Over the past few years, radiomics for the detection of intrahepatic cholangiocarcinoma (ICC) has been extensively studied. However, systematic evidence is lacking in the use of radiomics in this domain, which hinders its further development.

To address this gap, our study delved into the status quo and application value of radiomics in ICC and aimed to offer evidence-based support to promote its systematic application in this field.

PubMed, Web of Science, Cochrane Library, and Embase were comprehensively retrieved to determine relevant original studies. The study quality was appraised through the Radiomics Quality Score. In addition, subgroup analyses were undertaken according to datasets (training and validation sets), imaging sources, and model types.

Fifty-eight studies encompassing 12,903 patients were eligible, with an average Radiomics Quality Score of 9.21. Radiomics-based machine learning (ML) was mainly used to diagnose ICC (n=30), microvascular invasion (n=8), gene mutations (n=5), perineural invasion (PNI; n=2), lymph node (LN) positivity (n=2), and tertiary lymphoid structures (TLSs; n=2), and predict overall survival (n=6) and recurrence (n=9). The C-index, sensitivity (SEN), and specificity (SPC) of the ML model developed using clinical features (CFs) for ICC detection were 0.762 (95% CI 0.728-0.796), 0.72 (95% CI 0.66-0.77), and 0.72 (95% CI 0.66-0.78), respectively, in the validation dataset. In contrast, the C-index, SEN, and SPC of the radiomics-based ML model for detecting ICC were 0.853 (95% CI 0.824-0.882), 0.80 (95% CI 0.73-0.85), and 0.88 (95% CI 0.83-0.92), respectively. The C-index, SEN, and SPC of ML constructed using both radiomics and CFs for diagnosing ICC were 0.912 (95% CI 0.889-0.935), 0.77 (95% CI 0.72-0.81), and 0.90 (95% CI 0.86-0.92). The deep learning-based model that integrated both radiomics and CFs yielded a notably higher C-index of 0.924 (0.863-0.984) in the task of detecting ICC. Additional analyses showed that radiomics demonstrated promising accuracy in predicting overall survival and recurrence, as well as in diagnosing microvascular invasion, gene mutations, PNI, LN positivity, and TLSs.

Radiomics-based ML demonstrates excellent accuracy in the clinical diagnosis of ICC. However, studies involving specific tasks, such as diagnosing PNI and TLSs, are still scarce. The limited research on deep learning has hindered both further analysis and the development of subgroup analyses across various models. Furthermore, challenges such as data heterogeneity and interpretability caused by segmentation and imaging parameter variations require further optimization and refinement. Future research should delve into the application of radiomics to enhance its clinical use. Its integration into clinical practice holds great promise for improving decision-making, boosting diagnostic and treatment accuracy, minimizing unnecessary tests, and optimizing health care resource usage.

Cholangiocarcinomas (CCAs) are a heterogeneous group of malignant tumors that originate from the biliary tract. They are usually diagnosed in advanced stages, leading to a poor prognosis for affected patients. As CCA often arises as a sporadic cancer in individuals lacking specific risk factors or with heterogeneous backgrounds, and there are no defined high-risk groups, the implementation of effective surveillance programs for CCA is problematic. The identification and validation of new biomarkers useful for risk stratification, diagnosis, prognosis, and prediction of treatment response remains an unmet need for patients with CCA, even though numerous studies have been conducted lately to try to discover and validate CCA biomarkers. In this review, we overview the available information about the different types of biomarkers that have been investigated in recent years using minimally invasive biospecimens (blood, serum/plasma, bile, and urine) and their potential usefulness in diagnosis, prognosis, and risk stratification. It is widely accepted that early detection of CCA will impact patients' outcomes, by improving survival rates, quality of life, and the possibility of less invasive and/or curative treatments; however, challenges to its translation and clinical application for patients with CCA need to be resolved.

