Serum Alpha-fetoprotein Levels Research Articles

Peripheral immune signatures associated with the risk of hepatocarcinogenesis in cirrhotic Egyptian HCV patients before and after treatment with direct-acting antivirals.

Although direct-acting antivirals (DAAs) have revolutionized the management of chronic HCV, the debatable association with hepatocellular carcinoma (HCC) occurrence/recurrence has raised major concerns about their long-term use, especially in cirrhotic cases. The role of epithelial tight junction proteins (TJPs) in hepatocarcinogenesis has been highlighted; however, the association of their expression in peripheral blood mononuclear cells (PBMCs) with HCC has rarely been reported. This study aimed to explore the role of peripheral claudin (Cldn)1 in liver pathogenesis and its crosstalk with soluble immune mediators in HCC prognosis. The study population included six independent subgroups: healthy controls, cirrhotic/non-cirrhotic treatment-naïve HCV patients, DAA-SVR patients, and anticancer treatment-naïve de novo HCC patients. The laboratory tests included serum levels of alpha-fetoprotein (AFP), albumin, liver transaminases, total bilirubin, and CBC profiling. The serum levels of soluble cluster of differentiation (sCD)163, IL-10, and IL-12 were estimated by corresponding ELISA kits, whereas the levels of Cldn1 and transforming growth factor (TGF)-β in PBMCs were quantified using quantitative PCR (qPCR). Serum sCD163, IL-10, and IL-12 levels were significantly higher in the HCC patient group than in the control and non-malignant patient groups (P < 0.0001). No significant difference was detected in the serum levels of the three markers between cirrhotic and non-cirrhotic patients, whereas their levels were significantly different between cirrhotic and non-cirrhotic patients (P < 0.0001). Similarly, the transcriptional levels of peripheral Cldn1 and TGF-β were significantly higher in patients with HCC and non-malignant cirrhosis than in patients without cirrhosis (P = 0.0185-<0.0001 and 0.0089-<0.0001, respectively). Logistic regression analysis revealed a significant association between all the abovementioned markers and HCC (P = 0.0303 to < 0.0001), which was further confirmed by the results of receiver operating characteristic (ROC) analysis, which revealed an area under the curve (AUC) value ranging from 0.883 to 0.996. The calculated cutoff values demonstrated remarkable prognostic capacity, with ranges of 88-99.41% and 82.14-97.92% and positive/negative predictive values ranging from 84.62 to 98.3% and 92-98%, respectively. The proposed HCC predictors are novel non-invasive HCC biomarkers that maintain their predictive power under different pathological conditions and circumvent the drawbacks of conventional prognostic markers in patients with mild cirrhosis and/or normal AFP, albumin, and/or platelet counts.

CK19 is associated with poor survival in patients with dual-phenotype hepatocellular carcinoma

Objective: To study the role of CK19 in the survival of patients diagnosed with DPHCC in Fujian, China, which has a high incidence of hepatocellular carcinoma (HCC). Methods: Patients with DPHCC (n=84) who had undergone surgical interventions at the 900th Hospital of Joint Logistic Support Force between 2013 and 2019 were retrospectively analyzed using the log-rank test and Kaplan-Meier method. Univariate and multivariate Cox model analyses were also conducted to further understand the correlation between CK19 and patient survival. Results: (1)Tumor size, differentiation, peripheral hepatic fibrosis, liver capsule invasion, microvascular invasion (MVI) and serum CA-199 level showed a correlation with CK19, as per the outcomes of Chi-squared tests. (2)According to the univariate analysis, the expression of CK19, MVI, the number of tumor lesions, necrosis, differentiation, peripheral hepatic fibrosis, and serum levels of both alpha-fetoprotein (AFP) and CA-199 showed a strong correlation with overall survival. (3)Necrosis and serum AFP levels were strongly related to an increased risk of death, according to the multivariate analysis. Conclusions: The expression of CK19 may correlate with the survival of patients with DPHCC and could potentially serve as a prognostic predictor of survival.

