Search

BACKGROUND: Health status and life expectancy are important considerations for assessing potential benefits and harms of colorectal cancer (CRC) screening programs, particularly among older adults. METHODS: We examined receipt of past-year CRC screening according to predicted 10-year mortality risk among 25,888 community-dwelling adults aged 65-84 years who were not up-to-date with screening in the nationwide National Health Interview Survey. Ten-year mortality risk was estimated using a validated index; from the lowest to highest quintiles of the index, risk was 12%, 24%, 39%, 58%, and 79%, respectively. We also examined the proportion of screening performed among adults with life expectancy <10 years. RESULTS: The prevalence of past-year CRC screening was 39.5%, 40.6%, 38.7%, 36.4%, and 35.4%, from the lowest to highest quintile of 10-year mortality risk. Odds of CRC screening did not differ between adults in the lowest vs highest quintile (adjusted odds ratio 1.05, 95% confidence interval: 0.93-1.20). One-quarter (27.9%) of past-year CRC screening occurred in adults with life expectancy <10 years, and more than half (50.7%) of adults aged 75-84 years had 10-year mortality risk ≥50% at the time of screening. In an exploratory analysis, invasive but not noninvasive screening increased as 10-year mortality risk increased (P < 0.05) among adults aged 70-79 years. DISCUSSION: Past-year CRC screening does not differ by predicted 10-year mortality risk. An age-based approach to CRC screening results in underscreening of older, healthier adults and overscreening of younger adults with chronic conditions. Personalized screening with incorporation of individual life expectancy may increase the value of CRC screening programs. [ABSTRACT FROM AUTHOR]

Simple Summary: Atezolizumab plus bevacizumab (atezo + bev) is a preferred front-line treatment for unresectable hepatocellular carcinoma (HCC). However, there is limited real-world evidence regarding the use of atezo + bev and subsequent HCC therapies in clinical practice. This retrospective cohort study aimed to characterize the time to discontinuation of atezo + bev, sequencing of systemic therapy after atezo + bev, and time to next treatment. We identified 825 adults with HCC who were initiated on atezo + bev between June 2020 and June 2022. During a median follow-up of 15.3 months, most patients (72%) discontinued atezo + bev, with a median time to discontinuation of 3.5 months. Less than one in five (19%) received subsequent therapies (median time to subsequent treatment of 5.4 months); the most common subsequent agents were lenvatinib (6%), cabozantinib (4%), and nivolumab (4%). Further research is needed to identify those most likely to benefit from atezo + bev and evaluate optimal sequential HCC therapies to maximize overall survival. Real-world (RW) evidence is needed to evaluate atezolizumab plus bevacizumab (atezo + bev) utilization for hepatocellular carcinoma (HCC) in clinical practice. This retrospective cohort study used administrative claims databases to evaluate treatment patterns in individuals with HCC ≥18 years of age who were initiated on atezo + bev between June 2020 and June 2022. The endpoints of this study were the proportion of individuals who discontinued atezo + bev and received subsequent systemic therapies, time to discontinuation (TTD), and time to next treatment. Overall, 825 individuals were eligible (median age 67 years; 80% male). Over a median follow-up of 15.3 months, most (72%) discontinued atezo + bev, with a median TTD of 3.5 months. A minority (19%) received subsequent therapies, with the most common second-line agents being lenvatinib (6%), cabozantinib (4%), and nivolumab (4%). The median time from index to next treatment post-atezo + bev was 5.4 months. Further research is needed to identify the patients who are most likely to benefit from atezo + bev as well as later-line HCC therapies to optimize overall survival. [ABSTRACT FROM AUTHOR]

Major research efforts in liver cancer have been devoted to increasing the efficacy and effectiveness of surveillance for hepatocellular carcinoma (HCC). As with other cancers, surveillance programmes aim to detect tumours at an early stage, facilitate curative-intent treatment, and reduce cancer-related mortality. HCC surveillance is supported by a large randomised-controlled trial in patients with chronic HBV infection and several cohort studies in cirrhosis; however, effectiveness in clinical practice is limited by several barriers, including inadequate risk stratification, underuse of surveillance, and suboptimal accuracy of screening tests. There are several proposed strategies to address these limitations, including risk stratification algorithms and biomarkers to better identity at-risk individuals, interventions to increase surveillance, and emerging imaging- and blood-based surveillance tests with improved sensitivity and specificity for early HCC detection. Beyond clinical validation, data are needed to establish clinical utility, i.e. increased early tumour detection and reduced HCC-related mortality. If successful, these data could facilitate a precision screening paradigm in which surveillance strategies are tailored to individual HCC risk to maximise overall surveillance value. However, practical and logistical considerations must be considered when designing and implementing these validation efforts. To address these issues, ILCA (the International Liver Cancer Association) adjourned a single topic workshop on HCC risk stratification and surveillance in June 2022. Herein, we present a white paper on these topics, including the status of the field, ongoing research efforts, and barriers to the translation of emerging strategies. [ABSTRACT FROM AUTHOR]

Background: COVID-19 has resulted in over 1 million deaths in the U.S. as of June 2022, with continued surges after vaccine availability. Information on related attitudes and behaviors are needed to inform public health strategies. We aimed to estimate the prevalence of COVID-19, risk factors of infection, and related attitudes and behaviors in a racially, ethnically, and socioeconomically diverse urban population. Methods: The DFW COVID-19 Prevalence Study Protocol 1 was conducted from July 2020 to March 2021 on a randomly selected sample of adults aged 18–89 years, living in Dallas or Tarrant Counties, Texas. Participants were asked to complete a 15-minute questionnaire and COVID-19 PCR and antibody testing. COVID-19 prevalence estimates were calculated with survey-weighted data. Results: Of 2969 adults who completed the questionnaire (7.4% weighted response), 1772 (53.9% weighted) completed COVID-19 testing. Overall, 11.5% of adults had evidence of COVID-19 infection, with a higher prevalence among Hispanic and non-Hispanic Black persons, essential workers, those in low-income neighborhoods, and those with lower education attainment compared to their counterparts. We observed differences in attitudes and behaviors by race and ethnicity, with non-Hispanic White persons being less likely to believe in the importance of mask wearing, and racial and ethnic minorities more likely to attend social gatherings. Conclusion: Over 10% of an urban population was infected with COVID-19 early during the pandemic. Differences in attitudes and behaviors likely contribute to sociodemographic disparities in COVID-19 prevalence. [ABSTRACT FROM AUTHOR]

Abdominal ultrasound, with or without alpha-fetoprotein, is the recommended strategy for hepatocellular carcinoma (HCC) surveillance but misses over one-third of HCC at an early stage. Emerging imaging modalities, including computed tomography and magnetic resonance imaging, have early data showing high sensitivity for early-stage HCC, but potential issues such as radiologic capacity, patient acceptance, cost-effectiveness, and need for validation in Western non-hepatitis B virus populations still need to be evaluated. Similarly, blood-based biomarker panels, including GALAD and liquid biopsy techniques, have shown promising data in phase II case-control studies and may concurrently help address issues of surveillance underuse; however, these tools require validation in phase III and IV cohort studies. While awaiting prospective validation data for these emerging strategies, ultrasound with or without alpha-fetoprotein remains the current gold standard HCC surveillance strategy. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, and the incidence in the United States (USA) is increasing. Generally curative therapies are only possible for early-stage cancers, thus biomarkers that can be used to detect early-stage cancers are needed. Here, we describe the identification of a new biomarker that when used as a part of an algorithm can be used for the early detection of HCC with high accuracy. We have previously identified alterations in glycosylation on serum proteins from patients with HCC and developed plate-based assays using lectins to detect the change in glycosylation. However, heterophilic antibodies, which increase with non-malignant liver disease, compromised these assays. To address this, we developed a method of polyethylene glycol (PEG) precipitation that removed the contaminating IgG and IgM but allowed for the lectin detection of the relevant glycoprotein. We found that this PEG-precipitated material itself could differentiate between cirrhosis and HCC. In the analysis of three training cohorts and one validation cohort, consisting of 571 patients, PEG-IgG had AUC values that ranged from 0.713 to 0.810. In the validation cohort, which contained samples from patients at a time of 1–6 months prior to HCC detection or 7+ months prior to detection, the AUC of this marker remained consistent (0.813 and 0.846, respectively). When this marker was incorporated into a biomarker algorithm that also consisted of AFP and fucosylated kininogen, the AUROC increased to 0.816–0.883 in the training cohort and was 0.909 in the external validation cohort. Biomarker performance was also examined though the analysis of partial ROC curves, at false positive values less than 10% (90-ROC), ≤20% (80-ROC) or ≤30% (70-ROC), which highlighted the algorithm's improvement over the individual markers at clinically relevant specificity values. [ABSTRACT FROM AUTHOR]

