Interobserver agreement of current and new proposed endoscopic scores for postoperative recurrence in Crohn's disease.

BACKGROUND AND AIMS: The modified Rutgeerts' score (mRS) is widely used for the assessment of endoscopic postoperative recurrence (ePOR) in Crohn's disease (CD) after ileocolic resection to guide therapeutic decisions. To improve the validity and prognostic value of this endoscopic assessment, two new scores have been proposed. This study assessed the interobserver agreement of the current (mRS) and new endoscopic scores for ePOR in CD. METHODS: Sixteen Dutch academic and non-academic IBD specialists assessed endoscopic videos (n=71) of postoperative CD patients (n=66) retrieved from nine Dutch centers. Each video was assessed for the degree of inflammation by four gastroenterologists using the mRS and the new proposed endoscopic score: REMIND score (separate score of anastomosis and neoterminal ileum) and updated Rutgeerts score (assessment of lesions at the anastomotic line, ileal inlet, ileal body and neoterminal ileum). In addition, lesions at the ileal body, ileal inlet, neoterminal ileum, colonic and/or ileal blind loop were separately assessed. Interobserver agreement was assessed using Fleiss' weighted kappa. RESULTS: Fleiss' weighted kappa for the mRS was 0.67 (95% confidence interval [CI] 0.59-0.74). The weighted kappa for the REMIND score was 0.73 (95% CI 0.65-0.80) for lesions in the neoterminal ileum and 0.46 (95% CI 0.35-0.58) for anastomotic lesions. The weighted kappa for the updated Rutgeerts' score was 0.69 (95% CI 0.62-0.77). The weighted kappa for lesions in the ileal body, ileal inlet, neoterminal ileum, colonic and ileal blind loop was 0.61 (95% CI 0.49-0.73), 0.63 (95% CI 0.54-0.72), 0.61 (95% CI 0.49-0.74), 0.83 (95% CI 0.62-1.00) and 0.68 (95% CI 0.46-0.89). CONCLUSION: The interobserver agreement of the mRS is substantial. Similarly, the interobserver agreement is substantial for the updated Rutgeerts' score. According to the REMIND score, the interobserver agreement was substantial for lesions in the neoterminal ileum, whereas only moderate for anastomotic lesions. Since therapeutic decisions in clinical practice are based on these assessments and these scores are used as outcome measure in clinical studies, further improvement of the interobserver agreement is essential.

Endoscopic and surgical treatment outcomes of colitis-associated advanced colorectal neoplasia: a multicenter cohort study.

BACKGROUND: Inflammatory bowel disease (IBD) patients are at increased risk of advanced neoplasia (high-grade dysplasia or colorectal cancer). The authors aimed to (1) assess synchronous and metachronous neoplasia following (sub)total or proctocolectomy, partial colectomy or endoscopic resection for advanced neoplasia in IBD, and (2) identify factors associated with treatment choice. MATERIAL AND METHODS: In this retrospective multicenter cohort study, the authors used the Dutch nationwide pathology databank (PALGA) to identify patients diagnosed with IBD and colonic advanced neoplasia (AN) between 1991 and 2020 in seven hospitals in the Netherlands. Logistic and Fine & Gray's subdistribution hazard models were used to assess adjusted subdistribution hazard ratios for metachronous neoplasia and associations with treatment choice. RESULTS: The authors included 189 patients (high-grade dysplasia n =81; colorectal cancer n =108). Patients were treated with proctocolectomy ( n =33), (sub)total colectomy ( n =45), partial colectomy ( n =56) and endoscopic resection ( n =38). Partial colectomy was more frequently performed in patients with limited disease and older age, with similar patient characteristics between Crohn's disease and ulcerative colitis. Synchronous neoplasia was found in 43 patients (25.0%; (sub)total or proctocolectomy n =22, partial colectomy n =8, endoscopic resection n =13). The authors found a metachronous neoplasia rate of 6.1, 11.5 and 13.7 per 100 patient-years after (sub)total colectomy, partial colectomy and endoscopic resection, respectively. Endoscopic resection, but not partial colectomy, was associated with an increased metachronous neoplasia risk (adjusted subdistribution hazard ratios 4.16, 95% CI 1.64-10.54, P <0.01) compared with (sub)total colectomy. CONCLUSION: After confounder adjustment, partial colectomy yielded a similar metachronous neoplasia risk compared to (sub)total colectomy. High metachronous neoplasia rates after endoscopic resection underline the importance of strict subsequent endoscopic surveillance.

