Clinical Decision Making and Its Impact on Long-Term Outcome

Changes in breast cancer therapy because of pathology second opinions

Ulcerative Colitis Care Pathway

Serial biopsy in ulcerative colitis

Assessing Severity of Disease in Patients with Ulcerative Colitis

Inflammatory Bowel Disease: An Expanding Global Health Problem

Inflammatory bowel disease epidemiology

Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review

Recent advances in the management of perianal fistulizing Crohn's disease: Lessons for the clinic

A comprehensive review and update on Crohn's disease

Ileocecal Anastomosis Type Significantly Influences Long-Term Functional Status, Quality of Life, and Healthcare Utilization in Postoperative Crohn's Disease Patients Independent of Inflammation Recurrence

Inflammatory bowel disease unclassified and indeterminate colitis: The role of the pathologist

Indeterminate colitis

North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition; Colitis Foundation of America. Differentiating ulcerative colitis from Crohn disease in children and young adults: Report of a working group of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the Crohn's and Colitis Foundation of America

ECCO Guidelines on Therapeutics in Crohn's Disease: Surgical Treatment. J. Crohn's Colitis 2020

First-Line Biologics or Small Molecules in Inflammatory Bowel Disease: A Practical Guide for the Clinician

ESPEN practical guideline: Clinical Nutrition in inflammatory bowel disease

Diagnostic Approach to Monogenic Inflammatory Bowel Disease in Clinical Practice: A Ten-Year Multicentric Experience

Linking bacterial enterotoxins and alpha Defensin 5 expansion in the Crohn's colitis: A new insight into the etiopathogenetic and differentiation triggers driving colonic inflammatory bowel disease

Inflammatory bowel disease

Clinical outcome of ulcerative colitis in children

Recent trends in ileoanal anastomosis

Proctocolectomy with ileal reservoir and anal anastomosis

Human Alpha Defensins are Differentially Expressed Between the Inflammatory Colitides

Proteomic patterns of colonic mucosal tissues delineate Crohn's colitis and ulcerative colitis

Impact of High-Dose Vitamin D3 Supplementation in Patients with Crohn's Disease in Remission: A Pilot Randomized Double-Blind Controlled Study

The efficacy and safety of either infliximab or adalimumab in 362 patients with anti-TNF-alpha naive Crohn's disease

Letter: Comparative safety and efficacy of infliximab vs. adalimumab in Crohn's disease-should one consider disease location? Authors' reply

Adaptive Returns of Deficient Systemic Plasma Immunoglobulin G Levels as Rehabilitation Biomarker after Emergency Colectomy for Fulminant Ulcerative Colitis

British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults

A Challenging Case of Ileosigmoid Knotting in an Elderly

The lateral rectus abdominis positioned stoma (LRAPS) trephine: The hope in Pandora's box

AGA Technical Review on the Management of Moderate to Severe Ulcerative Colitis

Interleukin-27 as a Novel Therapy for Inflammatory Bowel Disease: A Critical Review of the Literature

How to fund IBD nurses

Microbiota and mucosal defense in IBD: An update

Diagnosis and management of pouchitis

Diagnosis and management of postoperative ileal pouch disorders

Sa130 Mechanical stress plays a critical role in intestinal fibrosis and smooth muscle hyperplasia in rodent model of Crohn's disease

Novel insights into the mechanism of action of exclusive enteral nutrition in Crohn's disease: Pre-clinical study in a rodent model of Crohn's-like colitis

Endoscopy in inflammatory bowel diseases during the COVID-19 pandemic and post-pandemic period

Coronavirus and Patients with Inflammatory Bowel Disease: Management Strategies for the Practicing Clinician

Inflammatory bowel disease amid the COVID-19 pandemic: Impact, management strategies, and lessons learned

The impact of a dedicated contact centre on the clinical outcome of patients with inflammatory bowel disease during the COVID-19 outbreak

How to manage inflammatory bowel disease during the COVID-19 pandemic: A guide for the practicing clinician

COVID-19 and IBD drugs: Should we change anything at the moment? Gut

Innovation in IBD Care during the COVID-19 Pandemic: Results of a Cross-Sectional Survey on Patient-Reported Experience Measures

Noninvasive monitoring of inflammatory bowel disease in the post COVID-19 era

Practical management of inflammatory bowel disease patients during the COVID-19 pandemic: Expert commentary from the Gastroenterological Society of Australia Inflammatory Bowel Disease faculty

AGA Rapid Recommendations for Gastrointestinal Procedures during the COVID-19 Pandemic

Interim Clinical Guidance for Management of Patients with Confirmed Coronavirus Disease (COVID-19)