Cost-Effectiveness of Multitarget Stool DNA Testing vs Colonoscopy or Fecal Immunochemical Testing for Colorectal Cancer Screening in Alaska Native People.

OBJECTIVE: To estimate the cost-effectiveness of multitarget stool DNA testing (MT-sDNA) compared with colonoscopy and fecal immunochemical testing (FIT) for Alaska Native adults. PATIENTS AND METHODS: A Markov model was used to evaluate the 3 screening test effects over 40 years. Outcomes included colorectal cancer (CRC) incidence and mortality, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). The study incorporated updated evidence on screening test performance and adherence and was conducted from December 15, 2016, through November 6, 2019. RESULTS: With perfect adherence, CRC incidence was reduced by 52% (95% CI, 46% to 56%) using colonoscopy, 61% (95% CI, 57% to 64%) using annual FIT, and 66% (95% CI, 63% to 68%) using MT-sDNA. Compared with no screening, perfect adherence screening extends life by 0.15, 0.17, and 0.19 QALYs per person with colonoscopy, FIT, and MT-sDNA, respectively. Colonoscopy is the most expensive strategy: approximately $110 million more than MT-sDNA and $127 million more than FIT. With imperfect adherence (best case), MT-sDNA resulted in 0.12 QALYs per person vs 0.05 and 0.06 QALYs per person by FIT and colonoscopy, respectively. Probabilistic sensitivity analyses supported the base-case analysis. Under varied adherence scenarios, MT-sDNA either dominates or is cost-effective (ICERs, $1740-$75,868 per QALY saved) compared with FIT and colonoscopy. CONCLUSION: Each strategy reduced costs and increased QALYs compared with no screening. Screening by MT-sDNA results in the largest QALY savings. In Markov model analysis, screening by MT-sDNA in the Alaska Native population was cost-effective compared with screening by colonoscopy and FIT for a wide range of adherence scenarios.

Presence of cagPAI genes and characterization of vacA s, i and m regions in Helicobacter pylori isolated from Alaskans and their association with clinical pathologies.

Introduction. Gastric cancer is a health disparity in the Alaska Native people. The incidence of Helicobacter pylori infection, a risk factor for non-cardia gastric adenocarcinoma, is also high. Gastric cancer is partially associated with the virulence of the infecting strain.Aim. To genotype the vacA s, m and i and cag pathogenicity island (cagPAI) genes in H. pylori from Alaskans and investigate associations with gastropathy.Methodology. We enrolled patients with gastritis, peptic ulcer disease (PUD) and intestinal metaplasia (IM) in 1998-2005 and patients with gastric cancer in 2011-2013. Gastric biopsies were collected and cultured and PCR was performed to detect the presence of the right and left ends of the cagPAI, the cagA, cagE, cagT and virD4 genes and to genotype the vacA s, m and i regions.Results. We recruited 263 people; 22 (8 %) had no/mild gastritis, 121 (46 %) had moderate gastritis, 40 (15%) had severe gastritis, 38 (14 %) had PUD, 30 (11 %) had IM and 12 (5 %) had gastric cancer. H. pylori isolates from 150 (57%) people had an intact cagPAI; those were associated with a more severe gastropathy (P≤0.02 for all comparisons). H. pylori isolates from 77 % of people had either the vacA s1/i1/m1 (40 %; 94/234) or s2/i2/m2 (37 %; 86/234) genotype. vacA s1/i1/m1 was associated with a more severe gastropathy (P≤0.03 for all comparisons).Conclusions. In this population with high rates of gastric cancer, we found that just over half of the H. pylori contained an intact cagPAI and 40 % had the vacA s1/i1/m1 genotype. Infection with these strains was associated with a more severe gastropathy.

A prospective cohort analysis of gut microbial co-metabolism in Alaska Native and rural African people at high and low risk of colorectal cancer.

