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BACKGROUND AND AIMS: Perianal fistulation is a challenging phenotype of Crohn's disease with significant impact on quality of life. Historically, fistulae have been classified anatomically in relation to the sphincter complex, and management guidelines have been generalised, with lack of attention to the clinical heterogenicity seen. The recent 'TOpClass classification system' for perianal fistulising Crohn's disease (PFCD) addresses this issue, and classifies patients into defined groups, which provide a focus for fistula management that aligns with disease characteristics and patient goals. In this article, we discuss the clinical applicability of the TOpClass model and provide direction on its use in clinical practice. METHODS: An international group of perianal clinicians participated in an expert consensus to define how the TOpClass system can be incorporated into real-life practice. This included gastroenterologists, IBD surgeons, and radiologists specialised in PFCD. The process was informed by the multi-disciplinary team management of eight high-volume fistula centres in North America, Europe, and Australia. RESULTS: The process produced position statements to accompany the classification system and guide PFCD management. The statements range from the management of patients with quiescent perianal disease to those with severe PFCD requiring diverting-ostomy and/or proctectomy. The optimisation of medical therapies, as well as the use of surgery, in fistula closure and symptom management is explored across each classification group. CONCLUSION: This article provides an overview of the system's use in clinical practice. It aims to enable clinicians to have a pragmatic and patient-goal centred approach to medical and surgical management options for individual patients with PFCD.
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BACKGROUND: Retrospective research suggests that excision of the affected mesentery can improve outcomes after an ileocoecal resection in Crohn's disease. However, prospective data from randomised controlled trials are scarce. We aimed to compare rates of postoperative recurrence in patients with Crohn's disease who underwent extended mesenteric resection. METHODS: This international, randomised controlled trial was done in six hospitals and tertiary care centres in the Netherlands and Italy. Eligible patients were aged 16 years or older and had Crohn's disease that was previously confirmed by endoscopy in the terminal ileum or ileocolic region (L1 or L3 disease), with an imaging update in the past 3 months (ultrasound, MRI, or CT enterography). Eligible patients were scheduled to undergo primary ileocolic resection with ileocolic anastomosis. Enrolled patients were assigned by use of simple random allocation (1:1) to either extended mesenteric resection (intervention) or conventional mesenteric sparing resection (control). The primary endpoint was endoscopic recurrence 6 months after surgery. Analyses were done in all patients with primary endpoint data, excluding those who had no anastomosis, a postoperative diagnosis other than Crohn's disease, or withdrew consent. This trial was registered with ClinicalTrials.gov, NCT04538638. FINDINGS: Between Feb 19, 2020, and April 24, 2023, we assessed 217 patients for eligibility. 78 patients were excluded due to failure to meet the inclusion criteria or refusal to participate. 139 patients were enrolled and randomly assigned to either extended mesenteric resection (n=71) or mesenteric sparing resection (n=68). All 139 patients underwent surgery. Six patients were excluded after random assignment due to withdrawal of consent (n=2), postoperative diagnosis other than Crohn's disease (n=2) and no anastomosis performed (in case of a stoma; n=2). Two patients were lost to follow-up, and two more patients deviated from the protocol by undergoing investigations other than endoscopy 6 months after. 133 patients were included in the baseline analysis (67 in the extended resection group and 66 in the sparing resection group) of whom 57 (43%) were male. Baseline characteristics were similar between the groups, and median patient age was 36 years (IQR 25-54). 131 patients were analysed for the primary outcome. There was no difference between groups in the rate of endoscopic recurrence at 6 months after surgery (28 [42%] of 66 patients in the extended mesenteric resection group vs 28 [43%] of 65 patients in the mesenteric sparing resection group, relative risk 0·985, 95% CI 0·663-1·464; p=1·0). Five (8%) of 66 patients in the extended mesenteric resection group had anastomotic leakage within the 30 days after surgery, as did one (2%) of 65 in the mesenteric sparing group. Postoperative complications of Clavien-Dindo grade IIIa or higher were reported in seven (11%) patients in the mesenteric resection group and five (8%) in the mesenteric sparing group. INTERPRETATION: Extended mesenteric resection was not superior to conventional resection with regard to endoscopic Crohn's disease recurrence. These data support the guideline-recommended mesenteric sparing approach. FUNDING: Topconsortia voor Kennis en Innovatie-Topsector Life Sciences & Health.
