(1) Background: While prior data showed an increasing incidence of colorectal cancer (CRC) in young adults, the contribution of adenocarcinoma (ADC) and neuroendocrine tumors (NETs) to this trend is not well studied. Therefore, we conducted a comparative analysis of the incidence rates and time trends of colorectal ADC and NETs in young adults (aged 24–54) using the United States Cancer Statistics (USCS) database. (2) Methods: Age-adjusted CRC incidence rates between 2001 and 2020 were calculated and categorized by sex, histopathology, and stage at diagnosis. Annual percentage change (APC) and average APC (AAPC) were computed via joinpoint regression utilizing weighted Bayesian information criteria to generate the simplest trend. Pairwise comparative analysis of ADC and NETs was conducted using tests of identicalness and parallelism. (3) Results: In this study, 514,875 patients were diagnosed with early-onset-CRC between 2001 and 2020 (54.8% men). While CRC incidence was significantly increased, including both ADC (448,670 patients) and NETs (36,205 patients), a significantly greater increase was seen for NETs (AAPC = 2.65) compared to ADC (AAPC = 0.91), with AAPC difference = 1.73 (p = 0.01) and non-identical non-parallel trends (p-values < 0.001). This was most notable in males (AAPC difference = 1.81, p = 0.03) and for early-stage tumors (AAPC difference = 3.56, p < 0.001). (4) Conclusions: Our study, covering ~98% of the U.S. population provides the first comparative analysis of early-onset CRC histopathological subtypes, showing that the rate of increase of NETs in young adults is much greater than that of ADC. Given that patients with NETs with malignant behavior can experience significant mortality, our findings are importance, highlighting the rapidly increasing NET incidence in young adults and encouraging early screening that can improve outcomes.

Background: Colorectal cancer remains the second leading cause of cancer-related death in the US. As early-onset colorectal cancer (EO-CRC) becomes more prevalent in the US, research attention has shifted towards identifying at-risk populations. Previous studies have highlighted the rising rate of early-onset adenocarcinoma (ADC) and neuroendocrine tumors (NET) in the US. However, data on geographical variations of EO-CRC are scarce. Hence, our study aims to analyze time trends in EO-CRC incidence rates across various US regions and to assess these trends by sex and histopathological subtypes (ADC and NET). Methods: We analyze data spanning from 2001 to 2020 from the United States Cancer Statistics (USCS) database, covering nearly 98% of the US population. Using SEER*Stat software version (8.4.2, NCI), we calculated EO-CRC incidence rates among adults aged 20–54 years, adjusting for the age standard 2000 US population. The rates were categorized by sex and US geographical regions into west, midwest, northeast, and south. Time trends, reported as annual percentage change (APC) and average APC (AAPC), were generated via Joinpoint Regression software (v.5.0.2, NCI) utilizing the weighted Bayesian Information Criteria “BIC” method to generate the best-fit trends with a two-sided p-value cutoff at 0.05. The rates were also stratified by histopathology into ADC and NET. Results: Between 2001 and 2020, a total of 514,875 individuals were diagnosed with early-onset CRC in the US, with 54.78% being men. Incidence rates and trends varied across geographical regions. In the western region (comprising 106,685 patients, 54.85% men), incidence rates significantly increased in both women (AAPC = 1.37, p < 0.001) and men (AAPC = 1.34, p < 0.001). Similarly, in the midwestern region (with 110,380 patients, 55.46% men), there were significant increases in incidence rates among women (AAPC = 1.06, p < 0.001) and men (AAPC = 1.35, p < 0.001). The northeastern region (with 94,758 patients, 54.53% men) also witnessed significant increases in incidence rates for both women (AAPC = 0.71, p < 0.001) and men (AAPC = 0.84, p < 0.001). In contrast, the southern region (with 203,052 patients, 54.48% men) experienced slower increases in incidence rates among both women and men (AAPC = 0.25, p < 0.05 in women; AAPC = 0.66, p < 0.05 in men). When stratified by histopathology, incidence rates for adenocarcinomas (ADC) increased in all regions, most notably in the west (AAPC = 1.45, p < 0.05), and least in the south (AAPC = 0.46, p < 0.05). Conversely, for neuroendocrine tumors (NET), while incidence rates increased similarly across all regions, the pace was notably faster compared to ADC, particularly in the west (AAPC = 3.26, p < 0.05) and slower in the south (AAPC = 2.24, p < 0.05) Discussion: Our analysis of nationwide US data spanning two decades and encompassing over half a million early-onset CRC patients, representing nearly 98% of the US population, highlights significant temporal variation in incidence rates across various geographical regions. The most substantial increases in incidence rates were observed in the west, while the least pronounced changes were noted in the south, affecting both men and women. These trends persisted across the main CRC histopathological subtypes, with NET exhibiting a notably swifter pace of increase compared with ADC. These findings hold important implications for public health strategies and underscore the need for targeted interventions to address the rising burden of early-onset CRC across different regions in the US.

