Search Results (362)

Malignant mediastinal tumors are a group representing some of the most demanding oncological challenges for early, multi-level, and successful management. The timely identification of any suspicious clinical symptomatology is urgent in achieving an accurate, staged histological diagnosis, in order to follow up with an equally detailed medical therapeutic plan (interventional or not) and determine the principal goals regarding efficient overall treatment in these patients. We report a case of a 24-year-old male patient with an incident-free prior medical history. An initial chest X-ray was performed after the patient reported short-term, consistent moderate chest pain symptomatology, early work fatigue, and shortness of breath. The following imaging procedures (chest CT, PET-CT) indicated the presence of an anterior mediastinal mass (meas. ~11 cm × 10 cm × 13 cm, SUV: 8.7), applying additional pressure upon both right heart chambers. The Alpha-Fetoprotein (aFP) blood levels had exceeded at least 50 times their normal range. Two consecutive diagnostic attempts with non-specific histological results, a negative-for-malignancy fine-needle aspiration biopsy (FNA-biopsy), and an additional tumor biopsy, performed via mini anterior (R) thoracotomy with “suspicious” cellular gatherings, were performed elsewhere. After admission to our department, an (R) Video-Assisted Thoracic Surgery (VATS) was performed, along with multiple tumor biopsies and moderate pleural effusion drainage. The tumor’s measurements had increased to DMax: 16 cm × 9 cm × 13 cm, with a severe degree of atelectasis of the Right Lower Lobe parenchyma (RLL) and a pressure-displacement effect upon the Superior Vena Cava (SVC) and the (R) heart sinus, based on data from the preoperative chest MRA. The histological report indicated elements of a combined, non-seminomatous germ-cell mediastinal tumor, posthuberal-type teratoma, and embryonal carcinoma. The imminent chemotherapeutic plan included a “BEP” (Bleomycin^®/Cisplatin^®/Etoposide^®) scheme, which needed to be modified to a “VIP” (Cisplatin^®/Etoposide^®/Ifosfamide^®) scheme, due to an acute pulmonary embolism incident. While the aFP blood levels declined, even reaching normal measurements, the tumor’s size continued to increase significantly (DMax: 28 cm × 25 cm × 13 cm), with severe localized pressure effects, rapid weight loss, and a progressively worsening clinical status. Thus, an emergency surgical intervention took place via median sternotomy, extended with a complementary “T-Shaped” mini anterior (R) thoracotomy. A large, approx. 4 Kg mediastinal tumor was extracted, with additional RML and RUL “en-bloc” segmentectomy and partial mediastinal pleura decortication. The following histological results, apart from verifying the already-known posthuberal-type teratoma, indicated additional scattered small lesions of combined high-grade rabdomyosarcoma, chondrosarcoma, and osteosarcoma, as well as numerous high-grade glioblastoma cellular gatherings. No visible findings of the previously discovered non-seminomatous germ-cell and embryonal carcinoma elements were found. The patient’s postoperative status progressively improved, allowing therapeutic management to continue with six “TIP” (Cisplatin^®/Paclitaxel^®/Ifosfamide^®) sessions, currently under his regular “follow-up” from the oncological team. This report underlines the importance of early, accurate histological identification, combined with any necessary surgical intervention, diagnostic or therapeutic, as well as the appliance of any subsequent multimodality management plan. The diversity of mediastinal tumors, especially for young patients, leaves no place for complacency. Such rare examples may manifest, with equivalent, unpredictable evolution, obliging clinical physicians to stay constantly alert and not take anything for granted. Full article

