Carbohydrate Antigen Research Articles

Preoperative prediction of early recurrence in resectable pancreatic cancer integrating clinical, radiologic, and CT radiomics features

ObjectivesTo use clinical, radiographic, and CT radiomics features to develop and validate a preoperative prediction model for the early recurrence of pancreatic cancer.MethodsWe retrospectively analyzed 190 patients (150 and 40 in the development and test cohort from different centers) with pancreatic cancer who underwent pancreatectomy between January 2018 and June 2021. Radiomics, clinical-radiologic (CR), and clinical-radiologic-radiomics (CRR) models were developed for the prediction of recurrence within 12 months after surgery. Performance was evaluated using the area under the curve (AUC), Brier score, sensitivity, and specificity.ResultsEarly recurrence occurred in 36.7% and 42.5% of the development and test cohorts, respectively (P = 0.62). The features for the CR model included carbohydrate antigen 19-9 > 500 U/mL (odds ratio [OR], 3.60; P = 0.01), abutment to the portal and/or superior mesenteric vein (OR, 2.54; P = 0.054), and adjacent organ invasion (OR, 2.91; P = 0.03). The CRR model demonstrated significantly higher AUCs than the radiomics model in the internal (0.77 vs. 0.73; P = 0.048) and external (0.83 vs. 0.69; P = 0.038) validations. Although we found no significant difference between AUCs of the CR and CRR models (0.83 vs. 0.76; P = 0.17), CRR models showed more balanced sensitivity and specificity (0.65 and 0.87) than CR model (0.41 and 0.91) in the test cohort.ConclusionsThe CRR model outperformed the radiomics and CR models in predicting the early recurrence of pancreatic cancer, providing valuable information for risk stratification and treatment guidance.

A case of rapidly progressing sarcomatous intrahepatic cholangiocarcinoma with suddenly appearing lymph node metastasis

BackgroundThe sarcomatous variant of carcinoma is relatively rare in intrahepatic cholangiocarcinoma (ICC). Sarcomatous ICC (SICC) is associated with a poorer prognosis compared with ICC. SICC is rarely diagnosed before surgery due to non-descriptive findings; it progresses rapidly, resulting in miserable prognosis. Here, we report a case of rapidly progressing SICC that showed a clinically significant tumor growth rate.Case presentationA 77-year-old woman who had undergone ileocecal resection for cecal cancer 5 years previously was found to have elevated levels of the tumor marker carbohydrate antigen 19-9. Although an abdominal computed tomography (CT) scan did not detect any liver mass lesions until 3 months before this serum examination, the subsequent CT scan revealed a hypodensity 20 mm mass lesion in the right anterior section. Contrast-enhanced CT and magnetic resonance imaging revealed peripheral enhancement in the arterial-to-equilibrium phase. Fluorodeoxyglucose positron emission tomography revealed uptake in the lesion. None of the imaging modalities showed lymph node swelling or distant metastases. She underwent hepatectomy under the diagnosis of ICC or an atypical metastasis from previous cecal cancer. Although preoperative images showed no suspicious lymph node metastasis 3 weeks prior, the hilar lymph node swelled 3 cm and contained adenocarcinoma. Consequently, the patient underwent right anterior sectionectomy and lymph node dissection of the hepatoduodenal ligament. Histopathological examination revealed that the liver tumor was a poorly differentiated adenocarcinoma with sarcomatous pattern. While the patient received adjuvant gemcitabine and S-1 therapy, lymph node metastasis appeared in the mediastinum 13 months after the surgery. She received gemcitabine + cisplatin + S-1 therapy but died 20 months after surgery.ConclusionSICC and lymph node metastasis clinically appeared within 3 months and 3 weeks, respectively. Suspected ICC that rapidly progresses should be considered SICC and treated with early resection. SICC is often missed in clinical diagnosis and has a poor prognosis, even after curative resection. While an alternative strategy involving preoperative biopsy and neoadjuvant therapy may be beneficial, it should be approached with discretion due to the potential risks of tumor progression and peritoneal dissemination.

Evaluating combined bevacizumab and XELOX in advanced colorectal cancer: Serum markers carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 199 analysis.

