A photoelectrochemical (PEC) biosensor composed entirely of carbon nanomaterials was synthesized to detect carbohydrate antigen 19-9 (CA 19-9). The biosensor platform integrated graphitic carbon nitride (GCN), known for its light sensitivity, polythiophene (PTh), an organic conductive and optically active material, and 1-pyrenebutyric acid N-hydroxysuccinimide (PBASE), which functions both as a biolinker to conjugate CA 19-9 antibody and antigen and as an electron mediator to facilitate electron transfer from GCN to PTh. The formation of a Schottky heterojunction between PTh and GCN reduced the bandgap of GCN from 2.66 to 1.96 eV, which enhanced transfer of photogenerated electrons for cathodic photocurrent generation. The improvement of charge transfer due to heterojunction formation and π-π stacking between GCN and the pyrene group of PBASE is confirmed by cyclic voltammetry (CV), electron impedance spectroscopy (EIS), and chronoamperometry (CA) findings. The highest current of 1.31 μA is observed for combination of 5 wt% PTh with a GCN/PBASE ratio of 1:0.5. Besides evaluating the electron mobility of GCN/PBASE/PTh, CV, EIS, and CA were also used to evaluate the sensor performance. Optimization studies revealed that 0.6 μg of CA 19-9 antibody and 1 h of antigen-antibody immobilization time significantly improved the biosensor response. The GCN/PBASE/PTh biosensor demonstrated high sensitivity to CA 19-9 antigen across a concentration of 50-1000 U/ml and a detection limit as low as 0.052 U/ml. The reported working range is within the limits required for diagnostic testing of patients with hepatic and heart problems as well as for post-treatment monitoring of colorectal and pancreatic cancer patients.

Intraductal papillary mucinous neoplasm (IPMN) is the most common type of pancreatic cyst often incidentally detected in asymptomatic patients. The current consensus guidelines, largely based on imaging features, have high sensitivity but low specificity in differentiating benign from malignant IPMNs, leading to unnecessary surgeries. Discovering biomarkers is thus warranted to improve the preoperative risk stratification of IPMN. Pancreatic cyst fluid samples were obtained from patients with pathologically confirmed low-grade (n = 73) or high-grade/invasive (n = 18) IPMN. Global proteome quantitation was performed using liquid chromatography-tandem mass spectrometry. Differentially expressed proteins (DEPs) between the two groups were analyzed using Wilcoxon rank-sum test. 152 upregulated and 74 downregulated DEPs were discovered by comparing low-grade IPMN with high-grade/invasive IPMN (all p < 0.05). The enriched upstream regulators of these DEPs included let-7, miR-122, IL15, and FLT1 (p = 6.76 × 10-5 - 5.97 × 10-3). Five discriminatory biomarkers with the largest LASSO coefficients and each with AUCs of >0.75 (FAHD2A, TCEAL3, TWF1, MMUT, and NTPCR) were identified. The combined five-protein model achieved a bootstrap-corrected AUC of 0.94. A combined analysis of TCGA and GTEx databases showed TWF1 overexpression in pancreatic cancer (p = 2.22 × 10-16) that was associated with poor prognosis (p = 0.0063). The present study identified several cyst fluid proteins (particularly TWF1) that are predictive of malignant pancreatic cyst lesions. If validated in other patient populations, these biomarkers may enhance the accuracy of the preoperative detection of high-risk IPMN and thereby improve patient outcomes.

Pancreatic cancers have high mortality and rising incidence rates which may be related to unhealthy western-type dietary and lifestyle patterns as well as increasing body weights and obesity rates. Recent data also suggest a role for the gut microbiome in the development of pancreatic cancer. Here, we review the experimental and observational evidence for the roles of the oral, gut and intratumoural microbiomes, impaired gut barrier function and exposure to inflammatory compounds as well as metabolic dysfunction as contributors to pancreatic disease with a focus on pancreatic ductal adenocarcinoma (PDAC) initiation and progression. We also highlight some emerging gut microbiome editing techniques currently being investigated in the context of pancreatic disease. Notably, while the gut microbiome is significantly altered in PDAC and its precursor diseases, its utility as a diagnostic and prognostic tool is hindered by a lack of reproducibility and the potential for reverse causality in case-control cohorts. Future research should emphasise longitudinal and mechanistic studies as well as integrating lifestyle exposure and multi-omics data to unravel complex host-microbiome interactions. This will allow for deeper aetiologic and mechanistic insights that can inform treatments and guide public health recommendations.

Surgery is the only curative therapeutic option for resectable extrahepatic cholangiocarcinoma, but recurrence is common, and prognosis is poor. There is an unmet clinical need for improved decision-making regarding adjuvant chemotherapy (ACT). Herein, we evaluated the usefulness of monitoring longitudinal circulating tumor DNA (ctDNA) for molecular residual disease (MRD) in patients from the STAMP trial, which compared the efficacy of adjuvant capecitabine (CAP) vs. gemcitabine plus cisplatin (GemCis).

Between July 2017 and November 2020, 101 patients were randomized 1:1 to receive GemCis (n = 50) or CAP (n = 51). Efficacy outcomes were analyzed with an extended follow-up of 19 months from the previous report. From a biomarker cohort of 89 patients, longitudinal plasma samples (n = 254) were prospectively collected post-surgery before ACT, and on-ACT at 12 and 24 weeks from cycle 1 day 1 (C1D1). ctDNA was evaluated using a personalized, tumor-informed, 16-plex PCR next-generation sequencing assay and was correlated with clinical outcomes.

