Carcinoma Surveillance Research Articles

Improved Survival in At-Risk Patients Undergoing Surveillance for Hepatocellular Carcinoma - A Nationwide Swedish Register-Based Study.

Surveillance for hepatocellular carcinoma (HCC) is recommended in at-risk patients, but its effectiveness in Western populations has been questioned. The purpose was to evaluate the effect of surveillance in patients with HCC in a Northern European setting. Data on patients diagnosed with HCC between 2009 and 2019 were collected from the nationwide Swedish National Registry for Tumors of the Liver and Bile Ducts (SweLiv). Patients who had undergone HCC surveillance were compared to those who had not (but had an obvious indication for surveillance, ie, liver cirrhosis or hepatic porphyria and an age of ≥50 years) regarding etiology, tumor burden, presence of extrahepatic spread, treatment and lead-time adjusted overall survival. A total of 4979 patients with index HCC were identified and information regarding surveillance was available in 4116 patients. Among these, 1078 had got their HCC diagnosis during surveillance, whereas 1647 had been diagnosed without surveillance despite a presumed indication. The most common underlying etiologies for HCC were hepatitis C (28.2%) and alcoholic liver disease (26.9%), and 94.8% had cirrhosis. The surveillance cohort more frequently met the University of California San Francisco-criteria (79% vs 53%, p <0.001), more often received a potentially curative treatment (62% vs 28%, p <0.001) and had less extrahepatic spread (7.6% vs 22.4% p <0.001). After adjustment for lead-time bias (sojourn time of 270 days), the surveillance group had a significantly longer estimated median survival time than the non-surveillance group (34 months vs 11 months, p <0.001). A multivariable cox regression analysis showed an adjusted hazard ratio of 0.59 (95% CI 0.51-0.67) in favor of surveillance. Surveillance for HCC in at-risk patients is associated with diagnosis at an earlier tumor stage, treatment with curative intent and with improved lead-time adjusted overall survival. These findings encourage HCC surveillance of at-risk patients also in a Western population.

Revolutionising hepatocellular carcinoma surveillance: Harnessing contrast-enhanced ultrasound and serological indicators for postoperative early recurrence prediction.

This study aimed to develop a noninvasive predictive model for identifying early postoperative recurrence of hepatocellular carcinoma (within 2 years after surgery) based on contrast-enhanced ultrasound and serum biomarkers. Additionally, the model's validity was assessedthrough internal and external validation. Clinical data were collected from patients who underwent liver resection at the First Hospital of Quanzhou and Mengchao Hepatobiliary Hospital. The data included general information, contrast-enhanced ultrasound parameters, Liver Imaging Reporting and Data System (LI-RADS) classification, and serum biomarkers. The data from Mengchao Hospital were divided into 2 groups, with a ratio of 6:4, to form the modeling and internal validation sets, respectively. On the other hand, the data from the First Hospital of Quanzhou served as the external validation group. The developed model was named the Hepatocellular Carcinoma Early Recurrence (HCC-ER) prediction model. The predictive efficiency of the HCC-ER model was compared with other established models. The baseline characteristics were found to be well-balanced across the modeling, internal validation, and external validation groups. Among the independent risk factors identified for early recurrence, LI-RADS classification, alpha-fetoprotein, and tumor maximum diameter exhibited hazard ratios of 1.352, 1.337, and 1.135 respectively. Regarding predictive accuracy, the HCC-ER, Tumour-Node-Metastasis, Barcelona Clinic Liver Cancer, and China Liver Cancer models demonstrated prediction errors of 0.196, 0.204, 0.201, and 0.200 in the modeling group; 0.215, 0.215, 0.218, and 0.212 in the internal validation group; 0.210, 0.215, 0.216, and 0.221 in the external validation group. Using the HCC-ER model, risk scores were calculated for all patients, and a cutoff value of 50 was selected. This cutoff effectively distinguished the high-risk recurrence group from the low-risk recurrence group in the modeling, internal validation, and external validation groups. However, the calibration curve of the predictive model slightly overestimated the risk of recurrence. The HCC-ER model developed in this study demonstrated high accuracy in predicting early recurrence within 2 years after hepatectomy. It provides valuable information for developing precise treatment strategies in clinical practice and holds considerable promise for further clinical implementation.