Colorectal cancer ranks third and second among common and fatal cancers. The treatment of metastatic colorectal cancer (mCRC) is generally based on XELOX in clinical practice, which includes capecitabine (CAP) and oxaliplatin. Serum tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 125 and CA199 are prognostic factors for various tumors. To investigate evaluating combined bevacizumab (BEV) and XELOX in advanced colorectal cancer: Serum markers CEA, CA125, CA199 analysis. In this retrospective study, a total of 94 elderly patients diagnosed with mCRC were recruited and subsequently categorized into two groups based on the distinct treatment modalities they received. The control group was treated with XELOX plus CAP (n = 47), while the observation group was treated with XELOX plus CAP and BEV (n = 47). Several indexes were assessed in both groups, including disease control rate (DCR), incidence of adverse effects, serum marker levels (CEA, CA125, and CA19) and progression-free survival (PFS). After 9 wk of treatment, the serum levels of CEA, CA199 and CA125 in the observation group were significantly lower than those in the control group (P < 0.05). Moreover, the PFS of the observation group (9.12 ± 0.90 mo) was significantly longer than that of the control group (6.49 ± 0.64 mo). Meanwhile, there was no statistically significant difference in the incidence of adverse reactions and DCR between the two groups during maintenance therapy (P > 0.05). On the basis of XELOX treatment, the combination of BEV and CAP can reduce serum tumor marker levels and prolong PFS in patients with mCRC.

The prognosis-based classification model in resectable pancreatic cancer

AimPancreatic ductal adenocarcinoma treatment is mainly based on the anatomical resectability classification. However, prognosis-based classification may be more reasonable. In this study, we stratified resectable pancreatic ductal adenocarcinoma according to preoperative factors and reconsidered treatment strategies. MethodsWe retrospectively evaluated 131 patients who underwent upfront surgery for resectable pancreatic ductal adenocarcinoma between 2007 and 2019. Recurrence within 1 year after surgery was defined as early recurrence, and the risk factors for early recurrence were identified using preoperative factors. Subsequently, we calculated the scores and stratified the participant groups. ResultsFifty-five (42 %) patients who relapsed within 1 year showed significantly poorer survival than those without recurrence (median overall survival, 14.0 vs. 80.6 months; p < 0.01). Multivariate analysis revealed that a tumor diameter of ≥24 mm (p < 0.01) and preoperative serum carbohydrate antigen 19-9 level of ≥380 U/mL (p = 0.04) were the independent risk factors for early recurrence. Early recurrence score was created using these factors, stratifying the participant group into three groups of 0–2 points, and the prognosis was significantly different (median overall survival, 49.3 vs. 31.2 vs. 16.0 months; p < 0.01). ConclusionWe stratified the upfront surgical cases of resectable pancreatic ductal adenocarcinoma. The group with a score of 0 had a good prognosis, and upfront surgery was possibly not futile on patients in poor general condition. The group with a score of 2 had a poor prognosis and may require stronger preoperative treatment.

Serum CEA as a Prognostic Marker for Overall Survival in Patients with Localized Pancreatic Adenocarcinoma and Non-Elevated CA19-9 Levels Treated with FOLFIRINOX as Initial Treatment: A TAPS Consortium Study.

About 25% of patients with localized pancreatic adenocarcinoma have non-elevated serum carbohydrate antigen (CA) 19-9 levels at baseline, hampering evaluation of response to preoperative treatment. Serum carcinoembryonic antigen (CEA) is a potential alternative. This retrospective cohort study from five referral centers included consecutive patients with localized pancreatic adenocarcinoma (2012-2019), treated with one or more cycles of (m)FOLFIRINOX, and non-elevated CA19-9 levels (i.e., < 37U/mL) at baseline. Cox regression analyses were performed to assess prognostic factors for overall survival (OS), including CEA level at baseline, restaging, and dynamics. Overall, 277 patients were included in this study. CEA at baseline was elevated (≥5ng/mL) in 53 patients (33%) and normalized following preoperative therapy in 14 patients (26%). In patients with elevated CEA at baseline, median OS in patients with CEA normalization following preoperative therapy was 33 months versus 19 months in patients without CEA normalization (p = 0.088). At time of baseline, only elevated CEA was independently associated with (worse) OS (hazard ratio [HR] 1.44, 95% confidence interval [CI] 1.04-1.98). At time of restaging, elevated CEA at baseline was still the only independent predictor for (worse) OS (HR 1.44, 95% CI 1.04-1.98), whereas elevated CEA at restaging (HR 1.16, 95% CI 0.77-1.77) was not. Serum CEA was elevated in one-third of patients with localized pancreatic adenocarcinoma having non-elevated CA19-9 at baseline. At both time of baseline and time of restaging, elevated serum CEA measured at baseline was the only predictor for (worse) OS. Therefore, serum CEA may be a useful tool for decision making at both initial staging and time of restaging in patients with non-elevated CA19-9.

Pleural fluid carbohydrate antigen 72-4 and malignant pleural effusion: a diagnostic test accuracy study.

