Currently, the main targets of drug therapy for ulcerative colitis [UC] are endoscopic and clinical remission. However, there is active discussion about the additional advantages of including histological remission as a target. Accumulating evidence indicates that microscopic activity persists in endoscopically quiescent UC, that histological changes may lag behind clinical remission after treatment, and that absence of histological activity predicts lower rates of relapse, hospitalization, surgery and subsequent neoplasia. Obtaining useful information from mucosal biopsies in this setting depends on accurate and consistent evaluation of histological features. However, there is no standardization of biopsy procedures, histological sample processing technique or histological scoring systems, and there is no agreement on the definitions of histological remission, response or activity. Accordingly, a consensus expert panel convened by the European Crohn’s and Colitis Organisation [ECCO] reviewed the literature and agreed a number of position statements regarding harmonization of UC histopathology. The objective was to provide evidence-based guidance for the standardization and harmonization of procedures, definitions and scoring systems for histology in UC, and to reach expert consensus where possible. We propose the absence of intraepithelial neutrophils, erosion and ulceration as a minimum requirement for the definition of histological remission. For randomized control trials we recommend the use of the Robarts histopathology index [RHI] or the Nancy index [NI]. For observational studies or in clinical practice we recommend the use of the NI. To predict the risk of future neoplasia in UC, cumulative histological scores over time are more useful than single scores.

Background: Fecal calprotectin (FC) is a non‐invasive marker of gut inflammation which is frequently used to guide therapeutic decisions in patients with inflammatory bowel diseases (IBD). Each step of FC measurement can influence the results, leading to misinterpretations and potentially impacting the management of IBD patients. To date, there is high heterogeneity between FC measurements and no current method is universally accepted as a standard.Aims: Our aim was to provide clear position statementsabout the pre‐analytical and the analytical phases of FC measurement to homogenize FC levels and to minimize variability and risk of misinterpretation through aninternational consensus.Materials & Methods: Fourteen physicians with expertise in the field of IBD and FC from 11 countries attended a virtual international consensus meeting on July 17th, 2020. A systematic literature was conducted and the literature evidence was shared and discussedamong the participants. Statements were formulated, discussed, and voted. Statements were considered approved if all participants agreed.Results: Nine statements were formulated and approved. Based on the available evidence, quantitative tests should be preferred for measuring FC. Furthermore, FC measurement, if possible, should always be performed with the same method and factors influencing FC levels should be taken into account when interpreting the results.Discussion: FC has an increasingly important role in the management of patients with IBD. However, large multicenter studies should be conducted to define the reproducibility and to confirm the diagnostic accuracy of the available FC tests.Conclusion: FC concentrations guide clinicians' treatment decisions. Our statements have a relevant impact in daily practice and could be applied in clinical trials to standardize FC measurement.

Inflammatory breast cancer (IBC) is a rare and rapidly progressive form of invasive breast cancer. The aim of this study was to explore the clinical evolution, stromal tumour-infiltrating lymphocytes (sTIL) infiltration and programmed death-ligand 1 (PD-L1) expression in a large IBC cohort. Data were collected prospectively from patients with IBC as part of an international collaborative effort since 1996. In total, 143 patients with IBC starting treatment between June 1996 and December 2016 were included. Clinicopathological variables were collected, and sTIL were scored by two pathologists on standard H&E stained sections. PD-L1 expression was assessed using a validated PD-L1 (SP142) assay. A validation cohort of 64 patients with IBC was used to test our findings. Survival outcomes of IBC remained poor with a 5-year overall survival (OS) of 45.6%. OS was significantly better in patients with primary non-metastatic disease who received taxane-containing (neo)adjuvant therapy (P = 0.01), had a hormone receptor-positive tumour (P = 0.001) and had lower cN stage at diagnosis (P = 0.001). PD-L1 positivity on immune cells (42.9%) was higher in IBC than in non-IBC in both our patient samples and the validation cohort. Furthermore, PD-L1 expression predicted pCR (P = 0.002) and correlated with sTIL infiltration (P < 0.001). sTIL infiltration of more than 10% of the stroma was a significant predictor of improved OS (HR 0.47, 95% CI 0.27–0.81, P = 0.006) in a multivariate model. IBC is characterised by poor survival and high PD-L1 immunoreactivity on sTIL. This suggests a role for PD1/PD-L1 inhibitors in the treatment of IBC. Furthermore, we showed that PD-L1 expression predicts response to neo-adjuvant therapy and that sTIL have prognostic significance in IBC.

