IOIBD Recommendations for Clinical Trials in Ulcerative Proctitis: The PROCTRIAL Consensus.

BACKGROUND & AIMS: Clinical trials evaluating biologics and small molecules in patients with ulcerative colitis are predominantly excluding ulcerative proctitis. The objective of the Definition and endpoints for ulcerative PROCtitis in clinical TRIALs initiative was to develop consensus statements for definitions, inclusion criteria, and endpoints for the evaluation of ulcerative proctitis in adults. METHODS: Thirty-five international experts held a consensus meeting to define ulcerative proctitis, and the endpoints to use in clinical trials. Based on a systematic review of the literature, statements were generated, discussed, and approved by the working group participants using a modified Delphi method. Consensus was defined as at least 75% agreement among voters. RESULTS: The group agreed that the diagnosis of ulcerative proctitis should be made by ileocolonoscopy and confirmed by histopathology, with the exclusion of infections, drug-induced causes, radiation, trauma, and Crohn's disease. Ulcerative proctitis was defined as macroscopic extent of lesions limited to 15 cm distance from the anal verge in adults. Primary and secondary endpoints were identified to capture response of ulcerative proctitis to therapy. A combined clinical and endoscopic primary endpoint for the evaluation of ulcerative proctitis disease activity was proposed. Secondary endpoints that should be evaluated include endoscopic remission, histologic remission, mucosal healing, histologic endoscopic mucosal improvement, disability, fecal incontinence, urgency, constipation, and health-related quality of life. CONCLUSIONS: In response to the need for guidance on the design of clinical trials in patients with ulcerative proctitis, the Definition and end points for ulcerative PROCtitis in clinical TRIALs consensus provides recommendations on the definition and endpoints for ulcerative proctitis clinical trials.

Earlier Anti-Tumor Necrosis Factor Therapy of Crohn's Disease Correlates with Slower Progression of Bowel Damage.

INTRODUCTION: Crohn's disease (CD) follows a relapsing and remitting course incurring cumulative bowel damage over time. The question of whether or not the timing of the initiating biologic therapy affects long-term disease progression remains unanswered. Herein, we calculated rates of change in the Lémann index-which quantifies accumulated bowel damage-as a function of the time between the disease onset and initiation of biologic therapy. We aimed to explore the impact of the earlier introduction of biologics on the rate of progression of long-term cumulative bowel damage. METHODS: Medical records of CD patients treated during 2009-2014 at The Mount Sinai Hospital were queried. Inclusion criteria were two comprehensive assessments allowing calculation of the index at t1 and t2: two time-points ≥ 1 year apart. Patients with biologics introduced before or within 3 months at inclusion (t1) were defined as Bio-pre-t1 and those who did not as Bio-post-t1. The rate of disease progression was calculated as the change in the index per year during t1-t2. RESULTS: A total of 88 patients were studied: 58 Bio-pre-t1 and 30 Bio-post-t1. Among the 58 Bio-pre-t1 cases, damage progressed in 29 (50%), regressed in 20 (34.5%), and stabilized in 9 (15.5%). Median time to initiation of biologics among patients whose index improved was nominally shorter compared to that in patients whose index progressed (8 vs. 15 years). Earlier introduction of biologics tended to correlate with the slower rate of progression (ρ = 0.241; p = 0.069). CONCLUSIONS: Earlier introduction of biologics tended to correlate with the slower progression of bowel damage in CD, reflected by the reduced rate of Lémann index progression.

Small Bowel Lesions Mimicking Crohn's Disease.

PURPOSE OF REVIEW: Not all injuries of the terminal ileum are Crohn's disease. It is the purpose of this review to consider the differential diagnosis of other acute and chronic ileal lesions. RECENT FINDINGS: The recognition of a granulomatous disease of the terminal ileum, distinct from tuberculosis, dates back over 85 years and perhaps much farther, but over the past decades, many other clinical pathologic entities have been described that are neither tuberculosis nor Crohn's eponymous regional enteritis. In recent years, the catalog of lesions mimicking Crohn's disease of the small bowel and proposals for differential diagnosis and treatment have expanded to include newly reported appendiceal pathology, primary cancers and lymphomas of the intestine, unexpected metastases from distant organs, unusual infections, vasculitides and other ischemic conditions, Behçet's disease, endometriosis, and drug reactions. A diagnosis of Crohn's disease should not be a reflex action in the face of small bowel structural or inflammatory lesions without consideration of pathology in adjacent organs, primary and metastatic lesions of the small intestine, infections, vascular diseases, infiltrative diseases, drug injury, or other "idiopathic" conditions.