Testicular germ cell tumors (TGCTs) are the most common malignancies affecting young men between the ages of 14 and 44, accounting for about 95% of all testicular cancers. Despite being relatively rare compared to other cancers (~3.0 cases per 100,000 population, with high worldwide variability), TGCTs’ incidence is increasing, particularly in industrialized countries. The initial phase of TGCT diagnosis is performed by detecting in the blood the presence of three proteins, i.e., alpha-fetoprotein (AFP), lactate dehydrogenase (LDH), and human chorionic gonadotropin (hCG). Despite these proteins being defined as markers of TGCTs, they present limitations in specificity. Indeed, AFP is not elevated in pure seminomas; LDH serum levels can be elevated in other conditions, such as liver disease or tissue damage, and hCG can be elevated in both seminomas and non-seminomas, reducing its ability to differentiate between tumor types. However, the existence of hCG variants, characterized by distinct glycosylation profiles that are differentially expressed in TGCT types and subtypes, may increase the diagnostic and prognostic potential of this hormone. Furthermore, emerging molecular biomarkers, including miRNAs and tumor cells-related epigenetic status, may offer new promising alternatives to improve diagnostic accuracy. Nonetheless, standardized diagnostic protocols still need to be implemented. Finally, understanding the biological roles of hCG isoforms and their “canonical” (e.g., LHCGR) and “non-canonical” (e.g., TGF-βR) receptor interactions may help in understanding tumor biology and therapeutic targeting. Full article

Background/Objectives: Biomarkers such as lens agglutinin-reactive alpha-fetoprotein and des-gamma-carboxy prothrombin, as well as biomarker- and/or clinical-parameter-derived composite models (GALAD, GAAP, ASAP, aMAP, Doylestown), may improve detection in addition to alpha-fetoprotein, yet comparative data across diverse populations remain limited. Methods: In this biobank-based case–control study, we evaluated 562 adults (120 healthy controls, 277 chronic liver disease, 165 hepatocellular carcinoma) from January 2019 to 2024. Diagnostic performance for any-stage and early-stage hepatocellular carcinoma was assessed across three thresholds: Youden-index-derived optimal cut-offs, research-established cut-offs, and cut-offs ensuring 90% specificity. Receiver operating characteristic analysis was performed. Subgroup analyses were stratified by etiology and alpha-fetoprotein status. Results: At optimal cut-offs, GALAD showed the highest sensitivity for any-stage (90.3%) and early-stage (89.1%) hepatocellular carcinoma, with 70–80% specificity. Using established cut-offs, GALAD retained the highest sensitivity for any-stage (75.8%) and early-stage (57.8%) hepatocellular carcinoma, with 93.5% specificity. GALAD demonstrated the best performance in non-viral hepatocellular carcinomas (area under the curve 0.872), whereas GAAP and ASAP showed similarly high area under the curve values in viral etiology (area under the curve 0.955–0.960). Conclusions: Our results demonstrate the consistent performance of the GALAD score across diverse populations and underscore its superiority over individual biomarkers and other composite models. Notably, the GAAP and ASAP scores—which use one less biomarker (AFP-L3)—exhibited comparable performance, particularly in viral etiology. These findings support the integration of the composite biomarker models into tailored hepatocellular carcinoma surveillance strategies. Full article

A young adult patient presented to the gastrointestinal outpatient department with a suspected hepatic tumor. The patient was in a traffic accident ten years ago and underwent splenectomy and distal pancreatectomy at another medical institution. The physical examination was unremarkable. The liver function tests and tumor markers were within normal limits, with the alpha-fetoprotein level at 1.38 ng/mL. Both hepatitis B surface antigen and anti-HCV were negative. Based on the clinical history, intrahepatic splenosis was suspected first. Dynamic computed tomography revealed a 2.3 cm lesion exhibiting suspicious early wash-in and early wash-out enhancement patterns. As previous studies have reported, this finding makes hepatocellular carcinoma and metastatic lesions the major differential diagnoses. For further evaluation, dynamic magnetic resonance imaging was performed, and similar enhancing features were observed, along with restricted diffusion. As hepatocellular carcinoma still could not be confidently ruled out, the patient underwent an ultrasound-guided biopsy. The diagnosis of intrahepatic splenosis was confirmed by the pathologic examination. Intrahepatic splenosis is a rare condition defined as an acquired autoimplantation of splenic tissue within the hepatic parenchyma. Diagnosis can be challenging due to its ability to mimic liver tumors in imaging studies. Therefore, in patients with a history of splenic trauma and/or splenectomy, a high index of suspicion and awareness is crucial for accurate diagnosis and for prevention of unnecessary surgeries or interventions. Full article

