Increased Proportion of Colorectal Cancer in Patients With Ulcerative Colitis Undergoing Surgery in the Netherlands.

INTRODUCTION: The aim of the current study was to assess whether there is an indication shift for surgery in patients with ulcerative colitis (UC) from refractory disease to malignant degeneration over the past 3 decades. METHODS: All patients with histologically confirmed UC who underwent a colorectal resection between 1991 and 2020 were extracted from the nationwide Dutch Pathology Registry. The primary outcome was the proportion of colorectal cancer (CRC) in the colon specimens. Outcomes were compared between 3 periods (P1: 1991-2000, P2: 2001-2010, and P3: 2011-2020). RESULTS: Overall, 6,094 patients with UC were included of which 4,854 underwent a (procto)colectomy and 1,240 a segmental resection. In 1,031 (16.9%) patients, CRC was demonstrated in the pathological resection specimen after a median disease duration of 11 years (IQR 3.0-19.0). The proportion of CRC increased from 11.3% in P1, to 16.1% in P2, and 22.8% in P3 ( P < 0.001). Median disease duration at the time of resection increased from 4 years in P1, to 10 years in P2, and 17 years in P3 ( P < 0.001). The proportion of patients diagnosed with advanced malignancy (pT3/T4) (P1: 61.2% vs P2: 65.2% vs P3: 62.4%, respectively, P = 0.633) and lymph node metastasis (N+) (P1: 33.0% vs P2: 41.9% vs P3: 38.2%, respectively, P = 0.113) did not change over time. DISCUSSION: This nationwide pathology study demonstrated an increased proportion of surgery for CRC over the past 3 decades. We hypothesize that the expanding therapeutic armamentarium for UC leads to exhausting medical options and hence postponed colectomy. This, however, might be at the expense of an increased risk of CRC in the long term.

Short-term anti-TNF therapy with surgical closure versus anti-TNF therapy in the treatment of perianal fistulas in Crohn's disease (PISA-II): a patient preference randomised trial.

BACKGROUND: Guidelines on Crohn's perianal fistulas recommend anti-tumour necrosis factor (TNF) treatment and suggest considering surgical closure for patients with surgically amenable disease. However, long-term outcomes following these two strategies have not been directly compared. The aim of this study was to assess radiological healing in patients who received short-term anti-TNF treatment and surgical closure compared with those who received anti-TNF treatment alone. METHODS: The PISA-II trial was a multicentre, patient preference study done in nine hospitals in the Netherlands and one hospital in Italy. Adult patients with Crohn's disease and an active high perianal fistula with a single internal opening were eligible for inclusion. After counselling, patients with no treatment preference were randomly assigned (1:1) using random block randomisation (block sizes of six without statification), to 4-month anti-TNF therapy and surgical closure or anti-TNF therapy for 1 year, after seton insertion. Patients with a treatment preference received their preferred therapy. The primary outcome was radiological healing assessed by MRI at 18 months, defined as a complete fibrotic tract or a MAGNIFI-CD (Magnetic Resonance Index for Fistula Imaging in Crohn's Disease) score of 0, assessed according to the intention-to-treat principle. Secondary outcomes included clinical closure, number of patients undergoing surgical reintervention and number of reinterventions, recurrences, and impact on quality of life measured by the Perianal Disease Activity Index (PDAI). Analyses were performed on an intention-to-treat basis and additionally an as-treated analysis for radiological healing and clinical closure. This study was registered at the Dutch Trial Registry, NL7625, and with EudraCT, 2018-002064-15, and is closed to accrual due to completion. FINDINGS: Between Sept 14, 2013, and Dec 7, 2019, 94 patients were enrolled onto the trial, of whom 32 (34%) were randomly assigned and 62 (66%) chose a specific treatment. 38 (40%) patients were assigned to the surgical closure group and 56 (60%) patients to the anti-TNF group. At 18 months, radiological healing was significantly more common in the surgical closure group (12 [32%] patients) than in the anti-TNF group (five [9%] patients; p=0·005). By contrast, clinical closure was not significantly different between the two treatment groups (26 [68%] patients in the surgical closure group vs 29 [52%] patients in the anti-TNF group; p=0·076). Significantly fewer patients required a reintervention in the surgical closure group than in the anti-TNF therapy group (five [13%] patients in the surgical closure group, median one reintervention [IQR one to three] vs 24 [43%] patients in the anti-TNF group, median two reinterventions [one to two]; p=0·005). Among patients who reached clinical closure during follow-up, four (14%) of 29 in the surgical closure group and five (16%) of 31 in the anti-TNF therapy group had a recurrence, which occurred only in patients without radiological healing. PDAI was significantly lower in the surgical closure group than in the anti-TNF group after 18 months (p=0·031). Adverse events and serious adverse events were similar in both treatment groups and mostly entailed reinterventions. Ten (11%) patients had side-effects associated with anti-TNF treatment. Two serious adverse events unrelated to study treatment occurred (appendicitis and myocardial infarction). One patient died from a tongue base carcinoma, unrelated to study treatment. INTERPRETATION: Short-term anti-TNF treatment combined with surgical closure induces long-term MRI healing more frequently than anti-TNF therapy in patients with Crohn's perianal fistulas. These data suggest that patients with Crohn's perianal fistula amenable for surgical closure should be counselled for this therapeutic approach. FUNDING: Netherlands Organisation for Health Research and Development and Broad Medical Research Program.

Fibrosis and MAGNIFI-CD Activity Index at Magnetic Resonance Imaging to Predict Treatment Outcome in Perianal Fistulizing Crohn's Disease Patients.

BACKGROUND AND AIMS: Characteristic magnetic resonance imaging [MRI] features associated with long-term perianal fistula closure are still being discussed. This study evaluated the predictive value of degree of fibrosis and disease activity (MAGNIFI-CD index) at MRI for long-term clinical closure of Crohn's perianal fistulas. METHODS: Crohn's disease [CD] patients treated with surgical closure following anti-tumour necrosis factor [anti-TNF] induction or anti-TNF alone for high perianal fistulas as part of a patient preference randomized controlled trial [PISA-II] between 2013 and 2020 with a post-treatment MRI and long-term clinical follow-up data were retrospectively included. Two radiologists scored the degree of fibrosis and MAGNIFI-CD index at pre- and post-treatment MRI. The accuracy of post-treatment MRI findings in predicting long-term clinical closure [12 months after the MRI] was evaluated using receiver operating characteristics [ROC] analysis. RESULTS: Fifty patients were included: 31 female, median age 33 years (interquartile range [IQR] 26-45). Fourteen patients showed a 100% fibrotic fistula at post-treatment MRI, all of which had long-term clinical closure. Median MAGNIFI-CD index at post-treatment MRI was 0 [IQR 0-5] in 25 patients with long-term clinical closure and 16 [IQR 10-20] in 25 patients without. ROC analysis showed an area under the curve of 0.90 (95% confidence interval [CI] 0.82-0.99) for degree of fibrosis and 0.95 [95% CI 0.89-1.00] for the MAGNIFI-CD index, with a Youden cut-off point of 6 [91% specificity, 87% sensitivity]. CONCLUSIONS: Degree of fibrosis and MAGNIFI-CD index at post-treatment MRI are accurate in predicting long-term clinical closure and seem valuable in follow-up of perianal CD. A completely fibrotic tract at MRI is a robust indicator for long-term fistula closure. EUDRACT: 2013-002932-25 and 2018-002064-15.