Case report: Primary vulvar adenocarcinoma of mammary gland type-its genetic characteristics by focused next-generation sequencing.

Mammary-like vulvar adenocarcinoma (MLVA) is an exceedingly rare subtype of vulvar adenocarcinoma that shares features with mammary gland tissue. Due to its rarity and lack of consensus, MLVA presents diagnostic challenges to pathologists. We present the case of a 59-year-old female with an ulcerated mass on the right side of the external genitalia, diagnosed as MLVA. Comprehensive immunohistochemistry (IHC) and gene sequencing studies were performed to characterize the tumor. IHC analysis revealed triple expression of hormonal receptors (estrogen receptor, progesterone receptor, and HER2), supporting the mammary gland origin of the tumor. Gene sequencing identified unique genetic mutations associated with the expression of hormonal markers. One fusion gene (ERBB2-NAGLU) has not been reported in any tumors, and other mutations with unique mutation types have not been previously reported in MLVA. Our findings shed light on the molecular characteristics of MLV and may help improve the diagnosis and treatment of this rare type of vulvar adenocarcinoma.

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.

Impact of Social Distancing and Travel Restrictions on Non-Coronavirus Disease 2019 (Non-COVID-19) Respiratory Hospital Admissions in Young Children in Rural Alaska.

Hospitalizations due to non-coronavirus disease 2019 (non-COVID-19) respiratory illnesses decreased dramatically after social distancing was implemented in a high-risk population in rural Alaska; an unprecedented decline compared to the past 10 respiratory seasons. This demonstrates the potential secondary benefits of implementing social distancing and travel restrictions on respiratory illnesses.

Respiratory syncytial virus and influenza hospitalizations in Alaska native adults.

BACKGROUND: Alaska Native (AN) infants from Yukon Kuskokwim Delta (YKD) have the highest U.S. infant hospitalization rate for respiratory syncytial virus (RSV). RSV can cause significant morbidity and mortality in adult populations, although the RSV burden in AN adults is unknown. Here we investigate RSV, influenza, and human metapneumovirus (hMPV) in hospitalized rural AN adults. METHODS: YKD AN adults, hospitalized with acute respiratory illness between November 2016 and October 2018 were enrolled prospectively. Nasopharyngeal (NP) swabs were tested for RSV, influenza and hMPV using polymerase chain reaction. Hospitalization rates were calculated. RESULTS: Of 251 patients who had an NP swab, RSV was detected in 8 (3.2 %), influenza in 31 (12.4 %), and hMPV in no patients. Weighted annual rates of lower respiratory tract infection (LRTI), RSV and influenza hospitalization were 192.0 (95 % CI: 176.5-208.4), 9.1 (6.0-13.3), and 42.2 (35.1-50.2) per 10,000. The most common discharge diagnosis was pneumonia (57.0 %), followed by chronic obstructive pulmonary disease (51.4 %). Ninety-eight percent (246/251) had a medical co-morbidity and 49.8 % (125/251) lived in a house with a smoker. Overall, 6.4 % (16/251) required mechanical ventilation, and 3.6 % (9/251) died during hospitalization. Only 35.7 % (66/185) of patients admitted during influenza season had received the annual influenza vaccine. DISCUSSION: We examined adult LRTI, influenza, and RSV hospitalization rates in an AN population with high infant RSV hospitalization rates. While we confirmed a high rate of hospitalization from LRTIs and influenza, we did not find a high rate due to RSV or hMPV. Improving influenza vaccination rates, and addressing co-morbidities could reduce respiratory hospitalizations.

Molecular Classification of Gastric Cancer among Alaska Native People.

Gastric cancer is an aggressive and heterogeneous malignancy that often varies in presentation and disease among racial and ethnic groups. The Alaska Native (AN) people have the highest incidence and mortality rates of gastric cancer in North America. This study examines molecular markers in solid tumor samples from eighty-five AN gastric adenocarcinoma patients using next-generation sequencing, immunohistochemistry, and in situ hybridization analysis. AN patients have a low mutation burden with fewer somatic gene mutations in their tumors compared to other populations, with the most common mutation being TP53. Epstein-Barr virus (EBV) was associated with 20% of AN gastric cancers, which is higher than the world average of 10%. The inflammation marker, cyclooxygenase-2 (COX-2), is highly expressed in patients with the lowest survival rates. Mismatch repair deficiency was present in 10% of AN patients and was associated with patients who were female, 50 years or older, gene mutations, and tumors in the distal stomach. Program death-ligand 1 (PD-L1) was expressed in 14% of AN patients who were more likely to have MMR deficiency, EBV-associated gastric cancers, and mutations in the PIK3CA gene, all of which have been linked to clinical response to PD-1 inhibitors. These studies suggest a portion of AN gastric cancer patients could be candidates for immunotherapy. Overall, this study highlights future avenues of investigation for clinical and translational studies, so that we can improve early detection and develop more effective treatments for AN patients.

