Investigating the Current Harmonization Status of Tumor Markers Using Global External Quality Assessment Programs: A Feasibility Study.

BACKGROUND: The harmonization status of most tumor markers (TMs) is unknown. We report a feasibility study performed to determine whether external quality assessment (EQA) programs can be used to obtain insights into the current harmonization status of the tumor markers α-fetoprotein (AFP), prostate specific antigen (PSA), carcinoembryonic antigen (CEA), cancer antigen (CA)125, CA15-3 and CA19-9. METHODS: EQA sample results provided by 6 EQA providers (INSTAND [Germany], Korean Association of External Quality Assessment Service [KEQAS, South Korea], National Center for Clinical Laboratories [NCCL, China], United Kingdom National External Quality Assessment Service [UK NEQAS, United Kingdom], Stichting Kwaliteitsbewaking Medische Laboratoriumdiagnostiek [SKML, the Netherlands], and the Royal College of Pathologists of Australasia Quality Assurance Programs [RCPAQAP, Australia]) between 2020 and 2021 were used. The consensus means, calculated from the measurement procedures present in all EQA programs (Abbott Alinity, Beckman Coulter DxI, Roche Cobas, and Siemens Atellica), was used as reference values. Per measurement procedure, the relative difference between consensus mean for each EQA sample and the mean of all patient-pool-based EQA samples were calculated and compared to minimum, desirable, and optimal allowable bias criteria based on biological variation. RESULTS: Between 19040 (CA15-3) and 25398 (PSA) individual results and 56 (PSA) to 76 (AFP) unique EQA samples were included in the final analysis. The mean differences with the consensus mean of patient-pool-based EQA samples for all measurement procedures were within the optimum bias criterion for AFP, the desirable bias for PSA, and the minimum bias criterion for CEA. However, CEA results <8 µg/L exceeded the minimum bias criterion. For CA125, CA15-3, and CA19-9, the harmonization status was outside the minimum bias criterion, with systematic differences identified. CONCLUSIONS: This study provides relevant information about the current harmonization status of 6 tumor markers. A pilot harmonization investigation for CEA, CA125, CA15-3, and CA19-9 would be desirable.

Diagnostic and economic value of carcinoembryonic antigen, carbohydrate antigen 19-9, and carbohydrate antigen 72-4 in gastrointestinal cancers.

BACKGROUND: The diagnostic and economic value of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and CA72-4 for gastrointestinal malignant tumors lacked evaluation in a larger scale. AIM: To reassess the diagnostic and economic value of the three tumor biomarkers. METHODS: A retrospective analysis of all 32857 subjects who underwent CEA, CA19-9, CA72-4, gastroscopy and colonoscopy from October 2006 to May 2018 was conducted. Then, we assessed the discrimination and clinical usefulness. Total cost, cost per capita and cost-effectiveness ratios were used to evaluate the economic value of two schemes (gastrointestinal endoscopy for all people without blood tests vs both gastroscopy and colonoscopy when blood tests were positive). RESULTS: The analysis of 32857 subjects showed that CEA was a qualified biomarker for colorectal cancer (CRC), while the diagnostic efficiencies of CA72-4 were catastrophic for all gastrointestinal cancers (GICs). Regarding early diagnosis, only CEA could be used for early CRC. The combination of biomarkers didn't greatly increase the area under the curve. The economic indicators of CEA were superior to those of CA19-9, CA72-4 and any combination. At the threshold of 1.8 µg/L to 10.4 µg/L, all four indicators of CEA were lower than those in the scheme that conducted gas-trointestinal endoscopy only. Subgroup analysis implied that the health checkup of CEA for people above 65 years old was economically valuable. CONCLUSION: CEA had qualified diagnostic value for CRC and superior economic value for GICs, especially for elderly health checkup subjects. CA72-4 was not suitable as a diagnostic biomarker.

Novel prognostic indicator combining inflammatory indicators and tumor markers for gastric cancer.

BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors worldwide, and we hope to identify an economical but practical prognostic indicator. It has been reported that inflammatory indicators and tumor markers are associated with GC progression and are widely used to predict prognosis. However, existing prognostic models do not comprehensively analyze these predictors. METHODS: This study retrospectively reviewed 893 consecutive patients who underwent curative gastrectomy from January 1, 2012, to December 31, 2015, in the Second Hospital of Anhui Medical University. Prognostic factors predicting overall survival (OS) were analyzed using univariate and multivariate Cox regression analyses. Nomograms including independent prognostic factors were plotted for predicting survival. RESULTS: Ultimately, 425 patients were enrolled in this study. Multivariate analyses demonstrated that the neutrophil-to-lymphocyte ratio (NLR, total neutrophil count/lymphocyte count × 100%) and CA19-9 were independent prognostic factors for OS (p=0.001, p=0.016). The NLR-CA19-9 score (NCS) is constructed as the combination of the NLR and CA19-9. We defined NLR<2.46 and CA19-9≤37 U/ml as an NCS of 0, NLR≥2.46 or CA19-9>37 U/ml as an NCS 1, and NLR≥2.46 and CA19-9>37 U/ml as an NCS of 2. The results showed that higher NCS was significantly associated with worse clinicopathological characteristics and OS (p<0.05). Multivariate analyses revealed that the NCS was an independent prognostic factor for OS (NCS1: p<0.001, HR=3.172, 95% CI=2.120-4.745; NCS2: p<0.001, HR=3.052, 95% CI=1.928-4.832). Compared with traditional predictive indices, the NCS had the highest AUC for a 12-month survival, a 36-month survival, a 60-month survival, and OS (AUC= 0.654, 0.730, 0.811, 0.803, respectively). The nomogram had a higher Harrell's C-index than the TNM stage alone (0.788 vs. 0.743). CONCLUSIONS: The NCS provides more accurate predictions of the prognosis of GC patients, and its predictive value is significantly better than that of traditional inflammatory indicators or tumor markers. It is an effective complement to existing GC assessment systems.

Assessment of main pancreatic duct cutoff with dilatation, but without visible pancreatic focal lesion on MDCT: a novel diagnostic approach for malignant stricture using a CT-based nomogram.

OBJECTIVES: To identify useful features to predict hidden pancreatic malignancies in patients with main pancreatic duct (MPD) abrupt cutoff and dilatation, but without visible focal pancreatic lesions on CT. METHODS: This retrospective study included 92 patients (mean age, 63.4 ± 10.6 years, 63 men and 29 women) with MPD abrupt cutoff and dilatation, but without visible focal pancreatic lesion on contrast-enhanced CT between 2009 and 2021. Two radiologists independently evaluated the CT imaging features. Multivariable logistic regression analysis was performed to identify clinical and CT imaging features for hidden pancreatic malignancies. A nomogram was developed based on these results and assessed its performance. RESULTS: Thirty-eight (41.3%) and 54 (58.7%) were classified into the malignant and benign groups, respectively. In the multivariable analysis, CA19-9 elevation (odds ratio [OR] 7.5, p = 0.003), duct cutoff site at the head/neck (OR 7.6, p = 0.006), parenchymal contour abnormality at the duct cutoff site (OR 13.7, p < 0.001), and presence of acute pancreatitis (OR 11.5, p = 0.005) were independent predictors of pancreatic malignancy. A combination of any two significant features showed an accuracy of 77.2%, and a combination of any three features exhibited a specificity of 100%. The CT-based nomogram showed an area under the curve (AUC) of 0.84 (95% confidence interval, 0.77-0.90). CONCLUSIONS: The three CT imaging features and CA19-9 elevation translated into a nomogram permit a reliable estimation of hidden pancreatic malignancies in patients with MPD abrupt cutoff without visible focal pancreatic lesion. It may facilitate determining whether to proceed to further diagnostic tests. KEY POINTS: • Isoattenuating pancreatic ductal adenocarcinoma can manifest only as an isolated main pancreatic duct (MPD) dilatation with abrupt cutoff, making it difficult to distinguish from benign strictures. • Along with the serum CA 19-9 elevation, MPD cutoff site at the pancreas head or neck, parenchymal contour abnormality at the duct cutoff site, and associated acute pancreatitis indicated a higher probability of the malignant MPD strictures. • The CT-based nomogram provided excellent diagnostic performance (AUC of 0.84) for hidden pancreatic malignancies in patients with MPD abrupt cutoff and dilatation.

