Search Results (3,566)

Background/Objective: Identifying patterns of diagnostic imaging workflow parallel to the influence of certain variables, such as pathology guidelines over time, provides valuable insight for clinical decision making. This study presents a recurring trend of initial imaging orders and follow-ups, up to the diagnosis of pancreatic neuroendocrine tumors (pNETs), across two decades, with scans which led to pathological investigation. Methods: Three readers evaluated common conventional imaging among initial and follow-up studies for lesion detection and localization. Inter-reader and intra-reader analyses were controlled as contributing factors to the imaging diagnostic trend. Results: Our results show that CT was the prominent initial scan in pNET workup, likely due to their wide availability, high spatial resolution, and rapid acquisition, with a sufficient detection rate throughout both decades, regardless of technical advances. However, MRI scans also gained soaring popularity, especially among syndromic patients, likely due to follow-up and anatomical surgery precision. Conclusions: Newer modalities may be eventually useful and only requested for pNETs staging and further treatment. Full article

Background/Objectives: Gastric cancer remains a leading cause of cancer mortality worldwide. Reliable biomarkers are crucial for early detection, prognostication, and therapy monitoring. While classical tumor markers such as carcinoembryonic antigen (CEA), cancer antigen (CA)19-9, CA72-4, and alpha-fetoprotein (AFP) are used in clinical practice, their accuracy can be limited. Tumor necrosis factor alpha (TNF-α) is an inflammatory cytokine implicated in tumor progression, yet its relationship with established gastric cancer tumor markers has not been fully clarified. This study aimed to determine whether elevated TNF-α correlates with key tumor markers and disease stage in gastric cancer. Methods: In this prospective observational study, we enrolled 80 gastric cancer patients and 20 non-neoplastic controls. Baseline clinical data, laboratory parameters, and tumor markers (CEA, CA19-9, CA72-4, AFP) were recorded. TNF-α concentrations were measured using enzyme-linked immunosorbent assays. Correlation analyses and multivariate regression were performed to assess the relationship of TNF-α with tumor markers, inflammatory indices, and disease stage. Results: TNF-α was significantly elevated in gastric cancer patients (median 4.5 pg/mL) compared to controls (2.9 pg/mL). TNF-α showed a robust correlation with CA19-9 (rho = 0.502) and CA72-4 (rho = 0.385), and a moderate correlation with CEA (rho = 0.279). TNF-α concentrations were highest in Stage IV disease and in the intestinal-type histology. In regression analysis, only CA19-9 and CA72-4 remained independent predictors of TNF-α after controlling for clinical confounders. Conclusions: TNF-α is strongly associated with CA19-9 and CA72-4 and rises with advancing stage, highlighting its potential as an adjunct marker for assessing gastric cancer burden. These findings provide a rationale for further research on TNF-α as both a prognostic biomarker and a possible therapeutic target in gastric cancer. Full article

Background/Objectives: As endoscopy is increasingly being used to diagnose superficial nonampullary duodenal epithelial tumors (SNADETs), there is a growing need for their early detection and minimally invasive treatment. This study investigated the diagnostic accuracy of biopsy specimens for SNADETs. Methods: We conducted a retrospective analysis of clinicopathologic data from 98 patients with SNADETs who had undergone endoscopic resection. The presurgical diagnosis, based on biopsy specimens, was compared with the histological diagnosis of the excised specimens. Results: Herein, preoperative biopsies were performed on 98 SNADETs specimens from 91 patients. Of the 68 adenomas and 30 carcinomas, 22.4% adenomas were later found to be carcinomas. Carcinoma biopsy diagnosis sensitivity, specificity, and accuracy were 54.6%, 80.0%, and 71.4%, respectively. Biopsy accuracy for carcinoma differed significantly by location to the papilla of Vater (p = 0.0455). The preoperative biopsy diagnostics’ sensitivity, specificity, and accuracy for oral and anal carcinomas to Vater papilla were 69.2%, 92.0%, and 84.2% and 42.1%, 73.2%, and 63.3%, respectively. Conclusions: The diagnostic accuracy of biopsy for SNADETs was low; however, it was higher on the oral side than the anal side of the papilla of Vater. The biopsy of duodenal lesions should be performed after an endoscopic examination, considering their location and reducing the risks of fibrosis. Full article