In the extended follow-up analysis, median disease-free survival (DFS) and overall survival did not significantly differ between the CAP and GemCis groups. Significantly inferior DFS was associated with ctDNA positivity before ACT (hazard ratio [HR] 1.8; p = 0.029), on-ACT at 12 weeks from C1D1 (HR 7.72; p <0.001), on-ACT at 24 weeks from C1D1 (HR 5.24; p <0.001), and anytime post-surgery (HR 3.81; p <0.001). Analysis of pre-treatment to on-treatment ctDNA dynamics revealed that serially ctDNA-negative patients exhibited a significantly longer DFS compared to those with sustained ctDNA positivity (HR 6.7; p <0.001) or those who turned ctDNA positive (HR 5.8; p <0.001).

In patients with resected extrahepatic cholangiocarcinoma, ctDNA status and dynamics predicted recurrence during adjuvant therapy, and may help optimize clinical decision-making.

The findings from this study highlight the critical role of ctDNA as a prognostic biomarker and monitoring tool for patients with resected extrahepatic cholangiocarcinoma. By demonstrating the superiority of ctDNA to predict disease recurrence compared to conventional biomarkers such as cancer antigen 19-9 and carcinoembryonic antigen, this study underscores its potential in guiding decision-making during adjuvant chemotherapy. These results may be crucial to refine post-surgical treatment strategies and improve patient outcomes. The practical application of ctDNA monitoring could lead to more personalized treatment approaches, enabling timely interventions based on molecular residual disease status.

NCT03079427.

Pancreatic head-type autoimmune pancreatitis (PH-AIP) with elevated CA19-9 is sometimes difficult to distinguish from pancreatic head cancer (PHC) with elevated CA19-9. At times, IgG4 proves inadequate in offering assistance. The study aimed to elucidate the performance of CA19-9/DBil in distinguishing between the two conditions.

This was a retrospective study. We collected serologic indicators from participants in PH-AIP and PHC Group. Three logistic regression equations were established ranging from non-adjustment (Model 1, only CA19-9/DBil included) to adjusting for sex, age, and CEA (Model 2 and Model 3) to explore the relationship between CA19-9/DBil and PH-AIP probability. ROC, Decision Curve Analysis (DCA), calibration curve were conducted. P for AUCs and net reclassification improvements (NRI) were computed to evaluate differences in discrimination and the improvement in risk reclassification between models.

The study included 90 PHC and 35 PH-AIP patients, all with elevated CA19-9. The ORs for CA19-9/DBil in three models were similar (0.915 to 0.921). ROC revealed that Model 1 had an AUC of 0.772. The sensitivity, specificity, and accuracy at the best threshold were all > 0.7. Model 1, although simple, was not inferior in its discriminative ability compared to complex models: the difference in discrimination between Model 1 and each of two adjusted models was not statistically significant (P > 0.05, both AUC and NRI). Additionally, calibration curve and DCA suggested that Model 1 had good calibration and clinical utility.

CA19-9/DBil exhibited promising diagnostic performance in differentiating between CA19-9-elevated PH-AIP and PHC.

Gastroenterology faces significant challenges due to the global burden of gastrointestinal (GI) diseases, driven by socio-economic disparities and their wide-ranging impact on health and healthcare systems. Advances in molecularly imprinted polymers (MIPs) offer promising opportunities for developing non-invasive, cost-effective diagnostic tools that enhance the accuracy and accessibility of GI disease detection. This research explores the potential of MIP-based sensors in revolutionizing gastrointestinal diagnostics and improving early detection and disease management. Biomarkers are vital in diagnosing, monitoring, and personalizing disease treatment, particularly in gastroenterology, where advancements like MIPs offer highly selective and non-invasive diagnostic solutions. MIPs mimic natural recognition mechanisms, providing stability and sensitivity even in complex biological environments, making them ideal for early disease detection and real-time monitoring. Their integration with advanced technologies, including conducting polymers, enhances their functionality, enabling rapid, point-of-care diagnostics for gastrointestinal disorders. Despite regulatory approval and scalability challenges, ongoing innovations promise to revolutionize diagnostics and improve patient outcomes through precise approaches.

Several pancreatic adenocarcinoma (PA) biomarkers beyond the traditional carbohydrate antigen (CA)19-9 have been identified but are lacking large-scale prospective validation. This prospective cohort study evaluated the prognostic impact of potential PA biomarkers.

We enrolled 238 of 288 patients with histologically proven PA. We assessed candidate biomarkers, including CA19-9, germline BRCA1/2, and ATM mutations, as well as mutant KRAS circulating tumor DNA (ctDNA) in blood samples. Additionally, we evaluated the expression of SLC29A1 (hENT1), DCK, CES2, and GATA6. We examined the association of candidate biomarkers with progression-free survival (PFS) and overall survival (OS).

We analyzed biomarker efficacy in 200 (median age 65 years; 55% male) of the enrolled patients who received chemotherapy. A high mutant KRAS ctDNA concentration (hazard ratio [HR]: 1.508 and 95% confidence interval [CI]: 1.052-2.161 for PFS; HR: 1.796 and 95% CI: 1.203-2.681 for OS) and high CA19-9 level (HR: 1.647 and 95% CI: 1.177-2.306 for PFS; HR: 1.803 and 95% CI: 1.248-2.605 for OS) were associated with poor prognosis. High GATA6 RNA expression was linked to longer PFS (HR: 0.336 and 95% CI: 0.195-0.582) and OS (HR: 0.304 and 95% CI: 0.165-0.560).

