Elevated Alpha-fetoprotein Research Articles

Sertoli-Leydig Cell Tumour in a Patient with Ambiguous Genitalia and Congenital Adrenal Hyperplasia

Background: Hyperandrogenism, characterized by elevated levels of male hormones such as testosterone, presents various clinical manifestations including secondary amenorrhea, hirsutism, and clitoromegaly. While often associated with polycystic ovarian syndrome, other differentials such as Sertoli-Leydig cell tumors and Congenital Adrenal Hyperplasia (CAH) are critical to consider. These conditions can manifest at different life stages and are seldom seen together. Objective: This case study aims to explore the rare co-presentation of CAH and a Sertoli-Leydig cell tumor in a patient presenting with secondary amenorrhea and ambiguous genitalia, and to discuss the diagnostic challenges and management strategies involved. Methods: A 16-year-old female presented with irregular menstrual cycles and secondary amenorrhea, alongside symptoms of hyperandrogenism such as voice deepening and hirsutism. Diagnostic procedures included physical examinations, ultrasound imaging, and hormone level assessments. A detailed ultrasound revealed a large right-sided ovarian mass, and biopsies confirmed a Sertoli-Leydig cell tumor. Surgical intervention involved the excision of the mass, with subsequent histopathological examination. The patient underwent three cycles of chemotherapy and was scheduled for reconstructive surgery. Results: Ultrasound dimensions of the ovarian mass were 7.2 x 13.4 x 16 cm, with the post-surgical tumor measuring 18 x 17 cm. Laboratory findings included testosterone levels above 200 ng/ml, and elevated alpha-fetoprotein levels. The histopathological report confirmed a poorly differentiated Sertoli-Leydig cell tumor (FIGO stage 1a). Post-treatment follow-up showed a marked reduction in androgen levels and stabilization of the patient's menstrual cycle. Conclusion: The coexistence of CAH and a Sertoli-Leydig cell tumor presents unique diagnostic and therapeutic challenges. This case emphasizes the importance of a thorough evaluation and a multidisciplinary approach in the management of complex hyperandrogenic states to achieve optimal clinical outcomes.

Hepatocellular Carcinoma Mimicking Focal Nodular Hyperplasia

Focal nodular hyperplasia (FNH) is a common benign liver lesion, mostly solitary, and with no evidence of malignant transformation over time. The diagnosis can usually be made by imaging modalities with distinct features in magnetic resonance imaging (MRI) and computed tomography (CT) scans. We present a case series of three patients with solitary liver tumors which were, based on radiological features, first diagnosed to be large FNH. The patients were sent to our center for second opinion and probable treatment. Indication for resection was given because of nonconclusive radiologic imaging in the first, substantial growth progression in the second and elevated alpha fetoprotein (AFP) in the third case. Histology revealed well to poor differentiated hepatocellular carcinoma (HCC). FNH tends to show a distinct pattern in imaging modalities, but HCC can mimic FNH. The MRI-scan using hepatotropic contrast agent is the most sensitive imaging modality to diagnose FNH. AFP is usually not elevated in FNH. Asymptomatic FNH does not require surgery but a reliable diagnosis is crucial. In case of an un-certain diagnosis surgery should be offered to patients. In cases with a progression in size, an elevated level of AFP should be suspicious. Generally, an over-therapy via surgery should be avoided and follow-ups of a newly diagnosed FNH including measurement of AFP are advisable to detect alterations.

