Examining breast cancer screening recommendations in Canada: The projected resource impact of screening among women aged 40-49.

OBJECTIVE: To quantify the resource use of revising breast cancer screening guidelines to include average-risk women aged 40-49 years across Canada from 2024 to 2043 using a validated microsimulation model. SETTING: OncoSim-Breast microsimulation platform was used to simulate the entire Canadian population in 2015-2051. METHODS: We compared resource use between current screening guidelines (biennial screening ages 50-74) and alternate screening scenarios, which included annual and biennial screening for ages 40-49 and ages 45-49, followed by biennial screening ages 50-74. We estimated absolute and relative differences in number of screens, abnormal screening recalls without cancer, total and negative biopsies, screen-detected cancers, stage of diagnosis, and breast cancer deaths averted. RESULTS: Compared with current guidelines in Canada, the most intensive screening scenario (annual screening ages 40-49) would result in 13.3% increases in the number of screens and abnormal screening recalls without cancer whereas the least intensive scenario (biennial screening ages 45-49) would result in a 3.4% increase in number of screens and 3.8% increase in number of abnormal screening recalls without cancer. More intensive screening would be associated with fewer stage II, III, and IV diagnoses, and more breast cancer deaths averted. CONCLUSIONS: Revising breast cancer screening in Canada to include average-risk women aged 40-49 would detect cancers earlier leading to fewer breast cancer deaths. To realize this potential clinical benefit, a considerable increase in screening resources would be required in terms of number of screens and screen follow-ups. Further economic analyses are required to fully understand cost and budget implications.

Age-specific colorectal cancer incidence trends in Canada, 1971-2021.

INTRODUCTION: Colorectal cancer (CRC) incidence among adults younger than 50 years has increased in recent decades, leading to some advocating for lowering the age to start CRC screening. Here, we estimate age-specific trends in CRC incidence in Canada and changes in risk by birth cohort. METHODS: CRC incidence data from 1971 to 2021 by province, sex, and five-year age group (35-64) were obtained from the National Cancer Incidence Reporting System and the Canadian Cancer Registry. Annual percent changes in age-specific or age-adjusted incidence rates were analyzed with joinpoint regression. Birth cohort effect was estimated with age-period-cohort models and reported as cohort incidence rate ratios (IRRs) with respect to the 1947-51 cohort. RESULTS: CRC incidence has increased among all age groups under 50 years, with the largest relative increases occurring in the youngest age group (35-39 years). Males and females had similar incidence trends, though males under age 50 had larger increases than females. The birth cohort analysis showed that males born since 1966 have a significantly higher risk than those born at any other time. CONCLUSIONS: These results up to 2021 confirm and update reports that CRC incidence is increasing among adults under age 50 in Canada and that the youngest birth cohorts carry the highest risk. Future studies should assess the effectiveness of CRC screening in younger populations.

Body mass index and the prevalence of high-risk colorectal adenomas in a population undergoing screening colonoscopy in Alberta, Canada.

PURPOSE: There is limited evidence regarding body mass index (BMI) as an early marker of high-risk adenoma (HRA) at the time of screening colonoscopy. Because high-risk adenomas (HRA) can develop into colorectal cancer (CRC), BMI could serve as an important clinical predictor of future risk of CRC. METHODS: We examined data from 1831 adults undergoing screening colonoscopy at the Forzani & MacPhail Colon Cancer Screening Center in Alberta, Canada. We fit multivariable logistic regression models to examine the association between BMI and HRA. Non-linear relationships for BMI on HRA were also evaluated using restricted cubic splines. RESULTS: The mean BMI in patients with HRA was 28.2 kg/m2 compared to 27.4 kg/m2 in patients without adenomas (t test: p = 0.003). In the adjusted models, those with a BMI over 30 kg/m2 had 1.45 (95% CI 1.05-2.00) times the odds of HRA detected during colonoscopy compared to those with a BMI below 25 kg/m2. Examining BMI as continuous, the odds of HRA were 1.20 (95% CI 1.04-1.37) times higher for every 5 kg/m2 increase in BMI. CONCLUSION: The findings of this study suggest that excess body mass is associated with higher risk of HRA among a screening population and may be useful an early marker of future disease.