Background/Objectives: Salvage liver transplantation (SLT) is a well-established option for hepatocellular carcinoma (HCC) recurrence after liver resection. Laparoscopic microwave ablation (L-MWA) represents another curative strategy for early-stage HCC. However, its role within this therapeutic framework remains unexplored. Methods: Between 2014 and 2023, we treated 1341 patients with HCC using L-MWA. From this cohort, patients with Child-Pugh class A liver function, HCC within the Milan criteria, no contraindications to transplantation, and ≥12 months of follow-up were selected. SLT failure was defined as non-transplantable recurrence or death, resulting in the loss of a potentially curative therapeutic opportunity. The primary endpoint was overall survival (OS); secondary endpoints included predictors of survival and SLT failure. Results: A total of 341 patients met the inclusion criteria. Five-year OS was 62%. Independent predictors of poorer survival included the presence of cardiac disease or oesophageal varices, a Child-Pugh score of 6, tumour size, and elevated alpha-fetoprotein (AFP) levels. Treatment was successful in 255 patients (74.8%): 102 (29.9%) underwent SLT, 67 (19.6%) received alternative therapies, and 93 (27.3%) remained recurrence-free. Treatment failure occurred in 86 patients (25.2%) due to non-transplantable recurrence or death. Independent predictors of failure included older age, non-HBV aetiology, and elevated AFP levels. Five-year OS rates were 79% in the success group and 22% in the failure group (p < 0.001). Conclusions: A combined L-MWA and SLT strategy is safe and effective, yielding a 62% 5-year OS rate. This approach supports more efficient graft use with a consequent increase in the population transplant benefit. Improved selection may further reduce failure rates. Full article

Background and Objectives: The use of antiseizure medications (ASMs) during pregnancy is critical to seizure control in women with epilepsy but raises concerns regarding the use of these drugs and their possible effect on the maternal serum biochemical markers used for second-trimester prenatal screening. The aim of this study was to assess the effect of ASMs on the levels of maternal serum alpha-fetoprotein (AFP), unconjugated estriol (uE3), and human chorionic gonadotropin (hCG) assessed in the serum biomarker analyses part of second-trimester prenatal screening. Materials and Methods: This retrospective cohort study included 43 pregnant women in the ASM-exposed group (levetiracetam, lamotrigine, carbamazepine, or combined therapy) and 43 matched controls without medication use. Groups were matched based on maternal age, gravidity, parity, abortion history, gestational age at testing, body mass index, and smoking status with propensity score matching. Serum AFP, uE3, and hCG levels measured at 15–20 weeks of gestation were compared between groups. The incidence of fetal congenital anomalies or aneuploidies was also compared between groups. Results: Pregnant women in the ASM-exposed group had significantly higher maternal serum AFP (1.34 ± 0.42 vs. 1.01 ± 0.31 MoM; p < 0.001) and uE3 (1.28 ± 0.39 vs. 1.05 ± 0.34 MoM; p = 0.004) than the controls. However, hCG did not differ significantly between the groups (1.07 ± 0.46 vs. 1.01 ± 0.42 MoM; p = 0.523). Regarding the ASM subgroups (levetiracetam, lamotrigine, and carbamazepine), there were no significant differences in the serum biomarkers (p > 0.05). There was no significant difference between the ASM-exposed and control groups in terms of the incidence of congenital anomalies or aneuploidies (2.3% in the ASM-exposed group vs. 2.3% in the control group; p = 1.000). Conclusions: The use of ASMs during pregnancy significantly alters second-trimester maternal serum biochemical markers, including our primary concerns, AFP and uE3, which could cause inaccurate interpretations of second-trimester prenatal screening. Clinicians should carefully consider maternal medication exposure when interpreting these biochemical markers in pregnant women with epilepsy to prevent the misclassification of fetal risks and avoid unnecessary invasive procedures. Full article

