Ferric carboxymaltose infusion versus oral iron supplementation for preoperative iron deficiency anaemia in patients with colorectal cancer (FIT): a multicentre, open-label, randomised, controlled trial.

BACKGROUND: A third of patients with colorectal cancer who are eligible for surgery in high-income countries have concomitant anaemia associated with adverse outcomes. We aimed to compare the efficacy of preoperative intravenous and oral iron supplementation in patients with colorectal cancer and iron deficiency anaemia. METHODS: In the FIT multicentre, open-label, randomised, controlled trial, adult patients (aged 18 years or older) with M0 stage colorectal cancer scheduled for elective curative resection and iron deficiency anaemia (defined as haemoglobin level of less than 7·5 mmol/L (12 g/dL) for women and less than 8 mmol/L (13 g/dL) for men, and a transferrin saturation of less than 20%) were randomly assigned to either 1-2 g of ferric carboxymaltose intravenously or three tablets of 200 mg of oral ferrous fumarate daily. The primary endpoint was the proportion of patients with normalised haemoglobin levels before surgery (≥12 g/dL for women and ≥13 g/dL for men). An intention-to-treat analysis was done for the primary analysis. Safety was analysed in all patients who received treatment. The trial was registered at ClincalTrials.gov, NCT02243735, and has completed recruitment. FINDINGS: Between Oct 31, 2014, and Feb 23, 2021, 202 patients were included and assigned to intravenous (n=96) or oral (n=106) iron treatment. Treatment began a median of 14 days (IQR 11-22) before surgery for intravenous iron and 19 days (IQR 13-27) for oral iron. Normalisation of haemoglobin at day of admission was reached in 14 (17%) of 84 patients treated intravenously and 15 (16%) of 97 patients treated orally (relative risk [RR] 1·08 [95% CI 0·55-2·10]; p=0·83), but the proportion of patients with normalised haemoglobin significantly increased for the intravenous treatment group at later timepoints (49 [60%] of 82 vs 18 [21%] of 88 at 30 days; RR 2·92 [95% CI 1·87-4·58]; p<0·0001). The most prevalent treatment-related adverse event was discoloured faeces (grade 1) after oral iron treatment (14 [13%] of 105), and no treatment-related serious adverse events or deaths were observed in either group. No differences in other safety outcomes were seen, and the most common serious adverse events were anastomotic leakage (11 [5%] of 202), aspiration pneumonia (5 [2%] of 202), and intra-abdominal abscess (5 [2%] 202). INTERPRETATION: Normalisation of haemoglobin before surgery was infrequent with both treatment regimens, but significantly improved at all other timepoints following intravenous iron treatment. Restoration of iron stores was feasible only with intravenous iron. In selected patients, surgery might be delayed to augment the effect of intravenous iron on haemoglobin normalisation. FUNDING: Vifor Pharma.

Early Biological Therapy in Operated Crohn's Disease Patients Is Associated With a Lower Rate of Endoscopic Recurrence and Improved Long-term Outcomes: A Single-center Experience.

BACKGROUND: Two-thirds of Crohn's disease (CD) patients require surgery during their disease course. However, surgery is not curative, and endoscopic recurrence is observed in up to 90% of cases. Our aim was to investigate the impact of postoperative biological therapy on the incidence of endoscopic recurrence and long-term outcomes in CD patients. METHODS: This retrospective cohort study was conducted at the Humanitas Research Hospital-IRCCS (Milan, Italy) between 2014 and 2021. All consecutive CD patients who underwent surgery and colonoscopy at 6-12 months postoperatively were eligible for inclusion. RESULTS: A total of 141 patients were included (42.6% female, mean age 44 years). Median follow-up was 28 months. About one-third of patients were treated with biologics at baseline colonoscopy. A higher rate of endoscopic recurrence was detected in patients without biologic therapy at the time of colonoscopy compared with those treated (80.8% vs 45.2%, P < .0001). Hospitalization and surgery occurred more in untreated patients than in subjects undergoing biological therapy (12.1% vs 0.0%, P = .01). The Kaplan-Meier curves showed that the no treatment group at baseline had a >23.3% 5-year rate of hospitalization and surgery (log-rank P = .0221) and a >49.7% 5-year rate of medical therapy escalation (log-rank P = .0013) compared with the treatment arm. In the logistic regression model, absence of biologic therapy was independently associated with the risk of endoscopic disease recurrence (odds ratio, 0.22; 95% CI, 0.1-0.51; P = .0004). CONCLUSION: Operated CD patients treated early with biologics experience decreased rates of endoscopic recurrence and improved long-term outcomes.