Plasma mutant KRAS ctDNA concentrations and GATA6 expression could serve as significant prognostic biomarkers in patients with PA, potentially guiding therapeutic decisions and prognostication.

Currently, those recommended to undergo pancreatic cancer (PC) surveillance include appropriately aged individuals at high risk of PC due to an identifiable genetic susceptibility or those without identifiable genetic susceptibility who nonetheless have a strong family history of PC. With increases in identification of individuals at high risk for PC and increased use of PC surveillance in clinical practice, there has been increasing debate about who should undergo surveillance as well as how surveillance should be performed including use of imaging and blood-based testing. Furthermore, there is increasing interest in the outcomes of PC surveillance in high-risk individuals with some studies demonstrating that surveillance leads to downstaging of PC and improvements in survival. In this review, we summarize the current state of PC surveillance in high-risk individuals, providing an overview of the risk factors associated with PC, selection of high-risk individuals for PC surveillance, and the current, but non-uniform, recommendations for performing PC surveillance. Additionally, we review approaches to apply various imaging and blood-based tests to surveillance and the outcomes of PC surveillance.

This study aimed to assess the significance of elevated carbohydrate antigen (CA) 19-9 in postoperative surveillance of extrahepatic bile duct cancer and to identify short-term recurrence predictors.

This retrospective study included patients with elevated CA 19-9 post-curative surgery. Patients were categorized into positive and negative CT groups based on the detection of recurrence at CA 19-9 elevation. Short-term recurrence was defined as recurrence within 6 months in the negative CT group. We identified the factors associated with short-term recurrence and devised a predictive nomogram.

Among the 190 patients, 91 (47.9 %) exhibited tumor recurrence with CA 19-9 elevation (CT-positive group), whereas 99 (52.1 %) showed no recurrence (CT-negative group). In the CT-negative group (n = 99), 22 (22.2 %) experienced short-term tumor recurrence within 6 months. Preoperative CA 19-9 (odds ratio [OR]: 1.5, p = 0.016), postoperative CA 19-9 (OR: 1.9, p = 0.047), adjuvant treatment (OR: 3.5, p = 0.032), and the absence of inflammation (OR: 3.5, p = 0.045) were predictors of short-term recurrence. The area under the curve of the nomogram was 0.80 (95 % CI: 0.69-0.90).

Despite elevated CA 19-9 levels, approximately 50 % of patients exhibited no recurrence during postoperative surveillance for extrahepatic bile duct cancer. Factors influencing short-term recurrence encompass pre- and postoperative CA 19-9, adjuvant treatment, and inflammatory status.

An isolated hydatid cyst of the spleen represents an exceptional pathology, and its association with high CA 19-9 serum levels was not previously reported. This case presents a patient with an isolated hydatid cyst of the spleen, with preoperative high CA 19-9 serum levels in the absence of other pathologies and normalization of CA 19-9 serum levels after surgery (i.e., splenectomy). The source and clinical value of high serum levels of CA 19-9 in hydatid cysts of the spleen remains unclear. High serum levels of CA 19-9 in the context of a splenic cyst may complicate diagnosis and challenge the therapeutic strategy.

The lack of predictive biomarkers contributes notably to the poor outcomes of patients with pancreatic ductal adenocarcinoma (PDAC). Cancer-associated fibroblasts (CAFs) are the key components of the prominent PDAC stroma. Data on clinical relevance of CAFs entering the bloodstream, known as circulating CAFs (cCAFs) are scarce. Here, we developed a combined liquid biopsy assay to detect cCAFs and circulating tumor cells (CTCs) in metastatic PDAC (mPDAC) and other metastatic gastrointestinal malignancies (mGI). In addition, we evaluated plasma hyaluronan (HA) levels as a complementary surrogate biomarker of the stromal extent in patients with PDAC.

A sequential liquid biopsy assay based on a two step-enrichment, combining marker dependent and independent cell enrichment, was established for cCAF and CTC detection and validated in mPDAC and mGI patients. The enriched cells were identified by multiplex immunofluorescence. HA measurement was performed by ELISA on blood samples from healthy blood donors (HD), localized and late-stage PDAC patients.

cCAFs (≥ 1cCAFs/7.5 mL blood) were detected in 95.4% of mPDAC and in 78.2% of mGI patients, with significantly higher numbers in mPDAC compared to mGI patients (mean number 22.7 vs. 11.0; P = 0.0318). mPDAC patients with ≥ 15 cCAFs/7.5 mL blood had a significant shorter median overall survival (mOS 3.2 months (95% confidence interval (CI) 0.801-5.855) vs. 14.2 months (95% CI 6.055-22.332); P = 0.013), whereby CTC levels were not associated with mOS. In mGI neither cCAFs nor CTCs had a significant impact on OS. HA plasma levels in mPDAC patients were significantly higher compared to HD (mean 123.0 ng/mL vs. 74.45 ng/mL, P = 0.015). High HA in localized and late-stage PDAC were associated with a significantly shorter mOS (mOSlocalized PDAC: 12.6 months vs. 23.5 months (P = 0.008); mOSmPDAC: 1.8 months vs. 5.3 months (P = 0.004)).

