Does salinity mediate the toxicity of perfluorooctanesulfonic acid (PFOS) in an estuarine fish?

Perfluorooctanesulfonic acid (PFOS) is detected in estuarine environments, where salinity levels fluctuate regularly. We investigated the effects of salinity on the toxicity of PFOS in embryos and larvae of Cyprinodon variegatus. We crossed six PFOS treatments (0, 1-10,000 µg/L) with two salinities (10, 30 ppt). Larvae exposed to the highest concentration of PFOS under high salinity accumulated over twice the amount of PFOS compared to larvae maintained under low salinity. Embryonic survival was unaffected by PFOS, salinity, or their interaction. PFOS delayed time to hatch and increased salinity reduced time to hatch regardless of PFOS treatment; however, no salinity by PFOS interactions were observed. Conversely, PFOS and salinity interacted in the larval stage, with decreased survival at 30 ppt salinity. This is one of the first studies evaluating interactive effects of PFOS and high salinity and highlights the importance of assessing PFAS toxicity across life stages.

Assessing the Combined Effects of Host and Parasite Exposure to Forever Chemicals in an Amphibian-Echinostome System.

Per- and polyfluoroalkyl substances (PFAS) are environmental contaminants of growing concern due to their potential negative effects on wildlife and human health. Per- and polyfluoroalkyl substances have been shown to alter immune function in various taxa, which could influence the outcomes of host-parasite interactions. To date, studies have focused on the effects of PFAS on host susceptibility to parasites, but no studies have addressed the effects of PFAS on parasites. To address this knowledge gap, we independently manipulated exposure of larval northern leopard frogs (Rana pipiens) and parasites (flatworms) via their snail intermediate host to environmentally relevant PFAS concentrations and then conducted trials to assess host susceptibility to infection, parasite infectivity, and parasite longevity after emergence from the host. We found that PFAS exposure to only the host led to no significant change in parasite load, whereas exposure of parasites to a 10-µg/L mixture of PFAS led to a significant reduction in parasite load in hosts that were not exposed to PFAS. We found that when both host and parasite were exposed to PFAS there was no difference in parasite load. In addition, we found significant differences in parasite longevity post emergence following exposure to PFAS. Although some PFAS-exposed parasites had greater longevity, this did not necessarily translate into increased infection success, possibly because of impaired movement of the parasite. Our results indicate that exposure to PFAS can potentially impact host-parasite interactions. Environ Toxicol Chem 2024;00:1-10. © 2024 SETAC.

Toxicities of Legacy and Current-Use PFAS in an Anuran: Do Larval Exposures Influence Responses to a Terrestrial Pathogen Challenge?

Legacy polyfluoroalkyl substances (PFAS) [perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA)] are being replaced by various other fluorinated compounds, such as hexafluoropropylene oxide dimer acid (GenX). These alternatives are thought to be less bioaccumulative and, therefore, less toxic than legacy PFAS. Contaminant exposures occur concurrently with exposure to natural stressors, including the fungal pathogen Batrachocytrium dendrobatidis (Bd). Despite evidence that other pollutants can increase the adverse effects of Bd on anurans, no studies have examined the interactive effects of Bd and PFAS. This study tested the growth and developmental effects of PFOS, PFOA, and GenX on gray treefrog (Hyla versicolor) tadpoles, followed by a Bd challenge after metamorphosis. Despite PFAS exposure only occurring during the larval stage, carry-over effects on growth were observed post metamorphosis. Further, PFAS interacted with Bd exposure to influence growth; Bd-exposed animals had significantly shorter SVL [snout-vent length (mm)] with significantly increased body condition, among other time-dependent effects. Our data suggest that larval exposure to PFAS can continue to impact growth in the juvenile stage after exposure has ended. Contrary to predictions, GenX affected terrestrial performance more consistently than its legacy congener, PFOA. Given the role of Bd in amphibian declines, further investigation of interactions of PFAS with Bd and other environmentally relevant pathogens is warranted.

Differential Developmental Neurotoxicity and Tissue Uptake of the Per- and Polyfluoroalkyl Substance Alternatives, GenX and PFBS.

