Effectiveness of mailed outreach and patient navigation to promote HCC screening process completion: a multicentre pragmatic randomised clinical trial.

BACKGROUND: Hepatocellular carcinoma (HCC) is plagued by failures across the cancer care continuum, leading to frequent late-stage diagnoses and high mortality. We evaluated the effectiveness of mailed outreach invitations plus patient navigation to promote HCC screening process completion in patients with cirrhosis. METHODS: Between April 2018 and September 2021, we conducted a multicentre pragmatic randomised clinical trial comparing mailed outreach plus patient navigation for HCC screening (n=1436) versus usual care with visit-based screening (n=1436) among patients with cirrhosis at three US health systems. Our primary outcome was screening process completion over a 36-month period, and our secondary outcome was the proportion of time covered (PTC) by screening. All patients were included in intention-to-screen analyses. RESULTS: All 2872 participants (median age 61.3 years; 32.3% women) were included in intention-to-screen analyses. Screening process completion was observed in 6.6% (95% CI: 5.3% to 7.9%) of patients randomised to outreach and 3.3% (95% CI: 2.4% to 4.3%) of those randomised to usual care (OR 2.05, 95% CI: 1.44 to 2.92). The intervention increased HCC screening process completion across most subgroups including age, sex, race and ethnicity, Child-Turcotte-Pugh class and health system. PTC was also significantly higher in the outreach arm than usual care (mean 37.5% vs 28.2%; RR 1.33, 95% CI: 1.31 to 1.35). Despite screening underuse, most HCC in both arms were detected at an early stage. CONCLUSION: Mailed outreach plus navigation significantly increased HCC screening process completion versus usual care in patients with cirrhosis, with a consistent effect across most examined subgroups. However, screening completion remained suboptimal in both arms, underscoring a need for more intensive interventions. TRIAL REGISTRATION NUMBER: NCT02582918.

Financial Burden of Hepatocellular Carcinoma Screening in Patients With Cirrhosis.

BACKGROUND: The overall value of hepatocellular carcinoma screening is defined by the balance of benefits and harms. Studies have only reported physical harms with none describing financial harms. METHODS: We conducted a multicenter pragmatic randomized clinical trial of hepatocellular carcinoma screening outreach among 2872 patients with cirrhosis from March 2018 to April 2021. Patients with positive or indeterminate results and matched patients with negative results completed surveys at baseline and at follow-up measuring financial harms via Cancer Self-Administered Questionnaire and financial burden via Comprehensive Score for Financial Toxicity Functional Assessment of Chronic Illness Therapy. Univariable and multivariable longitudinal regression analyses were performed to compare changes in financial harms across groups: true positive, true negative, false positive, and indeterminate. Semistructured interviews were conducted in a subset of patients, sampled by center and test result. RESULTS: Of 311 patients who completed at least 1 follow-up survey (75% response rate), 37 had true positive, 133 true negative, 64 false positive, and 77 indeterminate results. Financial harms increased in true positive and false positive patients with no significant changes noted among those with true negative or indeterminate results. At follow-up, 21.8% of patients reported moderate-severe financial burden, which was not significantly associated with test results. Semistructured interviews revealed variation in the frequency and severity of financial harms based on test results, with increased harm in those with false positive results. CONCLUSIONS: Financial harms of hepatocellular carcinoma screening vary by test result and can pose a barrier that must be considered when determining the optimal screening program.

Hepatocellular carcinoma surveillance may be associated with potential psychological harms in patients with cirrhosis.

BACKGROUND AND AIMS: The value of HCC surveillance is determined by the balance between benefits and harms; however, no studies have enumerated psychological harms. APPROACH AND RESULTS: We fielded surveys measuring psychological harms to patients with cirrhosis in a multicenter randomized trial of HCC surveillance outreach. All patients with positive or indeterminate surveillance results and matched patients with negative results were invited to complete surveys measuring (1) depression through the Patient Health Questionnaire-ninth version, (2) anxiety through State-Trait Anxiety Inventory, (3) HCC-specific worry through Psychological Consequences Questionnaire, and (4) decisional regret. Patients were classified into 4 groups: true positive (TP), false positive (FP), indeterminate, and true negative (TN). Multivariable longitudinal regression analysis using the generalized estimating equation method was performed to compare the means of measures across groups. We conducted 89 semistructured interviews in a subset of patients stratified by health system and test results. Of 2872 patients in the trial, 311 completed 1+ follow-up survey (63 FP, 77 indeterminate, 38 TP, and 133 TN). Moderate depression decreased in TN patients, increased in TP, and had intermittent but mild increases in those with FP and indeterminate results. High anxiety temporarily increased in patients with TP results but resolved over time and was stable in those with FP and indeterminate results. Decisional regret was low and did not differ across groups. In semistructured interviews, patients reported apprehension, anxiety, emotional distress, and coping related to HCC surveillance. CONCLUSIONS: Psychological harms of HCC surveillance appear mild but differ by test result. Future research should determine the impact of psychological harms on the value of HCC surveillance programs.