Retinoblastoma was one of the first malignant tumors to be described as a genetic disease and its development occurs from the loss of function of the retinoblastoma gene (RB1). The difficulty in accessing the tumor during diagnosis highlights the need for non-invasive diagnostic methods. Studies have shown that liquid biopsy, obtained from any fluid material in the body, for example blood, contains free tumor cells and free and circulating DNA or RNA, making it a convenient tool for diagnosis and prognosis during cancer treatment without the need for invasive procedures. Taking advantage of these events, given this situation, we investigated molecular alterations in samples from retinoblastoma cases, using the NGS strategy as a powerful tool for characterization and aid in diagnosis and prognosis. Genomic data from 76 patients diagnosed with retinoblastoma, comprising 162 samples, tumor (TU), aqueous humor (AH), and peripheral blood (PB), were analyzed using the Oncomine Childhood Cancer Research Panel (OCCRA^®). A total of 22 altered genes were detected, and 54 variants. Of the 76 cases, 29 included paired tumor (TU), aqueous humor (AH), and peripheral blood (PB) samples from the same patient. Alterations in the RB1 gene were detected in 16 of these 29 cases, with concordant alterations identified across all three sample types in three patients. In 12 out of 29 patients, the same genetic alteration was found in both TU and AH. In conclusion, the OCCRA panel enabled the detection, in different samples, of molecular alterations in the RB1 gene, as well as CNAs in the MYCN, ABL2, and MDM4 genes. Limitations of AH were observed, primarily due to the small volume of material available and the consequently low concentration of cell-free DNA (cfDNA). However, as AH provides a viable alternative for analyzing tumors, inaccessible to traditional biopsy methods, liquid biopsy holds significant potential to improve diagnostic accuracy and guide treatment strategies in retinoblastoma cases. Full article

Introduction: Low-malignant-potential adenocarcinoma has been defined as a type of non-mucinous tumor, which has a total tumor size measuring ≤ 3 cm, exhibits ≥ 15% lepidic growth, lacks non-predominant high-grade patterns (≥10% cribriform, ≥5% micropapillary, ≥5% solid), has an absence of angiolymphatic or visceral pleural invasion, spread through air spaces (STAS), necrosis and >1 mitosis per 2 mm². The aim of this study is to validate, with regard to cancer-specific survival (CSS) and disease-free survival (DFS), the proposed definition of LMP adenocarcinoma in an independent external cohort of lung adenocarcinoma patients having undergone surgical resection, and having presented with a long follow-up period. Methods: Clinicopathological characteristics of patients who underwent lung resection for adenocarcinoma from 1 January 2005 to 31 December 2014 were retrospectively analyzed. Patients with ground-glass opacity (GGO) and part-solid tumors, minimally invasive adenocarcinoma (MIA), adenocarcinoma in situ (AIS), tumors ≥5 cm in size, nodal involvement and/or distant metastases, patients who underwent neoadjuvant treatment, and those who had an incomplete follow-up or a follow-up shorter than 60 months were excluded. The proposed criteria for low-malignant-potential adenocarcinoma (LMPA) were tumor size ≤ 3 cm, invasive size ≥ 0,5 cm, lepidic growth ≥ 15%, and absence of the following: mitosis (>1 per 2 mm²), mucinous subtype, angiolymphatic invasion, visceral pleural invasion, spread through air spaces (STAS) and tumor necrosis. End points were disease-free survival (DFS) and cancer-specific survival (CSS). The log-rank test was used to assess differences between subgroups. Results: Out of 80 patients meeting the proposed criteria, 14 (17.5%) had the LMPA characteristics defined. The mean follow-up time was 67 ± 39 months. A total of 19 patients died, all in the non-LMPA category, and 33 patients experienced recurrence: 4 (28.5%) with LMPA and 29 (43.9%) with non-LMPA. Log-rank analysis showed 100% 10-year CSS for patients with LMPA and 77.4% for patients without LMPA, with this difference being statistically significant (p-value = 0.047). Univariate analysis showed a significant association with the cStage (AJCC eighth edition), both for CSS (p value = 0.005) and DFS (p-value = 0.003). LMPA classification did not show a statistically significant impact on CSS and DFS, likely due to the limited number of events (CSS p-value = 0.232 and DFS p-value = 0.213). No statistical association was found for CSS and DFS with pT, the number of resected nodes (< or >10) or the number of resected N2 stations (< or >2). Conclusions: Our study confirmed the prognostic role of LMPA features, with a low risk of recurrence and a good CSS and DFS. The criteria for diagnosis are replicable and feasible for application. The clinical implications of these findings, such as pre-operative prediction and surveillance scheduling, may be the topic of future prospective studies. Full article