BACKGROUND: Alaska Native (AN) people have the world's highest recorded incidence of sporadic colorectal cancer (CRC) (∼91:100,000), whereas rural African (RA) people have the lowest risk (<5:100,000). Previous data supported the hypothesis that diet affected CRC risk through its effects on the colonic microbiota that produce tumor-suppressive or -promoting metabolites. OBJECTIVES: We investigated whether differences in these metabolites may contribute to the high risk of CRC in AN people. METHODS: A cross-sectional observational study assessed dietary intake from 32 AN and 21 RA healthy middle-aged volunteers before screening colonoscopy. Analysis of fecal microbiota composition by 16S ribosomal RNA gene sequencing and fecal/urinary metabolites by 1H-NMR spectroscopy was complemented with targeted quantification of fecal SCFAs, bile acids, and functional microbial genes. RESULTS: Adenomatous polyps were detected in 16 of 32 AN participants, but not found in RA participants. The AN diet contained higher proportions of fat and animal protein and less fiber. AN fecal microbiota showed a compositional predominance of Blautia and Lachnoclostridium, higher microbial capacity for bile acid conversion, and low abundance of some species involved in saccharolytic fermentation (e.g., Prevotellaceae, Ruminococcaceae), but no significant lack of butyrogenic bacteria. Significantly lower concentrations of tumor-suppressive butyrate (22.5 ± 3.1 compared with 47.2 ± 7.3 SEM µmol/g) coincided with significantly higher concentrations of tumor-promoting deoxycholic acid (26.7 ± 4.2 compared with 11 ± 1.9 µmol/g) in AN fecal samples. AN participants had lower quantities of fecal/urinary metabolites than RA participants and metabolite profiles correlated with the abundance of distinct microbial genera in feces. The main microbial and metabolic CRC-associated markers were not significantly altered in AN participants with adenomatous polyps. CONCLUSIONS: The low-fiber, high-fat diet of AN people and exposure to carcinogens derived from diet or environment are associated with a tumor-promoting colonic milieu as reflected by the high rates of adenomatous polyps in AN participants.

Alaska Native Patient and Provider Perspectives on the Multitarget Stool DNA Test Compared With Colonoscopy for Colorectal Cancer Screening.

Objective: Alaska Native (AN) people have among the world's highest rate of colorectal cancer (CRC). We assessed perceptions of AN people and their health care providers of a new take-home multitarget stool DNA test (MT-sDNA; Cologuard) relative to colonoscopy. Methods: Cross-sectional surveys of AN people aged 40 to 75 years (mailed) and providers (online). Results: Participants included 1616 AN patients (19% response rate) and 87 providers (26% response rate; 57% AN people). Over half (58%) of patients preferred colonoscopy for CRC screening, while 36% preferred MT-sDNA. Unscreened patients were significantly more likely to state a preference for MT-sDNA than previously screened patients (42% vs 31%, P < .05) as were younger patients (<60 years old) compared with older patients (40% vs 30%, P < .05). Most providers thought that MT-sDNA would improve screening rates (69%), would recommend if available (79%), and be implementable (79%). Perceived barriers differed substantially between patients and providers in both type and magnitude. Leading colonoscopy barriers reported by patients were travel (44%) and bowel preparation (40%), while providers thought that fear of pain (92%) and invasiveness of the test (87%) were the primary barriers. For MT-sDNA, patients' belief that colonoscopy was better (56%) and not knowing how to do the test (40%) were primary barriers, while providers thought stool collection (67%) and having a stool sample in their home (63%) were leading barriers. Conclusions: This study found that MT-sDNA has potential acceptability among AN people and their health care providers. Both groups reported a willingness to use MT-sDNA and did not perceive major barriers to its use. This preference was especially true of unscreened and younger patients. The majority of providers indicated they would use MT-sDNA if available and that it would improve CRC screening rates. In this population, where colonoscopy access is limited, MT-sDNA has the potential to improve CRC screening adherence.

High Prevalence of Adenomatous Polyps in Alaska Native People Aged 40-49 years.

