Specific markers for colorectal cancer (CRC), preceded by colorectal adenoma (pre-CRC), are lacking. This study aimed to investigate whether microRNAs (miR-19a-3p, miR-92a-3p, miR-193a-3p, and miR-210-3p) from tissues and exosomes are potential CRC biomarkers and compare them to existing biomarkers, namely carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9. MiRNA was isolated in the samples of 52 CRC and 76 pre-CRC patients. Expression levels were analyzed by RT-qPCR. When comparing pre-CRC and CRC tissue expression levels, only miR-193a-3p showed statistically significant result (p < 0.0001). When comparing the tissues and exosomes of CRC samples, a statistically significant difference was found for miR-193a-3p (p < 0.0001), miR-19a-3p (p < 0.0001), miR-92a-3p (p = 0.0212), and miR-210-3p (p < 0.0001). A receiver-operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to evaluate the diagnostic value of CEA, CA 19-9, and miRNAs. CEA and CA 19-9 had good diagnostic values (AUCs of 0.798 and 0.668). The diagnostic value only of miR-193a-3p was highlighted (AUC = 0.725). The final logistic regression model, in which we put a combination of CEA concentration and the miR-193a-3p expression level in tissues, showed that using these two markers can distinguish CRC and pre-CRC in 71.3% of cases (AUC = 0.823). MiR-193a-3p from tissues could be a potential CRC biomarker.

UNASSIGNED: The aim of this study was to evaluate the prognostic value of imaging-based variables and tumor marker in predicting the progression-free survival (PFS) in treatment-naïve pancreatic cancer (PC) using baseline 18-fluorodeoxyglucose (18FDG) positron emission tomography/computed tomography (PET/CT).
UNASSIGNED: This retro-prospective study was conducted at PET/CT imaging facility of JCIA health-care facility of Pakistan. Total 68 patients with PCs were retrospectively included who had 18FDG PET/CT for staging from March 2017 to December 2020. Thirty-two patients had unresectable Stage IV disease on baseline imaging while the remaining 36 underwent Whipple\'s procedure and both categories were followed by chemotherapy with/without immunotherapy. These patients were followed for a median period of 18 months (1-62 months) for PFS. Logistic regression analysis and receiver operating characteristic (ROC) analysis were used for independent predictors of patients\' demographics, tumor characteristics, CA 19-9, and maximum standardized uptake value (SUVmax) in PFS. Kaplan-Meier\'s survival curves were analyzed to measure PFS using ROC-derived significant cutoff values of CA 19-9 and SUVmax.
UNASSIGNED: Median PFS was 18 months (11-45) with 60% (41/68) patients were either died or labelled having metabolic progressive disease (MPD. Using logistic regression analysis, significant correlations were found for Stage IV disease and pancreatic body/tail tumor with disease progression (odd ratio: 7.535 and 4.803, respectively; P < 0.05). Gender, obesity, histological tumor type, and 18FDG-avid regional nodes did not show a significant impact on PFS. On ROC analysis, SUVmax >5.3 of primary tumor and baseline CA 19-9 >197 U/ml were found to have a significant negative correlation with PFS (area under the curve: 0.827 and 0.911, respectively; P < 0.0001) and no association of age and primary tumor size in PFS. Significantly, shorter PFS was found using ROC-derived cutoff values of SUVmax >5.3 versus ≤5.3 of primary tumor (mean and 95% confidence interval [CI]: 16.7 vs. 48.5 and 10-23 vs. 41-56; log-rank = 25.014; P < 0.0001) and baseline CA 19-9 >197 versus ≤197 U/ml (mean and 95% CI: 11.8 vs. 46.9 and 7-16 vs. 39-55; log-rank = 38.217; P < 0.0001).
UNASSIGNED: SUVmax >5.3 of primary tumor and baseline CA 19-9 >197 U/ml were found to have a significant negative correlation with PFS in treatment-naïve PC patients. Among demographics, only Stage IV disease and pancreatic tail and body tumors were found to have a negative association with disease progression.