Prognostic assessment of tumor markers in lung carcinomas.

BACKGROUND: Serum tumor markers are molecules that are secreted by tumor cells and may be present in small amounts in the serum of healthy individuals. Their role as prognostic factors in lung cancer remains controversial. OBJECTIVE: To assess the prognostic role of CEA, CA 19-9, CA 15-3, and CA 125 in non-squamous non-small cell lung cancer. PATIENTS AND METHODS: A total of 112 patients with non-squamous non-small cell lung cancer from two Oncology Centers were retrospectively analyzed. Tumor marker levels were measured prior to treatment. Data regarding clinical characteristics and overall survival were collected. RESULTS: Median overall survival of all patients was 15.97 months. Pre-treatment elevations of CA 125 and CA 15-3 were associated with shorter overall survival (p=0.004 and p=0.014, respectively). Single CEA and CA 19-9 elevations were not associated with a worse prognosis. Patients with two or more elevated markers had a statistically significant decrease in overall survival (p=0.008). In the multivariate analysis, smoking status and number of positive tumor markers at diagnosis were independently associated with a worse prognosis. CONCLUSION: High pre-treatment levels of tumor markers were correlated with decreased survival in patients with non-squamous non-small cell lung cancer.

Risk stratification of LI-RADS M and LI-RADS 4/5 combined hepatocellular cholangiocarcinoma: prognostic values of MR imaging features and clinicopathological factors.

OBJECTIVES: To investigate the role of clinicopathological factors and MR imaging factors in risk stratification of combined hepatocellular cholangiocarcinoma (cHCC-CCA) patients who were classified as LR-M and LR-4/5. METHODS: We retrospectively identified consecutive patients who were confirmed as cHCC-CCA after surgical surgery in our institution from June 2015 to November 2020. Two radiologists evaluated the preoperative MR imaging features independently, and each lesion was assigned with a LI-RADS category. Preoperative clinical data were also collected. Multivariate Cox proportional hazards model was applied to separately identify the independent factors correlated with the recurrence of cHCC-CCAs in LR-M and LR-4/5. Risk stratifications were conducted separately in LR-M and LR-4/5. Recurrence-free survival (RFS) rates and overall survival (OS) rates were analyzed by using the Kaplan-Meier survival curves and log-rank test. RESULTS: A total of 131 patients with single primary lesion which met the 2019 WHO classification criteria were finally included. Corona enhancement, delayed central enhancement, and microvascular invasion (MVI) were identified as predictors of RFS in LR-M. Mosaic architecture, CA19-9, and MVI were independently associated with RFS in LR-4/5. Based on the number of these independent predictors, patients were stratified into favorable-outcome groups (LR-ML subgroup and LR-4/5L subgroup) and dismal-outcome groups (LR-MH subgroup and LR-4/5H subgroup). The corresponding median RFS for LR-ML, LR-MH, LR-5L, and LR-5H were 25.6 months, 8.2 months, 51.7 months, and 18.1 months. CONCLUSION: Our study explored the prognostic values of imaging and clinicopathological factors for LR-M and LR-4/5 cHCC-CCA patients, and different survival outcomes were observed among four subgroups after conducting risk stratifications. KEY POINTS: • Corona enhancement, delayed central enhancement, and MVI were identified as predictors of RFS in cHCC-CCAs which were classified into LR-M. Mosaic architecture, CA19-9, and MVI were independently associated with RFS in cHCC-CCAs which were classified into LR-4/5. • Based on the identified risk factors, LR-M and LR-4/5 cHCC-CCA patients could be stratified into two subgroups respectively, with significantly different RFS and OS. • cHCC-CCA patients from LR-M did not always have worse RFS and OS than those from LR-4/5 in some cases.