Background: Curative surgical treatments afford the best prognosis for patients with intrahepatic cholangiocarcinoma (iCCA); however, the comparative effectiveness of treatment options and factors associated with curative treatment receipt for early stage iCCA remain unknown.Methods: The authors identified patients who were diagnosed with early stage iCCA, defined as a unifocal tumor <3 cm, during 2004-2018 from the National Cancer Database. Multivariable logistic and Cox regression analyses were used to identify the factors associated with curative treatment and overall survival (OS), respectively.Results: The proportion of patients with early stage iCCA increased from 4.5% in 2004 to 7.3% in 2018, with the odds of early stage detection increasing by 3.1% per year (odds ratio [OR], 1.031; 95% CI, 1.015-1.049). Of 1093 patients who had early stage iCCA, 464 (42.5%) underwent resection, 113 (10.3%) underwent ablation, 62 (5.7%) underwent liver transplantation, and 454 (41.5%) received noncurative treatments. Hispanic patients (adjusted OR [aOR], 0.57; 95% CI, 0.33-0.97) and Black patients (aOR, 0.47; 95% CI, 0.28-0.77) were less likely to receive curative treatments than White patients. Compared with patients who underwent surgical resection, those who underwent liver transplantation had a trend toward improved OS (adjusted hazard ratio [aHR], 0.63; 95% CI, 0.37-1.08), whereas those who underwent local ablation (aHR, 1.39; 95% CI, 1.01-1.92) and noncurative treatments (aHR, 3.97; 95% CI, 3.24-4.88) experienced worse OS.Conclusions: More than one third of patients with early stage iCCA did not receive curative treatment, with Hispanic and Black patients being less likely to receive curative treatments than White patients. Surgical resection and liver transplantation were associated with improved survival compared with local ablation. Future studies should investigate disparities in curative treatment receipt and outcomes for early stage iCCA. [ABSTRACT FROM AUTHOR]

There is controversy regarding the overall value of hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis given the lack of data from randomized-controlled trials. To address this issue, we conducted a systematic review and meta-analysis of cohort studies evaluating the benefits and harms of HCC surveillance in patients with cirrhosis. We performed a search of the Medline and EMBASE databases and national meeting abstracts from January 2014 through July 2020 for studies reporting early-stage HCC detection, curative treatment receipt, or overall survival, stratified by HCC surveillance status, among patients with cirrhosis. Pooled risk ratios (RRs) and hazard ratios, according to HCC surveillance status, were calculated for each outcome using the DerSimonian and Laird method for random effects models. We identified 59 studies including 145,396 patients with HCC, which was detected by surveillance in 41,052 (28.2%) cases. HCC surveillance was associated with improved early-stage detection (RR 1.86, 95% CI 1.73–1.98; I2 = 82%), curative treatment receipt (RR 1.83, 95% CI 1.69–1.97; I2 = 75%), and overall survival (hazard ratio 0.67, 95% CI 0.61–0.72; I2 = 78%) after adjusting for lead-time bias; however, there was notable heterogeneity in all pooled estimates. Four studies examined surveillance-related physical harms due to false positive or indeterminate surveillance results, but no studies examined potential financial or psychological harms. The proportion of patients experiencing surveillance-related physical harms ranged from 8.8% to 27.5% across studies, although most harms were mild in severity. HCC surveillance is associated with improved early detection, curative treatment receipt, and survival in patients with cirrhosis, although there was heterogeneity in pooled estimates. Available data suggest HCC surveillance is of high value in patients with cirrhosis, although continued rigorous studies evaluating benefits and harms are still needed. There has been ongoing debate about the overall value of hepatocellular carcinoma (HCC) screening in patients with cirrhosis given the lack of data from randomized-controlled trials. In a systematic review of contemporary cohort studies, we found that HCC screening is associated with improved early detection, curative treatment receipt, and survival in patients with cirrhosis, although there were fewer data quantifying potential screening-related harms. Available data suggest HCC screening is of high value in patients with cirrhosis, although continued studies evaluating benefits and harms are still needed. [Display omitted] • HCC surveillance was associated with improved early-stage detection, curative treatment receipt, and prolonged survival. • Semi-annual surveillance intervals were associated with improved early HCC detection and overall survival. • Few studies evaluated surveillance outcomes in post-SVR or NAFLD patient populations; thus, future research is warranted. • Few studies characterized surveillance-related harms, although available data suggest surveillance harms are mild in severity. [ABSTRACT FROM AUTHOR]

Although precision medicine is typically discussed in the context of therapeutic decisions, there has been increasing interest in applying this concept to cancer screening. While studies have examined precision screening for breast, colorectal, and lung cancer screening programs, fewer data evaluate this concept for hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis. Across HCC risk scores, the NNB was substantially higher in patients at low risk of HCC compared with higher risk patients, whereas the NNH was relatively stable across risk groups. [Extracted from the article]

Non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of developing hepatocellular carcinoma (HCC), especially among those who have cirrhosis or advanced fibrosis, but 20–30% of cases of NAFLD-related HCC occur in the absence of advanced fibrosis. The prevalence of NAFLD-related HCC is increasing in most countries worldwide. There are few direct data to support or refute the efficacy or effectiveness of HCC surveillance in NAFLD or to guide its application. We use evidence on surveillance in other conditions and studies on the clinical course of patients with NAFLD to arrive at recommendations for rational approaches to HCC surveillance in this growing cohort of patients. We also outline gaps in research and practice, including opportunities to advance the field. [ABSTRACT FROM AUTHOR]

Background: High out-of-pocket (OOP) expenditure and inadequate insurance coverage may adversely affect cancer survivors. We aimed to characterize the extent and correlates of healthcare utilization, OOP expenditures, and underinsurance among insured cancer survivors. Methods: We used 2011–2015 Medical Expenditure Panel Survey data to identify a nationally representative sample of insured non-elderly adult (age 18–64 years) cancer survivors. We used negative binomial, two-part (logistic and Generalized Linear Model with log link and gamma distribution), and logistic regression models to quantify healthcare utilization, OOP expenditures, and underinsurance, respectively, and identified sociodemographic correlates for each outcome. Results: We identified 2738 insured non-elderly cancer survivors. Adjusted average utilization of ambulatory, non-ambulatory, prescription medication, and dental services was 14.4, 0.51, 24.9, and 1.4 events per person per year, respectively. Higher ambulatory and dental services utilization were observed in older adults, females, non-Hispanic Whites, survivors with a college degree and high income, compared to their counterparts. Nearly all (97.7%) survivors had some OOP expenditures, with a mean adjusted OOP expenditure of $1552 per person per year. Adjusted mean OOP expenditures for ambulatory, non-ambulatory, prescription medication, dental, and other health services were $653, $161, $428, $194, and $83, respectively. Sociodemographic variations in service-specific OOP expenditures were generally consistent with respective utilization patterns. Overall, 8.8% of the survivors were underinsured. Conclusion: Many insured non-elderly cancer survivors allocate a substantial portion of their OOP expenditure for healthcare-related services and experience financial vulnerability, resulting in nearly 8.8% of the survivors being underinsured. Utilization of healthcare services varies across sociodemographic groups. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Underutilization of hepatocellular cancer (HCC) surveillance has been reported, although data evaluating interventions to improve surveillance are sparse. We assessed the effect of a population-based HCC surveillance program on HCC surveillance utilization and outcomes. METHODS: In this retrospective cohort study, we assessed preinclusion and postinclusion HCC surveillance patterns among 597 patients with hepatitis C virus cirrhosis enrolled in a program at an integrated health system between 2013 and 2020. Adequate surveillance was defined as at least 5 surveillance studies within 36 months pre-enrollment and postenrollment; a secondary outcome was proportion of time covered by surveillance over 36 months. Tumor size, stage, and receipt of curative therapy were compared between HCC detected on the first imaging examination (prevalent HCC) and surveillance-detected HCC (incident HCC). We performed Kaplan-Meier analysis and multivariable competing risk analysis to characterize the association between surveillance and mortality. RESULTS: The surveillance program significantly improved surveillance completion (77.6% vs 5.0%, P < 0.001) and proportion time covered (80.9% vs 15.8%, P < 0.001). Compared with prevalent HCC, surveillance-detected cases were more likely unifocal (77.8% vs 44.8%, P < 0.001), early-stage (85.2% vs 44.8%, P < 0.001), with smaller maximum diameter (median 2.3 vs 3.2 cm), and more likely to undergo curative therapy (92.5% vs 72.4% P = 0.010). Survival was improved compared with prevalent cases hazard ratio (HR) 0.23 (0.11-0.51) after adjusting for age and Model for End Stage Liver Disease score. DISCUSSION: Implementation of a population-based program resulted in significant improvement in HCC surveillance use and clinical outcomes among patients with hepatitis C virus cirrhosis. These findings may inform similar interventions by other healthcare systems. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The value of hepatocellular carcinoma (HCC) surveillance is defined by the balance of benefits, i.e., early tumor detection, and potential harms, related to false positive and indeterminate results. Although physical harms can be observed in 15%--20% of patients with cirrhosis undergoing HCC surveillance, previous cost-effectiveness analyses have not incorporated costs of harms. We aimed to evaluate the cost-effectiveness of HCC surveillance including both benefits and harms. DESIGN: We constructed a Markov model to compare surveillance strategies of ultrasound (US) alone, US and alpha fetoprotein (AFP), and no surveillance in 1 million simulated patients with compensated cirrhosis. Harms included imaging and biopsy in patients undergoing surveillance for HCC. Model inputs were based on literature review, and costs were derived from the Medicare fee schedule, with all costs inflated to 2018 dollars. The primary outcome was the incremental cost-effectiveness ratio per incremental quality-adjusted life-year. RESULTS: In the base case analysis, US with AFP was the dominant strategy over both US alone and no surveillance. In a probabilistic sensitivity analysis, US with AFP was the most cost-effective strategy in 80.1% of simulations at a willingness-to-pay threshold of $100,000 per quality-adjusted life-year. In our threshold analyses, an HCC incidence >0.4% per year and surveillance adherence >19.5% biannually were necessary for US with AFP to be cost-effective compared with no surveillance. DISCUSSION: Accounting for both surveillance-related benefits and harms, USand AFP is more cost-effective for HCC surveillance than US alone or no surveillance in patients with compensated cirrhosis. [ABSTRACT FROM AUTHOR]

