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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.

Purpose: Gastric cancer is the fifth most common malignant tumor worldwide. Many attempts have been made over the years to investigate the relationship between tumor markers and the risk of recurrence. This study aims to explore the predictive value of tumor markers measured in peritoneal washing during staging laparoscopy, regarding peritoneal carcinomatosis and mortality within 1 year., Methods: Patients with locally advanced gastric cancer, staged as at least usT2anyNM0 were submitted to staging laparoscopy in a Portuguese single center. CA 19.9, CEA, CA 125, and CA 72.4 were measured in the peritoneal washing after being harvested during staging laparoscopy., Results: Thirty-eight patients were enrolled. After 1 year, 20 patients did not recur (52.5%), 11 (28.9%) developed carcinomatosis, and 7 (18.4%) had distant metastasis. Mortality reached 23.7% (n = 9). A statistically significant prediction of carcinomatosis was obtained for CA 125 (cutoff: 107.6 U/mL (p = 0.019)) and CEA (cutoff: 2.0 ng/mL (p = 0.020)) with 87.5% and 75% sensitivity, respectively. Prediction of mortality was significant for CA 125 (cutoff: 103.8 U/mL (p = 0.044)) and CA 125 + CEA (p = 0.030). CEA and CA 125 had NPVs of 87.9% and 93.1% regarding PC, respectively. NPVs of 88.9% and 89.2% were met concerning mortality, for the same tumor markers., Conclusion: Performing the peritoneal liquid harvest during staging laparoscopy makes this analysis cost effective, reproducible, and does not add further morbidity. CA 125 and CEA, individually and in association, are good predictors of progression of disease and mortality within a year of staging laparoscopy in GC patients., (© 2023. The Author(s).)

Introduction: To decide treatment of hepatic cysts diagnosis between simple hepatic cyst (SHC) and cystic mucinous neoplasm (CMN). Radiological features are not patognomonic. Some studies have suggested the utility of intracystic tumor markers., Methods: Retrospective analysis of our prospective database including patients treated due to symptomatic SHC from 2003 to 2021. The aim of the study was to evaluate the results of treatment of symptomatic SHC and the usefulness of the determination of intracystic "carcinoembryonic antigen" (CEA) and "carbohydrate antigen" CA 19.9., Results: 50 patients diagnosed and treated for symptomatic SHC were included. In 15 patients the first treatment was percutaneous drainage. In 35 patients the first treatment was laparoscopic fenestration. Four patients were diagnosed of premalignant or malignant liver cystic lesions (MCN, IPMN, lymphoma B); three of them required surgery after initial fenestration and pathological diagnosis. Median CEA and CA 19-9 were 196 μg/L and 227.321 U/mL respectively. Patients with malignant or premalignant pathology did not have higher levels of intracystic tumor markers. Positive predictive value was 0% for both markers, and negative predictive value was 89% and 91% respectively., Conclusion: Values of intracystic tumor markers CEA and CA 19-9 do not allow distinguishing simple cysts from cystic liver neoplasms. The most effective treatment for symptomatic simple liver cysts is surgical fenestration. The pathological analysis of the wall of the cysts enables the correct diagnosis, allowing to indicate a surgical reintervention in cases of hepatic cyst neoplasia., (Copyright © 2023. Published by Elsevier España, S.L.U.)

Objectives: Misidentification errors in tumor marker tests can lead to serious diagnostic and treatment errors. This study aims to develop a method for detecting these errors using a machine learning (ML)-based delta check approach, overcoming limitations of conventional methods., Methods: We analyzed five tumor marker test results: alpha-fetoprotein (AFP), cancer antigen 19-9 (CA19-9), cancer antigen 125 (CA125), carcinoembryonic antigen (CEA), and prostate-specific antigen (PSA). A total of 246,261 records were used in the analysis. Of these, 179,929 records were used for model training and 66,332 records for performance evaluation. We developed a misidentification error detection model based on the random forest (RF) and deep neural network (DNN) methods. We performed an in silico simulation with 1 % random sample shuffling. The performance of the developed models was evaluated and compared to conventional delta check methods such as delta percent change (DPC), absolute DPC (absDPC), and reference change values (RCV)., Results: The DNN model outperformed the RF, DPC, absDPC, and RCV methods in detecting sample misidentification errors. It achieved balanced accuracies of 0.828, 0.842, 0.792, 0.818, and 0.833 for AFP, CA19-9, CA125, CEA, and PSA, respectively. Although the RF method performed better than DPC and absDPC, it showed similar or lower performance compared to RCV., Conclusions: Our research results demonstrate that an ML-based delta check method can more effectively detect sample misidentification errors compared to conventional delta check methods. In particular, the DNN model demonstrated superior and stable detection performance compared to the RF, DPC, absDPC, and RCV methods., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Objective: To construct a stool-based human protein diagnostic system using the Luminex liquid chip system for early diagnosis of colorectal tumors., Methods: From January, 2021 to January, 2023, 70 patients with colorectal cancer (CRC), 42 patients with colorectal adenoma (CRA), and 38 healthy individuals were recruited from our hospital for detecting fecal protein levels of matrix metalloproteinase-9 (MMP-9), retinol-binding protein 4 (RBP4), chitinase-3-like protein 1 (CHI3L1), and complement component 3a (C3a) using Luminex liquid chip technology and serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) using chemiluminescence assay. Receiver-operating characteristic (ROC) curve analysis was used for assessing the diagnostic efficacy of the combination of MMP-9, RBP4, CHI3L1 and C3a and the combination of CEA and CA19-9 for colorectal tumors., Results: The fecal contents of MMP-9, RBP4, CHI3L1, and C3a were significantly higher in CRC patients than in healthy individuals ( P < 0.05). Fecal MMP-9 and CHI3L1 levels were significantly higher in CRC than in CRA patients ( P < 0.05), but RBP4 and C3a levels did not differ significantly ( P >0.05). CRC patients had significantly higher serum CEA and CA19-9 levels than healthy individuals and CRA patients ( P < 0.05), but the differences were not significant between the latter two groups ( P >0.05). ROC analysis showed that the sensitivity and specificity of the combination of MMP-9, RBP4, CHI3L1, and C3a was 91.4% and 100.0%, for diagnosing CRC, 81.0% and 89.5% for diagnosing CRA, and 83.9% and 97.4% for a combined diagnosis of CRC and CRA, respectively. Z-test analysis indicated that fecal MMP-9, RBP4, CHI3L1, and C3a contents had a greater diagnostic efficacy than serum tumor markers CEA and CA19-9 for a combined diagnosis of colorectal tumors ( P < 0.05)., Conclusion: The Luminex liquid chip detection system for detecting decal RBP4, MMP-9, CHI3L1, and C3a provides an effective means for early diagnosis of colorectal tumors with a greater diagnostic efficacy than serum CEA and CA19-9 levels.