A survey of current practice of venous thromboembolism prophylaxis in hospitalized inflammatory bowel disease patients in the United States.

BACKGROUND: Inflammatory bowel disease (IBD) patients are at an increased risk of thrombosis, particularly when hospitalized. Several clinical practice guidelines now recommend pharmacologic prophylaxis for hospitalized ulcerative colitis and Crohn's disease patients. It is unclear to what extent gastroenterologists are aware of these recommendations and whether they are administering pharmacologic venous thromboembolism (VTE) prophylaxis appropriately. Our aim was to explore current practice of VTE prophylaxis in hospitalized IBD patients in the United States. METHODS: A survey was mailed electronically to gastroenterologists whose electronic mail address was listed in the American College of Gastroenterology (ACG) database. This survey included clinical vignettes outlining scenarios for consideration of VTE prophylaxis. RESULTS: A total of 6227 surveys were sent to gastroenterologists nationwide, and 591 physicians chose to participate (response rate 9.5%). Respondents (80.6%) believed that hospitalized IBD patients have a higher risk of VTE than other inpatients. A total of 29.1% were unaware of any recommendations addressing pharmacologic prophylaxis included in ACG IBD guidelines and 34.6% would give pharmacologic VTE prophylaxis to a hospitalized patient with severe ulcerative colitis. Heparin VTE prophylaxis use was associated with gastroenterologists who indicated that their practices comprised more than 50% of patients with IBD (P=0.0001), being a physician at an academic hospital (P=0.0001) and providers having less than 5 years practice experience (P=0.003). CONCLUSIONS: Despite reasonable awareness of the increased risk of thrombosis in hospitalized IBD patients, many US gastroenterologists may not follow clinical practice guidelines and use pharmacologic VTE prophylaxis.

Inflammatory bowel disease: one or two diseases?

This chapter addresses the longstanding question of whether inflammatory bowel disease (IBD) is really one or two diseases. The straightforward answer is that ulcerative colitis (UC) and Crohn's disease (CD) embody separate diseases more than a single syndrome. In reality, however, the question is more complex. This chapter makes the case that there are actually many more than just two diseases under the rubric of IBD.

Difficult-to-treat inflammatory bowel disease: results from an international consensus meeting.

Many patients with inflammatory bowel disease (IBD) have persistent symptoms and disease activity despite the best available medical or surgical treatments. These patients are commonly referred to as having difficult-to-treat IBD and need additional therapeutic strategies. However, the absence of standard definitions has impeded clinical research efforts and comparisons of data. Under the guidance of the endpoints cluster of the International Organization for the Study of Inflammatory Bowel Disease, we held a consensus meeting to propose a common operative definition for difficult-to-treat IBD. 16 participants from 12 countries voted on 20 statements covering various elements of difficult-to-treat IBD, such as failure of medical and surgical treatments, disease phenotypes, and specific complaints from patients. "Agreement" was defined as at least 75% consensus. The group agreed that difficult-to-treat IBD is defined by the failure of biologics and advanced small molecules with at least two different mechanisms of action, or postoperative recurrence of Crohn's disease after two surgical resections in adults, or one in children. In addition, chronic antibiotic-refractory pouchitis, complex perianal disease, and comorbid psychosocial complications that impair disease management also qualified as difficult-to-treat IBD. Adoption of these criteria could serve to standardise reporting, guide enrolment in clinical trials, and help identify candidates for enhanced treatment strategies.

Long-Term Outcomes of the Excluded Rectum in Crohn's Disease: A Multicenter International Study.