BACKGROUND: Although colorectal cancer occurs earlier in life and at twice the frequency in Alaska Native (AN) people compared with the general population, the colorectal polyp burden in this group has not been quantified. In addition, an appropriate age for initial screening in ANs has not been defined. MATERIALS AND METHODS: A retrospective chart review of 766 AN people who had screening colonoscopy from 2015 to 2016 was performed. The polyp burden in patients aged 40-49 y was compared with that in those aged 50-59 y in both the AN and the general US populations. RESULTS: In total, 345 adenomas were removed: 121 (35%) from 40- to 49-year-olds and 224 (65%) from 50- to 59-year-olds. Twenty-six percent of AN people aged 40 y to 49 y and 40% of AN people aged 50 to 59 y had at least one adenoma. Low- and high-risk adenomas were significantly less frequent in the younger group (22% versus 29%, P = 0.048; 9.2% versus 15%, P = 0.035; respectively). Advanced adenomas were also less frequent in the younger group, although not statistically significant. Polyp histology, size, location, and morphology did not differ significantly between groups. CONCLUSIONS: The adenoma and advanced adenoma prevalence in 40- to 49-year-old AN people is high, suggesting colorectal cancer screening should begin at age 40 y in ANs.

H. pylori-associated pathologic findings among Alaska native patients.

Helicobacter pylori infection is common among Alaska native (AN) people, however scant gastric histopathologic data is available for this population. This study aimed to characterise gastric histopathology and H. pylori infection among AN people. We enrolled AN adults undergoing upper endoscopy. Gastric biopsy samples were evaluated for pathologic changes, the presence of H. pylori, and the presence of cag pathogenicity island-positive bacteria. Of 432 persons; two persons were diagnosed with gastric adenocarcinoma, two with MALT lymphoma, 40 (10%) with ulcers, and 51 (12%) with intestinal metaplasia. Fifty-five per cent of H. pylori-positive persons had cag pathogenicity island positive bacteria. The gastric antrum had the highest prevalence of acute and chronic moderate-severe gastritis. H. pylori-positive persons were 16 and four times more likely to have moderate-severe acute gastritis and chronic gastritis (p < 0.01), respectively. An intact cag pathogenicity island positive was correlated with moderate-severe acute antral gastritis (53% vs. 31%, p = 0.0003). H. pylori-positive persons were more likely to have moderate-severe acute and chronic gastritis compared to H. pylori-negative persons. Gastritis and intestinal metaplasia were most frequently found in the gastric antrum. Intact cag pathogenicity island positive was correlated with acute antral gastritis and intestinal metaplasia.

Stool DNA Testing for Screening Detection of Colorectal Neoplasia in Alaska Native People.

OBJECTIVE: To assess the accuracy of a multitarget stool DNA test (MT-sDNA) compared with fecal immunochemical testing for hemoglobin (FIT) for detection of screening-relevant colorectal neoplasia (SRN) in Alaska Native people, who have among the world's highest rates of colorectal cancer (CRC) and limited access to conventional screening approaches. PATIENTS AND METHODS: We performed a prospective, cross-sectional study of asymptomatic Alaska Native adults aged 40-85 years and older undergoing screening or surveillance colonoscopy between February 6, 2012, and August 7, 2014. RESULTS: Among 868 enrolled participants, 661 completed the study (403 [61%] women). Overall, SRN detection by MT-sDNA (49%) was superior to that by FIT (28%; P<.001); in the screening group, SRN detection rates were 50% and 31%, respectively (P=.01). Multitarget stool DNA testing detected 62% of adenomas 2 cm or larger vs 29% by FIT (P=.05). Sensitivity by MT-sDNA increased with adenoma size (to 80% for lesions ≥3 cm; P=.01 for trend) and substantially exceeded FIT sensitivity at all adenoma sizes. For sessile serrated polyps larger than 1 cm (n=9), detection was 67% by MT-sDNA vs 11% by FIT (P=.07). For CRC (n=10), detection was 100% by MT-sDNA vs 80% by FIT (P=.48). Specificities were 93% and 96%, respectively (P=.03). CONCLUSION: The sensitivity of MT-sDNA for cancer and larger polyps was high and significantly greater than that of FIT for polyps of any size, while specificity was slightly higher with FIT. These findings could translate into high cumulative neoplasm detection rates on serial testing within a screening program. The MT-sDNA represents a potential strategy to expand CRC screening and reduce CRC incidence and mortality, especially where access to endoscopy is limited.

A Process Evaluation of the Alaska Native Colorectal Cancer Family Outreach Program.

