Identification of breath volatile organic compounds to distinguish pancreatic adenocarcinoma, pancreatic cystic neoplasm, and patients without pancreatic lesions.

BACKGROUND: Volatile organic compounds (VOCs) are a promising potential biomarker that may be able to identify the presence of cancers. AIM: To identify exhaled breath VOCs that distinguish pancreatic ductal adenocarcinoma (PDAC) from intraductal papillary mucinous neoplasm (IPMN) and healthy volunteers. METHODS: We collected exhaled breath from histologically proven PDAC patients, radiological diagnosis IPMN, and healthy volunteers using the ReCIVA® device between 10/2021-11/2022. VOCs were identified by thermal desorption-gas chromatography/field-asymmetric ion mobility spectrometry and compared between groups. RESULTS: A total of 156 participants (44% male, mean age 62.6 ± 10.6) were enrolled (54 PDAC, 42 IPMN, and 60 controls). Among the nine VOCs identified, two VOCs that showed differences between groups were dimethyl sulfide [0.73 vs 0.74 vs 0.94 arbitrary units (AU), respectively; P = 0.008] and acetone dimers (3.95 vs 4.49 vs 5.19 AU, respectively; P < 0.001). After adjusting for the imbalance parameters, PDAC showed higher dimethyl sulfide levels than the control and IPMN groups, with adjusted odds ratio (aOR) of 6.98 (95%CI: 1.15-42.17) and 4.56 (1.03-20.20), respectively (P < 0.05 both). Acetone dimer levels were also higher in PDAC compared to controls and IPMN (aOR: 5.12 (1.80-14.57) and aOR: 3.35 (1.47-7.63), respectively (P < 0.05 both). Acetone dimer, but not dimethyl sulfide, performed better than CA19-9 in PDAC diagnosis (AUROC 0.910 vs 0.796). The AUROC of acetone dimer increased to 0.936 when combined with CA19-9, which was better than CA19-9 alone (P < 0.05). CONCLUSION: Dimethyl sulfide and acetone dimer are VOCs that potentially distinguish PDAC from IPMN and healthy participants. Additional prospective studies are required to validate these findings.

Screening for viral hepatitis B infection in cancer patients before receiving chemotherapy - A systematic review and meta-analysis.

AIM: We conducted a systematic review and meta-analysis to assess the hepatitis B virus (HBV) screening rate in cancer patients before systemic chemotherapy, aiming to identify those needing antiviral prophylaxis for HBV reactivation. METHODS: We searched PubMed, Embase, Scopus, and Google Scholar for relevant studies. The pooled screening rate was estimated using a random effects model. Subgroup analyses were conducted based on malignancy types, chemotherapy regimens, study period, and HBV endemic regions. RESULTS: The meta-analysis included 29 studies from various endemic regions (19 low-endemic, three lower intermediate-endemic, and seven higher intermediate-endemic). These studies encompassed hematologic malignancies (n = 10), solid-organ tumors (n = 4), and combinations (n = 15). Seven studies used rituximab-containing regimens, four did not, and the remaining 11 did not specify chemotherapy regimens. The pooled screening rate was 57% (95% confidence interval [95%CI]: 46%-68%, I2 = 100%). Over time, screening rates improved from 37% (95%CI: 23%-53%) in 2006-2010 to 68% (54%-80%) in 2011-2015 and 69% (48%-84%) in 2016-2020. Screening rates were highest at 89% (74%-96%) in high endemic countries, followed by 60% (45-73%) in lower-intermediate and 49% (34-64%) in low-endemic countries. Patients with hematological malignancies had a higher screening rate than those with solid organ tumors, 65% (55%-74%) versus 37% (21%-57%), respectively. A screening rate was higher in patients receiving rituximab-containing chemotherapy than non-rituximab regimens, 68% (55%-79%) versus 45% (27%-65%). CONCLUSION: Despite existing guidelines, pre-chemotherapy HBV screening rate remains unsatisfactory, with substantial heterogeneous rates globally. These findings underscore the need for effective strategies to align practices with clinical guidelines.

Risk Factors for Development of Cirrhosis in Chronic Viral Hepatitis B Patients Who Had Persistent Viral Suppression With Antiviral Therapy.