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with metastasis representing a pivotal factor in poor prognosis and high fatality rates. This review offers a comprehensive examination of the key molecular events and regulatory mechanisms driving HCC metastasis, with a particular focus on genetic mutations, epigenetic alterations, and dysregulated signaling pathways. Special emphasis is placed on the role of three-dimensional genome structural remodeling in HCC initiation and metastatic progression. Additionally, the latest advances in targeted therapies for advanced HCC are summarized, including both first-line and second-line treatments, highlighting their impact on controlling metastatic disease. The review also examines a variety of potential biomarkers linked to HCC metastasis, including circulating tumor cells, circulating tumor DNA, and exosomal contents, all of which demonstrate significant promise for the early detection, diagnosis, and therapeutic monitoring of HCC metastasis. By bridging molecular insights with clinical applications, this review provides valuable perspectives to guide future research in the diagnosis and treatment of HCC metastasis. Full article

Lung adenocarcinoma (LUAD), the predominant subtype of non-small cell lung cancer (NSCLC), presents significant challenges in early diagnosis and personalized treatment. Recent research has focused on the role of the tumor microenvironment, particularly tumor-associated fibroblasts (CAFs), in tumor progression. This study systematically analyzed CAF immune infiltration-related genes to construct a prognostic model for LUAD, confirming its predictive value for patient outcomes. The risk score derived from CAF-related genes (CAFRGs) was negatively correlated with immune microenvironment scores and linked to the expression of immune checkpoint genes, indicating that high-risk patients may exhibit immune escape characteristics. Analysis via the TIDE tool revealed that low-risk patients had more active T-cell immune responses. The risk score also correlated with anti-tumor drug sensitivity, particularly to doramapimod. Notably, COX6A1 emerged as a key gene in the model, with its upregulation associated with immune cell infiltration and immune escape. Further in vitro experiments demonstrated that COX6A1 regulates LUAD cell migration, proliferation, and senescence, suggesting its role in tumor immune evasion. Additionally, further co-culture studies of lung cancer cells and fibroblasts revealed that COX6A1 knockdown promotes the expression of CAF-related cytokines, enhancing CAF infiltration. Overall, this study provides a foundation for personalized treatment of LUAD and highlights COX6A1 as a promising therapeutic target within the tumor immune microenvironment, guiding future clinical research. Full article

Background: Ameloblastic carcinoma (AC) is a rare malignant odontogenic tumor with limited knowledge surrounding its pathogenesis, molecular pathways, clinical behavior, treatment, and prognosis. This 40-year literature scoping review aims to enhance the comprehension of this complex condition, looking closely at how AC works at molecular and pathophysiological levels and what causes it to develop. Methods: The PUBMED, Medline, Scopus, and Cochrane central databases were searched, including articles from 1984 to date. Articles reporting epidemiological, clinical, instrumental, and histopathological data were included. Results: Out of the 375 articles examined, 52 met the inclusion criteria, yielding a total of 80 cases of AC. All cases before 1984 were excluded from the analysis, as were all that did not provide information on patient survival. Several molecular mechanisms associated with its development and progression were identified; these help in early diagnosis. Moreover, AC can spread locally, making a radical surgical approach necessary. There is still no agreement on how to manage neck dissection. Surgical removal followed by monitoring is an important part of managing AC. Conclusions: Advancements in biological and molecular insights have the potential to facilitate earlier diagnosis and treatment. These could lead to improvements in patients’ quality of life and long-term survival. Full article