Effectiveness of Mindfulness-Based Cognitive Therapy in reducing psychological distress and improving sleep in patients with Inflammatory Bowel Disease: study protocol for a multicentre randomised controlled trial (MindIBD).

BACKGROUND: Many patients with Inflammatory Bowel Diseases (IBD) suffer from psychological distress, fatigue and sleep disturbances, which are associated with reduced quality of life (QoL) and increased societal costs. Only limited psychosocial treatment options are available. As Mindfulness-Based Cognitive Therapy (MBCT) has demonstrated to improve psychological distress, QoL and sleep in other populations, MBCT might also be effective in patients with IBD. METHODS: The MindIBD study is a prospective, multicentre, randomised controlled trial comparing MBCT plus Treatment As Usual (TAU) versus TAU alone in a targeted number of 136 IBD patients in remission, aged 16 years and older with at least mild psychological distress (Hospital Anxiety and Depression Scale (HADS) total score ≥ 11). Primary outcome is reduction of psychological distress post-intervention, measured by the HADS. In addition, the effect of MBCT on sleep quality (including actigraphy and electroencephalography recordings), fatigue, disease activity, perceived disease control, QoL and positive mental health will be examined. Assessments will be conducted at baseline and at 3, 6, 9 and 12 months follow-up. Cost-effectiveness will be determined and a process evaluation will be conducted. DISCUSSION: This study will provide valuable insight into the clinical effect of MBCT on psychological distress, sleep quality, fatigue and QoL in IBD patients and into the cost-effectiveness. If effective, MBCT can be a valuable addition to the available psychosocial interventions for patients with IBD. Moreover, findings from this study may also be applicable in patients with other chronic conditions. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04646785, registered on 30/11/2020.

Exposure to Thioguanine During 117 Pregnancies in Women With Inflammatory Bowel Disease.

BACKGROUND: Safety of thioguanine in pregnant patients with inflammatory bowel disease [IBD] is sparsely recorded. This study was aimed to document the safety of thioguanine during pregnancy and birth. METHODS: In this multicentre case series, IBD patients treated with thioguanine during pregnancy were included. Data regarding disease and medication history, pregnancy course, obstetric complications, and neonatal outcomes were collected. RESULTS: Data on 117 thioguanine-exposed pregnancies in 99 women were collected. Most [78%] had Crohn's disease and the mean age at delivery was 31 years. In 18 pregnancies [15%], IBD flared. Obstetric and infectious complications were seen in 15% [n = 17] and 7% [n = 8] of pregnancies, respectively. Ten pregnancies [8.5%] resulted in a first trimester miscarriage, one in a stillbirth at 22 weeks of gestational age and one in an induced abortion due to trisomy 21. In total, 109 neonates were born from 101 singleton pregnancies and four twin pregnancies. One child was born with a congenital abnormality [cleft palate]. In the singleton pregnancies, 10 children were born prematurely and 10 were born small for gestational age. Screening for myelosuppresion was performed in 16 neonates [14.7%]; two had anaemia in umbilical cord blood. All outcomes were comparable to either the general Dutch population or to data from three Dutch cohort studies on the use of conventional thiopurines in pregnant IBD patients. CONCLUSION: In this large case series, the use of thioguanine during pregnancy is not associated in excess with adverse maternal or neonatal outcomes.

Superior Effectiveness of Tofacitinib Compared to Vedolizumab in Anti-TNF-experienced Ulcerative Colitis Patients: A Nationwide Dutch Registry Study.