UNASSIGNED: Tumor markers are established laboratory tools that help to diagnose, estimate prognosis, and monitor the course of cancer. For meaningful decision-making in patient care, it is essential that methods and analytical platforms demonstrate high sensitivity, specificity, precision, and comparability. Regular participation at external quality assessment (EQA) schemes is mandatory for laboratories. Here, a longitudinal evaluation of EQA data was performed to assess the performance of tumor marker assays over time.
UNASSIGNED: Longitudinal data of the cancer antigens (CA) 15-3 (n = 5,492), CA 19-9 (n = 6,802), and CA 125 (n = 5,362) from 14 INSTAND EQAs conducted between 2019 and 2023 were evaluated. A median of 197, 244 and 191 laboratories participated at the EQAs for CA 15-3, CA 19-9 and CA 125, respectively. Data evaluation encompasses intra- and inter-manufacturer specific variations over time, assay precision, and adherence to the EQA limits of ±24% for CA 15-3, ±27% for CA 19-9 and ±36% for CA 125.
UNASSIGNED: The study showed median manufacturer-dependent differences of up to 107% for CA 15-3, 99% for CA 125, and even 549% for CA 19-9 between the highest and the lowest methods over the studied period. Regarding the normalized median of all methods, the values of the most deviant methods were 0.42 for CA 15-3, 7.61 for CA 19-9, and 1.82 for CA 125. Intra-manufacturer variability was generally low, with median coefficients of variation (CV) below 10%. As the methods were evaluated according to method-specific consensus values, most participants passed the EQAs within the acceptance criteria. When the criteria were consistently set at 24%, the central 90% of participants passed the EQAs in 78.6%-100% for CA 15-3 (with exception of AX), 89.3%-100% for CA 125, and 64.3%-100% for CA 19-9.
UNASSIGNED: While intra-method precision of most analytical platforms is acceptable for all three tumor markers, considerable inter-method variability was observed over the whole studied period demonstrating the necessity for better standardization and harmonization of the methods, development of international reference materials, and comprehensive commutability studies with patient samples.

Background/Objectives: Although the role of PET/CT imaging is well established in oncology, its diagnostic value in routine monitoring for recurrent colorectal cancer (CRC) is still controversial. The aim was to evaluate the diagnostic value of F-18 FDG PET/CT in detecting recurrent CRC in correlation with CEA, CA 19-9 levels, and conventional imaging modalities (CIM). Methods: Between 2009 and 2023, a retrospective study was performed including 134 CRC patients referred for PET/CT imaging on the suspicion of recurrence, based on elevated CEA and/or CA 19-9 and/or equivocal CIM findings. According to our institution\'s Tumor Board CRC protocol, after the initial treatment, which was dependent on the TNM stage (neoadjuvant therapy, primary resection, or adjuvant treatment), patients underwent a standard 5-year surveillance including CEA and CA 19-9 measurements, CIM, and colonoscopy, every six months. The statistics, including univariate and multivariate analyses were conducted using the IBM SPSS 20.0 statistical software. p-values < 0.05 were considered statistically significant. Results: Recurrent CRC was confirmed in 54/134 (40.3%) patients with elevated tumor markers. PET/CT showed high diagnostic performance in detecting recurrent CRC with sensitivity, specificity, PPV, NPV, and accuracy of 94.4%, 82.5%, 78.5%, 95.7%, and 87.3%, respectively. The CEA showed a high sensitivity of 98.1% but both low specificity and accuracy of 15% and 48.5%, respectively. The sensitivity, specificity, and accuracy for CA 19-9 and CIM for diagnosis of CRC recurrence were 44.4%, 67.5%, 58.2%, and 51.9%, 98.8%, 79.9%, respectively. The AUC for PET/CT, elevated CEA levels, CIM, and elevated CA 19-9 levels was 0.885 (95% CI: 0.824-0.946; p < 0.001), 0.844 (95% CI: 0.772-0.916; p < 0.001), 0.753 (95% CI: 0.612-0.844; p < 0.001), and 0.547 (95% CI: 0.442-0.652; p = 0.358), respectively. Univariate analysis showed that both PET/CT and CIM positive results were highly associated with CRC recurrence (p < 0.001 and p < 0.001, respectively). At the same time, gender, mucinous tumor type, presence of initial lymph node metastasis (N+), and presence of initial distant metastasis (M+) had no significance (p = 0.211, p = 0.158, p = 0.583, and p = 0.201, respectively). Our multivariate analysis showed that independent predictors for CRC recurrence are positive PET/CT scans (p < 0.001), positive CIM results (p = 0.001), and elevated CA 19-9 levels (p = 0.023). Although CA 19-9 was not detected as a statistically significant predictor in the univariate analysis (p = 0.358), in a multivariate analysis it was recognized as a significant predicting factor in detecting the CRC recurrence (p = 0.023). Conclusions: F-18 FDG PET/CT showed high diagnostic efficacy in CRC recurrence detection, in correlation with CEA levels, CA 19-9 levels, and CIM. This imaging modality should be routinely integrated into the post-operative follow-op in patients with elevated tumor markers.