This article presents the results of a process evaluation of the Alaska Native (AN) Colorectal Cancer (CRC) Family Outreach Program, which encourages CRC screening among AN first-degree relatives (i.e., parents, siblings, adult children; hereafter referred to as relatives) of CRC patients. Among AN people incidence and death rates from CRC are the highest of any ethnic/racial group in the United States. Relatives of CRC patients are at increased risk; however, CRC can be prevented and detected early through screening. The evaluation included key informant interviews (August to November 2012) with AN and non-AN stakeholders and program document review. Five key process evaluation components were identified: program formation, evolution, outreach responses, strengths, and barriers and challenges. Key themes included an incremental approach that led to a fully formed program and the need for dedicated, culturally competent patient navigation. Challenges included differing relatives' responses to screening outreach, health system data access and coordination, and the program impact of reliance on grant funding. This program evaluation indicated a need for more research into motivating patient screening behaviors, electronic medical records systems quality improvement projects, improved data-sharing protocols, and program sustainability planning to continue the dedicated efforts to promote screening in this increased risk population.

Case-control study of breast cancer and exposure to synthetic environmental chemicals among Alaska Native women.

BACKGROUND: Exposure to environmental chemicals may impair endocrine system function. Alaska Native (AN) women may be at higher risk of exposure to these endocrine disrupting chemicals, which may contribute to breast cancer in this population. OBJECTIVE: To measure the association between exposure to select environmental chemicals and breast cancer among AN women. DESIGN: A case-control study of 170 women (75 cases, 95 controls) recruited from the AN Medical Center from 1999 to 2002. Participants provided urine and serum samples. Serum was analyzed for 9 persistent pesticides, 34 polychlorinated biphenyl (PCB) congeners, and 8 polybrominated diethyl ether (PBDE) congeners. Urine was analyzed for 10 phthalate metabolites. We calculated geometric means (GM) and compared cases and controls using logistic regression. RESULTS: Serum concentrations of most pesticides and 3 indicator PCB congeners (PCB-138/158; PCB-153, PCB-180) were lower in case women than controls. BDE-47 was significantly higher in case women (GM=38.8 ng/g lipid) than controls (GM=25.1 ng/g lipid) (p=0.04). Persistent pesticides, PCBs, and most phthalate metabolites were not associated with case status in univariate logistic regression. The odds of being a case were higher for those with urinary mono-(2-ethylhexyl) phthalate (MEHP) concentrations that were above the median; this relationship was seen in both univariate (OR 2.16, 95% CI 1.16-4.05, p=0.02) and multivariable (OR 2.43, 95% CI 1.13-5.25, p=0.02) logistic regression. Women with oestrogen receptor (ER)-/progesterone receptor (PR)-tumour types tended to have higher concentrations of persistent pesticides than did ER+/PR+ women, although these differences were not statistically significant. CONCLUSIONS: Exposure to the parent compound of the phthalate metabolite MEHP may be associated with breast cancer. However, our study is limited by small sample size and an inability to control for the confounding effects of body mass index. The association between BDE-47 and breast cancer warrants further investigation.

Helmet use among Alaskan children involved in off-road motorized vehicle crashes.

BACKGROUND: Off-road motorized vehicle crashes are a common source of trauma among Alaska children. Injury morbidity is worse in Alaska Native children than non-Native children, but the reasons are unclear. OBJECTIVE: To evaluate the differences in helmet use between the Native and the non-Native children, and to assess the impact of helmet use on injury patterns and outcomes. DESIGN: This retrospective cohort study identified patients aged 17 or younger admitted after all-terrain vehicle, snowmobile or motorbike injury between 2001 and 2011 from the Alaska Trauma Registry. Helmeted and non-helmeted patients were compared with respect to demographics, central nervous system (CNS) injury and the overall risk of death or permanent disability. Logistic regression was used to evaluate predictors of helmet use and the effects of ethnicity and helmet use on outcomes. RESULTS: Of the 921 injured children, 51% were Alaska Native and 49% were non-Native. Helmet use was lower among Native versus non-Native patients on unadjusted comparison (24% vs. 71%) and multivariable logistic regression (OR 0.17, 95% CI 0.11-0.27, p<0.0001). Prevalence of CNS injury was higher among Native children (39.7% vs. 30.4%, p=0.016). However, on logistic regression with adjustment for helmet use, Native ethnicity was not a significant predictor of CNS injury (OR 1.07, 95% CI 0.68-1.68, p=0.78), whereas helmet use was strongly protective against CNS injury (OR 0.28, 95% CI 0.18-0.44, p<0.0001) as well as death or permanent disability (OR 0.26, 95% CI 0.10-0.67, p=0.006). CONCLUSIONS: Helmet use is lower among Alaska Native children involved in off-road motorized vehicle crashes. These ethnic disparities in helmet use contribute to higher rates of CNS injury among Native children. Helmet use significantly improves overall outcome. Helmet promotion efforts should be expanded, especially in Native communities.