Familial component of early-onset colorectal cancer: opportunity for prevention.

BACKGROUND: Individuals with a non-syndromic family history of colorectal cancer are known to have an increased risk. There is an opportunity to prevent early-onset colorectal cancer (age less than 50 years) (EOCRC) in this population. The aim was to explore the proportion of EOCRC that is preventable due to family history of colorectal cancer. METHODS: This was a retrospective multicentre European study of patients with non-hereditary EOCRC. The impact of the European Society of Gastrointestinal Endoscopy (ESGE), U.S. Multi-Society Task Force (USMSTF), and National Comprehensive Cancer Network (NCCN) guidelines on prevention and early diagnosis was compared. Colorectal cancer was defined as potentially preventable if surveillance colonoscopy would have been performed at least 5 years before the age of diagnosis of colorectal cancer, and diagnosed early if colonoscopy was undertaken between 1 and 4 years before the diagnosis. RESULTS: Some 903 patients with EOCRC were included. Criteria for familial colorectal cancer risk in ESGE, USMSTF, and NCCN guidelines were met in 6.3, 9.4, and 30.4 per cent of patients respectively. Based on ESGE, USMSTF, and NCCN guidelines, colorectal cancer could potentially have been prevented in 41, 55, and 30.3 per cent of patients, and diagnosed earlier in 11, 14, and 21.1 per cent respectively. In ESGE guidelines, if surveillance had started 10 years before the youngest relative, there would be a significant increase in prevention (41 versus 55 per cent; P = 0.010). CONCLUSION: ESGE, USMSTF, and NCCN criteria for familial colorectal cancer were met in 6.3, 9.4, and 30.4 per cent of patients with EOCRC respectively. In these patients, early detection and/or prevention could be achieved in 52, 70, and 51.4 per cent respectively. Early and accurate identification of familial colorectal cancer risk and increase in the uptake of early colonoscopy are key to decreasing familial EOCRC.

Management of Isolated Anal Strictures in Crohn's Disease.

BACKGROUND: Anorectal stricturing is a particularly morbid manifestation of Crohn's disease resulting in a diminished quality of life related to pain, incontinence, and recurrent operative interventions. OBJECTIVE: To determine the role of medical therapy, endoscopic dilation, and surgical intervention for the treatment of isolated anorectal stricturing. DATA SOURCES: An organized search of MEDLINE, PubMed, EMBASE, Scopus, and the Cochrane Database of Collected Reviews was performed from January 1, 1990 through May 1, 2020. STUDY SELECTION: Full text papers which included management of isolated anorectal strictures in the setting of Crohn's disease. INTERVENTION(S): Medical and surgical management. MAIN OUTCOME MEASURES: Symptomatic relief, need for proctocolectomy. RESULTS: Our search identified a total of 553 papers; after exclusion based on title (n = 430) and abstract (n = 47), 76 underwent full text review with 65 relevant to the management of anorectal strictures. A summary of the retrospective reports suggests that medical therapy can help control luminal inflammation, but fibrosis may ultimately set in resulting in a need for endoscopic or surgical intervention. Surgical options are limited in the anal canal due to inflammation and ulceration and concomitant perianal fistulizing disease. While fecal diversion can provide symptomatic relief, successful restoration of intestinal continuity remains uncommon and most patients ultimately undergo a total proctocolectomy with end ileostomy. LIMITATIONS: Limited literature published, all retrospective in nature. CONCLUSIONS: Despite significant advances in medical and surgical therapy in Crohn's disease over the last decades, there is clearly an unmet need in the management of anorectal strictures in Crohn's disease.

Management of patients with complex perianal fistulas in Crohn's disease: Optimal patient flow in the Italian clinical reality.

Perianal fistulizing Crohn's disease (PFCD) is a common, disabling and aggressive phenotype that negatively impacts on the quality of life of affected patients. Its successful treatment is still a struggle for both physicians and patients. Significant advances in the management of this condition have occurred in the last two decades holding promise for a better future. This culminated into the concept of a collaborative multidisciplinary approach using the latest medical therapies combined with modern surgical and endoscopic techniques. Despite this, PFCD management and treatment have not been standardized yet. Thus the gastroenterologist and surgeon have to be familiar with several approaches and/or techniques. The positioning of each therapeutic option will certainly evolve with new data, but for the time being it should be driven by patient's characteristics, physician's preference and/or experience, costs and availability in local practice. Additionally, patient's perception of benefits and risks of treatment may differ from those of physicians and recognition of this difference is a starting point for difficult clinical decision-making. In this paper, a multidisciplinary group of Italian IBD experts explore and discuss current medical and surgical therapeutic options, highlighting areas of unmet needs in PFCD, with particular focus on the optimal patient flow within the Italian clinical reality.

