Statin use is not associated with inflammation among Chilean women of Mapuche and non-Mapuche ancestry with gallstones.

Aim: Statins are associated with lower risk of gallstones due to anti-inflammatory effects. We assessed whether statins impact circulating inflammation among Chilean women with gallstones. Materials & methods: 200 Mapuche women were matched on statin use and age to 200 non-Mapuche women in the Chile Biliary Longitudinal Study. We analyzed 92 inflammatory biomarkers using multivariable-adjusted regression models, random forests and pathway analyses. Results: Statins were not significantly associated with any inflammation marker when women were analyzed jointly or stratified by ancestry. No significant associations were found through random forest methods and pathway analyses. Discussion: We did not find significant associations between statin use and inflammation markers in women with gallstones, suggesting that statins do not reduce inflammation once gallstones have formed.

Statins are prescribed to lower cholesterol and can also decrease the risk of gallstone formation by reducing inflammation. We assessed whether statin use reduces inflammation among women who have already developed gallstones. We analyzed 92 inflammation markers among 400 women in Chile, including 200 women with Mapuche Amerindian ancestry and 200 women of Latina/European ancestry. We found that statin use was not correlated with inflammation in this group of women overall nor by ancestry. This may mean that statin use does not reduce inflammation in women who already were diagnosed with gallstones.

Family-based psychosocial interventions for adult Latino patients with cancer and their caregivers: A systematic review.

Objective: This review aimed to systematically examine the characteristics and outcomes of family-based psychosocial interventions offered to adult Latino patients with cancer and their caregivers. Methods: We searched six databases from their inception dates through June 2022. Studies were eligible for inclusion if they (1) targeted both adult Latino patients diagnosed with cancer and their adult caregivers or reported subgroup analyses of Latino patients and caregivers; (2) included family-based psychosocial interventions; (3) used randomized controlled trial (RCT) or quasi-experimental designs; and (4) were published in English, Spanish or Portuguese. Members of our multidisciplinary team assessed the risk of bias in the reviewed studies using the Cochrane Collaboration's Risk of Bias Tool. Results: Our database searches yielded five studies. The studies were conducted in the U.S. and Brazil. Three studies were RCTs, and two used quasi-experimental designs. The sample sizes ranged from 18 to 230 patient-caregiver dyads. These studies culturally adapted the intervention contents and implementation methods and involved bilingual interventionists. The interventions had beneficial effects on multiple aspects of psychosocial outcomes for both patients and caregivers. We also identified methodological limitations in the reviewed studies. Conclusions: Findings from this systematic review help deepen our understanding of family-based psychosocial interventions for Latinos affected by cancer. The small number of psychosocial interventions focused on adult Latino cancer patients and their caregivers is concerning, considering that Latino populations are disproportionally burdened by cancer. Future research needs to design and evaluate culturally-appropriate interventions to support Latino patients and families who cope with cancer. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=274993, identifier CRD42021274993.

Association between salt intake and gastric atrophy by Helicobacter pylori infection: first results from the Epidemiological Investigation of Gastric Malignancy (ENIGMA).

PURPOSE: Gastric atrophy (GA), usually linked to chronic infection with Helicobacter pylori (H. pylori), may over time evolve into gastric malignancy. Besides H. pylori, high salt intake may play a role in GA development. This study evaluates cross sectionally the association between salt intake and GA in Chilean adults. METHODS: Population-based samples were recruited from two sites, Antofagasta and Valdivia, partaking in the Epidemiological Investigation of Gastric Malignancies. At recruitment, participants answered questionnaires and provided biospecimens. Salt intake (g/day) was estimated from casual spot urine samples using the Tanaka equation. GA was determined by serum pepsinogen levels. Only participants ≥ 40 to 70 years of age were considered in this analysis, n = 565. For the association between salt intake (as sex-specific quartiles) and GA, odds ratios (ORs) and the corresponding 95% confidence intervals (CI) were estimated through multivariable logistic regression. RESULTS: In women, the multivariable-adjusted OR for GA comparing quartile 4 of the estimated salt intake (12.8 g/day) to quartile 1 (6.6 g/day) was 1.18 (95% CI 0.52-2.68, P-trend = 0.87). The corresponding OR in men was 0.49 (95% CI 0.19-1.27, P-trend = 0.17) with salt intakes of 12.8 g/day and 7.1 g/day for quartiles 4 and 1, respectively. CONCLUSION: There was little evidence for an association between salt intake estimated from spot urine and GA risk in our cross-sectional analysis of middle aged and older adults in Chile. Reverse causation bias cannot be ruled out and the sample size was limited to provide more precise estimates.