Preoperative serum glutathione reductase activity and alpha-fetoprotein level are associated with early postoperative recurrence of hepatocellular carcinoma

Abstract Objectives The aim of this study is to investigate the correlation between preoperative serum glutathione reductase (GR) activity, alpha-fetoprotein (AFP) level, and early postoperative recurrence in patients diagnosed with hepatocellular carcinoma (HCC). Methods The data of 91 patients with HCC who underwent hepatectomy at Jinhua Hospital from January 2020 to December 2021 were retrospectively analyzed. A comparison of clinical characteristics between Non-Recurrent group and Recurrence group was conducted, and the association between GR activity, AFP levels, and early postoperative recurrence in HCC was investigated. Results Recurrence group (n=50) had a significantly higher AFP levels (median: 226.7 vs. 99.7 μg/L, p&lt;0.001) and significantly lower GR activity (median: 55.0 vs. 68.0 U/L, p&lt;0.0001) compared with Non-Recurrent group (n=41). The GR activity was negatively correlated with the AFP level (r=−0.4275, p&lt;0.01). Low GR activity (OR=0.948; 95 % CI: 0.910–0.988; p=0.011) and high AFP levels (OR=1.003; 95 % CI: 1.000–1.006; p=0.036) independently contribute to an increased risk of early postoperative recurrence in HCC patients. The area under receiver operating characteristic curve of GR activity and AFP level for predicting early postoperative recurrence of HCC was 0.790 and 0.708, respectively. Patients with GR &gt;60U/L had a higher early postoperative non-recurrence rate than patients with GR ≤60U/L (71.4 % [30/42] vs. 22.4 % [11/49]; HR=4.026; 95 % CI: 2.254–7.188; p&lt;0.01); Patients with AFP ≤100 μg/L had a higher early postoperative non-recurrence rate than patients with AFP &gt;100 μg/L (65.6 % [21/32] vs. 33.9 % [20/59]; HR=2.490; 95 % CI: 1.397–4.438; p&lt;0.01). Conclusions The preoperative serum GR activity and AFP level hold significant predictive value for early postoperative recurrence in HCC patients.

Clinical Rarity Unveiled: Adenocarcinoma with Enteroblastic Differentiation at the Gastroesophageal Junction in a Young Patient - A Diagnostic Challenge Shaping Therapeutic Paradigms

Abstract Introduction/Objective This report details a case of a young patient diagnosed with an adenocarcinoma with enteroblastic differentiation at the gastroesophageal junction (GEJ), characterized by Alpha-Fetoprotein (AFP) production. This manifestation previously rarely documented in young patients (25-44 years old), underscores the critical role of precise pathology diagnosis in guiding effective patient management. Methods/Case Report The patient’s clinical presentation included chest pain, abdominal pain, and weight loss, prompting imaging studies revealing liver masses, lesions in the lung and adrenal gland, and retroperitoneal adenopathy with unremarkable testicular findings. Rapidly progressing dysphagia led to a liver biopsy and esophagogastroduodenoscopy (EGD), where a fungating mass extending from the distal esophagus into the stomach was biopsied. A subsequent serologic test unveiled an elevated serum AFP level (approximally 31, 000 ng/ml). Results (if a Case Study enter NA) Histological examination revealed similarities between the liver and distal esophageal tumors, characterized by moderately differentiated carcinoma with solid and glandular growth patterns. The tumor cells, resembling fetal gut epithelium, exhibited positive immunostaining for SALL4, AFP, CK8-18, CK19, and CDX2. A diagnosis of adenocarcinoma with enteroblastic differentiation at the GEJ was determined, correlating with clinical and radiological assessments. Despite initiating one cycle of gastrointestinal related chemotherapy, the patient succumbed to tumor lysis syndrome within a month of diagnosis. Conclusion This case highlights the critical need for a comprehensive differential diagnosis when encountering young patients with AFP-producing malignancies. Although metastatic non-seminomatous germ cell cancer is a primary consideration, upper gastrointestinal adenocarcinoma with unique characteristics, as demonstrated in this case, requires distinct therapeutic approaches, emphasizing the importance of accurate and timely diagnosis.

Assessment of combined serum sST2 and AFP levels in the diagnosis of hepatocellular carcinoma

Background Hepatocellular carcinoma (HCC) is a common malignant tumor with high morbidity and mortality. Alpha-fetoprotein (AFP) is the most widely used diagnostic serum biomarker, but it still has limited accuracy in detecting HCC, suggesting the necessity of seeking more ideal biomarkers with high sensitivity and specificity. Soluble growth stimulation gene 2 (sST2) form of growth stimulating expression gene 2 (ST2), is expressed in various organs and can bind competitively to interleukin 33 (IL-33). Whether sST2 can serve as a serum biomarker for HCC is largely unknown. Objective To investigate the value of sST2 as a serum diagnostic marker for HCC. Methods This study included 93 newly diagnosed HCC patients (HCC group), 90 chronic hepatitis B patients (CHB group), and 90 healthy individuals (HCs group). Spearman correlation analysis was used to explore the relationships between sST2 and the experimental indicators in HCC group. The receiver operating characteristic (ROC) curve evaluated the efficacy of sST2 alone or in combination with AFP in the diagnosis of HCC. Result The median level of sST2 was significantly higher in HCC group (24.00 [15.20-49.90] ng/mL) compared to CHB group (19.55 [15.23-24.95] ng/mL) and HCs group (7.65 [5.20-10.53] ng/mL). No significant correlations were found between sST2 and other clinical indicators in HCC group. The Area Under Curve (AUC) of ROC curve to distinguish HCC patients from healthy controls and CHB group was 0.861 (sensitivity 82.80%, specificity 72.10%) and 0.709 (sensitivity 80.60%, specificity 52.50%), respectively. When combined with AFP, the AUC increased to 0.963 (sensitivity 82.90%, specificity 94.20%), and 0.895 (sensitivity 72.0%, specificity 100%), respectively. Conclusions The serum level of sST2 increased in HCC and its diagnostic performance is comparable to that of AFP, supporting its potential as a promising biomarker for detection of HCC. The combined use of sST2 and AFP enhances diagnostic efficacy for HCC.

