Alpha-fetoprotein Levels Research Articles

EVALUATION OF SOME LIVER ENZYMES AND ALPHA-FETOPROTEIN IN WORKERS OCCUPATIONALLY EXPOSED TO E-WASTE IN NNEWI, ANAMBRA STATE NIGERIA

BACKGROUND: The advent of electricity has spurred significant technological advancements, leading to the production of numerous electrical and electronic devices. This progress, however, has resulted in a surge of largely irreparable electronic waste (e-waste) being constantly shipped to Nnewi, a metropolitan city with large-scale commercial and industrialactivities. E-waste contains thousands of chemicals, many of which are toxic to humans upon exposure.AIM OF THE STUDY: To evaluate the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and serum levels of alpha-fetoprotein (AFP) in workers occupationally exposed to e-waste.METHODOLOGY: The study comprised 40 e-waste workers (exposed group) and 40 healthy individuals (control group). Approximately 5 ml of venous blood was collected from each participant. The liver enzymes – ALT, AST, and ALP were evaluated colorimetrically, while AFP was assayed by Enzyme-linked Immunosorbent Assay (ELISA) method. Data obtained was statistically analyzed using SPSS windows version 25 with significance set as p<0.05 at 95% confidence interval; Independent T-test, descriptive statistics and Pearson correlation were employed where relevant. Results were presented as means ± standard deviation in contingency tables.RESULT: There was no significant difference (p>0.05) in the activities of ALT, AST, ALP and serum level of AFP between the exposed subjects and the control. However, significantly negative correlation was found between age and ALT (r = -0.294; p= 0.024), while DOE also had negative correlation with ALP (r= -0.294; P= 0.024) - all among e-waste exposed group.CONCLUSION: This study has shown that exposure to e-waste may not have a harmful effect on the liver function, since there was no significant difference in the liver function enzymes, and serum levels of AFP. However, age and longer duration of exposure to e-waste could be detrimental to health.

Pre-operative enhanced magnetic resonance imaging combined with clinical features predict early recurrence of hepatocellular carcinoma after radical resection.

Indentifying predictive factors for postoperative recurrence of hepatocellular carcinoma (HCC) has great significance for patient prognosis. To explore the value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI) combined with clinical features in predicting early recurrence of HCC after resection. A total of 161 patients with pathologically confirmed HCC were enrolled. The patients were divided into early recurrence and non-early recurrence group based on the follow-up results. The clinical, laboratory, pathological results and Gd-EOB-DTPA enhanced MRI imaging features were analyzed. Of 161 patients, 73 had early recurrence and 88 were had non-early recurrence. Univariate analysis showed that patient age, gender, serum alpha-fetoprotein level, the Barcelona Clinic Liver Cancer stage, China liver cancer (CNLC) stage, microvascular invasion (MVI), pathological satellite focus, tumor size, tumor number, tumor boundary, tumor capsule, intratumoral necrosis, portal vein tumor thrombus, large vessel invasion, nonperipheral washout, peritumoral enhancement, hepatobiliary phase (HBP)/tumor signal intensity (SI)/peritumoral SI, HBP peritumoral low signal and peritumoral delay enhancement were significantly associated with early recurrence of HCC after operation. Multivariate logistic regression analysis showed that patient age, MVI, CNLC stage, tumor boundary and large vessel invasion were independent predictive factors. External data validation indicated that the area under the curve of the combined predictors was 0.861, suggesting that multivariate logistic regression was a reasonable predictive model for early recurrence of HCC. Gd-EOB-DTPA enhanced MRI combined with clinical features would help predicting the early recurrence of HCC after operation.

Conventional and machine learning-based risk scores for patients with early-stage hepatocellular carcinoma.

The performance of machine learning (ML) in predicting the outcomes of patients with hepatocellular carcinoma (HCC) remains uncertain. We aimed to develop risk scores using conventional methods and ML to categorize early-stage HCC patients into distinct prognostic groups. The study retrospectively enrolled 1,411 consecutive treatment-naïve patients with the Barcelona Clinic Liver Cancer (BCLC) stage 0 to A HCC from 2012 to 2021. The patients were randomly divided into a training cohort (n=988) and validation cohort (n=423). Two risk scores (CATS-IF and CATS-INF) were developed to predict overall survival (OS) in the training cohort using the conventional methods (Cox proportional hazards model) and ML-based methods (LASSO Cox regression), respectively. They were then validated and compared in the validation cohort. In the training cohort, factors for the CATS-IF score were selected by the conventional method, including age, curative treatment, single large HCC, serum creatinine and alpha-fetoprotein levels, fibrosis-4 score, lymphocyte-tomonocyte ratio, and albumin-bilirubin grade. The CATS-INF score, determined by ML-based methods, included the above factors and two additional ones (aspartate aminotransferase and prognostic nutritional index). In the validation cohort, both CATS-IF score and CATS-INF score outperformed other modern prognostic scores in predicting OS, with the CATSINF score having the lowest Akaike information criterion value. A calibration plot exhibited good correlation between predicted and observed outcomes for both scores. Both the conventional Cox-based CATS-IF score and ML-based CATS-INF score effectively stratified patients with early-stage HCC into distinct prognostic groups, with the CATS-INF score showing slightly superior performance.