Examining external control arms in oncology: A scoping review of applications to date.

OBJECTIVES: Randomized controlled trials (RCTs) are the gold standard for evaluating the comparative efficacy and safety of new cancer therapies. However, enrolling patients in control arms of clinical trials can be challenging for rare cancers, particularly in the context of precision oncology and targeted therapies. External Control Arms (ECAs) are a potential solution to address these challenges in clinical research design. We conducted a scoping review to explore the use of ECAs in oncology. METHODS: We systematically searched four databases, namely MEDLINE, EMBASE, Web of Science, and Scopus. We screened titles, abstracts, and full texts for eligible articles focusing on patients undergoing therapy for cancer, employing ECAs, and reporting clinical outcomes. RESULTS: Of the 629 articles screened, 23 were included in this review. The earliest included studies were published in 1996, while most studies were published in the past 5 years. 44% (10/23) of ECAs were employed in blood-related cancer studies. Geographically, 30% (7/23) of studies were conducted in the United States, 22% (5/23) in Japan, and 9% (2/23) in South Korea. The primary data sources used to construct the ECAs involved pooled data from previous trials (35%, 8/23), administrative health databases (17%, 4/23) and electronic medical records (17%, 4/23). While 52% (12/23) of the studies employed methods to align treatment and ECAs characteristics, 48% (11/23) lacked explicit strategies. CONCLUSION: ECAs offer a valuable approach in oncology research, particularly when alternative designs are not feasible. However, careful methodological planning and detailed reporting are essential for meaningful and reliable results.

Incidence, Predictors, and Outcomes of Clinically Significant Post-ERCP Bleeding: a Contemporary Multi-center Study.

BACKGROUND AIMS: Clinically significant post-endoscopic retrograde cholangiopancreatography (ERCP) bleeding (CSPEB) is common. Contemporary estimates of risk are lacking. We aimed to identify risk factors for and outcomes following CSPEB. METHODS: We analyzed multi-center prospective ERCP data between 2018-2023 with 30-day follow-up. The primary outcome was CSPEB, defined as hematemesis, melena, or hematochezia resulting in: hemoglobin drop ≥20 g/L or transfusion and/or endoscopy to evaluate suspected bleeding, and/or unplanned healthcare visitation and/or prolongation of existing admission. Firth logistic regression was employed. P-values <0.05 were significant, with odds ratios (ORs) and 95% confidence intervals reported. RESULTS: CSPEB occurred following 129 (1.5%) of 8,517 ERCPs (mean onset 3.2 days), with 110 of 4,849 events (2.3%) occurring following higher-risk interventions (sphincterotomy, sphincteroplasty, pre-cut sphincterotomy, and/or needle-knife access). CSPEB patients required endoscopy and transfusion in 86.0% and 53.5% of cases, respectively, with three cases (2.3%) being fatal. P2Y12 inhibitors were held for a median of 4 days (IQR 4) prior to higher-risk ERCP. Following higher-risk interventions, P2Y12 inhibitors (OR 3.33, 1.26-7.74), warfarin (OR 8.54, 3.32-19.81), dabigatran (OR 13.40, 2.06-59.96), rivaroxaban (OR 7.42, 3.43-15.24) and apixaban (OR 4.16, 1.99-8.20) were associated with CSPEB. Significant intraprocedural bleeding post sphincterotomy (OR 2.32, 1.06-4.60), but not post sphincteroplasty, was also associated. Concomitant cardiorespiratory events occurred more frequently within 30 days following CSPEB (OR 12.71, 4.75-32.54). CONCLUSIONS: Risks of antiplatelet-related CSPEB may be underestimated by endoscopists based on observations of suboptimal holding before higher-risk ERCP. Appropriate periprocedural antithrombotic management is essential and could represent novel quality initiative targets.

Projection du fardeau du cancer au Canada en 2024.