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.

Inflammatory profiles in Chilean Mapuche and non-Mapuche women with gallstones at risk of developing gallbladder cancer.

Chile has high incidence rates of gallbladder cancer globally, particularly among Amerindian women, who also have a high prevalence of gallstones. We examined differences in inflammatory biomarkers between Mapuche and non-Mapuche women from the Chile Biliary Longitudinal Study, a cohort of women with ultrasound-detected gallstones. We randomly selected 200 Mapuche women frequency matched to non-Mapuche women on age and statin use Inflammatory biomarkers were analyzed using a multiplex assay and linear regression to assess associations of a priori markers (CCL20, CXCL10, IL-6, and IL-8) with ethnicity. Novel biomarkers were analyzed using exploratory factor analysis (EFA) and sufficient dimension reduction (SDR) to identify correlated marker groups, followed by linear regression to examine their association with ethnicity. The mean values of IL-8 were higher in Mapuche than non-Mapuche women (P = 0.04), while CCL20, CXCL10, and IL-6 did not differ significantly by ethnicity. EFA revealed two marker groups associated with ethnicity (P = 0.03 and P < 0.001). SDR analysis confirmed correlation between the biomarkers and ethnicity. We found higher IL-8 levels among Mapuche than non-Mapuche women. Novel inflammatory biomarkers were correlated with ethnicity and should be studied further for their role in gallbladder disease. These findings may elucidate underlying ethnic disparities in gallstones and carcinogenesis among Amerindians.

Regional variations in Helicobacter pylori infection, gastric atrophy and gastric cancer risk: The ENIGMA study in Chile.

BACKGROUND: Regional variations in gastric cancer incidence are not explained by prevalence of Helicobacter pylori, the main cause of the disease, with several areas presenting high H. pylori prevalence but low gastric cancer incidence. The IARC worldwide H. pylori prevalence surveys (ENIGMA) aim at systematically describing age and sex-specific prevalence of H. pylori infection around the world and generating hypotheses to explain regional variations in gastric cancer risk. METHODS: We selected age- and sex-stratified population samples in two areas with different gastric cancer incidence and mortality in Chile: Antofagasta (lower rate) and Valdivia (higher rate). Participants were 1-69 years old and provided interviews and blood for anti-H. pylori antibodies (IgG, VacA, CagA, others) and atrophy biomarkers (pepsinogens). RESULTS: H. pylori seroprevalence (Age-standardized to world population) and antibodies against CagA and VacA were similar in both sites. H. pylori seroprevalence was 20% among children <10 years old, 40% among 10-19 year olds, 60% in the 20-29 year olds and close to or above 80% in those 30+ years. The comparison of the prevalence of known and potential H. pylori cofactors in gastric carcinogenesis between the high and the low risk area showed that consumption of chili products was significantly higher in Valdivia and daily non-green vegetable consumption was more common in Antofagasta. Pepsinogen levels suggestive of gastric atrophy were significantly more common and occurred at earlier ages in Valdivia, the higher risk area. In a multivariate model combining both study sites, age, chili consumption and CagA were the main risk factors for gastric atrophy. CONCLUSIONS: The prevalence of H. pylori infection and its virulence factors was similar in the high and the low risk area, but atrophy was more common and occurred at younger ages in the higher risk area. Dietary factors could partly explain higher rates of atrophy and gastric cancer in Valdivia. IMPACT: The ENIGMA study in Chile contributes to better understanding regional variations in gastric cancer incidence and provides essential information for public health interventions.