Dual-tracer PET/CT in the management of hepatocellular carcinoma

Background & AimsCombined 18F-fluorodeoxyglucose (FDG) and 11C-acetate (dual-tracer) positron emission tomography-computed tomography (PET-CT) is being increasingly performed for the management of hepatocellular carcinoma (HCC), although its role is not well defined. Therefore, we evaluated its effectiveness in (i) staging, (ii) characterization of indeterminate lesions on conventional imaging, and (iii) detection of HCC in patients with unexplained elevations in serum alpha-fetoprotein (AFP) levels. MethodsWe retrospectively assessed 525 consecutive patients from three tertiary centers between 2014 and 2020. For staging, we recorded new lesion detection rates, changes in the Barcelona Clinic Liver Cancer (BCLC) classification, and treatment allocation due to dual-tracer PET-CT. To characterize indeterminate lesions and unexplained elevation of serum AFP levels, the sensitivity and specificity of dual-tracer PET-CT in diagnosing HCC were evaluated. A Multidisciplinary external review and a cost-benefit analysis of patients for metastatic screening were also performed. ResultsDual-tracer PET/CT identified new lesions in 14.3% of 273 staging patients, resulting in BCLC upstaging in 11.7% and treatment modifications in 7.7%. It upstaged 8.1% of 260 patients undergoing metastatic screening, with an estimated savings of US$495 per patient. It had a sensitivity and specificity of 80.7% (95% CI 71.2-88.6%) and 94.8% (95% CI 90.4-98.6%), respectively, for diagnosing HCC in 201 indeterminate lesions. It detected HCC in 45.1% of 51 patients with unexplained elevations in serum AFP concentrations. External review revealed substantial agreement between local and external image interpretation and patient assessment (n=273, κ=0.822; 95% CI 0.803-0.864). ConclusionsDual-tracer PET/CT provides additional value to conventional imaging in HCC patients by improving staging, confirming HCC diagnosis with high accuracy in patients with indeterminate lesions, and detecting HCC in patients with unexplained elevation of serum AFP.• Impact and implications• Dual-tracer PET-CT detected 12% more disease in HCC patients undergoing staging than CT or MRI, resulting in change in treatment in 8% of cases and a cost saving of US$495 per patient.• It is also able to accurately detect HCC in high-risk cases where CT or MRI are equivocal or normal.• Dual-tracer PET/CT provides additional value to conventional imaging in HCC patients by improving staging, confirming HCC diagnosis with high accuracy in patients with indeterminate lesions, and detecting HCC in patients with unexplained elevation of serum AFP.

Can Dynamic Contrast-Enhanced MRI Be Used to Differentiate Hepatic Hemangioma from Other Lesions in Early Infancy?

Background Confident diagnosis of hepatic hemangioma on imaging can avoid biopsy in early infancy and helps guide conservative management. Purpose This article aims to determine if dynamic contrast-enhanced magnetic resonance imaging (MRI) can be used to differentiate liver hemangioma from other lesions in infants ≤ 100 days and to determine association of MRI features with hepatic lesions. Methods MRI performed for liver lesions were retrospectively reviewed to note imaging characteristics and the MRI diagnosis. Final diagnosis was assigned based on pathology in available cases and by corroborative standard of reference including overall clinical features, lab findings, and follow-up. Results Of 30 infants (18 boys, 12 girls; average age 42.2 days) included, 18 had solitary and 12 had multifocal lesions. Diagnoses in total 33 lesions included hemangiomas (23), hepatoblastoma (6), arteriovenous malformation (2), neuroblastoma metastases (1), and infarction (1). MRI and final diagnosis matched in 94% lesions with almost perfect agreement (kappa 0.86) for reader 1, and matched in 88% lesions with substantial agreement (kappa 0.71) for reader 2. Interobserver agreement for MRI diagnosis was substantial (kappa 0.62). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MRI in differentiating hemangioma from other lesions were 100, 90, 96, 100, and 97%, respectively. Centripetal (16/23) or flash (5/23) filling were only seen with hemangioma. There was no significant difference in alpha-fetoprotein elevation ( p 0.08), average size ( p 0.35), multifocality ( p 0.38), and intralesional hemorrhage ( p 1) between hemangioma and hepatoblastoma. Conclusion Centripetal filling on dynamic imaging and absence of washout are characteristic MRI features of hepatic hemangioma that can help to differentiate it from other lesions in early infancy.