Background and aims: Chronic viral hepatitis B (CHB)-infected patients occasionally develop cirrhosis despite having persistent viral suppression with antiviral therapy. We aimed to identify risk factors for developing cirrhosis in hepatitis B virus (HBV)-suppressed patients. Methods: We conducted a case-control study involving 120 noncirrhotic CHB-infected patients achieving viral suppression with antiviral treatment, with 40 cases developing cirrhosis and 80 age-, sex-, and Fibrosis-4 (FIB-4)-matched controls. Clinical and laboratory data at viral suppression, including body mass index (BMI), comorbidities, pretreatment HBV viral load, HBe antigen status, hepatitis C virus (HCV) and HIV coinfections, liver chemistries, and AST to Platelets Ratio Index (APRI) values, were retrospectively abstracted. Risk factors for cirrhosis post-HBV suppression were identified using Cox proportional hazard analysis. Results: Case and control groups had similar ages (51.4 ± 9.9 vs. 51.4 ± 10.2 years), proportions of males (80% vs. 80%), and FIB-4 values (1.32 vs. 1.31). The cirrhosis group showed significantly higher BMI (25.1 vs. 22.7, P = 0.01) and more diabetes prevalence (50.0% vs. 26.3%, P = 0.01), while other comorbidities and laboratory parameters were comparable (P > 0.05). By univariate analysis, BMI >23 kg/m2, diabetes, and APRI >0.7 were significantly associated with cirrhosis, with hazard ratios (HRs) (95%CI) of 2.99 (1.46-6.13), 2.31 (1.23-4.36), and 2.71 (1.05-6.99), P = 0.003, 0.010, and 0.039, respectively. In multivariate analyses adjusted for APRI, BMI>23 kg/m2 remained significantly associated with cirrhosis (aHR: 2.76, P = 0.006), while diabetes showed borderline significance (aHR: 1.99, P = 0.072). Conclusions: In HBV-infected patients achieving viral suppression with therapy, a BMI >23 kg/m2 increases the risk of cirrhosis. Therefore, a comprehensive approach addressing metabolic factors is imperative for preventing disease progression in HBV-infected patients.

Abbreviated MRI for Hepatocellular Carcinoma Surveillance - A Systematic Review and Meta-analysis.

BACKGROUND: Given the limited sensitivity of ultrasound in hepatocellular carcinoma (HCC) surveillance, this systematic review and meta-analysis were aimed to assess the diagnostic performance of non-contrast abbreviated MRI (NC-aMRI) compared to contrast-enhanced abbreviated MRI (CE-aMRI) for HCC surveillance, offering evidence-based guidance for clinical decision-making. METHODS: A comprehensive search was conducted across five databases, identifying studies on aMRI for HCC surveillance. The pooled sensitivity and specificity were estimated using a random effects model. Subgroup analyses and meta-regression were performed by study location, proportion of patients with cirrhosis and HCC, and underlying liver diseases. RESULTS: The meta-analysis included 27 studies (2009-2023), distributed between Western (n = 14) and Eastern (n = 13) countries. The pooled sensitivity and specificity (95%CI, I2) were 86% (83-88%, 63%) and 92% (90%-94%, 74%). The NC-aMRI protocols reported in 21 studies exhibited 83% (79-87%, 63%) sensitivity and 91% (88-93%, 67%) specificity, while the 15 studies on CE-aMRI protocols displayed 88% (84-91%, 64%) sensitivity and 94% (90-96%, 78%) specificity, with no statistically significant differences in sensitivity (p = 0.078) or specificity (p = 0.157). Subgroup analysis in NC-aMRI studies showed significant differences in sensitivity for high-prevalent chronic hepatitis B (87% vs. 78%, p = 0.003) and studies done in eastern countries (86% vs. 76%, p = 0.018). Additionally, specificity showed significant differences for high-prevalent chronic hepatitis C (94% vs. 90%, p = 0.009), with meta-regression identifying major sources of study heterogeneity as the inclusion of a majority of patients with chronic hepatitis B (p = 0.008) and the geographic regions where studies were conducted (p = 0.030). CONCLUSION: Surveillance aMRI protocols exhibit satisfactory performance for detecting HCC. NC-aMRI may be used effectively for HCC surveillance, especially in chronic hepatitis B prevalent settings.

Volatile organic compounds for diagnosis of early hepatocellular carcinoma in at-risk patients.