Subject(s)
Colon , Crohn Disease , Ileum , Mesentery , Recurrence , Humans , Crohn Disease/surgery , Crohn Disease/pathology , Male , Female , Adult , Mesentery/surgery , Mesentery/pathology , Ileum/surgery , Ileum/pathology , Colon/surgery , Colon/pathology , Colon/diagnostic imaging , Middle Aged , Treatment Outcome , Anastomosis, Surgical/methods , Anastomosis, Surgical/adverse effects , Colectomy/methods , Colectomy/adverse effectsABSTRACT
Objective: Guidelines advise to perform endoscopic surveillance following ileocolic resection (ICR) in Crohn disease (CD) for timely diagnosis of recurrence. This study aims to assess the variation in endoscopic recurrence (ER) rates in patients after ICR for CD using the most commonly used classification systems, the Rutgeerts score (RS) and modified Rutgeerts score (mRS) classifications. Methods: A systematic literature search using MEDLINE, Embase, and the Cochrane Library was performed. Randomized controlled trials and cohort studies describing ER < 12 months after an ICR for CD were included. Animal studies, reviews, case reports (<30 included patients), pediatric studies, and letters were excluded. The Newcastle-Ottawa Quality Assessment Scale and Cochrane Collaboration's tool were used to assess risk of bias. Main outcome was the range of ER rates within 12 months postoperatively, defined as RS ≥ i2 and/or mRS ≥ i2b. A proportional meta-analysis was performed. The final search was performed on January 4, 2022. The study was registered at PROSPERO, CRD42022363208. Results: Seventy-six studies comprising 7751 patients were included. The weighted mean of ER rates in all included studies was 44.0% (95% confidence interval, 43.56-44.43). The overall range was 5.0% to 93.0% [interquartile range (IQR), 29.2-59.0]. The weighted means for RS and mRS were 44.0% and 41.1%, respectively. The variation in ER rates for RS and mRS were 5.0% to 93.0% (IQR, 29.0-59.5) and 19.8% to 62.9% (IQR, 37.3-46.5), respectively. Within studies reporting both RS and mRS, the weighted means for ER were 61.3% and 40.6%, respectively. Conclusions: This study demonstrates a major variation in ER rates after ICR for CD, suggesting a high likelihood of inadequate diagnosis of disease recurrence, with potentially impact on quality of life and health care consumption. Therefore, there is an important need to improve endoscopic scoring of recurrent disease.
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BACKGROUND: The primary treatment of ulcerative colitis (UC) is medical therapy using a standard step-up approach. An appendectomy might modulate the clinical course of UC, decreasing the incidence of relapses and reducing need for medication. The objective of the ACCURE trial is to assess the efficacy of laparoscopic appendectomy in addition to standard medical treatment in maintaining remission in UC patients. This article presents the statistical analysis plan to evaluate the outcomes of the ACCURE trial. DESIGN AND METHODS: The ACCURE trial was designed as a multicentre, randomised controlled trial. UC patients with a new diagnosis or a disease relapse within the past 12 months, treated with 5-ASA, corticosteroids, or immunomodulators until complete clinical and endoscopic remission (defined as total Mayo score < 3 with endoscopic subscore of 0 or 1), were counselled for inclusion. Also, patients previously treated with biologicals who had a washout period of at least 3 months were considered for inclusion. Patients were randomised (1:1) to laparoscopic appendectomy plus maintenance treatment or a control group (maintenance therapy only). The primary outcome is the 1-year UC relapse rate (defined as a total Mayo-score ≥ 5 with endoscopic subscore of 2 or 3, or clinically as an exacerbation of symptoms and rectal bleeding or FCP > 150 or intensified medical therapy other than 5-ASA therapy). Secondary outcomes include number of relapses per patient, time to first relapse, disease activity, number of colectomies, medication usage, and health-related quality of life. DISCUSSION: The ACCURE trial will provide comprehensive evidence whether adding an appendectomy to maintenance treatment is superior to maintenance treatment only in maintaining remission in UC patients. TRIAL REGISTRATION: Dutch Trial Register (NTR) NTR2883 . Registered May 3, 2011. ISRCTN, ISRCTN60945764 . Registered August 12, 2019.