The prognosis of malignant pleural effusion (MPE) is poor. A timely and accurate diagnosis is the prerequisite for managing MPE patients. Carbohydrate antigen 72-4 (CA72-4) is a diagnostic tool for MPE. We aimed to evaluate the diagnostic accuracy of pleural fluid CA72-4 for MPE. A prospective, preregistered, and double-blind diagnostic test accuracy study. We prospectively enrolled participants with undiagnosed pleural effusions from two centers in China (Hohhot and Changshu). CA72-4 concentration in pleural fluid was measured by electrochemiluminescence. Its diagnostic accuracy for MPE was evaluated by a receiver operating characteristic (ROC) curve. The net benefit of CA72-4 was determined by a decision curve analysis (DCA). In all, 153 participants were enrolled in the Hohhot cohort, and 58 were enrolled in the Changshu cohort. In both cohorts, MPE patients had significantly higher CA72-4 levels than benign pleural effusion (BPE) patients. At a cutoff value of 8 U/mL, pleural fluid CA72-4 had a sensitivity, specificity, and area under the ROC curve (AUC) of 0.46, 1.00, and 0.79, respectively, in the Hohhot cohort. In the Changshu cohort, CA72-4 had a sensitivity, specificity, and AUC of 0.27, 0.94, and 0.86, respectively. DCA revealed the relatively high net benefit of CA72-4 determination. In patients with negative cytology, the AUC of CA72-4 was 0.67. Pleural fluid CA72-4 helps differentiate MPE and BPE in patients with undiagnosed pleural effusions.

Prognostic and diagnostic value of circulating IGFBP2 in pancreatic cancer.

Insulin-like growth factor binding protein 2 (IGFBP2) is overexpressed in tumor tissues of several malignancies, including pancreatic cancer. Because of its role in tumor progression, IGFBP2 has been investigated as a tumor biomarker. However, little is known about its utility in pancreatic cancer. Plasma IGFBP2 levels were determined using enzyme-linked immunosorbent assay in 75 patients with pancreatic ductal adenocarcinoma (PDAC), 73 matched healthy controls, and 17 chronic pancreatitis patients. Our results showed that the plasma IGFPB2 level was significantly higher in PDAC patients than in patients with chronic pancreatitis and healthy controls. At a cut-off value of 333.9 ng/mL, the specificity and sensitivity were 78.08 and 65.33%, respectively. IGFBP2 level alone did not outperform carbohydrate antigen 19-9 (CA19-9) in diagnostic accuracy, but it successfully identified 9 out of 24 PDAC patients who were misidentified by CA19-9. The combination of IGFBP2 and CA19-9 was more accurate in the detection of PDAC than CA19-9 alone. IGFBP2 was more accurate than the other in discriminating between chronic pancreatitis and PDAC. Plasma IGFBP2, rather than CA19-9, was higher in the new-onset diabetes, lymph node involvement, and distant metastasis subgroups. IGFBP2 level was notably higher in stage IV cases than in stage I/II or stage III disease. However, CA19-9 did not show a difference between stages. After adjusting for lymph node involvement and distant metastasis, plasma IGFBP2 was identified as an independent prognostic marker for PDAC. The median survival time for patients with an IGFBP2 level ≥333.9 ng/mL was significantly shorter than that for patients with an IGFBP2 level <333.9 ng/mL. Marked elevation of plasma IGFBP2 in PDAC is associated with poorer survival. IGFBP2 may be considered as a supplementary biomarker for the diagnosis and prognostic prediction in Chinese pancreatic cancer patients.

Clinical value of ACR O-RADS combined with CA125 in the risk stratification of adnexal masses.

To develop a combined diagnostic model integrating the subclassification of the 2022 version of the American College of Radiology (ACR) Ovarian-Adnexal Reporting and Data System (O-RADS) with carbohydrate antigen 125 (CA125) and to validate whether the combined model can offer superior diagnostic efficacy than O-RADS alone in assessing adnexal malignancy risk. A retrospective analysis was performed on 593 patients with adnexal masses (AMs), and the pathological and clinical data were included. According to the large differences in malignancy risk indices for different image features in O-RADS category 4, the lesions were categorized into groups A and B. A new diagnostic criterion was developed. Lesions identified as category 1, 2, 3, or 4A with a CA125 level below 35 U/ml were classified as benign. Lesions identified as category 4A with a CA125 level more than or equal to 35 U/ml and lesions with a category of 4B and 5 were classified as malignant. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the curve (AUC) of O-RADS (v2022), CA125, and the combined model in the diagnosis of AMs were calculated and compared. The sensitivity, specificity, PPV, NPV, accuracy, and AUCs of the combined model were 92.4%, 96.5%, 80.2%, 98.8%, 94.1%, and 0.945, respectively. The specificity, PPV, accuracy, and AUC of the combined model were significantly higher than those of O-RADS alone (all P < 0.01). In addition, both models had acceptable sensitivity and NPV, but there were no significant differences among them (P > 0.05). The combined model integrating O-RADS subclassification with CA125 could improve the specificity and PPV in diagnosing malignant AMs. It could be a valuable tool in the clinical application of risk stratification of AMs.