A preliminary study of optimal treatment response rates in patients undergoing hepatic arterial infusion chemotherapy combined with molecular targeting and immunotherapy.

This study aimed to examine the effectiveness of the best response rate (BRR) as a surrogate for overall survival (OS), using the modified Response Evaluation Criteria in Solid Tumors (mRECIST), in patients with unresectable hepatocellular carcinoma (HCC) undergoing hepatic arterial infusion chemotherapy (HAIC) with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) combined with molecular targeting and immunotherapy. This study enrolled 111 consecutive patients who had complete imaging data. The median age of patients was 58 years (IQR 50.5-65.0). Among the patients, those with Barcelona Clinic Liver Cancer (BCLC) stage A, BCLC stage B, and BCLC stage C comprised 6.4%, 19.1%, and 73.6%, respectively. The optimal threshold of BRR can be determined using restricted cubic splines (RCS) and the rank sum statistics of maximum selection. Survival curves of patients in the high rating and low rating groups were plotted. We then used the change-in-estimate (CIE) method to filter out confounders and the inverse probability of treatment weighting (IPTW) to balance confounders between the two groups to assess the robustness of the results. The median frequency of the combination treatment regimens administered in the overall population was 3 times (IQR 2.0-3.0). The optimal BRR truncation value calculated was -0.2. Based on this value, 77 patients were categorized as the low rating group and 34 as the high rating group. The differences in the OS between the high and low rating groups were statistically significant (7 months [95%CI 6.0-14.0] vs. 30 months [95%CI 30.0-]; p< 0.001). Using the absolute 10% cut-off value, the CIE method was used to screen out the following confounding factors affecting prognosis: successful conversion surgery, baseline tumor size, BCLC stage, serum total bilirubin level, number of interventional treatments, alpha-fetoprotein level, presence of inferior vena cava tumor thrombus, and partial thrombin activation time. The survival curve was then plotted again using IPTW for confounding factors, and it was found that the low rating group continued to have better OS than the high rating group. Finally, the relationship between BRR and baseline factors was analyzed, and inferior vena cava tumor thrombus and baseline tumor size correlated significantly with BRR. BRR can be used as a surrogate endpoint for OS in unresectable HCC patients undergoing FOLFOX-HAIC in combination with molecular targeting and immunotherapy. Thus, by calculating the BRR, the prognosis of HCC patients after combination therapy can be predicted. Inferior vena cava tumor thrombus and baseline tumor size were closely associated with the BRR.

The role of alpha-fetoprotein in the tumor microenvironment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a prevalent malignant cancer worldwide, characterized by high morbidity and mortality rates. Alpha-fetoprotein (AFP) is a glycoprotein synthesized by the liver and yolk sac during fetal development. However, the serum levels of AFP exhibit a significant correlation with the onset and progression of HCC in adults. Extensive research has demonstrated that the tumor microenvironment (TME) plays a crucial role in the malignant transformation of HCC, and AFP is a key factor in the TME, promoting HCC development. The objective of this review was to analyze the existing knowledge regarding the role of AFP in the TME. Specifically, this review focused on the effect of AFP on various cells in the TME, tumor immune evasion, and clinical application of AFP in the diagnosis and treatment of HCC. These findings offer valuable insights into the clinical treatment of HCC.

Role of the Clinical Features and MRI Parameters on Ki-67 Expression in Hepatocellular Carcinoma Patients: Development of a Predictive Nomogram.

To develop a nomogram using clinical features and the MRI parameters for preoperatively predicting the expression of Ki-67 in patients with hepatocellular carcinoma (HCC). One hundred and forty patients (training cohorts: n = 108; validation cohorts: n = 32) with confirmed HCC were investigated. Mann-Whitney U test, independent sample t-test, and chi-squared test were used to analyze the continuous and categorical variables. Univariate and multivariate logistic regression analyses were performed to examine the clinical variables and parameters from MRI associated with Ki-67 expression. As a result, a nomogram was developed based on these associations in patients with HCC. The performance of the nomogram was evaluated using the area under the receiver operating characteristic curve (AUC) and calibration curves. In the training set, multivariable logistic regression analysis revealed that lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) levels, protein induced by vitamin K absence or antagonist-II (PIVKA-II) levels, and tumor shape were independent predictors for Ki-67 expression (p < 0.05). These three variables and the apparent diffusion coefficient (ADC) value were used to establish a nomogram, while the ADC value was found to be a marginal significant predictor. The model demonstrated a strong ability to discriminate Ki-67 expression in both the training and validation cohorts (AUC = 0.862, 0.877). A non-invasive preoperative prediction method, which incorporates MRI variables and clinical features was developed, and showed effectiveness in evaluating Ki-67 expression in HCC patients.

