Management of colorectal neoplasia in IBD patients: current practice and future perspectives.

Inflammatory bowel disease (IBD) patients are at increased risk of developing colorectal neoplasia (CRN). In this review, we aim to provide an up-to-date overview and future perspectives on CRN management in IBD. Advances in endoscopic surveillance and resection techniques have resulted in a shift towards endoscopic management of neoplastic lesions in place of surgery. Endoscopic treatment is recommended for all CRN if complete resection is feasible. Standard (cold snare) polypectomy, endoscopic mucosal resection and endoscopic submucosal dissection should be performed depending on lesion complexity (size, delineation, morphology, surface architecture, submucosal fibrosis/invasion) to maximize the likelihood of complete resection. If complete resection is not feasible, surgical treatment options should be discussed by a multidisciplinary team. While (sub)total and proctocolectomy play an important role in management of endoscopically unresectable CRN, partial colectomy may be considered in a subgroup of patients in endoscopic remission with limited disease extent without other CRN risk factors. High synchronous and metachronous CRN rates warrant careful mucosal visualization with shortened intervals for at least 5 years after treatment of CRN.

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.

Clonal Patterns Between Pouch Neoplasia and Prior Colorectal Neoplasia in Inflammatory Bowel Disease Patients: An Exploratory Cohort Study.

Prior colorectal neoplasia is the strongest predictor of pouch neoplasia in inflammatory bowel disease, but the underlying mechanism is unknown. We observed clonality between colorectal and pouch neoplasia in 30% of patients, indicating that most pouch neoplasia develops clonally independent from prior colorectal lesions.

Bacterial Oncotraits Rather than Spatial Organization Are Associated with Dysplasia in Ulcerative Colitis.

BACKGROUND AND AIMS: Colonic bacterial biofilms are frequently present in ulcerative colitis [UC] and may increase dysplasia risk through pathogens expressing oncotraits. This prospective cohort study aimed to determine [1] the association of oncotraits and longitudinal biofilm presence with dysplasia risk in UC, and [2] the relation of bacterial composition with biofilms and dysplasia risk. METHODS: Faeces and left- and right-sided colonic biopsies were collected from 80 UC patients and 35 controls. Oncotraits [FadA of Fusobacterium, BFT of Bacteroides fragilis, colibactin [ClbB] and Intimin [Eae] of Escherichia coli] were assessed in faecal DNA with multiplex quantitative polymerase chain reaction [qPCR]. Biopsies were screened for biofilms [n = 873] with 16S rRNA fluorescent in situ hybridiation. Shotgun metagenomic sequencing [n = 265], and ki67-immunohistochemistry were performed. Associations were determined with a mixed-effects regression model. RESULTS: Biofilms were highly prevalent in UC patients [90.8%] with a median persistence of 3 years (interquartile range [IQR] 2-5 years). Biofilm-positive biopsies showed increased epithelial hypertrophy [p = 0.025] and a reduced Shannon diversity independent of disease status [p = 0.015], but were not significantly associated with dysplasia in UC: adjusted odds ratio [aOR] 1.45, 95% confidence interval [CI] 0.63-3.40. In contrast, ClbB independently associated with dysplasia [aOR 7.16, 95% CI 1.75-29.28], and FadA and Fusobacteriales were associated with a decreased dysplasia risk in UC [aOR 0.23, 95% CI 0.06-0.83, p <0.01]. CONCLUSIONS: Biofilms are a hallmark of UC; however, because of their high prevalence are a poor biomarker for dysplasia. In contrast, colibactin presence and FadA absence independently associate with dysplasia in UC and might therefore be valuable biomarkers for future risk stratification and intervention strategies.

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.

De-escalation of biological therapy in inflammatory bowel disease patients following prior dose escalation.

BACKGROUND: Limited data are available on biological therapy de-escalation after prior escalation in inflammatory bowel disease (IBD) patients. This study aimed to assess the frequency and success rate of de-escalation of biological therapy in IBD patients after prior dose escalation and to evaluate which measures are used to guide de-escalation. METHODS: This multicentre retrospective cohort study enrolled IBD patients treated with infliximab (IFX), adalimumab (ADA) or vedolizumab (VEDO) in whom therapy was de-escalated after prior biological escalation. De-escalations were considered pharmacokinetic-driven if based on clinical symptoms combined with therapeutic or supratherapeutic trough levels, and disease activity-driven if based on faecal calprotectin less than or equal to 200 µg/g or resolution of perianal fistula drainage or closure or endoscopic remission. Successful de-escalation was defined as remaining on the same or lower biological dose for greater than or equal to 6 months after de-escalation without the need for corticosteroids. RESULTS: In total, 206 IFX users, 85 ADA users and 55 VEDO users underwent therapy escalation. Of these patients, 34 (17%) on IFX, 18 (21%) on ADA and 8 (15%) on VEDO underwent therapy de-escalation. De-escalation was successful in 88% of IFX patients, 89% of ADA and 100% of VEDO. The probability of remaining on the de-escalated regimen or further de-escalation after 1 year was 85% for IFX, 62% for ADA and 100% for VEDO. Disease activity-driven de-escalations were more often successful (97%) than pharmacokinetic- and no marker-driven de-escalations (76%); P = 0.017. CONCLUSION: De-escalation after biological dose escalation was successful in the majority of carefully selected IBD patients. Objective assessment of remission increased the likelihood of successful de-escalation.

Patients Prioritize a Low-volume Bowel Preparation in Colitis-associated Colorectal Cancer Surveillance: A Discrete Choice Experiment.