Per- and polyfluoroalkyl substances (PFAS) are a class of synthetic chemicals with several applications. Multiple adverse health effects are reported for longer carbon chain (≤C8) PFAS. Shorter carbon chain PFAS, [e.g., hexafluoropropylene oxide dimer acid (HFPO-DA; GenX) and perfluorobutanesulfonic acid (PFBS)] were introduced as alternatives. Past studies indicate that longer-chain PFAS are neurotoxic targeting the dopamine pathway, but it is not known if shorter-chain PFAS act similarly. This study aimed to evaluate developmental neurotoxicity and tissue uptake of GenX and PFBS using the zebrafish (Danio rerio). First, acute toxicity was assessed by measuring LC50 at 120 h postfertilization (hpf). Body burden was determined after embryonic exposure (1-72 hpf) to sublethal concentrations of GenX or PFBS by LC-ESI-MS/MS. Locomotor activity using a visual motor response assay at 120 hpf and dopamine levels at 72 hpf was assessed after embryonic exposure. PFBS was more acutely toxic and bioaccumulative than GenX. GenX and PFBS caused hyperactivity at 120 hpf, but stronger behavioral alterations were observed for PFBS. An increase in whole organism dopamine occurred at 40 ppb of GenX, while a decrease was observed at 400 ppb of PFBS. Differences detected in dopamine for these two PFAS indicate differential mechanisms of developmental neurotoxicity.

Reconnaissance Survey of Organic Contaminants of Emerging Concern in the Kabul and Swat Rivers of Pakistan.

The Swat and Kabul rivers of northern Pakistan are within an important regional watershed that supports river-based livelihoods and is impacted by untreated effluent discharges and municipal solid waste. Evidence indicates that fish populations are decreasing in these rivers. One potential cause of poor aquatic health is pollution; therefore, we investigated the presence of contaminants of emerging concern (CECs) in the river systems. Water samples were collected in the Kabul River (n = 9) and Swat River (n = 10) during seasons of high (summer 2018) and low (winter 2019) river flow. Agrochemicals, pharmaceuticals, plasticizers, chemicals in personal care products, and hormones were quantified via liquid chromatography high-resolution mass spectrometry. In the Swat River, caffeine (18-8452 ng/L), N,N-diethyl-meta-toluamide (DEET; 16-56 ng/L), and plasticizers (13-7379 ng/L) were detected at all sites during both seasons, while butachlor (16-98 ng/L) was detected only during high flow. In the Kabul River, caffeine (12-2081 ng/L) and several plasticizers (91-722 ng/L) were detected at all sites during both seasons, while DEET (up to 97 ng/L) was detected only during high flow. During low flow, pharmaceuticals (analgesics and nonsteroidal anti-inflammatory drugs) were quantified in both rivers (up to 823 ng/L), with detection frequencies from 70% to 100% and 0% to 78% in the Swat and Kabul Rivers, respectively. Intermittent-use and natural seasonal processes (increased runoff and dilution from rainfall and snowmelt) yielded higher agrochemical concentrations and lower concentrations of continuous-use compounds (e.g., caffeine) during high flow. The present study provides the first insight into CEC concentrations in the Swat River, additional insight into the Kabul River stressors, and, overall, contaminant risks to aquatic life. Environ Toxicol Chem 2023;42:2599-2613. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Per- and polyfluoroalkyl substances in water treatment residuals: Occurrence and desorption.

Per- and polyfluoroalkyl substances (PFAS) in surface and ground waters supplying municipal drinking water are a growing concern. However, PFAS concentrations in water treatment residuals (WTRs)-a solid by-product of water treatment-have yet to be explored. In a first of its kind assessment, we examine PFAS occurrence in seven calcium (Ca)-, iron-, and aluminum-based drinking water treatment residuals (DWTRs) and one wastewater effluent treatment residual (WWETR) produced using aluminum chlorohydrate (ACH). Only perfluoroalkyl acids (PFAAs) were detected, with total PFAA concentrations in the seven DWTRs produced from naturally recharged water sources ranging from 0 to ∼3.3 µg kg-1 ; no PFAS were detected in either of the Ca-DWTRs. The ACH-WWETR contained the highest number and concentration of PFAAs (34 µg kg-1 ). Desorption of resident PFAAs from the WTRs was negligible for the carboxylates (PFCAs). Some desorption of the sulfonates (PFSAs) was detected, particularly for PFOS which had the highest concentration among all resident PFAAs. The ACH-WWETR was further evaluated for its potential to attenuate additional PFAAs (3500 µg mL-1 total PFAAs) in a biosolid-derived porewater matrix. Sorption was highest for long-chain PFAAs and subsequent desorption of the adsorbed PFAAs ranged from 0% to no more than 26%, with the WWETR mass added strongly affecting both PFSA and PFCA sorption/desorption. These findings suggest that WTRs, if introduced into the environment, are unlikely to be a major source of PFAS. Also, the use of particular WTRs as amendments may provide a beneficial reduction in PFAS mobility.