BACKGROUND: Volatile organic compounds (VOCs) have been shown as promising biomarkers for hepatocellular carcinoma (HCC) diagnosis. We aimed to investigate the performance of VOCs for diagnosing early-stage HCC in patients at-risk for HCC. METHODS: VOCs were identified in exhaled breath samples collected from 87 early-stage HCC patients, 90 cirrhotic patients, and 72 HBV-infected patients using thermal desorption-gas chromatography/field-asymmetric ion mobility spectrometry. The VOC levels were compared between the three groups. An association between VOCs and HCC was determined using logistic regression analysis. Diagnostic performance of VOCs was estimated using the AUROC and compared to serum alpha-fetoprotein (AFP). RESULTS: The levels of acetone monomer, dimethyl sulfide, 1,4-pentadiene, isopropyl alcohol, and acetone dimer were significantly different between the three groups. After adjusting for liver function test and AFP, acetone dimer was significantly associated with HCC. Acetone dimer significantly outperformed AFP with 86.2 % vs. 61.2 % sensitivity, 87.6 % vs. 66.2 % specificity, 86.9 % vs. 63.5 % for accuracy, and AUROC of 0.908 vs. 0.665, p = 0.007, <0.001, <0.001, and 0.001, respectively, for differentiating between HCC and cirrhosis. CONCLUSION: Acetone showed a better performance than AFP for diagnosing early HCC in at-risk patients. Further studies to validate the utility of VOCs as an HCC surveillance tool are needed.

Review and expert opinion on MAFLD, oxidative stress and multifunctional management.

Metabolic-associated fatty-liver disease (MAFLD), previously known as non-alcoholic fatty liver disease, is the most widespread and emerging chronic liver disease worldwide, with increasing prevalence rates also in the Asia-Pacific region. The disease has a high socio-economic burden as it negatively impacts the finances and quality of life of individuals affected and has a major burden on healthcare systems. The most important pathological event in MAFLD aetiopathogenesis is oxidative stress, which leads to functional and structural abnormalities in the liver as well as being involved in the development of other concomitant cardiometabolic diseases. MAFLD is a rather complex multisystemic clinical condition involving liver damage and a wide spectrum of extrahepatic manifestations such as obesity, type 2 diabetes, metabolic syndrome and cardiovascular diseases. This complexity requires the cooperation of multiple experts to identify MAFLD at an early stage, treat associated comorbidities, and promptly refer the patient to the hepatologist when needed. This review summarizes the current knowledge about MAFLD and reports the opinion of a group of experts on the increasing prevalence and burden of the disease in the southeast Asia region, the current journey of patients with MAFLD in developing countries, the role of oxidative stress and antioxidant treatment, and the importance of a multidisciplinary approach for early diagnosis and disease management. This article is part of the Current clinical use of silymarin in the treatment of toxic liver diseases: a case series Special Issue: https://www.drugsincontext.com/special_issues/current-clinical-use-of-silymarin-in-the-treatment-of-toxic-liver-diseases-a-case-series.

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

Background/Aims: 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. Methods: 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. Results: 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. Conclusions: 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.

Modified albumin-bilirubin predicted survival of unresectable hepatocellular carcinoma patients treated with immunotherapy.

BACKGROUND: Modified albumin-bilirubin (mALBI) grade has been established as a survival determinant in hepatocellular carcinoma (HCC) patients who receive locoregional and targeted therapies. AIM: To investigate whether mALBI could predict survival in unresectable HCC (uHCC) patients who were treated with atezolizumab plus bevacizumab (AB). METHODS: A single-center, retrospective cohort study enrolled uHCC patients who received AB treatment between September 2020 and April 2023 and were followed up until June 2023. An association between mALBI and patient survival was determined using Cox proportional hazards analysis. RESULTS: Of the 83 patients, 67 patients (80.7%) were male with the mean age of 60.6 years. Among them, 22 patients (26.5%) were classified as Barcelona Clinic Liver Cancer B, and 61 patients (73.5%) were classified as Barcelona Clinic Liver Cancer C. Cirrhosis was present in 76 patients (91.6%), with 58 patients classified as Child-Turcotte-Pugh (CTP) A and 18 as CTP B. The median overall survival (OS) and progression-free survival were 13.0 mo [95% confidence interval (CI): 5.2-20.8] and 9.0 mo (95%CI: 5.0-13.0), respectively. The patients were divided into two groups based on mALBI grades: 42 patients (50.6%) in the mALBI 1 + 2a group; and 41 patients (49.4%) in the mALBI 2b + 3 group. During the median follow-up period of 7.0 mo, the mALBI 1 + 2a group exhibited significantly better survival compared to the mALBI 2b + 3 group, with a median OS that was not reached vs 3.0 mo (95%CI: 0.1-6.0, P < 0.001). In a subgroup of patients with CTP A, the mALBI 1 + 2a group also showed significantly longer survival compared to the mALBI 2b + 3 group, with a median OS that was not reached vs 6.0 mo (95%CI: 3.4-8.6, P < 0.001). In the multivariate analysis, both CTP class and mALBI grade were independently associated with survival, with adjusted hazard ratios (95%CI) of 2.63 (1.19-5.78, P = 0.020) and 3.90 (1.71-8.90, P = 0.001), respectively. CONCLUSION: mALBI grades can determine survival of uHCC patients receiving AB treatment, particularly those who have mildly impaired liver function. This highlights the importance of assessing mALBI before initiating AB treatment to optimize therapeutic efficacy in clinical practice.