BACKGROUND & AIMS: Clinicians face difficulty in when and in what order to position biologics and Janus kinase inhibitors in patients with anti-tumor necrosis factor-alpha (TNF) refractory ulcerative colitis (UC). We aimed to compare the effectiveness and safety of vedolizumab and tofacitinib in anti-TNF-exposed patients with UC in our prospective nationwide Initiative on Crohn and Colitis Registry. METHODS: Patients with UC who failed anti-TNF treatment and initiated vedolizumab or tofacitinib treatment were identified in the Initiative on Crohn and Colitis Registry in the Netherlands. We selected patients with both clinical as well as biochemical or endoscopic disease activity at initiation of therapy. Patients previously treated with vedolizumab or tofacitinib were excluded. Corticosteroid-free clinical remission (Simple Clinical Colitis Activity Index ≤2), biochemical remission (C-reactive protein ≤5 mg/L or fecal calprotectin ≤250 µg/g), and safety outcomes were compared after 52 weeks of treatment. Inverse propensity score-weighted comparison was used to adjust for confounding and selection bias. RESULTS: Overall, 83 vedolizumab- and 65 tofacitinib-treated patients were included. Propensity score-weighted analysis showed that tofacitinib-treated patients were more likely to achieve corticosteroid-free clinical remission and biochemical remission at weeks 12, 24, and 52 compared with vedolizumab-treated patients (odds ratio [OR], 6.33; 95% confidence interval [CI], 3.81-10.50; P < .01; OR, 3.02; 95% CI, 1.89-4.84; P < .01; and OR, 1.86; 95% CI, 1.15-2.99; P = .01; and OR, 3.27; 95% CI, 1.96-5.45; P < .01; OR, 1.87; 95% CI, 1.14-3.07; P = .01; and OR, 1.81; 95% CI, 1.06-3.09; P = .03, respectively). There was no difference in infection rate or severe adverse events. CONCLUSIONS: Tofacitinib was associated with superior effectiveness outcomes compared with vedolizumab in anti-TNF-experienced patients with UC along with comparable safety outcomes.

Prophylactic Medication for the Prevention of Endoscopic Recurrence in Crohn's Disease: a Prospective Study Based on Clinical Risk Stratification.

BACKGROUND: To prevent recurrence after ileocolonic resection [ICR] in Crohn's disease [CD], postoperative prophylaxis based on risk stratification is recommended in international guidelines. This study aimed to evaluate postoperative CD recurrence after implementation of a clinical management algorithm and to determine the predictive value of clinical and histological risk factors [RFs]. METHODS: In this multicentre, prospective cohort study, CD patients [≥16 years] scheduled for ICR were included. The algorithm advised no postoperative medication for low-risk patients, and treatment with prophylaxis [immunosuppressant/biological] for high-risk patients [≥1 RF: active smoking, penetrating disease, prior ICR]. Clinical and histological RFs [active inflammation, granulomas, plexitis in resection margins] for endoscopic recurrence [Rutgeerts' score ≥i2b at 6 months] were assessed using logistic regression and ROC curves based on predicted probabilities. RESULTS: In total, 213 CD patients after ICR were included [age 34.5 years; 65% women] (93 [44%] low-risk; 120 [56%] high-risk: 45 [38%] smoking; 51 [43%] penetrating disease; 51 [43%] prior ICR). Adherence to the algorithm was 82% in low-risk [no prophylaxis] and 51% in high-risk patients [prophylaxis]. Endoscopic recurrence was higher in patients treated without prophylaxis than with prophylaxis in both low [45% vs 16%, p = 0.012] and high-risk patients [49% vs 26%, p = 0.019]. Clinical risk stratification including the prescription of prophylaxis corresponded to an area under the curve [AUC] of 0.70 (95% confidence interval [CI] 0.61-0.79). Clinical RFs combined with histological RFs increased the AUC to 0.73 [95% CI 0.64-0.81]. CONCLUSION: Adherence to this management algorithm is 65%. Prophylactic medication after ICR prevents endoscopic recurrence in low- and high-risk patients. Clinical risk stratification has an acceptable predictive value, but further refinement is needed.

Quality of Surveillance Impacts the Colitis-Associated Advanced Neoplasia Risk: A Multicenter Case-Control Study.

BACKGROUND AND AIMS: Although colorectal cancer (CRC) surveillance is embedded in clinical inflammatory bowel disease (IBD) practice, a subset of patients still develops advanced neoplasia (AN) (high-grade dysplasia [HGD] and/or CRC). We aimed to assess the impact of surveillance quality on AN risk in IBD. METHODS: In this multicenter case-control study, we searched the Dutch nationwide pathology databank to identify IBD cases with AN and controls with indefinite or low-grade dysplasia. The surveillance colonoscopy preceding the index lesion (first indefinite for dysplasia [IND]/low-grade dysplasia [LGD] or AN) was used to assess the impact of surveillance quality. We assessed intervals, bowel preparation, cecal intubation, and absence of inflammation as primary quality indicators. In addition, we assessed chromoendoscopy, endoscopist expertise, hospital setting, and biopsy strategy. Associations of quality indicators with AN risk were determined with multivariable logistic regression analyses with Firth's correction. RESULTS: We included 137 cases and 138 controls. Delayed intervals (58.2% vs 39.6%) and active inflammation (65.3% vs 41.8%) were frequently present in cases and controls and were associated with AN (delayed interval: adjusted odds ratio [aOR], 2.00; 95% confidence interval [CI], 1.07-3.81; P = .03; active inflammation: aOR, 2.46; 95% CI, 1.33-4.61; P < .01). Surveillance compliant with primary quality indicators was associated with a reduced AN risk (aOR, 0.43; 95% CI, 0.22-0.91; P = .03), similar to chromoendoscopy (OR, 0.11; 95% CI, 0.01-0.89; P = .01). Other indicators were not significantly associated with AN. CONCLUSIONS: Surveillance compliant with primary quality indicators is associated with a reduced colitis-associated AN risk. Delayed surveillance intervals and active inflammation were associated with an increased AN risk. This underlines the importance of procedural quality, including endoscopic remission to optimize the effectiveness of endoscopic surveillance.