Background: Early-onset colorectal cancer (EOCRC), defined as diagnosis before age 50, is increasing despite declining colorectal cancer (CRC) rates among older adults. Emerging evidence suggests widening racial and ethnic disparities. We aimed to characterize long-term EOCRC incidence and mortality trends across racial and ethnic groups in the United States with comparisons by tumor subtype. Methods: We conducted a population-based analysis using United States Cancer Statistics data (2001–2021) for EOCRC incidence and National Center for Health Statistics data (2000–2022) for mortality. Analyses were stratified by race/ethnicity and histology. Trends were quantified using average annual percent change (AAPC) with 95% confidence intervals (Cis). Results: Among 474,601 early-onset adenocarcinoma (EO-ADC) cases, incidence increased in all racial and ethnic groups except Non-Hispanic Black individuals, in whom incidence declined (AAPC = −0.35%, 95% CI −0.63 to −0.08; p = 0.01). The steepest incidence increases occurred among American Indian/Alaska Native (AIAN; AAPC = 3.39%, 95% CI 2.70–4.15), Hispanic (AAPC = 0.94%, 95% CI 0.61–1.30), and Asian/Pacific Islander populations (AAPC = 0.64%, 95% CI 0.37–0.95; all p < 0.001). EOCRC mortality increased among AIAN (AAPC = 2.67%, 95% CI 1.26–4.26; p = 0.001) and Hispanic populations (AAPC = 0.81%, 95% CI 0.39–1.27; p < 0.001), but declined among Black individuals (AAPC = −1.08%, 95% CI −1.29 to −0.77; p < 0.001). Neuroendocrine tumors increased more rapidly than adenocarcinomas across all groups. Conclusions: EOCRC incidence and mortality are rising most rapidly among AIAN and Hispanic populations. Distinct incidence trajectories of colorectal neuroendocrine tumors compared with adenocarcinomas highlight the importance of histology-specific analyses for accurate epidemiologic interpretation.

Objectives: Cholangiocarcinoma (CCA) is the second most lethal primary hepatic malignancy. It has been well-reported that most cancer patients prefer to die at home or in a hospice facility. However, there is limited data on the place of death for CCA patients. We evaluated trends and disparities in place of death for patients with CCA from 1999 to 2020. Methods: Using the CDC WONDER database (1999–2020), we calculated the frequency of CCA deaths at home/hospice and the average annual percentage change (AAPC) over this period stratified by race, age, gender, and region. We employed logistic regression to assess for associations between these variables and place of death for patients whose death was attributed to CCA. Results: Among 140,422 deaths, a rise in deaths occurred in home/hospice facilities compared to inpatient medical or nursing facilities across all variables examined. Blacks and individuals ≥ 85 had the highest proportion of deaths outside of home/hospice. However, Blacks showed the highest AAPC (8.56%) in home/hospice deaths, followed by Asians (AAPC 8.44%). In contrast, individuals aged 45–54 saw the lowest AAPC (4.27%). Non-whites were less likely to die at home/hospice, with Blacks demonstrating the lowest adjusted odds ratio (aOR 0.64). Those ≥ 85 were less likely to die in home/hospice (aOR 0.78), whereas individuals aged between 55–64 (aOR 1.11) and 65–74 (aOR 1.12) had increased odds of dying in these settings. Patients from the Western region were the most likely to die at home/hospice (aOR 1.04). Significance of results: Our study highlights disparities in place of death of patients with CCA amongst races, regions, and ages. Non-whites, extremes of ages, and patients from the Northeast have disproportionately poor outcomes in terms of end-of-life care in the US. These findings emphasize the need for efforts to address sociodemographic disparities in end-of-life care to improve patient-centered health outcomes.