Assessment of the Anti-Cancer Efficiency of Silver Moringa oleifera Leaves Nano-extract against Colon Cancer Induced Chemically in Rats.

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 ß-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.
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Clinical benefit of surveillance after resection of pancreatic ductal adenocarcinoma: A systematic review and meta-analysis.

BACKGROUND: The value of routine surveillance after resection of pancreatic ductal adenocarcinoma (PDAC) is unclear, and expert guidelines offer conflicting recommendations. This study is a systematic review of evidence for surveillance programs. METHODS: A systematic review of studies evaluating different surveillance methods was undertaken. A meta-analysis was performed for those studies reporting rates of asymptomatic recurrence, treatment of recurrence and overall survival, according to different surveillance methods. RESULTS: Ten studies were included in the literature review, with five studies appropriate for meta-analysis (1596 patients). Patients within active surveillance programs were more likely to have recurrence detected at an asymptomatic stage (Pooled Rate: 49.3% vs. 19.1%, p = 0.043). Within studies reporting these outcomes, patients with asymptomatic recurrence were more likely to receive treatment for recurrence (Odds Ratio 3.49; 95% CI: 1.73-7.07; p < 0.001) and had longer overall survival (Mean Difference: 9.5 months; 95% CI: 4.1-14.8; p < 0.001) than those with symptoms at time of recurrence. DISCUSSION: Routine surveillance after surgery for PDAC appears to detect more patients at an asymptomatic stage. Data from these non-randomised trials also suggest that treatment rates and survival may be superior in patients were recurrence is detected when asymptomatic. As such, these data suggest that routine surveillance may improve patient outcomes, although an appropriately conducted trial would be required to address concerns that various sources of bias may be affecting these results.

Assessment of structural protein expression by FTIR and biochemical assays as biomarkers of metabolites response in gastric and colon cancer.

Colon and gastric cancers are the widespread benign types of cancers which are synchronous and metachronous neoplasms. In terms of the progression and progress of the disease, metabolic processes and differentiation in protein structures have an important role in for treatment of the disease. In this study we proposed to investigate the metabolic process and the differentiation of protein secondary structure among colon and gastric cancer as well as healthy controls using biochemistry and Fourier Transform InfraRed spectroscopy (FTIR) methods. For this purpose, we measured blood serum of 133 patients, which were conducted upon oncology department (45 colon cancer, 45 gastric cancer and 43 control individuals). The obtained spectroscopic results and biochemical assays showed significant reduction in the amount of functional groups in cancer groups contrary with total protein measurements and structure of protein differences between colon and gastric cancers. Differentiations were visible in serum levels of CEA, CA-125, CA-15-3, CA-19-9 AFP (Alpha fetoprotein) of gastric and colon cancer patients as well as in amide III and secondly described amide I regions. Our findings suggest that amide I bonds in colon cancer cells can be helpful in diagnosis of colon cancer. Indeed, our results showed that metabolic processes were higher in gastric cancer group than in colon cancer. Hence, FTIR spectroscopy and curve-fitting analysis of amide I profile can be successfully applied as tools for identifying quantitative and qualitative changes of proteins in human cancerous blood serum. However, what is very important, in PCA analysis we see, that the scatter plot of PC1 (variability 80%) and PC2 (variability 15%) show that the data related to the control and two cancer groups are clustered together with different magnitudes and directions.

A presurgical prognostic stratification based on nutritional assessment and carbohydrate antigen 19-9 in pancreatic carcinoma: An approach with nonanatomic biomarkers.