Clinical Outcomes of Covid-19 in Patients With Inflammatory Bowel Disease: A Nationwide Cohort Study.

BACKGROUND AND AIMS: The COVID-19 risk and disease course in inflammatory bowel disease [IBD] patients remains uncertain. Therefore, we aimed to assess the clinical presentation, disease course, and outcomes of COVID-19 in IBD patients. Second, we determined COVID-19 incidences in IBD patients and compared this with the general population. METHODS: We conducted a multicentre, nationwide IBD cohort study in The Netherlands and identified patients with COVID-19. First, we assessed the COVID-19 disease course and outcomes. Second, we compared COVID-19 incidences between our IBD study cohort and the general Dutch population. RESULTS: We established an IBD cohort of 34 763 patients. COVID-19 was diagnosed in 100/34 763 patients [0.29%]; 20/100 of these patients [20%] had severe COVID-19 defined as admission to the intensive care unit, mechanical ventilation, and/or death. Hospitalisation occurred in 59/100 [59.0%] patients and 13/100 [13.0%] died. All patients who died had comorbidities and all but one were ≥65 years old. In line, we identified ≥1 comorbidity as an independent risk factor for hospitalisation (odds ratio [OR] 4.20, 95% confidence interval [CI] 1.58-11.17,; p = 0.004). Incidences of COVID-19 between the IBD study cohort and the general population were comparable (287.6 [95% CI 236.6-349.7] versus 333.0 [95% CI 329.3-336.7] per 100000 patients, respectively; p = 0.15). CONCLUSIONS: Of 100 cases with IBD and COVID-19, 20% developed severe COVID-19, 59% were hospitalised and 13% died. A comparable COVID-19 risk was found between the IBD cohort [100/34 763 = 0.29%] and the general Dutch population. The presence of ≥1 comorbidities was an independent risk factor for hospitalisation due to COVID-19.

Long-term Risk of Advanced Neoplasia After Colonic Low-grade Dysplasia in Patients With Inflammatory Bowel Disease: A Nationwide Cohort Study.

BACKGROUND AND AIMS: The long-term risk of high-grade dysplasia [HGD] and colorectal cancer [CRC] following low-grade dysplasia [LGD] in inflammatory bowel disease [IBD] patients is relatively unknown. We aimed to determine the long-term cumulative incidence of advanced neoplasia [HGD and/or CRC], and to identify risk factors for advanced neoplasia in a nationwide IBD cohort with a history of LGD. METHODS: This is a nationwide cohort study using data from the Dutch National Pathology Registry [PALGA] to identify all IBD patients with LGD between 1991 and 2010 in the Netherlands. Follow-up data were collected until January 2016. We determined the cumulative incidence of advanced neoplasia and identified risk factors via multivariable Cox regression analysis. RESULTS: We identified 4284 patients with colonic LGD with a median follow-up of 6.4 years after initial LGD diagnosis. The cumulative incidence of subsequent advanced neoplasia was 3.6, 8.5, 14.4 and 21.7%, after 1, 5, 10 and 15 years, respectively. The median time to develop advanced neoplasia after LGD was 3.6 years. Older age [≥ 55 years] at moment of LGD (hazard ratio [HR] 1.73, 95% confidence interval [CI] 1.44-2.06), male sex [HR 1.33, 95% CI 1.10-1.60], and follow-up at an academic [vs non-academic] medical centre [HR 1.37, 95% CI 1.07-1.76] were independent risk factors for advanced neoplasia following LGD. CONCLUSIONS: In a large nationwide cohort with long-term follow-up of IBD patients with LGD, the cumulative incidence of advanced neoplasia was 21.7% after 15 years. Older age at LGD [≥55 years], male sex and follow-up by a tertiary IBD referral centre were independent risk factors for advanced neoplasia development after initial LGD.