Background/Aims: Semiannual hepatocellular carcinoma (HCC) surveillance is recommended in patients with cirrhosis; however, recent studies have raised questions over its utility. We investigated the impact of surveillance on early detection and survival in a nationally representative database. Methods: We included patients with cirrhosis and HCC from the Optum database (2001‐2015) with >6 months of follow‐up between cirrhosis and HCC diagnoses. Surveillance adherence was defined as proportion of time covered (PTC), with each 6‐month period after abdominal imaging defined as 'covered'. To determine the association between surveillance and mortality, we compared PTC between fatal and non‐fatal HCC. Results: Of 1001 patients with cirrhosis and HCC, 256 died with median follow‐up 30 months. Median PTC by any imaging was greater in early‐stage vs late‐stage HCC (43.6% vs 37.4%, P =.003) and non‐fatal vs fatal HCC (40.8% vs 34.3%, P =.001). In multivariable analyses, each 10% increase in PTC was associated with increased early HCC detection (OR 1.07, 95% CI 1.01‐1.12) and decreased mortality (HR 0.95; 95% CI 0.90‐1.00). On subgroup analysis, PTC by CT/MRI was associated with early tumour detection and decreased mortality; however, PTC by ultrasound was only associated with early detection but not decreased mortality. These findings were robust across sensitivity analyses. Conclusions: In a US cohort of privately insured HCC patients, PTC by any imaging modality was associated with increased early detection and decreased mortality. Continued evaluation of HCC surveillance strategies and effectiveness is warranted. [ABSTRACT FROM AUTHOR]

The burden of hepatocellular carcinoma (HCC) is highest in East Asia and Africa, although its incidence and mortality are rapidly rising in the United States and Europe. With the implementation of hepatitis B vaccination and hepatitis C treatment programmes worldwide, the epidemiology of HCC is shifting away from a disease predominated by viral hepatitis – an increasing proportion of cases are now attributable to non-alcoholic steatohepatitis. Surveillance using ultrasound, with or without alpha-fetoprotein, every 6 months has been associated with improved early detection and improved overall survival; however, limitations in implementation lead to a high proportion of HCC being detected at late stages in clinical practice. Herein, we review the current state of HCC surveillance and highlight areas for future research, including improved risk stratification of at-risk patients, surveillance tools with higher sensitivity and specificity for early HCC, and interventions to increase surveillance utilisation. [ABSTRACT FROM AUTHOR]

Purpose: To determine the prevalence and clinical significance of discordant LI-RADS® (Liver Imaging Reporting and Data System) liver observations on multiphase contrast-enhanced (MCE) magnetic resonance imaging (MRI) in patients with cirrhosis. Methods: This cross-sectional study included 93 cirrhosis patients who underwent 1.5 or 3 T MCE MRI for evaluation of hepatocellular carcinoma (HCC). Two abdominal radiologists independently reviewed T1-, T2-, diffusion-weighted unenhanced images as well as MCE T1-weighted fat-suppressed images and reported liver observations using LI-RADS®. Concordance were recorded for detection (co-detected by both radiologists or not), size category (< 10; 10–19; ≥ 20 mm), and LI-RADS® category assignment as reportable (LR-3/4/5/M) and actionable (LR-4/5/M). The overall concordance (i.e., concordant in detection, size, and LR-category) was calculated with 95% confidence interval [CI], and separately for detection, size, and LR-category. Clinical significance of discordance was assessed as impact on follow-up imaging, referral for biopsy, liver transplant eligibility, or treatment modality. Results: Reportable and actionable observations were overall concordant between two radiologists only in 32.3% [24.6, 41.0] and 40.1% [29.5, 51.5] of cases, respectively. Poor overall concordance was related to detection concordance of 52.0% [44.3, 59.5] and 62.5% [52.3, 71.8], as well as LR-category concordance of 73.7% [61.6, 83.1] and 70.9% [57.3, 81.6], for reportable and actionable observations, respectively. Discordant LI-RADS® observations would have impacted clinical management in 30 subjects (43.5%), most (66.7%) of whom were due to discordant detection. Conclusion: Discordant MRI LI-RADS® observations are common in patients with cirrhosis and may have potential implications for patient management. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer is projected to become the second leading cause of cancer‐related deaths by 2030. Endoscopic retrograde cholangiopancreatography (ERCP) is recommended as first‐line therapy for biliary decompression in pancreatic cancer. The aim of our study was to characterize geographic and racial/ethnic disparities in ERCP utilization among patients with pancreatic cancer. Methods: Retrospective cohort study using the US Surveillance, Epidemiology, and End Results (SEER)‐Medicare database to identify patients diagnosed with pancreatic cancer from 2003‐2013. The primary outcome was receipt of ERCP, with or without stent placement, vs any non‐ERCP biliary intervention. Results: Of the 36 619 patients with pancreatic cancer, 37.5% (n = 13 719) underwent an ERCP, percutaneous drainage, or surgical biliary bypass. The most common biliary intervention (82.6%) was ERCP. After adjusting for tumor location and stage, Blacks were significantly less likely to receive ERCP than Whites (aOR 0.84, 95% CI 0.72, 0.97) and more likely to receive percutaneous transhepatic biliary drainage (PTBD) (aOR 1.38, 95% CI 1.14, 1.66). Patients in the Southeast and the West were more likely to receive ERCP than those in the Northeast (Southeast aOR 1.21, 95% CI 1.04, 1.40; West aOR 1.16, 95% CI 1.01, 1.32). Conclusion: Racial/ethnic and geographic disparities in access to biliary interventions including ERCP exist for patients with pancreatic cancer in the United States. Our results highlight the need for further research and policies to improve access to appropriate biliary intervention for all patients. [ABSTRACT FROM AUTHOR]