BACKGROUND: Nutritional status and tumor markers are important prognostic indicators for surgical decisions in pancreatic carcinoma. This study aimed to stratify the probability of surviving pancreatic carcinoma based on systematically chosen nonanatomic biomarkers. METHODS: We included 187 consecutive patients that underwent surgical resections for pancreatic carcinoma. We performed multivariable analyses to evaluate prognostic indicators, including 4 blood-test indexes: the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, prognostic nutritional index, and the modified Glasgow prognostic score; and 4 body-composition indexes: the normalized total psoas muscle area, the normalized total elector spine muscle area, the psoas muscle computed tomography value, and the elector spine muscle computed tomography value. RESULTS: Poor survival was associated with 2 independent risk factors: neutrophil-to-lymphocyte ratio ≥3.0 (hazard ratio, 1.54) and prognostic nutritional index <36 (hazard ratio, 1.60), and with high carbohydrate antigen 19-9 levels (≥37 IU/mL). The 2 indexes were not significantly associated with clinicopathological factors, including carbohydrate antigen 19-9. Patients with no risk factors had significantly better survival than those with 1 (P = .007) or 2 risk factors (P = .001), and survival was similar in the latter 2 groups (P = .253). A presurgical nonanatomic scoring system (range, 0-2) was constructed: 0 points for no risk factors, 1 point for 1 or 2 nutritional risk factors, and 1 point for carbohydrate antigen 19-9 ≥37 IU/mL. Survival rate at 3 years decreased with increasing scores (76% for score 0, 42% for score 1, and 21% for score 2; all P < .05). CONCLUSION: Neutrophil-to-lymphocyte ratio and prognostic nutritional index were independent prognostic risk factors in pancreatic carcinoma and integrating these indexes with carbohydrate antigen 19-9 levels could successfully stratify survival.

Comparative Assessment of Two Strategies for Interpreting Tumor Markers in Ascitic Effusions.

BACKGROUND/AIM: There are two strategies for the interpretation of tumor markers (TM) in fluid effusions: i) high cut-off and ii) fluid/serum ratio (F/S) and low cut-off. The objective of this study is to compare these two strategies and to determine whether diagnostic accuracy improves by the identification of possible false positives using Adenosine deaminase (ADA), C reactive protein (CRP) and % of polymorphonuclear cells (%PN). PATIENTS AND METHODS: We studied 157 ascitic fluids, 74 of which were malignant. ADA, CRP and %PN were determined in ascitic fluid, and Carcinoembryonic antigen (CEA), Cancer antigen 72-4 (CA72-4), Cancer antigen CA19-9 and Cancer antigen 15-3 (CA15-3) in both fluid and serum. RESULTS: The strategy of high cut-off showed 59.5% sensitivity at 100% specificity. The F/S strategy showed 75.7% sensitivity at 95.2% specificity. Subclassifying cases with ADA, CRP and %PN negative showed 67.5% sensitivity at 100% specificity for high cut-off and for the F/S strategy was 81.7% sensitivity at 98.7% specificity. CONCLUSION: The strategy of F/S with negative ADA, CRP and %PN allow the best interpretation for TM in the ascitic fluid.

The assessment of serum and diagnostic peritoneal lavage concentration of matrix metalloproteinase-2, matrix metalloproteinase-9, carbohydrate antigen 19-9, and carcinoembryonic antigen in patients with pancreatic cancer and chronic pancreatitis.

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.

Retooling a Blood-Based Biomarker: Phase I Assessment of the High-Affinity CA19-9 Antibody HuMab-5B1 for Immuno-PET Imaging of Pancreatic Cancer.

PURPOSE: In patients with cancer who have an abnormal biomarker finding, the source of the biomarker in the bloodstream must be located for confirmation of diagnosis, staging, and therapy planning. We evaluated if immuno-PET with the radiolabeled high-affinity antibody HuMab-5B1 (MVT-2163), binding to the cancer antigen CA19-9, can identify the source of elevated biomarkers in patients with pancreatic cancer. PATIENTS AND METHODS: In this phase I dose-escalating study, 12 patients with CA19-9-positive metastatic malignancies were injected with MVT-2163. Within 7 days, all patients underwent a total of four whole-body PET/CT scans. A diagnostic CT scan was performed prior to injection of MVT-2163 to correlate findings on MVT-2163 PET/CT. RESULTS: Immuno-PET with MVT-2163 was safe and visualized known primary tumors and metastases with high contrast. In addition, radiotracer uptake was not only observed in metastases known from conventional CT, but also seen in subcentimeter lymph nodes located in typical metastatic sites of pancreatic cancer, which were not abnormal on routine clinical imaging studies. A significant fraction of the patients demonstrated very high and, over time, increased uptake of MVT-2163 in tumor tissue, suggesting that HuMab-5B1 labeled with beta-emitting radioisotopes may have the potential to deliver therapeutic doses of radiation to cancer cells. CONCLUSIONS: Our study shows that the tumor antigen CA19-9 secreted to the circulation can be used for sensitive detection of primary tumors and metastatic disease by immuno-PET. This significantly broadens the number of molecular targets that can be used for PET imaging and offers new opportunities for noninvasive characterization of tumors in patients.