Background: Major pathologic response (MPR) following neoadjuvant therapy (NAT) in pancreatic ductal adenocarcinoma (PDAC) patients undergoing resection is associated with improved survival. We sought to determine whether racial disparities exist in MPR rates following NAT in patients with PDAC undergoing resection., Methods: Patients with potentially operable PDAC receiving at least 2 cycles of neoadjuvant FOLFIRINOX or gemcitabine/nab-paclitaxel ± radiation followed by pancreatectomy (2010-2019) at 7 high-volume centers were reviewed. Self-reported race was dichotomized as Black and non-Black, and multivariable models evaluated the association between race and MPR (i.e., pathologic complete response [pCR] or near-pCR). Cox regression evaluated the association between race and disease-free (DFS) and overall survival (OS)., Results: Results of 486 patients who underwent resection following NAT (mFOLFIRINOX 56%, gemcitabine/nab-paclitaxel 25%, radiation 29%), 67 (13.8%) patients were Black. Black patients had lower CA19-9 at diagnosis (median 67 vs. 204 U/mL; P = 0.003) and were more likely to undergo mild/moderate chemotherapy dose modification (40 vs. 20%; P = 0.005) versus non-Black patients. Black patients had significantly lower rates of MPR compared with non-Black patients (13.4 vs. 25.8%; P = 0.039). Black race was independently associated with worse MPR (OR 0.26, 95% confidence interval [CI] 0.10-0.69) while controlling for NAT duration, CA19-9 dynamics, and chemotherapy modifications. There was no significant difference in DFS or OS between Black and non-Black cohorts., Conclusions: Black patients undergoing pancreatectomy appear less likely to experience MPR following NAT. The contribution of biologic and nonbiologic factors to reduced chemosensitivity in Black patients warrants further investigation., (© 2022. Society of Surgical Oncology.)

Background Imaging studies have limitations in evaluating pancreatic ductal adenocarcinoma (PDAC) treatment response. Purpose To investigate the effectiveness of combined CT and carbohydrate antigen 19-9 (CA 19-9) evaluation at 8 weeks after first-line treatment to predict overall survival (OS) of patients with nonmetastatic PDAC. Materials and Methods Patients with nonmetastatic PDAC who received first-line treatment with either chemotherapy or concurrent chemoradiation in a single-center PDAC cohort registry were retrospectively enrolled in the study between January 2013 and December 2016. Follow-up CT images obtained 8 weeks after treatment were evaluated according to Response Evaluation Criteria in Solid Tumors. Patients with partial response (PR) or stable disease (SD) were defined as CT responders, and those with progressive disease (PD) were defined as CT nonresponders. Patients with a normalized CA 19-9 level at 8-week follow-up were defined as CA 19-9 responders, and those with a nonnormalized or nonelevated CA 19-9 level were defined as CA 19-9 nonresponders. OS was compared using the Kaplan-Meier method with Breslow analysis. Results A total of 197 patients (mean age ± standard deviation, 65 years ± 10; 107 men) were evaluated. Patients with PD ( n = 17) showed shorter OS than those with SD ( n = 147; P < .001) or PR ( n = 33; P = .003). OS did not differ between the patients with PR and those with SD ( P = .60). When the CT and CA 19-9 responses were integrated, OS was longest in CT and CA 19-9 responders (group 1, n = 27; median OS, 26.6 months [95% CI: 9.0, 44.1]), followed by CT responders but CA 19-9 nonresponders (group 2, n = 153; median OS, 15.9 months [95% CI: 13.3, 18.5]; P = .007 vs group 1) and CT and CA 19-9 nonresponders (group 3, n = 17; median OS, 6.5 months [95% CI: 0.8, 12.2]; P < .001 vs group 2). Conclusion Integrated evaluation with CT and carbohydrate antigen 19-9 response allowed more accurate stratification of survival in patients with pancreatic ductal adenocarcinoma in the early treatment period than did evaluation according to Response Evaluation Criteria in Solid Tumors. © RSNA, 2022 Online supplemental material is available for this article.

Abstract: Locally advanced and borderline resectable pancreatic cancers are being increasingly recognized as a result of significant improvements in imaging modalities. The main tools used in diagnosis of these tumors include endoscopic ultrasound, computed tomography, magnetic resonance imaging, and diagnostic laparoscopy. The definition of what constitutes a locally advanced or borderline resectable tumor is still controversial to this day. Borderline resectable tumors have been treated with neoadjuvant therapy approaches that aim at reducing tumor size, thus improving the chances of an R0 resection. Both chemotherapy and radiotherapy (solo or in combination) have been used in this setting. The main chemotherapy agents that have shown to increase resectability and survival are FOLFORINOX (a combination of folinic acid, fluorouracil, irinotecan, and oxaliplatin) and gemcitabine-nab-paclitaxel. Surgery on these tumors remains a significantly challenging task for pancreatic surgeons. More studies are needed to determine the best agents to be used in the neoadjuvant and adjuvant settings, biologic markers for prognostic and operative predictions, and validation of previously published retrospective results., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Colorectal cancer (CRC) categorized as the most common type of gastrointestinal cancers affected both genders equally. Chemotherapeutic drugs became limited due to their deleterious side effects. Therefore, efficiency of M. oleifera leaves extract increased by incorporating silver nanoparticles (Ag-NPs) then studied against colon cancer induced by azoxymethane (AOM) in rats., Methods: Different hematological and biochemical measurements in addition to specific tumor and inflammatory markers were quantified. Histopathological examination for Colonic tissues was performed. Native proteins and isoenzyme patterns were electrophoretically detected in addition to assaying expression of Tumor Protein P53 (TP53) and Adenomatous Polyposis Coli (APC) genes in colonic tissues., Results: M. oleifera nano-extract restored levels of the hematological and biochemical measurements in addition to levels of tumor and inflammatory markers to normalcy in both of nano-extract simult- and post-treated groups. Also, it minimized severity of the histopathological alterations in the simult-treated group and prevented it completely in the post-treated group. The lowest similarity index (SI%) values were noticed with electrophoretic protein (SI=61.54%), lipid (SI=0.00%) and calcium (SI=75.00%) moieties of protein patterns, catalase (SI=85.71%), peroxidase (SI=85.71%), α-esterase (SI=50.00%) and β-esterase (SI=50.00%) isoenzymes in addition to altering the relative quantities of total protein and isoenzyme bands in colon of cancer induced group. Moreover, levels of TP53 and APC gene expression increased significantly (P≤0.05) in colon cancer induced group. The nano-extract prevented the qualitative and quantitative alterations in the different electrophoretic patterns in addition to restoring levels of the gene expressions to normalcy in both of simult- and post-treated groups., Conclusion: M. oleifera nano-extract exhibited ameliorative effect against the biochemical, physiological and molecular alterations induced by AOM in nano-extract simult- and post-treated groups., .

Background: Identification of metastatic pancreatic cancer (mPC) patients with the worst prognosis could help to tailor therapy. We evaluated readily available biomarkers for the prediction of 90-day mortality in a nationwide cohort of mPC patients., Methods: Patients with synchronous mPC were included from the Netherlands Cancer Registry (2015-2017). Baseline CA19-9, albumin, CRP, LDH, CRP/albumin ratio, and (modified) Glasgow Prognostic Score ((m)GPS composed of albumin and CRP) were evaluated. Multivariable logistic regression analyses were performed to identify predictors of 90-day mortality. Prognostic value per predictor was quantified by Nagelkerke's partial R 2 ., Results: Overall, 4248 patients were included. Median overall survival was 2.2 months and 90-day mortality was 59.4% (n = 1629). All biomarkers predicted 90-day mortality in univariable analysis, and remained statistically significant after adjustment for clinically relevant factors and all other biomarkers (all p  < 0.001). The prognostic value of the biomarkers combined was similar to WHO performance status. Patients who received chemotherapy had better outcomes than those who did not, regardless of biomarker levels., Conclusions: In mPC patients, albumin, CA19-9, CRP, LDH, CRP/albumin ratio, and (m)GPS are prognostic for poor survival. Biomarkers did not predict response to chemotherapy. These readily available biomarkers can be used to better inform patients and to stratify in clinical trials.

