High AFP Level Research Articles

Comparison of laparoscopic hepatectomy and radiofrequency ablation for small hepatocellular carcinoma patients: a SEER population-based propensity score matching study.

This study was designed to compare the efficacy of laparoscopic hepatectomy (LH) and radiofrequency ablation (RFA) in terms of their therapeutic effect on small hepatocellular carcinoma (SHCC). The SEER database was employed to integrate SHCC patients who had received treatment with either LH (n = 1132) or RFA (n = 797). The LH group (n = 623) and the RFA group (n = 623) were matched with 1:1 propensity score matching (PSM) in order to reduce the possibility of selection bias. The Kaplan-Meier method and Cox proportional hazards regression method were employed to ascertain the prognostic factors associated with overall survival (OS) and disease-specific survival (DSS). Both before and after PSM, the 1, 3 and 5-years OS and DSS were significantly higher in the LH groups compared to the RFA group. Besides, for SHCC with tumor size ≤ 2cm (n = 418), even P values not reaching statistical significance, the survival curves were compatible with a superiority of LH over RFA for OS and DSS in overall (P = 0.054 and P = 0.077), primary SHCC (P = 0.110 and P = 0.058) and recurrent SHCC (P = 0.068 and P = 1.000) cohorts. In contrast, for SHCC with tumor size between 2 and 3 cm (n = 828), LH group always had a better OS and DSS in the all cohorts (all P < 0.05). In addition, higher AFP level, poor differentiation grade, recurrent tumor and treatment type were independent prognostic factors for OS, while poor differentiation grade, larger tumor size and treatment type were the independent prognostic factors for DSS (all P < 0.05). LH was associated with better OS and DSS than RFA in SHCC patients. Even in tumor size ≤ 2cm, LH still should be the first choice as its long-term survival benefits.

Positivity of high-sensitivity HBsAg test, not previous HBV infection, indicates poor prognosis in patients with non-HBV-related HCC.

The prognostic impact of previous-HBV-infection (pHBV) in non-HBV-related hepatocellular carcinoma (non-HBV-related-HCC) and the prevalence, characteristics and significance of recently developed high-sensitivity HBs antigen positivity (hHBsAg+) in these patients remain unclear. We aimed to close these gaps. We retrospectively screened patients with newly diagnosed non-HBV-related-HCC (standard HBsAg-test negative) at Hokkaido University. Patients with complete clinical information and preserved serum for hHBsAg+ were included. We evaluated the prevalence, characteristics and prognostic impact of pHBV and hHBsAg+ in non-HBV-related-HCC. A total of 401 non-HBV-related-HCC patients were included (288 with pHBV/113 without pHBV). In non-HBV-related-HCC, pHBV did not affect overall survival (OS). Among non-HBV-related-HCC patients with pHBV, 11.8% (34/288) were hHBsAg+ and had more advanced stages of HCC, higher AFP levels, higher vascular invasion rates, and significantly shorter OS than others (OS: 19.3 vs. 61.4 months, p = 0.012). Comparison of OS among non-HBV-related-HCC patients without pHBV (group 1), those with pHBV and without hHBsAg+ (group 2), and those with pHBV and hHBsAg+ (group 3) revealed significantly shorter OS in group 3 (19.3, 56.6 and 66.4 months in groups 1, 2 and 3, respectively; p = 0.036). Multivariate Cox regression indicated that compared with group 1, only group 3 was significantly and independently associated with shorter OS (HR: 2.044, p = 0.011). Subgroup analysis revealed that this association was particularly evident in non-HBV-related-HCC patients with non-B-non-C aetiology and advanced HCC. In non-HBV-related-HCC patients, hHBsAg+, not pHBV, is significantly and independently associated with poor prognosis.

