The Chile Biliary Longitudinal Study: A Gallstone Cohort.

Gallbladder cancer (GBC) is a highly fatal cancer that can be cured through cholecystectomy if identified early. The presence of gallstones is the primary risk factor for GBC, but few people with gallstones develop GBC. A key question is what drives the development of GBC among persons with gallstones. We initiated the Chile Biliary Longitudinal Study (Chile BiLS) to address this question. From 2016 to 2019, Chile BiLS enrolled 4,726 women aged 50-74 years with ultrasound-detected gallstones from southern-central Chile, accounting for an estimated 36% of eligible women with gallstones in the study area. The median age was 59 years; 25% of the women were Amerindian (Mapuche), 60% were obese, 25% had diabetes, and 6% had cardiovascular disease. Participants will be followed for gallbladder dysplasia or cancer for 6 years. As of April 30, 2020, over 91% of those eligible completed the year 2 follow-up visit. Data being collected include epidemiologic and sociodemographic information, anthropometric measurements, blood pressure, and tooth counts. Biosamples being taken include baseline plasma, buffy coat, red blood cells, serum, blood clot from serum, and PAXgene whole blood (PreAnalytiX GmbH, Hombrechtikon, Switzerland). Complete gallbladder sampling is conducted for most participants undergoing cholecystectomy. The Chile BiLS cohort study will increase our understanding of GBC etiology and could identify potential risk stratification and early detection strategies in high-risk areas.

Distribution of dysplasia and cancer in the gallbladder: an analysis from a high cancer-risk population.

Gallbladder dysplasia can progress to cancer and may be associated with increased cancer risk at other biliary tract sites. Thus, its accurate identification is relevant both for etiologic understanding and for clinical purposes. Data on the frequency and distribution of gallbladder dysplasia are lacking owing to limited gallbladder sampling and inability to visualize dysplasia grossly. An expert pathology group used consensus criteria to review 140 totally sampled consecutive cholecystectomy specimens from Chilean women. Three cases (2%) revealed incidental invasive carcinoma, all T2, along with high-grade dysplasia (HGD). The surface areas covered by dysplasia or cancer in these cases were 9%, 37%, and 87%. Although the first longitudinal ("diagnostic") section of the whole gallbladder captured HGD or cancer in all 3 cases, the deepest focus of invasive carcinoma was not present in this section. Fourteen additional cases (10%) had low-grade dysplasia (LGD), which was typically very focal (covering <5% of the surface) and most often occurred in the fundus. LGD was not present in the diagnostic section of 5 cases (38%) and would have been missed without additional sampling. None of the cancers or dysplasias were grossly visible. Although HGD and carcinoma are likely to be identified in "diagnostic" sections, accurate staging requires total sampling. LGD is typically very focal and would often be missed in routine practice. To identify cancer precursors, additional sampling, particularly of the fundus, may be warranted. The predominance of LGD in the fundus also provides etiologic insight, supporting the contribution of gallstones and chronic inflammation.

The PLCO Biorepository: Creating, Maintaining, and Administering a Unique Biospecimen Resource.

Inclusion of biospecimens in population-based studies is an integral part of understanding disease etiology, identifying biomarkers and developing prevention and treatment strategies. The Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial collected, processed and stored biospecimens from participants to create a biorepository of specimens which serves as a useful resource for a broad research community. PLCO collected blood samples from consented screening arm participants at six screening rounds and a buccal sample from consented control arm participants. In addition, formalin-fixed paraffin embedded tumor tissue specimens were collected for participants in both arms for selected cancer sites. Collection of biospecimens at multiple timepoints (i.e. serial samples) and prior to cancer diagnosis, paired with rich epidemiologic and screening data, makes the PLCO collection of biospecimens a uniquely valuable resource. As such, access to the PLCO biorepository is granted to investigators by a rigorous scientific review process and guided by a steering committee which is responsible for developing and implementing the biospecimen use policies. Here, we describe the procedures for biospecimen collection, processing, storage, requisition, and distribution, as well as data management employed in PLCO. We also provide examples of how the biospecimens have been used to advance cancer research and describe relevant lessons learned to help inform cohorts wishing to add or modify biospecimen collection.

Organochlorine pesticides and polychlorinated biphenyls (PCBs) in eggs of red-legged frogs (Rana aurora) and northwestern salamanders (Ambystoma gracile) in an agricultural landscape.

Organochlorine pesticides were widely used in the past in Sumas Prairie, British Columbia, Canada. In the 1990s, the hatching success of amphibians from agricultural sites was significantly depressed in the Sumas Prairie compared to reference sites. Therefore, in this study, organochlorine pesticides and polychlorinated biphenyls (PCBs) were measured in eggs of red-legged frogs (Rana aurora) and northwestern salamanders (Ambystoma gracile) from the Sumas Prairie. Egg masses were sampled from three agricultural sites that were exposed to agricultural runoff, and three reference sites that had lower agricultural runoff exposures. Not only was there little difference in contamination between agricultural and reference sites, but the levels of pesticides and PCBs found were lower than the concentrations reported to cause developmental or behavioural problems in amphibians.

Effects of agricultural runoff on native amphibians in the Lower Fraser River Valley, British Columbia, Canada.

Hatching success, deformity rates, and survivorship of northern red-legged frogs (Rana aurora) and northwestern salamanders (Ambystoma gracile) were assessed at three agricultural and three reference sites in the Sumas Prairie, British Columbia, Canada. In 1997 and 1998, eggs of both species and eggs of R. aurora, respectively, were placed in Nytex mesh cages (Irwindale, CA, USA) in roadside ditches at each site. Concurrently in 1997, eggs of R. aurora were reared in the laboratory but were exposed to water samples from each of the study sites. Hatching success was significantly lower at all agricultural sites compared to the reference sites for both species. However, no differences were observed in hatching success among sites for eggs of R. aurora reared in the laboratory. Water chemistry differed among all sites, but the largest differences were between reference and agricultural sites. Ammonia (maximum of 1.27 mg/L), total phosphate (maximum of 8.14 mg/L), and biological oxygen demand (maximum of 79.00 mg/L) were high at some of the agricultural sites during the development period. Results suggest that agricultural runoff may contribute to lower reproductive success and ultimately to reduced population viability of amphibian populations in the Lower Fraser Valley (BC, Canada).