CONTEXTE: Les données de surveillance du cancer sont essentielles pour mieux comprendre les lacunes et les progrès réalisés dans la lutte contre le cancer. Nous avons cherché à résumer les répercussions prévues du cancer au Canada en 2024, en effectuant des projections sur les nouveaux cas de cancer et les décès par cancer, par sexe et par province ou territoire, pour tous les âges confondus. MÉTHODES: Nous avons obtenu les données sur les nouveaux cas de cancer (c.-à-d., l'incidence, 1984­2019) et les décès par cancer (c.-à-d., la mortalité, 1984­2020) du Registre canadien du cancer et de la Base canadienne de données de l'état civil ­ Décès, respectivement. Nous avons projeté les chiffres et les taux d'incidence du cancer et de mortalité jusqu'en 2024 pour 23 types de cancer, par sexe et par province ou territoire. Nous avons calculé des taux normalisés selon l'âge au moyen de données de la population type canadienne de 2011. RÉSULTATS: En 2024, les nombres de nouveaux cas de cancer et de décès causés par le cancer devraient atteindre 247 100 et 88 100, respectivement. Le taux d'incidence normalisé selon l'âge (TINA) et le taux de mortalité normalisé selon l'âge (TMNA) devraient diminuer légèrement par rapport aux années précédentes, tant chez les hommes que chez les femmes, avec des taux plus élevés chez les hommes (TINA de 562,2 pour 100 000, et TMNA de 209,6 pour 100 000 chez les hommes; TINA de 495,9 pour 100 000 et TMNA de 152,8 pour 100 000 chez les femmes). Les TINA et les TMNA de plusieurs cancers courants devraient continuer à diminuer (p. ex., cancer du poumon, cancer colorectal et cancer de la prostate), tandis que ceux de plusieurs autres cancers devraient augmenter (p. ex., cancer du foie et des voies biliaires intrahépatiques, cancer du rein, mélanome et lymphome non hodgkinien). INTERPRÉTATION: Bien que l'incidence globale du cancer et la mortalité connexe sont en déclin, il devrait y avoir une augmentation des nouveaux cas et des décès au Canada en 2024, en grande partie en raison de la croissance et du vieillissement de la population. Les efforts en matière de prévention, de dépistage et de traitement ont atténué les répercussions de certains cancers, mais ces projections à court terme soulignent l'effet potentiel du cancer sur les gens et les systèmes de soins de santé au Canada.

Projected estimates of cancer in Canada in 2024.

BACKGROUND: Cancer surveillance data are essential to help understand where gaps exist and progress is being made in cancer control. We sought to summarize the expected impact of cancer in Canada in 2024, with projections of new cancer cases and deaths from cancer by sex and province or territory for all ages combined. METHODS: We obtained data on new cancer cases (i.e., incidence, 1984-2019) and deaths from cancer (i.e., mortality, 1984-2020) from the Canadian Cancer Registry and Canadian Vital Statistics Death Database, respectively. We projected cancer incidence and mortality counts and rates to 2024 for 23 types of cancer, overall, by sex, and by province or territory. We calculated age-standardized rates using data from the 2011 Canadian standard population. RESULTS: In 2024, the number of new cancer cases and deaths from cancer are expected to reach 247 100 and 88 100, respectively. The age-standardized incidence rate (ASIR) and mortality rate (ASMR) are projected to decrease slightly from previous years for both males and females, with higher rates among males (ASIR 562.2 per 100 000 and ASMR 209.6 per 100 000 among males; ASIR 495.9 per 100 000 and ASMR 152.8 per 100 000 among females). The ASIRs and ASMRs of several common cancers are projected to continue to decrease (i.e., lung, colorectal, and prostate cancer), while those of several others are projected to increase (i.e., liver and intrahepatic bile duct cancer, kidney cancer, melanoma, and non-Hodgkin lymphoma). INTERPRETATION: Although the overall incidence of cancer and associated mortality are declining, new cases and deaths in Canada are expected to increase in 2024, largely because of the growing and aging population. Efforts in prevention, screening, and treatment have reduced the impact of some cancers, but these short-term projections highlight the potential effect of cancer on people and health care systems in Canada.

Risk factors for early-onset colorectal cancer: A Canadian prospective cohort study.