Colorectal adenocarcinoma with enteroblastic differentiation: a clinicopathological analysis of eight cases

Objective: To investigate the clinicopathological features of colorectal adenocarcinoma with enteroblastic differentiation (CAED). Methods: Eight cases of CAED diagnosed at the Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China from January 2017 to August 2023 were collected. The histopathological, immunohistochemical, molecular and prognostic features of 8 CAED cases were analyzed. The relevant studies were also reviewed. Results: Among the eight patients, there were six males and two females, with an average age of 58 years (range: 29-77 years, median age: 61.5 years). Preoperative serum alpha-fetoprotein levels were elevated in five patients (14.0-286.6 μg/L). Four tumors were located in the colon, and four tumors in the rectum. Two patients were clinically staged as advanced stage (stage Ⅳ), and distant metastasis occurred at the initial diagnosis (one case had liver metastasis, and the other had lung, bone and multiple lymph nodes metastases). Six patients were clinically staged as locally-advanced stage (Stage Ⅱ-Ⅲ). Three of them developed distant metastases after surgery (one case had liver metastasis, one case had lung metastasis, and one case had peritoneal metastasis). Additionally, two patients died at 9 months and 24 months after surgery, respectively. The tumors were composed of various proportions of adenocarcinoma components with enteroblastic differentiation (30%-100%) and classical tubular adenocarcinoma components. The component with enteroblastic differentiation exhibited morphology similar to embryonic intestinal epithelium: cuboidal or columnar tumor cells arranged in tubular, papillary, cribriform, or solid nest patterns, with clear cytoplasm. Immunohistochemical studies showed that tumor cells expressed at least one oncofetal protein (SALL4, Glypican-3, and AFP). In addition, focal squamous differentiation was observed in 3 cases (3/8). Compared to the primary tumor, both CAED and squamous differentiation components were increased in the metastatic tumors. Based on the sequencing results of KRAS, NRAS and BRAF of the primary and/or metastatic tumors, 5 cases were wild-type, while KRAS exon 2 (G13D) mutations were identified in 2 cases. Conclusions: CAED is a rare colorectal malignancy with a dismal prognosis. Accurate pathological diagnosis is prognostically valuable. The histological features of enteroblastic differentiation, elevated serum AFP levels, and the expression of oncofetal proteins play an important role in the tumor diagnosis.

Prognostic Indicators of Overall Survival in Hepatocellular Carcinoma Patients Undergoing Liver Resection.

Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer and the third contributor to malignancy-related deaths worldwide. The hepatic venous pressure gradient (HVPG), transient elastography-liver stiffness measurement (TE-LSM), and the association between TBS (tumor burden score), alpha-fetoprotein levels, and the Child-Pugh classification (TAC score) can serve as valuable prognostic indicators for these patients. Therefore, the main objective of our research was to analyze the prognostic value of the HVPG, TE-LSM, TBS, and TAC scores. An observational and survival study was conducted on 144 subjects. Our findings indicated that HVPG greater than 10 mmHg, AFP surpassing 400 ng/mL, an advanced C-P class, and low TAC score are independent predictors of overall survival. During the multivariate analysis, AFP serum levels and C-P class proved statistically significant. The present study revealed significant differences in overall survival between the two groups divided upon HVPG values and settled by the cutoff of 10 mmHg (p = 0.02). Moreover, by dividing the cohort into three groups based on the TAC score (very low, low, and moderate), statistically significant differences in overall survival were observed across the groups (p = 0.004).

High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Salvage Therapy of Relapsed/Refractory Germ Cell Tumors: A Single-Center Experience

Introduction: The optimal management of relapsed/refractory germ cell tumors remains unsettled. In this study, we aimed to evaluate the efficacy of high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) as salvage therapy in patients who progressed after at least one line of cisplatin-based chemotherapy. Methods: We retrospectively reported the results of 133 patients who underwent HDCT and ASCT as salvage therapy from 2016 to 2021. Patients received 3 cycles of paclitaxel, ifosfomide and cisplatin (TIP) regimen as induction and 1 cycle of carboplatin 700 mg/m2 on days 1–3 plus etoposide 750 mg/m2 on days 1–3, followed by ASCT. Demographic and clinicopathological features of patients, the International Germ Cell Cancer Collaborative Group (IGCCCG) risk group at diagnosis, serum alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (HCG) levels before HDCT, treatment-related complications and survival outcomes were recorded. Results: The median age of the patients was 31 (range 18–62). The median follow-up was 31.1 months (95% CI, 28.9–33.3 months). During the median follow-up period, 74 of the 133 patients were still alive, and 63 of these were in complete remission. The median progression-free survival (PFS) was 25.8 months (95% CI, 8.1–43.4 months). The 2-year PFS rate was 50.3% and the 2-year overall survival (OS) rate was 60.8%. Variables that remained statistically significant in multivariable analysis and were associated with poor prognosis were mediastinal primary tumor location, presence of brain metastases, and higher AFP and HCG levels at baseline. Conclusion: One course of HDCT and ASCT after induction with TIP is an effective and feasible treatment option for salvage treatment of relapsed/refractory germ cell tumors, with cure rates of up to 60%.