A blood-based metabolomic signature predictive of risk for pancreatic cancer.

Emerging evidence implicates microbiome involvement in the development of pancreatic cancer (PaCa). Here, we investigate whether increases in circulating microbial-related metabolites associate with PaCa risk by applying metabolomics profiling to 172 sera collected within 5 years prior to PaCa diagnosis and 863 matched non-subject sera from participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cohort. We develop a three-marker microbial-related metabolite panel to assess 5-year risk of PaCa. The addition of five non-microbial metabolites further improves 5-year risk prediction of PaCa. The combined metabolite panel complements CA19-9, and individuals with a combined metabolite panel + CA19-9 score in the top 2.5th percentile have absolute 5-year risk estimates of >13%. The risk prediction model based on circulating microbial and non-microbial metabolites provides a potential tool to identify individuals at high risk of PaCa that would benefit from surveillance and/or from potential cancer interception strategies.

Chronic Exposure to a PFAS Mixture Resembling AFFF-Impacted Surface Water Decreases Body Size in Northern Leopard Frogs (Rana pipiens).

Per- and polyfluoroalkyl substances (PFAS) occur in the environment as mixtures, yet mixture toxicity remains poorly understood. Aqueous film-forming foams (AFFFs) are a common source of PFAS. Our objective was to examine chronic effects of a complex PFAS mixture on amphibian growth and development. We tested toxicity of a five-chemical PFAS mixture summing to 10 µg/L and that accounts for >90% of the PFAS in AFFF-affected surface waters: perfluorooctane sulfonate (PFOS, 40%), perfluorohexane sulfonic acid (PFHxS, 30%), perflurooctanoic acid (PFOA, 12.5%), perfluorohexanoic acid (PFHxA, 12.5%), and perfluoropentanoic acid (PFPeA, 5%). We also included treatments to determine whether PFOS drove mixture toxicity and whether PFOS and mixture components act additively. We exposed Northern leopard frog (Rana pipiens) larvae through metamorphosis (∼130 d) in outdoor mesocosms. After 21 days of exposure, the larval body condition fell ∼5% relative to controls in the 4 µg/L PFOS treatment and mixtures lacking PFOS. At metamorphosis, the full 5-component 10 µg/L PFAS mixture reduced mass by 16% relative to controls. We did not observe effects on development. Our results indicate that toxicity of PFOS and other PFAS mixtures typical of AFFF sites act additively and that PFOS is not more inherently toxic than other mixture components.

High Persistence of Novel Polyfluoroalkyl Betaines in Aerobic Soils.

Some contemporary aqueous film-forming foams (AFFFs) contain n:3 and n:1:2 fluorotelomer betaines (FTBs), which are often detected at sites impacted by AFFFs. As new chemical replacements, little is known about their environmental fate. For the first time, we investigated the biotransformation potential of 5:3 and 5:1:2 FTBs and a commercial AFFF that mainly contains n:3 and n:1:2 FTBs (n = 5, 7, 9, 11, and 13). Although some polyfluoroalkyl compounds are precursors to perfluoroalkyl acids, 5:3 and 5:1:2 FTBs exhibited high persistence, with no significant changes even after 120 days of incubation. While the degradation of 5:3 FTB into suspected products such as fluorotelomer acids or perfluoroalkyl carboxylic acids (PFCAs) could not be conclusively confirmed, we did identify a potential biotransformation product, 5:3 fluorotelomer methylamine. Similarly, 5:1:2 FTB did not break down or produce short-chain hydrogen-substituted polyfluoroalkyl acids (n:2 H-FTCA), hydrogen-substituted PFCA (2H-PFCA), or any other products. Incubating the AFFF in four soils with differing properties and microbial communities resulted in 0.023-0.25 mol % PFCAs by day 120. Most of the products are believed to be derived from n:2 fluorotelomers, minor components of the AFFF. Therefore, the findings of the study cannot be fully explained by the current understanding of structure-biodegradability relationships.

PFAS release from wastewater residuals as a function of composition and production practices.