Comparison between pancreatoblastoma (PB) and solid pseudopapillary neoplasm (SPN) in pediatric patients with enhanced CT

Rationale and objectivesTo investigate whether computed tomography features can differentiate pancreatoblastoma (PB) from solid pseudopapillary tumor (SPN) in children. Materials and methodsClinical and imaging data of 18 cases of PB and 61 cases of SPN confirmed by surgery or biopsy were retrospectively analyzed. All enrolled patients underwent 3 phases (non-contrast, arterial, and portal venous phases) of CT scanning. Qualitative CT analysis (location, margin, solid/cystic component proportion, calcification, hemorrhage, peritumoral vascularity, bile duct dilatation, pancreatic duct dilatation, pancreatic atrophy, vascular invasion, peripancreatic invasion, and distant metastases) and quantitative analysis (maximum tumor diameter, interface between tumor and parenchyma [delta], arterial enhancement ratio [AER], and portal enhancement ratio [PER]) were performed. The general CT morphologic features, age and tumor markers were compared also compared between the groups. Univariate analysis and the F test were conducted to identify features of PB. Then logistic Regression classifier was trained using the top five features with the highest F-value. Moreover, we used 5-fold cross-validation techniques for the validation of our model. ResultsPB exhibited a significantly higher frequency of location in the body/tail, larger tumor size, poorly defined margins, calcification, peritumoral vascularity, pancreatic atrophy, and less hemorrhage. In addition, PB had higher AER, PER and lower delta relative to SPN (p < 0.05). PB presented a younger age and higher levels of AFP. Results of the F test indicated that AFP, AER, Age, calcification and pancreatic atrophy were the top five features included in the model that could differentiate pediatric PB from SPN. The combined model of CT and clinical features performed well in differentiating PB from SPN, with an AUC of 0.981 in the training cohort and 0.953 in the validation cohort. ConclusionsAFP, AER, age, calcification and pancreatic atrophy are robust CT and clinical features for differentiating pediatric PB from SPN. A combination of qualitative and quantitative CT features may provide good diagnostic accuracy in differentiating PB from SPN in children.

Assessment of Alpha Feto Protein in Patients with Hepatocellular Carcinoma Presenting to HCC Clinic During Era of COVID19 Pandemic

Abstract Background Hepatocellular carcinoma (HCC), a major health problem worldwide, is one of the most common primary neoplasms of the liver and one of the most common solid tumors in the world. More than 500,000 new cases were diagnosed each year. HCC accounts for between 85% and 90% of primary liver cancer. It is the fifth most common cancer worldwide and the third most common cause of cancer mortality. Aim of the Work The aim of this study is to assess of alpha fetoprotein in patients who are diagnosed with hepatocellular carcinoma after COVID-19 infection. Patients and Methods This is cross Sectional Study on 60 Egyptian patients with HCC presenting to multidisciplinary clinic during era of Covid 19 pandemic divided into two subgroups: Group I: 30 patients with HCC and COVID 19 infection and group II: 30 patients with HCC who weren’t infected with COVID 19. Results In this study we found that there was insignificant difference between both studied groups as regards age and sex (p = 0.92 and p = 0.119, respectively). In this study we demonstrated that there was insignificant difference between both studied groups as regards etiology of HCC (p &amp;gt; 0.05). In this thesis we cleared that there was highly significant difference between both studied groups as regards Liver presentations (P &amp;lt; 0.001). In this thesis we found that there was significant difference between both studied groups as regards CBC (p &amp;lt; 0.05). In this study we demonstrated that there was significant difference between both studied groups as regards liver function tests (p &amp;lt; 0.05). Our results showed that that there was highly significant difference between both studied groups as regards AFP (p = 0.002). In study in our hands, we found that there was highly significant difference between both studied groups as regards tumor size and tumor stage (p &amp;lt; 0.001). In this study we found that there was highly significant difference between both studied groups as regards MELD score (p &amp;lt; 0.001). In this study we illustrated that Child Pugh class, MELD score, AFP and COVID-19 infection were the independent risk factors associated with poor survival among HCC patients Conclusion Our study concluded that tumor marker parameters, including AFP, can be used as Prognostic tools for HCC patients with СOVID-19. In which there were higher mortality rate among HCC with COVID-19 with higher levels of AFP.