Abstract CT211: Safety of prompt initiation of durvalumab or STRIDE (single tremelimumab regular interval durvalumab) regimen as hepatocellular carcinoma (HCC) treatment for patients with chronic active hepatitis B

Abstract Background: Chronic hepatitis B is an etiology of HCC. Clinical trials using immune checkpoint inhibitors (ICIs) as HCC treatment typically exclude patients with chronic active hepatitis B (serum hepatitis B virus [HBV] viral load &amp;gt; 2000 IU/mL) or require the HBV viral load to be below a certain level using anti-HBV medications. In the phase 3 HIMALAYA study, the STRIDE regimen was superior to sorafenib and durvalumab was noninferior to sorafenib in overall survival benefits. This study explored the safety of concurrent administration of STRIDE or durvalumab with anti-HBV mediations for patients with chronic, active hepatitis B infection. Methods: We enrolled patients with advanced HCC, Child-Pugh A liver function reserve, and chronic active hepatitis B not under anti-HBV treatment. Initially, only patients naïve to ICIs were eligible, and patients received durvalumab 1500mg iv every 4 weeks until disease progression, occurrence of unacceptable toxicities, or the maximum treatment duration of 2 years. After the positive results of the HIMALAYA study, we added tremelimumab 300mg iv on D1 following the STRIDE regimen and allowed enrollment of patients who had received prior programmed cell death-1 blockade therapy. Patients initiated entecavir as HBV treatment within 7 days of starting ICI therapy. The plan was to enroll 30 patients, with the primary outcome of HBV reactivation (a ≥2 log increase in serum HBV DNA compared to the baseline level). Results: The study is still ongoing and as of 31 Aug 2023, 19 patients were enrolled. Two patients were female, and the median age was 65.5 years. Ten patients received durvalumab alone, and 9 received the STRIDE regimen. The ALBI grade was 1 and 2 in 3 (16%) and 16 (84%) patients, respectively. Macrovascular invasion and extrahepatic spread were present in 11 (58%) and 11 (58%) patients, respectively; 12 (63%) patients had alpha-fetoprotein level ≥ 400 ng/mL. Eleven (58%) patients had received prior systemic therapy for HCC, such as sorafenib (n = 9), lenvatinib (n = 5), and regorafenib (n = 4). The mean±standard deviation baseline HBV viral load was 1.18±0.44 mIU/mL. With the median follow-up on 6.1 months, no patients experienced HBV reactivation or HBV-associated hepatitis. Hepatitis flare (ALT increase to ≥3 times the baseline level) was noted in 4 (21%) patients, but none were considered HBV-associated. The best objective tumor response was complete and partial response in 0 and 5 (26.3%) patients, respectively, and the disease control rate was 63.2%. Conclusion: In the preliminary results, simultaneous initiation of immunotherapy and anti-HBV medications in patients with HCC and chronic active hepatitis B did not increase HBV reactivation rate. This study was supported by AstraZeneca (NCT04294498). Citation Format: Yu-Yun Shao, Ching-Tso Chen, Tsung-Che Wu, Tsung-Hao Liu, Chien-Huai Chuang, Ann-Lii Cheng, Chih-Hung Hsu. Safety of prompt initiation of durvalumab or STRIDE (single tremelimumab regular interval durvalumab) regimen as hepatocellular carcinoma (HCC) treatment for patients with chronic active hepatitis B [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT211.

Long noncoding RNA small nucleolar RNA host genes as prognostic molecular biomarkers in hepatocellular carcinoma: A meta-analysis.

Recently, increasing data have suggested that the lncRNA small nucleolar RNA host genes (SNHGs) were aberrantly expressed in hepatocellular carcinoma (HCC), but the association between the prognosis of HCC and their expression remained unclear. The purpose of this meta-analysis was to determine the prognostic significance of lncRNA SNHGs in HCC. We systematically searched Embase, Web of Science, PubMed, and Cochrane Library for eligible articles published up to February 2024. The prognostic significance of SNHGs in HCC was evaluated by hazard ratios (HRs) and 95% confidence intervals (CIs). Odds ratios (ORs) were used to assess the clinicopathological features of SNHGs. This analysis comprised a total of 25 studies covering 2314 patients with HCC. The findings demonstrated that over-expressed SNHGs were associated with larger tumor size, multiple tumor numbers, poor histologic grade, earlier lymphatic metastasis, vein invasion, advanced tumor stage, portal vein tumor thrombosis (PVTT), and higher alpha-fetoprotein (AFP) level, but not with hepatitis B virus (HBV) infection, and cirrhosis. In terms of prognosis, patients with higher SNHG expression were more likely to have shorter overall survival (OS), relapse-free survival (RFS), and disease-free survival (DFS). In conclusion, upregulation of SNHGs expression correlates with shorter OS, RFS, DFS, tumor size and numbers, histologic grade, lymphatic metastasis, vein invasion, tumor stage, PVTT, and AFP level, suggesting that SNHGs may serve as prognostic biomarkers in HCC.