PURPOSE: The incidence of early-onset (<50 years of age) colorectal cancer (eoCRC) has been steadily increasing in high-income countries including Canada. Despite this increase in incidence, the etiology of eoCRC remains unclear and prospective cohort studies of potential risk factors are limited. METHODS: We examined two prospective cohorts of healthy individuals (<50 years of age) who completed baseline questionnaires in the Ontario Health Study and Alberta's Tomorrow Project. We examined the associations between demographic characteristics, chronic health conditions, and lifestyle behaviours with the development of eoCRC using Cox proportional hazard models. Cohorts were analyzed separately and hazard ratios for each risk factor were pooled with random effects meta-analyses. RESULTS: During an average follow-up of 6.63 years, 98 eoCRC cases occurred among study participants (n=127,852). A family history of CRC alone or with a history of other cancer types was associated with an increased risk of developing eoCRC (HR: 2.76, 95% CI: 1.43-5.32), but a family history of a non-CRC cancer only was not (HR: 1.18, 95% CI: 0.61-2.30). Heavy smokers (≥ 10 pack-years) at baseline had a higher risk of eoCRC compared to non-smokers (HR: 1.87, 95% CI: 1.00-3.52). Sex, socioeconomic factors, diabetes, alcohol consumption, among other factors were not significantly associated with the risk of eoCRC. CONCLUSION: Our findings indicate that specific CRC risk factors are also associated with developing eoCRC. The data in the study offers valuable insights that could be integrated in future meta-analyses. Additional prospective cohort studies are required to understand the etiology of eoCRC.

The Association between Mutational Signatures and Clinical Outcomes among Patients with Early-Onset Breast Cancer.

Early-onset breast cancer (EoBC), defined by a diagnosis <40 years of age, is associated with poor prognosis. This study investigated the mutational landscape of non-metastatic EoBC and the prognostic relevance of mutational signatures using 100 tumour samples from Alberta, Canada. The MutationalPatterns package in R/Bioconductor was used to extract de novo single-base substitution (SBS) and insertion-deletion (indel) mutational signatures and to fit COSMIC SBS and indel signatures. We assessed associations between these signatures and clinical characteristics of disease, in addition to recurrence-free (RFS) and overall survival (OS). Five SBS and two indel signatures were extracted. The SBS13-like signature had higher relative contributions in the HER2-enriched subtype. Patients with higher than median contribution tended to have better RFS after adjustment for other prognostic factors (HR = 0.29; 95% CI: 0.08-1.06). An unsupervised clustering algorithm based on absolute contribution revealed three clusters of fitted COSMIC SBS signatures, but cluster membership was not associated with clinical variables or survival outcomes. The results of this exploratory study reveal various SBS and indel signatures may be associated with clinical features of disease and prognosis. Future studies with larger samples are required to better understand the mechanistic underpinnings of disease progression and treatment response in EoBC.

Plecanatide Improves Abdominal Bloating and Bowel Symptoms of Irritable Bowel Syndrome with Constipation.

BACKGROUND: Bloating is a bothersome symptom in irritable bowel syndrome with constipation (IBS-C). AIM: To evaluate plecanatide efficacy in patients with IBS-C stratified by bloating intensity. METHODS: Pooled phase 3 data (2 randomized, controlled IBS-C trials) from adults treated with plecanatide 3 mg or placebo for 12 weeks were analyzed. Patients were stratified post-hoc by baseline bloating severity (11-point scale: mild [≤ 5] and moderate-to-severe [> 5]). Assessments included change from baseline in bloating, abdominal pain, and complete spontaneous bowel movement (CSBM) frequency. Abdominal pain and bloating composite responders were defined as patients with ≥ 30% improvement from baseline in both bloating and abdominal pain at Week 12. RESULTS: At baseline, 1104/1436 patients with IBS-C (76.9%) reported moderate-to-severe bloating. In the moderate-to-severe bloating subgroup, plecanatide significantly reduced bloating severity versus placebo (least-squares mean change [LSMC]: - 1.7 vs - 1.3; P = 0.002), reduced abdominal pain (- 1.7 vs - 1.3; P = 0.006), and increased CSBM frequency (1.4 vs 0.8; P < 0.0001). In the mild bloating subgroup, significant improvements were observed with plecanatide versus placebo for abdominal pain (LSMC: - 1.3 vs - 1.0; P = 0.046) and CSBM frequency (2.0 vs 1.2; P = 0.003) but not bloating (- 0.9 vs - 0.8; P = 0.28). A significantly greater percentage of patients were abdominal pain and bloating composite responders with plecanatide versus placebo (moderate-to-severe bloating: 33.6% vs 26.8% [P = 0.02]; mild bloating: 38.4% vs 27.2% [P = 0.03]). CONCLUSION: Plecanatide treatment improved IBS-C abdominal and bowel symptoms, including in those who present with moderate-to-severe bloating.