In this month's Editorial Caitlin C. Murphy and Amit Singal discuss the increasing incidence of early-onset colorectal cancer in patients under the age of 50. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Effectiveness of fecal occult blood test (FOBT) for colorectal cancer (CRC) screening depends on annual testing, but little is known about patterns of repeat stool-based screening within different settings. Our study’s objective was to characterize screening patterns and identify factors associated with repeat screening among patients who completed an index guaiac FOBT (gFOBT) or fecal immunochemical test (FIT).METHODS: We performed a multi-center retrospective cohort study among people who completed a FOBT between January 2010 and December 2011 to characterize repeat screening patterns over the subsequent 3 years. We studied at 4 large health care delivery systems in the United States. Logistic regression analyses were used to identify factors associated with repeat screening patterns. We included individuals aged 50-71 years who completed an index FOBT and had at least 3 years of follow-up. We excluded people with a history of CRC, colonoscopy within 10 years or flexible sigmoidoscopy within 5 years before the index test, or positive index stool test. Consistent screening was defined as repeat FOBT within every 15 months and inconsistent screening as repeat testing at least once during follow-up but less than consistent screening.RESULTS: Among 959,857 eligible patients who completed an index FIT or gFOBT, 344,103 had three years of follow-up and met inclusion criteria. Of these, 46.6% had consistent screening, 43.4% inconsistent screening, and 10% had no repeat screening during follow-up. Screening patterns varied substantially across healthcare systems, with consistent screening proportions ranging from 1 to 54.3% and no repeat screening proportions ranging from 6.9 to 42.8%. Higher consistent screening proportions were observed in health systems with screening outreach and in-reach programs, whereas the safety-net health system, which uses opportunistic clinic-based screening, had the lowest consistent screening. Consistent screening increased with older age but was less common among racial/ethnic minorities and patients with more comorbidities.CONCLUSIONS: Adherence with annual FOBT screening is highly variable across healthcare delivery systems. Settings with more organized screening programs performed better than those with opportunistic screening, but evidence-based interventions are needed to improve CRC screening adherence in all settings. [ABSTRACT FROM AUTHOR]

Background: Regorafenib, a multikinase inhibitor, has demonstrated prolonged survival by 2.8 months as a second-line agent in patients with hepatocellular carcinoma (HCC) who progress on sorafenib therapy. The objective of the current study was to examine the cost effectiveness of regorafenib for the treatment of HCC.Methods: The authors constructed a Markov simulation model of patients with unresectable HCC and Child-Pugh A cirrhosis who received treatment with regorafenib versus best supportive care. Model inputs for regorafenib effectiveness and rates of adverse events in patients with HCC were based on published clinical trial data and literature review. Quality-adjusted life years (QALYs) were calculated along with the incremental cost-effectiveness ratio (ICER) of regorafenib therapy. One-way sensitivity analyses also were conducted simultaneously on all model parameters and on various Monte-Carlo simulation parameters, and the regorafenib cost threshold at which cost effectiveness would be achieved was determined.Results: Regorafenib provided an increase of 0.18 QALYs at a cost of $47,112. The ICER for regorafenib, compared with best supportive care, was $224,362. In 1-way sensitivity analyses, there were no scenarios in which regorafenib was cost effective. In cost threshold analysis, regorafenib would have to be priced at or below $67 per pill to be cost effective at an ICER of $100,000.Conclusions: Regorafenib is not cost effective as a second-line agent in the treatment of HCC, with a marginal increase in QALYs at a high cost. Lowering the cost of regorafenib or improving the selection of patients who can achieve maximal survival benefit would improve its value as a second-line treatment option for patients with HCC. Cancer 2017;123:3725-3731. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Importance: Mailed fecal immunochemical test (FIT) outreach is more effective than colonoscopy outreach for increasing 1-time colorectal cancer (CRC) screening, but long-term effectiveness may need repeat testing and timely follow-up for abnormal results.Objective: Compare the effectiveness of FIT outreach and colonoscopy outreach to increase completion of the CRC screening process (screening initiation and follow-up) within 3 years.Design, Setting, and Participants: Pragmatic randomized clinical trial from March 2013 to July 2016 among 5999 participants aged 50 to 64 years who were receiving primary care in Parkland Health and Hospital System and were not up to date with CRC screenings.Interventions: Random assignment to mailed FIT outreach (n = 2400), mailed colonoscopy outreach (n = 2400), or usual care with clinic-based screening (n = 1199). Outreach included processes to promote repeat annual testing for individuals in the FIT outreach group with normal results and completion of diagnostic and screening colonoscopy for those with an abnormal FIT result or assigned to colonoscopy outreach.Main Outcomes and Measures: Primary outcome was screening process completion, defined as adherence to colonoscopy completion, annual testing for a normal FIT result, diagnostic colonoscopy for an abnormal FIT result, or treatment evaluation if CRC was detected. Secondary outcomes included detection of any adenoma or advanced neoplasia (including CRC) and screening-related harms (including bleeding or perforation).Results: All 5999 participants (median age, 56 years; women, 61.9%) were included in the intention-to-screen analyses. Screening process completion was 38.4% in the colonoscopy outreach group, 28.0% in the FIT outreach group, and 10.7% in the usual care group. Compared with the usual care group, between-group differences for completion were higher for both outreach groups (27.7% [95% CI, 25.1% to 30.4%] for the colonoscopy outreach group; 17.3% [95% CI, 14.8% to 19.8%] for FIT outreach group), and highest in the colonoscopy outreach group (10.4% [95% CI, 7.8% to 13.1%] for the colonoscopy outreach group vs FIT outreach group; P < .001 for all comparisons). Compared with usual care, the between-group differences in adenoma and advanced neoplasia detection rates were higher for both outreach groups (colonoscopy outreach group: 10.3% [95% CI, 9.5% to 12.1%] for adenoma and 3.1% [95% CI, 2.0% to 4.1%] for advanced neoplasia, P < .001 for both comparisons; FIT outreach group: 1.3% [95% CI, -0.1% to 2.8%] for adenoma and 0.7% [95% CI, -0.2% to 1.6%] for advanced neoplasia, P < .08 and P < .13, respectively), and highest in the colonoscopy outreach group (colonoscopy outreach group vs FIT outreach group: 9.0% [95% CI, 7.3% to 10.7%] for adenoma and 2.4% [95% CI, 1.3% to 3.3%] for advanced neoplasia, P < .001 for both comparisons). There were no screening-related harms in any groups.Conclusions and Relevance: Among persons aged 50 to 64 years receiving primary care at a safety-net institution, mailed outreach invitations offering FIT or colonoscopy compared with usual care increased the proportion completing CRC screening process within 3 years. The rate of screening process completion was higher with colonoscopy than FIT outreach.Trial Registration: clinicaltrials.gov Identifier: NCT01710215. [ABSTRACT FROM AUTHOR]

A study by Ha and colleagues in this issue adds to the evidence base demonstrating racial and ethnic health disparities in health care. However, the evidence base for developing interventions to eliminate these disparities is limited, largely because of a lack of granularity in the available administrative data sets. See also pages 2512‐23. [ABSTRACT FROM AUTHOR]

In this Perspective, Neehar Parikh and Amit Singal discuss the advantages of the ITA.LI.CA staging system for prognoses of liver cancer developed by Alessandro Vitale and colleagues. [ABSTRACT FROM AUTHOR]

Background: The effectiveness of colorectal cancer (CRC) screening is limited by underuse, particularly among underserved populations. Among a racially diverse and socioeconomically disadvantaged cohort of patients, the authors compared the effectiveness of fecal immunochemical test (FIT) outreach and colonoscopy outreach to increase screening participation rates, compared with usual visit-based care.Methods: Patients aged 50 to 64 years who were not up-to-date with CRC screening but used primary care services in a large safety-net health system were randomly assigned to mailed FIT outreach (2400 patients), mailed colonoscopy outreach (2400 patients), or usual care with opportunistic visit-based screening (1199 patients). Patients who did not respond to outreach invitations within 2 weeks received follow-up telephone reminders. The primary outcome was CRC screening completion within 12 months after randomization.Results: Baseline patient characteristics across the 3 groups were similar. Using intention-to-screen analysis, screening participation rates were higher for FIT outreach (58.8%) and colonoscopy outreach (42.4%) than usual care (29.6%) (P <.001 for both). Screening participation with FIT outreach was higher than that for colonoscopy outreach (P <.001). Among responders, FIT outreach had a higher percentage of patients who responded before reminders (59.0% vs 29.7%; P <.001). Nearly one-half of patients in the colonoscopy outreach group crossed over to complete FIT via usual care, whereas <5% of patients in the FIT outreach group underwent usual-care colonoscopy.Conclusions: Mailed outreach invitations appear to significantly increase CRC screening rates among underserved populations. In the current study, FIT-based outreach was found to be more effective than colonoscopy-based outreach to increase 1-time screening participation. Studies with longer follow-up are needed to compare the effectiveness of outreach strategies for promoting completion of the entire screening process. [ABSTRACT FROM AUTHOR]