Effects of TP regimen combined with intraperitoneal hyperthermic perfusion chemotherapy on immune function, quality of life and prognosis of patients with advanced ovarian cancer.

To evaluate the effect of paclitaxel and cisplatin (TP regimen) combined with intraperitoneal hyperthermic perfusion chemotherapy on immune function and quality of life in patients with advanced ovarian cancer. This retrospective study involved 107 patients with advanced ovarian cancer who were treated in Baoji Central Hospital between March 2016 and March 2020. The control group was treated with the TP regimen alone (n=48), while the observation group received additional intraperitoneal heat infusion chemotherapy containing 60 mg of cisplatin on the 8th day following the final chemotherapy (n=59). Immunoglobulin (IgG, IgA, IgM) levels, quality of life, tumor marker levels, incidence of adverse effects, and 3-year survival were compared between the two groups. Besides, factors affecting patients' prognosis were detected by unifactorial and multifactorial analyses. Before treatment, there was no significant difference between the two groups in terms of IgG, IgA, and IgM levels (all P>0.05). After treatment, the observation group showed significantly higher levels of IgG, IgA, and IgM than those in the control group (all P<0.05). There were no significant differences in pre-treatment Kamofsky (KPS) score, carcinoembryonic antigen (CEA), and carbohydrate antigen 125 (CA125) between the two groups (all P>0.05). However, after treatment, the KPS score was significantly increased in the observation group as compared to pre-treatment or control group (both P<0.05), while CEA and CA125 significantly decreased in the observation group as compared to pre-treatment or control group (all P<0.05). Nevertheless, the incidence of gastrointestinal reactions in the observation group was higher than that in the control group (P<0.05). The survival rate of the observation group was significantly higher than that of the control group (P<0.05). The AUC of post-treatment IgG for predicting 3-year survival of patients was 0.743. The 3-year survival rate of patients with IgG≥10.950 g/L was significantly higher than that of patients with IgG<10.950 g/L (P<0.05). Multifactorial Cox regression analysis revealed that higher FIGO stage, presence of ascites, higher post-treatment IgG level, and higher post-treatment CEA and CA125 levels were independent risk factors for patients' 3-year mortality. TP regimen combined with intraperitoneal hyperthermic perfusion chemotherapy significantly improves immune function and quality of life in patients with advanced ovarian cancer, although it increases the incidence of gastrointestinal reactions. Higher FIGO stage, presence of ascites, higher IgG after treatment, higher CEA, and higher CA125 were independent risk factors for patients' 3-year mortality.

Predicting epithelial ovarian cancer prognosis: correlation of posttreatment 18F-fluorodeoxyglucose positron emission tomography-computed tomography metabolic parameters, serum carbohydrate antigen, and human epididymis protein levels with overall survival.

Identifying reliable prognostic indicators can aid in improving patient care. The aim of this study was to establish the association of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) whole-body metabolic parameters, serum carbohydrate antigen 125 (CA125), and human epididymis protein 4 (HE4) with overall survival (OS) in patients with epithelial ovarian cancer (EOC) after surgery combined with platinum-based chemotherapy. From May 2014 to May 2019, a total of 79 patients with EOC who underwent posttreatment 18F-FDG PET/CT in the First Affiliated Hospital of Chongqing Medical University were included. Clinical data and laboratory indicators were obtained. The whole-body maximum standardized uptake value (WBSUVmax), whole-body metabolic tumor volume (WBMTV), and whole-body total lesion glycolysis (WBTLG) were measured and calculated on 18F-FDG PET/CT. The follow-up was conducted until February 2023, and the endpoint was death from any cause. Pearson correlation analysis, Kaplan-Meier, and Cox proportional regression were used in this study. The PET-positive (PET-P) patients had significantly decreased OS based on either Kaplan-Meier survival analysis (P<0.001) or univariate Cox regression analysis [hazard ratio (HR) =40.177, 95% confidence interval (CI): 2.690-600.134; P=0.007]. "Ln" is a logarithmic transformation with a base of "e" (natural logarithm). LnWBMTV, lnWBTLG, and therapy after PET were independent predictors of OS in a cohort of 63 PET-P patients. The difference in OS between groups sorted by the median WBMTV (4.16; P<0.001) and WBTLG (14.71; P<0.001) was statistically significant. There were statistically significant differences in CA125 and HE4 levels between patients in the PET-P and PET-negative (PET-N) groups (P<0.001). In the PET-P patient cohort, serum HE4 levels were substantially correlated with WBMTV and WBTLG. Kaplan-Meier survival analysis suggested a reduction in OS after treatment in patients with EOC positive for CA125, HE4, and PET (P<0.001). Post-PET/CT treatment strategy, WBMTV, and WBTLG demonstrated significant prognostic utility in predicting posttreatment OS in patients with EOC. Patients who tested positive for both tumor markers CA125 and HE4 and had a positive PET scan demonstrated a significantly poorer prognosis in terms of posttreatment OS.