Prognostic role of computed tomography analysis using deep learning algorithm in patients with chronic hepatitis B viral infection.

The prediction of clinical outcomes in patients with chronic hepatitis B (CHB) is paramount for effective management. This study aimed to evaluate the prognostic value of computed tomography (CT) analysis using deep learning algorithms in patients with CHB. This retrospective study included 2,169 patients with CHB without hepatic decompensation who underwent contrast-enhanced abdominal CT for hepatocellular carcinoma (HCC) surveillance between January 2005 and June 2016. Liver and spleen volumes and body composition measurements including subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and skeletal muscle indices were acquired from CT images using deep learning-based fully automated organ segmentation algorithms. We assessed the significant predictors of HCC, hepatic decompensation, diabetes mellitus (DM), and overall survival (OS) using Cox proportional hazard analyses. During a median follow-up period of 103.0 months, HCC (n=134, 6.2%), hepatic decompensation (n=103, 4.7%), DM (n=432, 19.9%), and death (n=120, 5.5%) occurred. According to the multivariate analysis, standardized spleen volume significantly predicted HCC development (hazard ratio [HR]=1.01, P=0.025), along with age, sex, albumin and platelet count. Standardized spleen volume (HR=1.01, P<0.001) and VAT index (HR=0.98, P=0.004) were significantly associated with hepatic decompensation along with age and albumin. Furthermore, VAT index (HR=1.01, P=0.001) and standardized spleen volume (HR=1.01, P=0.001) were significant predictors for DM, along with sex, age, and albumin. SAT index (HR=0.99, P=0.004) was significantly associated with OS, along with age, albumin, and MELD. Deep learning-based automatically measured spleen volume, VAT, and SAT indices may provide various prognostic information in patients with CHB.

Comparison of patient-reported outcomes between active surveillance and immediate surgery for low-risk papillary thyroid carcinoma: A longitudinal study with one-year follow-up

Comparison of patient-reported outcomes between active surveillance and immediate surgery for low-risk papillary thyroid carcinoma: A longitudinal study with one-year follow-up

Long-Term outcomes of active surveillance for low-risk papillary thyroid carcinoma: is lifelong follow-up necessary?

Long-Term outcomes of active surveillance for low-risk papillary thyroid carcinoma: is lifelong follow-up necessary?

Utility of fusion imaging for the evaluation of ultrasound quality in hepatocellular carcinoma surveillance.

This study evaluated the quality of surveillance ultrasound (US) for hepatocellular carcinoma (HCC) utilizing fusion imaging. This research involved a secondary analysis of a prospectively recruited cohort. Under institutional review board approval, participants referred for surveillance US who had undergone liver computed tomography (CT) or magnetic resonance imaging (MRI) within the past year were screened between August 2022 and January 2023. After patient consent was obtained, the US visualization score in the Liver Imaging Reporting and Data System was assessed with fusion imaging at the time of examination. This score was compared to that of conventional US using the extended McNemar test. Multivariable logistic regression analysis was used to identify factors independently associated with a US visualization score of B or C. Factors limiting visualization of focal lesions were recorded during fusion imaging. Among the 105 participants (mean age, 59±11 years; 66 men), US visualization scores of B and C were assigned to 57 (54.3%) and 17 (16.2%) participants, respectively, by conventional US and 54 (51.4%) and 32 (30.5%) participants, respectively, by fusion imaging. The score distribution differed significantly between methods (P=0.010). Male sex was independently associated with US visualization scores of B or C (adjusted odds ratio, 3.73 [95% confidence interval, 1.30 to 10.76]; P=0.015). The most common reason (64.5%) for lesion nondetection was a limited sonic window. Conventional US may underestimate the limitations of the sonic window relative to real-time fusion imaging with pre-acquired CT or MRI in the surveillance of HCC.