Remarkable alpha-fetoprotein elevation and pseudo-infarction of cirrhotic liver: case report

This is a case of remarkable alpha-fetoprotein in a female patient with known cryptogenic liver cirrhosis. Both ultrasound and triphasic computed tomography (CT) abdomen cannot diagnose or exclude hepatocellular carcinoma (HCC). It turns out to be a case of portal vein thrombosis and hepatic pseudo-infarction. It is better to postpone the therapeutic intervention, whether surgical or chemotherapeutic, in cases not confirmed to be HCC for at least 3 months to avoid misdiagnosis of hepatic pseudo-infarction.

Lean body mass index is a marker of advanced tumor features in patients with hepatocellular carcinoma.

Obesity is an independent risk factor for the development of hepatocellular carcinoma (HCC) and may influence its outcomes. However, after diagnosis of HCC, like other malignancies, the obesity paradox may exist where higher body mass index (BMI) may in fact confer a survival benefit. This is frequently observed in patients with advanced HCC and cirrhosis, who often present late with advanced tumor features and cancer related weight loss. To explore the relationship between BMI and survival in patients with cirrhosis and HCC. This is a retrospective cohort study of over 2500 patients diagnosed with HCC between 2009-2019 at two United States academic medical centers. Patient and tumor characteristics were extracted manually from medical records of each institutions' cancer registries. Patients were stratified according to BMI classes: < 25 kg/m2 (lean), 25-29.9 kg/m2 (overweight), and > 30 kg/m2 (obese). Patient and tumor characteristics were compared according to BMI classification. We performed an overall survival analysis using Kaplan Meier by the three BMI classes and after adjusting for Milan criteria. A multivariable Cox regression model was then used to assess known risk factors for survival in patients with cirrhosis and HCC. A total of 2548 patients with HCC were included in the analysis of which 11.2% (n = 286) were classified as non-cirrhotic. The three main BMI categories: Lean (n = 754), overweight (n = 861), and obese (n = 933) represented 29.6%, 33.8%, and 36.6% of the total population overall. Within each BMI class, the non-cirrhotic patients accounted for 15% (n = 100), 12% (n = 94), and 11% (n = 92), respectively. Underweight patients with a BMI < 18.5 kg/m2 (n = 52) were included in the lean cohort. Of the obese cohort, 42% (n = 396) had a BMI ≥ 35 kg/m2. Out of 2262 patients with cirrhosis and HCC, 654 (29%) were lean, 767 (34%) were overweight, and 841 (37%) were obese. The three BMI classes did not differ by age, MELD, or Child-Pugh class. Chronic hepatitis C was the dominant etiology in lean compared to the overweight and obese patients (71%, 62%, 49%, P < 0.001). Lean patients had significantly larger tumors compared to the other two BMI classes (5.1 vs 4.2 vs 4.2 cm, P < 0.001), were more likely outside Milan (56% vs 48% vs 47%, P < 0.001), and less likely to undergo transplantation (9% vs 18% vs 18%, P < 0.001). While both tumor size (P < 0.0001) and elevated alpha fetoprotein (P < 0.0001) were associated with worse survival by regression analysis, lean BMI was not (P = 0.36). Lean patients with cirrhosis and HCC present with larger tumors and are more often outside Milan criteria, reflecting cancer related cachexia from delayed diagnosis. Access to care for hepatitis C virus therapy and liver transplantation confer a survival benefit, but not overweight or obese BMI classifications.

The Utility of Serum Alpha-fetoprotein for Monitoring for Relapse of Alpha-fetoprotein-Positive Hepatoblastoma.

