Current Drug Targets - Volume 20, Issue 13, 2019

Background: The isolated effect of vedolizumab on increased postoperative complications remains debated, similar to the controversial data on anti-TNF and postoperative complications. Objective: To determine the risk of vedolizumab on postoperative complications. Methods: A review of the literature available to date on studies comparing postoperative outcomes in vedolizumab-treated versus non-vedolizumab-treated patients was performed. Studies were stratified by those which combined all inflammatory bowel disease together, those specifically focusing on Crohn’s disease or ulcerative colitis individually, and those which included pediatric patients alone. Results: The data remains controversial in both the adult and pediatric literature regarding the association of vedolizumab and increased postoperative complications. The strongest association between vedolizumab and an increased risk of postoperative infectious complications seems to be in the Crohn’s disease literature. Conclusion: Vedolizumab may be associated with an increased risk of postoperative infectious complications in Crohn’s disease, but the literature remains controversial due to difficulty in isolating the effect of the biologic alone in a chronically ill, heterogeneous patient population who are on multiple medications including corticosteroids.

Corticosteroids are frequently used in the management of Inflammatory Bowel Disease. Although they can be very useful, their potential adverse effects have to be kept in mind. One of the situations in which these drugs should be avoided, if possible, is the perioperative setting. If a patient reaches surgery while on steroids, surgical complications will be more likely to occur, both infectious and non-infectious. Attention should be paid to this fact, within a multidisciplinary approach, that also takes into account other factors, such as nutrition.

Crohn’s disease (CD) is an immune-mediated condition characterized by the transmural inflammation of the gut tissue, associated with progressive bowel damage often leading to surgical intervention. As operative resection of the damaged segment is not curative, a majority of patients undergoing intestinal resections for complicated CD present disease recurrence within 3 years after the intervention. Postoperative recurrence can be defined as endoscopic, clinical, radiological or surgical. Endoscopic recurrence rates within 1 year exceed 60% and the severity, according to the Rutgeerts’ score, is associated with worse prognosis and can predict clinical recurrence (in up to 1/3 of the patients). Most importantly, about 50% of patients will undergo a reoperation after 10 years of their first intestinal resection. Therefore, the prevention of postoperative recurrence in CD remains a challenge in clinical practice and should be properly managed. We aim to summarize the most recent data on the definition, risk factors, assessment and treatment of postoperative CD recurrence.

Background: Biological therapy with anti-Tumour Necrosis Factor (TNF)-α agents revolutionised the treatment of inflammatory bowel disease over the last decades. However, there may be an increased risk of postoperative complications in Crohn’s disease (CD) patients treated with anti-TNF-α agents prior to abdominal surgery. Objective: To evaluate the effects of preoperative anti-TNF-α therapy on the incidence of complications after surgery. Methods: A critical assessment of the results of clinical trial outcomes and meta-analyses on the available data was conducted. Results: Based on the outcomes of previous reports including meta-analyses, preoperative use of anti- TNF-α agents modestly increased the risk of overall complications and particularly infectious complications after abdominal surgery for CD. Nevertheless, previous studies have several limitations. The majority of them were retrospective research with heterogeneous outcome measures and single centre trials with relatively small sample size. In retrospective studies, the standard protocol for assessing various types of postoperative complications was not used. The most serious limitation of the previous studies was that multiple confounding factors such as malnutrition, use of corticosteroids, and preoperative sepsis were not taken into consideration. Conclusion: Among patients treated with preoperative anti-TNF-α therapy, the risk of overall complications and infectious complications may slightly increase after abdominal surgery for CD. Nevertheless, the previous reports reviewed in this study suffered from limitations. To rigorously evaluate the risk of anti-TNF-α therapy prior to surgery, large prospective studies with standardised criteria for assessing surgical complications and with proper adjustment for confounding variables are warranted.

Since the approval in 2005 of anti-TNF drugs for the treatment of ulcerative colitis, concerns have been raised about the potential detrimental effect of these agents on postoperative infectious complications related to pouch surgery. Data on this topic are controversial and mostly derived from retrospective underpowered cohort studies largely affected by relevant bias. Three meta-analyses have been published with contradictory results. Moreover, the correlation between serum levels of infliximab at the time of surgery and the occurrence of septic postoperative complication is far to be proven and remains an answered research question. The construction of an ileal pouch-anal anastomosis (IPAA) as first surgical step in patients with ulcerative colitis (UC) refractory to medical treatment seems to be associated with an increased risk of septic complications. Population-based data from the United States show a shift towards stage surgery for patients with refractory UC as a consequence of the widespread use of biological agents and the increased tendency to consider surgery as ultimate resort (step-up approach). In this setting, the classic 3-stage procedure (ileoanal pouch and diversion ileostomy after initial total colectomy) together with the modified 2-stage approach (ileoanal pouch without diversion ileostomy after initial total colectomy) are both effective options. Whether or not a diversion ileostomy could prevent pouch complications at the time of the pouch construction during the second stage of surgery is still a matter of debate. Emerging data seem to claim for increased risk of small bowel obstructions related to the presence of a stoma without proven effect on the prevention of anastomotic leak.