The Association and diagnostic value between Maternal Serum Placental Markers and Placenta Previa

ObjectiveThis study aims to evaluate the correlation and diagnostic value of maternal serum placental markers: pregnancy-associated plasma protein-A (PAPP-A), free beta human chorionic gonadotropin (free β-hCG), and alpha fetoprotein (AFP) in relation to placenta previa. MethodsA retrospective case-control study was conducted to gather data on 137 pregnant women who were hospitalized for delivery at Hangzhou Obstetrics and Gynecology Hospital. These women participated in the late stage of early and mid-term maternal serum prenatal screening between January 2018 and December 2020. Of the 137 women, 45 were diagnosed with placenta previa, while 92 were selected at random as the control group, in a ratio of 1:2. Independent samples t-test or Mann-Whitney U test were utilized to compare the quantitative data of the two groups, and the Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of maternal serum placental marker levels for placenta previa. ResultsThe levels of first trimester and second trimester free beta subunit of human chorionic gonadotropin (FT-Free β-hCG; ST-Free β-hCG) in the placenta previa group were higher than those in the normal group [1.38 (0.55-6.03) MoM vs.1.08 (0.32-4.00) MoM, 1.38 (0.39-4.10) MoM vs.1.01 (0.29-4.12) MoM], and the differences between the groups were statistically significant (Z = 2.830, Z = 2.846, both P < 0.05). The AFP level was higher than the normal group [1.13 (0.65-2.15) MoM vs. 0.94 (0.51-2.02) MoM], and the difference was statistically significant (Z = 2.551, P < 0.05). There was no significant difference in PAPP-A between the placenta previa group and the normal group (Z = 1.396, P > 0.05). The ROC curve analysis results showed that the AUCs of FT-Free β-hCG and ST-Free β-hCG for placenta previa were 0.649 (95% CI: 0.551-0.747, P=0.005), 0.634 (95% CI: 0.539-0.730, P=0.011), and 0.650 (95% CI: 0.554-0.746, P=0.004). Using PPV, NPV, FPR, FNR, +LR, and -LR as evaluation indicators for the 5 models, the results showed that FT-Free β-hCG was the best performer in terms of PPV, FPR, and +LR, with values of 0.725, 0.600, and 2.632, respectively. The three-indicator combined detection model (AFP + ST-Free β-hCG + FT-Free β-hCG) had the best performance in terms of NPV and -LR, with values of 0.770 and 0.298, respectively. ConclusionThe elevated maternal serum levels of Free β-hCG and AFP may be associated with placenta previa. The combined detection of maternal serum markers in the early and mid-trimesters has better diagnostic value for predicting placenta previa than individual detection.

Serum thymosin beta 10 level as a potential prognosis prediction of hepatocellular carcinoma and hepatic diseases

Thymosin Beta 10 (TMSB10) is a thymosin family member that has been identified as being overexpressed in a wide variety of human cancers. This study aimed to determine the expression level of TMSB10 in sera of patients with hepatocellular carcinoma (HCC) and liver cirrhosis. And to reveal the association between TMSB10 and different stages in patients with HCC. We also wanted to know how TMSB10 is predictive in HCC patients and its relation to the Barcelona Clinic's staging system. The study included 41 HCC patients, 15 liver cirrhosis patients, and 15 normal control subjects. The enzyme-linked immunosorbent assay was used to determine serum levels of TMSB10 and alpha-fetoprotein (AFP) in serum of normal control individuals and patients with liver cirrhosis and different stages of HCC, and to evaluate the relationship of AFP with TMSB10. The TMSB10 levels in patients with HCC were statistically different than in the control group and in the different stages of HCC. We found a statistically significant difference in the distribution of TMSB10 between the three study groups (p&lt; 0.001). There was an association between TMSB10 concentration and AFP. The level of TMSB10 in the serum of the HCC subgroups was then analyzed. The TMSB10 level increased with the advance of HCC stages. The TMSB10 level in HCC patients did not correlate with levels of liver function tests including aminotransferase, aspartate aminotransferase, albumin, prothrombin, bilirubin, or alkaline phosphatase. In conclusion, serum TMSB10 levels can be used as a potential prognostic marker for clinical stages of HCC.