A systematic analysis with the hierarchical cluster analysis strategy on the complex interaction of TERT and CTNNB1 somatic mutations in Vietnamese hepatocellular carcinoma patients

Telomerase reverse transcriptase (TERT) and β-catenin (CTNNB1) mutations may occur following the hepatocellular carcinoma (HCC) pathway signal. We conducted a Hierarchical cluster analysis study on 408 patients diagnosed with HCC by pathological surgery, identifying TERT promoter and CTNNB1 exon 3 mutations by sequencing. The overall preclinical characteristics, cumulative cut-point values, and the factors associated with these somatic mutations were analyzed in uni/multidimensional scaling model. HBV(+) HCV(−) HCC male patients who were older than 62.74 years old and have TERT promoter mutation as well as AFP > 489.78 ng/ml got a higher risk of HCC grade more than two from 27 % to 200 % with p < 0.05 (RR are from 1.27 [1.09–1.47] to 3.06 [2.04–4.61]). This mutation was a good indicator of grade 2 risk (HR = 0.37 [2.72–0.16], β = −1.00, p = 0.019). TERT promoter and CTNNB1 exon 3 mutations independently influenced tumor size and tumor site status in grade 3 and HBV(−) HCV (−) male HCC patients, where the hazard rates, respectively, were 0.28 [0.09–0.89], 0.023 [0.0023–0.23] and 0.06 [0.012–0.32] (β < 0 and p < 0.01). These two mutations inversely impacted each other the tumor sites status, especially in male HCC patients with grade 2 without B, C hepatitis virus (RRCTNNB1 exon 3 mutate - TERT promoter wildtype = 1.12 [1.04–1.20], p < 0.05). Consequently, the mutations in TERT promoter and CTNNB1 exon 3 may synchronize with other factors or independently impact the hepatocarcinogenesis and are important indicators for HCC prognostic in male patients with very high AFP levels or with moderately as well as poorly differentiated in tumor. Our results serve as the basis for further studies to understand the impact of different factors on the outcome of HCC, especially in monitoring and assessing the cancer risk of patients infect HBV and carry mutations.

Diagnosis of the Initial Stage of Hepatocellular Carcinoma: A Review.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide. There may be more than a million instances of hepatocellular carcinoma by 2025, making it a persistent concern for global health. The most common form of hepatocellular carcinoma accounts for more than 90% of cases. There is no known cure for hepatocellular carcinoma, which is usually detected late in life. Unlike most other common malignancies, such as lung, prostate, and breast cancers, where mortality rates are declining, rates of death are rising by around 2-3% every year. It is extremely difficult to diagnose hepatocellular carcinoma in its early stages. Alpha-fetoprotein serology studies and ultrasonography (US) monitoring were historically the primary methods for early detection of hepatocellular cancer. However, the sensitivity or specificity of ultrasonography/alpha-fetoprotein (US/AFP) is not high enough to detect hepatocellular carcinoma in its early stages. Alpha-fetoprotein, or AFP, is an amino acid that is normally produced by the liver or yolk sac of an embryonic baby. In adults, AFP levels are typically modest. Adults with high levels of AFP have been associated with several illnesses, the most well-known of which are certain types of cancer. It is still possible to diagnose hepatocellular carcinoma early because of current technological advancements. We address the advancements in the diagnosis of hepatocellular carcinoma in this article, with a focus on new imaging techniques and diagnostic markers for early-stage tumor identification.