Validation of the albumin-bilirubin score for identifying decompensation risk in patients with compensated cirrhosis.

BACKGROUND: The albumin-bilirubin (ALBI) score is an index of liver function recently developed to assess prognosis in patients with hepatocellular carcinoma (HCC). It can detect small changes in liver dysfunction and has been successfully applied to the prediction of survival in patients with non-malignant liver diseases of various etiologies. AIM: To investigate the ALBI score for identifying decompensation risk at the 3-year follow-up in patients with compensated cirrhosis. METHODS: One-hundred and twenty-three patients with compensated cirrhosis without HCC in King Chulalongkorn Memorial Hospital diagnosed by imaging were retrospectively enrolled from January 2016 to December 2020. A total of 113 patients (91.9%) had Child A cirrhosis with a median model for end-stage liver disease (MELD) score of less than 9. Baseline clinical and laboratory variables and decompensation events were collected. The ALBI score was calculated and validated to classify decompensation risk into low-, middle-, and high-risk groups using three ALBI grade ranges (ALBI grade 1: ≤ -2.60; grade 2: > -2.60 but ≤ -1.39; grade 3: > -1.39). Decompensation events were defined as ascites development, variceal bleeding, or grade 3 or 4 hepatic encephalopathy. RESULTS: Among 123 cirrhotic patients enrolled, 13.8% (n = 17) developed decompensating events at a median time of 25 [95% confidence interval (CI): 17-31] mo. Median baseline ALBI score in compensated cirrhosis was significantly lower than that of patients who developed decompensation events [-2.768 (-2.956 to -2.453) vs -2.007 (-2.533 to -1.537); P = 0.01]. Analysis of decompensation risk at 3 years showed that ALBI score had a time-dependent area under the curve (tAUC) of 0.86 (95%CI: 0.78-0.92), which was significantly better than that of ALBI-Fibrosis-4 (ALBI-FIB4) score (tAUC = 0.77), MELD score (tAUC = 0.66), Child-Pugh score (tAUC = 0.65), and FIB-4 score (tAUC = 0.48) (P < 0.05 for all). The 3-year cumulative incidence of decompensation was 3.1%, 22.6%, and 50% in the low-, middle-, and high-risk groups, respectively (P < 0.001). The odds ratio for decompensation in patients of the high-risk group was 23.33 (95%CI: 3.88-140.12, P = 0.001). CONCLUSION: The ALBI score accurately identifies decompensation risk at the 3-year follow-up in patients with compensated cirrhosis. Those cirrhotic patients with a high-risk grade of ALBI score showed a 23 times greater odds of decompensation.

Artificial intelligence assists operators in real-time detection of focal liver lesions during ultrasound: A randomized controlled study.