Prognosis of Patients with Hepatocellular Carcinoma Treated with TACE: A New Score Combining Alpha-Fetoprotein and Des-γ-Carboxy Prothrombin.

Hepatocellular carcinoma (HCC) represents a significant global health problem, requiring precise prognostic tools for optimal treatment stratification. This study aimed to develop a new risk prediction score, called AD score, based on the serum markers alpha-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP), to offer an objective and accurate preoperative assessment of HCC in patients undergoing transarterial chemoembolization (TACE). This was a retrospective study that included 295HCC patients who were subjected to TACE (training set, n=147; testing set, n=148). Serum AFP and DCP levels were log-transformed to construct the AD score. Multivariate Cox regression analysis on cirrhosis subgroups validated the objectivity of the model. Performance comparison of established models (Child Pugh, BCLC, ALBI, Up-to-seven, Six-and-twelve, Four and seven, HAP score, mHAP-II, FAIL-T score), was assessed through time-dependent receiver operating characteristic (ROC) curves and risk stratification. The AD score, incorporating lgAFP and lgDCP, demonstrated superior predictive accuracy than the existing models. Time-dependent ROC curve revealed the consistent superiority of the AD score over a 5-year period. The risk stratification into low, intermediate, and high group based on the AD score showed a significant survival difference in both training and testing set. For HCC patients undergoing TACE, the AD score serves as an objective and straightforward prognostic tool, enhancing predictive accuracy and showcasing its clinical utility. It demonstrates potential significance as a crucial addition to preoperative risk assessment for TACE.

Carbenoxolone upregulates TRAIL\\TRAILR2 expression and enhances the anti-neoplastic effect of doxorubicin in experimentally induced hepatocellular carcinoma in rats

AimsThis study investigates the in vivo anticancer activity of carbenoxolone (CBX) and its role in fighting hepatocellular carcinoma (HCC) progression and alleviating resistance against doxorubicin (DOX). Moreover, the molecular mechanism of action of CBX is explored. MethodsHCC was induced in Sprague Dawley rats via biweekly administration of thioacetamide (TAA) (200 mg/kg) intraperitoneally (i.p.) for 16 weeks after administering a single dose of diethylnitrosamine (DEN) (200 mg/kg, i.p.). A prophylactic model was established by treating rats with i.p. CBX (20 mg/kg/day) for 4 weeks starting on week 13 post-TAA injection. A therapeutic model was established by treating rats with CBX, DOX, or their combination for 7 weeks following 16 weeks of TAA administration. Serum Alpha-fetoprotein (AFP) and biochemical markers of hepatic functions were assessed. Histopathological examinations of hepatic tissues were performed. Immunohistochemical and qRT-PCR analyses were applied to assess the differential expressions of TRAIL/TRAILR2, Bcl-2, TGF-β1, and caspases 3,8, and 9. ResultsCBX markedly improved hepatic functions, reduced serum AFP levels, and alleviated TAA-induced hepatic histopathological alterations. CBX triggered apoptosis as evident by upregulating apoptotic markers: TRAIL/TRAILR2, caspases 3,8, and 9, and downregulating the antiapoptotic protein Bcl-2. CBX downregulated TGF-β1. Interestingly, CBX/DOX combination mitigated hepatic damage and induced apoptosis in a way that surpassed DOX-only treatment. ConclusionThe current study proposes that CBX is a promising anti-tumor compound, which can work effectively under prophylactic and therapeutic modes. Interestingly, CBX enhanced the anti-tumor effect of DOX. CBX exerted these effects via, in part, stimulating TRAIL-induced apoptosis along with attenuating fibrosis.

Unusual presentation of fetal ventriculomegaly: a case report

Fetal ventriculomegaly (VM) is a relatively common finding during prenatal examinations and occurs in approximately 0.2% of live births. Although there are various causes, obstructive VM due to cerebellar hemorrhage is exceedingly rare. A 33-year-old primigravida presented at 32 weeks of gestation with VM. At 36 weeks of age, a male infant was delivered via cesarean section. Postnatal imaging revealed severe bilateral hydrocephalus and space-occupying lesions in the cerebellum. Initial concerns about a potential germ cell tumor were raised due to elevated alpha-fetoprotein levels in both serum and cerebrospinal fluid. An external ventricular drain was placed to manage obstructive hydrocephalus. When the baby was 1 month old, surgical exploration revealed an old blood clot without any evidence of a tumor. Histopathological examination confirmed an old hemorrhage with no malignant cells. This case underscores the diagnostic challenges in distinguishing between hemorrhages and tumors in the context of fetal VM. Despite elevated alpha-fetoprotein levels, no tumors were identified. The underlying cause of cerebellar hemorrhage remains unclear despite extensive workups. Nevertheless, this case report details multifaceted diagnostic efforts to address the rare occurrence of cerebellar hemorrhage related to fetal VM, leading to a comprehensive case presentation.