Our liquid biopsy assay provides robust detection of cCAFs in mPDAC and mGI patients. The measurement of both circulatory stromal parameters, cCAFs and HA, adds valuable clinical information as they are associated with an unfavorable outcome in PDAC. These results highlight that stromal characteristics unique to PDAC could be leveraged to fill the current gap in discovering predictive biomarkers.

Serum levels of the tumor marker CA 19-9 are widely utilized in the diagnosis and monitoring pancreatic and biliary malignancies. However, serum levels of CA 19-9 have also been reportedly elevated in non-malignant conditions. Here, we present the rare case of a 65-year-old woman with a history of gallbladder malignancy who was found to have a new hepatic lesion on surveillance CT with an associated elevation in CA 19-9 to 5,866 U/mL. Drainage of the lesion and treatment with antibiotics resulted in a rapid decline in CA 19-9 levels, indicating that the elevation in CA 19-9 was due to a benign hepatic lesion. We review eight similar reported cases of CA 19-9 elevations due to benign hepatic abscesses, thereby highlighting a need to interpret the tumor marker with caution.

Carbohydrate antigen 19-9 (CA 19-9) is a tumor marker usually used for the diagnosis and follow-up of pancreatic, gastric, and hepatobiliary malignancies. However, it has a low specificity and can be elevated in a wide array of other conditions. CA 19-9 elevation in lung tumors seems to be associated with the worst prognosis, but its role in this condition is not fully established yet. We present the case of a 78-year-old woman with mild consumptive symptoms, consisting of unselective anorexia and weight loss, and isolated high levels of CA 19-9. Hepatobiliary and gastrointestinal lesions were excluded, and a suspicious lesion was found in the right lung. A biopsy, which was only possible several months after presentation due to the location and small dimensions of the lesion, confirmed the diagnosis of lung adenocarcinoma. After an initial indolent course, the patient evolved with disease progression and is currently under treatment with palliative chemotherapy. This case illustrates the thorough investigation performed to clarify the elevation of a tumor biomarker measured in a pauci-symptomatic patient, which led to the identification of a rare and unsuspected etiology of high levels of CA 19-9.

This study aimed to assess (1) the prognostic value of circulating tumor DNA (ctDNA) and (2) the ability of ctDNA to detect recurrence compared with standard surveillance in curatively resected early-stage biliary tract cancer (BTC).

This retrospective, multicenter cohort study evaluated serial ctDNA testing for surveillance in patients with early-stage BTC after curative resection. We evaluated the relapse-free survival (RFS) by ctDNA positivity. The sensitivity of ctDNA in detecting a confirmed recurrence of BTC, defined as a biopsy-proven or true progression by radiographic tumor dynamics, was evaluated. The lead time was calculated from the first ctDNA detection to the confirmed recurrence.

A total of 56 patients with curatively resected stage I-III BTC were included in this study, with a median follow-up of 12.8 months from the date of surgery. ctDNA detection during the molecular residual disease window period (median RFS, 6.6 months v not reached; hazard ratio [HR], 26 [95% CI, 2.6 to 265]; P < .0001) and during the surveillance period (median RFS, 19.3 months v not reached; HR, 20 [95% CI, 2.6 to 153]; P < .0001) were associated with poorer RFS. Sixteen patients had confirmed recurrence. ctDNA identified recurrence in 93.8.% (15/16) of the recurred patients with an average lead time of 3.7 months. Carbohydrate antigen 19-9 levels did not show any significant correlation with RFS (HR, 1.17 [95% Cl, 0.24 to 5.71]; P = .844) in contrast to ctDNA.

The findings from our real-world cohort study revealed the (1) promising value of ctDNA as a prognostic biomarker for relapse in curatively resected BTC and (2) potential early detectability of recurrence by ctDNA compared with standard surveillance.

To develop and validate a serum protein nomogram for colorectal cancer (CRC) screening.

The serum protein characteristics were extracted from an independent sample containing 30 colorectal cancer and 12 polyp tissues along with their paired samples, and different serum protein expression profiles were validated using RNA microarrays. The prediction model was developed in a training cohort that included 1345 patients clinicopathologically confirmed CRC and 518 normal participants, and data were gathered from November 2011 to January 2017. The lasso logistic regression model was employed for features selection and serum nomogram building. An internal validation cohort containing 576 CRC patients and 222 normal participants was assessed.

Serum signatures containing 27 secreted proteins were significantly differentially expressed in polyps and CRC compared to paired normal tissue, and REG family proteins were selected as potential predictors. The C-index of the nomogram1 (based on Lasso logistic regression model) which contains REG1A, REG3A, CEA and age was 0.913 (95% CI, 0.899 to 0.928) and was well calibrated. Addition of CA199 to the nomogram failed to show incremental prognostic value, as shown in nomogram2 (based on logistic regression model). Application of the nomogram1 in the independent validation cohort had similar discrimination (C-index, 0.912 [95% CI, 0.890 to 0.934]) and good calibration. The decision curve (DCA) and clinical impact curve (ICI) analysis demonstrated that nomogram1 was clinically useful.

This study presents a serum nomogram that included REG1A, REG3A, CEA and age, which can be convenient for screening of colorectal cancer.