PURPOSE: Detection of hepatocellular carcinoma (HCC) is crucial during surveillance by ultrasound. We previously developed an artificial intelligence (AI) system based on convolutional neural network for detection of focal liver lesions (FLLs) in ultrasound. The primary aim of this study was to evaluate whether the AI system can assist non-expert operators to detect FLLs in real-time, during ultrasound examinations. METHOD: This single-center prospective randomized controlled study evaluated the AI system in assisting non-expert and expert operators. Patients with and without FLLs were enrolled and had ultrasound performed twice, with and without AI assistance. McNemar's test was used to compare paired FLL detection rates and false positives between groups with and without AI assistance. RESULTS: 260 patients with 271 FLLs and 244 patients with 240 FLLs were enrolled into the groups of non-expert and expert operators, respectively. In non-experts, FLL detection rate in the AI assistance group was significantly higher than the no AI assistance group (36.9 % vs 21.4 %, p < 0.001). In experts, FLL detection rates were not significantly different between the groups with and without AI assistance (66.7 % vs 63.3 %, p = 0.32). False positive detection rates in the groups with and without AI assistance were not significantly different in both non-experts (14.2 % vs 9.2 %, p = 0.08) and experts (8.6 % vs 9.0 %, p = 0.85). CONCLUSIONS: The AI system resulted in significant increase in detection of FLLs during ultrasound examinations by non-experts. Our findings may support future use of the AI system in resource-limited settings where ultrasound examinations are performed by non-experts. The study protocol was registered under the Thai Clinical Trial Registry (TCTR20201230003), which is part of the WHO ICTRP Registry Network. The registry can be accessed via the following URL: https://trialsearch.who.int/Trial2.aspx?TrialID=TCTR20201230003.

Association between Liver Stiffness and Liver-Related Events in HCV-Infected Patients after Successful Treatment with Direct-Acting Antivirals.

Background and Objectives: Direct-acting antivirals (DAAs) are highly effective for the treatment of chronic hepatitis C virus (HCV) infection, but the risk of liver-related events and hepatocellular carcinoma (HCC) remains after successful therapy. We aimed to evaluate post-treatment changes in liver stiffness (LS) and identify a cut-off LS value for predicting such events in chronic HCV-infected patients receiving DAA. Materials and Methods: A total of 185 patients who had achieved sustained virologic response (SVR) after DAA therapy were included. Baseline characteristics and laboratory results were retrospectively abstracted. LS was measured by transient elastography at baseline, 12, 24, 48, and 96 weeks after SVR. FIB-4 index was assessed at baseline and 48 weeks after SVR. Development of liver-related events (hepatocellular carcinoma (HCC), portal-hypertension-related decompensation, listing for transplantation, and mortality) after SVR were identified. The association between liver fibrosis and the occurrence of liver-related events was analyzed using Cox regression analysis. Results: Significant differences in LS values were observed between baseline and 24, 48, 72, and 96 weeks after SVR. FIB-4 index at 48 weeks after SVR was significantly lower than the FIB-4 index at baseline. During the 41.6-month follow-up time, the incidence rates of all liver-related events and HCC were 2.36 and 1.17 per 100 person-years, respectively. Age, LS ≥8 kPa, and FIB-4 ≥1.35 at 48 weeks post-SVR were significantly associated with the occurrence of any liver-related events. By multivariate analysis, LS ≥8 kPa at 48 weeks post-SVR remained significantly associated with any liver-related events, with an adjusted hazard ratio (95%CI) of 5.04 (1.01-25.26), p = 0.049. Conclusions: Despite a significant reduction in LS after SVR, patients with LS ≥8 kPa at 48 weeks after SVR should be regularly monitored for liver-related complications, particularly HCC development.

VOCs from Exhaled Breath for the Diagnosis of Hepatocellular Carcinoma.

BACKGROUND: Volatile organic compound (VOC) profiles as biomarkers for hepatocellular carcinoma (HCC) are understudied. We aimed to identify VOCs from the exhaled breath for HCC diagnosis and compare the performance of VOCs to alpha-fetoprotein (AFP). The performance of VOCs for predicting treatment response and the association between VOCs level and survival of HCC patients were also determined. METHODS: VOCs from 124 HCC patients and 219 controls were identified using the XGBoost algorithm. ROC analysis was used to determine VOCs performance in differentiating HCC patients from controls and in discriminating treatment responders from non-responders. The association between VOCs and the survival of HCC patients was analyzed using Cox proportional hazard analysis. RESULTS: The combination of 9 VOCs yielded 70.0% sensitivity, 88.6% specificity, and 75.0% accuracy for HCC diagnosis. When differentiating early HCC from cirrhotic patients, acetone dimer had a significantly higher AUC than AFP, i.e., 0.775 vs. 0.714, respectively, p = 0.001. Acetone dimer classified HCC patients into treatment responders and non-responders, with 95.7% sensitivity, 73.3% specificity, and 86.8% accuracy. Isopropyl alcohol was independently associated with the survival of HCC patients, with an adjusted hazard ratio of 7.23 (95%CI: 1.36-38.54), p = 0.020. CONCLUSIONS: Analysis of VOCs is a feasible noninvasive test for diagnosing and monitoring HCC treatment response.

