Elevated Serum Alpha-fetoprotein Research Articles

Natural History of Indeterminate Liver Nodules in Patients With Advanced Liver Disease: A Multicenter Retrospective Cohort Study.

Indeterminate liver nodules (ILNs) are frequently encountered on diagnostic imaging after positive hepatocellular carcinoma (HCC) surveillance results, but their natural history remains unclear. We conducted a multicenter retrospective cohort study among patients with ≥1 newly detected LI-RADS 3 (LR-3) lesion ≥1 cm or LI-RADS 4 (LR-4) lesion of any size (per LI-RADS v2018) between January 2018 and December 2019. Patients were followed with repeat imaging at each site per institutional standard of care. Multivariable Fine-Gray models were used to evaluate associations between potential risk factors and patient-level time-to-HCC diagnosis, with death and liver transplantation as competing risks. Of 307 patients with ILNs, 208 had LR-3 lesions, 83 had LR-4 lesions, and 16 had both LR-3 and LR-4 lesions. HCC incidence rates for patients with LR-3 and LR-4 lesions were 110 (95% CI 70-150) and 420 (95% CI 310-560) per 1,000 person-year, respectively. In multivariable analysis, incident HCC among patients with LR-3 lesions was associated with older age, thrombocytopenia (platelet count ≤150 ×10 9 /L), and elevated serum alpha-fetoprotein levels. Among those with LR-4 lesions, incident HCC was associated with a maximum lesion diameter >1 cm. Although most patients had follow-up computed tomography or magnetic resonance imaging, 13.7% had no follow-up imaging and another 14.3% had follow-up ultrasound only. ILNs have a high but variable risk of HCC, with 4-fold higher risk in patients with LR-4 lesions than those with LR-3 lesions, highlighting a need for accurate risk stratification tools and close follow-up in this population.

Interleukin-41: a novel serum marker for the diagnosis of alpha-fetoprotein-negative hepatocellular carcinoma

BackgroundFor the lack of effective serum markers for hepatocellular carcinoma(HCC) diagnosis, it is difficult to detect liver cancer and identify its recurrence early.MethodsDatabases were used to analyze the genes potentially associated with alpha-fetoprotein(AFP). ELISA assay was used to detect the serum IL-41 in HCC, liver metastases, hepatitis, and healthy people. Immunohistochemical staining was used to analyze the relative quantification of IL-41 in HCC and paracancer tissues. Various survival curves were plotted according to clinical pathological data and helped us draw the ROC curve of IL-41 diagnosis of HCC.ResultsThe serum expression of IL-41 was highest in AFP negative HCC patients and significantly higher than that in AFP positive HCC and metastatic cancer patients. There was a significant negative correlation between elevated serum IL-41 and AFP(<1500ng/ml). The clinicopathological features suggested that the serum IL-41 level was significantly correlated with capsule invasion, low differentiation and AFP. High serum expression of IL-41 suggests poorer survival and earlier recurrence after resection, and IL-41 upregulated in patients with early recurrence and death. The expression of IL-41 was higher in HCC tissues of patients with multiple tumors or microvascular invasion. The ROC curve showed that serum IL-41 had a sensitivity of 90.17 for HCC and a sensitivity of 96.63 for AFP-negative HCC, while the specificity was higher than 61%.ConclusionIL-41 in serum and tissue suggests poor prognosis and postoperative recurrence in HCC patients and could be a new serum diagnostic marker for AFP negative patients.

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.

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.

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.

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).

Biological Response Assessment in Hepatocellular Carcinoma Post Stereotactic Body Radiotherapy