Paediatric trauma on the Last Frontier: an 11-year review of injury mechanisms, high-risk injury patterns and outcomes in Alaskan children.

BACKGROUND: Paediatric trauma system development in Alaska is complicated by a vast geographic coverage area, wide regional variations in environment and culture, and a lack of available published data. OBJECTIVE: To provide a detailed description of paediatric trauma mechanisms, high-risk injury patterns and outcomes in Alaska. DESIGN: This retrospective study included all children aged 17 years or younger in the State of Alaska Trauma Registry database admitted with traumatic injury between 2001 and 2011. Each injury record was reviewed individually and assigned a mechanism based on Centers for Disease Control E-codes. Geographic definitions were based on existing Emergency Medical Services regions. Mechanisms were compared by geographic region, patient demographics, injury characteristics and outcome. Subgroup analysis of fatal injuries was performed to identify causes of death. RESULTS: Of 5,547 patients meeting inclusion criteria, the most common mechanisms of injury were falls (39%), motor vehicle collisions (10%) and all-terrain vehicle (ATV) accidents (9%). The overall case fatality rate was 2%. Mechanisms with the greatest risk of death were gunshot wounds (21%), pedestrians struck by motorized vehicles (9%) and motor vehicle collisions (5%). These 3 mechanisms accounted for 15% of injuries but 60% of deaths in the overall cohort. Injury patterns involving combined central nervous system (CNS) and torso injuries were unusual but especially lethal, occurring in 3% of patients but carrying a case fatality rate of 18%. Although the distribution of mechanisms was generally similar for each geographic region, ATV and snowmobile injuries were significantly more common in remote areas (23% remote vs. 7% non-remote, p < 0.0001). CONCLUSIONS: Mechanisms of paediatric trauma in Alaska have widely varying impacts on outcome and show some variation by region. Highest-risk mechanisms include gunshot wounds and motorized vehicle-related accidents. Prevention efforts should give special attention to CNS injury prevention, ATV and snowmobile safety in remote areas, and optimization of management of multisystem trauma. Further studies should investigate predictors of outcome in greater detail.

Helicobacter pylori infection and markers of gastric cancer risk in Alaska Native persons: a retrospective case-control study.

BACKGROUND: Alaska Native persons experience gastric cancer incidence and mortality rates that are three to four times higher than in the general United States population. OBJECTIVE: To evaluate pepsinogen I, pepsinogen I/II ratio, anti-Helicobacter pylori and cytotoxin-associated gene A (CagA) antibody levels, and blood group for their associations with gastric cancer development in Alaska Native people. METHODS: The present analysis was a retrospective case-control study that matched gastric cancers reported to the Alaska Native Tumor Registry from 1969 to 2008 to three controls on known demographic risk factors for H pylori infection, using sera from the Alaska Area Specimen Bank. Conditional logistic regression evaluated associations between serum markers and gastric cancer. RESULTS: A total of 122 gastric cancer cases were included, with sera predating cancer diagnosis (mean = 13 years) and 346 matched controls. One hundred twelve cases (91.8%) and 285 controls (82.4%) had evidence of previous or ongoing H pylori infection as measured by anti-H pylori antibody levels. Gastric cancer cases had a 2.63-fold increased odds of having positive anti-H pylori antibodies compared with their matched controls (P=0.01). In a multivariate model, noncardia gastric cancer (n=94) was associated with anti-H pylori antibodies (adjusted OR 3.92; P=0.004) and low pepsinogen I level (adjusted OR 6.04; P=0.04). No association between gastric cancer and blood group, anti-CagA antibodies or pepsinogen I/II ratio was found. CONCLUSION: Alaska Native people with gastric cancer had increased odds of previous H pylori infection. Low pepsinogen I level may function as a precancer marker for noncardia cancer.