Diagnostic accuracy of magnetic resonance, computed tomography and contrast enhanced ultrasound in radiological multimodality assessment of peribiliary liver metastases.

PURPOSE: We compared diagnostic performance of Magnetic Resonance (MR), Computed Tomography (CT) and Ultrasound (US) with (CEUS) and without contrast medium to identify peribiliary metastasis. METHODS: We identified 35 subjects with histological proven peribiliary metastases who underwent CEUS, CT and MR study. Four radiologists evaluated the presence of peribiliary lesions, using a 4-point confidence scale. Echogenicity, density and T1-Weigthed (T1-W), T2-W and Diffusion Weighted Imaging (DWI) signal intensity as well as the enhancement pattern during contrast studies on CEUS, CT and MR so as hepatobiliary-phase on MRI was assessed. RESULTS: All lesions were detected by MR. CT detected 8 lesions, while US/CEUS detected one lesion. According to the site of the lesion, respect to the bile duct and hepatic parenchyma: 19 (54.3%) were periductal, 15 (42.8%) were intra-periductal and 1 (2.8%) was periductal-intrahepatic. According to the confidence scale MRI had the best diagnostic performance to assess the lesion. CT obtained lower diagnostic performance. There was no significant difference in MR signal intensity and contrast enhancement among all metastases (p>0.05). There was no significant difference in CT density and contrast enhancement among all metastases (p>0.05). CONCLUSIONS: MRI is the method of choice for biliary tract tumors but it does not allow a correct differential diagnosis among different histological types of metastasis. The presence of biliary tree dilatation without hepatic lesions on CT and US/CEUS study may be an indirect sign of peribiliary metastases and for this reason the patient should be evaluated by MRI.

The role of urinary KIM-1, NGAL, CA19-9 and ß2-microglobulin in the assessment of ureteropelvic junction obstruction in adults.

PURPOSE: The objective of this study is to evaluate the diagnostic properties of urinary biomarkers in adults with ureteropelvic junction obstruction: KIM-1, NGAL, CA19-9, and ß2-microglobulin. We also assessed urinary biomarker concentrations following pyeloplasty. MATERIAL AND METHODS: We prospectively studied adults from December 2013 to February 2015. We included 47 patients with a mean age of 38.6 ± 12.7 years. Each patient provided four samples of voided urine for biomarker measurement, one at pre-operative consultation and the others at 1, 3, and 6 months of post-operative follow-up. The control group consisted of 40 healthy individuals with no hydronephrosis on ultrasound evaluation. RESULTS: KIM-1 had an area under the curve of 0.79 (95% CI 0.70-0.89), NGAL 0.71 (95% CI 0.61-0.83), CA19-9 0.70 (95% CI 0.60-0.81), and ß2-microgloblin 0.61 (95% CI 0.50-0.73). KIM-1 was the most sensitive marker with a cut-off of 170.4 pg/mg creatinine (sensitivity 91.4%, specificity 59.1%), whereas CA19-9 was the most specific with a cut-off of 51.3 U/mg creatinine (sensitivity 48.9%, specificity 88.0%). Urinary concentrations of biomarkers decreased after pyeloplasty. CONCLUSIONS: The evaluation of urinary biomarkers is useful in adults undergoing pyeloplasty. KIM-1, NGAL, and CA19-9 were elevated and significantly decreased after surgery.

Use of Tumor Markers in Gastrointestinal Cancers: Surgeon Perceptions and Cost-Benefit Trade-Off Analysis.