Normal Glypican-3 Serum Levels Do Not Eliminate the Risk of Hepatocellular Carcinoma

Introduction. Hepatocellular carcinoma (HCC) is a malignancy that primarily affects patients with liver cirrhosis. Early diagnosis is crucial for improving patient outcomes. The study aimed to investigate the potential role of glypican-3 (GPC3) serum levels, both alone and in combination with alpha-fetoprotein (AFP) and gamma-glutamyl transpeptidase (GGT) serum levels, as diagnostic biomarkers for HCC. Methods. The study included 53 patients with liver cirrhosis and confirmed HCC, who were admitted to the Department of Infectious Diseases, Tropical Diseases and Hepatology at the Medical University of Warsaw, Warsaw, Poland, underwent physical examination and laboratory testing and were compared with 29 healthy volunteers. GPC3, along with demographic data, Child-Pugh and Model for End-Stage Liver Disease (MELD) scores, AFP, and GGT levels, was analyzed in relation to HCC diagnosis. The sensitivity and specificity of GPC3 alone and in combination with AFP and GGT were evaluated for diagnosing HCC. Results. The difference in serum GPC3 levels between patients with HCC and the control group was statistically insignificant (p=0.765). However, a significant correlation was found between GPC3 and AFP serum levels in patients with HCC (p=0.009). Additionally, a correlation was observed between higher GPC3 serum levels within the normal range and the occurrence of HCC. The sensitivity for GPC3 levels greater than 75 ng/ml for detecting HCC was 93.1%, while the specificity was 49.1%. The utility of GPC3, when combined with AFP and GGT, was inconsistent across different thresholds in detecting HCC. Conclusions. The serum levels of GPC3 do not provide satisfactory effectiveness in detecting HCC, and the disease can occur in patients with GPC3 serum concentrations within the normal range. In patients with liver cirrhosis, serum GPC3 levels above 75.00 ng/ml may suggest an increased risk of HCC development. Additionally, the combination of AFP, GPC3, and GGT demonstrates some utility in detecting HCC; however, it shows no superiority over GPC3 alone.

Clinical Significance of Biliary Invasion at Diagnosis in Barcelona Clinic Liver Cancer Stage B–C Hepatocellular Carcinoma: A Nationwide Cohort Analysis in South Korea

Introduction: Evidence of biliary invasion as a prognostic factor in patients with hepatocellular carcinoma (HCC) is unclear. We aimed to verify the significance of clinically diagnosed biliary involvement in patients with Barcelona Clinic Liver Cancer stage B–C (BCLC B–C) HCC. Methods: The Korean Liver Cancer Study Group randomly extracted data of patients with HCC enrolled in the Korean Central Cancer Registry between 2011 and 2016 from approximately 50 hospitals nationwide. After excluding records without information regarding serum bilirubin level, alpha-fetoprotein (AFP) level, and Child-Pugh class, a pre-propensity score matching cohort comprising 4,077 patients was included. Considering age, sex, body mass index, viral cause, serum bilirubin level, AFP, Child-Pugh class, tumor size, multiplicity, portal invasion, and extrahepatic metastasis, patients with and without bile duct invasion at initial imaging diagnosis were matched at a ratio of 1:2 from the pre-propensity score matching cohort to form a matched cohort (propensity score matching cohort). Results: The pre-propensity score matching cohort included 4,077 patients with BCLC B–C and 165 (4.0%) with biliary invasion at diagnosis. Regarding biliary invasion at diagnosis, 1- and 2-year overall survival (OS) rates were 41.2% and 29.1% (with invasion) and 54% and 40.9% (without invasion), respectively (p < 0.0001). Corresponding cancer-specific survival (CSS) rates at 1 and 2 years were 43.4% and 30.7% (with invasion) and 56.6% and 44% (without invasion), respectively (p < 0.0001). Although biliary invasion was a significant factor affecting overall and CSS rates in a univariate analysis, it was not statistically significant in multivariate analyses for overall (p = 0.153) and cancer-specific (p = 0.198) survival rates. The propensity score matching cohort included 165 patients with biliary invasion at diagnosis and 330 without biliary invasion. In the propensity score matching cohort, biliary invasion at diagnosis was not a significant factor affecting overall (p = 0.603) or cancer-specific (p = 0.960) survival rates in the univariate analyses. One- and 2-year OS were 41.2% and 29.1% (with invasion) and 36.1% and 28.2% (without invasion), respectively. The corresponding CSS at one and 2 years were 43.4% and 30.7% (with invasion) and 39.8% and 31.4% (without invasion), respectively. Multivariate analyses revealed that AFP levels, Child-Pugh class, tumor singularity, tumor size, portal invasion, lymph node metastases, and distant metastases significantly affected both overall and CSS rates. Conclusion: Biliary invasion at diagnosis in patients with BCLC B–C does not affect overall or CSS rates; however, other prognostic factors associated with biliary invasion could have a greater impact.