: Amit Singal and colleagues conducted a systematic review of the evidence that surveillance for hepatocellular carcinoma in patients with cirrhosis improves early detection, receipt of curative treatment, and overall survival. Please see later in the article for the Editors' Summary [ABSTRACT FROM AUTHOR]

Objectives:The PNPLA3 rs738409 single-nucleotide polymorphism is known to promote nonalcoholic steatohepatitis (NASH), but its association with fibrosis severity and hepatocellular carcinoma (HCC) risk is less well-defined. The objectives of this study were to determine the association between PNPLA3 and liver fibrosis severity, HCC risk, and HCC prognosis among patients with liver disease.Methods:We performed a systematic literature review using the Medline, PubMed, Scopus, and Embase databases through May 2013 and a manual search of national meeting abstracts from 2010 to 2012. Two investigators independently extracted data on patient populations, study methods, and results using standardized forms. Pooled odds ratios (ORs), according to PNPLA3 genotype, were calculated using the DerSimonian and Laird method for a random effects model.Results:Among 24 studies, with 9,915 patients, PNPLA3 was associated with fibrosis severity (OR 1.32, 95% confidence interval (CI) 1.20-1.45), with a consistent increased risk across liver disease etiologies. Among nine studies, with 2,937 patients, PNPLA3 was associated with increased risk of HCC in patients with cirrhosis (OR 1.40, 95% CI 1.12-1.75). On subgroup analysis, increased risk of HCC was demonstrated in patients with NASH or alcohol-related cirrhosis (OR 1.67, 95% CI 1.27-2.21) but not in those with other etiologies of cirrhosis (OR 1.33, 95% CI 0.96-1.82). Three studies, with 463 patients, do not support an association between PNPLA3 and HCC prognosis but are limited by heterogeneous outcome measures. For all outcomes, most studies were conducted in homogenous Caucasian populations, and studies among racially diverse cohorts are needed.Conclusions:PNPLA3 is associated with an increased risk of advanced fibrosis among patients with a variety of liver diseases and is an independent risk factor for HCC among patients with nonalcoholic steatohepatitis or alcohol-related cirrhosis. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Predictive models for hepatocellular carcinoma (HCC) have been limited by modest accuracy and lack of validation. Machine-learning algorithms offer a novel methodology, which may improve HCC risk prognostication among patients with cirrhosis. Our study's aim was to develop and compare predictive models for HCC development among cirrhotic patients, using conventional regression analysis and machine-learning algorithms.METHODS:We enrolled 442 patients with Child A or B cirrhosis at the University of Michigan between January 2004 and September 2006 (UM cohort) and prospectively followed them until HCC development, liver transplantation, death, or study termination. Regression analysis and machine-learning algorithms were used to construct predictive models for HCC development, which were tested on an independent validation cohort from the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial. Both models were also compared with the previously published HALT-C model. Discrimination was assessed using receiver operating characteristic curve analysis, and diagnostic accuracy was assessed with net reclassification improvement and integrated discrimination improvement statistics.RESULTS:After a median follow-up of 3.5 years, 41 patients developed HCC. The UM regression model had a c-statistic of 0.61 (95% confidence interval (CI) 0.56-0.67), whereas the machine-learning algorithm had a c-statistic of 0.64 (95% CI 0.60-0.69) in the validation cohort. The HALT-C model had a c-statistic of 0.60 (95% CI 0.50-0.70) in the validation cohort and was outperformed by the machine-learning algorithm. The machine-learning algorithm had significantly better diagnostic accuracy as assessed by net reclassification improvement (P<0.001) and integrated discrimination improvement (P=0.04).CONCLUSIONS:Machine-learning algorithms improve the accuracy of risk stratifying patients with cirrhosis and can be used to accurately identify patients at high-risk for developing HCC. [ABSTRACT FROM AUTHOR]

Background: Evaluation of new treatment policies is often costly and challenging in complex conditions, such as hepatitis C virus (HCV) treatment, or in limited-resource settings. We sought to identify hypothetical policies for HCV treatment that could best balance the prevention of cirrhosis while preserving resources (financial or otherwise).Methods: The cohort consisted of 3792 HCV-infected patients without a history of cirrhosis or hepatocellular carcinoma at baseline from the national Veterans Health Administration from 2015 to 2019. To estimate the efficacy of hypothetical treatment policies, we utilized historical data and reinforcement learning to allow for greater flexibility when constructing new HCV treatment strategies. We tested and compared four new treatment policies: a simple stepwise policy based on Aspartate Aminotransferase to Platelet Ratio Index (APRI), a logistic regression based on APRI, a logistic regression on multiple longitudinal and demographic indicators that were prespecified for clinical significance, and a treatment policy based on a risk model developed for HCV infection.Results: The risk-based hypothetical treatment policy achieved the lowest overall risk with a score of 0.016 (90% CI 0.016, 0.019) while treating the most high-risk (346.4 ± 1.4) and the fewest low-risk (361.0 ± 20.1) patients. Compared to hypothetical treatment policies that treated approximately the same number of patients (1843.7 vs. 1914.4 patients), the risk-based policy had more untreated time per patient (7968.4 vs. 7742.9 patient visits), signaling cost reduction for the healthcare system.Conclusions: Off-policy evaluation strategies are useful to evaluate hypothetical treatment policies without implementation. If a quality risk model is available, risk-based treatment strategies can reduce overall risk and prioritize patients while reducing healthcare system costs. [ABSTRACT FROM AUTHOR]

Background & Aims: Hemorrhagic ascites can pose diagnostic and therapeutic dilemmas in patients with cirrhosis. We aimed at exploring the characteristics and outcomes of patients with cirrhosis and hemorrhagic ascites. Methods: The records of all patients with cirrhosis and ascites, who underwent paracentesis between 2003 and 2010 at Parkland Memorial Hospital, were retrospectively reviewed. Hemorrhagic ascites was defined as an ascitic fluid red blood cell (RBC) count ⩾10,000/μl. We compared each patient with 3 age- and gender-matched controls (cirrhotic patients with ascites and an ascitic RBC count <10,000/μl). Survival curves were generated using Kaplan–Meier plots and compared using the log rank test. Results: 1113 cirrhotic patients underwent paracentesis; 214 (19%) had hemorrhagic ascites. Patients with hemorrhagic ascites had higher rates of spontaneous bacterial peritonitis (p <0.001), acute kidney injury (AKI, p <0.001), and were more likely to require intensive care unit (ICU)-level care (p =0.01) compared to patients without hemorrhagic ascites. Patients with hemorrhagic ascites had a higher mortality than controls at one month (87% vs. 72%), 1year (72% vs. 50%) and 3years (61% vs. 41%). Using multivariate regression analysis, hemorrhagic ascites was also an independent predictor of mortality (HR 1.34, 95% CI 1.07–1.68) after adjusting for the model for end-stage liver disease score (HR 1.04, 1.03–1.05), ICU-level care (HR 2.02, 1.63–2.51) and presence of hepatocellular carcinoma (HR 2.27, 1.61–3.19). Conclusions: Patients with hemorrhagic ascites had a significantly higher rate of ICU care, AKI, and mortality than patients with portal hypertension and ascites but without hemorrhagic ascites. We conclude that hemorrhagic ascites is a marker of advanced liver disease and poor outcome. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Only 40% of patients with hepatocellular carcinoma (HCC) are diagnosed at an early stage, suggesting breakdowns in the surveillance process. The aim of our study was to assess the reasons behind surveillance process failures among patients in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis Trial (HALT-C), which prospectively collected HCC surveillance data on a large cohort of patients.METHODS:Binary regression analysis was used to identify predictors of consistent surveillance, which was defined as having an ultrasound and alpha-fetoprotein every 12 months. Surveillance failures among patients who developed HCC were classified into one of three categories: absence of screening, absence of follow-up, or absence of detection.RESULTS:Over a mean follow-up of 6.1 years, 692 (68.9%) of 1,005 patients had consistent surveillance. Study site was the strongest predictor of consistent surveillance (P<0.001). After adjusting for study site, patient-level predictors of consistent surveillance included platelet count >150,000/mm3 (hazard ratio (HR) 1.28; 95% confidence interval (CI): 1.05-1.56) and complete clinic visit adherence (HR 1.72, 95% CI: 1.11-2.63). Of 83 patients with HCC, 23 (27.7%) were detected beyond Milan criteria. Three (13%) had late-stage HCC due to the absence of screening, 4 (17%) due to the absence of follow-up, and 16 (70%) due to the absence of detection.CONCLUSIONS:Surveillance process failures, including absence of screening or follow-up, are common and potentially contribute to late-stage tumors in one-third of cases. However, the most common reason for finding HCC at a late stage was an absence of detection, suggesting better surveillance strategies are needed. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, in part because of inadequate early detection strategies. Current recommendations for screening consist of semi-annual abdominal ultrasound with or without serum alpha-fetoprotein in patients with cirrhosis and in demographic subgroups with chronic hepatitis B infection. However, this screening strategy has several deficiencies, including suboptimal early-stage sensitivity, false positives with subsequent harms, inter-operator variability in ultrasound performance, and poor adherence. A blood-based biomarker with sufficient performance characteristics for early-stage disease could overcome several of these barriers to improving early-stage detection. However, prior to use of a biomarker for screening in clinical practice, a multistep validation is required in order to understand test performance characteristics. These steps include case-control validation, followed by validation in prospective cohorts of at-risk patients. Until recently, we lacked adequate longitudinal validation cohorts for early HCC detection; however, several validation cohorts are maturing, including the Hepatocellular Carcinoma Early Detection Study and the Texas Hepatocellular Carcinoma Consortium, which will allow for rigorous validation of candidate biomarkers. While there are several promising biomarkers awaiting validation, in order to supplant abdominal ultrasound, a candidate biomarker must show adequate test performance and overcome practical hurdles to ensure adoption in clinical practice. The promise of blood-based biomarkers is significant, especially given the limitations of ultrasound-based screening; however, they require adequate validation and several logistical obstacles must be overcome prior to clinical implementation. [ABSTRACT FROM AUTHOR]