Regional Differences in Admissions and Treatment Outcomes for Hepatocellular Carcinoma Patients in Thailand.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the commonest cancers in Thailand. We report the stage and survival of patients who were admitted under the public universal health fund (NHSO) covering 47 million people to determine if there were regional disparities in the treatment outcomes in the country. METHOD: We used the 2009-2013 Nationwide Hospital Admission Data, Thailand. Patients with hepatocellular carcinoma (HCC) were identified by the ICD10 code C22.0. Procedures were identified by ICD9-CM codes, and deaths were confirmed from the NHSO database and the national citizen registry. Thailand is divided into 6 regions and Bangkok. Hospitals were identified according to their specific reimbursement codes. Survival time started from the day of first admission and was estimated using the Kaplan-Meier method. The statistical method used to compare regions was Chi-squared tests (Pearson, likelihood ratio, linear-by linear association and Mantel-cox). RESULTS: There were 36,956 HCC patients admitted during the study period. The overall median survival was 36 days. 1.63% of the patients had surgery, 0.96% had radiofrequency ablation (RFA), and 5.24% had trans-arterial chemoembolization (TACE). 90.24% did not have any tumor-specific therapy. The proportion of patients admitted for tumor-specific therapy vs. no tumor-specific therapy was significantly different between regions in all treatment modalities (p<0.01). Each treatment modality showed a wide range of median survival values across the regions (p<0.01). The best survival was seen in Bangkok, the South and the North (for surgery, RFA and TACE) and was often more than twice as long as the regions with the lowest survival, Central, East and West. CONCLUSIONS: There was a large previously-unreported disparity in admissions and outcomes in Thailand for different treatment modalities for HCC. Bangkok and the South had the best treatment outcomes and often had median survivals more than twice as long as those in the West and East. Public policy to reduce this disparity will need to be implemented in the future.

Circulating tumor cells as a prognostic biomarker in patients with hepatocellular carcinoma.

Circulating tumor cells (CTCs) have been shown as a surrogate for cancer progression and prognostication. We aimed to determine an association between CTCs and survival of hepatocellular carcinoma (HCC) patients. Peripheral blood was obtained from 73 HCC patients to enumerate for epithelial CTCs/8 mL blood. CTCs were detected by immunoaffinity-based method using epithelial cell adhesion molecule (EpCAM) and mucin1 (MUC1). The CTCs detection rates of BCLC stages A, B, and C patients were 65.4% (17/26), 77.3% (17/22), and 96% (24/25), respectively, p = 0.018. Patients with CTCs < 5 cells/8 mL had significantly longer survival than those with CTCs ≥ 5 cells/8 mL (>36 vs. 4.6 months, p < 0.001). In multivariate analysis, CTP B, BCLC B, BCLC C, AFP ≥ 400 ng/mL, and CTC ≥ 5 cells/8 mL were independently associated with survival, with adjusted HRs (95%CI) of 4.1 (2.0-8.4), 3.5 (1.1-11.4), 4.7 (1.4-15.4), 2.4 (1.1-5.0), and 2.6 (1.2-8.4); p < 0.001, 0.036, 0.011, 0.025 and 0.012, respectively. The combination of CTCs ≥ 5 cells/8 mL and AFP ≥ 400 ng/mL provided additively increased HR to 5.3 (2.5-11.1), compared to HRs of 4.0 (2.0-8.0) and 3.5 (1.8-6.7) for CTCs ≥ 5 cells/8 mL and AFP ≥ 400 ng/mL, p < 0.001, respectively. The larger number of peripheral CTCs is correlated with higher tumor aggressive features and poorer survival of HCC patients. CTCs can potentially become novel prognostic biomarker in HCC.

Establishment and Characterization of a New Human Intrahepatic Cholangiocarcinoma Cell Line LIV27.

Cholangiocarcinoma (CCA) is a highly lethal cancer arising from the biliary tract epithelium. The cancer biology of this neoplasm is not well understood. To date, only a few CCA cell lines have been reported, which were mostly developed from Asian patients. In this study, we report and characterize a new intrahepatic CCA cell line, LIV27, derived from a surgically resected tumor in a 67-year-old Caucasian woman with primary sclerosing cholangitis (PSC). LIV27 cells grow well in collagen-coated flasks or plates with a doubling time of 57.8 h at passage 14. LIV27 cells have high tumorigenicity in nude mice and stain positive for CK7 and CK19, markers that differentiate CCA from hepatocellular carcinoma. Karyotype analysis showed that LIV27 is aneuploid. We established a single-locus short tandem repeat profile for the LIV27 cell line. This newly established cell line will be a useful model for studying the molecular pathogenesis of, and developing novel therapies for, cholangiocarcinoma.