Oral cancer continues to cause profound suffering and is associated with high mortality rates. Early detection techniques are crucial in enhancing patient outcomes. This review paper thoroughly evaluates the significance of biomarkers and recent advancements in oral cancer detection, emphasizing cutting-edge electrochemical methods. The paper provides an epidemiological and etiological overview, outlining its clinical importance and reviewing the current state of the art in detection methods. Despite considerable progress, conventional methods exhibit limitations such as invasiveness, long wait times, and a lack of accuracy, creating a critical need for more robust technologies. This review emphasizes the significance of oral cancer biomarkers, which are considered promising cues for early detection, facilitating the development of innovative biosensing technologies. This review seeks to illuminate the recent advances in early detection and precision diagnostics, along with the usage of artificial intelligence strategies, ultimately contributing to significant progress in the battle against oral cancer.

Monitoring changes in serum tumor marker concentrations can help in the early diagnosis of non-small cell lung cancer (NSCLC). However, there are few methods to monitor the efficacy and prognosis of radiotherapy in NSCLC patients. The present research aimed to explore the correlation between radiotherapy efficacy and squamous cell carcinoma antigen (SCCA) and cytokeratin 19 soluble fragment (CYFRA21-1) levels in NSCLC patients. Serum CYFRA21-1 and SCCA were detected with an automatic chemiluminescence immunoassay analyzer. Patients with NSCLC were followed up by telephone at regular intervals for 35 months. The χ2 test was used to compare clinical characteristics such as age, gender, smoking history and other count data between groups. Predictive value of serum SCCA and CYFRA21-1 on the efficacy of radiotherapy was analyzed by Receiver Operating Characteristic (ROC) curves. The survival of the patients was analyzed by Kaplan-Meier method. The serum SCCA and CYFRA21-1 levels in the NSCLC group were apparently higher by comparison with control group. The SCCA and CYFRA21-1 concentration were both positive relevant to Tumor Node Metastasis (TNM) stage. The Area Under Curve (AUC) of serum SCCA and CYFRA21-1 were 0.732 and 0.721, respectively. In addition, high serum SCCA and CYFRA21-1 levels could predict poor radiotherapy outcomes. Patients with high serum concentration of SCCA and CYFRA21-1 have shorter survival times. High serum SCCA and CYFRA21-1 levels could predict poor prognosis and unfavorable efficacy of radiotherapy in invalids with NSCLC.

Thyroid carcinoma has an increasing incidence of endocrine system cancers. Fine needle aspiration cytology (FNAC) and thyroglobulin (Tg) are the primary diagnostic modalities employed for assessing metastatic lymph nodes (LNs) in thyroid cancer. Due to the limited accuracy, rare patients benefited from these procedures. In this research, we aimed to discover a dependable biomarker that could increase the accuracy of FNAC's ability to diagnose metastatic LNs among patients suffering from papillary thyroid cancer (PTC). From March 2021 to July 2023, 99 LNs from PTC patients who had thyroid ultrasonography suspicions of metastases were examined. All patients underwent FNAC, washout Tg and CYFRA 21-1 measurements. Surgical histology and a subsequent FNAC were utilized to validate the outcomes of LNs. In our study, the optimal cut-off value for CYFRA 21-1 washout fluid was 1.145 ng/mL, with a specificity of 94.00 % (slightly lower than Tg and FNAC at 98 %). However, CYFRA 21-1 demonstrated significantly higher diagnostic sensitivity (85.71 %) and accuracy (86.41 %) compared to Tg (71.43 %, 81.55 %) and FNAC (69.39 %, 80.58 %). Furthermore, FNAC plus washout CYFRA 21-1 performed better in diagnosing the metastatic LNs in PTC than FNAC plus Tg, which may indicate a novel solution for metastatic LNs diagnosis in PTC.