Subject(s)
Colitis, Ulcerative , Humans , Colitis, Ulcerative/drug therapy , Appendectomy , Quality of Life , Remission Induction , Neoplasm Recurrence, Local , Mesalamine , Recurrence , Disease ProgressionABSTRACT
BACKGROUND: The most common intestinal operation in Crohn's disease (CD) is an ileocolic resection. Despite optimal surgical and medical management, recurrent disease after surgery is common. Different types of anastomoses with respect to configuration and construction can be made after resection for example, handsewn (end-to-end and Kono-S) and stapled (side-to-side). The various types of anastomoses might affect endoscopic recurrence and its assessment, the functional outcome, and costs. The objective of the present study is to compare the three types of anastomoses with respect to endoscopic recurrence at 6 months, gastrointestinal function, and health care consumption. METHODS: This is a randomized controlled multicentre superiority trial, allocating patients either to side-to-side stapled anastomosis as advised in current guidelines or a handsewn anastomoses (an end-to-end or Kono-S). It is hypothesized that handsewn anastomoses do better than stapled, and end-to-end perform better than the saccular Kono-S. Two international studies with a similar setup will be conducted mainly in the Netherlands (End2End) and Italy (HAND2END). Patients diagnosed with CD, aged over 16 years in the Netherlands and 18 years in Italy requiring (re)resection of the (neo)terminal ileum are eligible. The first part of the study compares the two handsewn anastomoses with the stapled anastomosis. To detect a clinically relevant difference of 25% in endoscopic recurrence, a total of 165 patients will be needed in the Netherlands and 189 patients in Italy. Primary outcome is postoperative endoscopic recurrence (defined as Rutgeerts score ≥ i2b) at 6 months. Secondary outcomes are postoperative morbidity, gastrointestinal function, quality of life (QoL) and costs. DISCUSSION: The research question addresses a knowledge gap within the general practice elucidating which type of anastomosis is superior in terms of endoscopic and clinical recurrence, functionality, QoL and health care consumption. The results of the proposed study might change current practice in contrast to what is advised by the guidelines. TRIAL REGISTRATION: NCT05246917 for HAND2END and NCT05578235 for End2End ( http://www. CLINICALTRIALS: gov/ ).
Subject(s)
Crohn Disease , Humans , Anastomosis, Surgical/methods , Colon/surgery , Crohn Disease/surgery , Ileum/surgery , Quality of Life , Randomized Controlled Trials as Topic , Recurrence , Adolescent , AdultABSTRACT
BACKGROUND AND AIMS: An appendectomy for appendiceal inflammation has been suggested to ameliorate the clinical course of patients with ulcerative colitis (UC). In contrast, for Crohn's disease (CD) an inverse association has been suggested with a higher incidence of CD and worse prognosis after appendectomy. The aim of this study was to analyse the clinical relevance of an inflamed appendix in CD patients undergoing ileocoecal resection (ICR). METHODS: All consecutive patients undergoing primary ICR between 2007 and 2018 were considered for inclusion. Microscopic data of available appendiceal resection specimens (n=99) were revised by a dedicated IBD-pathologist and scored as inflamed or not inflamed. Eighteen patients had a previous appendectomy. Pathological findings were correlated with disease characteristics and recurrence rates (clinical, endoscopic and intervention-related). RESULTS: In total, 117 patients were included: 77 (65.8%) females with a median age of 30 years [IQR 24 - 43] with a median follow up of 102 months [IQR 76-114]. Of patients without previous appendectomy (n=99), 39% had an inflamed appendix. No significant differences in disease characteristics (e.g. disease location, behaviour, time to surgery) or prognosis could be demonstrated between the two groups. In contrast, previous appendectomy (n=18) was associated with penetrating disease and numerically shorter disease duration at the time of resection. Furthermore, a trend was seen towards a stronger association with postoperative recurrence. CONCLUSION: The current study could not confirm a different prognosis for CD patients with and without an inflamed appendix. In contrast, in patients with a previous appendectomy a trend was seen towards increased postoperative recurrence, which might be related to the higher incidence of penetrating disease.