Physician- and patient-reported barriers to hepatocellular carcinoma surveillance: A nationwide survey.

Hepatocellular carcinoma (HCC) surveillance rates are suboptimal. We aimed to identify HCC surveillance barriers from both physician's and patient's perspectives and assess the effectiveness of physician education using social networks. A nationwide survey with 513 physicians and another single-center survey with 315 HCC-risk patients were conducted. Barriers to suboptimal surveillance were identified using univariate and multivariate logistic regression analysis. We educated 143 physicians by sending brief notes on HCC surveillance guidelines via social networks and re-evaluated their knowledge after 60 days using t test. Surveys showed 458 (86.3%), 254 (47.8%), and 225 (42.4%) physicians recommended surveillance in patients with cirrhosis, at-risk hepatitis B virus, and hepatitis C virus infection, respectively. Only 228 (42.9%) and 241 (38.0%) respondents adhered to recommended surveillance tools and interval, respectively. The main surveillance barriers among physicians were the lack of knowledge and resource limitations. The lack of a doctor's prescription was identified as a major barrier by patient' perspectives (odds ratio 1.4, 95% CI: 1.1-1.8, P = .024). Education via social networks enhanced physicians' knowledge, with pre- and post-education scores for guideline awareness of 63.0% versus 84.3% (P < .001) and for surveillance indication and tools of 40.0% versus 63.0% (P = .001), and 42.0% versus 59.3% (P = .015), respectively. Physicians' knowledge gap is a primary barrier for adherence to HCC surveillance protocols. Brief education via social networks shows effectiveness at increasing physicians' knowledge of HCC surveillance.

The feasibility to use artificial intelligence to aid detecting focal liver lesions in real-time ultrasound: a preliminary study based on videos.

Despite the wide availability of ultrasound machines for hepatocellular carcinoma surveillance, an inadequate number of expert radiologists performing ultrasounds in remote areas remains a primary barrier for surveillance. We demonstrated feasibility of artificial intelligence (AI) to aid in the detection of focal liver lesions (FLLs) during ultrasound. An AI system for FLL detection in ultrasound videos was developed. Data in this study were prospectively collected at a university hospital. We applied a two-step training strategy for developing the AI system by using a large collection of ultrasound snapshot images and frames from full-length ultrasound videos. Detection performance of the AI system was evaluated and then compared to detection performance by 25 physicians including 16 non-radiologist physicians and 9 radiologists. Our dataset contained 446 videos (273 videos with 387 FLLs and 173 videos without FLLs) from 334 patients. The videos yielded 172,035 frames with FLLs and 1,427,595 frames without FLLs for training on the AI system. The AI system achieved an overall detection rate of 89.8% (95%CI: 84.5-95.0) which was significantly higher than that achieved by non-radiologist physicians (29.1%, 95%CI: 21.2-37.0, p < 0.001) and radiologists (70.9%, 95%CI: 63.0-78.8, p < 0.001). Median false positive detection rate by the AI system was 0.7% (IQR: 1.3%). AI system operation speed reached 30-34 frames per second, showing real-time feasibility. A further study to demonstrate whether the AI system can assist operators during ultrasound examinations is warranted.

Exhaled volatile organic compounds for diagnosis of hepatocellular carcinoma.

Volatile organic compounds (VOCs) profile for diagnosis and monitoring therapeutic response of hepatocellular carcinoma (HCC) has not been well studied. We determined VOCs profile in exhaled breath of 97 HCC patients and 111 controls using gas chromatography-mass spectrometry and Support Vector Machine algorithm. The combination of acetone, 1,4-pentadiene, methylene chloride, benzene, phenol and allyl methyl sulfide provided the highest accuracy of 79.6%, with 76.5% sensitivity and 82.7% specificity in the training set; and 55.4% accuracy, 44.0% sensitivity, and 75.0% specificity in the test set. This combination was correlated with the HCC stages demonstrating by the increased distance from the classification boundary when the stage advanced. For early HCC detection, d-limonene provided a 62.8% sensitivity, 51.8% specificity and 54.9% accuracy. The levels of acetone, butane and dimethyl sulfide were significantly altered after treatment. Patients with complete response had a greater decreased acetone level than those with remaining tumor post-treatment (73.38 ± 56.76 vs. 17.11 ± 58.86 (× 106 AU, p = 0.006). Using a cutoff of 35.9 × 106 AU, the reduction in acetone level predicted treatment response with 77.3% sensitivity, 83.3% specificity, 79.4%, accuracy, and AUC of 0.784. This study demonstrates the feasibility of exhaled VOCs as a non-invasive tool for diagnosis, monitoring of HCC progression and treatment response.

