Model-Based Estimation of Colorectal Cancer Screening and Outcomes During the COVID-19 Pandemic.

Importance: COVID-19 has decreased colorectal cancer screenings. Objective: To estimate the degree to which expanding fecal immunochemical test-based colorectal cancer screening participation during the COVID-19 pandemic is associated with clinical outcomes. Design, Setting, and Participants: A previously developed simulation model was adopted to estimate how much COVID-19 may have contributed to colorectal cancer outcomes. The model included the US population estimated to have completed colorectal cancer screening pre-COVID-19 according the American Cancer Society. The model was designed to estimate colorectal cancer outcomes between 2020 and 2023. This analysis was completed between July and December 2020. Exposures: Adults screened for colorectal cancer and colorectal cancer cases detected by stage. Main Outcomes and Measures: Estimates of colorectal cancer outcomes across 4 scenarios: (1) 9 months of 50% colorectal cancer screenings followed by 21 months of 75% colorectal cancer screenings; (2) 18 months of 50% screening followed by 12 months of 75% screening; (3) scenario 1 with increased use of fecal immunochemical tests; and (4) scenario 2 with increased use of fecal immunochemical tests. Results: In our simulation model, COVID-19-related reductions in care utilization resulted in an estimated 1 176 942 to 2 014 164 fewer colorectal cancer screenings, 8346 to 12 894 fewer colorectal cancer diagnoses, and 6113 to 9301 fewer early-stage colorectal cancer diagnoses between 2020 and 2023. With an abbreviated period of reduced colorectal cancer screenings, increasing fecal immunochemical test use was associated with an estimated additional 588 844 colorectal cancer screenings and 2836 colorectal cancer diagnoses, of which 1953 (68.9%) were early stage. In the event of a prolonged period of reduced colorectal cancer screenings, increasing fecal immunochemical test use was associated with an estimated additional 655 825 colorectal cancer screenings and 2715 colorectal cancer diagnoses, of which 1944 (71.6%) were early stage. Conclusions and Relevance: These results suggest that the increased use of fecal immunochemical tests during the COVID-19 pandemic was associated with increased colorectal cancer screening participation and more colorectal cancer diagnoses at earlier stages. If our estimates are borne out in real-world clinical practice, increasing fecal immunochemical test-based colorectal cancer screening participation during the COVID-19 pandemic could mitigate the consequences of reduced screening rates during the pandemic for colorectal cancer outcomes.

The efficacy of rapid on-site evaluation during endoscopic ultrasound-guided fine needle aspiration of pancreatic masses.

BACKGROUND: Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) has become the preferred method to diagnose pancreatic masses due to its minimally invasive approach and diagnostic accuracy. Many studies have shown that rapid on-site evaluation (ROSE) improves diagnostic yield by 10-30%; however, more recent studies have demonstrated effective diagnostic accuracy rates without ROSE. Our study aims to examine whether the current standard of performing ROSE after each FNA pass adds diagnostic value during EUS-guided FNA of pancreatic masses. METHODS: We conducted a retrospective case series on patients who underwent EUS-guided FNA of pancreatic masses between February 2011 and October 2014. All cases were performed by one of three endoscopists at Emory University Hospital. Patient demographics, radiologic details of pancreatic masses and pathology reports of the biopsied pancreatic masses were examined. RESULTS: A total of 184 procedures performed in 171 patients were reviewed. The final pathology reports of the biopsied pancreatic masses showed 128 (70%) with confirmed malignancy. Only 64 (50%) of these 128 cases initially showed malignant cells during ROSE. Among these 64 cases, 23% required 5 or more FNA passes to first detect malignant cells. CONCLUSIONS: The use of ROSE during EUS-guided FNA of pancreatic masses may increase the diagnostic yield, since malignant cells were often detected during later FNA passes that would otherwise be missed if tissue sampling stopped prematurely. In addition, sample preparation for ROSE may be suboptimal, since malignant cells were only detected in 50% of cases.

The effect of solid pancreatic mass lesions on pancreatic duct diameter at endoscopic ultrasound.