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Background: The PISA-II trial showed that short-term anti-tumour necrosis factor (anti-TNF) therapy followed by surgical closure induces radiological healing of perianal fistulas in patients with Crohn's disease more frequently than anti-TNF therapy alone after 18 months. This study aimed to compare long-term outcomes of both treatment arms. Methods: Follow-up data were collected from patients who participated in the PISA-II trial, an international patient preference randomised controlled trial. This multicentre trial was performed in nine hospitals in the Netherlands and one hospital in Italy. Patients with Crohn's disease above the age of 18 years with an active high perianal fistula and a single internal opening were asked to participate. Patients were allocated to anti-TNF therapy (intravenous infliximab, or subcutaneous adalimumab, at the discretion of the gastroenterologist) for one year, or surgical closure combined with 4-months anti-TNF therapy. Patients without a treatment preference were randomised (1:1) using random block randomisation (block sizes of six without stratification), and patients with a treatment preference were treated according to their preferred treatment arm. For the current follow-up study, data were collected until May 2022. Primary outcome was radiological healing on magnetic resonance imaging (MRI), including all participants with a MRI made less than 6 months ago at the time of data collection. Analysis was based on observed data. Findings: Between September 14, 2013, and December 7, 2019, 94 patients were enrolled in the trial. Long-term follow-up data were available in 91 patients (36/38 (95%) anti-TNF + surgical closure, 55/56 (98%) anti-TNF). A total of 14/36 (39%) patients in the surgical closure arm were randomly assigned, which was not significantly different in the anti-TNF treatment arm (16/55 (29%) randomly assigned). Median follow-up was 5.7 years (interquartile range (IQR) 5-7). Radiological healing occurred significantly more often after anti-TNF + surgical closure (15/36 = 42% versus 10/55 = 18%; P = 0.014). Clinical closure was comparable (26/36 = 72% versus 34/55 = 62%; P = 0.18) in both groups. However, clinical closure in the surgical group was achieved with less re-interventions 4/26 (= 15%) versus 18/34 (= 53%), including (redo-)surgical closure procedures. Recurrences occurred in 0/25 (0%) patients with radiological healing versus 27/76 (36%) patients with clinical closure, sometime during follow-up. Anti-TNF trough levels were higher in patients with long-term clinical closure in both groups (P = 0.031 and P = 0.014). In 6/11 (55%) patients in the anti-TNF group with available trough levels, recurrences were diagnosed within three months of a drop under 3.5ug/ml. 36 patients stopped anti-TNF, after which 0/14 (0%) patients with radiological healing developed a recurrence and 9/22 (41%) with clinical closure. Self-rated (in)continence was comparable between groups, and 79% (60/76) of patients indicated comparable/improved continence after treatment. Decision-regret analysis showed that all (30/30) anti-TNF + surgical closure patients agreed or strongly agreed that surgery was the right decision versus 78% (36/46) in the anti-TNF arm. All surgical closure patients would go for the same treatment again, whereas this was 89% (41/46) in the anti-TNF arm. Interpretation: This study confirmed that surgical closure should be considered in amenable patients with perianal fistulas and Crohn's disease as long-term outcomes were favourable, and that radiological healing should be the aim of treatment as recurrences only occurred in patients without radiological healing. In patients with complete MRI closure, anti-TNF could be safely stopped. Funding: None.
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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.
Subject(s)
Anemia, Iron-Deficiency , Colorectal Neoplasms , Adult , Male , Humans , Female , Iron , Anemia, Iron-Deficiency/etiology , Anemia, Iron-Deficiency/complications , Hemoglobins , Dietary Supplements , Colorectal Neoplasms/complications , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/surgeryABSTRACT
AIM: Creation of a diverting stoma in patients with Crohn's disease (CD) can counteract luminal inflammation. The clinical utility of a diverting stoma with the prospect of restoration of gastrointestinal continuity warrants further investigation. The aim of this work was to evaluate the long-term effects of creation of a diverting stoma on the disease course in patients with luminal colonic CD. METHOD: In this retrospective, multicentre cohort study we investigated the disease course of patients who received a diverting stoma in the biological era. Clinical characteristics, medication use and surgical course were assessed at the time of creation of the diverting stoma and during follow-up. The primary outcome was the rate of successful and lasting reestablishment of gastrointestinal continuity. RESULTS: Thirty six patients with refractory luminal CD from four institutions underwent creation of a diverting stoma. Of the overall cohort, 20 (56%) patients had their gastrointestinal continuity reestablished after initial stoma creation and 14 (39%) who had their stoma reversed remained stoma-free during a median of 3.3 years follow-up (interquartile range 2.1-6.1 years). Absence of stoma reversal was associated with the presence of proctitis (p = 0.02). Colorectal resection after creation of a diverting stoma was performed in 28 (78%) patients, with 7 (19%) having a less extensive resection and 6 (17%) having a more extensive resection compared with the surgical plan before stoma creation. CONCLUSION: A diverting stoma could potentially be an alternative to immediate definitive stoma placement in specific populations consisting of patients with luminal colonic CD, especially in the absence of proctitis.