Biological Response in Hepatocellular carcinoma (HCC) is measured in terms of serum alpha-fetoprotein (AFP) which is elevated in nearly 60% HCC patients at baseline and is directly related to the severity of the disease. This biological response is defined as the reduction of more than 50% from the baseline levels and is associated with an increased percentage of tumor necrosis and is directly related to increased loco-regional control. Patients diagnosed with HCC have very limited treatment modalities. With the recent advances in the field of radiation therapy and the development of Stereotactic Body radiotherapy (SBRT), the role of radiotherapy has increased as a loco-regional modality for HCC. In this single-arm prospective study, we evaluated the biological response post-SBRT in patients diagnosed with HCC. We conducted a prospective study that included patients diagnosed with HCC with baseline elevation of serum AFP, Child-Turcotte Pugh (CTP) Class A/B with a maximum score of 7. Patient's serum AFP levels were recorded at baseline, pre-treatment, and post-treatment. The biological response was measured at 3 months post-treatment and compared with the baseline serum AFP levels using Wilcoxon signed rank test. A total of 14 patients with HCC were recruited and received SBRT to the target lesion, with a dose between 30-42 Gy over 6 fractions treated on alternate days. Patients were assessed post-treatment at one month with triphasic CEMRI and serum AFP levels. 12 out of 14 patients (85.71%) had a biological response at 3 months follow-up and levels showed further decline unless a progression was found. The median (IQR) serum AFP level was 1131 ng/ml (359-5668 ng/ml) at baseline. Post-treatment serum AFP levels had a median (IQR) value of 156 ng/ml (15-372 ng/ml) showing a near reduction of 86% from baseline, which was significant. 2/14 pts (14.28%) showed no reduction or even increase in serum AFP levels post-treatment. This prospective single-arm study demonstrated the vital role of SBRT in the treatment of HCC and its importance in achieving a better disease control. The response was achieved in 86% of patients with marked reduction of nearly 90% in serum AFP levels as compared to the baseline and increased median OS and PFS as compared to patients not receiving radiotherapy. Further prospective studies are warranted to confirm our findings.

A case of alpha-fetoprotein-positive thymic small cell carcinoma: a case report

BackgroundAn alpha-fetoprotein (AFP)-positive neuroendocrine tumor of the thymus is a rare thoracic malignancy. Few cases of AFP-positive thymic large cell neuroendocrine carcinoma have been reported, with no known previous report of an AFP-positive thymic small cell carcinoma. We encountered a patient with an AFP-positive small cell carcinoma and report here the clinical course.Case presentationA 40-year-old man was transferred to our hospital for a large anterior mediastinal tumor and showed an elevated serum AFP level. Computed tomography-guided biopsy results led to diagnosis of small cell carcinoma. Induction chemoradiotherapy was performed before surgery because of pulmonary artery invasion. The response to Induction chemoradiotherapy varied among sites, with the main tumor showing shrinkage and the metastasis site growth. This discrepancy suggested a histologic type unresponsive to or cancer cells potentially resistant to chemotherapy, thus a surgical re-biopsy was performed and histological findings revealed AFP-positive small cell carcinoma. Additional chemotherapy was performed, though could not control cancer progression, and the patient died 8 months after the first medical examination.ConclusionsOur present clinical experience indicates the importance of histological examination for determining AFP-positive anterior mediastinal tumor treatment. Although AFP-positive neuroendocrine tumor of the thymus is relatively rarer than germ cell carcinoma, differential diagnosis with use of a histological examination should be considered because of the potentially poorer prognosis. The present clinical findings for an AFP-positive neuroendocrine tumor of the thymus case are considered useful for establishing an optimal treatment strategy in the future.

Stereotactic radiosurgery for tumors of the pineal region: A single-center experience.

Tumors of the pineal region (TPRs) are rare neoplasms that are surgically challenging to resect. Conventional treatment strategies are available, but gamma knife radiosurgery (GKRS) is an alternative approach. This study presents a single-center experience with GKRS performed for TPR with and without histopathological diagnoses. The cases of 25 patients with TPRs treated with GKRS were retrospectively analyzed. Thirteen of these 25 patients had histopathological confirmation, and 13 had elevated serum alpha-fetoprotein and beta-human chorionic gonadotropin levels. The 25 patients had a mean follow-up duration of 61 months. The total response rate to GKRS was 60%, and a 53.8% decrease in the alpha-fetoprotein and beta human chorionic gonadotropin levels was observed. The findings of this study indicate that GKRS is a safe procedure for TPRs, even in the event of insufficient histopathological findings. This treatment approach provides increased Karnofsky performance scores and an extended life expectancy.