Pancreatic cancer is a highly aggressive tumor with a poor prognosis due to a low early detection rate and a lack of biomarkers. Most of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC). Alterations in the N-glycosylation of plasma immunoglobulin G (IgG) have been shown to be closely associated with the onset and development of several cancers and could be used as biomarkers for diagnosis. The study aimed to explore intact N-glycosylation profile of IgG in patients with PDAC and find relation between intact N-glycosylation profile of IgG and clinical information such as diagnosis and prognosis.

In this study, we employed a well-evaluated approach (termed GlycoQuant) to assess the site-specific N-glycosylation profile of human plasma IgG in both healthy individuals and patients with pancreatic ductal adenocarcinoma (PDAC). The datasets generated and analyzed during the current study are available in the ProteomeXchange Consortium ( http://www.proteomexchange.org/ ) via the iProX partner repository, with the dataset identifier PXD051436.

The analysis of rapidly purified IgG samples from 100 patients with different stages of PDAC, in addition to 30 healthy controls, revealed that the combination of carbohydrate antigen 19 - 9 (CA19-9), IgG1-GP05 (IgG1-TKPREEQYNSTYR-HexNAc [4]Hex [5]Fuc [1]NeuAc [1]), and IgG4-GP04 (IgG4-EEQFNSTYR- HexNAc [4]Hex [5]Fuc [1]NeuAc [1]) can be used to distinguish between PDAC patients and healthy individuals (AUC = 0.988). In addition, cross validation of the diagnosis model showed satisfactory result.

The study demonstrated that the integrated quantitative method can be utilized for large-scale clinical N-glycosylation research to identify novel N-glycosylated biomarkers. This could facilitate the development of clinical glycoproteomics.

Background: Carbohydrate antigen 19-9 (CA19-9) is used as a marker to predict recurrence and survival of patients with pancreatic ductal adenocarcinoma (PDAC). Recently, fecal elastase-1 (FE-1) has been shown to correlate with prognosis in patients with PDAC. Method: A total of 536 patients who underwent curative intent surgery between 2010 and 2019 were included in the study. The cutoff points of preoperative CA19-9 and FE-1 levels were extracted from the Youden index and previous studies. Cox proportional hazard models were used to investigate the association between preoperative tumor marker levels and survival after surgery. Results: Patients with CA19-9 ≥ 385 had more advanced T-/N-stages and lower survival rates compared to those with CA19-9 < 385. Multivariate Cox analyses demonstrated that combining preoperative tumor markers was associated with worse 3-year overall survival (both CA19-9 and FE-1 low, HR = 1.41, p = 0.044; both high, HR = 1.44, p = 0.047; CA19-9 high and FE-1 low, HR = 2.00, p < 0.001; and p for trend < 0.001). The same trend was confirmed in the analysis with recurrence-free survival. Conclusions: This study presents a new predictive strategy using combined CA19-9 and FE-1 levels to determine the treatment for resectable pancreatic cancer.

Cholangiocarcinoma (CCA) is the second most common primary malignancy of the hepatobiliary system and presents as a heterogeneous disease with three distinct morphological subtypes: mass-forming, periductal-infiltrating, and intraductal-growing, each characterized by distinguishing imaging features. Accurate diagnosis of CCA is challenging due to the overlap of imaging findings with a broad range of benign and malignant conditions. Therefore, it is essential for radiologists to recognize these mimickers and offer a reasonable differential diagnosis, as this has a significant impact on patient management. Although histopathological confirmation is often required for a definitive diagnosis, understanding specific imaging characteristics that differentiate CCA from its mimickers is crucial. This article highlights a variety of benign and malignant conditions that resemble CCA on imaging, emphasizing features that enhance diagnostic accuracy in clinical practice.

Esophageal and gastric varices hemorrhage (EGVH) is a life-threatening condition with the 6-week mortality rate of 15-25%. Up to 60% of patients with EGVH may experience rebleeding with a mortality rate of 33%. The existing scoring systems, such as RS scoring system (Rockall score, RS) and GBS scoring system (Glasgow-Blatchford score, GBS), have limitations in predicting the risk of rebleeding. Our study was to construct and validate a novel predictive model for the risk of rebleeding in patients with EGVH and to compare the predictive power of the predictive model with GBS and pRS.

Data of patients with EGVH was collected in the First Affiliated Hospital of Dalian Medical University from January 2016 to June 2020. Binary logistic and stepwise regression was performed to construct a predictive model. We compared the predictive power of the new predictive model to the GBS and pRS scoring systems.

Clinical data from a total of 265 patients with EGVH was collected. Six factors including systolic blood pressure, transfusion requirement, CA199, platelet count, upper esophageal varices and severity of esophageal varices were included in our new predictive model. The AUCs of the specificity of the predictive model, GBS and pRS are 0.82, 0.60 and 0.56.

This study successfully constructed a predictive model for the risk of rebleeding in patients with EGVH. This predictive model demonstrated higher predictive ability than pRS and GBS scoring systems for assessing rebleeding risk in EGVH patients.

The dynamics of postoperative carcinoembryonic antigen (CEA) in pancreatic ductal adenocarcinoma (PDAC) patients have not been well assessed. This study investigated the correlation between postoperative CEA elevations and tumor recurrence.

Medical records were retrospectively analyzed for 84 patients who received curative resection for PDAC from January 2019 to December 2020. Postoperative CEA levels were monitored for a minimum of 12 months. False-positive CEA elevation was defined as a CEA level exceeding 5 ng/mL without evidence of recurrence in imaging studies.