OBJECTIVES: To evaluate the effect of solid pancreatic masses on the pancreatic duct (PD) at the endoscopic ultrasound (EUS) and the relationship of the location/size of a mass and PD dilation. MATERIALS AND METHODS: Patients who underwent EUS for pancreatic indications from 2011 to 2013 at a single center were retrospectively identified. Those with biopsies that revealed adenocarcinoma or neuroendocrine tumors in the pancreas were identified and PD size was ascertained from EUS, computed tomography, or magnetic resonance imaging. RESULTS: Of the 475 patients who had a pancreatic EUS, 239 had a dilated PD and 236 had a normal PD. Patients with a dilated PD had a significantly higher incidence of pancreatic malignancy than those with a normal PD diameter (106/239, 44.4% vs. 32/236, 13.6%, P< 0.001). Of the 138 patients with a pancreatic malignancy, 106 (76.8%) had a dilated PD at some location in the pancreas. Over 80% of patients with a mass within the head, neck, or body had a dilated PD. For a mass located at the uncinate process or the tail, PD dilation was 65% and 23%, respectively. Fifty-six (80.0%) of the masses in the head, 11 (78.6%) masses in the neck, and 16 (76.2%) masses in the body had a dilated PD upstream of the mass. In addition, a step-wise increase in the incidence of PD dilation was correlated with an increase in mass size. About 67.6% of patients with masses measuring in the 1st quartile had dilated a PD, while 77.8%, 91.0%, and 71.4% of those with masses measuring in the 2nd, 3rd, and 4th quartiles, respectively, had a dilated PD. CONCLUSION: PD dilation is a warning sign for pancreatic malignancies, however, small masses or masses at the uncinate process or the tail of the pancreas may not affect the size of the PD.

Necrotizing enterocolitis in infants with congenital heart disease: the role of red blood cell transfusions.

Necrotizing enterocolitis (NEC) is a rare but catastrophic complication that may occur in newborns with congenital heart disease (CHD). In the preterm population, transfusion of red blood cells (RBCs) and use of RBCs with longer storage time have been independently associated with the development of NEC. To date, it is not known whether similar associations exist for the term newborn with CHD. This retrospective study identified the incidence of NEC among 1,551 newborns admitted to the authors' cardiac intensive care unit between 7 January 2002 and 7 January 2010. The study was limited to term newborns (>36 weeks gestation). To understand the impact of RBC transfusions on the development of NEC, a nested 2:1 matched case-control analysis was undertaken to compare RBC transfusion patterns between an age-matched group and a cardiac lesion-matched control group. In the study population, NEC developed in 45 term infants during the postoperative period. Of these 45 infants, 30 (66.7%) had single-ventricle heart defects, whereas 22 (48.8%) required surgery for aortic arch obstruction. The median patient age at NEC diagnosis was 21 days. The RBC transfusion rate was higher among the patients who experienced NEC (0.21/day) than among the control subjects (0.10/day) (p = 0.048). A multivariate analysis indicated that onset of NEC was associated with a greater number of RBC transfusions (odds ratio [OR] 1.83; 95% confidence interval [CI] 1.07-7.47; p = 0.045). The duration of RBC storage was not significantly longer in the NEC group (9 days) than in the control cohort (7 days) (p = 0.16). Increased exposure to RBC transfusions is associated with the development of NEC in term infants with CHD. Longer storage of RBCs does not appear to increase this risk. Although causality cannot be confirmed, these data prompt a careful review of RBC transfusion practices with this population.

Sorting mouse jejunal epithelial cells with CD24 yields a population with characteristics of intestinal stem cells.

Intestinal stem cells (ISCs) have been studied for more than three decades; however, their isolation has remained a challenge. We hypothesized that, just as for stem cells of other tissues, one or more membrane markers would allow positive selection of ISCs by antibody-based sorting. To explore this hypothesis, microarray data of putative ISC fractions generated by side population sorting and laser capture microdissection were subjected to bioinformatic analysis to identify common membrane antigens. The microarray comparison suggested CD24 as a candidate surface marker, and immunohistochemistry showed expression of CD24 in epithelial cells of crypt bases. Flow cytometry of jejunal epithelial preparations revealed a CD24(+) CD45(-) fraction comprising ∼1% of the cells. Analysis with epithelial cell adhesion molecule and CD31 confirmed that the cell preparations were epithelial and without endothelial contamination. Cycling cells identified by prior injection with 5-ethynyl-2'-deoxyuridine were found predominantly in the CD24(lo) subfraction. Transcript analysis by real-time RT-PCR showed this subfraction to be enriched in the ISC markers leucine-rich-repeat-containing G-protein-coupled receptor 5 (40-fold) and Bmi1 (5-fold), but also enriched in lysozyme (10-fold). Flow cytometry with anti-lysozyme antibodies demonstrated that Paneth cells comprise ∼30% of the CD24(lo) subfraction. Additional flow analyses with leucine-rich-repeat-containing G-protein-coupled receptor 5-enhanced green fluorescent protein (EGFP) epithelium demonstrated colocalization of EGFP(hi) and CD24(lo). In contrast, CD24 cells were negative for the quiescent ISC marker doublecortin and CaM kinase-like-1. Culture of CD24(lo) cells in Matrigel generated organoid structures, which included all four epithelial lineages, thus giving functional evidence for the presence of ISCs. We conclude that the CD24(lo) fraction of jejunal epithelium is highly enriched with cycling ISCs. This isolation method should be useful to many investigators in the field to advance both the basic understanding of ISC biology and the therapeutic applications of ISCs.