Computed tomographic colonography (CTC) is a non-invasive screening test for colorectal cancer (CRC) with high sensitivity and low risk of complications. We used a nationally representative sample of screening-eligible adults to examine trends in and factors associated with CTC use. We examined CTC use among 58,058 adults in the National Health Interview Survey in 2010, 2015, 2018, 2019, and 2021. For each survey year, we estimated CTC use by sociodemographic and health factors. We used multivariable logistic regression to identify factors associated with CTC use. A total of 1.7 % adults reported receiving CTC across all survey years. CTC use was similar in 2010 (1.3 %), 2015 (0.8 %), 2018 (1.4 %), and 2019 (1.4 %) but increased in 2021 (3.5 %, p < 0.05). In multivariable analysis, survey year 2021 [vs. 2010, odds ratio (OR) 2.51, 95 % confidence interval (CI) 1.83–3.43], Hispanic (OR 1.73, 95 % CI 1.34–2.23), non-Hispanic Black (OR 2.07, 95 % CI 1.67–2.57), and household income <200 % federal poverty level (vs. >400 %, OR 1.25, 95 % CI 1.01–1.57) was associated with CTC use. Further, adults with a history of diabetes (OR 1.20, 95 % CI 1.01–1.45), chronic obstructive pulmonary disease (OR 1.58, 95 % CI 1.25–1.99), cancer (OR 1.29, 95 % CI 1.05–1.58), or past-year hospital admissions (OR 1.44, 95 % CI 1.18–1.78) were more likely to receive CTC. CTC use remained low from 2010 to 2019 but increased in 2021. CTC use was more frequent among adults with chronic health conditions, minorities, and adults with lower income, and may help reduce disparities in CRC screening. • The use of CT Colonography more than doubled from 2019 to 2021 after remaining similar for the previous decade. • Hispanic and Non-Hispanic Black individuals are more likely to use CT Colonography than individuals of any other race. • Certain chronic health conditions, such as COPD and cancer, are associated with increased use of CT Colonography. [ABSTRACT FROM AUTHOR]

Summary: Background/Aims: Patients with hepatocellular cancer (HCC) are vulnerable to psychological distress given a new cancer diagnosis superimposed on pre‐existing chronic liver disease. We aimed to characterise the psychiatric burden in HCC, risk factors for incident diagnosis and treatment patterns over time. Methods: Using IQVIA PharMetrics® Plus for Academics—a nationally representative claims database of the commercially insured US population—we identified psychiatric diagnoses and treatment among patients with newly diagnosed HCC. Multivariable logistic regression modelling identified factors associated with psychiatric diagnosis and treatment. Results: Of 11,609 patients with HCC, 2166 (18.6%) had a psychiatric diagnosis after cancer diagnosis with depression (58.3%) and anxiety (53.0%) being most common. Women (aOR 1.33, 95% CI [1.19–1.49]), pre‐existing psychiatric diagnoses (aOR 9.12 [8.08–10.3]) and HCC treatment type (transplant: aOR 2.15 [1.66–2.77]; locoregional therapies: aOR 1.74 [1.52–1.99]; hospice: aOR 2.43 [1.79–3.29]) were significantly associated with psychiatric diagnosis. Female sex, ascites, higher comorbidity and treatment type were associated with incident psychiatric diagnosis. Pharmacotherapy was used in 1392 (64.3%) patients with a psychiatric diagnosis, with antidepressants (46.2%) and anxiolytics (32.8%) being most common. Psychiatric diagnoses increased from 14.8% in 2006–2009 to 21.1% in 2018–2021 (p < 0.001). In almost 20% of patients with pre‐existing psychiatric conditions, therapy was discontinued after HCC diagnosis. Conclusions: Nearly 2 of 10 patients with HCC were diagnosed with a psychiatric condition after cancer diagnosis with unique sociodemographic and clinical risk factors identified. This highlights a risk for increased psychological burden in need of early evaluation and treatment among patients with newly diagnosed HCC. [ABSTRACT FROM AUTHOR]

Background & Aims: We aimed to compare the performance of gadoxetic acid-enhanced abbreviated MRI (AMRI)-based surveillance and ultrasound-only surveillance in high-risk patients for hepatocellular carcinoma (HCC). Methods: Prospectively recruited high-risk patients (>5% annual risk of HCC) who underwent one to three rounds of complete gadoxetic acid-enhanced MRI (CMRI) and ultrasound at 6-months intervals were retrospectively analysed. AMRI consisted of diffusion-weighted, T2-weighted, and hepatobiliary phase imaging. The sensitivity, specificity, and accuracy of CMRI followed by AMRI (CAA), AMRI-only (AAA), and ultrasound-only (US) were compared using generalized estimating equations. Image quality was assessed. Results: In 382 patients, HCC was diagnosed in 43 (11.3%), including 42 with early-stage HCCs. The sensitivities of CAA (90.7%, 39/43) and AAA (86.0%, 37/43) were higher than US (27.9% [12/43]; P < 0.001), whereas the sensitivities of the two MRI approaches did not significantly differ (P = 0.56). The specificity of CAA (97.1%, 983/1012) was higher than AAA (95.6% [967/1012]; P = 0.01) and not significantly different from US (96.3% [975/1012]; P = 0.59). The CAA approach had the best accuracy of 96.9% (1022/1055), higher than the AAA approach (95.2% [1004/1055]; P = 0.01) and the US approach (93.6% [987/1055]; P = 0.01). Image quality was inadequate in 33.7% (356/1055) of US examinations but in only 10.0% (105/1055) of the AAA and 11.1% (117/1055) of the CAA approach. Conclusions: In high-risk patients, AMRI-based surveillance approaches had higher sensitivities than ultrasound-only surveillance for early-stage HCC. A sequential MRI approach of CMRI followed by AMRIs showed superior accuracy than the AMRI-only or ultrasound-only approach. [ABSTRACT FROM AUTHOR]