BACKGROUND: Prenatal air pollution exposure has been associated with individual inflammatory, cardiovascular, and metabolic biomarkers in mothers and neonates. However, studies of air pollution and a comprehensive panel of biomarkers across maternal and cord blood samples remain limited. Few studies used data-driven methods to identify biomarker groupings that converge biomarkers from multiple biological pathways. This study aims to investigate the impacts of prenatal air pollution on groups of biomarkers in maternal and cord blood samples.
METHODS: In the Maternal And Developmental Risks from Environmental and Social Stressors (MADRES) cohort, 87 biomarkers were quantified from 45 trimester 1 maternal blood and 55 cord blood samples. Pregnancy and trimester 1-averaged concentrations of particulate matter ≤2.5 μm and ≤10 μm in diameter (PM2.5 and PM10), nitrogen dioxide (NO2), and ozone (O3) were estimated, using inverse distance squared weighted spatial interpolation from regulatory air monitoring stations. Traffic-related NOx was assessed using California Line Source Dispersion Model: freeway/highway roads, non-freeway major roads, non-freeway minor roads, and their sum as total NOx. Elastic Net (EN) regression within the rexposome R package was used to group biomarkers and assess their associations with air pollution.
RESULTS: In maternal samples, trimester 1-averaged PM10 was associated with elevated inflammation biomarkers and lowered cardiovascular biomarkers. NO2 exhibited positive associations with cardiovascular and inflammation markers. O3 was inversely associated with inflammation, metabolic, and cardiovascular biomarkers. In cord blood, pregnancy-averaged PM2.5 was associated with higher cardiovascular biomarkers and lower metabolic biomarkers. PM10 was associated with lower inflammation and higher cardiovascular biomarkers. Total and major road NOx was associated with lower cardiovascular biomarkers.
CONCLUSIONS: Prenatal air pollution exposure was associated with changes in biomarkers related to inflammation, cardiovascular, metabolic, cancer, and neurological function in both mothers and neonates. This study shed light on mechanisms by which air pollution can influence biological function during pregnancy.

UNASSIGNED: Differential diagnosis of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) in hospitalized patients is crucial for appropriate treatment choice.
UNASSIGNED: To investigate the relevance of serum tumor markers (STMs) and their combinations for the differentiation of NSCLC and SCLC subtypes.
UNASSIGNED: Between 2000 and 2003, 10 established STMs were assessed retrospectively in 311 patients with NSCLC, 128 with SCLC prior systemic first-line therapy and 51 controls with benign lung diseases (BLD), by automatized electrochemiluminescence immunoassay technology. Receiver operating characteristic (ROC) curves and logistic regression analyses were used to evaluate the diagnostic efficacy of both individual and multiple STMs with corresponding sensitivities at 90% specificity. Standards for Reporting of Diagnostic Accuracy (STARD guidelines) were followed.
UNASSIGNED: CYFRA 21-1 (cytokeratin-19 fragment), CEA (carcinoembryonic antigen) and NSE (neuron specific enolase) were significantly higher in all lung cancers vs BLD, reaching AUCs of 0.81 (95% CI 0.76-0.87), 0.78 (0.73-0.84), and 0.88 (0.84-0.93), respectively. By the three marker combination, the discrimination between benign and all malignant cases was improved resulting in an AUC of 0.93 (95% CI 0.90-0.96). In NSCLC vs. BLD, CYFRA 21-1, CEA and NSE were best discriminative STMs, with AUCs of 0.86 (95% CI 0.81-0.91), 0.80 (0.74-0.85), and 0.85 (0.79-0.91). The three marker combination also improved the AUC: 0.92; 95% CI 0.89-0.96). In SCLC vs. BLD, ProGRP (pro-gastrin-releasing peptide) and NSE were best discriminative STMs, with AUCs of 0.89 (95% CI 0.84-0.94) and 0.96 (0.93-0.98), respectively, and slightly improved AUC of 0.97 (95% CI 0.95-0.99) when in combination. Finally, discrimination between SCLC and NSCLC was possible by ProGRP (AUC 0.86; 95% CI 0.81-0.91), NSE (AUC 0.83; 0.78-0.88) and CYFRA 21-1 (AUC 0.69; 0.64-0.75) and by the combination of the 3 STMs (AUC 0.93; 0.91-0.96), with a sensitivity of 88% at 90% specificity.
UNASSIGNED: The results confirm the power of STM combinations for the differential diagnosis of lung cancer from benign lesions and between histological lung cancer subtypes.

