Background:Pregnancies affected by metabolic dysfunction-associated steatotic liver disease (MASLD) have tripled over the past decade. However, tools to assess MASLD in pregnancy are limited to ultrasound, which has shown poor reproducibility and does not provide quantitative data. Current guidelines for non-pregnant adults recommend the use of vibration-controlled transient elastography (VCTE) with controlled attenuation parameter (CAP) for staging and monitoring of liver disease. Given the limitations of ultrasound and the scarcity of data on use of VCTE in pregnancy, we evaluated the use of VCTE to determine the prevalence of MASLD in a pregnant population. Also, we determined the association between increased VCTE-derived CAP scores and adverse pregnancy outcomes. Methods:Pregnant individuals with no history of liver disease presenting for routine prenatal care were followed up throughout pregnancy and had VCTE-derived CAP assessments at 24-32 weeks of gestation. Postpartum VCTE-derived CAP assessments were also obtained. Multivariable logistic regression was performed to evaluate for predictors of liver steatosis (CAP) and liver stiffness (liver stiffness measurement [LSM]) and association with adverse pregnancy outcomes. Findings:247 pregnant individuals (mean age 30·0 years [SD 6·0]; mean pre-pregnancy BMI 30 kg/m² [SD 6·1]) had VCTE assessments during pregnancy. The prevalence of MASLD was 11% (95% CI 7-15%) based on VCTE-derived CAP and evidence of cardiometabolic disease. On multivariable analyses, pre-pregnancy BMI was a predictor of increased CAP scores (odds ratio [OR] 1·13, 95% CI 1·05-1·22), whereas polycystic ovary syndrome was a predictor of liver stiffness (4·79, 1·11-20·65). Increased CAP scores were associated with the development of intrahepatic cholestasis of pregnancy (OR 12·07, 95% CI 1·97-73·87) and LSM with large for gestational age (8·33, 1·02-67·87). Of those with postpartum follow-up (n=41), 24 (59%) individuals had an increase in postpartum CAP scores by at least 10%. Interpretation:We found a high prevalence of MASLD in pregnancy that might not have otherwise been diagnosed. Pre-pregnancy BMI was the strongest predictor of liver steatosis and polycystic ovary syndrome for liver stiffness. Increased VCTE-derived CAP assessment results were associated with certain adverse pregnancy outcomes; however, this result should be interpreted with caution given the small sample size. VCTE-derived CAP assessment could be a useful non-invasive bedside tool to diagnose and assess liver disease in the obstetric context. The prognostic value of VCTE-derived CAP requires further investigation. Funding:National Institutes of Health-The National Heart, Lung, and Blood Institute, and Irma T Hirschl Monique Weill-Caulier Trust.

OBJECTIVES:Men who have sex with men living with HIV (MSMLWH) are at highest risk for human papillomavirus (HPV)-associated anal cancer, which may originate from the anal canal, verge or perianal skin. Perianal lesions are frequently overlooked during examination, and their (pre)malignant burden in this population remains poorly characterized. METHODS:A total of 308 MSMLWH who underwent high-resolution anoscopy (HRA)-guided perianal biopsy between 2018 and 2024 were analysed. Demographics, clinical HIV parameters, smoking history, HPV vaccination status, anal cytology, high-risk HPV test results and histologic diagnoses were collected. Risk factors for perianal (pre)cancer were assessed using chi-square and rank-sum tests. RESULTS:Median age was 52 years (range 27-72). Prevalence of abnormal anal cytology (atypical squamous cells of undetermined significance [ASCUS] or worse), high-risk HPV and HPV16 was 85%, 77% and 30%, respectively. Intra-anal high-grade squamous intraepithelial lesion (HSIL) was detected in 48%. Histologic diagnoses of perianal lesions included negative (n = 12, 4%), low-grade squamous intraepithelial lesions (LSIL) (n = 236, 77%), HSIL (n = 55, 18%), basal cell carcinoma (n = 1, <1%) and superficially invasive squamous cell carcinoma (SISCCA, n = 4, 1%). Perianal HSIL without intra-anal HSIL occurred in 8% of participants, with 82% of HSILs found in verrucous lesions. Perianal HSIL/SISCCA was strongly associated with high-risk HPV, HPV16 and intra-anal HSIL (p = 0.002). HPV16 was the strongest predictor (odds ratio [OR] 5.6; 95% CI 2.9-10.8). CONCLUSIONS:Perianal lesions in MSMLWH have significant (pre)malignant potential, particularly in the context of HPV16 infection. Thorough examination and low threshold for biopsy are essential for effective cancer prevention.