Development and validation of nomograms based on pre-/post-operative CEA and CA19-9 for survival predicting in stage I-III colorectal cancer patients after radical resection.

Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are the predominant serum tumour markers (STMs) for predicting the prognosis of colorectal cancer (CRC). The objective of this research is to develop clinical prediction models based on preoperative and postoperative CEA and CA19-9 levels. 1,452 consecutive participants with stage I-III colorectal cancer were included. Kaplan-Meier method, log-rank test, and multivariate COX regression were used to evaluate the significance of preoperative and postoperative STMs. Patients were grouped into a discovery cohort (70%) and a validation cohort (30%). Variables for the nomograms were selected according to the Akaike information criterion (AIC). Subsequently, two clinical predictive models were constructed, evaluated, validated, and then compared with the AJCC 8th TNM stage. The overall survival (OS) rate and disease-free survival(DFS) rate declined progressively as the number of positive tumour markers(NPTMs) before and after surgery increased. For both OS and DFS, age, sex, pN stage, and NPTMs before and after surgery were independent prognostic factors, and then clinical prediction models were developed. The Concordance index (C-index), Receiver operating characteristic (ROC) curve, calibration curve, Decision curve analysis (DCA), and risk score stratification all indicated that the models possessed robust predictive efficacy and clinical applicability. The Net reclassification index (NRI) and Integrated discrimination improvement (IDI) indicated that the performance of models was significantly superior to the TNM stage. Nomograms based on pre-and postoperative CEA and CA19-9 can accurately predict survival and recurrence for stage I-III CRC patients after radical surgery, and were significantly better than the AJCC 8th TNM stage.

CA125-Associated Activated Partial Thromboplastin Time and Thrombin Time Decrease in Patients with Adenomyosis.

Adenomyosis patients are in a hypercoagulable state, and studies have shown that carbohydrate antigen125 (CA125) may relate to the hypercoagulability and thrombosis of patients with adenomyosis, but there is still a lack of clarity regarding the changes in CA125-related coagulation indicators. This study was to explore the changes and influencing factors of CA125-related coagulation parameters in patients with adenomyosis. Retrospective observational study conducted on 200 patients with adenomyosis (AM group), 240 patients with uterine leiomyoma (LM group) and 81 patients with cervical intraepithelial neoplasia (CIN)-III (control group), of which the coagulation parameters were detected by clinical blood sample collection and statistical method analysis and informed consent was obtained. The level of CA125 in the AM group was significantly higher than that in the LM group and control group. However, thrombin time (TT) shortened in the AM group when compared with the LM and control group. Activated partial thromboplastin time (APTT) in the AM group was shorter than in the control group. Multivariate logistic regression analysis found that adenomyosis was associated with CA125 level (OR=323.860, 95% CI 90.424-1159.924, P<0.001), APTT (OR=1.295, 95% CI 1.050-1.598, P=0.016), TT (OR=0.642, 95% CI 0.439-0.938, P=0.022), menorrhagia (OR=7.363, 95% CI 2.544-21.315, P<0.001), dysmenorrhea (OR=22.590, 95% CI 8.185-62.347, P<0.001). Correlation analysis revealed that APTT (r= -0.207) and TT (r = -0.174) were negatively correlated with the level of CA125. The shortening of CA125-related APTT and TT indicates that it is meaningful to detect coagulation parameters of patients with elevated CA125 levels early, dysmenorrhea and menorrhagia, and maybe further discover the hypercoagulability and prevent the occurrence of thrombus in adenomyosis.

Effects of Yipi Huayu decoction on tumor markers, immune function, and adverse reactions during chemotherapy in gastric cancer patients: a retrospective propensity score-matched study.