Hepatoblastoma is the most common liver malignancy in children. Treatment typically involves surgery and cisplatin-based chemotherapy. After therapy completion, children undergo repetitive surveillance imaging to screen for relapse, which occurs in <12% of cases. Monitoring for relapse has gradually shifted to serial determination of serum alpha-fetoprotein (AFP) alone as most cases have AFP elevation at the time of relapse. Little primary data supports, such a practice, however, and herein we present both our institutional experience with relapsed hepatoblastoma and a careful review of published literature on this topic. While serial AFP monitoring may suffice for most patients, certain clinical characteristics should give pause to the practitioner, when considering posttreatment monitoring with serum AFP alone.

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.

46, XX disorder of sexual development associated with mixed germ cell tumor of the prostate: a rare case report

BackgroundExtragonadal germ cell tumors originating from the prostate are exceptionally rare. To the best of our knowledge, there have been no reported cases of mixed germ cell tumors in individuals with 46 XX disorder of sex development. In this study, we conducted a comprehensive analysis using whole genome sequencing to investigate the clinicopathological and molecular genetic characteristics of a submitted case, with the objective of elucidating its underlying pathogenesis.Case presentationA 40-year-old male patient was diagnosed with a combination of 46, XX disorder of sex development and a primary prostate mixed germ cell tumor with yolk sac tumor and teratoma components. Whole-genome sequencing revealed that the tumor cells had a high somatic mutational load. Analysis of genomic structural variations and copy number variants confirmed the patient's karyotype as 46, XX (SRY +). Additionally, the patient exhibited short stature, small bilateral testes, slightly enlarged breasts, elevated serum alpha-fetoprotein concentrations, elevated follicle-stimulating hormone and luteinizing hormone levels, and low testosterone levels.DiscussionA case of 46, XX disorder of sex development, along with a primary prostatic mixed germ cell tumor, was diagnosed. This diagnosis has contributed to advancing our understanding of the genetic and phenotypic profile of the disease and may provide some insights for its treatment.

Clonorchis sinensis infection amplifies hepatocellular carcinoma stemness, predicting unfavorable prognosis.

Extensive evidence links Clonorchis sinensis (C. sinensis) to cholangiocarcinoma; however, its association with hepatocellular carcinoma (HCC) is less acknowledged, and the underlying mechanism remains unclear. This study was designed to investigate the association between C. sinensis infection and HCC and reveal the relationship between C. sinensis infection and cancer stemness. A comprehensive analysis of 839 HCC patients categorized into C. sinensis (-) HCC and C. sinensis (+) HCC groups was conducted. Chi-square and Mann-Whitney U tests were used to assess the association between C. sinensis infection and clinical factors. Kaplan-Meier and Cox regression analyses were used to evaluate survival outcomes. Immunohistochemistry was used to determine CK19 and EpCAM expression in HCC specimens. Compared to C. sinensis (-) HCC patients, C. sinensis (+) HCC patients exhibited advanced Barcelona Clinic Liver Cancer (BCLC) stage, higher male prevalence and more liver cirrhosis as well as elevated alpha-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), eosinophil, complement 3 (C3), and complement 4 (C4) values. C. sinensis infection correlated with shorter overall survival (OS) (p < 0.05) and recurrence-free survival (RFS) (p < 0.05). Furthermore, Cox multivariate analysis revealed that C. sinensis infection was an independent prognostic factor for OS in HCC patients. Importantly, C. sinensis infection upregulated the expression of HCC cancer stem cell markers CK19 and EpCAM. HCC patients with C. sinensis infection exhibit a poor prognosis following hepatectomy. Moreover, C. sinensis infection promotes the acquisition of cancer stem cell-like characteristics, consequently accelerating the malignant progression of HCC. Clonorchis sinensis (C. sinensis) is a prominent food-borne parasite prevalent in regions such as China, particularly in Guangxi. C. sinensis has been associated with various hepatobiliary system injuries, encompassing inflammation, periductal fibrosis, cholangiocarcinoma and even hepatocellular carcinoma (HCC). A substantial body of evidence links C. sinensis to cholangiocarcinoma, However, the connection between C. sinensis and HCC and the intricate mechanisms underlying its contribution to HCC development remain incompletely elucidated. Our study demonstrates clear clinicopathological associations between C. sinensis and HCC, such as gender, BCLC stage, liver cirrhosis, MVI, AFP, CA19-9, circulating eosinophils and complements. Furthermore, we found that the co-occurrence of C. sinensis exhibited a significant association with shorter OS and RFS in patients diagnosed with HCC. A major finding was that C. sinensis infection promotes the acquisition of cancer stem cell-like characteristics, consequently accelerating the malignant progression of HCC. Our results provide a more comprehensive comprehension of the interplay between C. sinensis and HCC, shedding fresh light on the carcinogenic potential of C. sinensis.