Crohn’s Disease (CD) and Ulcerative Colitis (UC), known as Inflammatory Bowel Diseases (IBD), are multifactorial, potentially debilitating diseases with probable genetic heterogeneity and unknown etiology. During the disease course of IBD, periods of inflammatory activity alternate with periods of remission. Severe complications in IBD often result in surgery. In the last two decades, major advances in medical treatment have changed the management of IBD. The advent of monoclonal antibodies targeting cytokines and adhesion molecules has brought a revolution in the treatment of IBD refractory to conventional therapy. However, it is not well established if these treatments could influence the long-term course of the diseases and the need for surgical treatment, though they have no severe adverse effects and improve quality of life. It has been shown that in the era of biologic agents, there has been a relative reduction in surgery rate for mild disease presentation, while the incidence of emergency or urgent surgery both for CD and UC remains unmodified. We summarized key data about current surgical rates in IBD after the advent of biologic agents.

Despite changing medical paradigm, still a significant proportion of patients with IBD require surgery. The patient's general condition, including nutritional status and the use of immunosuppressive medications is of great importance with regard to surgical complications, as well as the choice of optimal surgical strategy. The indication and the timing of surgery are key factors for the multidisciplinary management of IBD patients. The purpose of this review is to provide an overview on the impact of medical treatment on surgical strategies in IBD.

Crohn’s disease (CD) is a chronic inflammatory condition of the intestinal tract that is characterised by a relapsing and remitting course. Despite advancements in therapeutic options for CD, a substantial number of patients still require surgery for medically refractory disease or disease-related complications. Given the widespread adoption of biologic therapies for the management of patients with moderate-to-severe CD, a high number of patients are likely to be on biologic therapy at the time of needing intestinal surgery: the safety of biologics in perioperative setting is of great interest. While more clinical data are available for TNF antagonists and vedolizumab, the safety data for ustekinumab, an IL 12/23 inhibitor, is lacking. Here, we review the available data from published literature on the postoperative outcomes for CD patients exposed to ustekinumab perioperatively.

Fistulising perianal Crohn’s disease (pCD) is an aggressive phenotype, and patients not only suffer from perianal manifestations but also a worsening course for their luminal disease. This article describes the 6 key steps clinicians need to consider when managing patients with pCD which include; (i) ensuring a prompt diagnosis, (ii) multi-disciplinary management, (iii) psychological support, (iv) using multimodal medical and surgical treatment strategies, (v) continually monitoring and optimising therapy and (vi) ensuring that patients have a way of accessing care if required. Patients with fistulising pCD often have an unpredictable disease course and complete remission can be elusive. As such, a considered and nuanced approach is essential keeping the wider multi-disciplinary team and the patient involved in all decision making.

Crohn’s disease may severely impact the quality of life and being a chronic disease it requires both medical and surgical treatment aimed at induction and maintenance of remission to prevent relapsing symptoms and the need for further surgery. Surgery in Crohn’s disease often has to be performed in patients with well-known risk factors of post-operative complications, particularly intraabdominal septic complications. This review will look at the current knowledge of immunomodulating therapies in the peri-operative phase of Crohn’s disease. The influence of immunomodulators on postoperative complications is evaluated by reviewing available clinical reports and data from animal studies. Furthermore, the effect of immunomodulators on preventing or deferring primary as well as repeat surgery in Crohn’s disease is reviewed with particular consideration given to high-risk cohorts and timing of prophylaxis.

Approximately 50% of patients who have undergone IPAA surgery for Ulcerative Colitis (UC) develop at least 1 episode of pouchitis. Patients with pouchitis have a wide range of symptoms, endoscopic and histologic features, disease course, and prognosis. To date, there are no universally accepted diagnostic criteria in terms of endoscopy and histology; though, semi-objective assessments to diagnose pouchitis in patients with ileal pouch- anal anastomosis (IPAA) have been proposed using composite scores such as the Pouchitis Triad, Heidelberg Pouchitis Activity Score and Pouchitis Disease Activity Index (PDAI). In a systematic review that included four randomized trials evaluating five agents for the treatment of acute pouchitis, ciprofloxacin was more effective at inducing remission as compared with metronidazole. Rifaximin was not more effective than placebo, while budesonide enemas and metronidazole were similarly effective for inducing remission of acute pouchitis. Patients with pouchitis relapsing more than three times per year are advised maintenance therapy, and guidelines recommend ciprofloxacin or the probiotic VSL#3. In patients with antibiotic-refractory pouchitis, secondary factors associated with an antibiotic-refractory course should be sought and treated. In this review, we will discuss the prevention and management of pouchitis in Ulcerative Colitis patients.