Diagnostic performance of US LI-RADS in hepatocellular carcinoma surveillance

BackgroundLiver cirrhosis and chronic infection with hepatitis B virus are major risk factors for hepatocellular carcinoma (HCC). Guidelines recommend ultrasound (US) surveillance for population at risk of HCC. The US Liver Imaging Reporting and Data System (LI-RADS) aims at standardization of interpretation, reporting, and management recommendations for US surveillance examinations. The aim of this study is to assess the diagnostic accuracy of US LI-RADS in early HCC detection in patients at risk.ResultsThis retrospective study included patients with surveillance US between January 2018 and January 2020 who had a contrast-enhanced CT or MRI of the liver within 1 month from the date of US examination. Visualization scores and US categories were assigned according to the US LI-RADS lexicon. A total of 264 participants were eligible for the study. HCC was diagnosed in 33 participants. The US-3 category had a 39.4% sensitivity and 93.5% specificity for HCC detection. The US-2 category had a 45.4% sensitivity and 87% specificity for HCC detection. The visualization score C showed the highest number of HCC (19/33) and had the highest false-negative rate (76%, 13 of 17).ConclusionsBoth US-2 and US-3 categories showed high specificity and low sensitivity for HCC detection in the setting of surveillance of patients at high risk. Visualization score C had the highest risk for HCC and the highest rate of false-negative results. Intense surveillance by contrast-enhanced CT or MRI might be beneficial for patients with limited visualization scores B and C.

Exploring Opportunities to Enhance the Screening and Surveillance of Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease (NAFLD) through Risk Stratification Algorithms Incorporating Ultrasound Elastography.

Non-alcoholic fatty liver disease (NAFLD), with its progressive form, non-alcoholic steatohepatitis (NASH), has emerged as a significant public health concern, affecting over 30% of the global population. Hepatocellular carcinoma (HCC), a complication associated with both cirrhotic and non-cirrhotic NAFLD, has shown a significant increase in incidence. A substantial proportion of NAFLD-related HCC occurs in non-cirrhotic livers, highlighting the need for improved risk stratification and surveillance strategies. This comprehensive review explores the potential role of liver ultrasound elastography as a risk assessment tool for HCC development in NAFLD and highlights the importance of effective screening tools for early, cost-effective detection and improved management of NAFLD-related HCC. The integration of non-invasive tools and algorithms into risk stratification strategies could have the capacity to enhance NAFLD-related HCC screening and surveillance effectiveness. Alongside exploring the potential advancement of non-invasive tools and algorithms for effectively stratifying HCC risk in NAFLD, we offer essential perspectives that could enable readers to improve the personalized assessment of NAFLD-related HCC risk through a more methodical screening approach.

Hepatocellular Carcinoma Surveillance Patterns and Outcomes in Patients With Cirrhosis

Hepatocellular carcinoma (HCC) surveillance is associated with improved early detection and reduced mortality, although practice patterns and effectiveness vary in clinical practice. We aimed to characterize HCC surveillance patterns in a large, diverse cohort of patients with HCC. We conducted a retrospective cohort study of patients diagnosed with HCC between January 2008 and December 2022 at 2 large US health systems. We recorded imaging receipt in the year before HCC diagnosis: ultrasound plus α-fetoprotein (AFP), ultrasound alone, multiphasic contrast-enhanced computed tomography (CT)/magnetic resonance imaging (MRI), and no liver imaging. We used multivariable logistic and Cox regression analysis to compare early tumor detection, curative treatment receipt, and overall survival between surveillance strategies. Among 2028 patients with HCC (46.7% Barcelona Clinic Liver Cancer stage A), 703 (34.7%) had ultrasound plus AFP, 293 (14.5%) had ultrasound alone, 326 (16.1%) had multiphasic CT/MRI, and 706 (34.8%) had no imaging in the year before HCC diagnosis. Over the study period, proportions without imaging were stable, whereas use of CT/MRI increased. Compared with no imaging, CT/MRI and ultrasound plus AFP, but not ultrasound alone, were associated with early stage HCC detection and curative treatment. Compared with ultrasound alone, CT/MRI and ultrasound plus AFP were associated with increased early stage detection. HCC surveillance patterns vary in clinical practice and are associated with differing clinical outcomes. While awaiting data to determine if CT or MRI surveillance can be performed in a cost-effective manner in selected patients, AFP has a complementary role to ultrasound-based surveillance, supporting its adoption in practice guidelines.

