Digital spatial profiling identifies molecular changes involved in development of colitis-associated colorectal cancer

ObjectiveChronic colonic inflammation seen in inflammatory bowel disease (IBD) is a risk factor for colorectal cancer (CRC). Colitis-associated cancers (CAC) are molecularly different from sporadic CRC. This study aimed to evaluate spatially defined molecular changes associated with neoplastic progression to identify mechanisms of action and potential biomarkers for prognostication.DesignIBD patients who had undergone colectomy for treatment of their IBD or dysplasia were identified from an institutional database. Formalin-fixed paraffin embedded samples from areas of normal, inflamed, dysplastic and adenocarcinoma tissue were identified for digital spatial profiling using the Nanostring GeoMx™ Cancer Transcriptome Atlas. RNA expression and quantification of 1812 genes was measured and analysed in a spatial context to compare differences in gene expression.ResultsSixteen patients were included, nine patients had CAC, two had dysplasia only and five had colitis only. Significant, step-wise differences in gene expression were seen between tissue types, mainly involving progressive over-expression of collagen genes associated with stromal remodelling. Similarly, MYC over-expression was associated with neoplastic progression. Comparison of normal and inflamed tissue from patients who progressed to those who did not also showed significant differences in immune-related genes, including under-expression of thte chemokines CCL18, CCL25 and IL-R7, as well as CD3, CD6 and lysozyme. The known oncogene CD24 was significantly overexpressed.ConclusionBoth tissue types and patient groups are molecularly distinguishable on the basis of their gene expression patterns. Further prospective work is necessary to confirm these differences and establish their clinical significance and potential utility as biomarkers

A Systematic Review and Meta-Analysis of Patient Decision Aids for Socially Disadvantaged Populations:Update from the International Patient Decision Aid Standards (IDPAS)

International audienceBackground. The effectiveness of patient decision aids (PtDAs) and other shared decision-making (SDM) interventions for socially disadvantaged populations has not been well studied. Purpose. To assess whether PtDAs and other SDM interventions improve outcomes or decrease health inequalities among socially disadvantaged populations and determine the critical features of successful interventions. Data Sources. MEDLINE, CINAHL, Cochrane, Psy-cINFO, and Web of Science from inception to October 2019. Cochrane systematic reviews on PtDAs. Study Selection. Randomized controlled trials of PtDAs and SDM interventions that included socially disadvantaged populations. Data Extraction. Independent double data extraction using a standardized form and the Template for Intervention Description and Replication checklist. Data Synthesis. Twenty-five PtDA and 13 other SDM intervention trials met our inclusion criteria. Compared with usual care, PtDAs improved knowledge (mean difference = 13.91, 95% confidence interval [CI] 9.01, 18.82 [I 2 = 96%]) and patient-clinician communication (relative risk = 1.62, 95% CI 1.42, 1.84 [I 2 = 0%]). PtDAs reduced decisional conflict (mean difference = 29.59; 95% CI 218.94, 20.24 [I 2 = 84%]) and the proportion undecided (relative risk = 0.39; 95% CI 0.28, 0.53 [I 2 = 75%]). PtDAs did not affect anxiety (standardized mean difference = 0.02, 95% CI 20.22, 0.26 [I 2 = 70%]). Only 1 trial looked at clinical outcomes (hemoglobin A1C). Five of the 12 PtDA studies that compared outcomes by disadvantaged standing found that outcomes improved more for socially disadvantaged participants. No evidence indicated which intervention characteristics were most effective. Results were similar for SDM intervention trials. Limitations. Sixteen PtDA studies had an overall unclear risk of bias. Heterogeneity was high for most outcomes. Most studies only had short-term follow-up. Conclusions. PtDAs led to better outcomes among socially disadvantaged populations but did not reduce health inequalities. We could not determine which intervention features were most effective