Cholangiocarcinoma is a lethal malignancy of the biliary epithelium that can arise anywhere along the biliary tract. Surgical resection confers the greatest likelihood of long-term survivability. However, its insidious onset, difficult diagnostics, and resultant advanced presentation render the majority of patients unresectable, highlighting the importance of early detection with novel biomarkers. Developing liver-directed therapies and emerging targeted therapeutics may offer improved survivability for patients with unresectable or advanced disease. In this article, the authors review the current multidisciplinary standards of care in resectable and unresectable cholangiocarcinoma, with an emphasis on novel biomarkers for early detection and nonsurgical locoregional therapy options.

As a consequence of breakthroughs in the area of guidelines research, the therapy for cholangiocarcinoma has significantly improved the efficacy rate of diagnosis and survival outcomes. We compared the most recently updated clinical practice guidelines and consensus to provide recommendations based on the diagnostic and therapeutic equipment available in various countries. Following a systematic review, we discovered that these guidelines and consensus had both similarities and differences in terms of what organizations or groups drafted the guidelines and the approach, applicability, content and recent updates of the guidelines as well as in terms of diagnostic and treatment algorithms. The disparities could be attributable to a variety of etiological factors, high risk patients, health resources, medical technology, treatment options, and income levels. Additionally, while complete adoption of guidelines may benefit physicians, patients, and authorities, there remains a disconnect between expected goals and implementation.

Regardless of anatomic origin, cholangiocarcinoma is generally an aggressive malignancy with a relatively high case fatality. Surgical resection with curative intent remains the best opportunity to achieve meaningful long-term survival. Most patients present, however, with advanced disease and less than 20% of patients are candidates for surgical resection. Unfortunately, even patients who undergo resection have a 5-year survival that ranges from 20 to 40%. Biomarkers are indicators of normal, pathologic, or biologic responses to an intervention and can range from a characteristic (i.e., blood pressure reading which can detect hypertension) to specific genetic mutations or proteins (i.e., carcinoembryonic antigen level). Novel biomarkers and improved molecular diagnostics represent an attractive opportunity to improve detection as well as to identify novel therapeutic targets for patients with cholangiocarcinoma. We herein review the latest advances in molecular diagnostics and biomarkers related to the early detection and treatment of patients with cholangiocarcinoma.

Cholangiocarcinoma (CCA) arises from the ductular epithelium of the biliary tree, either within the liver (intrahepatic CCA) or more commonly from the extrahepatic bile ducts (extrahepatic CCA). This disease has a poor prognosis and a growing worldwide prevalence. The poor outcomes of CCA are partially explained by the fact that a final diagnosis is challenging, especially the differential diagnosis between hepatocellular carcinoma and intrahepatic CCA, or distal CCA and pancreatic head adenocarcinoma. Most patients present with an advanced disease, unresectable disease, and there is a lack in non-surgical therapeutic modalities. Not least, there is an acute lack of prognostic biomarkers which further complicates disease management. Therefore, there is a dire need to find alternative diagnostic and follow-up pathways that can lead to an accurate result, either singlehandedly or combined with other methods. In the "-omics" era, this goal can be attained by various means, as it has been successfully demonstrated in other primary tumors. Numerous variants can reach a biomarker status ranging from circulating nucleic acids to proteins, metabolites, extracellular vesicles, and ultimately circulating tumor cells. However, given the relatively heterogeneous data, extracting clinical meaning from the inconsequential noise might become a tall task. The current review aims to navigate the nascent waters of the non-invasive approach to CCA and provide an evidence-based input to aid clinical decisions and provide grounds for future research.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer with an increasing worldwide mortality rate. Cholangiocarcinoma (CCA) is the second most common primary liver cancer. In both types of cancers, early detection is very important. Biomarkers are a relevant part of diagnosis, enabling non-invasive detection and control of cancer recurrence, as well as in the application of screening tests in high-risk groups. Furthermore, some of these biomarkers are useful in controlling therapy and treatment selection. Detection of some markers presents higher sensitivity and specificity in combination with other markers when compared with a single detection. Some gene aberrations are also prognostic markers in the two types of cancers. In the following review, we discuss the most common biomarkers and genetic markers currently being used in the diagnosis of hepatocellular carcinoma and cholangiocarcinoma.