Cost-Utility Analysis of Non-Contrast Abbreviated Magnetic Resonance Imaging for Hepatocellular Carcinoma Surveillance in Cirrhosis.

Ultrasonography has a low sensitivity for detecting early-stage hepatocellular carcinoma (HCC) in cirrhotic patients. Non-contrast abbreviated magnetic resonance imaging (aMRI) demonstrated a comparable performance to that of magnetic resonance imaging without the risk of contrast media exposure and at a lower cost than that of full diagnostic MRI. We aimed to investigate the cost-effectiveness of non-contrast aMRI for HCC surveillance in cirrhotic patients, using ultrasonography with alpha-fetoprotein (AFP) as a reference. Cost-utility analysis was performed using a Markov model in Thailand and the United States. Incremental cost-effectiveness ratios were calculated using the total costs and quality-adjusted life years (QALYs) gained in each strategy. Surveillance protocols were considered cost-effective based on a willingness-to-pay value of $4,665 (160,000 Thai Baht) in Thailand and $50,000 in the United States. aMRI was cost-effective in both countries with incremental cost-effectiveness ratios of $3,667/QALY in Thailand and $37,062/QALY in the United States. Patient-level microsimulations showed consistent findings that aMRI was cost-effective in both countries. By probabilistic sensitivity analysis, aMRI was found to be more cost-effective than combined ultrasonography and AFP with a probability of 0.77 in Thailand and 0.98 in the United States. By sensitivity analyses, annual HCC incidence was revealed as the most influential factor affecting cost-effectiveness. The cost-effectiveness of aMRI increased in settings with a higher HCC incidence. At a higher HCC incidence, aMRI would remain cost-effective at a higher aMRI-to-ultrasonography with AFP cost ratio. Compared to ultrasonography with AFP, non-contrast aMRI is a cost-effective strategy for HCC surveillance and may be useful for such surveillance in cirrhotic patients, especially in those with high HCC risks.

Hepatocellular carcinoma surveillance - utilization, barriers and the impact of changing aetiology.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. Surveillance for HCC is critical for early detection and treatment, but fewer than one-quarter of individuals at risk of HCC undergo surveillance. Multiple failures across the screening process contribute to the underutilization of surveillance, including limited disease awareness among patients and health-care providers, knowledge gaps, and difficulty recognizing patients who are at risk. Non-alcoholic fatty liver disease and alcohol-associated liver disease are the fastest-rising causes of HCC-related death worldwide and are associated with unique barriers to surveillance. In particular, more than one-third of patients with HCC related to non-alcoholic fatty liver disease do not have cirrhosis and therefore lack a routine indication for HCC surveillance on the basis of current practice guidelines. Semi-annual abdominal ultrasound with measurement of α-fetoprotein levels is recommended for HCC surveillance, but the sensitivity of this approach for early HCC is limited, especially for patients with cirrhosis or obesity. In this Review, we discuss the current status of HCC surveillance and the remaining challenges, including the changing aetiology of liver disease. We also discuss strategies to improve the utilization and quality of surveillance for HCC.

Sex and Race Disparities in Hepatocellular Carcinoma Surveillance in Patients With Chronic Hepatitis B During COVID-19: A Single-Center Retrospective Review.