Utility of Alpha-Fetoprotein and Ultrasound in the Diagnosis and Prognosis of Patients with Hepatocellular Liver Cancer.

To investigate the utility of alpha-fetoprotein (AFP) and ultrasound in the diagnosis and prognosis of patients with hepatocellular liver cancer (HCC). Using retrospective convenience sampling, 401 patients with HCC who underwent transarterial chemoembolisation at the Department of Oncology of The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University between June 2015 and January 2020 were recruited and assigned to the case group. Simultaneously, patients matched to the case group in terms of gender and age but excluded for HCC were enrolled at a 1:1 ratio and classified as the control group. Relevant parameters were collected from both groups for comparison. Both AFP levels and ultrasound results demonstrated diagnostic value for patients with HCC (P < 0.05). Their combined use exhibited the highest diagnostic accuracy for the cancer, with an area under the curve of 0.896 (95% confidence interval [CI]: 0.876, 0.923), a sensitivity of 67.65% and a specificity of 91.22%. In terms of overall survival (OS), statistically significant differences in the OS rates were observed between the low-AFP (L-AFP) group and high-AFP (H-AFP) group as well as between the low-tumour-diameter (LTD) group and high-tumour-diameter (HTD) group (81.31% vs 52.22% and 85.11% vs 63.41%, respectively; P < 0.05). Regarding the progression-free survival (PFS), significant differences in the PFS rates were also noted between the L-AFP and H-AFP groups and between the LTD and HTD groups (81.31% vs 52.22% and 85.11% vs 63.41%, respectively; P < 0.05). Ultrasound and AFP display notable distinctions when used in the diagnosis of HCC. The sensitivity of ultrasound as a standalone diagnostic tool surpasses that of AFP alone. However, their combined use results in much higher specificity than the use of either test individually. In addition, both techniques hold predictive value for patients' OS and PFS, enabling timely prognostic assessment.

Paraneoplastic Syndromes in Hepatocellular Carcinoma, Epidemiology, and Survival: A Retrospective Seven Years Study.

Background and Objectives: Liver cancer poses a significant global health threat, ranking among the top three causes of cancer-related deaths. Patients with hepatocellular carcinoma (HCC) often present with symptoms associated with neoplasms or unusual clinical features such as paraneoplastic syndromes (PNS), including hypoglycemia, hypercholesterolemia, thrombocytosis, and erythrocytosis. Our study aimed to investigate the prevalence, clinical characteristics, and survival outcomes associated with PNS in HCC patients and assess each PNS's impact on patient survival. Materials and Methods: We conducted a retrospective analysis of PNS clinical features and survival among consecutive HCC patients diagnosed at our department over seven years, comparing them with HCC patients without PNS. The study involved a retrospective data evaluation from 378 patients diagnosed with HCC between January 2016 and October 2023. Results: We obtained a PNS prevalence of 25.7%, with paraneoplastic hypercholesterolemia at 10.9%, hypoglycemia at 6.9%, erythrocytosis at 4.5%, and thrombocytosis at 3.4%. Patients with PNS tended to be younger and predominantly male. Multivariate analysis revealed a strong correlation between PNS and levels of alpha-fetoprotein and tumor size, with diabetes also showing a significant statistical association (p < 0.05). Subgroup analysis based on specific paraneoplastic syndromes demonstrated shorter survival in patients with PNS, albeit without significant statistical differences, except for hypoglycemia (p < 0.0001). Matched analysis indicated a shorter survival rate for patients with PNS, although no significant statistical differences were observed. Conclusions: PNS are frequently observed in HCC cases and are associated with unfavorable prognoses and decreased survival rates due to their correlation with increased tumor burdens. However, they do not independently predict poor survival. The impact of individual PNS on HCC prognosis varies.

Surgical Intervention After Lenvatinib Treatment in Patients With Advanced Hepatocellular Carcinoma.

The survival and prognostic factors in patients with advanced hepatocellular carcinoma (HCC) who underwent surgical intervention after lenvatinib treatment is not well-understood. Seventy-six patients with advanced HCC who had lenvatinib treatment were retrospectively analyzed. Of 70 patients who were treated with lenvatinib, 14 patients underwent surgical intervention after lenvatinib treatment for 4-28 weeks. Progression-free survival (PFS) was significantly longer in patients who underwent surgical intervention than in patients with non-surgical treatment (median, 8.6 vs. 5.1 months, p=0.019). Non-significantly longer overall survival (OS) was also observed in patients with surgical intervention compared to patients with non-surgical treatment (median, unreached vs. 21.0 months, p=0.206). In patients who underwent surgical intervention, two patients had a partial response, and 12 had stable disease according to RECIST ver. 1.1 criteria. The serum alpha-fetoprotein (AFP) level was significantly lower after lenvatinib treatment than before lenvatinib treatment (median, 19.2 vs. 196.5 ng/ml, p=0.0081). Eleven patients underwent curative surgery with a 14% major postoperative complication (Clavien-Dindo ≥IIIa) rate. Patients who exhibited decreases in AFP levels or maintained AFP levels within the normal range during lenvatinib treatment had significantly longer PFS (median, 8.6 vs. 3.0 months, p=0.0009) and OS (median, unreached vs. 12.4 months, p=0.012) compared to those with persistently elevated AFP levels beyond the normal range. Surgical intervention after lenvatinib treatment for advanced HCC was associated with longer PFS. Patients exhibiting decreased AFP levels or maintaining AFP levels within the normal limit may be suitable candidates for surgical intervention after lenvatinib treatment for advanced HCC.