BACKGROUND: Patients with inflammatory bowel disease (IBD) undergo surveillance colonoscopies at fixed intervals to reduce the risk of colorectal cancer (CRC). Taking patients' preferences for determining surveillance strategies into account could improve adherence and patient satisfaction. This study aimed to determine patient preferences for CRC surveillance in IBD. METHODS: We conducted a web-based, multicenter, discrete choice experiment among adult IBD patients with an indication for surveillance. Individuals were repeatedly asked to choose between 3 hypothetical surveillance scenarios. The choice tasks were based on bowel preparation (0.3-4 L), CRC risk reduction (8% to 1%-6%), and interval (1-10 years). Attribute importance scores, trade-offs, and willingness to participate were calculated using a multinomial logit model. Latent class analysis was used to identify subgroups with similar preferences. RESULTS: In total, 310 of 386 sent out questionnaires were completed and included in the study. Bowel preparation was prioritized (attribute importance score 40.5%) over surveillance interval and CRC risk reduction (31.1% and 28.4%, respectively). Maximal CRC risk reduction, low-volume bowel preparation (0.3 L laxative with 2 L clear liquid) with 2-year surveillance was the most preferred combination. Three subgroups were identified: a "surveillance avoidant," "CRC risk avoidant," and "surveillance preferring" groups. Membership was correlated with age, educational level, perceived CRC risk, the burden of bowel preparation, and colonoscopies. CONCLUSIONS: Inflammatory bowel disease patients consider bowel preparation as the most important element in acceptance of CRC surveillance. Heterogeneity in preferences was explained by 3 latent subgroups. These findings may help to develop an individualized endoscopic surveillance strategy in IBD patients.

This discrete choice experiment identified volume of bowel preparation as the attribute impacting patients' preferences regarding colitis-associated colorectal cancer surveillance most. Three subgroups were identified with similar preferences and distinct clinical characteristics.

Better quality of life and less caregiver strain in young-onset Parkinson's disease: a multicentre retrospective cohort study.

BACKGROUND: Parkinson's disease (PD) is typically considered as a disease of the elderly. However, there is a sizeable subgroup of patients where PD starts at a younger age, known as young-onset PD (YOPD). We evaluated the differences in quality of life and caregiver strain between YOPD and later onset PD (LOPD) patients in a large cohort. METHODS: In collaboration with the Parkinson Foundation Quality Improvement Initiative (PF-QII), we conducted a retrospective three-year analysis on 962 PD patients of the QII database (starting date May 2016). Of these, 272 patients had YOPD, and 690 had LOPD. The Parkinson's Disease Questionnaire-39 (PDQ-39) total score served as primary outcome measure. Furthermore, we analysed group differences in modified caregiver strain index (MCSI) total score, three cognition functions, and number of falls. A regression analysis adjusting for covariates was used to assess the association of age at onset with PDQ-39 and MCSI. RESULTS: PDQ scores were better in YOPD patients, MCSI scores on social constraint were lower in YOPD patients, but scores on financial constraint were higher in this group. After adjusting for covariates, YOPD patients had better quality of life and less caregiver strain at all follow-up moments, but not at baseline. Decline over time for all outcomes was lower in the YOPD group compared to the LOPD group. Cognitive functioning and number of falls progressed slower in the YOPD group compared to the LOPD group. CONCLUSION: Compared to LOPD patients, YOPD patients had a better quality of life, less caregiver strain, fewer falls and better cognitive functioning after their first follow-up visit, and also a slower decline over time.

The placebo response of injectable GLP-1 receptor agonists vs. oral DPP-4 inhibitors and SGLT-2 inhibitors: a systematic review and meta-analysis.

AIMS: The size of the placebo response in type 2 diabetes (T2DM) treatment and its relation to the route of drug administration have not been systematically reviewed. We aimed to determine weight loss, change in HbA1c and incidence of adverse events after treatment with injectable placebo GLP-1 receptor agonist (GLP-1ra), compared with oral placebo DPP-4 inhibitor (DPP-4i) and placebo SGLT-2 inhibitor (SGLT-2i). METHODS: PubMed, EMBASE and Central were searched up to September 2014 for randomized placebo controlled trials investigating GLP-1ra, DPP-4i or SGLT2-i. Data on placebo groups were extracted and pooled using a generic inverse variance random effects model. RESULTS: Sixty-seven trials were included, involving 2522, 5290 and 2028 patients randomized to placebo GLP-1ra, placebo DPP-4i and placebo SGLT-2i, respectively. Body weight decreased by -0.67 kg (95% CI -1.03, -0.31) after treatment with placebo GLP-1ra (-0.76 kg [95% CI -1.10, -0.43] with placebo short acting GLP-1ra and -0.32 kg [95% CI -1.75, 1.10] with placebo long acting GLP-1ra) and by -0.31 kg (95% CI -0.64, 0.01) with placebo DPP-4i (P = 0.06 for difference with placebo short acting GLP-1ra). Placebo SGLT-2i resulted in an intermediate -0.48 kg (95% CI -0.81, -0.15) weight loss. Weight loss with placebo showed a strong correlation with the active comparator drug (r(2)  = 0.40-0.78). HbA1c changed little with placebo treatment (-0.23%, 0.10% and -0.13% for placebo GLP-1ra, DPP-4i and SGLT-2i). Adverse events occurred frequently with placebo, were often similar to the active comparator drug and led to drop-out in 2.0-2.7% of cases. CONCLUSIONS: The response to placebo treatment was related to its active comparator, with injectable placebo GLP-1ra showing a relevant response on weight, whereas oral placebo DPP4i showed no significant response. These findings may suggest that subjective expectations influence T2DM treatment efficacy, which can possibly be employed therapeutically.