The management of patients with chronic hepatitis B (CHB) is complex and spans multiple medical specialties. As a result of this complexity, patients with CHB often do not receive adequate monitoring including hepatocellular carcinoma (HCC) surveillance with abdominal ultrasonography. Previous studies have identified multiple factors associated with decreased HCC surveillance. We aimed to identify the impact of race and sex on HCC surveillance in patients with CHB. We performed a single health system chart review between January 2018 and January 2022. Differences between sex and race were evaluated using the Chi-square test and Fisher's exact test, and continuous variables were analyzed using analysis of variance (ANOVA). A total of 248 patient records between January 2018 and January 2022 were evaluated. In total 37% of females were adequately screened for HCC in any of the 6-month time frames compared to 26% of males. During the coronavirus disease 2019 (COVID-19) surge, surveillance rates were reduced in both men and women. During the first 6 months of the COVID-19 surge, there was a significant difference in screening between men and women (19% vs. 35%, P = 0.026). There was a decrease in HCC screening across all races during the COVID-19 surge; however, no significant difference when comparing races was found. Men received less HCC surveillance compared to women. These differences were more pronounced during the COVID-19 pandemic surge. Obtaining appropriate surveillance is important and retrospective evaluations can help us determine the presence of health-related social needs so that progress can be made toward achieving health equity.

Value of Adherence to Posttreatment Follow-Up Guidelines for Head and Neck Squamous Cell Carcinoma.

The utility of intensive posttreatment surveillance of head and neck squamous cell carcinoma (HNSCC) has been debated. The objective is to investigate adherence to the National Comprehensive Cancer Network (NCCN) posttreatment follow-up guidelines and assess the association with recurrence and survival. A total of 452 patients diagnosed with HNSCC at an academic medical center in a socioeconomically disadvantaged, urban setting were categorized by adherence to NCCN follow-up guidelines. Survival analyses were conducted to study the association between adherence and the 5-year overall survival and disease-specific survival in the entire cohort and subset of patients with documented recurrence. We found that 23.5% of patients were adherent to NCCN follow-up guidelines in the first year after treatment, and 15.9% were adherent over 5 years. Adherence in the first year was significantly associated with 5-year overall survival (HR 0.634; 95% CI 0.443-0.906; p = 0.0124) and disease-specific survival (HR 0.556; 95% CI 0.312-0.992; p = 0.0470), but consistent adherence over 5 years did not show a significant association. Among the 21.7% of the cohort with recurrence, adherence was not associated with early-stage recurrence (AJCC stage I/II). In this subset, first year adherence was associated with improved disease-specific but not overall survival, and adherence over 5 years was not associated with survival. Adherence to NCCN follow-up guidelines in the first year after treatment was associated with a better chance of 5-year overall and disease-specific survival, but this significant association was not observed among those who demonstrated consistent adherence over 5 years. 3 Laryngoscope, 134:708-716, 2024.

US LI-RADS in surveillance for recurrent hepatocellular carcinoma after curative treatment.

To investigate the performance of US LI-RADS in surveillance for recurrent hepatocellular carcinoma (RHCC) after curative treatment. This study enrolled 644 patients between January 2018 and August 2018 as a derivation cohort, and 397 patients from September 2018 to December 2018 as a validation cohort. The US surveillance after HCC curative treatment was performed. The US LI-RADS observation categories and visualization scores were analyzed. Four criteria using US LI-RADS or Alpha-fetoprotein (AFP) as the surveillance algorithm were evaluated. The sensitivity, specificity, and negative predictive value (NPV) were calculated. A total of 212 (32.9%) patients in derivation cohort and 158 (39.8%) patients in validation cohort were detected to have RHCCs. The criterion of US-2/3 or AFP ≥ 20µg/L had higher sensitivity (derivation, 96.7% vs 92.9% vs 81.1% vs 90.6%; validation, 96.2% vs 90.5% vs 80.4% vs 89.9%) and NPV (derivation, 95.7% vs 93.3% vs 88.0% vs 91.8%; validation, 94.6% vs 89.4% vs 83.6% vs 89.0%), but lower specificity (derivation, 35.9% vs 48.2% vs 67.6% vs 51.9%; validation, 43.5% vs 52.7% vs 66.1% vs 54.0%) than criterion of US-2/3, US-3, and US-3 or AFP ≥ 20µg/L. Analysis of the visualization score subgroups confirmed that the sensitivity (89.2-97.6% vs 81.0-83.3%) and NPV(88.4-98.0% vs 80.0-83.3%) of score A and score B groups were higher than score C group in criterion of US-2/3 in both two cohorts. In the surveillance for RHCC, US LI-RADS with AFP had a high sensitivity and NPV when US-2/3 or AFP ≥ 20µg/L was considered a criterion. The criterion of US-2/3 or AFP ≥ 20µg/L improves sensitivity and NPV for RHCC surveillance, which provides a valuable reference for patients in RHCC surveillance after curative treatment. • US LI-RADS with AFP had high sensitivity and NPV in surveillance for RHCC when considering US-2/3 or AFP ≥ 20µg/L as a criterion. • After US with AFP surveillance, patients with US-2/3 or AFP ≥ 20µg/L should perform enhanced imaging for confirmative diagnosis. Patients with US-1 or AFP < 20µg/L continue to repeat US with AFP surveillance. • Patients with risk factors for poor visualization scores limited the sensitivity of US surveillance in RHCC.