Purpose: Colorectal cancer remains a leading cause of cancer deaths, highlighting the need for early detection. Cologuard ^® , a non-invasive stool DNA test, detects biomarkers for CRC and precancerous lesions but requires follow-up colonoscopy and has a high false-positive rate. This study evaluates colonoscopy follow-up rates and diagnostic outcomes after positive Cologuard ^® results. Methods: We conducted a retrospective cohort study using the TriNetX database, a global federated real-world data platform, to analyze patients aged ≥ 18 years who tested positive on Cologuard. The primary outcome was whether patients underwent an endoscopic procedure (colonoscopy) within 12 months of a positive result. The secondary outcome was the diagnoses made during follow-up colonoscopy, including malignant neoplasms (colorectal cancer) and benign neoplasms (polyps). Results: A total of 3,916 patients underwent Cologuard ^® testing, with 61.3% being female, 35% male, and 3.7% other genders. Of the 385 patients who tested positive for Cologuard ^® (mean age 65 ± 8.75 years), 171 (44%) underwent follow-up colonoscopy within 12 months. Of these, 10 cases (5.8%) were diagnosed with malignant neoplasms, and 56 cases (32.7%) were diagnosed with benign neoplasms (polyps). Conclusion: The study found poor follow-up adherence, with only 44% completing colonoscopy and a high false positive rate with just 38.5% of positive Cologuard ^® results showing significant lesions. These findings emphasize the need for better patient education, streamlined care pathways, and improved communication to enhance follow-up compliance.

Introduction: Diabetic gastroparesis increases the risk of aspiration, pneumonia, and sepsis, yet the impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on these outcomes is uncertain because of their gastric-emptying effects. Methods: We performed a retrospective cohort study using the TriNetX Global Research Network. Adults (≥18 years) with diabetes mellitus and gastroparesis were identified and divided into two cohorts based on GLP-1 RA exposure. Propensity score matching (1:1) balanced demographics, comorbidities, and antidiabetic medications, yielding 23,371 patients per cohort. Outcomes, assessed from 180 days after index, included pneumonia, pneumonitis, mechanical ventilation, ventilator-associated pneumonia, sepsis, bacteremia, empyema, lung abscess, acute respiratory distress syndrome (ARDS), and need for enteral feeding. Risk ratios (RRs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated. Results: Compared with GLP-1 users, non-GLP-1 patients had higher incidences of pneumonitis (3.6% vs. 2.5%; HR 1.76, 95% CI 1.58–1.95), pneumonia (13.2% vs. 12.2%; HR 1.34, 95% CI 1.27–1.41), mechanical ventilation (4.4% vs. 3.3%; HR 1.63, 95% CI 1.49–1.79), sepsis (12.8% vs. 11.1%; HR 1.44, 95% CI 1.37–1.52), and bacteremia (5.2% vs. 4.4%; HR 1.46, 95% CI 1.35–1.59) (all p < 0.001). Empyema and ARDS were also numerically lower among GLP-1 users, while ventilator-associated pneumonia and lung abscess were rare and similar between groups. No patients required percutaneous endoscopic gastrostomy or nasal enteral feeding. Conclusions: In patients with diabetes and gastroparesis, GLP-1 RA therapy was associated with significantly fewer pulmonary and systemic infectious complications. These data suggest that the systemic benefits of GLP-1 RAs may outweigh concerns regarding delayed gastric emptying in this high-risk population.