Detecting microvascular invasion in hepatocellular carcinoma using the impeded diffusion fraction technique to sense macromolecular coordinated water.

Impeded diffusion fraction (IDF) is a novel and promising diffusion-weighted imaging (DWI) technique that allows for the detection of various diffusion compartments, including macromolecular coordinated water, free diffusion, perfusion, and cellular free water. This study aims to investigate the clinical potential of IDF-DWI in detecting microvascular invasion (MVI) in hepatocellular carcinoma (HCC). 66 patients were prospectively included. Metrics derived from IDF-DWI and the apparent diffusion coefficient (ADC) were calculated. Multivariate logistic regression was employed to identify clinical risk factors. Diagnostic performance was evaluated using the area under the receiver operating characteristics curve (AUC-ROC), the area under the precision-recall curve (AUC-PR), and the calibration error (cal-error). Additionally, a power analysis was conducted to determine the required sample size. The results suggested a significantly higher fraction of impeded diffusion (FID) originating from IDF-DWI in MVI-positive HCCs (p < 0.001). Moreover, the ADC was found to be significantly lower in MVI-positive HCCs (p = 0.019). Independent risk factors of MVI included larger tumor size and elevated alpha-fetoprotein (AFP) levels. The nomogram model incorporating ADC, FID, tumor size, and AFP level yielded the highest diagnostic accuracy for MVI (AUC-PR = 0.804, AUC-ROC = 0.783, cal-error = 0.044), followed by FID (AUC-PR = 0.693, AUC-ROC = 0.760, cal-error = 0.060) and ADC (AUC-PR = 0.570, AUC-ROC = 0.651, cal-error = 0.164). IDF-DWI shows great potential in noninvasively, accurately, and preoperatively detecting MVI in HCC and may offer clinical benefits for prognostic prediction and determination of treatment strategy.

Clinical analysis of 12 cases of ovarian yolk sac tumor

Objective: To investigate the diagnosis, treatment and prognosis of ovarian yolk sac tumor (OYST). Methods: The clinicopathological data and follow-up data of 12 patients with OYST admitted to the Affiliated Hospital of Qingdao University from January 2013 to December 2020 were retrospectively analyzed, and the diagnosis, treatment and prognosis of OYST patients were summarized. Results: (1) The age of 12 patients with OYST ranged from 11 to 37 years, with a median age of 20 years. At the first visit, all 12 patients had pelvic masses. Reasons for seeing a doctor: 6 cases of abdominal distension and abdominal pain, 4 cases of mass in the lower abdomen, 1 case of vaginal bleeding, and 1 case of appendicitis. International Federation of Obstetrics and Gynecology (FIGO) 2014 staging: 4 cases in stage Ⅰa, 2 cases in stage Ⅰc, 1 case in stage Ⅱc, 4 cases in stage Ⅲc, and 1 case in stage Ⅳb. (2) All 12 patients were examined by color Doppler ultrasound before operation, among which 10 cases showed unilateral adnexal masses and 2 cases bilateral adnexal masses. The median maximum diameter of tumor was 16.5 cm (range: 6.0-28.0 cm). The preoperative levels of alpha fetoprotein (AFP) in 12 patients (all >1 210 μg/L) were significantly higher than normal (<25 μg/L). Among the 11 patients with cancer antigen 125 (CA125) detection results, 9 patients showed elevated serum CA125 levels. (3) Among the 12 patients, 8 young infertile patients who needed to preserve their reproductive function underwent appendectomy, 3 infertile patients underwent staged surgery for ovarian malignant germ cell tumor, and only one bilateral lesion and infertile patient underwent unsatisfactory staged surgery for ovarian malignant germ cell tumor. Of the 12 patients, 11 patients were given combined chemotherapy regimen of bleomycin, cisplatin, and etoposide (BEP) after operation. One patient without chemotherapy developed metastasis 3 months after operation, and was given BEP chemotherapy, and her condition was controlled. (4) The deadline for follow-up was December 31st, 2022, and the median follow-up time was 60 months (range: 25-115 months). All the 12 patients survived without tumor during the follow-up period, and the median disease-free survival time was 84.5 months (range: 25-115 months). Conclusions: OYST mostly occurs in children and young women. Color Doppler ultrasound examination and serum AFP and CA125 detection have diagnostic value for OYST. Surgical treatment after diagnosis of OYST includes surgery to preserve reproductive function and timely and standardized chemotherapy after operation. The prognosis of patients is good regardless of stage.