To analyze the effects of Yianpi Huayu Decoction on tumor markers, immune function and adverse reactions during chemotherapy in patients with gastric cancer. The clinical data of 154 patients with progressive gastric cancer who attended Baoji Maternal and Child Health Hospital (Daijiawan Branch) from January 2020 to March 2022 were retrospectively analyzed. The patients were divided into an observation group (61 cases) and a control group (93 cases) according to the treatment method and were matched using propensity score matching (PSM). The control group was given SOX neoadjuvant chemotherapy regimen (oxaliplatin + tiglio), and the observation group was given spleen-strengthening and blood-stasis-reducing tonics as adjuvant treatment on the basis of the treatment given to the control group. Clinical efficacy in the two groups was observed, as well as Carbohydrate Antigen 19-9 (CA19-9), Carbohydrate Antigen 72-4 (CA72-4), and Carcinoembryonic Antigen (CEA) levels, immune function (IgA, IgM, and IgG), Karnofsky Performance Scale (KPS), and occurrence of adverse reactions. After matching, there was no significant difference in the total clinical efficiency between the two groups (P > 0.05). After matching, there were no differences in CA19-9, CA72-4, and CEA levels between the observation group and the control group before or after treatment (P > 0.05). After matching, the IgA, IgM, and IgG levels in the observation group were significantly better than those in the control group after treatment (P < 0.05). The incidence of leukopenia (P = 0.011) and diarrhea (P = 0.011) during treatment was higher in the control group than in the observation group after matching. The KPS score of the observation group was higher than that of the control group after matching (P < 0.05). After matching, Cox regression analysis found that the treatment regimen (P < 0.001, HR = 2.527), TNM staging (P = 0.001, HR = 0.471), local recurrence (P = 0.001, HR = 2.147), and pretreatment CEA (P = 0.011, HR = 1.131) were independent prognostic factors affecting patients' 2-year survival. While the spleen-enhancing and blood-stasis-removing herbal formula combined with the SOX chemotherapy regimen did not improve therapeutic outcomes in gastric cancer patients, it did enhance immune function, reduce adverse reactions, and improve quality of life.

Digital multimeter-based portable photoelectrochemical immunoassay with enzyme-catalyzed precipitation for screening carbohydrate antigen 125.

The degree of the carbohydrate antigen 125 (CA-125) level in serum is positively correlated with the severity of ovarian cancer. In this study, a facile photoelectrochemical (PEC) immunoassay was devised for sensitive detection of CA-125 employing enzyme-catalyzed precipitation to weaken the photocurrent of hollow porous In2O3 nanotubes incorporating CdS nanoparticles. Upon the addition of the target analyte, horseradish peroxidase (HRP) enriches as a result of the formation of the sandwich immunocomplex, which can catalyze the conversion of 4-chloro1-naphthol (4-CN) to benzo-4-chlorohexadienone (4-CD) employing H2O2 as a cofactor. The as-produced insoluble precipitate acts as an obstacle to hinder the absorption of visible light by photoactive materials, thereby resulting in a decrease in photocurrent. Moreover, the weakened signal can be easily read out by a digital multimeter (DMM), advancing the convenience of the detection system. The preliminary analysis data indicate that the PEC immunoassay shows an efficient response to CA-125 levels ranging from 0.1 to 100 U mL-1 with a limit of detection (LOD) as low as 0.046 U mL-1 (S/N = 3). Most importantly, the proposed portable method has shown satisfactory performance in terms of selectivity, reproducibility, stability, and analysis in complex biological matrices.

Blood-Based microRNA Biomarker Signature of Early-Stage Pancreatic Ductal Adenocarcinoma With Lead-Time Trajectory in Prediagnostic Samples

Clinically validated biomarker of pancreatic ductal adenocarcinoma (PDAC), carbohydrate antigen 19-9 (CA19-9), has limited sensitivity and specificity for early-stage disease. Circulating miRNAs in plasma associated with cancer relevant pathways were developed as early detection biomarkers. 2083 miRNAs in 15 μl of plasma from multicenter age-matched cohorts (N= 203: healthy controls, n= 46; pancreatitis controls, n= 36; diagnosed cases: n= 121) and a prediagnostic Prostate, Lung, Colorectal, and Ovarian age- and gender-matched cohort (N=96; controls, n= 48; prediagnosed cases, n= 48) were interrogated. A three-miRNA biomarker signature was developed for early-stage PDAC. The three-miRNA signature (let-7i-5p, miR-130a-3p and miR-221-3p) detected PDAC from healthy controls independently (area under the curve [AUC] of stage I, II, I-IV= 0.970, 0.975, 0.974) and in combination with CA19-9 (AUC of stage I, II, I-IV= 1.000, 0.992, 0.995). It also discriminated chronic pancreatitis (AUC of stage I, II, I-IV= 0.932, 0.931, 0.929), improving performance of CA19-9 alone (AUC of stage I, II, I-IV= 0.763, 0.701, 0.735) in combination (AUC of stage I, II, I-IV= 0.971, 0.943, 0.951). Blinded validation in prediagnostic Prostate, Lung, Colorectal, and Ovarian cohort revealed lead-time trajectory increase in AUC from 0.702 to 0.729 to 0.757 at twelve-, six-, and three-months before PDAC diagnosis, respectively. The signature also helped stratification of patients with different circulating tumor DNA and imaging subtypes. Plasma miRNAs associated with oncogenic pathways may serve as PDAC early detection biomarkers.

The Effect of Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic on the Metabolic Tumor Markers: A Real-World Retrospective Study.