Post-Operative Functional Outcomes in Early Age Onset Rectal Cancer

Background: Impairment of bowel, urogenital and fertility-related function in patients treated for rectal cancer is common. While the rate of rectal cancer in the young (<50 years) is rising, there is little data on functional outcomes in this group. Methods: The REACCT international collaborative database was reviewed and data on eligible patients analysed. Inclusion criteria comprised patients with a histologically confirmed rectal cancer, <50 years of age at time of diagnosis and with documented follow-up including functional outcomes. Results: A total of 1428 (n=1428) patients met the eligibility criteria and were included in the final analysis. Metastatic disease was present at diagnosis in 13%. Of these, 40% received neoadjuvant therapy and 50% adjuvant chemotherapy. The incidence of post-operative major morbidity was 10%. A defunctioning stoma was placed for 621 patients (43%); 534 of these proceeded to elective restoration of bowel continuity. The median follow-up time was 42 months. Of this cohort, a total of 415 (29%) reported persistent impairment of functional outcomes, the most frequent of which was bowel dysfunction (16%), followed by bladder dysfunction (7%), sexual dysfunction (4.5%) and infertility (1%). Conclusion: A substantial proportion of patients with early-onset rectal cancer who undergo surgery report persistent impairment of functional status. Patients should be involved in the discussion regarding their treatment options and potential impact on quality of life. Functional outcomes should be routinely recorded as part of follow up alongside oncological parameters

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Table_1_Digital spatial profiling identifies molecular changes involved in development of colitis-associated colorectal cancer.xlsx

ObjectiveChronic colonic inflammation seen in inflammatory bowel disease (IBD) is a risk factor for colorectal cancer (CRC). Colitis-associated cancers (CAC) are molecularly different from sporadic CRC. This study aimed to evaluate spatially defined molecular changes associated with neoplastic progression to identify mechanisms of action and potential biomarkers for prognostication.DesignIBD patients who had undergone colectomy for treatment of their IBD or dysplasia were identified from an institutional database. Formalin-fixed paraffin embedded samples from areas of normal, inflamed, dysplastic and adenocarcinoma tissue were identified for digital spatial profiling using the Nanostring GeoMx™ Cancer Transcriptome Atlas. RNA expression and quantification of 1812 genes was measured and analysed in a spatial context to compare differences in gene expression.ResultsSixteen patients were included, nine patients had CAC, two had dysplasia only and five had colitis only. Significant, step-wise differences in gene expression were seen between tissue types, mainly involving progressive over-expression of collagen genes associated with stromal remodelling. Similarly, MYC over-expression was associated with neoplastic progression. Comparison of normal and inflamed tissue from patients who progressed to those who did not also showed significant differences in immune-related genes, including under-expression of thte chemokines CCL18, CCL25 and IL-R7, as well as CD3, CD6 and lysozyme. The known oncogene CD24 was significantly overexpressed.ConclusionBoth tissue types and patient groups are molecularly distinguishable on the basis of their gene expression patterns. Further prospective work is necessary to confirm these differences and establish their clinical significance and potential utility as biomarkers.</p

Management of rectal cancer in the era of total neoadjuvant therapy and watch and wait: A multidisciplinary team discussion at the Australasian Gastro-Intestinal Trials Group (AGITG) Annual Scientific Meeting 2022.

Rectal cancer is a common malignancy. The management of rectal cancer has recently evolved and has undergone a paradigm shift with the advent of treatment approaches such as total neoadjuvant therapy and the watch-and-wait approach. However, despite the recently available evidence, there is no consensus on the optimal management approach in the setting of locally advanced rectal cancer. To address some of the controversies, a joint multidisciplinary panel discussion was conducted at the Australasian Gastro-Intestinal Trials Group (AGITG) Annual Scientific Meeting in November 2022. Members from different subspecialties formed two panels and discussed three clinical cases in a debate format. Each case represented some of the complex issues faced by clinicians in this setting. The discussion is now presented in this manuscript, which depicts the different available management approaches and reiterates the importance of a multidisciplinary approach