Background: Serum CA19-9 concentration may be useful in triaging patients with pancreatic cancer for more intensive staging investigations. Our aim was to identify the CA19-9 cut-point with the greatest accuracy for detecting unresectable features not identified by CT scan, and to examine the performance of this and other cut-points in predicting the outcome of staging laparoscopy (SL)., Methods: Patients with pancreatic cancer were drawn from two state-wide cancer registries between 2009 and 2011. We used classification and regression tree (CART) analysis to identify the CA19-9 cut-point which best predicted the presence of imaging-occult unresectable features, and compared its performance with that of a number of alternative cut-points. We then used logistic regression to test the association between CA19-9 concentration and detection of unresectable features in patients who underwent SL., Results: From the CART analysis, the optimal CA19-9 cut-point was 440 U/mL. CA19-9 ≥ 150 U/mL had a similar Youden Index, but greater sensitivity (69% versus 47%). This remained true for those who had obstructive jaundice at the time of CA19-9 sampling. CA19-9 concentration greater than or equal to 110 U/mL, 150 U/mL and 200 U/mL was associated with significantly greater odds of unresectable features being detected during SL., Conclusion: Elevated serum CA19-9 concentration is a valid marker for CT-occult unresectable features; the most clinically appropriate cut-point appears to be ≥ 150 U/mL irrespective of the presence of jaundice. Clinical trials which evaluate the value of CA19-9 in the staging algorithm for pancreatic cancer are needed before it is routinely used in clinical practice., (Copyright © 2020. Published by Elsevier B.V.)

Background/objectives: Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) is important as PDAC can lead to mortality; however, no specific biomarker has been identified for its early diagnosis. We previously identified fibrinogen α chain as a promising biomarker for differentiating between patients with and without PDAC using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Here, we aimed to validate the clinical usefulness of serum fibrinogen as a biomarker for PDAC., Methods: From 2009 to 2011, blood samples of 67 PDAC patients and 43 healthy adults (controls) were prospectively collected. Serum fibrinogen levels and their clinical significances were evaluated., Results: Mean fibrinogen levels were significantly higher in the PDAC group than in the control group (3.08 ± 0.565 vs. 2.54 ± 0.249 log 10  ng/mL, P < 0.001). In the receiver operating characteristic analysis, overall sensitivity, and specificity of serum fibrinogen levels for differentiating PDAC patients from control patients were 67.4% and 83.6%, respectively, with a 427-ng/mL cutoff value. Serum fibrinogen levels were significantly higher in PDAC patients with distant metastasis than in those without distant metastasis (3.38 ± 0.581 vs. 2.93 ± 0.499 log 10  ng/mL, P = 0.002). Median overall survival was significantly longer in PDAC patients with low fibrinogen levels (<1000 ng/mL) than in those with high fibrinogen levels (≥1000 ng/mL) [489 days (95% confidence interval, 248.1-729.9) vs. 172 days (58.4-285.6) (P = 0.008)]. Although serum fibrinogen levels were poorly correlated with carbohydrate antigen 19-9 levels, these two biomarkers together predicted survival better., Conclusions: Serum fibrinogen levels may be a useful biomarker for diagnosing and predicting PDAC prognosis., (Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: The clinical characteristic differences at the initial recurrence site after resection for pancreatic ductal adenocarcinoma (PDAC) remain unknown. We investigated the clinical characteristics in patients with lung recurrence after surgical resection and evaluated the outcome of resection for isolated lung recurrence., Methods: Of 442 consecutive PDAC patients who underwent surgical resection between 2002 and 2018, 229 had recurrence on imaging. Initial recurrence sites were the liver, lung, local, peritoneal, multiple organs, and others. We analyzed the clinicopathologic factors and outcomes, comparing by initial recurrence site, and investigated the outcomes of resection for isolated lung recurrence., Results: Liver recurrences were the most frequent (n = 60, 26%), followed by lung recurrence (n = 48, 21%). The interval from surgery to recurrence was significantly longer in lung recurrence (P = 0.0001). Patients with lung recurrence had significantly longer overall survival after diagnosis (P < 0.0001). Patients who underwent surgical resection of lung recurrence had a significantly prolonged overall survival rate after recurrence diagnosis (P = 0.004)., Conclusions: Patients with lung recurrence had significantly prolonged survival than those with other recurrence patterns. Resection for isolated lung recurrence represented relatively good prognosis, and possibly may be beneficial in highly-selected patients., Competing Interests: Conflicts of interest None., (Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Pancreatic cancer and chronic pancreatitis are still significant diagnostic and clinical problems. A tumor marker that would eliminate the imperfection of preoperative serum carbohydrate antigen 19-9 (CA19-9) concentration is still being sought. This study aimed to conduct a comparative analysis of the concentrations in serum and peritoneal cavity of matrix metalloproteinases: metalloproteinase-2 (MMP-2), metalloproteinase-9 (MMP-9), CA19-9, and carcinoembryonic antigen (CEA) in patients with pancreatic cancer (PC), chronic pancreatitis (CP) and a control group (CG). The study was performed in a group of 90 patients. Group 1 consisted of 30 patients with PC, group 2 consisted of 30 patients with CP. There was no case of pancreatic cancer in the CP group. Group 3 (CG) consisted of 30 individuals, who were recruited among patients operated for non-inflammatory cholelithiasis. The serum samples and intraperitoneal fluid, when present or samples of peritoneal lavage were taken from patients and the concentration of MMP-2, MMP-9, and CA19-9 were evaluated. The revealed intraperitoneal fluid concentrations of the MMP-2, MMP-9, and CA19-9 were significantly higher in both PC and CP groups in comparison to CG. There were no statistically significant differences between intraperitoneal fluid concentrations of the MMP2, MMP9, and CA19-9 in PC and CP groups. The revealed serum concentration of the MMP-2 and MMP-9 in the PC, CP, and CG were significantly higher compared to the intraperitoneal fluid. There was no significant correlation between serum and intraperitoneal fluid concentration of the MMP-2, MMP-9, and CA19-9 and the presence of cancer cells in the intraperitoneal fluid conventional cytological examination. The elevated preoperative intraperitoneal fluid concentration of MMP-2 and MMP-9 and serum concentration of CA19-9 and CEA showed significant sensitivity and specificity in PC prediction. The preoperative serum concentrations of MMP-2 and MMP-9, serum, and intraperitoneal fluid concentrations of CA19-9 and CEA have been shown to have a statistically significant effect on predicting cancer progression and the presence of distant metastases. Presented findings suggest the usefulness of MMP-2 and MMP-9 as a potential predictor of PC and marker of dissemination but its usefulness in the differential diagnosis between PC and CP is limited, however more studies on a large population are needed to support our result. To our knowledge, this was the first study evaluating not only MMP-2 and MMP-9 concentrations in serum but also the concentration of these metalloproteinases in peritoneal fluid in patients with PC and CP.