Risk-Based Prenatal Hepatitis C Testing Practices and Results, Alaska 2013-2016.

Hepatitis C virus (HCV) infection in pregnant women is of concern as it presents a health threat not only to the mother, but also to her infant. A retrospective analysis was performed to evaluate HCV testing and exposure in women who delivered infants between 2013 and 2016 at a referral hospital in Alaska. Multiple risk behaviors were evaluated, including drug dependency or abuse (drug abuse), tobacco use, alcohol dependency or abuse, and late presentation to prenatal care. Of the 2856 women who delivered between 2013 and 2016, 470 (16.5%) were tested for HCV during pregnancy and 1356 (47.5%) were tested at any time prior to delivery (including pregnancy); 62 (2.2%) were positive for HCV antibodies. Of the 162 women with a documented history of drug abuse, 95 (58.6%) were tested for HCV during pregnancy and 143 (88.3%) were tested at any time prior to delivery (including pregnancy); 30 (18.5%) were positive for HCV antibodies. Forty-nine women (34%) with a documented history of drug abuse who were not previously known to be HCV positive were not tested for HCV during their pregnancy. In conclusion, approximately 2% of pregnant women in the study population were known to have been exposed to HCV by the time of their delivery. One-third of women with documented drug abuse did not have an HCV test during pregnancy, revealing gaps in HCV testing of pregnant women. Further studies are needed to understand the full costs and benefits of risk-based screening versus universal screening in this and other populations.

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.

Rickets and vitamin D deficiency in Alaska native children.

BACKGROUND: Rickets and vitamin D deficiency appeared to increase in Alaskan children starting in the 1990s. We evaluated the epidemiology of rickets and vitamin D deficiency in Alaska native (AN) children in 2001-2010. METHODS: We analyzed 2001-2010 visits with rickets or vitamin D deficiency diagnosis for AN and American Indian children and the general US population aged <10 years. We conducted a case-control study of AN rickets/vitamin D deficient cases and age- and region-matched controls. RESULTS: In AN children, annual rickets-associated hospitalization rate (2.23/100,000 children/year) was higher than the general US rate (1.23; 95% CI 1.08-1.39). Rickets incidence increased with latitude. Rickets/vitamin D deficiency cases were more likely to have malnutrition (OR 38.1; 95% CI 4.9-294), had similar breast-feeding prevalence, and were less likely to have received vitamin D supplementation (OR 0.23; 95% CI 0.1-0.87) than controls. CONCLUSIONS: Our findings highlight the importance of latitude, malnutrition, and lack of vitamin D supplementation as risk factors for rickets.

Patterns of clinical response to PSA elevation in American Indian/Alaska Native men: a multi-center pilot study.

OBJECTIVE: To assess clinical treatment patterns and response times among American Indian/Alaska Native men with a newly elevated PSA. METHODS: We retrospectively identified men ages 50-80 receiving care in one of three tribally-operated clinics in Northern Minnesota, one medical center in Alaska, and who had an incident PSA elevation (> 4 ng/ml) in a specified time period. A clinical response was considered timely if it was documented as occurring within 90 days of the incident PSA elevation. RESULTS: Among 82 AI/AN men identified from medical records with an incident PSA elevation, 49 (60%) received a timely clinical response, while 18 (22%) had no documented clinical response. CONCLUSIONS: One in five AI/AN men in our study had no documented clinical action following an incident PSA elevation. Although a pilot study, these findings suggest the need to improve the documentation, notification, and care following an elevated PSA at clinics serving AI/AN men.

HPV genotypes detected in cervical cancers from Alaska Native women, 1980-2007.

BACKGROUND: Human papillomavirus (HPV) vaccine prevents cervical pre-cancers and cancers caused by HPV types 16 and 18. This study provides information on the HPV types detected in cervical cancers of Alaska Native (AN) women. METHODS: Cases of invasive cervical cancer diagnosed in AN women aged 18 and above between 1980 and 2007 were identified from the Alaska Native Tumor Registry. A representative formalin-fixed, paraffin-embedded archived pathology block was retrieved and serially sectioned to allow histologic confirmation of lesion (first and last sections) and PCR testing of intervening sections. Extracted DNA was tested for HPV using Linear Array HPV Genotyping Test (Roche Diagnostics) with additional INNO-LiPA HPV Genotyping Assay (Innogenetics) testing on negative or inadequate specimens. All specimens were tested for a minimum 37 HPV types. RESULTS: Of 62 cervical cancer specimens evaluated, 57 (91.9%) contained one or more HPV types. Thirty-eight (61.2%) cancers contained HPV types 16 or 18, and 18 (29%) contained an oncogenic type other than type 16 or 18. CONCLUSIONS: Overall, almost two-thirds (61.2%) of the archived cervical cancers had detectible HPV types 16 or 18, a finding similar to studies of US women. As expected, a proportion of cancers would not be prevented by the current vaccines. HPV vaccination and cervical cancer screening are important prevention strategies for AN women.