Radiation Exposure from GEP NET Surveillance.

BACKGROUND: Neuroendocrine tumors (NET) are neoplasms that secrete peptides and neuroamines. For gastroenteropancreatic (GEP) NET, surgical resection represents the only curative option. Ten-year imaging surveillance programs are recommended due to long time-to-recurrence following resection. We performed retrospective chart review evaluating radiation exposure and practice patterns from surveillance of completely resected GEP NET. METHODS: We performed a retrospective cohort study of cases with well-differentiated GEP NET from January 2005 to July 2020. Location of primary, modality of imaging, and duration of follow-up were collected. Dosimetry data was collected to calculate effective dose. RESULTS: 62 cases were included with 422 surveillance scans performed. Cross-sectional imaging was used in 82% and functional imaging was used in 18% of scans. Mean number of scans per year was 1.25 (0.42-3). Mean total effective dose was 56.05 mSv (SD 45.56; 0 to 198 mSv) while mean total effective dose per year was 10.62 mSv (SD 9.35; 0 to 45 mSv). Over the recommended ten years of surveillance the estimated total effective dose was 106 mSv. CONCLUSIONS: Surveillance of completely resected GEP NET results in cumulative radiation doses in the range associated with secondary malignancy development. Strategies to minimize radiation exposure in surveillance should be considered in future guideline development.

Global Incidence of Acute Pancreatitis Is Increasing Over Time: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: Acute pancreatitis is a common disease with significant associated morbidity and mortality. We performed a systematic review and meta-analysis of population-based studies to explore the changing temporal trends of acute pancreatitis incidence globally. METHODS: We performed a systematic literature search to identify population-based studies reporting the annual incidence of acute pancreatitis. Abstracts were assessed independently to identify applicable articles for full-text review and data extraction. Joinpoint temporal trend analyses were performed to calculate the average annual percent change (AAPC) with 95% confidence intervals (CIs). The AAPCs were pooled in a meta-analysis to capture the overall and regional trends in acute pancreatitis incidence over time. Temporal data were summarized in a static map and an interactive, web-based map. RESULTS: Forty-four studies reported the temporal incidence of acute pancreatitis (online interactive map: https://kaplan-acute-pancreatitis-ucalgary.hub.arcgis.com/). The incidence of acute pancreatitis has increased from 1961 to 2016 (AAPC, 3.07%; 95% CI, 2.30% to 3.84%; n = 34). Increasing incidence was observed in North America (AAPC, 3.67%; 95% CI, 2.76% to 4.57%; n = 4) and Europe (AAPC, 2.77%; 95% CI, 1.91% to 3.63%; n = 23). The incidence of acute pancreatitis was stable in Asia (AAPC, -0.28%; 95% CI, -5.03% to 4.47%; n = 4). CONCLUSIONS: This meta-analysis provides a comprehensive overview of the global incidence of acute pancreatitis over the last 56 years and demonstrates a steadily rising incidence over time in most countries of the Western world. More studies are needed to better define the changing incidence of acute pancreatitis in Asia, Africa, and Latin America.

Adverse events associated with endoscopic retrograde cholangiopancreatography: protocol for a systematic review and meta-analysis.

INTRODUCTION: Endoscopic retrograde cholangiopancreatography (ERCP) is performed to diagnose and manage conditions of the biliary and pancreatic ducts. Though effective, it is associated with common adverse events (AEs). The purpose of this study is to systematically review ERCP AE rates and report up-to-date pooled estimates. METHODS AND ANALYSIS: A comprehensive electronic search will be conducted of relevant medical databases through 10 November 2020. A study team of eight data abstracters will independently determine study eligibility, assess quality and abstract data in parallel, with any two concordant entries constituting agreement and with discrepancies resolved by consensus. The primary outcome will be the pooled incidence of post-ERCP pancreatitis, with secondary outcomes including post-ERCP bleeding, cholangitis, perforation, cholecystitis, death and unplanned healthcare encounters. Secondary outcomes will also include rates of specific and overall AEs within clinically relevant subgroups determined a priori. DerSimonian and Laird random effects models will be used to perform meta-analyses of these outcomes. Sources of heterogeneity will be explored via meta-regression. Subgroup analyses based on median dates of data collection across studies will be performed to determine whether AE rates have changed over time. ETHICS AND DISSEMINATION: Ethics approval is not required for this study as it is a planned meta-analysis of previously published data. Participant consent is similarly not required. Dissemination is planned via presentation at relevant conferences in addition to publication in peer-reviewed journals.PROSPERO registration numberCRD42020220221.