Of the examined patients, 59 (70%) exhibited CEA > 5 ng/mL within the observation period. The sensitivity and specificity of elevated CEA levels for detecting recurrence were 84% and 41%, respectively. CEA elevations without tumor recurrence were observed in 27 patients, indicating a false-positive rate of 59%. More than half of these patients demonstrated peak CEA levels between 5 and 10 ng/mL, while only true-positive patients exhibited CEA levels exceeding 40.0 ng/mL.

CEA may rise in more than half of postoperative PDAC patients without recurrence. CEA alone is not a robust postoperative marker.

The aggressiveness of pancreatic ductal adenocarcinoma is primarily due to lack of effective early detection biomarkers. Circulating non-coding RNAs serve as diagnostic or prognostic biomarkers in multiple types of cancer. Comparison of their expression between diseased tissue and relevant body fluids such as saliva, urine, bile, pancreatic juice, blood etc. may reveal mechanistic involvement of common non-coding RNAs. piwi-interacting RNAs (piRNAs) are a class of non-coding RNAs. The aim of the present study was to investigate plasma and tumour tissue piRNA changes in patients with pancreatic cancer (PC) and explore the possible role in tumorigenesis and pancreatic inflammation. Sequencing of circulating plasma small RNAs from patients with PC and chronic pancreatitis (CP) was performed and differentially expressed piRNAs were compared with those in tissues. Subsequent search for target genes for those piRNAs was performed followed by pathway and cluster analysis. A total of 36 piRNAs were shown to be deregulated in pancreatic tumour tissue and alteration of 11 piRNAs was detected in plasma of patients with PC. piRNAs hsa-piR-23246, hsa-piR-32858 and hsa-piR-9137 may serve a key role in PC development as their expression was correlated in both plasma and tumour tissue. Key piRNA-target interactions interfering with key biological pathways were also characterized. A total of 19 deregulated piRNAs in plasma samples of patients with CP was identified; these targeted genes responsible for chronic inflammation. Therefore, the present study provides a comprehensive description of piRNA alteration in pancreatic malignancy and inflammation; these may be explored for biomarker potential in future.

Exosomes, extracellular vesicles carrying a cargo rich in various non-coding RNAs (ncRNAs), have emerged as crucial mediators of intercellular communication. Their stability, abundance, and specificity make exosomal ncRNAs promising candidates for biomarker discovery. The discovery of exosomal ncRNAs has unveiled a novel avenue for the exploration of biomarkers in tumor early diagnosis. This review consolidates current knowledge on the role of exosomal ncRNAs as potential biomarkers in the early detection of various tumors. We provide an overview of recent studies demonstrating the diagnostic potential of exosomal ncRNAs across multiple cancer types, highlighting their sensitivity, specificity, and feasibility for early detection. This review underscores the potential of exosomal ncRNAs as non-invasive biomarkers for early tumor diagnosis, paving the way for improved clinical outcomes through timely intervention and personalized management strategies.

A woman in her early 20's presented with fever and unintentional weight loss of 4 kg over a period of 1 month and abdominal pain for 10 days. Empirical antibiotic therapy administered prior to hospitalisation was not successful. Evaluation for fever was unrewarding except for an abnormal ultrasound which showed two cysts with the largest dimension of 9 cm in the right adnexal region. All blood cultures were sterile. She underwent laparoscopic cystectomy. Bacterial culture of cyst fluid grew Salmonella enterica subspecies enterica serotype Typhi which was found to be resistant to fluoroquinolones. The case emphasises the fact that localised infection of the ovarian cyst can occur in extraintestinal salmonellosis that can have a negative blood culture and can mimic ovarian malignancy.

Pancreatic ductal adenocarcinoma (PDAC) is frequently detected in late stages, which leads to limited therapeutic options and a dismal overall survival rate. To date, no robust method for the detection of early-stage PDAC that can be used for targeted screening approaches is available. Liquid biopsy allows the minimally invasive collection of body fluids (typically peripheral blood) and the subsequent analysis of circulating tumor cells or tumor-associated molecules such as nucleic acids, proteins, or metabolites that may be useful for the early diagnosis of PDAC. Single biomarkers may lack sensitivity and/or specificity to reliably detect PDAC, while combinations of these circulating biomarkers in multimarker panels may improve the sensitivity and specificity of blood test-based diagnosis. In this narrative review, we present an overview of different liquid biopsy biomarkers for the early diagnosis of PDAC and discuss the validity of multimarker panels.

This report provides an overview of the most common diagnostic methods that bring to light incidental findings of pancreatic cancer. It reviews the impact of medical imaging and genetic assessment on the definitions of incidental findings and incidentaloma of the pancreas. For different diagnostic approaches (eg, MRI and CT) and for different affections (cysts/intraductal papillary mucinous neoplasia, solid lesions), specific guidelines have been proposed and some are established. Based on this, we summarise the differences between the traditional methods with those applied in the PANCAID project. Biomarkers, genetic predispositions, mutations and circulating tumour cells give rise to different levels of concern. The final part of the report discusses the risks and the opportunities associated with further diagnostic procedures and surgical interventions. From the ethical perspective, the most urging question is, can a screening based on liquid biopsy and blood samples open a gateway for the prevention of pancreatic cancer-even if morbidity and lethality of today's surgical interventions is still very high?