Multimode immunoassays based on multiple response mechanisms have received great attention due to their capacity to effectively improve the accuracy and reliability of biosensing platforms. However, few strategies have been reported for triple-mode immunoassays due to the shortage of multifunctional sensing materials and the incompatibility of signal transduction methods in different detection modes. In this work, a fluorescent–electrochemical–colorimetric triple-mode immunoassay platform was proposed with Cu-based metal–organic frameworks (MOFs) as the signal labels. The captured Cu-MOFs were successfully decomposed under an acidic condition, leading to the release of numerous Cu²⁺ ions and 2-aminobenzene-1,4-dicarboxylic acid (NH₂-BDC) ligands. The released NH₂-BDC were determined by fluorescence titration. Meanwhile, the released Cu²⁺ were readily quantified by differential pulse voltammetry (DPV) and simply detected through the catalytic oxidation of chromogenic substrate 3,3′,5,5′-tetramethylbenzidine (TMB). Taking alpha-fetoprotein (AFP) as a model analyte, the designed triple-mode immunoassays showed good performances with the linear range of 10–200 pg/mL, 10–200 pg/mL, and 1–100 pg/mL for the fluorescent, electrochemical, and colorimetric modes, respectively. The proposed triple-mode biosensing platforms show great potential for the applications in disease diagnosis, since they can be easily extended to other bioassays by changing the targets and recognition elements. Full article

Background/Objectives: Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality, with diagnostic limitations of existing biomarkers such as alpha-fetoprotein (AFP). This study evaluates plasma Fibrinogen chain A mRNA (FGA mRNA), alone and combined with AFP, for improving HCC diagnosis. Methods: A semi-nested RT-PCR assay was developed to quantify plasma FGA mRNA in 80 HCC patients and 74 controls (57 chronic liver disease [CLD] and 17 healthy donors [HDs]). Receiver operating characteristic (ROC) analysis was used to assess diagnostic performance, and logistic regression evaluated the combined biomarker model. Results: Plasma FGA mRNA levels were significantly higher in HCC patients than in CLD and HD controls (p < 0.0001). The area under the curve (AUC) for HCC vs. the combined control group (CLD + HD) was 0.721 (95% CI: 0.643–0.790), improving to 0.866 (95% CI: 0.782–0.927) when comparing HCC to HDs alone but declining for HCC vs. CLD (AUC = 0.678, 95% CI: 0.592–0.755). Combining FGA mRNA with AFP significantly enhanced diagnostic accuracy for HCC vs. CLD (AUC = 0.859, 95% CI: 0.790–0.913), with a sensitivity of 87.50% and specificity of 71.93%. In patients with low AFP levels (<20 ng/mL), the combined model identified 68.75% of HCC cases, outperforming AFP alone. Conclusions: FGA mRNA alone provides moderate diagnostic utility but substantially improves accuracy when combined with AFP, especially in low-AFP cases. This multi-biomarker approach holds promise for improving HCC detection and warrants further validation in larger cohorts. Full article

Background and aims: Metabolic dysfunction-associated steatotic liver disease (MASLD)-related hepatocellular carcinoma (HCC) may have distinct biological characteristics influencing systemic treatment response. However, the prognostic impact of MASLD vs. alcohol-related HCC in patients receiving lenvatinib remains unclear. This study aimed to assess lenvatinib’s effectiveness and safety in these populations. Methods: A multicenter cohort of 378 HCC patients treated with lenvatinib (2019–2024) was analyzed. Propensity score matching was performed based on age, sex, tumoral stage, alpha-fetoprotein levels and Child–Pugh class. Survival was estimated using Kaplan–Meier analysis and compared with the log-rank test. Results were expressed as HR and 95% CI. Results: After matching, 115 patients per group were compared. Median OS was 21 months (95% CI: 20–23) in the group with metabolic dysfunction-associated steatohepatitis (MASH) and 19 months (95% CI: 18–21) in the group with alcohol etiology (p = 0.18). In multivariate analysis, only Child–Pugh class (HR 2.67, 95% CI: 1.84–5.41) and tumor stage (HR 2.18, 95% CI: 1.57–6.93) resulted as significant predictors of OS. Median PFS was 9 months (95% CI: 8–9) in patients with MASH and 9 months (95% CI: 7–10) in patients with alcohol etiology (p = 0.33). Only the Child–Pugh class was a significant predictor of PFS in univariate analysis (HR 1.56, 95% CI: 1.15–3.41; p = 0.03). No difference in terms of adverse event rate was observed between the two groups. Conclusions: Lenvatinib is effective in patients with both MASH- and alcohol-related HCC, with no difference in oncological outcomes between the two groups. Full article