Background: Malignant Ectomesenchymoma (MEM) is a rare, aggressive soft tissue neoplasm with both neuroectodermal and mesenchymal differentiation. Congenital cases are extremely uncommon, posing significant diagnostic and therapeutic challenges. Case Presentation: We report a case of a full-term male neonate presenting with a large congenital neck mass and respiratory distress at birth. Imaging revealed a lobulated, heterogeneously enhancing mass in the left submandibular region with a mass effect on the airway. Open biopsy and gross resection on day six of life confirmed MEM with rhabdomyoblastic and neuroectodermal differentiation. Post-surgical staging classified the tumor as Stage I, Clinical Group II. Despite initial chemotherapy with Vincristine, Actinomycin, and Cyclophosphamide (VAC), tumor recurrence was detected at week nine of chemotherapy, necessitating a transition to Vincristine, Irinotecan, and Temozolomide (VIT). Discussion: MEM is an extremely rare neoplasm in infants, particularly in congenital presentations. Diagnosis is challenging due to its mixed histopathological features and broad differential diagnosis, including rhabdomyosarcoma, fibrosarcoma, lymphangioma, and neuroblastoma. Management typically involves multimodal therapy, with surgical resection being the mainstay of treatment. Chemotherapy is often tailored to the tumor’s most aggressive component, though standardized treatment protocols remain undefined. Conclusions: This case highlights the importance of early recognition and a multidisciplinary approach in managing congenital MEM, as a differential diagnosis of soft tissue masses in infants, particularly in the head and neck region. Full article

Background/Objectives: Composite hemangioendothelioma (CHE) is a rare vascular endothelial tumor with borderline malignancy. This study presents a case of CHE and an updated systematic review of previously reported cases, providing insights into recurrence patterns and survival outcomes. Methods: A comprehensive electronic search was conducted across PubMed, Scopus, the Cochrane Library, and Web of Science up to 31 December 2024, to identify eligible case reports. Kaplan–Meier curves were used to estimate event-free survival. Results: We report a 61-year-old man with a splenic lesion associated with weight loss and abdominal pain persisting for 1 year. Intraoperative findings revealed an enlarged spleen and multiple hepatic deposits. Splenectomy and liver biopsy revealed a well-demarcated, nodular tumor measuring 160 × 145 × 100 mm, with histological and immunohistochemical findings consistent with CHE, complicated by hepatic metastasis. Of 405 potentially eligible studies, 59 were included in the review, covering cases from 2000 to 2024, with a peak in 2020 and 2023. The median age of patients was 42 years, with the most common tumor sites being the lower extremities (30.48%), followed by the face, head, and neck (20.95%), and upper extremities (18.1%). Surgical intervention was the most common treatment (60.95%). Recurrence-free survival was observed in 42.86% of cases, while 15.24% experienced recurrence with or without metastasis. Two patients (1.90%) died from the disease. The median recurrence-free survival was 48 months (95% CI: 7.3–88.7). Conclusions: CHE exhibits significant morphological variation and can mimic other vascular tumors. Accurate diagnosis is crucial for proper prognosis and avoiding overtreatment due to misdiagnosis as more aggressive neoplasms. Patients with high-risk CHE should undergo closer surveillance to ensure timely detection of progression. Full article

Breast cancer is an aggressive disease of multiple subtypes with varying phenotypic, hormonal, and clinicopathological features, offering enhanced resistance to conventional therapeutic regimens. There is an unmet need for reliable molecular biomarkers capable of detecting the malignant transformation from the early stages of the disease to enhance diagnosis and treatment outcomes. A subset of small non-coding nucleic acid molecules, micro ribonucleic acids (microRNAs/miRNAs), have emerged as promising biomarkers due to their role in gene regulation and cancer pathogenesis. This review discusses, in detail, the different origins and hormone-like regulatory functionalities of miRNAs localized in tumor tissue and in the circulation, as well as their inherent stability and turnover that determines the utility of miRNAs as biomarkers for disease detection, monitoring, prognosis, and therapeutic targets. Full article

Meningiomas arise from the meningeal layers covering the central nervous system structures. Although most are benign, meningiomas can still cause neurological morbidity due to the mass effect and compression of the surrounding parenchyma. The prognosis also depends on several factors such as growth pattern or location. Morphological imaging approaches, such as MRI and CT, that emphasize intracranial calcifications, vascular patterns, or invasion of major vessels act as the basis of the diagnosis; PET/CT imaging is a valuable diagnostic tool for assessing somatostatin receptor activity in tumors. It enables the visualization and quantification of somatostatin receptor expression, providing insights into tumor biology, receptor status, and potential therapeutic targets. Aside from radiosurgery and neurosurgical intervention, peptide receptor radionuclide therapy (PRRT) has also shown promising results. Somatostatin receptors 1 and 2 are nearly universally expressed in meningioma tissue. This characteristic is increasingly exploited to identify patients eligible for adjuvant therapy using DOTA-conjugated somatostatin receptor-targeting peptides PET. In the treatment of relapsed/refractory meningiomas, PRRT is increasingly considered a safe and effective therapeutic option. It is often supported by artificial intelligence strategies for dose optimization and side-effect monitoring. The objective of this study is to evaluate the safety and benefits of these strategies based on the latest findings. Full article