Autoimmune pancreatitis (AIP) is a diagnosis-challenging disease that often mimics pancreatic malignancy. Pancreatic resection is considered to be a curative treatment for pancreatic ductal adenocarcinoma (PDAC). This meta-analysis aims to study the incidence of AIP in patients who have undergone pancreatic resection for clinical manifestation of cancer.

A comprehensive search was conducted in three databases, PubMed, Embase and the Cochrane Library, using the terms 'autoimmune pancreatitis' and 'pancreatic resection' and supplemented by manual checks of reference lists in all retrieved articles.

Ten articles were included in the final analysis. 8917 pancreatic resections were performed because of a clinical suspicion of pancreatic cancer. AIP accounted for 140 cases (1.6%). Type 1 AIP comprised the majority of cases, representing 94% (132 cases), while type 2 AIP made up the remaining 6% (eight cases) after further classification. AIP accounted for almost 26% of all cases of benign diseases involving unnecessary surgery and was overrepresented in males in 70% of cases compared to 30% in females. The mean age for AIP patients was 59 years. Serum CA 19 - 9 levels were elevated in 23 out of 47 (49%) AIP patients, where higher levels were detected more frequently in patients with type 1 AIP (51%, 22 out of 43) than in those with type 2 AIP (25%, 1 out of 4). The sensitivity of IgG4 levels in type 1 AIP was low (43%, 21/49 patients).

Even with modern diagnostic methods, distinguishing between AIP and PDAC can still be challenging, thus potentially resulting in unnecessary surgical procedures in some cases. Serum CA 19 - 9 levels are not useful in distinguishing between AIP and PDAC. Work must thus be done to improve diagnostic methods and avoid unnecessary complicated surgery.

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.

EUS-guided radiofrequency ablation (EUS-RFA) has emerged as an alternative for the local treatment of unresectable pancreatic ductal adenocarcinoma (PDAC). We assessed the feasibility and safety of EUS-RFA in patients with unresectable PDAC.

This study followed an historic cohort compounded by locally advanced (LA-) and metastatic (m)PDAC-naïve patients who underwent EUS-RFA between October 2019 and March 2022. EUS-RFA was performed with a 19-gauge needle electrode with a 10-mm active tip for energy delivery. Study primary endpoints were feasibility, safety, and clinical follow-up, whereas secondary endpoints were performance status (PS), local control, and overall survival (OS).

Twenty-six patients were selected: 15 with locally advanced pancreatic duct adenocarcinoma (LA-PDAC) and 11 with metastatic pancreatic duct adenocarcinoma (mPDAC). Technical success was achieved in all patients with no major adverse events. Six months after EUS-RFA, OS was seen in 11 of 26 patients (42.3%), with significant PS improvement (P = .03). Local control was achieved, with tumor reduction from 39.5 mm to 26 mm (P = .04). A post-treatment hypodense necrotic area was observed at the 6-month follow-up in 11 of 11 patients who were still alive. Metastatic disease was a significant factor for worsening OS (hazard ratio, 5.021; 95% confidence interval, 1.589-15.87; P = .004).

EUS-RFA for the treatment of pancreatic adenocarcinoma is a minimally invasive and safe technique that may have an important role as targeted therapy for local treatment of unresectable cases and as an alternative for poor surgical candidates. Also, RFA may play a role in downstaging cancer with a potential increase in OS in nonmetastatic cases. Large prospective cohorts are required to evaluate this technique in clinical practice.

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related deaths and is associated with a poor prognosis. The majority of these cancers are detected at a late stage, contributing to the bad prognosis. This underscores the need for novel, enhanced early detection strategies to improve the outcomes. While population-based screening is not recommended due to the relatively low incidence of PDAC, surveillance is recommended for individuals at high risk for PDAC due to their increased incidence of the disease. However, the outcomes of pancreatic cancer surveillance in high-risk individuals are not sorted out yet. In this review, we will address the identification of individuals at high risk for PDAC, discuss the objectives and targets of surveillance, outline how surveillance programs are organized, summarize the outcomes of high-risk individuals undergoing pancreatic cancer surveillance, and conclude with a future perspective on pancreatic cancer surveillance and novel developments.

"Serum tumor markers expression (CA19-9, CA242, and CEA) and its clinical implications in type 2 diabetes mellitus" authored by Meng and Shi presents an observational case-control study investigating the correlation between tumor markers and type 2 diabetes mellitus (T2DM). The study explores the diagnostic accuracy of tumor markers, particularly cancer antigen 19-9 (CA19-9), CA242, and carcinoembryonic antigen, in poorly controlled T2DM patients with hemoglobin A1c levels exceeding 9%, employing receiver operating characteristic curve analysis. Though study offers valuable insights into the potential utility of tumor markers in clinical practice, caution is advised regarding routine tumor marker testing due to challenges such as limited availability and cost. Additionally, the study overlooks potential confounding factors like smoking and alcohol consumption. Variations in CA19-9 and CA242 expression underscore the complex interplay between tumor markers and systemic diseases, warranting further investigation into their diagnostic and prognostic implications. While Meng and Shi represent a significant contribution to the field, more extensive research is needed to fully elucidate the role of tumor markers in diabetes management and beyond.