Estudio de metales urinarios y plomo en sangre: parámetros poblacionales en Antofagasta, 2018 / Urinary heavy metals and blood lead levels among residents of Antofagasta, Chile

Background: The presence of toxic metals in human populations is strongly associated with chronic diseases. Aim: To determine levels of lead, chromium, cadmium, mercury and inorganic arsenic (AsIn) in the general population aged over 5 years in Antofagasta, Chile. Material and Methods: People living in Urban Antofagasta for at least five years were considered eligible. Biological samples were obtained to measure heavy metals. Results: One thousand two hundred three participants with a median age of 43 years (656 women) were studied. Their mean time of residence in the city was 30 years, and 52% smoked. Eight percent of the adult population and 12% of children had AsIn values above 35 µg/L, while 75% of the population had levels below 21.9 µg/L. The other metals were below the risk levels defined by the health authority (10 µg/L for chromium, 10 µg/L for mercury, 2 µg/L for cadmium, 5 and 10 μg/dL for blood lead for children and adults, respectively). The factors associated with high levels of AsIn in adults were male sex, living more than 200 meters from monitoring points, and low schooling. In children, the associated variables were high intake of seafood products and having a caregiver with less than 8 years of schooling. Contrary to expectations, the greatest risk of presenting altered levels of the metals occurred in the population living more than 500 meters from the identified risk sources (90% of the population). Conclusions: The findings of this study suggest that all potential sources of exposure to AsIn should be evaluated, and surveillance actions should be established to reduce involuntary exposure to this metalloid.

[Urinary heavy metals and blood lead levels among residents of Antofagasta, Chile]. / Estudio de metales urinarios y plomo en sangre: parámetros poblacionales en Antofagasta, 2018.

BACKGROUND: The presence of toxic metals in human populations is strongly associated with chronic diseases. AIM: To determine levels of lead, chromium, cadmium, mercury and inorganic arsenic (AsIn) in the general population aged over 5 years in Antofagasta, Chile. MATERIAL AND METHODS: People living in Urban Antofagasta for at least five years were considered eligible. Biological samples were obtained to measure heavy metals. RESULTS: One thousand two hundred three participants with a median age of 43 years (656 women) were studied. Their mean time of residence in the city was 30 years, and 52% smoked. Eight percent of the adult population and 12% of children had AsIn values above 35 µg/L, while 75% of the population had levels below 21.9 µg/L. The other metals were below the risk levels defined by the health authority (10 µg/L for chromium, 10 µg/L for mercury, 2 µg/L for cadmium, 5 and 10 µg/dL for blood lead for children and adults, respectively). The factors associated with high levels of AsIn in adults were male sex, living more than 200 meters from monitoring points, and low schooling. In children, the associated variables were high intake of seafood products and having a caregiver with less than 8 years of schooling. Contrary to expectations, the greatest risk of presenting altered levels of the metals occurred in the population living more than 500 meters from the identified risk sources (90% of the population). CONCLUSIONS: The findings of this study suggest that all potential sources of exposure to AsIn should be evaluated, and surveillance actions should be established to reduce involuntary exposure to this metalloid.

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.

Salmonella enterica serovar Typhi and gallbladder cancer: a case-control study and meta-analysis.