Abstract 4547: A novel drug combination with improved therapeutic efficacy over sorafenib in multiple preclinical models of hepatocellular carcinoma

Abstract Introduction: Due to the heterogeneity of hepatocellular carcinoma (HCC), the incidence of resistance and toxicity to first-line therapy sorafenib is high. Combinations of drugs can be used to exploit synergistic effects to reduce adverse events, while improving efficacy and survival. In-vitro studies performed by our team identified irinotecan and sonidegib to have potential for synergistic therapeutic effects in combination with sorafenib. Follow up in-vivo dose optimization studies in a murine NASH induced HCC found this 3-drug combination to be more effective than sorafenib-alone at arresting tumor development and progression. In this study, we tested the in-vivo efficacy of the combination in two separate preclinical cell-line derived xenograft (CDX) models. Experimental Procedure: HCC CDX models were generated by injecting two distinct HCC cell lines, Huh7 and HepG2, subcutaneously in the flank of male NOD.Cg-PrkdcscidIL2rgtm1Wjl/SzJ (NSG) mice. Mice were administered either vehicle, sorafenib, or a 3-drug combination, and mouse tumor volumes and weights were tracked for duration of study. Mice were all euthanized at study endpoint and tissues collected for analysis, including the assessment of tumor weights, differentiation, grade, necrosis, and proliferation status. Serum collected from endpoint blood was measured for human alpha fetoprotein (AFP) and alanine transaminase (ALT) levels. Changes in protein expression of tumors were assessed by western blot analysis. Results: Huh7 and HepG2 tumors were both sensitive to sorafenib-alone treatment. However, Huh7 tumors treated with the 3-drug combination had a significant decrease in tumor volume and weight at endpoint compared to the vehicle and sorafenib-alone. HepG2 tumors treated with the combination also had a significant decrease in tumor volume and weight at endpoint compared to the vehicle. Though the difference in tumor volume and weight was not statistically significant for the combination compared to sorafenib, a trend towards decrease was observed. This was further confirmed by significantly reduced AFP levels in the combination compared to the vehicle and sorafenib in HepG2 and Huh7. Drug toxicities, measured by mouse weights and ALT levels, were not significantly different. Histological and immunohistochemical assessment of tumors showed necrosis and Ki67 staining to be significantly elevated in vehicle and sorafenib-alone compared to the 3-drug group. The targets for all three drugs present in the combination were downregulated in the combination compared to the vehicle and sorafenib-alone. Conclusion: This study provides strong evidence that a novel 3-drug combination of irinotecan, sonidegib, and low dose sorafenib can significantly reduce tumor proliferation and burden in multiple independent pre-clinical in-vivo HCC models compared to high dose sorafenib monotherapy. Citation Format: Anastasia Chambers, Sunaina Shrestha, Alexandra Ladd, Sergio Duarte, Ali Zarrinpar. A novel drug combination with improved therapeutic efficacy over sorafenib in multiple preclinical models of hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4547.

Abstract 772: Investigation of gender disparity in liver tumor formation using a hydrodynamic tail vein injection mouse model

Abstract The incidence of hepatocellular carcinoma (HCC), the major form of liver cancer, is 4 times higher in men than in women. This gender disparity is difficult to study since it is believed to be multifactorial, due in part to differences in risk factors, behaviors, and hormones. The liver is a sexually dimorphic organ that is extremely susceptible to interactions with estrogens and androgens. Estrogen has been proven to have a protective effect against HCC with a demonstrable gender-related hormonal effect on the growth of HCC, though the underlying mechanisms are not fully understood. The hydrodynamic tail vein injection (HTVI) mouse model allows for the induction of liver tumors in the host. Eliminating the social and behavioral aspects of the gender disparity will allow us to determine what role estrogen plays in tumor development. In our study, a gender disparity in tumor development was observed between 6-week-old male and female FVB/NJ mice injected via HTVI of plasmids expressing c-MET, a mutated beta-catenin (b-Cat) and Sleeping Beauty transposon. HTVI of a Luciferase and Sleeping Beauty transposon expressing plasmid showed no significant difference in photon flux by bioluminescence imaging between male and female mice 24 hours after injection. When imaging was repeated one week after injection, the photon flux reduced by an order of magnitude in both male and female mice with the female mice showing more uniform reduction than the male mice. Similar luciferase gene copy number was detected in the liver tissue of male and female mice. These data suggest that there appears to be no gender difference in the transient expression and stable integration of the transfected plasmid. Plasma alpha-fetoprotein (AFP) was used to monitor tumor formation in the mice that were injected with c-MET and b-Cat without luciferase as luciferase is immunogenic. The male mice had significantly higher AFP levels at 3.5 weeks, 8 weeks, and 12 weeks post-injection than the female mice. At termination, the liver weight confirmed that female mice had much lower tumor burden than the males. We are currently using quantitative PCR to confirm similar copy number of exogenous c-MET and b-Cat inserted in the tumor cell genome and using RT-qPCR and Western blotting to determine whether the transgene expression is different in tumors from male and female mice. To determine whether estrogen played a role in preventing tumor development and progression in female mice, six-week-old male and ovariectomized female mice have been injected with the same oncogene plasmid combination plus the sleeping beauty. Interestingly, AFP levels between male and ovariectomized female mice were comparable when measured at 3 weeks. We will present our findings at the meeting. Citation Format: Araceli Bernal, Morgana McLaughlin, Ankur Tiwari, Francisco Cigarroa, LuZhe Sun. Investigation of gender disparity in liver tumor formation using a hydrodynamic tail vein injection mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 772.