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related mortality in the United States, with poor overall survival across all stages. Less than 20% of patients are eligible for curative surgical resection at diagnosis, and despite adjuvant chemotherapy, most will experience disease recurrence within two years. The incorporation of immune-based strategies in the adjuvant setting remains an area of intense investigation with unrealized promise. It offers the potential of providing durable disease control for micro-metastatic disease following curative intent surgery and enabling personalized treatments based on mutational neoantigen profiles derived from resected specimens. However, most of these attempts have failed to demonstrate significant clinical success, likely due to the immunosuppressive tumor microenvironment (TME) and individual genetic heterogeneity. Despite these challenges, immune-based strategies, such as therapeutic vaccines targeted towards neoantigens, have demonstrated promise via immune activation and induction of T-cell tumor infiltration. In this review, we will highlight the foundational lessons learned from previous clinical trials of adjuvant immunotherapy, discussing the knowledge gained from analyses of trials with disappointing results. In addition, we will discuss how these data have been incorporated to design new agents and study concepts that are proving to be exciting in more recent trials, such as shared antigen vaccines and combination therapy with immune-checkpoint inhibitors and chemotherapy. This review will evaluate novel approaches in ongoing and future clinical studies and provide insight into how these immune-based strategies might evolve to address the unique challenges for treatment of PDAC in the adjuvant setting. Full article

Cholangiocarcinoma (CCA) is an aggressive malignancy with limited methods for early detection, necessitating the development of reliable biomarkers for diagnosis and management. However, conventional tumor markers, such as CA19-9 and CEA, exhibit insufficient diagnostic accuracy. Recent advancements in molecular genetics have identified several actionable mutations in CCA, enabling molecularly targeted therapies that improve survival in patients harboring these genetic alterations. Cancer panels, which facilitate multiplex genetic profiling, are critical for identifying these mutations. Studies indicate that several actionable mutations are detected in CCA cases, with patients receiving mutation-guided therapies achieving markedly better outcomes. Liquid biopsies, including cell-free DNA and circulating tumor DNA, offer real-time, non-invasive approaches to monitoring tumor dynamics, heterogeneity, and treatment responses. Furthermore, numerous studies have identified non-coding RNAs in serum and bile as promising biomarkers for the diagnosis and management of CCA. On the other hand, immunotherapy, particularly immune checkpoint inhibitors, has shown efficacy in subsets of CCA patients. However, the success of these therapies is often affected by the status of the tumor immune microenvironment (TME), underscoring the need for comprehensive TME analysis to predict responses to immune checkpoint inhibitors. Despite these advances, no single biomarker currently demonstrates sufficient sensitivity or specificity for clinical application. The integration of multi-omics approaches with cutting-edge technologies holds promise for enhancing diagnostic accuracy, optimizing treatment stratification, and advancing precision medicine in CCA. These developments highlight the transformative potential of biomarkers to improve early detection, prognostic assessment, and personalized therapeutic interventions for CCA. Full article

Background: Chromosomal instability (CIN) and clonal heterogeneity (CH) are fundamental hallmarks of breast cancer that drive tumor evolution, disease progression, and therapeutic resistance. Understanding the mechanisms underlying these phenomena is essential for improving cancer diagnosis, prognosis, and treatment strategies. Methods: In this review, we provide a comprehensive overview of the biological processes contributing to CIN and CH, highlighting their molecular determinants and clinical relevance. Results: We discuss the latest advances in detection methods, including single-cell sequencing and other high-resolution techniques, which have enhanced our ability to characterize intratumoral heterogeneity. Additionally, we explore how CIN and CH influence treatment responses, their potential as therapeutic targets, and their role in shaping the tumor immune microenvironment, which has implications for immunotherapy effectiveness. Conclusions: By integrating recent findings, this review underscores the impact of CIN and CH on breast cancer progression and their translational implications for precision medicine. Full article