BACKGROUND Plasmacytoid urothelial carcinoma (PUC) is a rare and aggressive variant of urothelial cancers. Herein, we report a patient with CDH-1 mutated PUC who presented with disseminated peritoneal metastasis and high levels of CA 19-9. CASE REPORT A 65-year-old female presented to the hospital with vomiting, obstructive jaundice, and acute renal failure. Imaging studies showed bilateral hydronephrosis, bladder wall thickening without masses, and dilation of both common bile and pancreatic ducts without pancreatic masses. Carbohydrate antigen (CA) 19-9 was elevated at >17 000 U/mL. Repeated cystoscopies demonstrated no masses within the bladder, but with nodularity and inflamed mucosa, and random biopsies were obtained and showed PUC. Ascitic fluid cytology revealed metastatic PUC. A targeted exome next-generation sequencing (NGS) revealed pathogenic mutations in TP53, CDH-1, RB1, and ARIDA1A. The patient was debilitated, and hospice care was recommended. She passed away after 2 months of her initial presentation. CONCLUSIONS PUC is a rare and aggressive histological variant of bladder cancer. Advanced stage at diagnosis and high relapse rates after treatment with cytotoxic regimens are common. At the molecular level, somatic alterations in cadherin-1 (CDH-1) gene seem to be characteristic. Exploring the molecular sphere of this disease is prudent to identify possible new therapeutic targets.

Objective: The aim of the study was to clarify the diagnostic impact of measuring serum anti-p53 antibody (S-p53Ab) in predicting the histological grades of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas., Methods: We compared the measured values and positive prevalence of S-p53Ab across the different histological grades of 111 resected IPMN cases. We also evaluated the TP53 alterations using immunohistochemistry and next-generation sequencing., Results: Serum anti-p53 antibody were detected in 6 of 111 cases, all of their histological grades were high-grade dysplasia (HGD) and invasive carcinoma (INV). Positive prevalence of S-p53Ab was higher in cases with INV (4/35 cases, 11.4%) than those with HGD (2/38 cases, 5.3%), whereas S-p53Abs were undetectable in cases with low-grade dysplasia. Measured S-p53Ab values were not correlated with either carcinoembryonic antigen (CEA) or carbohydrate antigen 19-9 (CA 19-9). In 4 of 6 S-p53Ab-positive cases, the TP53 alterations-somatic pathogenic mutations or aberrant immunoreactivity-were identified in their IPMN lesions. A combination assay of S-p53Ab, CEA, and CA 19-9 revealed a 38.4% sensitivity and 81.6% specificity for predicting HGD/INV., Conclusions: Serum anti-p53 antibody can serve as a surrogate marker for TP53 alterations and help predict the presence of HGD/INV in cases with IPMN, in combination with CEA and CA 19-9.

Early diagnosis and treatment of colorectal cancer (CRC) are important for improving patients' survival. Metadherin is an oncogene that plays a pivotal role in carcinogenesis and can be suggested as a cancer biomarker. This study aimed to elucidate the efficacy of serum Metadherin mRNA expression as a potential non-invasive biomarker for early diagnosis of CRC in relation to other screening markers as carcinoembryonic antigen (CEA), carbohydrate antigen 19.9 (CA19.9) and Fecal occult blood (FOB) and also to assess its relationship with the tumor stage and survival rate. A convenience series of 86 CRC cases (group I) were recruited with 78 subjects as controls (group II). Serum Metadherin mRNA expression level was determined using reverse transcription polymerase chain reaction (RT-PCR). Serum Metadherin mRNA expression level was significantly elevated in CRC cases when compared with controls (P < 0.001). For CRC diagnosis; Receiver operator characteristic (ROC) analyses revealed that the diagnostic accuracy of serum Metadherin mRNA (AUC = 0.976) was significantly higher than other routine CRC screening markers as CEA, CA19.9 and FOB. The combined accuracy of these markers (AUC = 0.741) was increased when used with serum Metadherin mRNA (AUC = 0.820). High serum Metadherin mRNA expression was associated with poorly differentiated histological grade, advanced tumor stage and lower survival rate. AUC of Metadherin was 0.820 for differentiating advanced versus early tumor stages. Serum Metadherin mRNA expression is a useful non-invasive biomarker for CRC. It can be used for screening and early diagnosis of CRC and can increase the efficacy of other routine CRC screening markers when it is estimated in CRC patients with them. It is also associated with advanced tumor stage and a lower survival rate.

Objective: To examine clinic pathological features of mucinous cystic neoplasms (MCN) of the pancreas and explore the prognosis factors associated with malignant transformation of MCN of the pancreas. Methods: This multicenter retrospective study included all patients with pancreatic MCN underwent surgery at Department of Pancreatic Surgery, Zhongshan Hospital of Fudan University between January 2008 and December 2018 and patients with MCN who confirmed by postoperative pathology from Multicenter Pancreatic Cystic Tumor Database. There were 50 males (14.4%) and 297 females (85.6%) and the mean age was 48.6 years (range: 24-77 years). According to the pathological results, all patients were divided into benign lesion group (including MCN and which associated with low/medium grade dysplasia) and malignant lesion group (including MCN with high-grade dysplasia or invasive carcinoma) . The preoperative clinical pathology and imaging features of the two groups were analyzed, and the risk factors associated with malignant transformation of MCN were statistically analyzed. Results: This multicenter retrospective study included 347 patients. Twenty-four of the 347 patients were malignant, including 7 males and 17 females. Univariate analysis showed that age, gender, carcino-embryonic antigen (CEA) , CA19-9, CA125, tumor maximum diameter, and tumor location were remarkably different in the two groups ( P< 0.05) . Logistic regression analysis found that the preoperative tumor maximum diameter ( OR= 1.023, 95 % CI : 1.002-1.045, P= 0.035) was an independent risk factor for MCN malignant transformation. Conclusions: Age, gender, CEA, CA19-9, CA125, tumor maximum diameter, and tumor location are important features of MCN malignant lesions.The maximum diameter of the preoperative tumor is an independent risk factor for MCN malignant transformation.