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis with a 5-year survival of less than 10%. More knowledge of the immune response developed in patients with PDAC is pivotal to develop better combination immune therapies to improve clinical outcome. In this study, we used mass cytometry time-of-flight to undertake an in-depth characterization of PBMCs from patients with PDAC and examine the differences with healthy controls and patients with benign diseases of the biliary system or pancreas. Peripheral blood mononuclear cells from patients with PDAC or benign disease are characterized by the increase of pro-inflammatory cells, as CD86+ classical monocytes and memory T cells expressing CCR6+ and CXCR3+, associated with T helper 1 (Th1) and Th17 immune responses, respectively. However, PBMCs from patients with PDAC present also an increase of CD39+ regulatory T cells and CCR4+CCR6-CXCR3- memory T cells, suggesting Th2 and regulatory responses. Concluding, our results show PDAC develops a multifaceted immunity, where a proinflammatory component is accompanied by regulatory responses, which could inhibit potential antitumor mechanisms.

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.

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.

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.

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 and Objective: Colorectal cancer (CRC) is among the most common types of cancer. Although the disease is treatable in its early stages, five-year survival falls below 20% in the later stages. CEA and CA19-9 are tumor markers used in the diagnosis and follow-up of the disease in clinical practice; however, their diagnostic effectiveness is insufficient. Therefore, the identification of biomarkers that can be easily studied from serum and can diagnose CRC and determine its severity is highly important. In this context, dickkopf1 (DKK1) and cytoskeleton-associated protein 4 (CKAP4) are both promising biomarkers. Materials and Methods: Serum DKK1 and CKAP4 levels were measured in 55 patients with CRC and 40 healthy controls. The patients with CRC were divided into groups based on pathological stages and histological differentiation. The serum levels of both proteins in patients with CRC were measured preoperatively and 10 and 30 days postoperatively. Results: Serum DKK1 and CKAP4 were significantly higher in the CRC group than in the healthy controls (p < 0.05). Serum levels of both proteins rose in line with the disease stage and grade but decreased following surgical resection. A positive correlation was observed between tumor diameter and protein blood levels. The diagnostic efficacy of DKK1 and CKAP4 in CRC (approximately 95%) was higher than that of markers such as CEA and CA19-9. Conclusions: The DKK1 and CKAP4 serum values of patients with CRC are promising biomarkers. They can potentially be used in CRC management, namely, in the diagnosis and treatment of tumor response access and in tumor aggressiveness prediction.

Pancreatic cancer is a highly lethal malignant tumor, which has the characteristics of occult onset, low early diagnosis rate, rapid development and poor prognosis. The reason for the high mortality is partly that pancreatic cancer is usually found in the late stage and missed the best opportunity for surgical resection. As a promising detection technology, liquid biopsy has the advantages of non-invasive, real-time and repeatable. In recent years, the continuous development of liquid biopsy has provided a new way for the detection and screening of pancreatic cancer. The update of biomarkers and detection tools has promoted the development of liquid biopsy. Circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating tumor RNA (ctRNA) and extracellular vesicles (EVs) provide many biomarkers for liquid biopsy of pancreatic cancer, and screening tools around them have also been developed. This review aims to report the application of liquid biopsy technology in the detection of pancreatic cancer patients, mainly introduces the biomarkers and some newly developed tools and platforms. We have also considered whether liquid biopsy technology can replace traditional tissue biopsy and the challenges it faces.

Intraductal papillary mucinous neoplasms are relatively common and entail a variable risk of malignant potential. The Fukuoka guidelines present criteria for the risk of malignant transformation and are used for risk stratification and treatment decision-making. However, these guidelines entail some fallibility with limited sensitivity and specificity. In this case, we present an individual who had many of the hallmarks of malignant transformation but was found to have no evidence of malignancy or high-grade dysplasia. We discuss the suspected etiology of this individual's condition and how it might arise in others, as well as a brief review of the literature on risk factors in intraductal papillary mucinous neoplasms.

Serum carbohydrate antigen 19-9 (CA19-9) is used for recurrence surveillance in patients with resected pancreatic ductal adenocarcinoma (PDAC). This report describes the association of increasing CA19-9 in a male PDAC survivor with presence of prostatic hyperplasia. Unexplained elevation of CA19-9 in male PDAC survivors might be attributable to benign prostatic conditions.

A novel label-free electrochemical immunosensor was prepared for the detection of carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) as biomarkers of cholangiocarcinoma (CCA). A nanocomposite of gold nanoparticles, molybdenum trioxide, and chitosan (Au-MoO3-Chi) was layer-by-layer assembled on the porous graphene (PG) modified a dual screen-printed electrode using a self-assembling technique, which increased surface area and conductivity and enhanced the adsorption of immobilized antibodies. The stepwise self-assembling procedure of the modified electrode was further characterized morphologically and functionally. The electroanalytical detection of biomarkers was based on the interaction between the antibody and antigen of each marker via linear sweep voltammetry using ferrocyanide/ferricyanide as an electrochemical redox indicator. Under optimized conditions, the fabricated immunosensor showed linear relationships between current change (ΔI) and antigen concentrations in two ranges: 0.0025-0.1 U mL-1 and 0.1-1.0 U mL-1 for CA19-9, and 0.001-0.01 ng mL-1 and 0.01-1.0 ng mL-1 for CEA. The limits of detection (LOD) were 1.0 mU mL-1 for CA19-9 and 0.5 pg mL-1 for CEA. Limits of quantitation (LOQ) were 3.3 mU mL-1 for CA19-9 and 1.6 pg mL-1 for CEA. The selectivity of the developed immunosensor was tested on mixtures of antigens and was then successfully applied to determine CA19-9 and CEA in human serum samples, producing satisfactory results consistent with the clinical method.