Cholangiocarcinoma (CCA) is a deadly complication observed in the setting of primary sclerosing cholangitis (PSC). When symptoms develop and CCA is diagnosed, it is usually at an advanced stage. Median survival is less than 12 months. Early identification of CCA leads to improved outcomes. Although diagnostic tests have excellent specificity, they are plagued by low sensitivity. No surveillance strategies have been widely agreed upon, but most societies recommend measurement of serum carbohydrate antigen 19-9 and MRCP every 6 to 12 months in patients with PSC. Advances in understanding of the genetic factors that lead to CCA are awaited.

UNASSIGNED: Therapeutic possibilities for non-small cell lung cancer (NSCLC) have considerably increased during recent decades.
UNASSIGNED: To summarize the prognostic relevance of serum tumor markers (STM) for early and late-stage NSCLC patients treated with classical chemotherapies, novel targeted and immune therapies.
UNASSIGNED: A PubMed database search was conducted for prognostic studies on carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA 21-1), neuron-specific enolase, squamous-cell carcinoma antigen, progastrin-releasing-peptide, CA125, CA 19-9 and CA 15-3 STMs in NSCLC patients published from 2008 until June 2022.
UNASSIGNED: Out of 1069 studies, 141 were identified as meeting the inclusion criteria. A considerable heterogeneity regarding design, patient number, analytical and statistical methods was observed. High pretherapeutic CYFRA 21-1 levels and insufficient decreases indicated unfavorable prognosis in many studies on NSCLC patients treated with chemo-, targeted and immunotherapies or their combinations in early and advanced stages. Similar results were seen for CEA in chemotherapy, however, high pretherapeutic levels were sometimes favorable in targeted therapies. CA125 is a promising prognostic marker in patients treated with immunotherapies. Combinations of STMs further increased the prognostic value over single markers.
UNASSIGNED: Protein STMs, especially CYFRA 21-1, have prognostic potential in early and advanced stage NSCLC. For future STM investigations, better adherence to comparable study designs, analytical methods, outcome measures and statistical evaluation standards is recommended.

BACKGROUND: Previously considered inoperable patients (borderline resectable, locally advanced, synchronous oligometastatic or metachronous pancreatic adenocarcinoma (PDAC)) are starting to become resectable thanks to advances in chemo/radiotherapy and the reduction in operative mortality.
METHODS: This narrative review presents a chosen literature selection, giving a picture of the current state of treatment of these patients.
RESULTS: Neoadjuvant therapy (NAT) is generally recognized as the treatment of choice before surgery. However, despite the increased efficacy, the best pathological response is still limited to 10.9-27.9% of patients. There are still limited data on the selection of possible NAT responders and how to diagnose non-responders early. Multidetector computed tomography has high sensitivity and low specificity in evaluating resectability after NAT, limiting the resection rate of resectable patients. Ca 19-9 and Positron emission tomography are giving promising results. The prediction of early recurrence after a radical resection of synchronous or metachronous metastatic PDAC, thus identifying patients with poor prognosis and saving them from a resection of little benefit, is still ongoing, although some promising data are available.
CONCLUSIONS: In conclusion, high-level evidence demonstrating the benefit of the surgical treatment of such patients is still lacking and should not be performed outside of high-volume centers with interdisciplinary teams of surgeons and oncologists.

Two-needle 3D stochastic microsensors based on boron- and nitrogen-decorated gra-phenes, modified with N-(2-mercapto-1H-benzo[d]imidazole-5-yl), were designed and used for the molecular recognition and quantification of CA 72-4, CA 19-9, CEA and CA 125 biomarkers in biological samples such as whole blood, urine, saliva and tumoral tissue. The NBGr-2 sensor yielded lower limits of determination. For CEA, the LOD was 4.10 × 10-15 s-1 g-1 mL, while for CA72-4, the LOD was 4.00 × 10-11 s-1 U-1 mL. When the NBGr-1 sensor was employed, the best results were obtained for CA12-5 and CA19-9, with values of LODs of 8.37 × 10-14 s-1 U-1 mL and 2.09 × 10-13 s-1 U-1 mL, respectively. High sensitivities were obtained when both sensors were employed. Broad linear concentration ranges favored their determination from very low to higher concentrations in biological samples, ranging from 8.37 × 10-14 to 8.37 × 103 s-1 U-1 mL for CA12-5 when using the NBGr-1 sensor, and from 4.10 × 10-15 to 2.00 × 10-7 s-1 g-1 mL for CEA when using the NBGr-2 sensor. Student\'s t-test showed that there was no significant difference between the results obtained utilizing the two microsensors for the screening tests, at a 99% confidence level, with the results obtained being lower than the tabulated values.