Serum tumor markers have been discovered to be elevated in individuals with diabetes mellitus (DM); however, their significance in diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemia (HHS) is unknown. We evaluated these indicators in the patients with DKA and HHS. We retrospectively collected the laboratory data of 565 diabetic patients from Shanghai Pudong Hospital between Jan, 2019 and May, 2023, including 300 patients with type 2 diabetes mellitus (T2DM), 206 with DKA, and 59 with HHS. Serum tumor biomarkers and further clinical laboratory tests were compared among the three groups. Patients with conspicuous tumor evidence were excluded from the study. We found significantly higher levels of carbohydrate antigen 199 (CA199) in DKA (p<0.01), carcinoembryonic antigen (CEA), complex prostate specific antigen (CPSA) (p<0.01), prostate specific antigen (PSA) (p<0.05) in HHS, as well as the plasma lipid profile, iron, and electrolytes, in addition to decreased thyroid function, hepatic and renal function, and cardiac function (p<0.05). A Spearman correlational study revealed that osmolar levels were significantly positively correlated with myoglobin (MYO) and cardiac troponin I (cTNI), whereas serum iron concentration (r=0.520) was positively correlated with CEA levels in HHS. pH was negatively correlated with CA199 (r=-0.195), while HbA1c (r=0.22), globin (r=0.341), and total cholesterol (TC) (r=0.191) were positively correlated with elevated CA199 levels. Moreover, the multilinear regression investigation identified osmolarity as a significant determinant for CEA, as well as other parameters, and all proved to be proper predictors for CEA in HHS via ROC curve establishment. Elevated CA199 levels in DKA were associated with acidosis, whereas HHS with elevated CEA levels may be related to iron homeostasis and could be predicted via the osmolar degree and other predictors.

A label-free electrochemical biosensor based on a bimetallic organic framework for the detection of carbohydrate antigen 19-9.

Carbohydrate antigen 19-9 (CA19-9) is an important marker for pancreatic cancer, ovarian cancer and other tumors, and its rapid and stable detection is the basis for early diagnosis and treatment. In this paper, a label-free electrochemical immunosensor for the sensitive detection of CA19-9 has been developed. First, the synthesis of two novel core-shell bimetallic nanomaterials, namely Ce-MOF-on-Fe-MOF and Fe-MOF-on-Ce-MOF, was accomplished using the MOF-on-MOF approach. The poor electrical conductivity of MOF materials was addressed by incorporating polyethylenimide (PEI) functionalized rGO with Ce-MOF-on-Fe-MOF and Fe-MOF-on-Ce-MOF nanomaterials. Simultaneously, toluidine blue (Tb) was employed as a redox probe and physically adsorbed onto the synthesized materials, resulting in the formation of two nanomaterials: rGO@Ce-MOF-on-Fe-MOF@Tb and rGO@Fe-MOF-on-Ce-MOF@Tb. The fundamental characterization reveals that the sensing performance of the rGO@Ce-MOF-on-Fe-MOF@TB-based immune sensor surpasses that of the rGO@Fe-MOF-on-Ce-MOF@TB-based immune sensor, which is attributed to the fact that, unlike the interlayer-constrained structure of Fe-MOF-on-Ce-MOF, in Ce-MOF-on-Fe-MOF, Ce-MOF penetrates into Fe-MOF to form a heterogeneous structure due to the relatively large pore size of Fe-MOF, which better combines the excellent biocompatibility and strong anchoring effect of Fe MOFs on antibodies, as well as the high electrochemical activity and conductivity of Ce-MOF, to enhance sensing performance. The proposed label-free immunosensor based on rGO@Ce-MOF-on-Fe-MOF@Tb has a wide linear range (1-100 000 mU mL-1), a low detection limit (0.34 mU mL-1), good stability, reproducibility, and repeatability, and satisfactory applicability, which provides a potential platform for clinical applications.

CA19-9-Positive Extracellular Vesicle Is a Risk Factor for Cancer-Associated Thrombosis in Pancreatic Cancer

Cancer-associated venous thromboembolism (VTE) is a frequent complication associated with high mortality in patients with cancer, particularly pancreatic cancer. While biological factors such as coagulation factors released from cancer cells may underlie the mechanisms of cancer-associated VTE, the detailed mechanisms have not been determined. Here, we aimed to determine whether extracellular vesicles carrying a glycan sialyl-Lewisa, known as carbohydrate antigen 19-9 (CA19-9), which is a clinically used serum tumor marker and selectin ligand, are a significant cause of cancer-associated VTE. Risk factors for cancer-associated VTE were determined using clinical data. EVs derived from CA19-9-deficient or overexpressing pancreatic cancer cells were characterized. The protein levels of coagulation factors on the surface of the EVs were quantified using our newly developed sensitive method. Higher CA19-9 levels in the sera of patients were significantly associated with the occurrence of VTE. Using CA19-9-negative or overexpressing pancreatic cancer cells, we found that EVs derived from these cells interacted with E-selectin of endothelial cells in a CA19-9-dependent manner in cell-based assays and invitro blood vessel models. EVs derived from cancer cells have higher tissue factor levels on their surfaces, and increased tissue factor activity is induced locally, where CA19-9-positive EVs bind to activated endothelial cells. These results suggest that the binding between CA19-9-positive EVs released fromcancer cells and endothelial cell E-selectin explains theincreased frequency of VTE in patients with pancreatic cancer.