A Systematic Review and Meta-Analysis of Patient Decision Aids for Socially Disadvantaged Populations:Update from the International Patient Decision Aid Standards (IDPAS)

BACKGROUND: The effectiveness of patient decision aids (PtDAs) and other shared decision-making (SDM) interventions for socially disadvantaged populations has not been well studied.PURPOSE: To assess whether PtDAs and other SDM interventions improve outcomes or decrease health inequalities among socially disadvantaged populations and determine the critical features of successful interventions.DATA SOURCES: MEDLINE, CINAHL, Cochrane, PsycINFO, and Web of Science from inception to October 2019. Cochrane systematic reviews on PtDAs.STUDY SELECTION: Randomized controlled trials of PtDAs and SDM interventions that included socially disadvantaged populations.DATA EXTRACTION: Independent double data extraction using a standardized form and the Template for Intervention Description and Replication checklist.DATA SYNTHESIS: Twenty-five PtDA and 13 other SDM intervention trials met our inclusion criteria. Compared with usual care, PtDAs improved knowledge (mean difference = 13.91, 95% confidence interval [CI] 9.01, 18.82 [I2 = 96%]) and patient-clinician communication (relative risk = 1.62, 95% CI 1.42, 1.84 [I2 = 0%]). PtDAs reduced decisional conflict (mean difference = -9.59; 95% CI -18.94, -0.24 [I2 = 84%]) and the proportion undecided (relative risk = 0.39; 95% CI 0.28, 0.53 [I2 = 75%]). PtDAs did not affect anxiety (standardized mean difference = 0.02, 95% CI -0.22, 0.26 [I2 = 70%]). Only 1 trial looked at clinical outcomes (hemoglobin A1C). Five of the 12 PtDA studies that compared outcomes by disadvantaged standing found that outcomes improved more for socially disadvantaged participants. No evidence indicated which intervention characteristics were most effective. Results were similar for SDM intervention trials.LIMITATIONS: Sixteen PtDA studies had an overall unclear risk of bias. Heterogeneity was high for most outcomes. Most studies only had short-term follow-up.CONCLUSIONS: PtDAs led to better outcomes among socially disadvantaged populations but did not reduce health inequalities. We could not determine which intervention features were most effective.[Box: see text].</p

Long term outcomes of initial infliximab therapy for inflammatory pouch pathology:a multi-Centre retrospective study

Background: Restorative proctocolectomy with ileal pouch-anal anastomosis is considered the procedure of choice in patients with ulcerative colitis refractory to medical therapy. Subsequent inflammation of the pouch is a common complication and in some cases pouchitis fails to respond to antibiotics, the mainstay of treatment. In such cases, corticosteroids, immunomodulatory or biologic treatments are options. However, our understanding of the efficacy of anti-tumour necrosis factor medications in both chronic pouchitis and Crohn’s-like inflammation are based on studies that include relatively small numbers of patients. Methods: This was an observational, retrospective, multi-centre study to assess the long-term effectiveness and safety of infliximab for inflammatory disorders related to the ileoanal pouch. The primary outcome was the development of infliximab failure defined by early failure to infliximab or secondary loss of response to infliximab. Results: Thirty-four patients met the inclusion criteria; 18/34 (53%) who were initiated on infliximab for inflammatory disorders of the pouch had infliximab failure, 3/34 (8%) had early failure, and 15/34 (44%) had secondary loss of response with a median follow-up of 280 days (range 3-47 months). In total, 24/34 (71%) avoided an ileostomy by switching to other medical therapies at a median follow-up of follow-up of 366 days (1-130 months). Conclusions: Initial infliximab therapy for pouch inflammatory conditions is associated with Infliximab failure in just over half of all patients. Despite a high failure rate, an ileostomy can be avoided in almost three quarters of patients at four years by using other medical therapies