A near-infrared (NIR) photothermal immunoassay was designed for the sensitive monitoring of CA 19-9 on the capture antibody-coated microplate, coupling a 3D-printed device with a digital thermometer in this work. Prussian blue nanoparticles (PBNPs)-encapsulated CaCO 3 microspheres were not only utilized for labeling of detection antibody, but used as the photo-heat conversion materials for the signal amplification. With the sandwiched immunocomplex, the as-released PBNPs under acidic conditions adsorbed and converted NIR-light wavelength to heat under 808-nm laser irradiation, thereby resulting in the temperature change of the detection solution. Under optimum conditions, a linear range from 1.0 U mL -1 to 100 U mL -1 and a detection limit of 0.83 U mL -1 were acquired for the CA 19-9 detection on the portable photothermal immunosensing platform with PBNP-CaCO 3 -labeling system. Relative standard deviations for reproducibility were ≤9.7% for intra-assay and ≤11.9% for inter-assay. High specificity, long-time storage stability (>10 months) and good accuracy (relative to gold standard with commercial human ELISA kit) with the photothermal immunoassay were encountered for the evaluation of target CA 19-9 in complex system., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The measurement performance of 13 biochemistry parameters (CEA, CA 19-9, amylase, lipase, sodium, potassium, chloride, creatinine, glucose, protein, albumin, LDH, triglycerides) was tested in a panel of biological fluids other than blood and urine (peritoneal, pleural, pancreatic fluids ...). Our protocol, based on a risk analysis, allowed us to justify our choices and compare the performance obtained with those of the serum or plasma matrix already validated. Thus, the coefficients of variation obtained in body fluids are comparable. The assessment of accuracy (spiking and dilution tests) shows the absence of bias, which is consistent with the absence of matrix effect. The linearity studied by dilution tests shows that the upper limits of the measurement interval communicated by the supplier are applicable to body fluids. The absence of contamination and stability have been also confirmed. All analytes are stable for 3 days at room temperature, 7 days between 2 and 8̊C, and 6 months at -20̊C; except LDH and lipase. For most analytes, at least one interference (hemolysis, icterus, lipemia) was found. Finally, a bibliographical study, confronted with the experience of prescribers, led us to define optimal thresholds to help interpret patients' results. In conclusion, this work has allowed us to validate analytical methods for body fluids testing after relying on their comparability to the blood matrix. We have also been able to adapt our practices and finally be accredited according to the standard NF IN ISO 15189.

This paper introduces a cheap simple MWCNTs@paper biosensor for the detection of CA19-9, which is a biomarker of pancreatic cancer. By adding the CA19-9 antibody to the surface of MWCNTs which are deposited on the microporous filter paper, the correlation between the concentration of CA19-9 and resistance of biosensor element was linear due to the site-specific binding of antigen and antibody. The detection range is wide (0 U/mL-at least 1000 U/mL), and even in the low concentration of CA19-9, the linearity remains satisfying. Based on this property, it could be used for the detection of early-stage pancreatic cancer. Besides, this research originally introduces a vacuum freeze-drying method for the long-term preservation of biosensor, prolonging its storage time from 3 h to at least 7 days, which signifcantly promoted its value in practical application. One piece of the MWCNTs@paper biosensor only cost $2 (about 30 times cheaper than ELISA) approximately, and the detection speed is satisfying (2 h, 12 times faster than ELISA), which will possibly increase its opportunity of mass production and clinical practice., Competing Interests: Declaration of Competing Interest The authors declared that there is no conflict of interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background/aims: The aim of the present study was to investigate whether pancreas cyst fluids should be divided into two for cytological diagnosis and biochemical tests., Materials and Methods: The present study was conducted with fluids aspirated from 12 pancreas cysts. The fluids were divided into two and sent to the cytopathology (fluid 1) and biochemistry (fluid 2) laboratories. Fluid 1 was centrifuged at the cytopathology laboratory. Cytology slides were prepared from the deposit, and the supernatant was sent to the biochemistry laboratory. Fluid 2 was centrifuged at the biochemistry laboratory, and amylase, carcinoembryonic antigen, and cancer antigen 19.9 levels were determined in the supernatant. These procedures were repeated for fluid 1 from the cytopathology laboratory. The remaining fluid 2 was sent to the cytopathology laboratory. Fluid 1-like slides were prepared from fluid 2 in the cytopathology laboratory. Cytological diagnoses of fluid 1 and fluid 2 were compared, and the Pearson correlation coefficient for biochemical test results was identified., Results: 92% of fluid 1 and 50% of fluid 2 were diagnostic. Biochemical test results of fluid 1 and fluid 2 were similar, and the Pearson correlation coefficient was high., Conclusion: Our results showed that pancreatic cyst fluids did not need to be divided into two for cytological diagnosis and biochemical tests. Following centrifugation of the whole fluid at the cytopathology laboratory, the deposit and the supernatant can be used for cytological diagnosis and for biochemical tests, respectively. With this protocol, the sensitivity of cytological diagnoses and biochemical tests of pancreatic cyst fluids may increase.

Objective: The objective of this study was to explore the exact relationship between the arterial radiomics score (rad-score) and lymph node (LN) metastasis in pancreatic ductal adenocarcinoma (PDAC)., Methods: A total of 225 patients with pathologically confirmed PDAC who underwent multislice computed tomography within 1 month of resection from December 2016 to August 2017 were retrospectively studied. For each patient, 1029 radiomics features of arterial phase were extracted, which were reduced using the least absolute shrinkage and selection operator logistic regression algorithm. Multivariate logistic regression models were used to analyze the association between the arterial rad-score and LN metastasis., Results: Lymph node-negative and LN-positive patients accounted for 107 (47.56%) and 118 (52.44%) of the cohort, respectively. The rad-score, which consisted of 12 selected features of the arterial phase, was significantly associated with LN status (P < 0.05). Univariate analysis revealed that the arterial rad-score and T stage were independently and positively associated with risk of LN metastasis (P < 0.05). Multivariate analyses revealed a significant association between the arterial rad-score and the LN metastasis (P < 0.0001). Higher arterial rad-score was associated with LN metastasis (P for trend <0.0001)., Conclusions: The arterial rad-score is independently and positively associated with the risk of LN metastasis in PDAC.

Ampullary cancer represents approximately 6% of the malignant periampullary tumors. An early occurrence of symptoms leads to a 5-year survival rate after curative surgery of 30 to 67%. In addition to the tumor stage, the immunohistological subtypes appear to be important for postoperative prognosis. The aim of this study was to analyze the different subtypes regarding their prognostic relevance. A total of 170 patients with ampullary cancer were retrospectively analyzed between 1999 until 2016 after pancreatic resection. Patients were grouped according to their pathohistological subtype of ampullary cancer (pancreatobiliary, intestinal, mixed). Characteristics among the groups were analyzed using univariate and multivariate models. Survival probability was analyzed by the Kaplan-Meier method. An exact subtyping was possible in 119 patients. A pancreatobiliary subtype was diagnosed in 69 patients (58%), intestinal in 41 patients (34.5%), and a mixed subtype in 9 patients (7.6%). Survival analysis showed a significantly worse 5-year survival rate for the pancreatobiliary subtype compared with the intestinal subtype (27.5% versus 61%, p < 0.001). The mean overall survival of patients with pancreatobiliary, intestinal, and mixed subtype was 52.5, 115 and 94.7 months, respectively (p < 0.001). The pathohistological subtypes of ampullary cancer allows a prediction of the postoperative prognosis.