The projected health and economic impact of increased colorectal cancer screening participation among Canadians by income quintile.

OBJECTIVES: Disparities in colorectal cancer (CRC) screening uptake by socioeconomic status have been observed in Canada. We used the OncoSim-Colorectal model to evaluate the health and economic outcomes associated with increasing the participation rates of CRC screening programs to 60% among Canadians in different income quintiles. METHODS: Baseline CRC screening participation rates were obtained from the 2017 Canadian Community Health Survey. The survey participants were categorized into income quintiles using their reported household income and 2016 Canadian Census income quintile thresholds. Within each quintile, the participation rate was the proportion of respondents aged 50-74 who reported having had a fecal test in the past two years. Using the OncoSim-Colorectal model, we simulated an increase in CRC screening uptake to 60% across income quintiles to assess the effects on CRC incidence, mortality, and associated economic costs from 2024 to 2073. RESULTS: Increasing CRC screening participation rates to 60% across all income quintiles would prevent 69,100 CRC cases and 36,600 CRC deaths over 50 years. The improvement of clinical outcomes would also translate to increased person-years and health-adjusted person-years. The largest impact was observed in the lowest income group, with 22,200 cases and 11,700 deaths prevented over 50 years. Increased participation could lead to higher screening costs ($121 million CAD more per year) and lower treatments costs ($95 million CAD less per year), averaged over the period 2024-2073. CONCLUSION: Increased screening participation will improve clinical outcomes across all income groups while alleviating associated treatment costs. The benefits of increased participation will be strongest among the lowest income quintile.

RéSUMé: OBJECTIFS: Des disparités dans le recours au dépistage du cancer colorectal (CCR) selon le statut socioéconomique sont observées au Canada. Nous avons utilisé le modèle OncoSim-Colorectal pour évaluer les résultats cliniques et économiques associés à une augmentation à 60 % des taux de participation aux programmes de dépistage du CCR chez les Canadiennes et les Canadiens appartenant à différents quintiles de revenu. MéTHODE: Les taux de participation de référence au dépistage du CCR provenaient de l'Enquête sur la santé dans les collectivités canadiennes de 2017. Nous avons catégorisé les participantes et les participants de l'enquête en quintiles de revenu à l'aide du revenu du ménage déclaré et des seuils de quintiles de revenu du Recensement du Canada de 2016. Dans chaque quintile, le taux de participation était la proportion des répondantes et des répondants de 50 à 74 ans ayant dit avoir subi un test fécal au cours des deux années antérieures. À l'aide du modèle OncoSim-Colorectal, nous avons simulé une augmentation à 60 % du recours au dépistage du CCR dans tous les quintiles de revenu pour en évaluer les effets sur l'incidence, la mortalité et les coûts économiques associés du CCR entre 2024 et 2073. RéSULTATS: L'augmentation des taux de participation au dépistage du CCR à 60 % dans tous les quintiles de revenu préviendrait 69 100 cas de CCR et 36 600 décès dus au CCR sur 50 ans. L'amélioration des résultats cliniques se traduirait aussi par une augmentation des personnes-années et des personnes-années corrigées en fonction de la santé. Nous avons observé l'effet le plus marquant dans la catégorie de revenu inférieure, avec la prévention de 22 200 cas et de 11 700 décès sur 50 ans. La participation accrue pourrait entraîner une hausse des coûts de dépistage (121 millions de dollars canadiens de plus par année) et une baisse des coûts de traitement (95 millions de dollars canadiens de moins par année), en moyenne, sur la période de 2024 à 2073. CONCLUSION: La participation accrue au dépistage améliorera les résultats cliniques dans toutes les catégories de revenu tout en réduisant les coûts de traitement associés. Les avantages d'une participation accrue seront les plus marquants dans le quintile de revenu inférieur.