Background: Hepatocellular carcinoma (HCC) with hepatic vein invasion (HVI) is classified as advanced stage and palliative management is the primary treatment option. This study compared the long-term outcomes of curative and non-curative treatments in patients of HCC with HVI. Methods: Data were obtained from a retrospective multicenter cohort of the Korean Primary Liver Cancer Registry. We reviewed 18,315 patients newly diagnosed with HCC between 2008 and 2019. After propensity score matching based on the albumin-bilirubin (ALBI) score; tumor number, and tumor size, clinical outcomes were compared between the curative group (n = 42, 29.0%) undergoing surgical resection or local ablation and the non-curative group (n = 103, 71.0%) receiving other treatments. Results: Tumor burdens such as tumor number, maximum tumor size, levels of alpha-fetoprotein (AFP), and protein induced by absence of vitamin K or antagonist-II did not differ significantly between the groups (p = 0.672, p = 0.143, p = 0.153 and p = 0.651, respectively). In long-term outcomes, the overall survival (OS) and cancer-specific survival (CSS) were significantly better in the curative group compared to the non-curative group (p < 0.001, both). Multivariate analysis indicated that non-curative treatment, ALBI grade ≥ 2, and AFP ≥ 400 ng/mL were common risk factors for OS and CSS. Conclusions: Curative-intent treatment has the potential to significantly enhance long-term outcomes in selected patients of HCC with HVI who preserved liver function and performance status. Full article

Background/Objectives: Different cutoffs have been proposed to be the optimal resection margin of liver resection for hepatocellular carcinoma (HCC). The aim of this study was to perform a systematic review, investigating the different impacts on disease-free survival (DFS) and overall survival (OS) of different margin cutoffs. Methods: The PubMed, Embase, and Cochrane databases were searched for comparative studies evaluating the oncological impacts of different types of liver resection margin for HCC. Results: A total of 48 studies were included in the final analysis. Among them, 36 evaluated the impact of resection margin width on OS and 42 on DFS. The margin cutoffs assessed varied widely, including 20 mm, 10 mm, 5 mm, 4 mm, 2 mm, and 1 mm. While wider margins (≥10 mm) were generally associated with improved outcomes, particularly in high-risk subgroups such as patients with microvascular invasion (MVI), elevated alpha-fetoprotein (AFP) levels, or a non-cirrhotic liver, other studies reported no significant differences. The findings were highly heterogeneous across the studies due to differences in patient populations, tumor biology, and surgical approaches. Consequently, the evidence suggests that the optimal margin is context-dependent rather than universal. Conclusions: Wider resection margins should be considered in select high-risk patients, while a tailored, case-by-case approach remains necessary given the overall heterogeneity of HCC presentations. Full article

Ataxia-telangiectasia is a rare autosomal recessive disorder that is difficult to diagnose due to its unpredictable presentation. It is characterized by cerebellar degeneration, telangiectasias, immunodeficiency, frequent pulmonary infections, and tumors. Immune system abnormalities manifest as disruptions in both cellular and humoral immunity. The most common findings include decreased levels of immunoglobulin classes (IgA, IgM, IgG, and IgG subclasses) and a reduced number of T and B lymphocytes. A four-year-old girl was initially evaluated and treated for skin lesions that presented as crusts spreading across her body. She was monitored by a pulmonologist due to frequent bronchial obstructions. Over time, she developed bilateral scleral telangiectasia, saccadic eye movements, and impaired convergence. Her gait was wide-based and unstable, with truncal ataxia and a positive Romberg sign. Laboratory tests revealed decreased immunoglobulin G levels, subclass IgG4 levels, elevated alpha-fetoprotein, and a reduced number of T and B lymphocytes. Brain magnetic resonance imaging showed cerebellar atrophy. Whole-exome sequencing identified heterozygous variants c.1564-165del, p.(Glu5221lefsTer43), and c.7630-2A>C in the serine/threonine-protein kinase ATM (ataxia-telangiectasia mutated) gene, confirming the diagnosis of ataxia-telangiectasia. Following diagnosis, treatment with intravenous immunoglobulin replacement was initiated along with infection prevention and management. The goal of this case report is to raise awareness of the atypical initial presentation that may lead to a diagnostic delay. We emphasize the importance of considering ataxia-telangiectasia in the differential diagnosis, even when classical neurological signs are not yet evident. Full article