Comparison of fecal occult blood tests for colorectal cancer screening in an Alaska Native population with high prevalence of Helicobacter pylori infection, 2008-2012.

INTRODUCTION: Alaska Native colorectal cancer (CRC) incidence and mortality rates are the highest of any ethnic/racial group in the United States. CRC screening using guaiac-based fecal occult blood tests (gFOBT) are not recommended for Alaska Native people because of false-positive results associated with a high prevalence of Helicobacter pylori-associated hemorrhagic gastritis. This study evaluated whether the newer immunochemical FOBT (iFOBT) resulted in a lower false-positive rate and higher specificity for detecting advanced colorectal neoplasia than gFOBT in a population with elevated prevalence of H. pylori infection. METHODS: We used a population-based sample of 304 asymptomatic Alaska Native adults aged 40 years or older undergoing screening or surveillance colonoscopy (April 2008-January 2012). RESULTS: Specificity differed significantly (P < .001) between gFOBT (76%; 95% CI, 71%-81%) and iFOBT (92%; 95% CI, 89%-96%). Among H. pylori-positive participants (54%), specificity of iFOBT was even higher (93% vs 69%). Overall, sensitivity did not differ significantly (P = .73) between gFOBT (29%) and iFOBT (36%). Positive predictive value was 11% for gFOBT and 32% for iFOBT. CONCLUSION: The iFOBT had a significantly higher specificity than gFOBT, especially in participants with current H. pylori infection. The iFOBT represents a potential strategy for expanding CRC screening among Alaska Native and other populations with elevated prevalence of H. pylori, especially where access to screening endoscopy is limited.

The effect of Helicobacter pylori infection on iron stores and iron deficiency in urban Alaska Native adults.

BACKGROUND: Helicobacter pylori (H. pylori) infection has been correlated with low serum ferritin and iron deficiency. As a secondary analysis of a study of H. pylori reinfection, we investigated the association of H. pylori infection and the effect of its eradication on serum ferritin and iron deficiency. METHODS: Alaska Native adults undergoing esophagogastroduodenoscopy had sera collected and a (13) C urea breath test (UBT) was performed. Those H. pylori positive were treated with an antibiotic regimen; those who tested negative 2 months after treatment were evaluated at 4, 6, 12, and 24 months by UBT and serum ferritin with an immunoradiometric assay. We excluded persons from further analysis if they were prescribed iron by their provider. RESULTS: We measured serum ferritin for 241 persons; 121/241 were H. pylori positive. The geometric mean ferritin (GMF) for persons with and without H. pylori infection was 37 µg/L and 50 µg/L, respectively (p = .04). At enrollment, 19/121 H. pylori-positive persons had iron deficiency compared with 8/120 H. pylori negative (p = .02). Among 66 persons tested at 24 months, the GMF was higher at 24 months (49.6 µg/L) versus enrollment (36.5 µg/L; p = .02). Six of 11 persons with iron deficiency at enrollment no longer had iron deficiency and had a higher GMF (p = .02) 24 months after treatment. CONCLUSIONS: H. pylori infection was correlated with lower serum ferritin and iron deficiency. After H. pylori eradication, serum ferritin increased and approximately half of persons resolved their iron deficiency. Testing for H. pylori infection and subsequent treatment of those positive could be considered in persons with unexplained iron deficiency.

Colorectal cancer in alaska native people, 2005-2009.

BACKGROUND: Colorectal cancer (CRC) is the most frequently diagnosed cancer among Alaska Native (AN) people, and the second leading cause of cancer death. The incidence rate for the combined years 1999 through 2003 was 30% higher than the rate among U.S. whites (USWs) for the same period. Current incidence rates may serve to monitor the impact of screening programs in reducing CRC in the AN population. METHODS: Incidence data are from the Alaska Native Tumor Registry and the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) Program. We compared AN CRC incidence, survival rates, and stage at diagnosis with rates in USWs for cases diagnosed from 2005 through 2009. Relative survival calculations were produced in SEER*Stat by the actuarial method. RESULTS: The CRC age-adjusted incidence rate among AN men and women combined was higher than those in USW men and women (84 vs. 43/100,000; P < .05; AN:USW rate ratio [RR] = 2.0). The greatest differences between rates in AN people and USWs were for tumors in the hepatic flexure (RR = 3.1) and in the transverse (RR = 2.9) and sigmoid (RR = 2.5) regions of the colon. Rectal cancer rates among AN people were significantly higher than rates in USWs (21 vs.12/100,000). Five-year relative survival proportions by stage at diagnosis indicate that the CRC 5-year relative survival was similar in AN people and USWs for the period 2004 through 2009. CONCLUSIONS: The high rate of CRC in AN people emphasizes the need for screening programs and interventions to reduce known modifiable risks. Research in methods to promote healthy behaviors among AN people is greatly needed.