Relative Efficacies of Interventions to Improve the Quality of Screening-Related Colonoscopy: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND & AIMS: Significant variability exists in colonoscopy quality indicators, including adenoma detection rate (ADR). We synthesized evidence from randomized trials in a network meta-analysis on interventions to improve colonoscopy quality. METHODS: We included trials from database inceptions to September 25, 2023, of patients undergoing screening-related colonoscopy and presented efficacies of interventions within domains (periprocedural parameters, endoscopist-directed interventions, intraprocedural techniques, endoscopic technologies, distal attachment devices, and additive substances) compared to standard colonoscopy. The primary outcome was ADR. We used a Bayesian random-effects model using Markov-chain Monte Carlo simulation, with 10,000 burn-ins and 100,000 iterations. We calculated odds ratios with 95% credible intervals and present surface under the cumulative ranking (SUCRA) curves. RESULTS: We included 124 trials evaluating 37 interventions for the primary outcome. Nine interventions resulted in statistically significant improvements in ADR compared to standard colonoscopy (9-minute withdrawal time, dual observation, water exchange, i-SCAN [Pentax Ltd], linked color imaging, computer-aided detection, Endocuff [Olympus Corp], Endocuff Vision [Olympus Corp], and oral methylene blue). Dual observation (SUCRA, 0.84) and water exchange (SUCRA, 0.78) ranked highest among intraprocedural techniques; i-SCAN (SUCRA, 0.95), linked color imaging (SUCRA, 0.85), and computer-aided detection (SUCRA, 0.78) among endoscopic technologies; WingCap (A&A Medical Supply LLC) (SUCRA, 0.87) and Endocuff (SUCRA, 0.85) among distal attachment devices and oral methylene blue (SUCRA, 0.94) among additive substances. No interventions improved detection of advanced adenomas, and only narrow-band imaging improved detection of serrated lesions (odds ratio, 2.94; 95% credible interval, 1.46-6.25). CONCLUSIONS: Several interventions are effective in improving adenoma detection and overall colonoscopy quality, many of which are cost-free. These results can inform endoscopists, unit managers, and endoscopy societies on relative efficacies.

Overview of the Engagement Process to Develop the Future of Cancer Impact (FOCI) Report in Alberta: The Power of Collective Action.

This commentary provides a detailed overview of the extensive stakeholder engagement efforts critical to the development of the Future of Cancer Impact (FOCI) in Alberta report. The overarching aim of the FOCI report was to support informed and strategic discussions and actions that will help key stakeholders in the province prepare for a future with increasing cancer incidence and survival. Employing a comprehensive approach and a diverse range of engagement activities, insights from a wide spectrum of stakeholders were gathered and subsequently used to shape the content of the report. This inclusive process ensured broad representation of perspectives, contributing to a deeper understanding of the complexities in cancer care. The outcome is a robust, consensus-driven report with recommendations set to drive significant transformations within the healthcare system. These efforts highlight the critical role of extensive, inclusive, and collaborative engagement in shaping healthcare initiatives and advancing discussions crucial for the future of cancer care in Alberta.

Progress in site-specific cancer mortality in Canada over the last 70 years.