BACKGROUND: Many patients with Crohn's disease (CD) require fecal diversion. To understand the long-term outcomes, we performed a multicenter review of the experience with retained excluded rectums. METHODS: We reviewed the medical records of all CD patients between 1990 and 2014 who had undergone diversionary surgery with retention of the excluded rectum for at least 6 months and who had at least 2 years of postoperative follow-up. RESULTS: From all the CD patients in the institutions' databases, there were 197 who met all our inclusion criteria. A total of 92 (46.7%) of 197 patients ultimately underwent subsequent proctectomy, while 105 (53.3%) still had retained rectums at time of last follow-up. Among these 105 patients with retained rectums, 50 (47.6%) underwent reanastomosis, while the other 55 (52.4%) retained excluded rectums. Of these 55 patients whose rectums remained excluded, 20 (36.4%) were symptom-free, but the other 35 (63.6%) were symptomatic. Among the 50 patients who had been reconnected, 28 (56%) were symptom-free, while 22(44%) were symptomatic. From our entire cohort of 197 cases, 149 (75.6%) either ultimately lost their rectums or remained symptomatic with retained rectums, while only 28 (14.2%) of 197, and only 4 (5.9%) of 66 with initial perianal disease, were able to achieve reanastomosis without further problems. Four patients developed anorectal dysplasia or cancer. CONCLUSIONS: In this multicenter cohort of patients with CD who had fecal diversion, fewer than 15%, and only 6% with perianal disease, achieved reanastomosis without experiencing disease persistence.

Patients with distal Crohn's disease often undergo colon resection with a stoma to divert the intestinal stream from the rectum in hopes of achieving sufficient healing to allow ultimate re-establishment of intestinal continuity. Patients and practitioners alike should be aware of the long-term success rates of this procedure. Our retrospective study of 197 patients found that half required later proctectomy and an additional one-quarter remained symptomatic with excluded rectums. Only 14% remained symptom-free after reanastomosis, and only 6% if perianal disease was the initial surgical indication. These data provide estimation of long-term surgical outcomes.

Infliximab in Crohn's disease-associated toxic megacolon.

Refractory medical treatment of Crohn disease-associated toxic megacolon usually requires surgery, which carries substantial morbidity and mortality. We report a case of a woman with steroid and antibiotic-refractory fulminant Crohn colitis and ileitis, complicated by a toxic megacolon, who was successfully treated with infliximab. Infliximab induced rapid clinical response and remission, thereby avoiding emergency (ileo) colectomy. This is the first report of treatment of Crohn disease-associated toxic megacolon with infliximab.

Endpoints for extraintestinal manifestations in inflammatory bowel disease trials: the EXTRA consensus from the International Organization for the Study of Inflammatory Bowel Diseases.

Extraintestinal manifestations occur frequently in patients with inflammatory bowel disease (IBD) and remain a diagnostic and therapeutic challenge. The aim of the Endpoints for Extraintestinal Manifestations in Inflammatory Bowel Disease Trials (EXTRA) initiative was to achieve international expert consensus on how to assess these manifestations in IBD trials. A systematic literature review was done to identify methods to diagnose extraintestinal manifestations in patients with IBD and measure treatment outcomes. A consensus meeting involving a panel of 41 attendees, including gastroenterologists and referral specialists, was held on March 31, 2021, as part of an International Organization for the Study of Inflammatory Bowel Diseases initiative. The panel agreed that a specialist's expertise is needed to confirm the diagnosis of extraintestinal manifestations before the inclusion of a patient in IBD trials, except for axial spondyloarthritis, for which typical symptoms and MRI can be sufficient. Easy-to-measure endpoints were identified to assess the response of extraintestinal manifestations to treatment without needing specialist involvement. For uveitis, peripheral spondyloarthritis, and arthralgia, endpoint measurements need specialist expertise. The timing of endpoint measurements was discussed for individual extraintestinal manifestations. The EXTRA consensus proposes guidelines on how to thoroughly evaluate extraintestinal manifestations within IBD trials, and recommends that these guidelines are implemented in future trials to enable prospective assessment of these manifestations and comparison between studies.

Diversion proctocolitis and the problem of the forgotten rectum in inflammatory bowel diseases: A systematic review.

BACKGROUND AND AIMS: Diversion proctocolitis (DP) is a non-specific mucosal inflammation arising in the defunctionalized colon and/or rectum following faecal diversion (colostomy, ileostomy). Differential diagnosis of DP from the underlying disease in patients with inflammatory bowel diseases (IBD) is often unclear. As a result, it might be difficult to undertake any specific treatment. We aimed to systematically review the literature evidence on DP in IBD patients. METHODS: For this qualitative systematic review, we searched PubMed, EMBASE and Scopus to identify all studies published until July 2021 including IBD patients affected by DP. RESULTS: Overall, 37 papers published between 1982 and 2021 were included. A total of 1.211 IBD patients were included: 613 UC (50.6%), 524 CD (43.3%), 66 IBD-unclassified (IBD-U) (5.4%), 8 unspecified patients (0.7%). Most patients with DP are asymptomatic, although inflammation is detectable in almost all patients with a rectal stump. Reduced short-chain fatty acids and an altered microbiome, may trigger mucosal inflammation and have been proposed as causing factors. An increased risk of developing cancer on DP has been reported in patients with a history of previous dysplasia/cancer. CONCLUSIONS: The etiopathogenesis of DP is still unknown. The efficacy of mesalamine, corticosteroids or short-chain fatty acids has not been proven by randomized trials yet. Since the incidence of cancer of the rectal stump can reach 4.5 per 1.000 diverted patients-year, IBD patients undergoing subtotal colectomy with end-ileostomy should undergo close endoscopic surveillance, being eventually counseled for surgery with or without the restoration of the intestinal continuity.