Per- and polyfluoroalkyl substances (PFAS) are a class of highly persistent contaminants that have been linked to human health effects at low exposure concentrations. Public concerns exist that land-application of biosolids may result in the release of PFAS into terrestrial and aquatic ecosystems. The relative importance of inorganic constituents such as Fe and Al, which are known to impact PFAS retention/release behavior in soils, on PFAS release from wastewater residuals (WWRs, i.e., biosolids and sewage sludges) is not well understood. Here, we examine native concentrations and WWR-water partition coefficients of a range of PFAS in the context of WWRs characteristics including oxalate-extractable Fe and Al, organic matter (OM), dissolved organic carbon, and total protein content. Total PFAS concentrations, which included perfluoroalkyl carboxylates, perfluoroalkyl sulfonates, fluorotelomer sulfonates and some sulfonamides, ranged from ∼480 to 3500 µg PFAS kg-1 dry weight. PFAS WWR-water partition coefficients ranged from ∼10 to 20,000 L kg-1, consistent with the literature. PFAS partitioning was significantly correlated to oxalate extractable Al and Fe as well as bulk OM and protein content. These results have important implications for wastewater treatment facilities that recycle Al- and Fe-based drinking water treatment residuals in terms of both PFAS retention and loading.

Electric Field-Assisted Nanofiltration for PFOA Removal with Exceptional Flux, Selectivity, and Destruction.

Per- and polyfluoroalkyl substances (PFAS) pose significant environmental and human health risks and thus require solutions for their removal and destruction. However, PFAS cannot be destroyed by widely used removal processes like nanofiltration (NF). A few scarcely implemented advanced oxidation processes can degrade PFAS. In this study, we apply an electric field to a membrane system by placing a nanofiltration membrane between reactive electrodes in a crossflow configuration. The performance of perfluorooctanoic acid (PFOA) rejection, water flux, and energy consumption were evaluated. The reactive and robust SnO2-Sb porous anode was created via a sintering and sol-gel process. The characterization and analysis techniques included field emission scanning electron microscopy (FE-SEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), ion chromatography, mass spectroscopy, porosimeter, and pH meter. The PFOA rejection increased from 45% (0 V) to 97% (30 V) when the electric field and filtration were in the same direction, while rejection capabilities worsened in opposite directions. With saline solutions (1 mM Na2SO4) present, the induced electro-oxidation process could effectively mineralize PFOA, although this led to unstable removal and water fluxes. The design achieved an exceptional performance in the nonsaline feed of 97% PFOA rejection and water flux of 68.4 L/m2 hr while requiring only 7.31 × 10-5 kWh/m3/order of electrical energy. The approach's success is attributed to the proximity of the electrodes and membrane, which causes a stronger electric field, weakened concentration polarization, and reduced mass transfer distances of PFOA near the membrane. The proposed electric field-assisted nanofiltration design provides a practical membrane separation method for PFAS removal from water.

ACG Clinical Guideline: Diagnosis and Management of Gastrointestinal Subepithelial Lesions.

Subepithelial lesions (SEL) of the GI tract represent a mix of benign and potentially malignant entities including tumors, cysts, or extraluminal structures causing extrinsic compression of the gastrointestinal wall. SEL can occur anywhere along the GI tract and are frequently incidental findings encountered during endoscopy or cross-sectional imaging. This clinical guideline of the American College of Gastroenterology was developed using the Grading of Recommendations Assessment, Development, and Evaluation process and is intended to suggest preferable approaches to a typical patient with a SEL based on the currently available published literature. Among the recommendations, we suggest endoscopic ultrasound (EUS) with tissue acquisition to improve diagnostic accuracy in the identification of solid nonlipomatous SEL and EUS fine-needle biopsy alone or EUS fine-needle aspiration with rapid on-site evaluation sampling of solid SEL. There is insufficient evidence to recommend surveillance vs resection of gastric gastrointestinal stromal tumors (GIST) <2 cm in size. Owing to their malignant potential, we suggest resection of gastric GIST >2 cm and all nongastric GIST. When exercising clinical judgment, particularly when statements are conditional suggestions and/or treatments pose significant risks, health-care providers should incorporate this guideline with patient-specific preferences, medical comorbidities, and overall health status to arrive at a patient-centered approach.

Occurrence and implications of per and polyfluoroalkyl substances in animal feeds used in laboratory toxicity testing.