Cryopreserved Interleukin-4-Treated Macrophages Attenuate Murine Colitis in an Integrin ß7 - Dependent Manner.

The adoptive transfer of alternatively activated macrophages (AAMs) has proven to attenuate inflammation in multiple mouse models of colitis; however, the effect of cryopreservation on AAMs, the ability of previously frozen AAMs to block dinitrobenzene sulfonic acid (DNBS) (Th1) and oxazolone (Th2) colitis and their migration postinjection remains unknown. Here we have found that while cryopreservation reduced mRNA expression of canonical markers of interleukin (IL)-4-treated macrophages [M(IL-4)], this step did not translate to reduced protein or activity, and the cells retained their capacity to drive the suppression of colitis. The anticolitic effect of M(IL-4) adoptive transfer required neither T or B cell nor peritoneal macrophages in the recipient. After injection into the peritoneal cavity, M(IL-4)s migrated to the spleen, mesenteric lymph nodes and colon of DNBS-treated mice. The chemokines CCL2, CCL4 and CX3CL1 were expressed in the colon during the course of DNBS-induced colitis. The expression of integrin ß7 on transferred M(IL-4)s was required for their anticolitic effect, whereas the presence of the chemokine receptors CCR2 and CX3CR1 were dispensable in this model. Collectively, the data show that M(IL-4)s can be cryopreserved M(IL-4)s and subsequently used to suppress colitis in an integrin ß7-dependent manner, and we suggest that these proof-of-concept studies may lead to new cellular therapies for human inflammatory bowel disease.

The pro-inflammatory cytokine, interleukin-6, enhances the polarization of alternatively activated macrophages.

Macrophages are important innate immune cells that are associated with two distinct phenotypes: a pro-inflammatory (or classically activated) subset with prototypic macrophage functions such as inflammatory cytokine production and bactericidal activity, and an anti-inflammatory (or alternatively activated (AAM)) subset linked with wound healing and tissue repair processes. In this study, we examined the effect of interlukein-6 on human and murine macrophage polarization. The results indicate that despite being commonly associated with pro-inflammatory functions and being implicated in the pathogenesis/pathophysiology of numerous inflammatory diseases, interleukin-6 can enhance the polarization of AAMs, based on increased expression of hallmark markers: arginase-1, Ym1 and CD206; this effect required the AAM differentiating cytokines, IL-4 and IL-13. Co-treatment of AAMs with IL-6 resulted in spontaneous release of IL-10, suppressed LPS-induced nitric oxide production and inhibited cytokine production by activated CD4+ T cells - immunoregulatory features not observed in the 'parent' IL-4+IL-13-induced AAM. The effect of IL-6 required signal transducer and activator of transcription (STAT)-3, was partially dependent on up-regulation of the IL4Rα chain, and was independent of autocrine IL-10. In the presence of IFNγ, IL-6 promoted the production of IL-1ß and TNFα suggesting that this cytokine can enhance the phenotype to which a macrophage has committed. This finding may explain the pleiotrophic nature of IL-6, where it is associated with the perpetuation and enhancement of disease in inflammatory situations, but is also necessary for resolution of inflammation and adequate wound healing to occur in others. Thus, the potential benefit of IL-6 in promoting an AAM, with its' anti-inflammatory and wound healing ability, may need to be considered in immunotherapies aimed at in vivo modulation or inhibition of IL-6.