Aggregation-induced electrochemiluminescence reagent, a distyrylbenzene derivative with donor-acceptor conjugated nanosheet structure, namely TPAPCN, was used as a trace label and modified on the electrode through the formation of classical sandwich complex of antibody-antigen-antibody in this work. In aggregate state, TPAPCN with twisted structure was limited in nanometer space through intermolecular π - π stacking interactions, which not only restricts the intramolecular motions but also combines a large number of singlet excitons to greatly trigger electrochemiluminescence (ECL). The ECL signal of this system enhanced with more captured cytokeratin 19 fragment 21-1 (CYFRA21-1) on the modified electrode. Three-dimensional graphene/platinum nanoparticles with large specific surface, and excellent electroconductivity and biocompatibility were prepared and acted as excellent carriers for thionine handling (3D-GN/PtNPs/Th), which was employed for improving the loading of antibodies and generating internal electrochemical signal. Consequently, a novel ratiometric sandwich immunosensor for CYFRA21-1 detection was fabricated based on TPAPCN and 3D-GN/PtNPs/Th, that is, a rapid and reliable detection was achieved through the ratio between ECL and electrochemical signals. The prepared sensor performed good linearity in the range of 50 fg/mL to 1 ng/mL with a detection limit as low as 16 fg/mL. Moreover, the detection results revealed well in the analysis of human serum samples, demonstrating a significant application for clinical monitoring and biomolecules detection.

Introduction:Although advances in understanding the molecular basis of cholangiocarcinoma (CCA) have been made, surgery is the only curative therapy option and the overall prognosis of patients suffering from the disease remains poor. Therefore, estimation of prognosis based on known and novel biomarkers is essential for therapy guidance of CCA in both, curative and palliative settings.Areas covered:An extensive literature search on biomarkers for CCA with special emphasis on prognosis was performed. Based on this, prognostic biomarkers from serum, tumor tissue and other compartments that are currently in use or under evaluation for CCA were summarized in this review. Furthermore, an overview of new biomarkers was provided including those determined from extracellular vesicles (EVs), metabolites and nucleic acids. Finally, prognostic markers associated with potential new therapy options for the treatment of CCA were summed up.Expert opinion:So far, an optimal prognostic biomarker for CCA has not been described. However, based on the increasing knowledge about the molecular basis of CCA but also due to novel, innovative technologies, a plethora of novel prognostic biomarkers is currently under evaluation and will be available for CCA in future.

A novel ratiometric electrochemical (EC) sensing platform was established for sensitive immunoassay of target cytokeratin 19 fragment 21-1 (CYFRA21-1) biomarker by combining competitive immunoreaction and multisignal output. This immunosensor utilized Ag nanoparticles (NPs)-functionalized urchin-like Fe₃O₄@polydopamine (u-Fe₃O₄@PDA-Ag) as a matrix to immobilize CYFRA21-1 antigens and methylene blue (MB)-absorbed Ni₃Si₂O₅(OH)₄-Au nanotubes (NTs) to label the anti-CYFRA21-1 (Ab). During the competitive immunoreaction, square wave voltammetric (SWV) current changes of Ag NPs from u-Fe₃O₄@PDA-Ag indicator and MB from Ni₃Si₂O₅(OH)₄-Au/MB indicator are relevant to the dosage of CYFRA21-1-acquired Ni₃Si₂O₅(OH)₄-Au/MB/Ab. More importantly, numerous CYFRA21-1 loaded stably on u-Fe₃O₄@PDA-Ag exhibited strong competitive capacity toward the target-CYFRA21-1 to combine Ni₃Si₂O₅(OH)₄-Au/MB/Ab, causing sensitive changes in the ratio of two measured SWV currents. Prominently, "ΔI = ΔI_MB + |ΔI_Ag NPs|" (ΔI_MB and |ΔI_Ag NPs| represents the change values of the oxidation peak currents of MB and Ag NPs, respectively) could be regarded as significantly amplifying the signal response and ultimately improving the sensitivity of CYFRA21-1 detection, from which we derived a wide dynamic range from 500 fg/mL to 50 ng/mL and a low detection limit of 0.39 pg/mL (S/N = 3). This work may exert a profound impact on monitoring other biomarkers in early diagnosis of diseases.