Intrahepatic Cholangiocarcinoma in a Patient with Alcoholic Liver Cirrhosis and Markedly Elevated Serum Alpha-Fetoprotein

Intrahepatic Cholangiocarcinoma in a Patient with Alcoholic Liver Cirrhosis and Markedly Elevated Serum Alpha-Fetoprotein

Elevated Serum Alpha-fetoprotein Levels in Non-alcoholic Steatohepatitis: Possible Molecular Mechanisms and Potential Clinical Significance

With the improvement of living standards in recent years, up to 90% of obese patients have nonalcoholic fatty liver disease (NAFLD). The number of nonalcoholic steatohepatitis (NASH)-related deaths will gradually increase, and NASH is expected to be the most common cause of liver-related deaths in the future. Therefore, there is an urgent need to find effective and reliable serum biomarkers to distinguish simple hepatic steatosis (SS) from NASH. Liver cell regeneration, oxidative stress-induced DNA methylation, and biliary epithelial cell proliferation were reported to increase serum alpha-fetoprotein (AFP) levels. AFP has long been used as a tool to monitor liver cancer. However, the function of AFP in NAFLD, especially NASH, has not been clarified. Moreover, whether an elevated AFP level indicates the occurrence of NASH or serves as a serum biomarker remains to be elucidated. The miRNA-122 pathway, DNA methylation and DNA damage, and activation of resident stem cells and/or progenitor cells in the liver, as well as necrosis, regeneration, and repair of liver cells, may contribute to slight increases in AFP levels in the development of NASH in patients with NAFLD. Furthermore, mildly elevated AFP levels may indicate the development of NASH. This review explores the role of elevated AFP levels in the development of NASH, with a specific focus on the underlying molecular mechanisms and the clinical significance.

Diagnosis and treatment of primary seminoma of the prostate: A case report and review of literature

Primary seminoma of the prostate (PSP) is a rare type of extragonadal germ cell tumour that is easily misdiagnosed, owing to the lack of specific clinical features. It is therefore necessary for clinicians to work toward improving the accuracy of PSP diagnosis. A 59-year-old male patient presenting with acute urinary retention was admitted to a local hospital. A misdiagnosis of benign prostatic hyperplasia led to an improper prostatectomy. Histopathology revealed PSP invading the bladder neck and bilateral seminal vesicles. Further radiotherapy treatment for the local lesion was performed, and the patient had a disease-free survival period of 96 mo. This case was analysed along with 13 other cases of PSP identified from the literature. Only four of the cases (28.6%) were initially confirmed by prostate biopsy. In these cases, imaging examinations showed an enlarged prostate (range 6-11 cm) involving the bladder neck (13/14). Of the 14 total cases, 11 (78.6%) presented typical pure seminoma cell features, staining strongly positive for placental alkaline phosphatase, CD117, and OCT4. The median age at diagnosis was 51 (range 27-59) years, and patients had a median progression-free survival time of 48 (range 6-156) mo after treatment by cisplatin-based chemotherapy combined with surgery or radiotherapy. The remaining three were cases of mixed embryonal tumours with focal seminoma, which had clinical features similar to those of pure PSP, in addition that they also had elevated serum alpha-fetoprotein, beta-human chorionic gonadotropin, and lactose dehydrogenase. PSP should be considered in patients younger than 60 years with an enlarged prostate invading the bladder neck. Further prostate biopsies may aid in proper PSP diagnosis. Cisplatin-based chemotherapy is still the main primary therapy for PSP.

MP50-08 POST-CHEMOTHERAPY RETROPERITONEAL LYMPH NODE DISSECTION (PC-RPLND) FOR SEMINOMA: IS SURGERY EFFECTIVE?