Diagnostic accuracy of tests for Helicobacter pylori in an Alaska Native population.

AIM: To evaluate the accuracy of two non-invasive tests in a population of Alaska Native persons. High rates of Helicobacter pylori (H. pylori) infection, H. pylori treatment failure, and gastric cancer in this population necessitate documentation of infection status at multiple time points over a patient's life. METHODS: In 280 patients undergoing endoscopy, H. pylori was diagnosed by culture, histology, rapid urease test, (13)C urea breath test (UBT), and immunoglobulin G antibodies to H. pylori in serum. The performances of (13)C-UBT and antibody test were compared to a gold standard defined by a positive H. pylori test by culture or, in case of a negative culture result, by positive histology and a positive rapid urease test. RESULTS: The sensitivity and specificity of the (13)C-UBT were 93% and 88%, respectively, relative to the gold standard. The antibody test had an equivalent sensitivity of 93% with a reduced specificity of 68%. The false positive results for the antibody test were associated with previous treatment for an H. pylori infection [relative risk (RR) = 2.8]. High levels of antibodies to H. pylori were associated with chronic gastritis and male gender, while high scores in the (13)C-UBT test were associated with older age and with the H. pylori bacteria load on histological examination (RR = 4.4). CONCLUSION: The (13)C-UBT outperformed the antibody test for H. pylori and could be used when a non-invasive test is clinically necessary to document treatment outcome or when monitoring for reinfection.

Characterization of Helicobacter pylori cagA and vacA genotypes among Alaskans and their correlation with clinical disease.

Helicobacter pylori infection is common in Alaska. The development of severe H. pylori disease is partially determined by the virulence of the infecting strain. Here we present vacA and cagA genotype data for H. pylori strains isolated from Alaskans and their correlation with clinical disease. We enrolled patients scheduled for esophagogastroduodenoscopy and positive for H. pylori infection. Gastric biopsy specimens from the stomach antrum and fundus were cultured. We performed PCR analysis of the H. pylori vacA gene and for the presence of the cagA gene and cagA empty site. We genotyped 515 H. pylori samples from 220 Native and 66 non-Native Alaskans. We detected the cagA gene in 242/286 (85%) persons; of 222 strains that could be subtyped, 95% (212) were non-Asian cagA and 3% (6) were East Asian cagA. After removing mixed infections (n = 17), 83% of H. pylori strains had either the vacA s1m1 (120/269) or s2m2 (103/269) genotype. Sixty-six percent (68/103) of H. pylori strains with the vacA s2m2 genotype also contained the cagA gene. Infection with an H. pylori strain having the cagA gene or vacA s1m1 genotype (compared with s1m2 and s2m2) was associated with a decreased risk of esophagitis (P = 0.003 and 0.0003, respectively). Infection with an H. pylori strain having the vacA s1m1 genotype (compared with s1m2 and s2m2) was associated with an increased risk of peptic ulcer disease (PUD) (P = 0.003). The majority of H. pylori strains in this study carried the non-Asian cagA gene and either the vacA s1m1 or s2m2 genotype. A majority of H. pylori strains with the vacA s2m2 genotype also contained the cagA gene. There was an association of H. pylori genotype with esophagitis and PUD.

Development of a flexible sigmoidoscopy training program for rural nurse practitioners and physician assistants to increase colorectal cancer screening among Alaska Native people.

At the Alaska Native Medical Center in Anchorage, colorectal cancer screening rates improved dramatically with the initiation of a dedicated flexible sigmoidoscopy screening program staffed by mid-level providers. We describe the development and implementation of a program to train rural nurse practitioners and physician assistants in flexible sigmoidoscopy.