Development and Multicenter Case-Control Validation of Urinary Comprehensive Genomic Profiling for Urothelial Carcinoma Diagnosis, Surveillance, and Risk-Prediction.

Urinary comprehensive genomic profiling (uCGP) uses next-generation sequencing to identify mutations associated with urothelial carcinoma and has the potential to improve patient outcomes by noninvasively diagnosing disease, predicting grade and stage, and estimating recurrence risk. This is a multicenter case-control study using banked urine specimens collected from patients undergoing initial diagnosis/hematuria workup or urothelial carcinoma surveillance. A total of 581 samples were analyzed by uCGP: 333 for disease classification and grading algorithm development, and 248 for blinded validation. uCGP testing was done using the UroAmp platform, which identifies five classes of mutation: single-nucleotide variants, copy-number variants, small insertion-deletions, copy-neutral loss of heterozygosity, and aneuploidy. UroAmp algorithms predicting urothelial carcinoma tumor presence, grade, and recurrence risk were compared with cytology, cystoscopy, and pathology. uCGP algorithms had a validation sensitivity/specificity of 95%/90% for initial cancer diagnosis in patients with hematuria and demonstrated a negative predictive value (NPV) of 99%. A positive diagnostic likelihood ratio (DLR) of 9.2 and a negative DLR of 0.05 demonstrate the ability to risk-stratify patients presenting with hematuria. In surveillance patients, binary urothelial carcinoma classification demonstrated an NPV of 91%. uCGP recurrence-risk prediction significantly prognosticated future recurrence (hazard ratio, 6.2), whereas clinical risk factors did not. uCGP demonstrated positive predictive value (PPV) comparable with cytology (45% vs. 42%) with much higher sensitivity (79% vs. 25%). Finally, molecular grade predictions had a PPV of 88% and a specificity of 95%. uCGP enables noninvasive, accurate urothelial carcinoma diagnosis and risk stratification in both hematuria and urothelial carcinoma surveillance patients.

Serial increase and high alpha-fetoprotein levels predict the development of hepatocellular carcinoma in 6months.

Alpha-fetoprotein (AFP) checkup with abdominal ultrasonography for hepatocellular carcinoma (HCC) surveillance remains controversial. We evaluated a serial AFP-increase and high AFP levels in the prediction of HCC. At-risk patients with chronic liver disease underwent HCC surveillance with trimonthly AFP measurement were included and categorized into HCC and non-HCC groups. Their AFP levels at 12, 9, and 6months (-6M) before the outcome date were evaluated. Group-based trajectory analysis and multivariable regression analysis were performed to identify AFP trajectories as risk predictors for HCC. Overall, 2776 patients were included in the HCC (n=326) and non-HCC (n=2450) groups. Serial AFP levels were significantly higher in the HCC than the non-HCC groups. Trajectory analysis identified AFP-increase group (11%) increased 24-fold risks of HCC compared with the AFP-stable (89%) group. Compared with patients without the AFP-increase, a serial 3-month AFP-increase ≥10% elevated HCC risk by 12.1-fold (95% CI: 6.5-22.4) in 6months, and the HCC risks increased 13-60 fold in patients with cirrhosis, hepatitis B, or C receiving antiviral therapy, or AFP levels <20ng/ml. Combining serial AFP-increase ≥10% and AFP ≥20ng/ml at -6M significantly increased 41.7-fold (95% CI: 13.8-126.2) HCC risks. In patients who underwent biannual AFP checkups, those with both 6-month AFP-increase ≥10% and AFP ≥20ng/ml increased 22.1-fold (95% CI: 12.52-39.16) HCC risks in 6months. Most HCCs were detected at an early stage. Serial 3-6-month AFP-increase of ≥10% previously and AFP level of ≥20ng/ml significantly increased HCC risks in 6months.