A machine learning-based predictive model for biliary stricture attributable to malignant tumors: a dual-center retrospective study.

Biliary stricture caused by malignant tumors is known as Malignant Biliary Stricture (MBS). MBS is challenging to differentiate clinically, and accurate diagnosis is crucial for patient prognosis and treatment. This study aims to identify the risk factors for malignancy in all patients diagnosed with biliary stricture by Endoscopic Retrograde Cholangiopancreatography (ERCP), and to develop an effective clinical predictive model to enhance diagnostic outcomes. Through a retrospective study, data from 398 patients diagnosed with biliary stricture using ERCP between January 2019 and January 2023 at two institutions: the First People's Hospital affiliated with Jiangsu University and the Second People's Hospital affiliated with Soochow University. The study began with a preliminary screening of risk factors using univariate regression. Lasso regression was then applied for feature selection. The dataset was divided into a training set and a validation set in an 8:2 ratio. We analyzed the selected features using seven machine learning algorithms. The best model was selected based on the Area Under the Receiver Operating Characteristic (ROC) Curve (AUROC) and other evaluation indicators. We further evaluated the model's accuracy using calibration curves and confusion matrices. Additionally, we used the SHAP method for interpretability and visualization of the model's predictions. RF model is the best model, achieved an AUROC of 0.988. Shap result indicate that age, stricture location, stricture length, carbohydrate antigen 199 (CA199), total bilirubin (TBil), alkaline phosphatase (ALP), (Direct Bilirubin) DBil/TBil, and CA199/C-Reactive Protein (CRP) were risk factors for MBS, and the CRP is a protective factor. The model's effectiveness and stability were confirmed, accurately identifying high-risk patients to guide clinical decisions and improve patient prognosis.

Effect of Anatomical Pulmonary Segmentectomy and Lobectomy under Uniportal Video-Assisted Thoracoscopic Surgery on Cardiopulmonary Function and Serum Tumor Markers in Patients with Early-Stage Non-Small Cell Lung Cancer.

In patients with early non-small cell lung cancer (NSCLC), single-port thoracoscopic anatomical segmentectomy is the primary therapeutic approach. However, the recovery of lung function is slow after operation. Conversely, anatomical segmental pneumonectomy, which excises a smaller volume of lung tissue, may facilitate more rapid functional recovery. This study aims to elucidate the comparative efficacy of these two surgical interventions by analyzing postoperative changes in cardiopulmonary function parameters and serum tumor markers. A retrospective analysis was conducted on 120 patients with NSCLC between October 2020 and October 2023. The cohort was classified into two groups based on the surgical intervention: the pulmonary segmentectomy group (n = 57), which underwent uniportal video-assisted thoracoscopic anatomical pulmonary segmentectomy, and the lobectomy group (n = 63), which received uniportal video-assisted thoracoscopic anatomical lobectomy. Surgical parameters and perioperative stress indicators were recorded for both groups of patients. Additionally, cardiopulmonary function indicators and serum biomarker levels of the patients before and 3 months after operation were compared. The operation time of the segmentectomy group was longer than that of the lobectomy group, the intraoperative blood loss was higher, and the postoperative hospital stay, chest drainage volume and drainage tube indwelling time were shorter (p < 0.001). After treatment, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC and maximal voluntary ventilation (MVV) in the segmentectomy group were higher than those in the lobectomy group (p < 0.001). After treatment, stroke volume (SV) and left ventricular ejection fraction (LVEF) in the segmentectomy group were higher than those in the lobectomy group (p < 0.001). There were no significant differences in carbohydrate antigen 50 (CA50), carcinoembryonic antigen (CEA) and cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) levels between the two groups after treatment (p > 0.05). The levels of Epinephrine (E), Noradrenaline (NE) and Cortisol (Cor) in the segmentectomy group were lower than those in the lobectomy group at one day after operation (p < 0.001). Compared to uniportal video-assisted thoracoscopic anatomical lobectomy, anatomical pulmonary segmentectomy for the treatment of NSCLC is more effective in reducing surgical-induced damage to cardiopulmonary function and can lower perioperative oxidative stress response. However, both surgical approaches exhibit minimal impact on serum tumor marker levels.