Agrin as a prognostic biomarker in hepatocellular carcinoma.

559 Background: Hepatocellular carcinoma (HCC), the predominant form of hepatic cancer is associated with high mortality rates, both in the United States &amp; globally. Alpha-fetoprotein (AFP) &amp; Glypican-3 have been proposed as biomarkers for HCC, although they do not offer any prognostic benefit to model disease progression. Immunotherapy combinations increase patient survival to ~18 months but are not selected based on biomarkers. Agrin, a secreted proteoglycan is frequently overexpressed &amp; secreted in HCC &amp; plays a prominent role in liver tumor microenvironment to promote hepatocarcinogenesis. In this single center, retrospective study using banked materials, we assessed the role of agrin as a prognostic biomarker in HCC. Methods: With IRB approval, we studied 90 newly diagnosed unresectable hepatobiliary cancer patients, &amp; compared them to healthy controls matched for age, gender, &amp; BMI between February 2006 &amp; September 2013. Serum concentration (conc.) of agrin was assessed using enzyme-linked immunosorbent assay (ELISA). We correlated the level of agrin with AFP, a known biomarker in hepatocellular cancer. Comparisons between groups were made using Mann-Whitney U &amp; Kruskal Wallis tests. Survival analysis used both univariate &amp; multivariate Cox regression models to investigate the relationship between survival outcomes &amp; agrin concentration, in comparison to AFP. Results: Mean circulatory plasma agrin levels were higher in HCC patients (n=79) (7.97 ng/ml, SD 5.8) when compared to controls (4.27 ng/ml, SD 1.03). ECOG PS &gt; 2 was linked to higher agrin conc. (mean: 10.5 ng/ml, p 0.007). While agrin levels in healthy individuals did not change with smoking history, the mean agrin levels were significantly higher in smokers (9.49 ng/ml) vs non-smokers (6.84 ng/ml) (p 0.0001) amongst HCC patients. Agrin displayed a strong positive correlation with AFP (correlation coefficient (r) 0.31944, p 0.0137). Multivariate cox regression models indicated that agrin conc. of &gt; 9.3 ng/ml had greater predictable survival outcomes (Hazard ratio (HR) 8.51, p &lt;0.001) when compared to elevated AFP levels (HR 1.55, p 0.25) (Table). HCC patients with lower agrin conc. (4.9 to 6.3 ng/ml) exhibited a one-year survival rate of 63% &amp; a median survival time of 16 months, while those with higher agrin conc. exceeding 9.3 ng/ml had significantly lower one-year survival rate of 14% &amp; significantly shorter median survival time of 3 months (p 0.002). Conclusions: Our results suggest that agrin levels as a prognostic indicator fare better than AFP levels. Thus, further studies should be done to explore this as a therapeutic target and as a biomarker of response to targeted therapies. [Table: see text]

A multi-parameter intrahepatic cholangiocarcinoma scoring system based on modified contrast-enhanced ultrasound LI-RADS M criteria for differentiating intrahepatic cholangiocarcinoma from hepatocellular carcinoma.