Efficacy of radiofrequency ablation combined with sorafenib for treating liver cancer complicated with portal hypertension and prognostic factors.

Patients with liver cancer complicated by portal hypertension present complex challenges in treatment. To evaluate the efficacy of radiofrequency ablation in combination with sorafenib for improving liver function and its impact on the prognosis of patients with this condition. Data from 100 patients with liver cancer complicated with portal hypertension from May 2014 to March 2019 were analyzed and divided into a study group (n = 50) and a control group (n = 50) according to the treatment regimen. The research group received radiofrequency ablation (RFA) in combination with sorafenib, and the control group only received RFA. The short-term efficacy of both the research and control groups was observed. Liver function and portal hypertension were compared before and after treatment. Alpha-fetoprotein (AFP), glypican-3 (GPC-3), and AFP-L3 levels were compared between the two groups prior to and after treatment. The occurrence of adverse reactions in both groups was observed. The 3-year survival rate was compared between the two groups. Basic data were compared between the survival and non-surviving groups. To identify the independent risk factors for poor prognosis in patients with liver cancer complicated by portal hypertension, multivariate logistic regression analysis was employed. When comparing the two groups, the research group's total effective rate (82.00%) was significantly greater than that of the control group (56.00%; P < 0.05). Following treatment, alanine aminotransferase and aspartate aminotransferase levels increased, and portal vein pressure decreased in both groups. The degree of improvement for every index was substantially greater in the research group than in the control group (P < 0.05). Following treatment, the AFP, GPC-3, and AFP-L3 levels in both groups decreased, with the research group having significantly lower levels than the control group (P < 0.05). The incidence of diarrhea, rash, nausea and vomiting, and fatigue in the research group was significantly greater than that in the control group (P < 0.05). The 1-, 2-, and 3-year survival rates of the research group (94.00%, 84.00%, and 72.00%, respectively) were significantly greater than those of the control group (80.00%, 64.00%, and 40.00%, respectively; P < 0.05). Significant differences were observed between the survival group and the non-surviving group in terms of Child-Pugh grade, history of hepatitis, number of tumors, tumor size, use of sorafenib, stage of liver cancer, histological differentiation, history of splenectomy and other basic data (P < 0.05). Logistic regression analysis demonstrated that high Child-Pugh grade, tumor size (6-10 cm), history of hepatitis, no use of sorafenib, liver cancer stage IIIC, and previous splenectomy were independent risk factors for poor prognosis in patients with liver cancer complicated with portal hypertension (P < 0.05). Patients suffering from liver cancer complicated by portal hypertension benefit from the combination of RFA and sorafenib therapy because it effectively restores liver function and increases survival rates. The prognosis of patients suffering from liver cancer complicated by portal hypertension is strongly associated with factors such as high Child-Pugh grade, tumor size (6-10 cm), history of hepatitis, lack of sorafenib use, liver cancer at stage IIIC, and prior splenectomy.

Hepatitis B virus-related hepatocellular carcinoma has superior overall survival compared with other etiologies.

Whether the etiology of chronic liver disease (CLD) impacts the overall survival (OS) of patients with hepatocellular carcinoma (HCC) remains unclear. We aim to clarify this issue. Between 2011 and 2020, 3941 patients who were newly diagnosed with HCC at our institution were enrolled in this study. In patients with multiple CLD etiologies, etiology was classified using the following hierarchy: hepatitis C virus (HCV) > hepatitis B virus (HBV) > alcohol-related > all negative. All negative was defined as negative for HCV, HBV, and alcohol use disorder. Among 3941 patients, 1407 patients were classified with HCV-related HCC, 1677 patients had HBV-related HCC, 145 patients had alcohol-related HCC, and 712 patients had all-negative HCC. Using the all-negative group as the reference group, multivariate analysis showed that HBV is an independent predictor of mortality (hazard ratio: 0.856; 95% confidence interval: 0.745-0.983; p = 0.027). Patients with HBV-related HCC had superior OS compared with patients with other CLD etiologies (p<0.001). Subgroup analyses were performed, for Barcelona Clinic Liver Cancer (BCLC) stages 0-A (p<0.001); serum alpha-fetoprotein (AFP) levels≧20 ng/ml (p<0.001); AFP levels < 20 ng/ml (p<0.001); age > 65 years (p<0.001); and the use of curative treatments (p = 0.002). No significant difference in OS between HBV and other etiologies was observed among patients aged ≤ 65 years (p = 0.304); with BCLC stages B-D (p = 0.973); or who underwent non-curative treatments (p = 0.1). Patients with HBV-related HCC had superior OS than patients with other HCC etiologies.