Application of artificial intelligence for diagnosis of pancreatic ductal adenocarcinoma by EUS: A systematic review and meta-analysis.

EUS-guided tissue acquisition carries certain risks from unnecessary needle puncture in the low-likelihood lesions. Artificial intelligence (AI) system may enable us to resolve these limitations. We aimed to assess the performance of AI-assisted diagnosis of pancreatic ductal adenocarcinoma (PDAC) by off-line evaluating the EUS images from different modes. The databases PubMed, EMBASE, SCOPUS, ISI, IEEE, and Association for Computing Machinery were systematically searched for relevant studies. The pooled sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver operating characteristic curve were estimated using R software. Of 369 publications, 8 studies with a total of 870 PDAC patients were included. The pooled sensitivity and specificity of AI-assisted EUS were 0.91 (95% confidence interval [CI], 0.87-0.93) and 0.90 (95% CI, 0.79-0.96), respectively, with DOR of 81.6 (95% CI, 32.2-207.3), for diagnosis of PDAC. The area under the curve was 0.923. AI-assisted B-mode EUS had pooled sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 0.91, 0.90, 0.94, and 0.84, respectively; while AI-assisted contrast-enhanced EUS and AI-assisted EUS elastography had sensitivity, specificity, PPV, and NPV of 0.95, 0.95, 0.97, and 0.90; and 0.88, 0.83, 0.96 and 0.57, respectively. AI-assisted EUS has a high accuracy rate and may potentially enhance the performance of EUS by aiding the endosonographers to distinguish PDAC from other solid lesions. Validation of these findings in other independent cohorts and improvement of AI function as a real-time diagnosis to guide for tissue acquisition are warranted.

COVID-19 vaccine acceptance, hesitancy, and determinants among physicians in a university-based teaching hospital in Thailand.

BACKGROUND: The COVID-19 vaccines provide renewed hope in the fight against the recent pandemic. To ensure widespread vaccination, it is crucial to analyze vaccine willingness and its determinants among physicians, key health care influencers. This study aimed to assess acceptance rate and identify factors associated with vaccine hesitancy among Thai physicians. METHODS: A cross-sectional online-based questionnaire was distributed to all physicians at King Chulalongkorn Memorial Hospital during March 31, 2021 to April 30, 2021 in order to assess their attitudes toward receiving the COVID-19 vaccine. Reasons for vaccine acceptance and refusal as well as predictors of vaccine hesitancy were analyzed by bivariate and multivariable analysis. RESULTS: A total of 705 complete responses were received with 95.6% (n = 675) of physicians expressing willingness to receive a COVID-19 vaccine. Only one of the 31 physicians (4.4%) who expressed a hesitancy or unwillingness to be vaccinated was a faculty member; the others were physicians-in-training. Approximately one-fifths of physicians surveyed were also not willing to recommend the vaccine to their family members (21.4%, n = 151) or patients (18.7%, n = 132). Using multivariable logistic regression, vaccine hesitancy was independently associated with preference for particular vaccines over the government allocated option, especially for mRNA vaccine (aOR 8.86; 95% CI 1.1-71.54; p = 0.041). Vaccine literacy showed an inverse relationship (aOR 0.34; 95% CI 0.13-0.9; p = 0.029) with vaccine hesitancy. Uncertainty of the vaccine efficacy (83.9%) and fear of adverse events (48.4%) were major concerns contributing to vaccine hesitancy. CONCLUSION: This study revealed a high rate of physician willingness to take the COVID-19 vaccine especially among staffs; however, a significant proportion would not currently suggest vaccination to their families or patients. Restrictions on vaccine choice and vaccine illiteracy, together with concerns over adverse effects and uncertainty of efficacy, were associated with negative attitudes toward vaccination. To raise acceptance of the vaccination program, efforts should be made to balance individual preference for vaccine type in addition to increasing the availability of accurate data on safety and efficacy for each vaccine.