HEPATOCELLULAR CARCINOMA IN CHILDREN: 2 CASE REPORT

Background:Hepatocellular carcinoma (HCC) is the second most common liver cancer in children.In this article we sought, through our two observations, to examine the evolving clinical aspect as well as the therapeutic management of hepatocellular carcinoma in children, since this affection is rare in the childhood. Case presentation:We report two cases of hepato carcinoma. The first case of an 11-year-old girl from Marrakech with glycogenosis complicated by hepatic cirrhosis at the portal hypertension stage. After diagnostic confirmation; the patient benefited from systemic treatment with Atezolimumab + Bevacizumab with good progress in the short term (5 months follow-up). The second case concerns a 14-year-old girl from Marrakech region with hepato carcinoma on a healthy liver who received the same treatment but the evolution was marked in the long term by an increase in the size of the mass and portal hypertension and death at age 17 years old. Conclusion: HCC is rare in childhood. The etiological predisposition and biological behavior differ from adults. In cases of cirrhosis or liver disease, HCC must be suspected based on a high AFP level and an abnormal nodule on ultrasound. Hepatoblastoma should be considered first in the differential diagnosis. Treatment of pediatric HCC is difficult. Complete surgical resection is essential to cure it. For tumors that cannot be resected, liver transplantation is decided on a case-by-case basis. However , HCC remains difficult to treat as cure requires complete surgical resection.

Evaluation of the risk of developing hepatocellular carcinoma in chronic Hepatitis C patients receiving antiviral treatment.

Chronic HC leads to the development of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). The treatment of chronic HC with DAAs reduces mortality from LC and HCC.The study aimed to investigate the serological markers specific to HCC (PIVKA-II and AFP) in patients with chronic HC before and after DAA treatment. The study involved 35 HCV patients (mean age: 56.23 ± 1.45) divided into two groups. Group 1 included 15 HCV + HCC patients and Group 2 included 20 HCV non-HCC patients. At the end of treatment all the patients were HCV RNA negative. Three months after the end of antiviral treatment, HCV RNA was undetectable in all patients, while a complete biochemical and virological response was observed in 66.7% of HCV + HCC patients and 85.0% of HCV non-HCC patients. PIVKA-II levels before the initiation of antiviral treatment were high in all patients. At the end of the treatment, in the HCV non-HCC group, normalization of PIVKA-II levels was observed only in 20.0% cases, and in 60.0% of cases 3 months after the treatment. Meanwhile, in patients with HCC and chronic HCV, PIVKA-II levels were within the normal range 3 months after treatment in only 13.3% of patients. It is necessary to monitor HCV patients with cirrhosis (F4) and severe fibrosis (F3) without HCC, who have high PIVKA-II and AFP levels and/or ALT activity despite obtaining sustained virologic response 3 months after treatment with DAAs.

Hsa_circ_0079875 functions as a competitive endogenous RNA to promote hepatocellular carcinoma progression

ABSTRACT Circular RNA (circRNA) can influence the development of hepatocellular carcinoma (HCC) as a competitive endogenous RNA (ceRNA). However, there are still many circRNAs whose functions are unknown. Our research explores the role of a novel circRNA, hsa_circ_0079875, in HCC. The expression of hsa_circ_0079875 in HCC was verified by next-generation sequencing, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and fluorescence in situ hybridization (FISH). The distribution of hsa_circ_0079875 in HCC cells was investigated by RNA subcellular isolation and FISH assays. The functional effects on HCC proliferation, invasion, migration, cell cycle, and apoptosis were verified by overexpression and knockdown of hsa_circ_0079875. Moreover, xenograft mouse models and immunohistochemistry experiments were used to assess the function of hsa_circ_0079875 in vivo. Hsa_circ_0079875 was up-regulated in HCC tissues and mainly distributed in the cytoplasm. Higher hsa_circ_0079875 leads to larger tumor tissue, more microvascular invasion(MVI) and higher AFP levels, which in turn leads to a poor prognosis. Overexpression of hsa_circ_0079875 can promote the proliferation, migration, and invasion of HCC cells and inhibit apoptosis in vitro and in vivo. Knocking down hsa_circ_0079875 has the opposite effect. Sequencing and biological information predicted the target miRNA and mRNA of hsa_circ_0079875. Further bioinformatics and clinical correlation analysis revealed that hsa_circ_0079875 promote the malignant biological behaviors of HCC through hsa_circ_0079875/miR-519d-59/NRAS ceRNA net. Therefore, hsa_circ_0079875 can be a potential prognostic marker and therapeutic target for HCC.