You have accessJournal of UrologyCME1 Apr 2023MP50-08 POST-CHEMOTHERAPY RETROPERITONEAL LYMPH NODE DISSECTION (PC-RPLND) FOR SEMINOMA: IS SURGERY EFFECTIVE? Isamu Tachibana, Andre Alabd, Rumeal Whaley, Jacob Mcfadden, Alex Piroozi, Sean Kern, Nabil Adra, Richard Foster, Lawrence Einhorn, Clint Cary, and Timothy Masterson Isamu TachibanaIsamu Tachibana More articles by this author , Andre AlabdAndre Alabd More articles by this author , Rumeal WhaleyRumeal Whaley More articles by this author , Jacob McfaddenJacob Mcfadden More articles by this author , Alex PirooziAlex Piroozi More articles by this author , Sean KernSean Kern More articles by this author , Nabil AdraNabil Adra More articles by this author , Richard FosterRichard Foster More articles by this author , Lawrence EinhornLawrence Einhorn More articles by this author , Clint CaryClint Cary More articles by this author , and Timothy MastersonTimothy Masterson More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003298.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Patients with relapsed seminoma after first-line chemotherapy can be treated with salvage chemotherapy or post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND). Based on prior reported experience, surgical management can have worse efficacy and increased morbidity compared to non-seminomatous germ cell tumor. Our aim was to characterize the surgical efficacy and difficulty in a specific cohort of patients with definite progression but minimal disease burden. METHODS: The Indiana University testis cancer database was queried to identify men who underwent PC-RPLND for seminoma between January 2011 to December 2021. Included patients only underwent first-line chemotherapy and could not have any evidence of non-seminomatous elements on orchiectomy or have elevated serum alpha-fetoprotein (AFP). All patient demonstrated high suspicion of retroperitoneal disease prior to PC-RPLND was based on increasing size of tumor on standard CT imaging, progression of FDG avidity on PET imaging, or elevated tumor markers. RESULTS: We identified 889 patients that underwent PC-RPLND, of which only 14 patients were operated on for seminoma. One patient was excluded for lack of meaningful follow-up. Out of 13 patients, only 3 patients were disease free with surgery and did not have to undergo salvage chemotherapy. Median follow up time was 29.9 months (IQR: 22.6-53.7). Two patients died due to testicular cancer. The remaining 8 patients were treated successfully with salvage chemotherapy. For additional procedures, 4 patients required a nephrectomy, 1 patient required an aortic graft, 2 patients required a partial ureterectomy, and 3 patients required partial or complete caval resection CONCLUSIONS: The decision between salvage chemotherapy and PC-RPLND as second-line therapy can be challenging. Salvage chemotherapy is effective but is associated with short and long-term morbidity. Surgical efficacy in this setting seems to be limited, but careful selection of patients may lead to surgical success without life threatening morbidity or adjunctive procedures that may compromise the ability to receive salvage chemotherapy. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e687 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Isamu Tachibana More articles by this author Andre Alabd More articles by this author Rumeal Whaley More articles by this author Jacob Mcfadden More articles by this author Alex Piroozi More articles by this author Sean Kern More articles by this author Nabil Adra More articles by this author Richard Foster More articles by this author Lawrence Einhorn More articles by this author Clint Cary More articles by this author Timothy Masterson More articles by this author Expand All Advertisement PDF downloadLoading ...

Correlation between elevated maternal serum alpha-fetoprotein and ischemic placental disease: a retrospective cohort study

ABSTRACT Background To evaluate the correlation between elevated maternal serum alpha-fetoprotein (AFP) in the second trimester and ischemic placental disease (IPD). Methods A retrospective cohort study was conducted to analyze the data of 22,574 pregnant women who delivered in the Department of Obstetrics at Hangzhou Women’s Hospital from 2018 to 2020, and were screened for maternal serum AFP and free beta-human chorionic gonadotropin (free β-hCG) in the second trimester. The pregnant women were divided into two groups: elevated maternal serum AFP group (n = 334, 1.48%); and normal group (n = 22,240, 98.52%). Mann-Whitney U-test or Chi-square test was used for continuous or categorical data. Modified Poisson regression analysis was used to calculate the relative risk (RR) and 95% confidence interval (CI) of the two groups. Results The AFP MoM and free β-hCG MoM in the elevated maternal serum AFP group were higher than the normal group (2.25 vs. 0.98, 1.38 vs. 1.04) and the differences were all statistically significant (all P < .001). Placenta previa, hepatitis B virus carrying status of pregnant women, premature rupture of membranes (PROM), advanced maternal age (≥35 years), increased free β-hCG MoM, female infants, and low birth weight (RR: 2.722, 2.247, 1.769, 1.766, 1.272, 0.624, 2.554 respectively) were the risk factors for adverse maternal pregnancy outcomes in the elevated maternal serum AFP group. Conclusions Maternal serum AFP levels during the second trimester can monitor IPD, such as IUGR, PROM, and placenta previa. Maternal women with high serum AFP levels are more likely to deliver male fetuses and low birth weight infants. Finally, the maternal age (≥35 years) and hepatitis B carriers also increased maternal serum AFP significantly.