Ethnic Disparities in Early-Onset Gastric Cancer Persist across Rural-Urban Geographies.

BACKGROUND: The incidence of noncardia gastric cancer is increasing in adults ages less than 50 years old. Early-onset gastric cancer (EOGC) is characterized by ethnic disparities occurring more in Hispanic persons than non-Hispanic persons. It is unknown whether rural-urban disparities exist in EOGC and if this intersects with ethnic disparities. METHODS: We utilized the Surveillance Epidemiology and End Results 17 Census Tract-level Socioeconomic Status and Rurality Database from 2006 to 2018 to calculate incidence rates and incidence rate ratios of EOGC among Hispanic and non-Hispanic persons by census tract rural-urban location, age, gender, persistent poverty, and stage of disease. We used the Tiwari Method to estimate incidence rate ratios with 95% confidence intervals (CI). RESULTS: Hispanic persons had higher incidence rates of EOGC compared with non-Hispanic persons in both rural [incident rate ratios (IRR), 2.12; 95% confidence interval (CI), 1.64-2.73] and urban census tracts (IRR, 2.03; 95% CI, 1.91-2.16). Similar findings were seen when comparing Hispanic to non-Hispanic persons in rural and urban census tracts by age, stage of disease, and persistent poverty. CONCLUSIONS: Higher incidence rates of EOGC among Hispanic persons persist across rural-urban locations. Further research is needed to understand the etiology of this elevated risk in young Hispanics and interventions that may help to modify their outcome. IMPACT: While other cancers have ethnic disparities which may differ by rural-urban location, the ethnic disparity in EOGC among Hispanic and non-Hispanic persons does not differ by rural-urban residence.

Stage migration as a surrogate of survival in hepatocellular carcinoma treated with transarterial chemoembolization.

BACKGROUND AIMS: Locoregional therapies, including transarterial chemoembolization (TACE), are recommended for the treatment of HCC; however, clinical trials evaluating their effectiveness have been complicated by a lack of validated surrogate outcomes. We aimed to evaluate if stage migration could serve as a potential surrogate of overall survival in patients undergoing TACE. APPROACH: We conducted a retrospective cohort study of adult patients with HCC who underwent TACE as initial therapy from 3 centers in the US from 2008 to 2019. The primary outcome was overall survival from the date of the first TACE treatment, and the primary exposure of interest was Barcelona Clinic Liver Cancer stage migration to a more advanced stage within 6 months of TACE. Survival analysis was completed using Kaplan-Meier and multiple Cox proportional hazard models adjusted by the site. RESULTS: Of 651 eligible patients (51.9% Barcelona Clinic Liver Cancer stage A and 39.6% stage B), 129 (19.6%) patients experienced stage migration within 6 months of TACE. Those with stage migration had larger tumors (5.6 vs. 4.2 cm, p < 0.01) and higher AFP levels (median 92 vs. 15 ng/mL, p < 0.01). In multivariate analysis, stage migration was significantly associated with worse survival (HR: 2.82, 95% CI: 2.66-2.98), with a median survival of 8.7 and 15.9 months in those with and without stage migration. Other predictors of worse survival included the White race, higher AFP levels, a higher number of tumors, and a larger maximum HCC diameter. CONCLUSION: Stage migration is associated with increased mortality after TACE in patients with HCC and could serve as a surrogate end point in clinical trials evaluating locoregional therapies such as TACE.

Impact on follow-up strategies in patients with primary sclerosing cholangitis.

BACKGROUND & AIMS: Evidence for the benefit of scheduled imaging for early detection of hepatobiliary malignancies in primary sclerosing cholangitis (PSC) is limited. We aimed to compare different follow-up strategies in PSC with the hypothesis that regular imaging improves survival. METHODS: We collected retrospective data from 2975 PSC patients from 27 centres. Patients were followed from the start of scheduled imaging or in case of clinical follow-up from 1 January 2000, until death or last clinical follow-up alive. The primary endpoint was all-cause mortality. RESULTS: A broad variety of different follow-up strategies were reported. All except one centre used regular imaging, ultrasound (US) and/or magnetic resonance imaging (MRI). Two centres used scheduled endoscopic retrograde cholangiopancreatography (ERCP) in addition to imaging for surveillance purposes. The overall HR (CI95%) for death, adjusted for sex, age and start year of follow-up, was 0.61 (0.47-0.80) for scheduled imaging with and without ERCP; 0.64 (0.48-0.86) for US/MRI and 0.53 (0.37-0.75) for follow-up strategies including scheduled ERCP. The lower risk of death remained for scheduled imaging with and without ERCP after adjustment for cholangiocarcinoma (CCA) or high-grade dysplasia as a time-dependent covariate, HR 0.57 (0.44-0.75). Hepatobiliary malignancy was diagnosed in 175 (5.9%) of the patients at 7.9 years of follow-up. Asymptomatic patients (25%) with CCA had better survival if scheduled imaging had been performed. CONCLUSIONS: Follow-up strategies vary considerably across centres. Scheduled imaging was associated with improved survival. Multiple factors may contribute to this result including early tumour detection and increased endoscopic treatment of asymptomatic benign biliary strictures.