Interleukin-25 as a Potential Biomarker in Lung Metastasis of Hepatocellular Carcinoma with HBV History in Chinese Patients: A Single Center, Case-control Study.

Background: Interleukin-25 (IL-25) has been proved to play a role in the pathogenesis and metastasis of Hepatocellular carcinoma (HCC), but the relationship between the level of IL-25 and the metastasis and prognosis of HCC is still not clear. This study aimed to investigate the expression of IL-25 and other potential biochemical indicators among healthy people, HBV-associated HCC patients without lung metastasis and HBV-associated HCC patients with lung metastasis. Methods: From September 2019 to November 2021, 33 HCC patients without lung metastasis, 37 HCC patients with lung metastasis and 29 healthy controls were included in the study. IL-25 and other commonly used biochemical markers were measured to establish predictors of overall survival (OS) and progression-free survival (PFS) after treatment. Results: The serum level of IL-25 was increased in HCC patients than healthy controls (p < 0.001) and HCC patients with lung metastasis had higher IL-25 level than HCC patients without metastasis (p = 0.035). Lung metastasis also indicated higher death rate (p < 0.001) by chi-square test, higher GGT level (p = 0.024) and higher AFP level (p = 0.049) by non-parametric test. Kaplan-Meier analysis demonstrated that IL-25 was negatively associated with PFS (p = 0.024). Multivariate Cox-regression analysis indicated IL-25 (p = 0.030) and GGT (p = 0.020) to be independent predictors of poorer PFS, while IL-25 showed no significant association with OS. Conclusion: The level of IL-25 was significantly associated with disease progression and lung metastasis of HBV-associated HCC. The high expression of IL-25 predicted high recurrence rate and death probability of HCC patients after treatment. Therefore, IL-25 may be an effective predictor of prognosis in HCC.

Systemic Inflammation Score Using Pretherapeutic Inflammatory Markers to Predict Prognosis for Hepatocellular Carcinoma Patients After Hepatic Arterial Infusion Chemotherapy.

To assess the clinical value of the pretherapeutic systemic inflammation score (SIS) in predicting the prognosis of hepatocellular carcinoma (HCC) after hepatic arterial infusion chemotherapy (HAIC). From February 2016 to April 2021, 415 advanced HCC patients who underwent HAIC at Sun Yat-sen University Cancer Center were randomly divided into training (n = 277) and validation cohorts (n = 138) and analyzed. The aspartate aminotransferase-alanine aminotransferase ratio (AAR), lymphocyte × albumin (L × A), and neutrophil × monocyte (N × M) were used to construct the SIS score based on a multivariate Cox analysis in the training cohort. A nomogram consisting of the SIS score was created and evaluated by calibration plot, areas under the receiver operating characteristic (AUC) curve, and decision curve analysis (DCA). Univariate and multivariate Cox analyses revealed that the SIS score was an independent predictor of OS. A high SIS score was associated with large tumor size (P < 0.05), multiple lesions (P < 0.01), high AFP level (P < 0.01), extrahepatic metastasis (P < 0.05), and advanced BCLC stage (P < 0.01). Kaplan-Meier analysis showed that the patients with a high SIS had shorter OS than those with a low SIS in both the non-PD (p = 0.015) and PD group (p = 0.023). The calibration plots showed good concordance between the nomogram's prediction and the actual observations in both the training and validation cohorts. In the training cohort, the AUCs of the nomogram predicting the 2-year and 3-year survival rates were 0.749 and 0.739, respectively; in the validation cohort, they were 0.760 and 0.681, respectively. Based on the AUC and DCA, the nomogram showed better predictive ability than other predictors. The pretherapeutic SIS score is a potential prognostic predictor for HCC patients undergoing HAIC.

LGBQ affirmative practice and psychological well-being in China.