Stationary Trend in Elevated Serum Alpha-Fetoprotein Level in Hepatocellular Carcinoma Patients

A recent study from the US showed a decreasing trend in the elevated serum alpha-fetoprotein (AFP) level (i.e., ≥20 ng/mL) in hepatocellular carcinoma (HCC) patients at the time of diagnosis. Furthermore, advanced tumor stage and severe underlying liver disease were associated with elevated AFP levels. We aimed to evaluate this issue in an area endemic for hepatitis B virus (HBV). Between 2011 and 2020, 4031 patients were newly diagnosed with HCC at our institution. After excluding 54 patients with unknown AFP data, the remaining 3977 patients were enrolled in this study. Elevated AFP level was defined as ≥20 ng/mL. Overall, 51.2% of HCC patients had elevated AFP levels; this proportion remained stationary between 2011 and 2020 (51.8% vs. 51.1%). Multivariate analysis showed that female gender (odds ratio (OR) = 1.462; p < 0.001), tumor size per 10 mm increase (OR = 1.155; p < 0.001), multiple tumors (OR = 1.406; p < 0.001), Barcelona Clinic Liver Cancer stages B-D (OR = 1.247; p = 0.019), cirrhosis (OR = 1.288; p = 0.02), total bilirubin > 1.4 mg/dL (OR = 1.218; p = 0.030), and HBV- or hepatitis C virus (HCV)-positive status (OR = 1.720; p < 0.001) were associated with elevated AFP levels. In conclusion, a stationary trend in elevated serum AFP level in HCC patients has been noted in the past 10 years. Advanced tumor stage, severe underlying liver disease, viral etiology, and female gender are associated with elevated AFP levels in HCC patients.

Timing of maternal serum alpha fetoprotein testing in pregnancy and association with adverse perinatal outcomes

Elevated maternal serum alpha-fetoprotein (MS-AFP ≥2.5MoM) is associated with adverse pregnancy outcomes (APO); however, there is limited data on the association of gestational age [GA] timing of the MS-AFP assay and APO. We sought to determine if there was an optimal GA for the MS-AFP assay in the second trimester that best predicts APO.

Biochemical and ultrasonographic markers in fetal surveillance

Introduction/Objective. Fetal growth restriction (FGR) is associated with increased fetal and neonatal mortality and morbidity. The study objective was to investigate the correlation of maternal blood biochemical markers routinely determined in the first and second trimester screening and ultrasound fetal surveillance parameters in the prediction of fetal growth and condition in singleton pregnancies. Methods. In the first trimester we measured serum levels of beta subunit of human chorionic gonadotropin (?HCG) and pregnancy-associated plasma protein A (PAPP-A). In the second trimester we measured values of chorionic gonadotropin (HCG), alpha fetoprotein (AFP), unconjugated estriol (E3) and inhibin A, also examined ultrasonographic biometric fetal parameters, amniotic fluid index (AFI) and Doppler resistance indexes. FGR was defined as ultrasonographically determined fetal weight and growth parameters below the 10th percentile for the gestational age. Obtained biochemical and ultrasonographic parameters were correlated. Results. Study included 104 singleton pregnancies. ?HCG in the first trimester correlated negatively with fetal growth in the second and third trimester, and the second trimester AFI. Increased PAPP-A correlated positively with elevated resistance index in medial cerebral artery, lower biophysical profile scores, and intermediate type of non-stress test. Lower values of E3 were associated with FGR. Elevated serum AFP levels were linked to oligoamnion in the third trimester. There was no correlation of inhibin A levels with fetal condition. Conclusion. First and second trimester biochemical markers of pregnancy (?HCG, PAPP-A, HCG, AFP and E3) in combination with ultrasonographic biophysical parameters of fetus have predictive value for fetal growth and development.