Nanostructured capacitive biosensors, combined with inexpensive fabrication technologies, may provide simple, sensitive devices for detecting clinically relevant cancer biomarkers. Herein, we report a novel platform for detecting the pancreatic cancer biomarker CA19-9 using low-cost screen-printed interdigitated electrodes (SPIDEs). The SPIDEs were modified by carbon nano-onions (CNOs) and graphene oxide (GO) films, on which a layer of anti-CA19-9 antibodies was immobilized. The modification with CNOs and GO significantly improved the analytical performance of the biosensor, which displayed superior results to those prepared only with GO. The biossensor exhibited high reproducibility and a relatively low limit of detection of 0.12 U mL -1 . Using these devices in combination with information visualization methods we were able to detect CA19-9 in whole cell lysates of colorectal adenocarcinoma. The fabrication of these low-cost, disposable immunosensors is a successful attempt to explore CNOs in capacitive biosensors, which may be extended for detection of different cancer biomarkers., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background/aims: This study aimed to determine a predictive bioindicator that would detect the treatment response of patients diagnosed with rectal cancer and treated with neoadjuvant chemoradiotherapy (nCRT)., Materials and Methods: The data collected from 37 patients receiving nCRT were retrospectively evaluated. The p53 score and gene instability in MLH1 and MSH2, which are among the DNA mismatch repair (MMR) genes, were evaluated using immunohistochemical methods. The neutrophils-leukocytes ratio (NLR), carcinoembryonic antigen (CEA), and carbohydrate antigen (CA) 19-9 values were obtained as hematological parameters from computer records. The pathologic analysis of the therapy response after nCRT was classified according to the modified grading system by Ryan et al. Results: The changes in the NLR, CEA, and CA19-9 values before and after treatment were statistically significant (p<0.001 and p=0.005). A near significant effect of the decrease of the CEA value in the 5th week after treatment was detected on the pathological response score (p=0.075). The p53 mutation score in those patients with any residue was higher than the total response. Overall, 89.2% of the patients exhibited MMR positivity (stability), and 10.8% of the cases with MRM negativity (instability) had a macroscopic residue. Cases with pathological total response were MRM positive., Conclusion: Consequently, in most of the patients treated with nCRT, the treatment caused tumor and nodal remission. In the prediction of this therapy response, hematological and genetic parameters, such as NLR, P53, MLH1, and MSH2, play a predictive role.

BACKGROUND This study evaluated the performance of serum CYFRA 21-1 and placental growth factor (PIGF) as screening markers for endometriosis. MATERIAL AND METHODS In this prospective study included 81 female patients who underwent laparoscopy to treat benign ovarian tumors. Serum samples were obtained from all study patients before surgery. Serum marker levels, including CYFRA 21-1, PIGF, cancer antigen (CA)125, CA19-9, and human epididymis protein 4 (HE4) were measured using a fluorescence immunoassay technique. RESULTS Forty of the patients were diagnosed with endometriosis (the study group) and 41 women were diagnosed with other benign ovarian tumors (the control group). Mean serum CYFRA 21-1 and PIGF levels were not different between these 2 groups (P=0.179 and P=0.865, respectively). Elevated serum CA125 levels (>35 U/mL) and lower CYFRA 21-1 levels (≤2.29 ng/mL) were more frequently observed in the endometriosis study group than in the control group (P<0.0001, and P=048, respectively). High serum PIGF levels (>14.2 pg/mL) were observed in both groups (P=0.226). Mean serum CA19-9 levels and HE4 levels, as well as the ROMA (risk of ovarian malignancy Algorithm) score were similar between the 2 groups. Sensitivity (95.0%) and negative predictive value (NPV) (80.0%) of CYFRA 21-1 for diagnosing endometriosis were higher than those of CA125 (sensitivity 67.5%, NPV 74.5%) and PIGF (sensitivity 20.0%, NPV 53.6%). However, the specificity (PIGF 90.2%, CA125 92.7%) and positive predictive value (PPV) (PIGF 66.7%, CA125 87.1%) of PIGF and CA125 for diagnosing endometriosis were higher than those of CYFRA 21-1 (specificity 19.5%, PPV 53.5%). CONCLUSIONS CYFRA 21-1 and PIGF may be promising markers to identify patients with and without ovarian endometriosis.

Objectives: The aim of this study was to evaluate the diagnostic and prognostic impact of systemic inflammatory markers for IPMN with high-grade dysplasia (HGD)/invasive carcinoma., Methods: Neutrophil-to-lymphocyte ratio (NLR), derived NLR, platelet-to-lymphocyte ratio, and C-reactive protein-to-albumin ratio were compared across the different histological grades of 205 IPMN cases. We also tested the diagnostic performance for IPMN with HGD/invasive carcinoma., Results: The median (interquartile range) preoperative NLR was higher in IPMN with HGD/invasive carcinoma (2.03 [1.48-2.93]) than IPMN with low-grade dysplasia (1.74 [1.42-2.24], P = 0.0137). The C-reactive protein-to-albumin ratio and derived NLR values were also significant higher in cases with HGD/invasive carcinoma. A combination assay of NLR, carcinoembryonic antigen, and carbohydrate antigen 19-9 revealed a 58.8% sensitivity and 76.8% specificity. Among the cases with worrisome features, the high NLR values increased the positive predictive value (68.8%) compared with low values (31.8%). In IPMN cases with the associated invasive carcinoma, high NLR values showed association with the deeper vertical invasion and shorter survival periods., Conclusions: Preoperative NLR, combined with tumor markers and image findings, can be a useful predictive marker for the presence of HGD/invasive carcinoma in IPMNs. Preoperative NLR also predicts the long-term outcomes in IPMN cases with invasive carcinoma.

A novel screening method for protein aptamer selection was developed in this study. Aptamers with high affinity and specificity to the surface recombinant antigen of Helicobacter pylori (HP-Ag) and to tumor markers carcinoembryonic antigen (CEA), cancer antigen 125 (CA125) and cancer antigen 19-9(CA19-9) were screened using trypsin enhanced screening method. Briefly, the target proteins above were immobilized onto 96-well polystyrene plates and incubated with a single-stranded DNA (ssDNA) library for aptamer selection. Then, trypsin was introduced to digest the proteins and obtain ssDNA that bound to the target proteins with high specificity. The concentration of ssDNA that shed from protein-ssDNA complexes was detected. After sequencing, the enrichment of target-specific aptamers was monitored and the affinity of each aptamer was analyzed. Urea, which has been reported in other article, was used to compare with trypsin. The results revealed that trypsin was more effective than urea for protein aptamer selection. The protocol used in this study provided a novel method for generating aptamers., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The challenge of the early diagnosis of pancreatic cancer in routine clinical practice requires low-cost means of detection, and this may be achieved with immunosensors based on electrical or electrochemical principles. In this paper, we report a potentially low-cost immunosensor built with interdigitated gold electrodes coated with a self-assembled monolayer and a layer of anti-CA19-9 antibodies, which is capable of detecting the pancreatic cancer biomarker CA19-9 using electrical impedance spectroscopy. Due to specific, irreversible adsorption of CA19-9 onto its corresponding antibody, according to data from polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS), the immunosensor is highly sensitive and selective. It could detect CA19-9 in commercial samples with a limit of detection of 0.68 U mL -1 , in addition to distinguishing between blood serum samples from patients with different concentrations of CA19-9. Furthermore, by treating the capacitance data with information visualization methods, we were able to verify the selectivity and robustness of the immunosensor with regard to false positives, as the samples containing higher CA19-9 concentrations, including those from tumor cells, could be distinguished from those with possible interferents.