Obsessive-compulsive disorder as a first manifestation of Ataxia with Oculomotor Apraxia type 2 due to a novel mutation of SETX gene.

Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive disorder presenting with cerebellar ataxia, sensory-motor axonal neuropathy, oculomotor apraxia, cerebellar atrophy and high alpha-fetoprotein (AFP) serum level. AOA2 is due to coding mutations of the SETX gene, mapped to chromosome 9q34. Seldom noncoding mutations affecting RNA processing have been reported too. To date psychiatric symptoms have never been reported in AOA2. A 19 years-old man came to our attention for progressive gait ataxia debuted five years earlier. His past medical history was unremarkable, while his parents were consanguineous. On neurological examination, he had bilateral horizontal gaze-evoked nystagmus with hypometric saccades and saccadic horizontal smooth pursuit, appendicular ataxia, limbs and trunk myoclonic involuntary movements with hands' dystonic postures and dance of the tendons. Psychological evaluation described intrusive and obsessive thoughts experienced by the patient, then diagnosed as obsessive-compulsive disorder. Blood tests detected an elevated AFP level. Brain MRI showed cerebellar atrophy, while electroneuromyography revealed an axonal sensory-motor polyneuropathy. In the suspicion of a pathology belonging to the autosomal recessive cerebellar ataxias (ARCA) spectrum disorder, a direct search of point mutations by whole-exome sequencing was performed revealing a novel biallelic variant in SETX gene (c.6208+2dupT), which was classified as likely pathogenic. The present case expands the genotypic and phenotypic spectrum of AOA2, reporting a novel likely pathogenic SETX mutation (c.6208+2dupT) and highlighting an early psychiatric involvement in AOA2, suggesting the need for psychiatric assessment in these neurologic patients.

Clinical outcome and prognostic factors for immunotherapy-based treatments in patients with platinum-refractory germ cell tumor

BackgroundGerm cell tumors (GCTs) are a heterogeneous group of cancers associated with a favorable prognosis when treated with platinum-based chemotherapy. However, patients with platinum-refractory GCTs face limited options and poorer outcomes, necessitating innovative treatment approaches. This study aims to evaluate the clinical outcomes and identify prognostic factors associated with immunotherapy-based treatments in this challenging patient population. MethodsThis retrospective analysis included individuals with platinum-refractory GCTs treated with immunotherapy between 2017 and 2023. Clinical outcomes, safety, and biomarkers were analyzed. ResultsThe study included 37 male patients with a median age of 26 years (range: 18–65). The overall response rate was 24.32 %, with a median progression-free survival (PFS) and overall survival (OS) of 4.67 months and 22.67 months, respectively. Patients with both serum levels of alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) below 100 (AFP & hCG < 100) demonstrated significantly better PFS and OS. Multivariate analysis indicated that lower serum tumor marker levels (AFP & hCG < 100) and treatment initiation at earlier lines were significantly associated with improved PFS. Notably, genomic analysis revealed that one patient with an MDM4 mutation experienced hyperprogression after the initiation of immunotherapy. Immune-related adverse events occurred in two patients: one developed grade 1 hyperthyroidism, and the other experienced grade 2 immune-related pneumonitis. ConclusionsImmunotherapy offers a promising treatment option for selected patients with platinum-refractory GCTs, demonstrating moderate response rates and potential survival benefits in a real-world scenario. Identifying specific prognostic factors may help tailor treatment strategies and enhance outcomes in this challenging patient cohort.