Subject(s)
Colorectal Neoplasms , Crohn Disease , Proctitis , Humans , Crohn Disease/complications , Crohn Disease/surgery , Ileostomy/methods , Retrospective Studies , Cohort Studies , Colorectal Neoplasms/complicationsABSTRACT
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.
Subject(s)
Colitis, Ulcerative , Colorectal Neoplasms , Humans , Colitis, Ulcerative/epidemiology , Colitis, Ulcerative/surgery , Colitis, Ulcerative/complications , Netherlands/epidemiology , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/surgery , Colorectal Neoplasms/etiology , Colectomy/adverse effectsSubject(s)
Appendix , Colitis, Ulcerative , Humans , Colitis, Ulcerative/diagnostic imaging , Intestines , UltrasonographyABSTRACT
BACKGROUND AND AIMS: Adequate endoscopic scoring in Crohn's disease [CD] is crucial, as it dictates the need for initiating postoperative medical therapy and is utilized as an outcome parameter in clinical trials. Here we aimed to observe anastomotic wound healing in relation to endoscopic scoring of both inverted and everted stapled lines in side-to-side anastomoses. METHODS: Two prospective patient cohorts were included: ileocolic resection [ICR] for CD, and right-sided colon resection for colorectal cancer [CRC]. Videos taken during colonoscopy 6 months postoperatively were evaluated. The Simplified Endoscopic Activity Score for Crohn's Disease and modified Rutgeerts score were determined. The primary outcome was the presence of ulcerations in CD patients on both the inverted and the everted stapled lines. Secondary outcomes were the presence of anastomotic ulcerations in CRC patients and the number of cases having ulcerations exclusively at the inverted stapled line. RESULTS: Of the 82 patients included in the CD cohort, ulcerations were present in 63/82 [76.8%] at the inverted- vs 1/71 [1.4%] at the everted stapled line. Likewise in the CRC cohort, ulcerations were present in 4/6 [67.7%] at the inverted vs 0/6 [0%] at the everted stapled line. In total, 27% of the 63 patients in the CD cohort had ulcerations exclusively on the inverted stapled line. CONCLUSION: Inverted stapled lines heal with ulcerations, whereas everted stapled lines heal without any ulcerations, in both CD and non-CD patients. The abnormalities at the inverted stapled line might interfere with endoscopic scoring of recurrence, with potentially an impact on patients' quality of life and on healthcare costs if postoperative treatment is initiated incorrectly.
Subject(s)
Crohn Disease , Humans , Crohn Disease/surgery , Crohn Disease/etiology , Prospective Studies , Quality of Life , Ileum/surgery , Colon/surgery , Anastomosis, Surgical/adverse effects , Colonoscopy , Recurrence , Retrospective StudiesABSTRACT
BACKGROUND: Increasing evidence suggests that appendicectomy as alternative treatment for ulcerative colitis (UC), especially in patients with histopathological appendiceal inflammation. Intestinal ultrasound (IUS) is a non-invasive diagnostic modality to characterise appendiceal inflammation. AIMS: To assess appendiceal IUS characteristics in UC patients and compare findings to healthy controls (HC). METHODS: In this prospective study, appendiceal IUS was performed in consecutive UC patients with active (A; n = 35) or quiescent (Q; n = 30) disease and in HC (n = 30). Transverse appendiceal diameter (TAD) and additional IUS parameters (bowel wall thickness, submucosal layer thickness and colour Doppler signal) were assessed. RESULTS: The appendix was visualised in 41/65 UC patients (63.1%; A vs. Q: 23/35 vs. 18/30, p = 0.67) and 18/30 (60%) HC. UC patients had a higher TAD (A: 5.5 mm, Q: 5.0 mm, HC: 4.3 mm; A-HC p < 0.01; Q-HC p = 0.01, A-Q p = ns) and submucosal layer thickness (A: 1.0 mm, Q: 1.0 mm, HC: 0.7 mm; A-HC p < 0.01, Q-HC: p = 0.01, A-Q: p = ns) when compared to HC. A TAD ≥6 mm corresponding to an ultrasonographic suspicion of acute appendicitis was mainly reported in A-UC patients (A: 43%; Q: 6%; HC: 0%, p = 0.01) and occurred irrespective of disease extent. However, none of the patients had a clinical suspicion of acute appendicitis. CONCLUSION: A TAD ≥6 mm was predominantly seen in A-UC. TAD was higher in UC patients compared to HC irrespective of disease activity and was characterised by an increased submucosal layer thickness. IUS therefore has the potential to identify UC patients with appendiceal inflammation.