To establish a time-resolved fluorescence immunochromatographic assay for quantitative determination of carbohydrate antigen 19-9 (CA19-9) in serum, we prepared CA19-9 test strips by integrating double-antibody sandwich method and fluorescence immunochromatography technique. Carboxy fluorescent microspheres and nitrocellulose membrane were used as carriers for labeling and coating CA19-9 pairing antibodies. We optimized the process by adjusting the amount of labeling and coating antibody. According to the linear range, lowest detection limit and precision, We evaluated the time-resolved fluorescence immunochromatographic assay of CA19-9. When the amount of labeled antibody was 80 μg for 20 μL fluorescent microspheres, and the concentration of coated antibody on the test line was 1.5 mg/mL, the optimal reaction time was 15 minutes. Assay linear range was 12.5 to 800 U/mL and the minimum detection limit was 6.32 U/mL. The Within-run and between-run coefficient of variation were less than 15%. Average recovery rate was 101%. By detecting 50 clinical samples in parallel with Roche electrochemical luminescence detection kit, correlation coefficient was 0.980 6. The experiment, initially established a fluorescence immunochromatographic detection method to quantitative detection of serum CA19-9, which has a good clinical application prospect.

Background: In this study, we developed and validated a nomogram to predict lymph node metastasis before surgery in patients with intrahepatic cholangiocarcinoma (ICC)., Methods: Using the data from January 2006 to January 2015, we enrolled a total of 218 eligible patients with clinicopathologically confirmed ICC as a primary cohort to develop the nomogram. After various variables before surgery were analyzed by multivariable logistic regression, we combined the preoperative carbohydrate antigen 19-9, primary site of tumor, lymphonodus size on computed tomography imaging, tumor growth pattern, and (if applicable) histologic grade to make two different predictive nomograms. Then, the results were validated in 62 consecutive ICC patients from February 2015 to December 2016. We also compared the performance of the different nomograms via calibration, discrimination, and clinical use., Results: The nomogram displayed fine discrimination (the concordance index, 0.761) and fine calibration in the primary cohort. When applied to the validation cohort, the nomogram also showed fine discrimination (concordance index, 0.794) and fine calibration. After adding the histologic grade to the nomogram, the integrated discrimination for predictive performance improved significantly. Finally, the clinical usefulness of predictive nomogram was proven via the decision curve analysis., Conclusions: The proposed nomograms can be selectively used to achieve more accurate lymph node metastasis predictions before surgery in patients with ICC, and this information can help with clinical management., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Intrahepatic cholangiocarcinomas are the second most common malignant tumors of the liver with an unfavorable prognosis. The role of CA19-9 in terms of patient prognosis is still under debate in the literature., Objective: The aim of the present study was to investigate the prognostic value of preoperatively assessed CA19-9 levels in patients with intrahepatic cholangiocarcinoma after surgery., Material and Methods: A total of 63 patients suffering from intrahepatic cholangiocarcinoma underwent surgery between March 2001 and February 2013 at the West German Cancer Center in Essen, Germany. The follow-up ended in December 2017. The UICC stages, clinicopathological parameters and postoperative tumor-specific survival rates were analyzed with respect to preoperatively measured CA19-9 serum levels., Results: Increased CA19-9 serum levels correlated with higher UICC tumor stages and other unfavorable clinicopathological parameters. Moreover, patients with preoperative elevated CA19-9 serum levels displayed significantly reduced overall survival rates (especially >1000 U/ml vs. ≤1000 U/ml; median overall survival: 14.05 months vs. 42.40 months; p = 0.0003)., Conclusion: Preoperatively assessed CA19-9 levels >1000 U/ml are a strong negative prognostic factor of postoperative disease-specific survival in patients suffering from intrahepatic cholangiocarcinoma. Future studies are necessary to evaluate if patients with highly elevated CA19-9 serum levels should be considered for modified treatment strategies (e. g. neoadjuvant or adjuvant therapy).

Cholangiocarcinoma (CCA), a malignant tumor of the bile duct, is a major public health problem in many Southeast Asian countries, particularly Thailand. The slow progression makes it difficult for early diagnosis and most patients are detected in advanced stages. This study aimed to review all relevant articles related to the biomarkers for the diagnosis of CCA and point out potential biomarkers. A thorough search was performed in PubMed and ScienceDirect for CCA biomarker articles. Required data were extracted. A total of 46 articles that fulfilled the inclusion and had none of the exclusion criteria were included in the analysis (17, 22, 3, 4, and 1 articles on blood, tissue, bile, both blood and tissue, and urine biomarkers, respectively). Carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA), either alone or in combination with other biomarkers, are the most commonly studied biomarkers in the serum. Their sensitivity and specificity ranged from 47.2% to 98.2% and 89.7% to 100%, respectively. However, in the tissue, gene methylations and DNA-related markers were the most studied CCA biomarkers. Their sensitivity and specificity ranged from 58% to 87% and 98% to 100%, respectively. Some articles investigated biomarkers both in blood and tissues, particularly CA19-9 and CEA, with sensitivity and specificity ranging from 33% to 100% and 50% to 97.7%, respectively. Although quite a number of biomarkers with a potential role in the early detection of CCA have been established, it is difficult to single out any particular marker that could be used in the routine clinical settings.

Objectives: The aims of this study were to establish a scoring model for the differential diagnosis of pancreatic cancer (PC) and chronic pancreatitis (CP) and to evaluate its diagnostic efficacy., Methods: The data of 502 patients with PC and 210 patients with CP at the Peking Union Medical College Hospital from January 1999 to December 2013 were retrospectively analyzed. Binary logistic regression was applied to establish the prediction model for the differential diagnosis. The model was verified using the method of leave-one-out cross-validation., Results: The scoring system was established with 5 variables including age, carbohydrate antigen 19-9 level, splenic vein invasion, irregular dilatation of the pancreatic duct, and nontruncated pancreatic duct stenosis. The score range was from -2 to 3. The area under the receiver operating characteristic curve of the objects was 0.779 (95% confidence interval, 0.744-0.814) (P < 0.01), indicating that the scoring system is good at differentiation of PC with CP. With a score of 1 as the diagnostic cut-off value, the diagnostic sensitivity, specificity, positive predictive value, negative predictive value, and accuracy rate were 71.3%, 69.0%, 70.0%, 71.4%, and 70.2%, respectively., Conclusions: The scoring model may improve the differential diagnosis of PC and CP and be useful in clinical practice.

Determination of a glycolipid ligand can quickly reveal the carbohydrate epitope recognized by carbohydrate-binding proteins (CBP) which may include antibodies, lectins, toxins, and virulence factors. Thin layer chromatography (TLC) is a simple, well-known, and heavily used method to separate glycolipids based on their migration through a thin layer of chromatography media, usually silica gel, coated on the surface of a rigid plate. Reacting carbohydrate-binding proteins directly on a TLC plate of separated glycolipids is a powerful technique to quickly determine functional carbohydrate epitopes present in an entire glycolipid extract of a target cell type or tissue.