Sustained effectiveness, safety and therapeutic drug monitoring of tioguanine in a cohort of 274 IBD patients intolerant for conventional therapies.

BACKGROUND: Tioguanine (or thioguanine) is an alternative drug for IBD patients who fail prior conventional immunomodulating therapy. AIM: To report effectiveness, safety and therapeutic drug monitoring in a cohort of patients with prolonged tioguanine maintenance therapy. METHODS: In this nationwide, multicentre study, medical records of tioguanine- using IBD patients were retrospectively reviewed. Response to therapy was defined as clinical effectiveness without (re)initiation of corticosteroids, concurrent biological therapy or surgical intervention. All adverse events that occurred during the follow-up were listed and graded according to the common terminology criteria (CTC). RESULTS: Two hundred and seventy-four patients (female 63%, Crohn's disease in 68%) were included with median treatment duration of 51 months, 1567 patient-years of follow-up and median 20 mg/d tioguanine dosage. Tioguanine was tolerated in 79%, clinical effectiveness at 6 months was documented in 66% and sustained clinical effectiveness during 12 months in 51% of patients. Forty-one per cent of patients developed adverse events: 5% were graded as severe. Adverse events comprised infection requiring hospitalisation in three and skin cancer in eight patients (two melanomas). Asymptomatic nodular regenerative hyperplasia of the liver occurred in two out of 52 patients with liver biopsies (3.8%) and portal hypertension in three whereof one potentially associated with tioguanine (0.4%). Clinical effectiveness was correlated with 6-thioguanine nucleotide threshold concentrations >682 pmol/8×108 RBC (P < 0.05). CONCLUSIONS: Long-term tioguanine therapy for at least 12 months was effective in 51% and well tolerated as a maintenance treatment for IBD in about 70% of patients. Adverse events were common, but mainly mild or moderate. 6-Thioguanine nucleotide threshold concentration ≥ 700 pmol/8×108 RBC is proposed as target level with higher odds for clinical effectiveness.

[Abdominal pain with a microvascular cause]. / Buikpijn door een microvasculaire oorzaak.

A 50-year-old Caucasian man was admitted with unexplained abdominal pain. Based on CT scan results, a perforation resulting from colitis of the transverse colon was suspected. Additional colonoscopy showed ulcerative stenosis of the transverse colon. Initially, the patient recovered on conservative treatment; however, because of persistent stenosis, an elective resection of the transverse colon was performed. A CT scan revealed free gas around the anastomosis on the fourth postoperative day. Relaparotomy revealed leakage and diffuse ischaemic changes around the anastomosis as well as perforations at different sites on the small bowel. Postoperative CT angiography showed stenosis of the proximal celiac trunk, which was successfully stented. Digital subtraction angiography (DSA) revealed luminal irregularities of the superior mesenteric, the middle colic as well as the main hepatic and splenic arteries. Eventually, the clinical presentation and surgical, radiologic and histopathological findings together led to the diagnosis of polyarteritis nodosa (PAN). Aggressive treatment with glucocorticoids and cyclophosphamide resulted in the resolution of symptoms and the disappearance of radiologic abnormalities.

Cinacalcet for hyperparathyroidism in pregnancy and puerperium.

The efficacy and safety of various modes of medical treatment for primary hyperparathyroidism (PHPT) in pregnancy is largely unknown. This report describes two cases of PHPT in pregnancy that were temporarily treated with the calcimimetic cinacalcet. The first case was diagnosed in the 31st week of pregnancy. The patient was asymptomatic and had an albumin-corrected total calcium level (Ca(corr)) of 3.24 mmol/l. As serum calcium was only mildly elevated it was decided to postpone surgery to the postpartum period. Cinacalcet was started immediately after delivery to prevent a postpartum surge in serum calcium. The second patient presented with hypertension and symptomatic hypercalcemia (Ca(corr) 3.96 mmol/l) in the 32nd week of pregnancy. Surgery was postponed because of suspected pheochromocytoma. Treatment with a combination of cinacalcet and calcitonin reduced serum Ca(corr) to 3.0 mmol/l. This report describes the monitoring of mother and child, and explores the pros and cons of the use of calcimimetics during pregnancy and puerperium.