Background: The approved maintenance regimens for ustekinumab in Crohn’s disease [CD] are 90 mg every 8 or 12 weeks. Some patients will respond partially to ustekinumab or will experience a secondary loss of response. It remains poorly known if these patients may benefit from shortening the interval between injections. Methods: All patients with active CD, as defined by Harvey–Bradshaw score ≥ 4 and one objective sign of inflammation [C-reactive protein > 5 mg/L and/or faecal calprotectin > 250 µg/g and/or radiological and/or endoscopic evidence of disease activity] who required ustekinumab dose escalation to 90 mg every 4 weeks for loss of response or incomplete response to ustekinumab 90 mg every 8 weeks were included in this retrospective multicentre cohort study. Results: One hundred patients, with a median age of 35 years [interquartile range, 28–49] and median disease duration of 12 [7–20] years were included. Dose intensification was performed after a median of 5.0 [2.8–9.0] months of ustekinumab treatment and was associated with corticosteroids and immunosuppressants in respectively 29% and 27% of cases. Short-term clinical response and clinical remission were observed in respectively 61% and 31% after a median of 2.4 [1.3–3.0] months. After a median follow-up of 8.2 [5.6–12.4] months, 61% of patients were still treated with ustekinumab, and 26% were in steroid-free clinical remission. Among the 39 patients with colonoscopy during follow-up, 14 achieved endoscopic remission [no ulcers]. At the end of follow-up, 27% of patients were hospitalized, and 19% underwent intestinal resection surgery. Adverse events were reported in 12% of patients, including five serious adverse events. Conclusion: In this multicentre study, two-thirds of patients recaptured response following treatment intensification with ustekinumab 90 mg every 4 weeks.

Therapeutic drug monitoring involves therapeutic modifications based on the measurement of drug levels and antidrug antibodies. The viability of therapeutic drug monitoring in vedolizumab-treated patients with inflammatory bowel disease remains questioned. Accumulating evidence from clinical trials and real-world data suggests that an exposure–efficacy relationship may exist for vedolizumab in inflammatory bowel disease, but results are not as straightforward as they are for anti-tumour necrosis factor-α therapy. Robust target vedolizumab trough levels are currently missing, since available data are heterogenous and prospective, interventional pharmacokinetic–pharmacodynamic studies are lacking. The positioning of vedolizumab drug monitoring in therapeutic algorithms is yet to be defined. Therapeutic drug monitoring has the potential to improve the outcome parameters of vedolizumab-treated patients with inflammatory bowel disease. Before the therapeutic drug monitoring of vedolizumab can be implemented in a widespread fashion, prospective studies are needed to evaluate the effect of vedolizumab dose optimisation. These studies should focus on objective disease markers and vedolizumab drug levels, and define thresholds for optimal drug exposure.

Background and Aims: Treating beyond endoscopic remission, aiming for histological remission, is an emerging target in ulcerative colitis [UC]. Patient-reported outcome measurements [PROMs] become increasingly important, but their association with histology is unclear. Methods: Multiple PROMs were prospectively collected in UC patients undergoing colonoscopy. Mayo endoscopic sub-score [MES] and ulcerative colitis endoscopic index of severity [UCEIS] were determined, as well as the Nancy histological index [NHI] of the most affected area. Endoscopic remission was defined as MES and UCEIS 0, histological remission as NHI 0, and histo-endoscopic mucosal remission [HEMR] as a combination of both. Results: A total of 109 assessments were collected in 80 patients with endoscopic and HEMR remission rates of 24.8% and 16.5%, respectively. Patients with HEMR had a significantly lower overall inflammatory bowel disease [IBD] disability [p <0.001] and disease activity score [p <0.001] as compared with patients without. In line, NHI correlated with the overall IBD-disk [r = 0.36, p <0.001] and simple clinical colitis activity index [SCCAI] score [r = 0.44, p <0.001]. Many individual components of both differed significantly between patients with and without HEMR. Although the overall accuracy of the IBD-disk [0.78] or SCCAI score [0.83] for HEMR is lower [p 35.5 and an SSCAI score >3.5 have a high negative predictive value [98.6% and 100.0%, respectively] to exclude HEMR. Conclusion: Histo-endoscopic inactive disease is associated with reduced IBD disability, but not with complete absence thereof. PROMs for disability and clinical disease activity cannot fully replace histo-endoscopic findings, and should be considered complementary in patient-centred endpoint discussions. Nevertheless, PROMs have a high negative predictive value to rule out HEMR.