Background: Hohla et al. suggested that female gender could positively predict response to FOLFIRINOX in patients with advanced pancreatic cancer. In this study, we explored the response to the FOLFIRINOX regimen by gender within the trial PRODIGE4/ACCORD 11., Patients and Methods: Data were described by gender, both in FOLFIRINOX group and in the intention-to-treat population of the trial. The relative effect of gender (females in comparison to males) on overall survival (OS) and progression-free survival was estimated by using a Cox proportional hazard model and was presented with the Hazard Ratio and their 95% confidence interval. The analysis of prognostic factors of OS included also: age (older than 65 years), ECOG performance status, primary tumor location, synchronous metastases, number of metastatic sites, hepatic metastasis, pulmonary metastases, lymph node metastases, level of Albumin and level of serum carbohydrate antigen 19-9 and three domains from the EORTC Quality of Life QLQC-30 questionnaire., Results: The FOLFIRINOX group (N = 171 patients) included 106 women (62%) and 65 men. No significant differences were observed between genders regarding demographic and clinical parameters, excepted for lymph nodes metastasis (17% and 35% in women and men respectively; p = 0.012). Median OS was longer for females as compared to males in FOLFIRINOX group (13.1 versus 10.3 months respectively; HR = 0.73; 95% CI, 0.51-1.06). Similarly, median PFS was superior (7.2 versus 5.9 months; HR = 0.79; 95% CI, 0.57-1.10). Nevertheless, in both cases, the differences were not statistically significant (p = 0.10 et p = 0.169, respectively)., Conclusions: In this study, the overall survival and progression-free survival rates were not significantly higher for females than for males in FOLFIRINOX group (HR = 0.73; 95% CI, 0.51-1.06 and HR = 0.79; 95% CI, 0.57-1.10 respectively). Even if the percentage of patients with lymph node metastasis is higher for males than for females, the interaction between gender and lymph node metastasis was non-significant. Our exploratory analysis did not permit to definitively conclude about a possible effect of gender on the prognosis of patients under FOLFIRINOX. This subject deserves further evaluation., Trial Registration: ClinicalTrials.gov number: NCT00112658., Key Message: Our analysis suggests that FOLFIRINOX, as first-line option for patients with metastatic pancreatic cancer who are younger than 76 years and who have a good performance status (ECOG 0 or 1), no cardiac ischemia and normal or nearly normal bilirubin levels, is beneficial, but not particularly in female patients.

Pancreatic cancer remains a deadly disease with a 5-year survival rate of only 8%. Even after surgical resection, most patients have recurrence of their cancer. Over the last 10 years, improvements in chemotherapy regimens led to a doubling in median overall survival. Here we review the management of advanced pancreatic cancer and highlight vaccine therapy as a novel modality of treatment., (© 2017 Wiley Periodicals, Inc.)

Purpose: Transforming growth factor-beta inhibitors may enhance the antitumor activity of gemcitabine with acceptable safety and tolerability. This open-label, multicenter, non-randomized phase 1b study assessed the safety/tolerability, pharmacokinetics, and tumor response of galunisertib plus gemcitabine in Japanese patients with advanced or metastatic pancreatic cancer., Methods: During each 28-day cycle, galunisertib 150 mg was administered orally twice daily (300 mg/day) for 14 days, followed by 14 days of rest. Gemcitabine 1000 mg/m 2 was intravenously given on Days 8, 15, and 22. Safety was assessed by the incidence of dose-limiting toxicities (DLTs) in the first cycle and treatment-emergent adverse events (TEAEs). Efficacy was assessed by antitumor activity and changes in carbohydrate antigen 19-9 (CA19-9)., Results: No DLTs were reported. All 7 enrolled patients had ≥1 TEAE, of which the most common included anorexia, decreased neutrophil count, and decreased white blood cell count. Grade ≥3 TEAEs were observed in 6 patients; 4 patients had Grade ≥3 TEAEs (decreased neutrophil, white blood cell, and lymphocyte count; hypophosphatemia) considered possibly related to study drug(s). The pharmacokinetic profile of galunisertib in combination with gemcitabine was similar to that previously observed for galunisertib alone. The clinical response [complete response (CR), partial response (PR), or stable disease] rate was 42.9%, and the median progression-free survival was 64 days; no CR/PR were achieved., Conclusion: Galunisertib plus gemcitabine had an acceptable safety/tolerability profile with evidence of efficacy in Japanese patients with advanced or metastatic pancreatic cancer.

Purpose: The study aims to determine the possible effects of black tea consumption on the level of CA 19-9 antigen in the human body., Methods: The level of CA 19-9 was measured in 270 healthy individuals who consumed heavy amounts of black tea., Results: About 43.3 % of involved individuals were revealed to have elevated levels of CA 19-9. Males with high values of CA 19-9 represented the greatest number of involved individuals. The cutoff value of high levels of CA 19-9 in all individuals was ranged 69-105 U/ml., Conclusions: Consuming heavy amounts of black tea could be considered an important interfering factor that affects the levels of CA 19-9. The cutoff or predictive value of CA 19-9 in heavy-consuming people of black tea was determined.

Carbohydrate antigen 19-9 (CA19-9) is an important biomarker for the early diagnosis and clinical monitoring of pancreatic cancer. Reliable, simple, and accurate methods for the detection of CA19-9 are still urgently needed. In this study, polythionine-Au composites (AuNPs@ PThi) were designed and prepared through one-pot reaction using HAuCl 4 as the co-oxidant and raw material in thionine solution containing FeCl 3 as the oxidant. AuNPs@PThi-immobilized glassy carbon electrode was used as a sensitive redox probe for electrochemical interface. AuNPs@PThi not only favored the amplification of electrochemical signals but also facilitated excellent environmental friendliness for bioassay. Maximizing the electrochemical properties of AuNPs@PThi, an effective label-free electrochemical immunoassay for the ultrasensitive and reliable detection of CA19-9 was developed. Under optimal conditions, the linear range of the proposed immunosensor was estimated to range from 6.5 to 520 U/mL, with a detection limit of 0.26 U/mL at a signal-to-noise ratio of 3. The prepared immunosensor for CA19-9 detection showed high sensitivity, stability, and reproducibility. Furthermore, the fabricated immunosensor based on AuNPs@PThi can effectively detect and distinguish clinical serum samples of pancreatic cancer and normal control with accuracy and convenience., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Aim: To analyze the outcomes in pancreatic cancer (PC) cases with a microscopically-positive resection margin (R1 resection) treated with postoperative radiotherapy (PORT)., Patients and Methods: We retrospectively analyzed the outcomes in 62 patients who received PORT for PC with R1 resection between 2001 and 2012. All patients received three-dimensional conformal radiotherapy. Concurrent chemotherapy was administered to 58 patients., Results: The median follow-up was 20.1 months. The median survival was 22.0 months and the 3-year overall survival rate was 25%. The 3-year disease-free survival and local recurrence-free survival rates were 12% and 54%, respectively. Local recurrence occurred in 23 patients (44%), distant failure in 45 (87%), and both in 16 (31%). By multivariate analysis, the postoperative cancer antigen 19-9 (CA19-9) level and adjuvant chemotherapy were independent prognostic factors for survival., Conclusion: PORT is associated with a relatively favorable survival outcome in PC with R1 resection. Chemotherapy and postoperative CA19-9 level were significant prognostic factors for survival., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)