Ulcerative colitis practice guidelines in adults: American College Of Gastroenterology, Practice Parameters Committee.

Guidelines for clinical practice are aimed to indicate preferred approaches to medical problems as established by scientifically valid research. Double-blind placebo controlled studies are preferable, but compassionate-use reports and expert review articles are used in a thorough review of the literature conducted through Medline with the National Library of Medicine. When only data that will not withstand objective scrutiny are available, a recommendation is identified as a consensus of experts. Guidelines are applicable to all physicians who address the subject regardless of specialty training or interests and are aimed to indicate the preferable but not necessarily the only acceptable approach to a specific problem. Guidelines are intended to be flexible and must be distinguished from standards of care, which are inflexible and rarely violated. Given the wide range of specifics in any health-care problem, the physician must always choose the course best suited to the individual patient and the variables in existence at the moment of decision. Guidelines are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee and approved by the board of trustees. Each has been intensely reviewed and revised by the Committee, other experts in the field, physicians who will use them, and specialists in the science of decision analysis. The recommendations of each guideline are therefore considered valid at the time of composition based on the data available. New developments in medical research and practice pertinent to each guideline will be reviewed at a time established and indicated at publication to assure continued validity. The recommendations made are based on the level of evidence found. Grade A recommendations imply that there is consistent level 1 evidence (randomized controlled trials), grade B indicates that the evidence would be level 2 or 3, which are cohort studies or case-control studies. Grade C recommendations are based on level 4 studies, meaning case series or poor-quality cohort studies, and grade D recommendations are based on level 5 evidence, meaning expert opinion.

Is there physician bias against eliciting affective qualities of pain?

GOALS: The purpose of this study is to determine the weight given to each of 3 pain dimensions by physicians who assess patients' pain experiences. BACKGROUND: Pain is a subjective experience that has profound impact on the quality of life. The 101-Multidimensional Affect and Pain Survey (101-MAPS) is currently the only available instrument that takes into account all 3 validated dimensions of pain by classifying 101 items into "superclusters" of sensory pain, suffering, and well-being. STUDY: Fourteen gastroenterologists, 11 internists, and 11 medicine residents from 2 teaching hospitals rated the items on the 101-MAPS based on their perception of the items' relevance to pain in gastrointestinal diseases, on a scale of 0 (least relevant) to 5 (most relevant). RESULTS: Of the 101 items in the MAPS rated by gastroenterologists, 25 items received a median rating of 4 or above. Of these, 23 were selected from the 57 items in the sensory pain supercluster (40%) and only 1 item each from the 26 in the suffering (3.8%), and the 18 in the well-being (5.5%) dimensions. These proportions were significantly lower for the suffering (P<0.01) and well-being (P<0.05) superclusters than for the sensory pain dimension. CONCLUSIONS: These findings suggest a bias among physicians toward sensory and against affective qualities when eliciting patients' pain experiences. The results also suggest that this bias is found as early as residency training and persists among specialists.

Diverticulitis in immunosuppressed patients.

The differential diagnosis of abdominal pain should not rank diverticulitis any differently in immunosuppressed transplant or AIDS patients than in other patients of the same sex and age and with the same clinical presentation. Immunocompromised patients have increased postoperative infectious risks in direct proportion to the degree of their immune deficiency.

The Management of Intestinal Penetrating Crohn's Disease.