The exceptional thermal and chemical stability and the amphiphilicity of per- and polyfluoroalkyl substances (PFAS) have resulted in widespread use and subsequent contamination in environmental media and biota. Concerns surrounding toxicity have led to numerous animal-based toxicity studies. Due to the ubiquity of PFAS and the low parts per trillion (ppt) health advisory levels for drinking water, several contamination elimination protocols have been implemented. In addition, it is urgently necessary to perform low-dose experiments, but due to unknown pathways for entry of unwanted PFAS, low-dose studies are extremely challenging to conduct. However, animal feed sources are a likely route that could introduce unwanted PFAS into experiments, yet investigations of PFAS in common animal feeds are lacking. Here, we report the examination of PFAS levels in eighteen different animal feeds, representing a range of diets fed to diverse taxa. We evaluated whether PFAS levels in feeds were correlated with ingredient composition (plant versus animal-based) or dietary habits of lab animals (amphibian, fish, invertebrate, mammal). PFOS, PFHxS, PFOA, and short-chain perfluoroalkyl carboxylic acids had the highest detection levels and frequencies across all samples. Different food ingredients led to different PFAS profiles. No meaningful levels of PFAS precursors were detected. We demonstrate that PFAS contamination in animal feed is pervasive. Reducing food-sourced PFAS is a critical, albeit challenging task to improve interpretability of in vivo exposures.

Perfluoroalkyl acid transformation and mitigation by nNiFe-activated carbon nanocomposites in steady-state flow column studies.

The ongoing contamination of groundwater with per- and polyfluoroalkyl substances (PFAS) has resulted in a global and rapidly growing interest in PFAS groundwater remediation. Preferred technologies that lead to PFAS destruction are often limited by not addressing all PFAS, being energy-intensive or not being suited for in-situ application. We developed nNiFe-activated carbon (AC) nanocomposites and demonstrated varying degrees of PFAS reduction and fluoride generation with these nanocomposites in batch reactors for several PFAS. Here we explore nNiFe-AC's effectiveness to transform perfluoroalkyl acid acids (PFAAs) under steady-state flow (0.0044 to 0.15 mL/min) in nNiFe-AC:sand packed columns. Column experiments included, two perfluorooctane sulfonate (PFOS) in deionized water and two PFAA mixtures in deionized water or bicarbonate buffer containing five perfluoroalkyl carboxylates (PFCAs, C5-C9) and three perfluoroalkyl sulfonates (PFSAs, C4, C6 and C8) at temperatures of 50 or 60°C were evaluated. PFOS transformation was similar in PFOS-only and PFAA mixture column experiments. Overall, % PFAA transformation under flow conditions exceeded what we observed previously in batch reactors with up to 53% transformation of a PFAA mixture with ∼ 8% defluorination. Longer chain PFAS dominated the PFAAs transformed and a bicarbonate matrix appeared to reduce overall transformation. PFAA breakthrough was slower than predicted from only sorption due to transformation; some longer chain PFAS like PFOS did not breakthrough. Here, nNiFe-AC technology with both in-situ and ex-situ potential application was shown to be a plausible part of a treatment train needed to address the ongoing challenge for cleaning up PFAS-contaminated waters.

Effects of Per- and Polyfluoroalkyl Substance Mixtures on the Susceptibility of Larval American Bullfrogs to Parasites.

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants known to adversely affect health and development in many taxa. Although PFAS generally occur as mixtures in the environment, little is known about the effects of PFAS mixtures on organisms compared to single chemical exposures. Moreover, PFAS exposure in nature occurs alongside biotic factors such as parasitism. Even though host-parasite interactions are common in natural systems, there is little information about how PFAS affect these interactions. Here, we examined the effects of PFAS mixtures on the susceptibility of larval American bullfrogs (Rana catesbeiana) to echinostomes. Our PFAS treatments included perfluorooctanesulfonic acid (PFOS) at 4 and 10 ppb, two mixtures without PFOS as a component at 6 and 10 ppb total PFAS, and a mixture containing PFOS at 10 ppb total PFAS. We found that a 62-day PFAS exposure increased parasite loads by 42-100% in all treatments relative to the control. Additionally, we found that the singular exposure to PFOS increased parasite loads by ∼40% compared to a mixture containing PFOS suggesting antagonism among PFAS in mixtures. Our results highlight the need for further investigation into the effects of PFAS mixtures on organisms and how PFAS affect common ecological interactions.

An Environmentally Relevant Mixture of Perfluorooctanesulfonic Acid and Perfluorohexanesulfonic Acid Does Not Conform to Additivity in Northern Leopard Frogs Exposed Through Metamorphosis.