Modern management of perianal fistulas in Crohn's disease: future directions.

Perianal fistulae in patients with Crohn's disease (CD) can be associated with significant morbidity resulting in negative impact on quality of life. The last two decades have seen significant advancements in the management of perianal fistulas in CD, which has evolved into a multidisciplinary approach that includes gastroenterologists, colorectal surgeons, endoscopists and radiologists. Despite the introduction of new medical therapies such as antitumour necrosis factor and novel models of care delivery, the best fistula healing rates reported with combined medical and surgical approaches are approximately 50%. More recently, newer biologics, cell-based therapies as well as novel endoscopic and surgical techniques have been introduced raising new hopes that outcomes can be improved upon. In this review, we describe the modern management and the most recent advances in the management of complex perianal fistulising CD, which will likely impact clinical practice. We will explore optimal use of both older and newer biological agents, as well as new data on cell-based therapies. In addition, new techniques in endoscopic and surgical approaches will be discussed.

Surgical rates in the era of biological therapy: up, down or unchanged?

PURPOSE OF REVIEW: The aim of this review is to summarize data regarding surgical trends in inflammatory bowel disease in the prebiologic and biologic era, with a focus on population-based studies and randomized controlled trials (RCTs). RECENT FINDINGS: There is paucity of data in RCTs regarding surgical rates, with only a few clinical trials reporting them. From the available data, meta-analyses of RCTs have concluded that antitumor necrosis α agents (anti-TNF) reduce surgical rates in ulcerative colitis and Crohn's disease. A large body of evidence from population-based studies from different regions of the world is available to evaluate surgical trends before and after the introduction of anti-TNF agents. The risk of surgery decreased significantly over the past six decades; these decreasing trends continued in the biologic era, which might indicate a potential beneficial disease-modifying effect of biologics. There is lack of data with nonanti-TNF biologics (i.e. anti-integrins and ustekinumab) regarding the risk of surgery. SUMMARY: Although data from population-based studies and available RCTs suggest a protective effect from surgery of anti-TNF agents, definitive conclusions should be drawn only when more disease-modifying trials with different biologics and treatment strategies become available.

Refractory distal ulcerative colitis: is proctocolectomy always necessary?

Refractory distal ulcerative colitis (RDUC) is defined as persistence of symptoms caused by endoscopically proven colonic inflammation located at the rectum or left colon despite oral/topical steroids and 5-ASA. RDUC affects a small subset of patients and is associated with chronic disabling symptoms and increased social/medical costs. Moreover, patients with long-standing ulcerative colitis (UC) carry an elevated risk of developing colorectal cancer and colonic mucosa high-grade dysplasia. Alternative medical strategies in steroid refractory disease are unlikely to provide durable remission in all patients, carry potential severe side effects and, as immunosuppressants, the risk of other neoplasms, and may increase the short-term complication rate when surgery is finally required. Restorative proctocolectomy with ileal pouch-anal anastomosis (RP-IPAA) allows the complete removal of the diseased rectum and colon, virtually eliminating the risk of malignant transformation and reestablishing intestinal continuity with continence preservation. Since the introduction of this surgical procedure, morbidity and mortality rates have been drastically reduced. Despite the still notable rate of surgical complications, long-term quality of life assessment has shown excellent results in nearly all patients who have undergone RP-IPAA, comparing well with the general population. Furthermore, when performed for distal UC, RP-IPAA produces similar surgical outcomes with respect to pancolitis. In conclusion, RP-IPAA should always be considered in patients with RDUC, and multidisciplinary counseling should provide patients clear information about the advantages of surgery and possible complications as well as the chance to achieve disease remission with medical therapy.

Integrated models of care in managing inflammatory bowel disease: a discussion.

The World Health Organization has recommended the integrated model of care as the current best practice of care, and, in recent years, it has been gaining popularity worldwide in various settings. However, there have been very few reports on applications of this model to the care of patients with gastrointestinal problems and no reports in the case of inflammatory bowel disease (IBD). However, several IBD centres worldwide have been using the model as part of their standard care. This discussion paper aims to bring together these units' shared experiences with a range of integrated models of care in order to identify common features and provide recommendations on aspirational care for IBD patients.