To develop a multi-parameter intrahepatic cholangiocarcinoma (ICC) scoring system and compare its diagnostic performance with contrast-enhanced ultrasound (CEUS) liver imaging reporting and data system M (LR-M) criteria for differentiating ICC from hepatocellular carcinoma (HCC). This retrospective study enrolled 62 high-risk patients with ICCs and 62 high-risk patients with matched HCCs between January 2022 and December 2022 from two institutions. The CEUS LR-M criteria was modified by adjusting the early wash-out onset (within 45 s) and the marked wash-out (within 3 min). Then, a multi-parameter ICC scoring system was established based on clinical features, B-mode ultrasound features, and modified LR-M criteria. We found that elevated CA 19-9 (OR=12.647), lesion boundary (OR=11.601), peripheral rim-like arterial phase hyperenhancement (OR=23.654), early wash-out onset (OR=7.211), and marked wash-out (OR=19.605) were positive predictors of ICC, whereas elevated alpha-fetoprotein (OR=0.078) was a negative predictor. Based on these findings, an ICC scoring system was established. Compared with the modified LR-M and LR-M criteria, the ICC scoring system showed the highest area under the curve (0.911 vs. 0.831 and 0.750, both p<0.05) and specificity (0.935 vs. 0.774 and 0.565, both p<0.05). Moreover, the numbers of HCCs categorized as LR-M decreased from 27 (43.5%) to 14 (22.6%) and 4 (6.5%) using the modified LR-M criteria and ICC scoring system, respectively. The modified LR-M criteria-based multi-parameter ICC scoring system had the highest specificity for diagnosing ICC and reduced the number of HCC cases diagnosed as LR-M category.

Fetal and Placental Causes of Elevated Serum Alpha-Fetoprotein Levels in Pregnant Women.

The most common association related to alpha-fetoprotein (AFP) is fetal neural tube defect (NTD), and indeed, this is where the international career of this protein began. In times when ultrasonography was not yet technically advanced, the detection of high levels of AFP in maternal serum (MS-AFP) and amniotic fluid was the basis for suspecting neural tube defects. In cases where there was no confirmation of NTD, other causes were sought. It has been established that high titers of MS-AFP could originate in other defects or diseases, such as (1) increased proteinuria in severe fetal kidney diseases; (2) pathological overproduction in liver diseases; (3) penetration through the membranes of gastrointestinal organs exposed to amniotic fluid; (4) passage through the walls of skin vessels; and as a side effect of (5) hepatic hematopoiesis and increased transfer through the edematous placenta in fetal anemia. This article provides a review of the current literature on congenital defects and genetic diseases in the fetus where an elevated level of MS-AFP may serve as the initial diagnostic clue for their detection.

The Role of Lactate Dehydrogenase in Exploring the Immune Evasion in HCC Patients Who Underwent TACE: Implications for Clinical Application.

To examine the relationship between lactate dehydrogenase (LDH) levels and soluble programmed cell death-ligand 1 (sPD-L1) levels in hepatocellular carcinoma (HCC) patients undergoing transarterial chemoembolization (TACE). A total of 83hCC patients participated in this study. Patients were categorized into subgroups based on their alpha-fetoprotein (AFP) levels, presence or absence of extrahepatic metastasis, vascular invasion, Barcelona Clinic Liver Cancer (BCLC) stage, tumor response, tumor size, and number LDH and sPD-L1 levels were compared before and after TACE (3, 7, and 30 days post-TACE). LDH and sPD-L1 levels were significantly higher at 3 and 7 days post-TACE than at baseline. Positive correlations were observed between changes in LDH levels and sPD-L1 levels at 3 and 7 days post-TACE. LDH levels were higher in patients with elevated AFP compared to those in the normal AFP group at 3 and 7 days post-TACE, in the stable disease (SD) group compared to complete response (CR) and partial response (PR) groups at 7 days post-TACE, and in those with tumor > 5 cm compared with those with tumor ≤ 5 cm at 3 and 7 days after TACE (all P < 0.05). sPD-L1 levels were higher in patients with vascular invasion than those without vascular invasion at 3 and 7 days post-TACE, in the SD group compared to CR and PR groups at 3 and 7 days post-TACE, and in those with tumor > 5 cm compared to those with tumor < 5 cm at 3 and 7 days after TACE (all P < 0.05). A positive correlation was found between LDH expression and sPD-L1 levels, suggesting LDH as a potential biomarker for assessing immune status in HCC patients following TACE.