Subject(s)
Colitis, Ulcerative , Ultrasonography , Humans , Colitis, Ulcerative/diagnostic imaging , Prospective StudiesABSTRACT
PURPOSE: Since the introduction of ileo-pouch anal anastomosis (IPAA) surgery, various pouch designs have been applied. Recently, there has been renewed interest in creating larger pouch designs to reduce defecation frequency after pouch surgery. The aim of this study was to assess chronic pouch failure (PF) rates and causes in alternative S or septated (SP) pouches when compared to J pouches and B- shaped adaptations. METHODS: This retrospective cohort study included patients that underwent primary IPAA construction surgery from 1978-2000. Pouch designs were subdivided in J and B (J/B), and larger pouches (S/SP). PF included need for a pouch excision, redo pouch procedure, revisional pouch surgery, or permanent ileostomy surgery. Outcomes of this study were incidence and causes for PF per pouch design group. RESULTS: Out of 200 patients who underwent IPAA surgery, 19 had an S/SP design and 181 had a J/B design. After a follow-up of 27.0 (IQR 23.3 - 29.0) years, 45/200 (22.5%) patients who underwent IPAA surgery between 1975-2000 developed PF. Some 78.9% of patients with an S/SP pouch developed PF, compared to 16.7% of patients with a J/B pouch (p < 0.01). Mechanical outlet issues occurred more often in S/SP pouches when compared to J/B (42.1% vs. 1.1%, p < 0.01), and were predominantly caused by septal- or pouch wall intussusception and efferent loop kinking (S-pouch). CONCLUSION: Despite an inevitable proportion of bias, the current study revealed that S/SP pouches were characterized by an increased PF incidence due to emptying problems after long-term follow-up when compared to J/B pouches. Constructing an S pouch or large septated reservoir at index surgery should therefore be questioned because of a shorter longevity.
Subject(s)
Colitis, Ulcerative , Colonic Pouches , Proctocolectomy, Restorative , Humans , Retrospective Studies , Colitis, Ulcerative/surgery , Proctocolectomy, Restorative/adverse effects , Proctocolectomy, Restorative/methods , Colonic Pouches/adverse effects , Ileostomy/adverse effects , Anastomosis, Surgical/adverse effects , Anastomosis, Surgical/methods , Postoperative Complications/etiology , Postoperative Complications/surgeryABSTRACT
BACKGROUND: Myeloid cells are critical determinants of the sustained inflammation in Crohn's Disease (CD). Targeting such cells may be an effective therapeutic approach for refractory CD patients. Bromodomain and extra-terminal domain protein inhibitors (iBET) are potent anti-inflammatory agents; however, they also possess wide-ranging toxicities. In the current study, we make use of a BET inhibitor containing an esterase sensitive motif (ESM-iBET), which is cleaved by carboxylesterase-1 (CES1), a highly expressed esterase in mononuclear myeloid cells. METHODS: We profiled CES1 protein expression in the intestinal biopsies, peripheral blood, and CD fistula tract (fCD) cells of CD patients using mass cytometry. The anti-inflammatory effect of ESM-iBET or its control (iBET) were evaluated in healthy donor CD14+ monocytes and fCD cells, using cytometric beads assay or RNA-sequencing. RESULTS: CES1 was specifically expressed in monocyte, macrophage, and dendritic cell populations in the intestinal tissue, peripheral blood, and fCD cells of CD patients. ESM-iBET inhibited IL1ß, IL6, and TNFα secretion from healthy donor CD14+ monocytes and fCD immune cells, with 10- to 26-fold more potency over iBET in isolated CD14+ monocytes. Transcriptomic analysis revealed that ESM-iBET inhibited multiple inflammatory pathways, including TNF, JAK-STAT, NF-kB, NOD2, and AKT signaling, with superior potency over iBET. CONCLUSIONS: We demonstrate specific CES1 expression in mononuclear myeloid cell subsets in peripheral blood and inflamed tissues of CD patients. We report that low dose ESM-iBET accumulates in CES1-expressing cells and exerts robust anti-inflammatory effects, which could be beneficial in refractory CD patients.