Research has consistently shown the importance of affirmative practice when therapists work with lesbian, gay, bisexual, queer/questioning (LGBQ) clients. However, less is known about factors that may influence the extent to which clients benefit from affirmative practice. The present study intends to address this gap by examining whether LGBQ affirmative practice would be positively associated with psychological well-being, and whether individuals factors including internalized homophobia (IH), reciprocal filial piety (RFP; providing care and support for parents based on affective bonding), and authoritarian filial piety (AFP; showing unconditional obedience to parents based on parental authority) would moderate this relationship. A total of 128 Chinese LGBQ clients (50% male, 38.3% female, and 11.7% nonbinary/gender queer; age: M = 25.26 years, SD = 5.46) from 21 provinces and regions completed the online survey. Results revealed that LGBQ affirmative practice was positively associated with psychological well-being after controlling for LGBQ clients' pretherapy distress and therapists' credibility. Such association was greater for LGBQ clients who had higher levels of IH and AFP, whereas such effect did not vary with RFP. This study provides preliminary empirical evidence for the effectiveness of LGBQ affirmative practice in psychological health among Chinese LGBQ clients. Moreover, LGBQ affirmative practice might be more helpful for LGBQ clients with higher IH and AFP. These findings implicate that Chinese counselors and therapists should engage in LGBQ affirmative practice when they work with LGBQ clients, especially for those who have high levels of IH and AFP. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Outcomes of Radiation Segmentectomy for Hepatocellular Carcinoma in Patients with Non-Alcoholic Fatty Liver Disease versus Chronic Viral Hepatitis.

To compare the outcomes of radiation segmentectomy for early-stage hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD) versus hepatitis C virus (HCV). A retrospective analysis of consecutive patients with NAFLD- or HCV-related HCC treated with radiation segmentectomy from 01/2017-06/2022 was performed. Eligibility criteria included solitary tumor ≤8 cm or up to 3 HCC ≤3 cm, ECOG 0-1, and absence of vascular invasion or extrahepatic spread. Imaging best response was assessed per modified Response Evaluation Criteria in Solid Tumors. Target tumor and overall progression, time-to-progression (TTP), and overall survival (OS) were calculated. All outcomes were censored for liver transplantation (LT). Complete pathologic response (CPN) was assessed in patients who underwent LT. Of 142 patients included (NAFLD: 61; HCV: 81), most had cirrhosis (NAFLD: 87%; HCV: 86%) and small tumors (median size NAFLD: 2.3 cm; HCV: 2.5 cm). Patients with NAFLD had higher BMI (p<0.001) and worse ALBI scores (p=0.003). Patients with HCV were younger (p<0.001) and had higher AFP levels (p=0.034). Median radiation dose (NAFLD: 508 Gy; HCV: 452 Gy) and specific activity (NAFLD: 700 Bq; HCV: 698 Bq) were similar between cohorts. Objective response was 100% and 97% in the NAFLD and HCV cohorts, respectively. Target tumor progression occurred in 1 (2%) NAFLD and 8 (10%) HCV patients. Target tumor TTP was not met for either cohort. Overall progression occurred in 23 (38%) NAFLD and 39 (48%) HCV patients. Overall TTP was 17.4 months (95% CI 13.5-22.2) in NAFLD and 13.5 months (95% CI 0.4-26.6) in HCV patients (p=0.86). LT was performed in 27 (44%) NAFLD and 33 (41%) HCV patients, with a CPN rate of 63% and 54%, respectively. OS was not met in the NAFLD cohort and was 53.9 months (95% CI 32.1-75.7) in the HCV cohort (p=0.15). Although NAFLD and HCV are associated with different mechanisms of liver injury, patients with early-stage HCC treated with radiation segmentectomy achieve comparable outcomes.

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

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. 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. 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. 4.2cm, p < 0.01) and higher AFP levels (median 92 vs. 15ng/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. 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.

Focal Nodular Hyperplasia-Like Lesions With Glypican-3 Positivity in Infancy.