Contrast-enhanced ultrasound features of hepatic sarcomatoid carcinoma different from hepatocellular carcinoma.

Hepatic sarcomatoid carcinoma (HSC) is a rare malignancy of the liver. The ultrasound and clinical features of HSC have not been determined. To investigate and compare the ultrasound and clinical features of HSC and hepatocellular carcinoma (HCC), and to reveal the valuable features of HSC. The ultrasound features and clinical data of pathologically proven HSC (n = 37) were compared with HCC (n = 92) in a matching ratio of 1:4 using the propensity score (age, gender and tumor size). The HSC patients were more likely to accompany with clinical symptoms and vascular invasion than HCC patients (40.5% vs 17.4%, 24.3% vs 6.5%, P < 0.05). The size of HSCs was significantly larger than that of HCCs (P < 0.05). The proportion of patients with elevated alpha-fetoprotein was significantly lower in HSC (35.1% vs 54.3%, P < 0.05). On gray-scale ultrasound images, the HSCs were more likely to demonstrate as indistinct margin and irregular shape lesions compared to HCCs (78.4% vs 48.8%; 70.3% vs 23.9%, P < 0.05). Under color Doppler flow imaging (CDFI), the blood flow signals were more frequently detected in HSC lesions (75.7% vs 56.5%, P < 0.05). Resistance index (RI) was higher in HSCs than in HCCs [0.78 (0.70,0.82) vs 0.70 (0.62,0.76), P < 0.05]. On contrast-enhanced ultrasound (CEUS), HSCs mainly showed entirety heterogeneous hyper-enhancement (48.6%), entirety homogeneous enhancement (18.9%), peripheral and internal septal enhancement (18.9%). The incidence of non-enhanced areas inside HSC lesions was higher than that inside HCC lesions (56.8% vs 31.5%, P < 0.05). During the portal venous and late phases, most of the lesions revealed hypo-enhancement in both groups, whereas earlier washout was observed in HSCs [43.0 s (30.5,58.0) vs 60.0 s (46.3,100.0), P < 0.05]. CEUS features are useful in preoperative and non-invasive differentiation of hepatic sarcomatoid carcinoma and hepatocellular carcinoma.

Review on the clinical roles and limitations of AFP as marker for HCC and other diseases

The tumor marker for hepatocellular carcinoma, alpha-fetoprotein (AFP), has been utilized in association with ultrasound and other imaging methods (HCC). Its utility is constrained by low sensitivity and specificity, as well as differences between the various measurement methods. Also, depending on the patient's characteristics and the used AFP cut-off values, its accuracy fluctuates. Des-gamma-carboxyprothrombin, a new biomarker, was combined with AFP to significantly increase its ability to identify HCC. Elevated AFP levels are usually seen in patients with acute and chronic liver diseases, as well as cirrhosis, and could indicate the severity of hepatic damage and subsequent regeneration. AFP increases can also result from hereditary conditions and other non-hepatic diseases.ase can also result from hereditary conditions and other non-hepatic diseases.