HCC surveillance improves early detection, curative treatment receipt, and survival in patients with cirrhosis: A meta-analysis.

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. LAY SUMMARY: 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.

Increased Association between Previous Pregnancies and Use of Chemical Relaxers in 74 Women with Central Centrifugal Cicatricial Alopecia.

BACKGROUND: Central centrifugal cicatricial alopecia (CCCA) is a type of scarring alopecia exclusively seen in women of African descent. The etiology is unknown and epidemiologic studies including data on comorbidities in patients with CCCA are limited. Our primary objective was to identify possible etiologic and lifestyle associations in patients with CCCA. MATERIALS AND METHODS: A retrospective chart review was conducted for patients diagnosed with CCCA between January 1, 2013, and January 1, 2018, at a university dermatology outpatient clinic. Controls consisted of age-, sex-, and race-matched African-American women diagnosed with other hair loss conditions. Data from 74 cases and 96 controls were collected and analyzed via logistic regression. In addition, a phone survey was conducted in the CCCA cohort asking specific questions related to their condition and quality of life. RESULTS: A significant relationship was found between CCCA and previous pregnancies as well as the use of chemical relaxers: patients with CCCA were 11.71 times more likely to have had a previous pregnancy (P < 0.001) and 12.37 times more likely to have used chemical relaxers in the past (P < 0.001). Association with uterine fibroids was found not statistically significant (P > 0.05). CONCLUSION: We identified an association between previous pregnancies and use of chemical relaxers in patients diagnosed with CCCA when compared to controls. These findings may help to plan prospective studies aiming at establishing a more concrete link between hormones and CCCA.

Rapid improvement in organ procurement organization performance: Potential for change and impact of new leadership.

Recently proposed rulemaking from Centers for Medicare and Medicaid Services would change how organ procurement organizations (OPOs) are evaluated. The proposals include using national inpatient death data to define a standardized denominator to calculate comparable donation rates among OPOs. Based on these objective metrics, OPOs not performing at a prespecified threshold will be required to rapidly improve performance to avoid decertification. We sought to determine whether rapid OPO improvement was possible based on objective donation metrics, and whether leadership change was associated with rapid improvement. We evaluated United Network for Organ Sharing and Centers for Disease Control and Prevention (CDC) data from 2011 to 2018, and measured donation rates using CDC data on inpatient deaths from causes consistent with donation, based on the location of deaths. During the two 4-year cycles, we found that an OPO's ranking relative to other OPOs was fairly static, with more than 90% of the OPOs at risk of flagging at the end of each 4-year cycle (2014, 2018) being in the bottom 75% of OPOs in the preceding 3 years. In multivariable logistic regression models, leadership changes were only statistically significantly associated with an improvement in OPO rankings during the 2011-2014 cycle. These data demonstrate that rapid improvements in OPO performance are uncommon, and while leadership changes increase the odds of rapid improvement, they do not guarantee improvement.

Risk of gallbladder cancer in patients with primary sclerosing cholangitis and radiographically detected gallbladder polyps.

BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is associated with an increased risk of gallbladder cancer (GBC). Gallbladder polyps potentially harbour malignancy and thus international guidelines recommend prophylactic cholecystectomy for gallbladder polyps of any size in patients with PSC. To best inform patient care we sought to quantify the malignant risk of gallbladder polyps in patients with PSC. METHODS: A retrospective cohort study of patients followed in secondary and tertiary care settings in two large PSC clinics in North America was performed. RESULTS: In total, 453 patients were included with a median (IQR) follow-up time of 7.7 (4.1-12) years. A gallbladder polyp was radiographically detected in 16% (n = 71) with median size (range) of 4 (2-18) mm. In this group, post-cholecystectomy histology (n = 17) reported benign or no polyp in 77% (n = 13), dysplasia in 5.9% (n = 1) and malignancy in 18% (n = 3). The GBC rate was 8.8 (95% CI 1.8-25.7) per 1000 person-years in patients with a radiographically detected gallbladder polyp. GBC was associated with polyps >10 mm, interval growth or mass-like lesions on pre-operative imaging. In patients who did not have cholecystectomy (n = 50), the polyp was only transiently seen in 80% (n = 40), remained stable or decreased in size in 10% (n = 5) and increased in size in 6% (n = 3). The majority of gallbladder polyps did not show significant growth over time (0.041 mm/year [95% CI -0.017 to 0.249]). CONCLUSIONS: Most gallbladder polyps in patients with PSC are benign. Short-term surveillance imaging may be considered prior to recommending immediate cholecystectomy in patients with PSC without high-risk imaging features.