Pure post-pubertal yolk sac tumor of the testis: An extremely rare and aggressive entity

ContextPure post-pubertal yolk sac tumors (YSTs) are an extremely rare type of malignant germ cell tumor (GCT) that account for <1 % of testicular GCTs. Clinically, they are more aggressive compared to the more common pre-pubertal counterpart. The aim of this study is to analyze the clinical presentation, ancillary tests and clinical outcomes in addition to presenting a spectrum of histomorphological features, in a case series along with a literature review. DesignA retrospective review of 4 cases of pure post-pubertal YST of the testis was performed.Data collected for each patient included demographics, clinical presentation, serum markers, radiology and pathologic findings, treatment, and clinical outcomes. ResultsAll patients presented with a testicular mass with or without associated pain and elevated serum alpha-feto protein. Mean age at presentation was 36 years (range 25–68 years). Two patients presented with metastatic disease at the time of diagnosis. Histologic patterns and features are as follows: germ cell neoplasia in-situ (n = 4), reticular/microcystic, solid, glandular, papillary, endometrioid, cystic, necrosis and angiolymphatic invasion (n = 3). Fluorescent in-situ hybridization test performed on Case 2, showed presence of isochromosome 12p and next generation sequencing showed gains of 12p. Case 1, 2 and 4 showed metastatic disease on follow-up. ConclusionsDiagnosis of pure post-pubertal YST remains challenging due to the variety of morphologic patterns often present in these tumors. Extensive sampling along with use of ancillary tests is the key for diagnosis. In this study, 75 % of cases had metastatic disease at or after the diagnosis confirming the aggressive nature of this rare entity.

Glycosylation Profiling of the Neoplastic Biomarker Alpha Fetoprotein through Intact Mass Protein Analysis.

Elevated serum alpha-fetoprotein (AFP) can be observed in liver cirrhosis and hepatocellular carcinoma (HCC). The glycosylation patterns of AFP have been shown to differentiate these conditions, with AFP glycoforms with core fucosylation (AFP-L3) serving as a malignancy risk predictor for HCC. We have developed a method to detect endogenously present AFP proteoforms and to quantify the relative abundance of AFP-L3 glycoforms (AFP-L3%) in serum samples. This method consists of immune enrichment of endogenous AFP, followed by liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) intact protein analysis of AFP. Data are available via ProteomeXchange with identifier PXD038606. Based on the AFP profiles in authentic patient serum samples, we have identified that the frequently observed AFP glycoforms without core fucosylation (AFP-L1) are G2S2 and G2S1, and common AFP-L3 glycoforms are G2FS1 and G2FS2. The intensities of glycoforms in the deconvoluted spectrum are used to quantify AFP-L3% in each sample. The method evaluation included reproducibility, specificity, dilution integrity, and comparison of AFP-L3% with a lectin-binding gel shift electrophoresis (GSE) assay. The AFP-L1 and AFP-L3 proteoforms were reproducibly identified in multiple patient serum samples, resulting in reproducible AFP-L3% quantification. There was considerable agreement between the developed LC-HRMS and commercial GSE methods when quantifying AFP-L3% (Pearson r = 0.63) with a proportional bias.

Clinical Importance Of Elevated Levels Of Alpha-fetoprotein In Early Diagnosis Of Non-alcoholic Fatty Liver Disease In Native Population Of Southern Punjab, Pakistan

Objective: To evaluate the relationship between elevated levels of AFP (alpha-fetoprotein) and NAFLD (Non-Alcoholic Fatty Liver Disease) in the native population of Southern Punjab, Pakistan.Place of Study: Ibn-e-Siena Hospital &amp; research institute, MultanStudy Design: Descriptive Cross-Sectional StudyDuration of Study: December 2021 to July 2022Methodology: 800 patient samples were included in this study. All subjects showed elevated serum Alpha-fetoprotein (AFP) levels. To measure AFP sandwich immune detection FIA (fluorescence immunoassay) technique was used. The tests were performed on chroma for the quantitative analysis. A value above the cut-off value was 10.9 ng/mL was further investigated for the clinical history and full clinical record of anthropometric and biochemical tests.Results: Fatty Liver Disease (FLD) was diagnosed in 19.5% of subjects. Most of the cases were of Non-Alcoholic Fatty Liver Disease (NAFLD) with 98.71%. More males were affected with NAFLD with 11.5%. NAFLD was more observed in &gt;50years aged patients at 12.62% than in patients &lt; 50 years at 6.625%. There was a non-significant correlation between the residence type of the patient with the disease incidence. There was a significant relationship between NAFLD and Blood Pressure, Fasting Blood Sugar, Triglycerides, Total Cholesterol, HBA1C, and High-Density Lipids (HDL) with a p-value &lt;0.01.Conclusion: It is concluded that elevated levels of alpha-fetoproteins are clinically important and can be useful tools for the early diagnosis of fatty liver disease, especially NAFLD.