Per- and polyfluoroalkyl substances (PFAS) are chemicals associated with adverse health effects. At aqueous film-forming foam sites, they occur as mixtures, with perfluorooctanesulfonic acid (PFOS) and perfluorohexanesulfonic acid (PFHxS) commonly co-occurring in the highest concentrations. Although PFOS and PFHxS toxicities have been studied, few studies have tested their potential interaction. Using Rana pipiens, the present study compared toxicities of a 1:1 PFOS:PFHxS mixture to PFOS and PFHxS individually with the prediction that responses would be additive. Gosner stage 25 (GS 25) tadpoles were exposed through metamorphosis (GS 46) to 0.5 and 1 ppb PFOS or PFHxS alone or to a mixture of 0.5 ppb PFOS and 0.5 ppb PFHxS. Tadpoles were weighed and measured (snout-vent length [SVL]) at day 31, metamorphic climax (GS 42), and GS 46. These values were used to calculate the scaled mass index (SMI), a measure of body condition. Body burdens were quantified on day 31 and at GS 46. The PFOS and PFHxS body burdens were elevated relative to controls at GS 46. No effects were observed on survival, SVL, or mass. Single PFAS effects included a 17% reduction in SMI at day 31 (0.5 ppb PFHxS) and a 1.1-day longer metamorphic period (1 ppb PFHxS) relative to controls. Mixture results deviated from additivity-SMIs were higher than expected on day 31 and lower than expected at GS 42. In addition, time to GS 42 in the PFAS mixture exceeded expected additivity by 12 days. Results from a chronic exposure to a 1:1 PFOS:PFHxS mixture resulted in changes in body condition and length of metamorphosis that deviated from additivity. More PFAS mixture toxicity studies conducted at relevant ratios and concentrations are needed. Environ Toxicol Chem 2022;41:3007-3016. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Current updates and future directions in diagnosis and management of gastroenteropancreatic neuroendocrine neoplasms.

Gastroenteropancreatic neuroendocrine neoplasms are a heterogenous group of rare neoplasms that are increasingly being discovered, often incidentally, throughout the gastrointestinal tract with varying degrees of activity and malignant potential. Confusing nomenclature has added to the complexity of managing these lesions. The term carcinoid tumor and embryonic classification have been replaced with gastroenteropancreatic neuroendocrine neoplasm, which includes gastrointestinal neuroendocrine and pancreatic neuroendocrine neoplasms. A comprehensive multidisciplinary approach is important for clinicians to diagnose, stage and manage these lesions. While histological diagnosis is the gold standard, recent advancements in endoscopy, conventional imaging, functional imaging, and serum biomarkers complement histology for tailoring specific treatment options. In light of developing technology, our review sets out to characterize diagnostic and therapeutic advancements for managing gastroenteropancreatic neuroendocrine tumors, including innovations in radiolabeled peptide imaging, circulating biomarkers, and endoscopic treatment approaches adapted to different locations throughout the gastrointestinal system.

The Multicenter Cancer of Pancreas Screening Study: Impact on Stage and Survival.

PURPOSE: To report pancreas surveillance outcomes of high-risk individuals within the multicenter Cancer of Pancreas Screening-5 (CAPS5) study and to update outcomes of patients enrolled in prior CAPS studies. METHODS: Individuals recommended for pancreas surveillance were prospectively enrolled into one of eight CAPS5 study centers between 2014 and 2021. The primary end point was the stage distribution of pancreatic ductal adenocarcinoma (PDAC) detected (stage I v higher-stage). Overall survival was determined using the Kaplan-Meier method. RESULTS: Of 1,461 high-risk individuals enrolled into CAPS5, 48.5% had a pathogenic variant in a PDAC-susceptibility gene. Ten patients were diagnosed with PDAC, one of whom was diagnosed with metastatic PDAC 4 years after dropping out of surveillance. Of the remaining nine, seven (77.8%) had a stage I PDAC (by surgical pathology) detected during surveillance; one had stage II, and one had stage III disease. Seven of these nine patients with PDAC were alive after a median follow-up of 2.6 years. Eight additional patients underwent surgical resection for worrisome lesions; three had high-grade and five had low-grade dysplasia in their resected specimens. In the entire CAPS cohort (CAPS1-5 studies, 1,731 patients), 26 PDAC cases have been diagnosed, 19 within surveillance, 57.9% of whom had stage I and 5.2% had stage IV disease. By contrast, six of the seven PDACs (85.7%) detected outside surveillance were stage IV. Five-year survival to date of the patients with a screen-detected PDAC is 73.3%, and median overall survival is 9.8 years, compared with 1.5 years for patients diagnosed with PDAC outside surveillance (hazard ratio [95% CI]; 0.13 [0.03 to 0.50], P = .003). CONCLUSION: Most pancreatic cancers diagnosed within the CAPS high-risk cohort in the recent years have had stage I disease with long-term survival.