Background & Aims: We aimed to compare the performance of gadoxetic acid‐enhanced abbreviated MRI (AMRI)‐based surveillance and ultrasound‐only surveillance in high‐risk patients for hepatocellular carcinoma (HCC). Methods: Prospectively recruited high‐risk patients (>5% annual risk of HCC) who underwent one to three rounds of complete gadoxetic acid‐enhanced MRI (CMRI) and ultrasound at 6‐months intervals were retrospectively analysed. AMRI consisted of diffusion‐weighted, T2‐weighted, and hepatobiliary phase imaging. The sensitivity, specificity, and accuracy of CMRI followed by AMRI (CAA), AMRI‐only (AAA), and ultrasound‐only (US) were compared using generalized estimating equations. Image quality was assessed. Results: In 382 patients, HCC was diagnosed in 43 (11.3%), including 42 with early‐stage HCCs. The sensitivities of CAA (90.7%, 39/43) and AAA (86.0%, 37/43) were higher than US (27.9% [12/43]; P < 0.001), whereas the sensitivities of the two MRI approaches did not significantly differ (P = 0.56). The specificity of CAA (97.1%, 983/1012) was higher than AAA (95.6% [967/1012]; P = 0.01) and not significantly different from US (96.3% [975/1012]; P = 0.59). The CAA approach had the best accuracy of 96.9% (1022/1055), higher than the AAA approach (95.2% [1004/1055]; P = 0.01) and the US approach (93.6% [987/1055]; P = 0.01). Image quality was inadequate in 33.7% (356/1055) of US examinations but in only 10.0% (105/1055) of the AAA and 11.1% (117/1055) of the CAA approach. Conclusions: In high‐risk patients, AMRI‐based surveillance approaches had higher sensitivities than ultrasound‐only surveillance for early‐stage HCC. A sequential MRI approach of CMRI followed by AMRIs showed superior accuracy than the AMRI‐only or ultrasound‐only approach. [ABSTRACT FROM AUTHOR]

The authors reflect on the incidence and future burden of hepatocellular carcinoma (HCC) in the U.S. as of June 2019. Other topics include the susceptibility of cirrhosis patients to HCC, the prevalence of age-specific incidence rates of HCC to African Americans, Hispanics, and Asians, as well as the growing cases of HCC in older people with chronic hepatitis C (HCV) and non-alcoholic fatty liver disease (NAFLD).

INTRODUCTION: Hepatocellular carcinoma (HCC) surveillance is associated with improved early tumor detection, but effectiveness is limited by underuse. We characterized adherence to HCC surveillance using proportion of time covered (PTC) and estimated its association with clinical outcomes among patients with cirrhosis. METHODS: We conducted a retrospective cohort study of patients diagnosed with HCC between January 2008 and December 2022 at 2 largeUS health systems. We characterized PTC by imaging in the 12 and 24 months before HCC diagnosis. We used multivariable logistic and Cox regression analyses to assess the association between PTC and early HCC detection, receipt of curative treatment, and overall survival. RESULTS: Among 2,027 patients with HCC, 331 (51.4% Barcelona Clinic Liver Cancer 0/A) had been followed up for at least 12 months before diagnosis. The median PTC was 24.9% (interquartile range 1.1%--50.7%), with only 16.0% having semiannual imaging and 42.0% having annual surveillance. Semiannual and annual surveillance decreased to 6.3% and 29.6% when assessed over 24 months, although the median PTC remained unchanged at 24.9%. Receipt of gastroenterology/hepatology care had the strongest association with PTC, with median PTC of 36.7% and 3.8% for those with and without gastroenterology/hepatology care, respectively. PTC was independently associated with improved early HCC detection, curative treatment receipt, and overall survival. The median survival was 15.7, 26.8, and 32.7 months among those with PTC of <25% (n 5 168 patients), PTC 25%--50% (n 5 69 patients), and PTC >50% (n 5 94 patients), respectively. DISCUSSION: The proportion of time covered byHCC surveillance in patients with cirrhosis remains low, highlighting a need for multilevel interventions. [ABSTRACT FROM AUTHOR]

Simple Summary: There is controversy over the optimal recommended screening practice for colorectal cancer. Between direct visualization methods, colonoscopy is more used more frequently, although randomized data suggest benefits from sigmoidoscopy rather than colonoscopy. We used the SEER database to assess the proportion of cancers that could be visualized with each screening strategy and found that 58% could be seen by sigmoidoscopy, including 73% of tumors for patients diagnosed younger than 50 years (early onset colorectal cancer). We recommend consideration of recommending flexible sigmoidoscopy as a population-based screening strategy for younger individuals who may be hesitant to undergo colonoscopy. Objectives: The effectiveness of colonoscopy to reduce colorectal cancer (CRC) mortality is extrapolated from cohort studies in the absence of randomized controlled trial (RCT) data, whereas flexible sigmoidoscopy is supported by RCT data and may be easier to implement in practice. We characterized the anatomic distribution of CRC to determine the proportion that is visible with sigmoidoscopy. Methods: Patients with a primary diagnosis of colorectal adenocarcinoma were identified in the Surveillance, Epidemiology, and End Results program (2000–2020). Tumors from the rectum to the descending colon were categorized as visible by sigmoidoscopy, whereas more proximal tumors required colonoscopy. Differential prognosis between tumor locations, stratified by age groups and stage, was assessed using the overall restricted mean survival time (RMST) at 2, 5, and 10 years. Results: Among 309,466 patients, 58% had tumors visible by sigmoidoscopy, including 73% of those under age 50 (OR 2.10, 95% CI 2.03–2.16 age < 45, OR 2.20, 95% CI 2.13–2.27 age 45–49 versus age ≥ 50). Male sex (OR 1.54, 95% CI 1.51–1.56) and Asian or Pacific Islander race (OR 1.60, 95% CI 1.56–1.64) were also positively associated with tumors visualizable by sigmoidoscopy. Across age groups, for local disease, RMST was comparable for tumors visible versus not visible on sigmoidoscopy. For regional and metastatic cancer, patients with tumors visible by sigmoidoscopy had improved RMST versus those with more proximal tumors. Conclusions: 58% of CRC arises in locations visible by flexible sigmoidoscopy. Flexible sigmoidoscopy should be considered as a viable option for CRC screening, particularly in younger patients unwilling or unable to undergo colonoscopy. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Coronavirus Disease 2019 disrupted cancer-related care in early 2020. METHODS: We used population-based cancer registry data to estimate incidence and mortality rates of gastrointestinal cancers between 2016 and 2020. RESULTS: Incidence rates were unchanged from 2016 to 2019 but decreased in 2020, with the largest declines for colorectal cancer (rate ratio [RR] 0.88; 95% confidence interval [CI] 0.87-0.90) and hepatocellular carcinoma (RR 0.85; 95% CI 0.82-0.88). Mortality rates of colorectal cancer (RR 1.06; 95% CI 1.04-1.08) and esophageal adenocarcinoma (RR 1.06; 95% CI 1.00-1.13) increased in 2020. DISCUSSION: Incidence and mortality rates of gastrointestinal cancers may increase in the future given pandemic-related delays in 2020. [ABSTRACT FROM AUTHOR]

Background and Aims: The two most common interventions used to treat painless jaundice from pancreatic cancer are endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic biliary drainage (PTBD). Our study aimed to characterize the geographic distribution of ERCP‐performing hospitals among patients with pancreatic cancer in the United States and the association between geographic accessibility to ERCP‐performing hospitals and biliary interventions patients receive. Methods: This is a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER)‐Medicare database for pancreatic cancer from 2005 to 2013. Multilevel models were used to examine the association between accessibility to ERCP hospitals within a 30‐ and 45‐min drive from the patient's residential ZIP Code and the receipt of ERCP treatment. A two‐step floating catchment area model was used to calculate the measure of accessibility based on the distribution across SEER regions. Results: 7464 and 782 patients underwent ERCP and PTBD, respectively, over the study period. There were 808 hospitals in which 8246 patients diagnosed with pancreatic cancer in SEER regions from 2005 to 2013 received a procedure. Patients with high accessibility within both 30‐ and 45‐min drive to an ERCP‐performing hospital were more likely to receive an ERCP (30‐min adjusted odds ratio [aOR]: 1.53, 95% confidence interval [CI]: 1.17–2.01; 45‐min aOR: 1.31, 95% CI: 1.01–1.70). Furthermore, in the adjusted model, Black patients (vs. White) and patients with stage IV disease were less likely to receive ERCP than PTBD. Conclusions: Patients with pancreatic cancer and high accessibility to an ERCP‐performing hospital were more likely to receive ERCP. Disparities in the receipt of ERCP persisted for Black patients regardless of their access to ERCP‐performing hospitals. [ABSTRACT FROM AUTHOR]

Using Michigan public health data, we assessed geographical access to specialist providers for hepatitis C virus (HCV) treatment in urban and rural areas in Michigan and explored correlates of HCV in these areas to help inform HCV elimination planning and resource allocations. We found higher HCV incidence in urban areas, lower treatment specialist access in rural areas, but few correlates of HCV across adult populations in both areas. State and local HCV elimination planning should include population‐based screening among all adults and address geographical barriers to care. [ABSTRACT FROM AUTHOR]