Elevated Alpha-fetoprotein in a 3-month-old Infant: The Significance in a Patient With Beckwith-Wiedemann Syndrome

A 3-month-old female infant with omphalocele, posterior cleft palate and bilateral hydronephrosis was inadvertently discovered to have macroglossia, hepatomegaly, and facial nevus flammeus during hospitalisation for community-acquired pneumonia. A clinical diagnosis of Beckwith-Wiedemann syndrome (BWS), a disease with a higher predisposition to developing embryonal tumours was made. A liver ultrasound revealed a haemangioma at section VIII with the absence of hepatoblastoma. A serum alpha-fetoprotein (AFP) of 413 IU/mL was initially a concern given it was 60 times higher than the stated reference interval but was noted to be age-appropriate and related to the patient’s underlying disease. This case report highlights the importance of reporting an AFP age-specific reference interval as well as the necessity of monitoring AFP in a child with BWS due to the higher risk of hepatoblastoma.

HEPATOCELLULAR CARCINOMA IN OCCULT HEPATITIS B VIRUS INFECTION: A CASE REPORT

Occult hepatitis B virus infection is defined as the presence of hepatitis B virus DNA in the hepatocytes or serum of individuals who had tested negative for serum HBV surface antigen. Controversies remain as to the role of the occult HBV infection in the development of hepatocellular carcinoma (HCC) in immunocompetent individuals. It has been shown that the persistence of very low viral replicative activity during occult hepatitis B virus infection may induce mild liver necro-inflammation continuing for life, and substantial clinical evidence indicates that occult hepatitis B virus infection can accelerate the progression of liver disease towards cirrhosis that is considered the most important risk factor for hepatocellular carcinoma development. The aim of this case is to describe the clinical symptoms and laboratory data of the first case we encountered of HCC occurring in an OBI patient. A 52-year-old man came to the Infectious Diseases Unit because of right upper quadrant pain. Blood test showed negative for HBsAg, positivity for both anti-HBs and anti-HBc total, the quantitative assay of HBV DNA based on TaqMan technology was 2012 copies/mL, elevated serum alpha-fetoprotein level, the findings in abdominal ultrasonography and computed tomography showed a tumor in the right liver lobe with 12cm in size. The patient was transferred to the Military Hospital 175 Ho Chi Minh City for diagnosis of intermediate stage HCC, treated with transarterial chemoembolization (TACE) and antiviral treatment with tenofovir disoproxil fumarate (TDF).

Prognostic implications of alpha-fetoprotein and C-reactive protein elevation in hepatocellular carcinoma following resection (PACE): a large cohort study of 2770 patients

BackgroundRoutine clinical staging for hepatocellular carcinoma (HCC) incorporates liver function, general health, and tumor morphology. Further refinement of prognostic assessments and treatment decisions may benefit from the inclusion of tumor biological marker alpha-fetoprotein (AFP) and systemic inflammation indicator C-reactive protein (CRP).MethodsData from a multicenter cohort of 2770 HCC patients undergoing hepatectomy were analyzed. We developed the PACE risk score (Prognostic implications of AFP and CRP Elevation) after initially assessing preoperative AFP and CRP’s prognostic value. Subgroup analyzes were performed in BCLC cohorts A and B using multivariable Cox analysis to evaluate the prognostic stratification ability of the PACE risk score and its complementary utility for BCLC staging.ResultsPreoperative AFP ≥ 400ng/mL and CRP ≥ 10 mg/L emerged as independent predictors of poorer prognosis in HCC patients who underwent hepatectomy, leading to the creation of the PACE risk score. PACE risk score stratified patients into low, intermediate, and high-risk groups with cumulative 5-year overall (OS) and recurrence-free survival (RFS) rates of 59.6%/44.9%, 43.9%/38.4%, and 20.6%/18.0% respectively (all P < 0.001). Increased PACE risk scores correlated significantly with early recurrence and extrahepatic metastases frequency (all P < 0.001). The multivariable analysis identified intermediate and high-risk PACE scores as independently correlating with poor postoperative OS and RFS. Furthermore, the PACE risk score proficiently stratified the prognosis of BCLC stages A and B patients, with multivariable analyses demonstrating it as an independent prognostic determinant for both stages.ConclusionThe PACE risk score serves as an effective tool for postoperative risk stratification, potentially supplementing the BCLC staging system.