Crohn's disease (CD) leads to the development of complications through progressive uncontrolled inflammation and the transmural involvement of the bowel wall. Most of the available literature on penetrating CD focuses on the perianal phenotype. The management of nonperianal penetrating complications poses its own set of challenges and can result in significant morbidity and an increased risk of mortality. Few controlled trials have been published evaluating this subgroup of patients for clinicians to use for guidance. Utilizing the available evidence, we review the epidemiology, presentation, and modalities used to diagnosis and assess intestinal fistulas, phlegmons, and abscesses. The literature regarding the medical, endoscopic, and surgical management options are reviewed providing physicians with a therapeutic framework to comprehensively treat these nonperianal penetrating complications. Through a multidisciplinary evidence-based approach to the complex sequela of CD outcomes can be improved and patient's quality of life enhanced.10.1093/ibd/izx108_video1izx108_Video5754037501001.

Update on anti-tumor necrosis factor agents and other new drugs for inflammatory bowel disease.

The treatment of inflammatory bowel disease (IBD)-ulcerative colitis (UC) and Crohn's disease (CD)-has evolved beyond surgery with the introduction of biologic agents, primarily antibodies against mediators of inflammation and cell attraction. Anti-tumor necrosis factor (TNF) agents have been the first line treatment for moderate to severe ulcerative colitis and Crohn's disease for more than 15 years. During that time much has been learnt about how best to use these agents. This review will assess the evidence on how to optimize the use of anti-TNF agents; when and how to start treatment; how to monitor treatment and when to de-escalate it; and the potential adverse effects of these drugs. New and emerging treatments such as anti-attractants, anti-interleukins, and Janus kinase (JAK) inhibitors will also be discussed.

Autoimmune pancreatitis and inflammatory bowel disease: Case series and review of the literature.

BACKGROUND: An association between autoimmune pancreatitis (AIP) and inflammatory bowel disease (IBD) has been documented, but its clinical significance remains unclear. AIMS: Characterize the particular phenotypes of IBD and AIP in patients with both diseases (IBD-AIP). METHODS: Retrospective study of patients with IBD-AIP followed at our IBD referral centre and literature search to identify previous reports of IBD-AIP patients. RESULTS: We found 5 cases of IBD-AIP in our records and 5 prior studies reporting 47 additional IBD-AIP patients. A combined analysis showed that most IBD-AIP patients were young males with ulcerative colitis, usually extensive, and that in all Crohn's disease cases, the colon was involved. IBD severity was heterogeneous across studies, ranging from mild disease to severe disease requiring colectomy. The most frequent type of AIP was idiopathic duct-centric pancreatitis (type 2) and it most often occurred after the diagnosis of IBD. AIP presentation and treatment were similar to those in the general population. CONCLUSIONS: AIP occurs rarely with IBD; in the other way around, up to 1/3 of AIP patients, especially type 2, may have concomitant IBD. IBD-AIP patients are usually males presenting extensive colitis. More data are needed on the impact of AIP, if any, in IBD course.

Inflammatory Bowel Disease and Pancreatitis: A Review.

BACKGROUND AND AIMS: Pancreatic abnormalities are common in inflammatory bowel disease (IBD) patients and represent a heterogeneous group of conditions that include acute pancreatitis, chronic pancreatitis, autoimmune pancreatitis and asymptomatic abnormalities. We sought to review the available evidence concerning the aetiology, clinical presentation, diagnosis and treatment of pancreatic conditions in IBD patients. METHODS: A PubMed/Medline query was conducted addressing pancreatic disorders in IBD. Reference lists from studies selected were manually searched to identify further relevant reports. Relevant manuscripts about pancreatic disorders in patients with IBD were selected and reviewed. RESULTS: Thiopurines and gallstones are the most frequent causes of acute pancreatitis in IBD patients. Thiopurine-induced acute pancreatitis is usually uncomplicated and self-limited. Some evidence suggests that chronic pancreatitis may be more common in IBD. Most cases are idiopathic, affecting young males and patients with ulcerative colitis. Autoimmune pancreatitis is a relatively newly recognized disease and is increasingly diagnosed in IBD, particularly for type 2 autoimmune pancreatitis in ulcerative colitis patients. Asymptomatic exocrine insufficiency, pancreatic duct abnormalities and hyperamylasaemia have been identified in up to 18% of IBD patients, although their clinical significance and relationship with IBD remain undefined. CONCLUSIONS: The wide spectrum of pancreatic manifestations in IBD is growing and may represent a challenge to the clinician. A collaborative approach with a pancreas specialist may be the most productive route to determine aetiology, guide additional diagnostic workup, illuminate the aetiology and define the treatment and follow-up of these patients.