Subject(s)
Anti-Inflammatory Agents , Crohn Disease , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Carboxylic Ester Hydrolases , Crohn Disease/drug therapy , Crohn Disease/metabolism , Humans , Inflammation Mediators , Interleukin-6 , Myeloid Cells/metabolism , NF-kappa B , Proto-Oncogene Proteins c-akt , RNA , Tumor Necrosis Factor-alphaABSTRACT
INTRODUCTION: Surgical errors often occur because of human factor-related issues. A medical data recorder (MDR) may be used to analyze human factors in the operating room. The aims of this study were to assess intraoperative safety threats and resilience support events by using an MDR and to identify frequently discussed safety and quality improvement issues during structured postoperative multidisciplinary debriefings using the MDR outcome report. METHODS: In a cross-sectional study, 35 standard laparoscopic procedures were performed and recorded using the MDR. Outcome data were analyzed using the automated Systems Engineering Initiative for Patient Safety model. The video-assisted MDR outcome report reflects on safety threat and resilience support events (categories: person, tasks, tools and technology, psychical and external environment, and organization). Surgeries were debriefed by the entire team using this report. Qualitative data analysis was used to evaluate the debriefings. RESULTS: A mean (SD) of 52.5 (15.0) relevant events were identified per surgery. Both resilience support and safety threat events were most often related to the interaction between persons (272 of 360 versus 279 of 400). During the debriefings, communication failures (also category person) were the main topic of discussion. CONCLUSIONS: Patient safety threats identified by the MDR and discussed by the operating room team were most frequently related to communication, teamwork, and situational awareness. To create an even safer operating culture, educational and quality improvement initiatives should aim at training the entire operating team, as it contributes to a shared mental model of relevant safety issues.
Subject(s)
Patient Safety , Safety Management , Cross-Sectional Studies , Humans , Medical Errors/prevention & control , Operating Rooms , Patient Care TeamABSTRACT
Despite the longstanding awareness of the presence of mesenteric alterations in Crohn's disease, the functional and clinical consequences of these alterations remain a topic of debate. Guidelines advise a limited resection without resection of the adjacent mesentery to prevent short bowel syndrome and postoperative complications. However, recently mesenteric resection has been proposed as an alternative to reduce recurrence rates in Crohn's disease patients. Here, we evaluate the data available on this topic in terminal ileitis, both from a fundamental research point of view and clinical perspective.
ABSTRACT
Background: Increasing evidence is suggesting appendectomy as an alternative treatment for ulcerative colitis (UC), especially in case of histological appendiceal inflammation. Therefore, preoperative identification of appendiceal inflammation could be beneficial. This study aimed to assess the prevalence of peri-appendiceal red patch (PARP) on colonoscopy. In addition, prognostic relevance of PARP for disease course and its predictive value for histological appendiceal inflammation in patients undergoing appendectomy was assessed. Methods: UC patients undergoing colonoscopy in 2014/2015 were included to determine PARP-prevalence in a cross-sectional study. Findings were correlated to patient and disease characteristics, upscaling of treatment and colectomy rates after cross-sectional colonoscopy. In patients undergoing appendiceal resection, histopathological inflammation was assessed using the Robarts Histopathology Index (RHI). Results: In total, 249 patients were included of which 17.7% (44/249) had a PARP. Patients with PARP were significantly younger with a shorter disease course. The majority of patients with PARP (61.4%) was in endoscopic remission. Patients with PARP required more upscaling of medical therapy (81.8% vs. 58.0%, p < 0.01), and more PARP patients underwent colectomy (13.6% vs. 4.9%, p = 0.04). Patients with PARP had a higher median RHI in resection specimens (14 vs. 7, p < 0.01). Conclusion: PARP was present during colonoscopy regardless disease activity and was predominantly found in UC patients with younger age and shorter disease duration. PARP patients had a more severe course of UC, and in case of appendectomy, more severe histopathological appendiceal inflammation. Appendectomy as an experimental therapy for UC has been suggested to be predominantly effective in UC patients with appendiceal inflammation. This study demonstrates that presence of a PARP on colonoscopy predicts appendiceal inflammation. After consensus has been reached on the therapeutic effect of appendectomy, assessing PARP presence during colonoscopy could therefore contribute to identifying patients most likely to respond.