Alpha-fetoprotein (AFP) is a well-known biomarker for liver cancer, and its clinical utility is widely recognized. Recent studies have revealed that AFP plays a multifaceted role in various malignant tumors, including liver cancer. This suggests that AFP is not merely a biomarker but also contributes significantly to the complex process of tumor formation, emphasizing the importance of targeting AFP in therapeutic approaches. Consequently, innovative research and development are essential to overcome the current limitations of AFP-targeted therapies, enhance treatment efficacy, and minimize side effects. This review explores the role of AFP in cancer development and progression, highlights the biological functions of AFP and related pathways, and discusses the clinical implications of AFP-targeted therapies. Ongoing research on AFP will significantly contribute to our understanding of the biological mechanisms of cancer and aid in developing effective and safe treatments. Ultimately, advancements in AFP-targeted therapeutic approaches are expected to play a crucial role in the future of cancer management. Full article

Circular RNAs (circRNAs) are increasingly recognized as significant regulators in multiple cancers, such as hepatocellular carcinoma (HCC), frequently affecting microRNA (miRNA) expression. The diagnostic and prognostic roles of circRNAs, specifically circ_0009910 and circ_0027478, in conjunction with miR-1236-3p, in HCC, have not yet been fully investigated. In this pilot study, we assessed the expression levels of circ_0009910, circ_0027478, and miR-1236-3p in plasma samples from 100 patients diagnosed with HCC and 50 healthy controls through reverse transcriptase–quantitative polymerase chain reaction (RT-qPCR). The diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis, and correlations with clinicopathological features were examined. Circ_0009910 and circ_0027478 exhibited significant upregulation in patients with HCC (p < 0.05), whereas miR-1236-3p demonstrated downregulation (p < 0.05). Circ_0009910 demonstrated significant diagnostic accuracy (area under the curve [AUC] = 0.90), effectively differentiating HCC from controls and showing a correlation with tumor size, metastasis, and alpha-fetoprotein (AFP) levels (p < 0.05). Both circ_0009910 and circ_0027478 exhibited a positive correlation with clinicopathological features, whereas miR-1236-3p demonstrated an inverse correlation. Logistic regression validated the diagnostic and prognostic capabilities of these biomarkers. The results indicate that circ_0009910, circ_0027478, and miR-1236-3p, in conjunction with AFP three, present a promising diagnostic and prognostic profile for HCC. Additional validation in larger cohorts is required to establish their clinical utility. Full article

Isolated intrahepatic lymphoid follicles (ILFs), also referred to as reactive lymphoid hyperplasia, are rare benign lymphoid proliferations that can closely mimic hepatocellular carcinoma (HCC) on imaging. This case highlights the diagnostic complexity of hepatic mass lesions in chronic hepatitis B patients, particularly when radiologic and serologic features raise concern for malignancy. A 60-year-old man with chronic hepatitis B presented with a liver mass, elevated alpha-fetoprotein levels, and imaging findings of heterogeneous arterial enhancement, all suggestive of HCC. Despite initial treatment with atezolizumab plus bevacizumab, the lesion progressed, leading to an extended left hepatectomy. Histopathological examination revealed well-formed lymphoid follicles with reactive germinal centers, without evidence of malignancy or granulomatous inflammation. Serum IgG was elevated, and ANA was positive, supporting the possibility of an underlying immune-mediated process. The patient showed clinical and serologic improvement following corticosteroid therapy, with no evidence of recurrence at 10-month follow-up. This case underscores the importance of histopathological confirmation in hepatic masses with atypical features and highlights the need to consider benign immune-related mimickers in the differential diagnosis, particularly in the era of immunotherapy. Full article