Primary yolk sac tumor of the endometrium combined with situs inversus totalis: a case report and literature review

BackgroundYolk sac tumor (YST) is a highly malignant germ cell tumor, a majority of which originate from the gonads and are extremely rare from endometrium.Case presentationHere we present a case of a 42-year-old woman suffered from primary pure yolk sac tumor of the endometrium complicated with situs inversus totalis. The patient presented at our hospital with irregular vaginal bleeding. Imageological examination showed a space-occupying lesion in the cervix and the serum Alpha-fetoprotein (AFP) level was significantly high (more than 1210ng/ml). Then she underwent total hysterectomy, bilateral salpingo-oophorectomy and pelvic lymph node dissection. The subsequent postoperative pathological diagnosis was yolk sac tumor arising from the endometrium. Next, the patient was treated with 6 cycles of chemotherapy with Pingyangmycin, etoposide and cisplatin regimen and was alive without evidence of recurrence or distant metastases for 13 months.ConclusionsThis rare disease needs to be differentiated from endometrial epithelial neoplasia and the significant increase in AFP is helpful for diagnosis. Combined with previous literature reports, comprehensive staging laparotomy or maximum cytoreductive surgery complemented by standard chemotherapy can usually achieve a good efficacy.

The Value of Human Epididymal Protein 4, Carcinoembryonic Antigen and Alpha-Fetoprotein in the Early Diagnosis of Cervical Cancer

Objectives: This research aimed to unveil the value of human epididymal protein 4 (HE4), carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) in the early diagnosis of cervical cancer. Design: This was a clinical study. Participants: Sixty patients with cervical cancer stage IA-IIA (early stage cervical cancer group), 60 patients with cervical intraepithelial neoplasia (CIN) (disease control group), and 60 healthy women who had passed the physical examination (healthy control group) were selected. Setting: The review was conducted in a Jiaxing First Hospital. Methods: Sixty patients with cervical cancer stage IA-IIA (early stage cervical cancer group), 60 patients with CIN (disease control group), and 60 healthy women who had passed the physical examination (healthy control group) were selected. The expression levels of serum HE4, CEA, and AFP in the three groups were detected, and the correlation between the levels of serum HE4, CEA, and AFP and the clinicopathological characteristics of patients with early stage cervical cancer were analyzed, and the receiver operating characteristic (ROC) curves were plotted to identify the value of the single and triple tests of serum HE4, CEA, and AFP for the early stage diagnosis of cervical cancer. Results: The levels of serum HE4, CEA, and AFP in the early stage cervical cancer group were higher than those in the disease control and the healthy control groups (p < 0.05). The levels of serum HE4, CEA, and AFP were related to the FIGO stage as well as the histological grading of patients with early stage cervical cancer (p < 0.05). The results of the ROC curves revealed that the AUC areas of HE4, CEA, and AFP for single as well as triple diagnosis of patients with early stage cervical cancer were 0.725, 0.679, 0.663, and 0.811, respectively, and the AUC of the three combined tests was markedly higher than that of HE4, CEA, AFP single test (p < 0.05). Limitations: There is a lack of larger sample sizes to test whether the combined HE4, CEA, and AFP detection has sufficient validity at the individual level and there are not enough serum samples in this study to perform circulating HPV-DNA detection and compare it with the levels of serum markers. Conclusion: The combination of HE4, CEA, and AFP has good clinical reference value analysis in the auxiliary diagnosis of early stage cervical cancer, and it is worthy of further validation and popularization.

Non-progressive hepatic tumor with high levels of serum alpha-fetoprotein in two infants with trisomy 18.

Non-progressive hepatic tumor with high levels of serum alpha-fetoprotein in two infants with trisomy 18.

Association of serum alpha-fetoprotein (AFP) with indirect prognosis in gastric cancer

Aims: Alpha-fetoprotein (AFP) is a glycoprotein secreted from the yolk sac and hepatocytes during fetal life. Elevated levels in adults are considered markers for yolk sac tumors, hepatocellular carcinoma and gastric cancer. There is still no consensus on the definition of AFP-secreting gastric cancers, but AFP-secreting gastric cancers have been reported to have a worse prognosis. In this study, AFP levels in gastric cancers with high AFP were compared with pathology results and evaluated in terms of indirect prognosis. Methods: Patients with gastric cancer operated in the General Surgery Clinic of Ankara Bilkent City Hospital between 2019 and 2023 were retrospectively screened. Among the screened patients, those whose information could not be reached and those with incomplete information were excluded and 126 patients were included in the study. Serum AFP levels of these patients were compared with pathology results, stages and tumor sizes. Results: The mean age of the patients in our study was 66±11 years, 42 (33.6%) were female and 84 (66.7%) were male. Of the 126 patients analyzed in the study, 107 (84.9%) were AFP-negative and 19 (15.1%) were AFP-positive. There was no significant difference in AFP levels between all patients in terms of liver metastasis, peritoneal metastasis, disease stage, perineural invasion and tumor location. However, serum AFP levels were significantly higher in patients with lymphovascular invasion and lung metastases (p=0.042; p=0.024). In the analysis for serum AFP level in the presence of lymphovascular invasion, ROC value was 2.35 ng/ml, sensitivity 58.2%, specificity 55.9%, area under the curve (AUC) 0.618, 95% confidence interval (95% CI) 0.512-0.723 and p=0.028. Conclusion: Lymphovascular invasion is a poor prognostic factor in gastric cancer. In this study, a significant correlation was found between serum AFP value and lymphovascular invasion. In gastric cancers without AFP secretion, a serum AFP value above 2.35 ng/ml may be indirectly associated with poor prognosis because it predicts lymphovascular invasion.