Interventions to Improve Surveillance for Hepatocellular Carcinoma in High-Risk Patients: A Scoping Review.

Hepatocellular carcinoma (HCC) is most often a sequela of chronic liver disease or chronic hepatitis B infection. Among high-risk patients, surveillance for HCC every 6months is recommended by international guidelines. However, rates of HCC surveillance are suboptimal (11-64%). Barriers at the patient, provider, and healthcare delivery system levels have been identified. We performed a systemic scoping review to identify and characterize interventions to improve HCC surveillance that has previously been evaluated. Searches using key terms in PubMed and Embase were performed to identify studies examining interventions designed to improve the surveillance rate for HCC in patients with cirrhosis or chronic liver disease that were published in English between January 1990 and September 2021. Included studies (14) had the following study designs: (1) randomized clinical trials (3, 21.4%), (2) quasi-experimental (2, 14.3%), (3) prospective cohort (6, 42.8%), and (4) retrospective cohort (3, 21.4%). Interventions included mailed outreach invitations, nursing outreach, patient education with or without printed materials, provider education, patient navigation, chronic disease management programs, nursing-led protocols for image ordering, automated reminders to physicians and nurses, web-based clinical management tools, HCC surveillance databases, provider compliance reports, radiology-led surveillance programs, subsidized HCC surveillance, and the use of oral medications. It was found that HCC surveillance rates increased after intervention implementation in all studies. Despite improvements in HCC surveillance rates with intervention, compliance remained suboptimal. Further analysis of which interventions yield the greatest increases in HCC surveillance, design of multi-pronged strategies, and improved implementation are needed.

Hepatocellular Carcinoma Incidence Threshold for Surveillance in Virologically Cured Hepatitis C Individuals

Guidelines recommend biannual surveillance for hepatocellular carcinoma (HCC) in hepatitis C individuals with cirrhosis if the HCC incidence rate is above 1.5 per 100 person-years (PY). However, the incidence threshold for surveillance in individuals who achieve a virologic cure is unknown. We estimated the HCC incidence rate above which routine HCC surveillance is cost-effective in this growing population of virologically cured hepatitis C individuals with cirrhosis or advanced fibrosis. We developed a Markov-based microsimulation model of the natural history of HCC in individuals with hepatitis C who achieved virologic cure with oral direct-acting antivirals. We used published data on the natural history of hepatitis C, competing risk post virologic cure, HCC tumor progression, real-world HCC surveillance adherence, contemporary HCC treatment options and associated costs, and utilities of different health states. We estimated the HCC incidence above which biannual HCC surveillance using ultrasound and alpha-fetoprotein would be cost-effective. In virologically cured hepatitis C individuals with cirrhosis or advanced fibrosis, HCC surveillance is cost-effective if HCC incidence exceeds 0.7 per 100 PY using $100,000 per quality-adjusted life year willingness-to-pay. At this HCC incidence, routine HCC surveillance would result in 2650 and 5700 additional life years per 100,000 cirrhosis and advanced fibrosis persons, respectively, compared with no surveillance. At $150,000 willingness-to-pay, surveillance is cost-effective if HCC incidence exceeds 0.4 per 100 PY. Sensitivity analysis showed that the threshold mostly remained below 1.5 per 100 PY. The contemporary HCC incidence threshold is much lower than the previous 1.5% incidence value used to guide HCC surveillance decisions. Updating clinical guidelines could improve the early diagnosis of HCC.