Summary: Background: Advanced hepatocellular carcinoma (HCC) portends a poor prognosis; however recent advances in first‐line and second‐line treatment options should yield significant improvements in survival. Aim: To summarize the evolving landscape of treatment options for patients with advanced HCC. Methods: We reviewed published clinical trials conducted in patients with advanced HCC published in PubMed or presented at national conferences. Results: Sorafenib was approved for treatment of unresectable HCC in 2007 and remained the only therapy with proven survival benefit in advanced HCC for several years. Lenvatinib, another tyrosine‐kinase inhibitor, was recently shown to have non‐inferior survival vs sorafenib and is another first‐line treatment option. The tyrosine‐kinase inhibitors, regorafenib and cabozantinib, were shown to significantly improve survival in the second‐line setting after sorafenib failure. Ramucirumab, a VEGF inhibitor, can also improve survival in the second‐line setting among patients with AFP ≥ 400 ng/dL. Phase II data highlight potential durable objective responses with immune checkpoint inhibitors, prompting conditional FDA approval of nivolumab and pembrolizumab in the second‐line setting; however, recent phase III data have failed to demonstrate improved survival compared to other treatment options. Ongoing trials are evaluating combination immune checkpoint inhibitor and immune checkpoint inhibitors with tyrosine‐kinase inhibitors or VEGF inhibitors in hopes of further increasing objective responses and overall survival in this patient population. Conclusion: There are several first‐line and second‐line therapeutic options available for patients with advanced HCC. Further studies are needed to determine how best to select between and sequence the growing number of therapeutic options. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The efficacy and safety of combined immunotherapy and transarterial radioembolization (TARE) were suggested in preclinical and early-phase trials, but these were limited by small sample sizes. We sought to compare the efficacy of combined therapy and immunotherapy alone in patients with advanced hepatocellular carcinoma (HCC). METHODS: The National Cancer Database was used to identify patients with advanced HCC diagnosed between January 1, 2017, and December 31, 2019. We included patients who received combined therapy or immunotherapy alone as first-line treatment. Multivariable logistic regression was conducted to determine predictors of combined therapy. Kaplan-Meier and Cox regression approaches were used to identify predictors of overall survival and to compare hazards of mortality between the patients who received combined therapy and immunotherapy alone. RESULTS: Of 1,664 eligible patients with advanced-stage HCC, 142 received combined TARE/immunotherapy and 1,522 received immunotherapy alone. Receipt of combination therapy was associated with care at an academic center and inversely associated with racial/ethnic minority status (Hispanic and Black individuals). The median overall survival was significantly higher in the combination group than in the immunotherapy alone group (19.8 vs 9.5 months). In multivariable analysis, combined therapy was independently associated with reduced mortality (adjusted hazard ratio 0.50, 95% confidence interval: 0.36-0.68, P < 0.001). Results were consistent across subgroups and in sensitivity analyses using propensity score matching and inverse probability of treatment weighting. DISCUSSION: The combination of TARE and immunotherapy was associated with improved survival compared with immunotherapy alone in patients with advanced-stage HCC. Our findings underly the importance of large clinical trials evaluating combination therapy in these patients. [ABSTRACT FROM AUTHOR]

Background Incidence rates of colorectal cancer (CRC) are increasing among younger adults and in mid-life, implicating exposures in early life as risk factors. We examined the association between in-utero exposure to antibiotics and risk of CRC in adult offspring. Methods The Child Health and Development Studies is a prospective cohort of women receiving prenatal care between 1959 and 1966 in Oakland, California, with deliveries through June 1967. Diagnosed conditions and all prescribed medications were abstracted from mothers' medical records beginning 6 months prior to pregnancy through delivery. We identified mothers who received antibiotics in pregnancy, including penicillins, tetracyclines, short-acting sulfonamides and long-acting sulfonamides. Diagnoses of CRC in adult (age ≥18 years) offspring were ascertained through 2021 by linkage with the California Cancer Registry. Cox proportional models were used to estimate adjusted hazard ratios (aHR), with follow-up accrued from birth through cancer diagnosis, death or last contact. Results Of 18 751 liveborn offspring, about 15% (n  = 2635) were exposed in utero to antibiotics: 5.4% (n  = 1016) to tetracyclines, 4.9% (n  = 918) to penicillins, 4.2% (n  = 785) to short-acting sulfonamides and 1.5% (n  = 273) to long-acting sulfonamides. Compared with offspring not exposed, associations between in-utero exposure and CRC in adult offspring were: aHR 1.03 (95% CI 0.32, 3.31) for tetracyclines; aHR 1.12 (95% CI 0.35, 3.58) for penicillins; aHR 0.83 (95% CI 0.20, 3.42) for short-acting sulfonamides; and aHR 4.40 (95% CI 1.63, 11.88) for long-acting sulfonamides. Conclusion Our findings support an association between in-utero exposure to long-acting sulfonamides and CRC in adulthood. [ABSTRACT FROM AUTHOR]

Background: Biliary atresia (BA) remains the number one indication for paediatric liver transplantation (LT) worldwide but is an uncommon indication for older LT recipients. The impact of recent donor allocation changes, pervasive organ shortage and evolving LT practices on the BA LT population is unknown. Methods: We identified patients who underwent LT between January 2010 and December 2021 using the UNOS database. We compared clinical outcomes between patients with BA and those with non‐BA cholestatic liver disease. Groups were stratified by age, <12 years (allocated via PELD system) and ≥12 years (allocated via MELD system). Waitlist outcomes were compared using competing‐risk regression analysis, graft survival rates were compared using Kaplan–Meier time‐to‐event analysis and Cox proportional hazards modelling provided adjusted estimates. Results: There were 2754 BA LT waitlist additions and 2206 BA LTs (1937 <12 years [younger], 269 ≥12 years [older]). There were no differences in waitlist mortality between BA and non‐BA cholestatic patients. Among BA LT recipients, there were 441 (20.0%) living‐donor liver transplantations (LDLT) and 611 (27.7%) split deceased‐donor LTs. Five‐year graft survival was significantly higher among BA versus non‐BA cholestatic patients in the older group (88.3% vs. 79.5%, p <.01) but not younger group (89.3% vs. 89.5%). Among BA LT recipients, improved graft outcomes were associated with LDLT (vs. split LT: HR: 2, 95% CI: 1.03–3.91) and higher transplant volume (volume >100 vs. <40 BA LTs: HR: 3.41, 95% CI: 1.87–6.2). Conclusion: Liver transplant outcomes among BA patients are excellent, with LDLT and higher transplant centre volume associated with optimal graft outcomes. [ABSTRACT FROM AUTHOR]

Background: Professional societies recommend hepatocellular carcinoma screening in patients with cirrhosis, but high-quality data evaluating its effectiveness to improve early tumor detection and survival in "real world" clinical practice are needed. We aim to characterize the association between hepatocellular carcinoma screening and early tumor detection, curative treatment, and overall survival among patients with cirrhosis.Methods: We performed a retrospective cohort study of patients diagnosed with hepatocellular carcinoma between June 2012 and May 2013 at 4 health systems in the US. Patients were categorized in the screening group if hepatocellular carcinoma was detected by imaging performed for screening purposes. Generalized linear models and multivariate Cox regression with frailty adjustment were used to compare early detection, curative treatment, and survival between screen-detected and non-screen-detected patients.Results: Among 374 hepatocellular carcinoma patients, 42% (n = 157) were detected by screening. Screen-detected patients had a significantly higher proportion of early tumors (Barcelona Clinic Liver Cancer stage A 63.1% vs 36.4%, P <.001) and were more likely to undergo curative treatment (31% vs 13%, P = .02). Hepatocellular carcinoma screening was significantly associated with improved survival in multivariate analysis (hazards ratio 0.41; 95% confidence interval, 0.26-0.65) after adjusting for patient demographics, Child-Pugh class, and performance status. Median survival of screen-detected patients was 14.6 months, compared with 6.0 months for non-screen-detected patients, with the difference remaining significant after adjusting for lead-time bias (hazards ratio 0.59, 95% confidence interval, 0.37-0.93).Conclusion: Hepatocellular carcinoma screening is associated with increased early tumor detection and improved survival; however, a minority of hepatocellular carcinoma patients are detected by screening. Interventions to increase screening use in patients with cirrhosis may help curb hepatocellular carcinoma mortality rates. [ABSTRACT FROM AUTHOR]