In Chile, where gallbladder cancer (GBC) rates are high and typhoid fever was endemic until the 1990s, we evaluated the association between Salmonella enterica serovar Typhi (S. Typhi) antibodies and GBC. We tested 39 GBC cases, 40 gallstone controls, and 39 population-based controls for S. Typhi Vi antibodies and performed culture and quantitative polymerase chain reaction for the subset with bile, gallstone, tissue, and stool samples available. We calculated gender and education-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association with GBC. We also conducted a meta-analysis of >1000 GBC cases by combining our results with previous studies. GBC cases were more likely to have high Vi antibody titer levels than combined controls (OR: 4.0, 95% CI: 0.9-18.3), although S. Typhi was not recovered from bile, gallstone, tissue, or stool samples. In our meta-analysis, the summary relative risk was 4.6 (95% CI: 3.1-6.8, Pheterogeneity =0.6) for anti-Vi and 5.0 (95% CI: 2.7-9.3, Pheterogeneity  = 0.2) for bile or stool culture. Our results are consistent with the meta-analysis. Despite differences in study methods (e.g., S. Typhi detection assay), most studies found a positive association between S. Typhi and GBC. However, the mechanism underlying this association requires further investigation.

HPV16/18 genotyping for the triage of HPV positive women in primary cervical cancer screening in Chile.

BACKGROUND: We previously conducted a population-based screening trial of high-risk human papillomavirus (hrHPV) testing and conventional cytology, demonstrating higher sensitivity (92.7 % vs 22.1 % for CIN2+) but lower positive predictive value (10.5 % vs 23.9 %) of hrHPV testing. Here we report the performance of HPV16/18 genotyping to triage the hrHPV positive participants. METHODS: Women aged 25 years and older received hrHPV (Hybrid Capture 2) and Papanicolaou testing; positives by either test underwent colposcopy and directed biopsy, as did a sample of double-negatives. hrHPV positive women were reflex-tested with HPV16/18 genotyping (Digene HPV Genotyping PS Test). RESULTS: Among the 8,265 participants, 10.7 % were hrHPV positive, 1.7 % had ASCUS+ cytology, 1.2 % had CIN2+; 776 (88 %) hrHPV positive women had complete results, of whom 38.8 % were positive for HPV16 (24.0 %), HPV18 (9.7 %) or both (5.1 %). CIN2+ prevalence in HPV16/18 positive women (16.3 %, 95 % CI 12.3-20.9) was twice that of HPV16/18 negative women (8.0 %, 95 % CI 5.7-10.8). HPV16/18 genotyping identified 40.5 % of CIN2, 66.7 % of CIN3 and 75.0 % of cancers. Compared to hrHPV screening alone, HPV16/18 triage significantly reduced the referral rate (10.7 % vs 3.7 %) and the number of colposcopies required to detect one CIN2+ (9 vs 6). When HPV16/18 negative women with baseline ASCUS+ cytology were also colposcopied, an additional 14 % of CIN2+ was identified; referral increased slightly to 4.2 %. CONCLUSIONS: HPV16/18 triage effectively stratified hrHPV positive women by their risk of high-grade lesions. HPV16/18 positive women must be referred immediately; referral could be deferred in HPV16/18 negative women given the slower progression of non-HPV16/18 lesions, however, they will require active follow-up.

[Human papillomavirus testing in cervical cancer screening at a public health service of Santiago, Chile]. / Examen de detección de virus papiloma humano en el tamizaje de cáncer cervicouterino en un Servicio de Salud de Santiago, Chile.

BACKGROUND: Molecular techniques for human papillomavirus (HPV) detection have a good performance as screening tests and could be included in cervical cancer early detection programs. We conducted a population-based trial comparing HPV detection and Papanicolaou as primary screening tests, in a public health service in Santiago, Chile. AIM: To describe the experience of implementing this new molecular test and present the main results of the study. MATERIAL AND METHODS: Women aged 25 to 64 enrolled in three public health centers were invited to participate. In all women, samples were collected for Papanicolaou and HPV DNA testing, and naked-eye visual inspection of the cervix with acetic acid was performed. Women with any positive screening test were referred to the local area hospital for diagnostic confirmation with colposcopy and biopsy of suspicious lesions. RESULTS: Screening results were obtained for 8265 women, of whom 931 (11.3%) were positive to any test. The prevalence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was 1.1%; nine women had invasive cervical cancer. Sensitivities for the detection of CIN2+ were 22.1% (95% confidence interval (CI) 16.4-29.2) for Papanicolaou and 92.7% (95% CI 84.4-96.8) for HPV testing; specificities were 98.9% (95% CI 98.7-99.0) and 92.0% (95% CI 91.4-92.6) respectively. CONCLUSION: This experience showed that the implementation of a molecular test for cervical cancer screening is not a major challenge in Chile: it was well accepted by both the health team and the participants, and it may improve the effectiveness of the screening program.