Survival benefit of active surveillance for papillary thyroid carcinoma: a propensity score matching analysis based on SEER database.

Over-treatment of papillary thyroid microcarcinoma (PTMC) has become a common issue. Although active surveillance (AS) has been proposed as an alternative treatment to immediate surgery for PTMC, its inclusion criteria and mortality risk have not been clearly defined. The purpose of this study was to investigate whether surgery can achieve significant survival benefits in patients with larger tumor diameter of papillary thyroid carcinoma (PTC), in order to evaluate the feasibility of expanding the threshold for active surveillance. This study retrospectively collected data of patients with papillary thyroid carcinoma from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2019. The propensity score matching (PSM) method was used to minimize confounding factors and selection bias between the surgery and non-surgery groups, and to compare the clinical and pathological characteristics between the two groups based on the SEER cohort. Meanwhile, the impact of surgery on prognosis was compared using Kaplan-Meier estimates and Cox proportional hazard models. A total of 175,195 patients were extracted from the database, including 686 patients who received non-surgical treatment, and were matched 1:1 with patients who received surgical treatment using propensity score matching. The Cox proportional hazard forest plot showed that age was the most important factor affecting overall survival (OS) of patients, while tumor size was the most important factor affecting disease-specific survival (DSS) of patients. In terms of tumor size, there was no significant difference in DSS between PTC patients with tumor size of 0-1.0cm who underwent surgical treatment and those who underwent non-surgical treatment, and the relative survival risk began to increase after the tumor size exceeded 2.0cm. Additionally, the Cox proportional hazard forest plot showed that chemotherapy, radioactive iodine, and multifocality were negative factors affecting DSS. Moreover, the risk of death increased over time, and no plateau phase was observed. For patients with papillary thyroid carcinoma (PTC) staged as T1N0M0, AS is a feasible management strategy. As the tumor diameter increases, the risk of death without surgical treatment gradually increases, but there may be a threshold. Within this range, a non-surgical approach may be a potentially viable management strategy. However, beyond this range, surgery may be more beneficial for patient survival. Therefore, it is necessary to conduct more large-scale prospective randomized controlled trials to further confirm these findings.

Gene body hypomethylation of pyroptosis-related genes NLRP7, NLRP2, and NLRP3 facilitate non-invasive surveillance of hepatocellular carcinoma.

Programmed cell death (PCD) resistance is a key driver of cancer occurrence and development. The prognostic relevance of PCD-related genes in hepatocellular carcinoma (HCC) has attracted considerable attention in recent years. However, there is still a lack of efforts to compare the methylation status of different types of PCD genes in HCC and their roles in its surveillance. The methylation status of genes related to pyroptosis, apoptosis, autophagy, necroptosis, ferroptosis, and cuproptosis was analyzed in tumor and non-tumor tissues from TCGA. Whole-genome bisulfite sequencing (WGBS) data of paired tumor tissue and buffy coat samples were used to filter the potential interference of blood leukocytes in cell-free DNA (cfDNA). The WGBS data of healthy individuals' and early-stage HCC patients' cfDNA were analyzed to evaluate the distinguishing ability. The average gene body methylation (gbDNAme) of pyroptosis-related genes (PRGs) was significantly altered in HCC tissues relative to normal tissues, and their distinguishing ability was higher compared to the other types of PCD-related genes. The gbDNAme of NLRP7, NLRP2, and NLRP3 was reflective of the hypomethylation in HCC tissues, and methylation levels of NLRP3 correlated positively with its expression level (r=0.51). The candidate hypomethylated PRGs could discriminate between early HCC patients and healthy controls in cfDNA analysis with high accuracy (area under the receiver operation curve, AUC=0.94). Furthermore, the hypomethylation of PRGs was associated with poor prognosis of HCC. Gene body hypomethylation of PRGs is a promising biomarker for early HCC detection, monitoring of tumor recurrence, and prognosis prediction.