Leveraging SEER data through machine learning to predict distant lymph node metastasis and prognosticate outcomes in hepatocellular carcinoma patients.

This study aims to develop and validate machine learning-based diagnostic and prognostic models to predict the risk of distant lymph node metastases (DLNM) in patients with hepatocellular carcinoma (HCC) and to evaluate the prognosis for this cohort. Utilizing a retrospective design, this investigation leverages data extracted from the Surveillance, Epidemiology, and End Results (SEER) database, specifically the January 2024 subset, to conduct the analysis. The study cohort consists of 15,775 patients diagnosed with HCC as identified within the SEER database, spanning 2016 to 2020. In the construction of the diagnostic model, recursive feature elimination (RFE) is employed for variable selection, incorporating five critical predictors: age, tumor size, radiation therapy, T-stage, and serum alpha-fetoprotein (AFP) levels. These variables are the foundation for a stacking ensemble model, which is further elucidated through Shapley Additive Explanations (SHAP). Conversely, the prognostic model is crafted utilizing stepwise backward regression to select pertinent variables, including chemotherapy, radiation therapy, tumor size, and age. This model culminates in the development of a prognostic nomogram, underpinned by the Cox proportional hazards model. The outcome of the diagnostic model is the occurrence of DLNM in patients. The outcome of the prognosis model is determined by survival time and survival status. The integrated model developed based on stacking demonstrates good predictive performance and high interpretative variability and differentiation. The area under the curve (AUC) in the training set is 0.767, while the AUC in the validation set is 0.768. The nomogram, constructed using the Cox model, also demonstrates consistent and strong predictive capabilities. At the same time, we recognized elements that have a substantial impact on DLNM and the prognosis and extensively discussed their significance in the model and clinical practice. Our study identified key predictive factors for DLNM and elucidated significant prognostic indicators for HCC patients with DLNM. These findings provide clinicians with valuable tools to accurately identify high-risk individuals for DLNM and conduct more precise risk stratification for this patient subgroup, potentially improving management strategies and patient outcomes.

Impact of pre-sarcopenia on outcomes of transarterial chemoembolization in unresectable hepatocellular carcinoma

Sarcopenia’s impact on hepatocellular carcinoma (HCC) outcomes is well-documented, but the effects of pre-sarcopenia remain unclear. This study investigates the impact of pre-sarcopenia on tumor response and survival in patients with unresectable HCC undergoing transarterial chemoembolization (TACE). We retrospectively evaluated muscle volume using the SliceOmatic software in patients with unresectable HCC treated with TACE. Pre-sarcopenia was defined by Japan Society of Hepatology standards (men: 42 cm2/m2; women: 38 cm2/m2). Pre-sarcopenia and non-pre-sarcopenia groups were compared, and Cox proportional hazards model was used to identify survival-influencing variables. Subgroup analysis was conducted stratified by the tumor burden, using serum alpha-fetoprotein (AFP) levels at a diagnostic cutoff value of 200 ng/mL. Of the 100 patients, 39 had pre-sarcopenia. The presence of pre-sarcopenia was not associated with tumor complete response achievement. The median overall survival (OS) was significantly lower in the pre-sarcopenia group (18 months) than in the non-pre-sarcopenia group (30 months; log-rank P = 0.039). Subgroup analysis among 77 patients with AFP < 200 ng/mL revealed that OS was particularly poor in the pre-sarcopenia group (16 vs. 34 months; log-rank P < 0.001). Multivariate analysis identified increased AFP (adjusted hazard ratio [HR] per 10-unit increase 1.142; P < 0.001), higher Model for End-Stage Liver Disease score (adjusted HR per 1-unit increase 1.176; P < 0.001), and pre-sarcopenia (adjusted HR 2.965; P < 0.001) as predictors of shorter OS. Pre-sarcopenia is a significant predictor of increased mortality in patients with unresectable HCC undergoing TACE, especially in those with AFP < 200 ng/mL, suggesting its potential as a target for early intervention.