Glypican-3 is often used to discriminate between neoplastic and nonneoplastic liver. In focal lesions, positivity may be considered suggestive of a malignancy such as hepatoblastoma. However, glypican-3 is also normally expressed in the immature liver. We present a series of 5 cases of focal nodular hyperplasia (FNH)-like lesions arising in very young patients with glypican-3 expression and highlight the challenges these lesions present in the differential diagnosis of hepatoblastoma. Cases were obtained from the files of 3 tertiary pediatric hospitals. Clinical data were obtained from the electronic medical record and histopathologic material including immunohistochemical stains were reviewed. Patients were aged 2 weeks to 6 months with peak AFP levels ranging from 88.6 to 204,696 ng/mL. Microscopically, all were variably demarcated hepatocellular lesions with cords of hepatocytes, marked sinusoidal dilatation, and occasional fibrous bands and areas reminiscent of central scar with bile ducts. No significant cytologic atypia or increased mitotic activity were present. All showed glypican-3 expression and were negative for nuclear beta-catenin with intact reticulin framework. Our study highlights the pitfalls of evaluating focal liver lesions in infants when high AFP levels and glypican-3 expression may reflect immaturity rather than neoplasia.

Preoperative prediction of macrotrabecular-massive hepatocellular carcinoma based on B-Mode US and CEUS.

To develop a preoperative prediction model to identify macrotrabecular-massive hepatocellular carcinoma (MTM-HCC) and evaluate the model's diagnostic performance in differentiating MTM-HCC from HCC. We conducted a mono-center retrospective study in a grade A tertiary hospital in China. Consecutive patients with suspected HCC from February 2019 to December 2020 were eligible for inclusion. All consenting patients underwent CEUS examination and were histologically diagnosed. Based on the clinical and US features between the two groups, we developed a binary logistic regression model and a nomogram for predicting MTM-HCC. A total of 161 patients (median age, 57 years; interquartile range, 48-64 years; 129 men) were included in the analysis. Twenty-seven of the HCCs (16.8%) were of the MTM subtype. Binary logistic regression analysis indicated that PVP hypoenhancement (OR = 15.497; 95% CI: 1.369, 175.451; p = 0.027), AFP > 454.6 ng/mL (OR = 8.658; 95% CI: 3.030, 24.741; p < 0.001), ALB ≤ 29.9 g/L (OR = 3.937; 95% CI: 1.017, 15.234; p = 0.047), halo sign (OR = 3.868; 95% CI: 1.314, 11.391; p = 0.016), and intratumoral artery (OR = 2.928; 95% CI: 1.039, 8.255; p = 0.042) were predictors for MTM subtype. Combining any two criteria showed a high sensitivity (100.0%); combining all five criteria showed a high specificity (99.2%); and the AUC value of the logistic regression model was 0.88 (95% CI: 0.81, 0.92). BMUS and CEUS could be used for identifying patients suspected of having MTM-HCC. Combining clinical information, BMUS, and CEUS features could achieve a noninvasive diagnosis of MTM-HCC. • Contrast-enhanced ultrasound examination helps clinicians to identify MTM-HCCs preoperatively. • PVP hypoenhancement, high AFP levels, low ALB levels, halo signs, and intratumoral arteries could be used to predict MTM-HCCs. • A logistic regression model and nomogram were built to noninvasively diagnose MTM-HCCs with an AUC value of 0.88 (95% CI: 0.81, 0.92).

Surgical Outcomes for Hepatocellular Carcinoma in Patients with Child–Pugh Class B: a Retrospective Multicenter Study