BACKGROUND:Neural regulation contributes to pancreatic ductal adenocarcinoma (PDAC) development but effects of neural-targeting medications on presentation or outcomes remain unclear. METHODS:We conducted a retrospective study using the Veterans Affairs (VA) Corporate Data Warehouse (CDW) to identify patients with pancreatic cancer (2000-2020). Exposure to beta blocker, cholinergics or statins was defined by active prescriptions within 6 months before or 1 month after diagnosis. Outcomes included histologic subtype, stage, and overall survival (OS). Propensity score matching was performed for each medication class, with survival assessed using Kaplan-Meier and Cox regression models. RESULTS:Among 7,578 Veterans with pancreatic cancer, 76% had adenocarcinoma and 60% presented with stage IV disease. Beta blocker use was associated with lower odds of advanced stage (OR 0.55, 95% CI 0.5-0.63, p<0.0001) and improved OS (HR 0.89, 95%CI 0.84-0.95, p<0.0001). Cholinergic agonist use was associated with reduced likelihood of adenocarcinoma histology (OR 0.64, 95% CI 0.41-1.01, p=0.051) and advanced stage (OR 0.53, 95%CI 0.34-0.85, p=<0.0001), but not OS. Statin use was associated with adenocarcinoma histology (OR 1.24, 95%CI 1.09-1.43, p=0.002) and lower odds of advanced stage (OR 0.77, 95%CI 0.68-0.88, p=<0.0001). CONCLUSIONS:Beta blockers were associated with earlier stage and improved survival. Cholinergic agonists and statins were associated with earlier stage. Cholinergic agonists were linked to lower likelihood of adenocarcinoma histology, while statins to higher likelihood. These findings suggest neural and metabolic pathways may shape early PDAC biology. IMPACT:Autonomic and metabolic pathways may influence PDAC biology. Beta blockers merit mechanistic and clinical evaluation as adjunctive therapies.

INTRODUCTION: Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease of pregnancy, varying in incidence based on population and associated with adverse outcomes. We assessed the prevalence and outcomes of ICP categories defined by the 2023 European Association for the Study of the Liver guidelines in a diverse US population. METHODS: We conducted a retrospective cohort study (January 2009–April 2024) at our ethnically diverse health system. Suspected ICP patients were identified by pregnancy records with total serum bile acids (TSBA) ordered and categorized into Group A (normal TSBA, alanine aminotransferase [ALT]/aspartate aminotransferase [AST]), B (elevated ALT/AST, normal TSBA), or C (TSBA >19, normal or elevated ALT/AST). RESULTS: Among 165,503 pregnancies, we identified 4,386 (3.6%) suspected ICP cases. The cohort was classified as A (65%), B (24%), or C (11%). On multivariable analysis, a pre-existing history of autoimmune disease, metabolic dysfunction-associated steatotic liver disease, and gestational hypertension were significantly associated with Group B compared with A. Group C was more strongly associated with Hispanic ethnicity, history of hepatitis C, and immune-mediated liver diseases. Preeclampsia was 3 times as common in Groups B and C compared with A. Group C had the highest odds of spontaneous preterm birth, meconium-stained amniotic fluid, and neonatal respiratory distress. Group B and C had higher rates of incident postpartum hepatobiliary diseases. DISCUSSION: Our systematic evaluation of the 2023 European Association for the Study of the Liver guidelines for suspected ICP demonstrated that this novel group-based classification offers clinically meaningful risk stratification. Our findings support that both elevated TSBA (Group C) and elevated ALT/AST alone (Group B) warrant antepartum surveillance for adverse pregnancy outcomes. Group C's association with Hispanic ethnicity and pre-existing liver disease highlights the need for individualized monitoring during pregnancy. Group-specific increased incidence of postpregnancy hepatobiliary disease emphasizes the importance of targeted postpartum follow-up.