In Canada, the absolute number of cancer deaths has been steadily increasing, however, age-standardized cancer mortality rates peaked decades ago for most cancers. The objective of this study was to estimate the reduction in deaths for each cancer type under the scenario where peak mortality rates had remained stable in Canada. Data for this study were obtained the Global Cancer Observatory and Statistics Canada. We estimated age-standardized mortality rates (ASMR, per 100,000) from 1950 to 2022, standardized to the 2011 Canadian standard population. We identified peak mortality rates and applied the age-specific mortality rates from the peak year to the age-specific Canadian population estimates for subsequent years (up to 2022) to estimate the number of expected deaths. Avoided cancer deaths were the difference between the observed and expected number of cancer deaths. There have been major reductions in deaths among cancers related to tobacco consumption and other modifiable lifestyle habits (417,561 stomach; 218,244 colorectal; 186,553 lung; 66,281 cervix; 32,732 head and neck; 27,713 bladder; 22,464 leukemia; 20,428 pancreas; 8863 kidney; 3876 esophagus; 290 liver). There have been 201,979 deaths avoided for female-specific cancers (breast, cervix, ovary, uterus). Overall, there has been a 34% reduction in mortality for lung cancer among males and a 9% reduction among females. There has been a significant reduction in cancer mortality in Canada since site-specific cancer mortality rates peaked decades ago for many cancers. This shows the exceptional progress made in cancer control in Canada due to substantial improvements in prevention, screening, and treatment. This study highlights priority areas where more attention and investment are needed to achieve progress.

Development and validation of a practical clinical risk prediction model for post-endoscopic retrograde cholangiopancreatography pancreatitis.

Background: Pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP) can lead to significant morbidity and mortality. We aimed to develop an accurate post-ERCP pancreatitis risk prediction model using easily obtainable variables. Methods: Using prospective multi-center ERCP data, we performed logistic regression using stepwise selection on several patient-, procedure-, and endoscopist-related factors that were determined a priori. The final model was based on a combination of the Bayesian information criterion and Akaike's information criterion performance, balancing the inclusion of clinically relevant variables and model parsimony. All available data were used for model development, with subsequent internal validation performed on bootstrapped data using 10-fold cross-validation. Results: Data from 3021 ERCPs were used to inform models. There were 151 cases of post-ERCP pancreatitis (5.0% incidence). Variables included in the final model included female sex, pancreatic duct cannulation, native papilla status, pre-cut sphincterotomy, increasing cannulation time, presence of biliary stricture, patient age, and placement of a pancreatic duct stent. The final model was discriminating, with a receiver operating characteristic curve statistic of 0.79, and well-calibrated, with a predicted risk-to-observed risk ratio of 1.003. Conclusions: We successfully developed and internally validated a promising post-ERCP pancreatitis clinical prediction model using easily obtainable variables that are known at baseline or observed during the ERCP procedure. The model achieved an area under the curve of 0.79. External validation is planned as additional data becomes available.

Next Generation Weight Loss Drugs for the Prevention of Cancer?

Background: Western populations are losing the battle over healthy weight management, and excess body weight is a notable cancer risk factor at the population level. There is ongoing interest in pharmacological interventions aimed at promoting weight loss, including GLP-1 receptor agonists (GLP-1RA), which may be a useful tool to stem the rising tide of obesity-related cancers. Purpose: To investigate the potential of next generation weight loss drugs (NGWLD) like GLP-1RA in population-level chemoprevention.Research Design: We used the OncoSim microsimulation tool to estimate the population-level reductions in obesity and the potentially avoidable obesity-related cancers in Canada over the next 25 years.Results: We estimated a total of 71 281 preventable cancers by 2049, with 36 235 and 35 046 cancers prevented for females and males, respectively. Among the 327 254 total projected cancer cases in 2049, 1.3% are estimated to be preventable through intervention with NGWLD.Conclusions: Pharmacologic intervention is not the ideal solution for the obesity-related cancer crisis. However, these agents and subsequent generations provide an additional tool to rapidly reduce body weight and adiposity in populations that have been extremely challenging to reduce weight with standard diet and exercise approaches. Additional research is needed around approaches to prevent initial weight gain and maintain long-term weight loss.

Association between time to colonoscopy after positive fecal testing and colorectal cancer outcomes in Alberta, Canada.