BackgroundsLiver resection for hepatocellular carcinoma (HCC) in patients with Child–Pugh class (CPC) B increases the incidence of postoperative complication and in-hospital death and decreases the disease-free survival (DFS) and overall survival (OS) compared with those with CPC A. Conversely, some selected patients possibly gained benefits for liver resection. MethodsClinical records of 114 patients with CPC B who underwent liver resection for HCC were retrospectively reviewed. The risk of postoperative complications (Clavien–Dindo classification grade of ≥ II), postoperative recurrence, and death was analyzed. ResultsPostoperative complications occurred in 36 patients (31.6%), and 2 died within 90 days postoperatively due to the liver and respiratory failure, respectively. Multivariate analysis indicated that albumin-bilirubin (ALB) grade III and extended operation time were found as independent risk factors for postoperative complications. The DFS and OS rates at 3/5 years after liver resection were 30.8%/25.3% and 68.4%/48.9%, respectively. Multivariate analysis indicated that the extended blood loss, high α-fetoprotein (AFP) level (≥ 200 ng/mL), and Barcelona Clinic Liver Cancer stage C were found to be independent risk factors for postoperative recurrence. The high AFP level was also an independent prognostic factor for OS. Patients with high AFP levels had postoperative recurrence within 2 years and a higher number of extrahepatic recurrences than those with low AFP levels (< 200 ng/mL). ConclusionFor patients with HCC with CPC B who were scheduled for liver resection, ALBI grade III and high AFP level should be considered as unfavorable outcomes after liver resection.

Immature teratoma with very high AFP levels.

Immature teratoma with very high AFP levels.

Highly expressed FAM189B predicts poor prognosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most malignant tumors with persistently high morbidity and mortality. However, the expression, prognostic and clinical significance of FAM189 family genes in HCC remain largely unknown. In this study, the expression levels of FAM189 family genes in HCC were analyzed through TCGA-LIHC and ICGC-LIRI-JP cohorts, and further validated in multiple independent GEO datasets. It was found that the expression of FAM189B was significantly upregulated in HCC tumor tissues, while the expression of FAM189A1 and FAM189A2 was not significantly changed between tumor and adjacent tissues. Further analysis revealed that upregulated copy number variation contributed to increased expression of FAM189B in HCC. Survival analysis showed that highly expressed FAM189B was significantly correlated with unfavorable prognosis, including overall survival, disease-specific survival, and progression-free interval. Univariate and multivariate Cox regression analysis showed that FAM189B was a potential novel prognosis factor for HCC patients. In addition, the association between FAM189B expression and clinical and molecular characteristics was analyzed. High expression of FAM189B was associated with high AFP level, high predicted risk metastasis signature, and TP53 mutation, while there was no significant association between FAM189B expression and cancer stage or tumor grade of HCC. Gene set enrichment analysis revealed that highly expressed FAM189B was closely related with signal pathways and biological processes associated with cell proliferation and cell cycle in HCC. In conclusion, this study suggested that FAM189B was highly expressed in HCC and highly expressed FAM189B may serve as an effective prognostic indicator and a potential therapeutic target for HCC patients.

Potential Role of Tumor Cell Metabolic Subtype in the Clinical Course of Hepatocellular Carcinoma

INTRODUCTION: Tumor metabolism is critical in tumorigenesis and development. This study aims to evaluate the potential role and the prognostic value of tumor cell metabolism in the progression of hepatocellular carcinoma (HCC). METHODS: Systematic analyses were performed using genome, transcriptome, and clinical characteristics to evaluate the metabolic system in 673 HCC patients. We analyzed the impact of metabolism on the clinical course of HCC. Univariate and multivariate Cox proportional-hazards regression methods were used to screen overall survival (OS). RESULTS: Included HCC patients were categorized into cholesterogenic (25.3%), glycolytic (14.6%), mixed (10.4%), and quiescent (49.8%) types based on the glycolysis and cholesterol biosynthesis gene expression. The distribution of α-fetoprotein (AFP; <300 μg/L or ≥300 μg/L) but not TMN stages among the 4 metabolic subtypes showed significant differences (p < 0.05). The quiescent subtype was associated with a low AFP expression level (p < 0.05) and the glycolytic subtype was associated with a higher AFP level (p < 0.01). The mixed type and glycolytic type had a shorter median OS (p < 0.0001). And the metabolic subtype emerged as an independent predictor of HCC patients’ survival in multivariate analyses. CONCLUSION: These results suggest that the metabolic subtypes were consistent with AFP expression and may play a prognostic role in HCC patients. And the glycolytic metabolism-related genes may induce tumor progression in HCC.