BACKGROUND:Following the success of the ANCHOR (Anal Cancer-HSIL Outcomes Research) trial, the U.S. Department of Health and Human Services recommends anal cancer screening for high-risk persons, particularly men who have sex with men (MSM) with HIV. OBJECTIVE:To quantify the cost-effectiveness and benefits versus harms of different anal cancer screening strategies. DESIGN:Microsimulation model. DATA SOURCES:The ANCHOR trial and published literature. TARGET POPULATION:MSM with HIV. TIME HORIZON:Lifetime. PERSPECTIVE:Health care sector. INTERVENTION:Cytology alone and human papillomavirus (HPV) testing (high-risk HPV [hrHPV], HPV16/18, and HPV16), co-testing, and triage options; ages at which to begin screening (≥35, ≥40, or ≥45 years); screening interval (annual, biennial, triennial, or quadrennial). OUTCOME MEASURES:Incremental cost-effectiveness ratios (ICERs) of dollars per quality-adjusted life-year (QALY) and the tradeoff of harms (high-resolution anoscopies [HRAs]) versus benefits (cancer cases averted and life-years gained). RESULTS OF BASE-CASE ANALYSIS:Screening initiation at age 35 years or older using cytology dominated initiation at ages 40 and 45 years or older, with ICERs ranging from $87 731 for a quadrennial interval to $350 100 for an annual interval. In the comparative analysis, the following unique strategies were on the cost-effectiveness frontier: quadrennial HPV16, quadrennial HPV16/18, triennial HPV16/18, triennial hrHPV, biennial HPV16/18, biennial hrHPV, annual cytology with hrHPV triage, and annual hrHPV; ICERs ranged from $81 341 to $2 510 847. In the harm-to-benefit analysis, triage options offered the most efficient HRA use. RESULTS OF SENSITIVITY ANALYSIS:ICERs decreased for newly eligible persons. For 35-year-old newly eligible MSM with HIV, ICERs for cytology ranged from $70 750 (quadrennial) to $223 895 (annual). LIMITATION:Findings are not generalizable to other high-risk populations. CONCLUSION:Anal cancer screening among MSM with HIV aged 35 years or older is cost-effective, but value-based prioritization of strategies is needed to optimize screening use. PRIMARY FUNDING SOURCE:National Cancer Institute.

This cohort study estimates anal cancer incidence in women with a history of cervical cancer, by age and time since diagnosis.

Women with a history of vulvar cancer face a high risk of anal cancer; however, incidence according to histology, age-at, and time since vulvar cancer diagnosis remains unexplored. Using data from SEER-8 and SEER-17 registries, we identified 21,230 women with vulvar cancer, with 154,825 person-years follow-up from 1975 to 2021. We observed 95 anal cancer cases, resulting in an incidence of 61.4 per 100,000 person-years (95% CI, 49.6-75.0). Incidence was higher among women with vulvar squamous cell carcinoma (SCC) (78.7; 95% CI, 62.9-97.1) than vulvar non-SCC (19.8; 95% CI, 9.0-37.6). The highest incidence (>100 per 100,000) was observed in women <45 years old with vulvar SCC and those >10 years post-diagnosis. These findings could inform anal cancer screening guidelines, as women with vulvar cancer, particularly those diagnosed with SCC, may substantially benefit from heightened surveillance or targeted screening.