OBJECTIVE: To quantify the associations between time to colonoscopy after a positive fecal immunochemical test (FIT+) and colorectal cancer (CRC)-related outcomes in the context of a provincial, population-based CRC screening program. SETTING: Population-based, retrospective cohort study in Alberta, Canada, including Albertans aged 50-74 with at least one FIT+ in 2014-2017. METHODS: Study outcomes were CRC diagnosis after a FIT+ and a diagnostic follow-up colonoscopy in 2014-2019 and CRC stage at diagnosis. Multivariable logistic regression models were used to evaluate the relative risk of any CRC or advanced-stage CRC. Results were presented as crude odds ratio (OR) and adjusted OR (aOR) with 95% confidence intervals (CIs). RESULTS: Of the 787,967 participants who had a FIT, 63,232 (8%) had a FIT+ and met the study's eligibility criteria. The risk of any CRC or advanced-stage CRC stayed high and was relatively consistent for follow-up colonoscopies performed within 1-12 months of the FIT+. After 12 months, the risk of CRC was considerably higher, particularly for advanced-stage CRC. The OR and aOR for any CRC were 1.40 (95% CI: 1.13-1.73; p < 0.05) and 1.20 (95% CI: 0.96-1.49), respectively, and the OR and aOR for advanced-stage CRC were 1.42 (95% CI: 0.98-2.08) and 0.88 (95% CI: 0.59-1.32), respectively, for colonoscopy follow-up within 12-18 months versus 1-2 months. CONCLUSIONS: For Albertans who used FIT for CRC screening, a longer time interval between a FIT+ and follow-up colonoscopy, particularly over 12 months, increases the risk of having CRC and decreases the effectiveness of CRC screening programs.

Adjuvant Ovarian Function Suppression in Premenopausal Hormone Receptor-Positive Breast Cancer.

Importance: Few oncology studies have assessed the effectiveness of adjuvant ovarian function suppression (OFS) in observational settings for premenopausal hormone receptor-positive breast cancer. Target trial emulation is increasingly used for estimating treatment outcomes in observational cohorts. Objectives: To describe hormone therapy and OFS treatment patterns (aim 1), examine the association between adding OFS to tamoxifen (TAM) or aromatase inhibitor (AI) and survival (aim 2), and examine the association between duration of hormone treatment (TAM or AI) plus OFS (H-OFS) and survival (aim 3). Design, Setting, and Participants: This population-based cohort study included all premenopausal, early-stage breast cancer diagnoses between 2010 and 2020 in Alberta, Canada. Target trial emulation was conducted. Eligibility criteria were directly modeled after the Suppression of Ovarian Function Trial (SOFT) and Tamoxifen and Exemestane Trial (TEXT). Participants were followed up for a maximum of 5 years. Data were analyzed from July 2022 through March 2023. Exposures: For aim 2, exposures were receiving the following baseline treatments for 2 years: AI + OFS (AI-OFS), TAM + OFS (T-OFS), and TAM alone. For aim 3, exposures were a 2-year or greater and a less than 2-year duration of H-OFS. Main Outcomes and Measures: Recurrence-free survival was the primary outcome of interest. Marginal structural Cox models with inverse probability treatment and censoring weights were used to estimate hazard ratios (HRs), adjusted for baseline and time-varying confounding variables. Results: Among 3434 female patients with premenopausal, early-stage breast cancer diagnoses (median [IQR] age, 45 [40-48] years), 2647 individuals satisfied SOFT and TEXT eligibility criteria. There were 2260 patients who initiated TAM, 232 patients who initiated T-OFS, and 155 patients who initiated AI-OFS; 192 patients received H-OFS for 2 or more years, and 195 patients received H-OFS for less than 2 years. The 5-year recurrence risks were not significantly lower in AI-OFS vs TAM (HR, 0.76; 95% CI, 0.38-1.33) or T-OFS vs TAM (HR, 0.87; 95% CI, 0.50-1.45) groups. Patients receiving H-OFS for 2 or more years had significantly better 5-year recurrence-free survival compared with those receiving H-OFS for less than 2 years (HR, 0.69; 95% CI, 0.54-0.90). Conclusions and Relevance: This study found no significant reductions in recurrence risk for AI-OFS and T-OFS compared with TAM alone. H-OFS duration for at least 2 years was associated with significantly improved recurrence-free survival.