BACKGROUND: Gastrointestinal cancers constitute the third most common cancers worldwide. Tumor markers have long since been used in the postoperative surveillance of these malignancies; however, the true value in clinical practice remains undetermined. OBJECTIVE: This study aimed to evaluate the clinical utility of three tumor markers in colorectal and esophagogastric cancer. METHODS: A systematic review of the literature was undertaken to elicit the sensitivity, specificity, statistical heterogeneity and ability to predict recurrence and metastases for carcinoembryonic antigen (CEA), cancer antigen (CA) 19-9 and CA125. European surgeons were surveyed to assess their current practice and the characteristics of tumor markers they most valued. Data from the included studies and survey were combined in a cost-benefit trade-off analysis to assess which tumor markers are of most use in clinical practice. RESULTS: Diagnostic sensitivity and specificity were ranked the most desirable characteristics of a tumor marker by those surveyed. Overall, 156 studies were included to inform the cost-benefit trade-off. The cost-benefit trade-off showed that CEA outperformed both CA19-9 and CA125, with lower financial cost and a higher sensitivity, and diagnostic accuracy for metastases at presentation (area under the curve [AUC] 0.70 vs. 0.61 vs. 0.46), as well as similar diagnostic accuracy for recurrence (AUC 0.46 vs. 0.48). CONCLUSIONS: Cost-benefit trade-off analysis identified CEA to be the best performing tumor marker. Further studies should seek to evaluate new tumor markers, with investigation tailored to factors that meet the requirements of practicing clinicians.

Assessment of average of normals (AON) procedure for outlier-free datasets including qualitative values below limit of detection (LoD): an application within tumor markers such as CA 15-3, CA 125, and CA 19-9.

Average of normals (AON) is a quality control procedure that is sensitive only to systematic errors that can occur in an analytical process in which patient test results are used. The aim of this study was to develop an alternative model in order to apply the AON quality control procedure to datasets that include qualitative values below limit of detection (LoD). The reported patient test results for tumor markers, such as CA 15-3, CA 125, and CA 19-9, analyzed by two instruments, were retrieved from the information system over a period of 5 months, using the calibrator and control materials with the same lot numbers. The median as a measure of central tendency and the median absolute deviation (MAD) as a measure of dispersion were used for the complementary model of AON quality control procedure. The ubias values, which were determined for the bias component of the measurement uncertainty, were partially linked to the percentages of the daily median values of the test results that fall within the control limits. The results for these tumor markers, in which lower limits of reference intervals are not medically important for clinical diagnosis and management, showed that the AON quality control procedure, using the MAD around the median, can be applied for datasets including qualitative values below LoD.

Standardization of tumor markers - priorities identified through external quality assessment.

Tumor markers are often heterogeneous substances that may be present in elevated concentrations in the serum of cancer patients. Typically measured by immunoassay, they contribute to clinical management, particularly in screening, case-finding, prognostic assessment, and post-treatment monitoring. Data both from external quality assessment (EQA) schemes and clinical studies demonstrate significant variation in tumor marker results obtained for the same specimen using different methods. Between-method between-laboratory coefficients of variation (CV) reported by EQA schemes generally reflect the complexity of the measurand, ranging from <5% for the structurally relatively simple α-fetoprotein (AFP) to >25% for the complex mucinous cancer antigen 19-9 (CA19-9). Improving the standardization of tumor marker measurements is particularly important for three reasons. The primary use of tumor markers is in monitoring cancer patients over long periods of time. Clinical interpretation of trends may consequently be affected if results are obtained in different laboratories using different methods or if a laboratory has to change method. Differences in results may have major implications for adoption of area-wide decision cut-offs and make implementation of these difficult. Method-related differences also make it difficult to compare clinical studies. Improving comparability of tumor marker results requires broad international agreement about which molecular forms of the measurand have clinical utility, identifying and adopting pure molecular forms as calibrants, and defining antibody specificities for their optimal detection. These aims have been achieved to varying extents for the most frequently measured serum tumor markers as described in this paper.