Hepatocellular carcinoma (HCC) is a heterogeneous neoplasm, both from the molecular and histomorphological aspects. One example of heterogeneity is the expression of keratin 19 (K19) in a subset (4-28%) of HCCs. The presence of K19 expression in HCCs has important clinical implications, as K19-positive HCCs have been associated with aggressive tumor biology and poor prognosis. Histomorphologically, K19-positive HCCs demonstrate a more infiltrative appearance, poor histological differentiation, more frequent vascular invasion, and more intratumoral fibrous stroma than K19-negative conventional HCCs. From the molecular aspect, K19-positive HCCs have been matched with various gene signatures that have been associated with stemness and poor prognosis, including the G1-3 groups, S2 class, cluster A, proliferation signature, and vascular invasion signature. K19-positive HCCs also show upregulated signatures related to transforming growth factor-β pathway and epithelial-to-mesenchymal transition. The main regulators of K19 expression include hepatocyte growth factor-MET paracrine signaling by cancer-associated fibroblast, epidermal growth factor-epidermal growth factor receptor signaling, laminin, and DNA methylation. Clinically, higher serum alpha-fetoprotein levels, frequent association with chronic hepatitis B, more invasive growth, and lymph node metastasis have been shown to be characteristics of K19-positive HCCs. Radiologic features including atypical enhancement patterns, absence of tumor capsules, and irregular tumor margins can be a clue for K19-positive HCCs. From a therapeutic standpoint, K19-positive HCCs have been associated with poor outcomes after curative resection or liver transplantation, and resistance to systemic chemotherapy and locoregional treatment, including transarterial chemoembolization and radiofrequency ablation. In this review, we summarize the currently available knowledge on the clinico-radio-pathological and molecular features of K19-expressing HCCs, including a detailed discussion on the regulation mechanism of these tumors.

Oropharyngeal squamous cell carcinoma (OPSCC) is a kind of squamous cell carcinoma of head and neck, and its incidence is on the rise in recent years. A variety of prognostic markers for OPSCC have been reported in many studies, but they are expensive or difficult to obtain. So, we retrospectively studied the prognostic significance of cytokeratin 19 soluble fragment (Cyfra21-1) in patients with OPSCC, in order to provide theoretical basis for accurate prognosis assessment.

A retrospective analysis of the clinicopathological data of 85 OPSCC patients with concurrent radiotherapy and chemotherapy (CRT) admitted from January 2010 to June 2017. Serum Cyfra21-1 levels were measured before treatment. Analyze the relationship between Cyfra21-1 and clinical pathological characteristics of patients. The receiver operating characteristic (ROC) curve was used to calculate the cut-off value of Cyfra21-1. The Cox proportional hazard model was used to conduct univariate and multivariate analysis of related prognostic factors, and to determine the factors related to overall survival (OS) and progression-free survival (PFS).

The cutoff value for Cyfra21-1 was 2.93 ng/mL. The baseline data of patients in different Cyfra21-1 groups were balanced and comparable. In the univariate and multivariate analyses, it was found that Cyfra21-1 was associated with OS and PFS. A measurement of Cyfra21-1 ≥2.93 ng/mL indicated poor OS (P<0.001) and PFS (P=0.001). After adjusting for age and disease stage, Cyfra21-1 can independently affect the OS (HR =3.57, 95% CI: 1.60-7.99, P=0.002) and PFS (HR =2.89, 95% CI: 1.41-5.91, P=0.004) of patients with OPSCC treated with CRT.

Pre-treatment Cyfra21-1 can be used as a prognostic marker for patients with OPSCC treated with CRT, which has important clinical significance.