Examen de detección de virus papiloma humano en el tamizaje de cáncer cervicouterino en un Servicio de Salud de Santiago, Chile / Human papillomavirus testing in cervical cancer screening at a public health service of Santiago, Chile

Background: Molecular techniques for human papillomavirus (HPV) detection have a good performance as screening tests and could be included in cervical cancer early detection programs. We conducted a population-based trial comparing HPV detection and Papanicolaou as primary screening tests, in a public health service in Santiago, Chile. Aim: To describe the experience of implementing this new molecular test and present the main results of the study. Material and Methods: Women aged 25 to 64 enrolled in three public health centers were invited to participate. In all women, samples were collected for Papanicolaou and HPV DNA testing, and naked-eye visual inspection of the cervix with acetic acid was performed. Women with any positive screening test were referred to the local area hospital for diagnostic confirmation with colposcopy and biopsy of suspicious lesions. Results: Screening results were obtained for 8265 women, of whom 931 (11.3%) were positive to any test. The prevalence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was 1.1%; nine women had invasive cervical cancer. Sensitivities for the detection of CIN2+ were 22.1% (95% confidence interval (CI) 16.4-29.2) for Papanicolaou and 92.7% (95% CI 84.4-96.8) for HPV testing; specificities were 98.9% (95% CI 98.7-99.0) and 92.0% (95% CI 91.4-92.6) respectively. Conclusion: This experience showed that the implementation of a molecular test for cervical cancer screening is not a major challenge in Chile: it was well accepted by both the health team and the participants, and it may improve the effectiveness of the screening program.

Epidemiology of Helicobacter pylori infection in six Latin American countries (SWOG Trial S0701).

OBJECTIVE: To investigate the potential determinants of Helicobacter pylori infection between adults 21-65 years old. METHODS: Data are from the initial screening visit of a randomized clinical trial of three antibiotic regimens to eradicate H. pylori, conducted in seven sites (Santiago-Chile, Túquerres-Colombia, Guanacaste-Costa Rica, Copán-Honduras, Obregón and Tapachula-México, León-Nicaragua). Thousand eight hundred and fifty-nine adults from the general population were screened for H. pylori infection using an urea breath test (UBT) and were interviewed to assess socioeconomic-, demographic-, and symptom-related characteristics. Logistic regression was used to assess the relationship between these characteristics and H. pylori positivity at enrollment. RESULTS: Among the 1,852 eligible participants for whom a conclusive UBT result was obtained, H. pylori prevalence was 79.4 %, ranging from 70.1 to 84.7 % among the seven centers. Prevalence did not differ by sex (female: 78.4, male: 80.9; p = 0.20) or age (p = 0.08). H. pylori positivity increased with increasing number of siblings (p trend <0.0001). Participants with education beyond 12 years were less likely to be UBT-positive (OR 0.4: 0.3-0.6, compared to participants with 0-6 years of schooling) as were those employed outside the home (OR 0.7: 0.6-1.0). Odds of H. pylori infection increased with the presence of certain living conditions during childhood including having lived in a household with an earth floor (OR 1.8: 1.4-2.4), lack of indoor plumbing (OR 1.3: 1.0-1.8) and crowding (OR 1.4: 1.0-1.8, for having more than two persons per bedroom). Regarding current household conditions, living with more than 3 children in the household (OR 1.7: 1.2-2.5) and crowding (OR 1.8: 1.3-2.3) were associated with H. pylori infection. CONCLUSIONS: The prevalence of H. pylori in adults was high and differed significantly among the six Latin American countries studied (p < 0.001). Our findings confirm the strong link between poor socioeconomic conditions and H. pylori infection.