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.

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.

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.

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.

Y90 Radioembolization in chemo-refractory metastastic, liver dominant colorectal cancer patients: outcome assessment applying a predictive scoring system.

BACKGROUND: In treatment-refractory liver dominant metastatic colorectal cancer, the role of liver directed therapies still is unclear. We sought to determine a prognostic score for Y90 radioembolization in these patients. METHODS: We analyzed 106 patients with refractory liver dominant mCRC who had undergone a total of 178 Y90 radioembolizations with resin microspheres was collected. Potential factors influencing survival were analyzed using a Cox regression. The Log rank test served to establish prognostic factors and to form a clinical score for outcome prediction after Y90 radioembolization. RESULTS: Median survival of all patients was 6.7 months. Neither age nor prior surgical or systemic therapy nor metastatic spread had an effect on survival. In contrast, hepatic tumor load, Karnofsky index as well as CEA and CA19-9 serums level had a significant influence (p < 0.001, p = 0.037, p = 0.023 and p < 0.001, respectively). These three factors formed a score with 1 point each for tumor load >20 %, CEA >130 ng/ml or CA19-9 > 200U/ml and Karnofsky index <80 %. Patients with a score of 0 and 1 displayed a median OS of 10.4 months. Patients with a score of 2 and 3 demonstrated a median OS of 5.1 months only (p < 0.001). CONCLUSION: Overaggressive patient selection for Y90 radioembolization of liver dominant chemorefractory mCRC is of questionable benefit. A scoring system comprising hepatic tumor load, CEA and CA19-9 serum levels and Karnofsky index (TuCK-score) may support an improved patient selection. In our cohort of liver only versus liver dominant disease, extrahepatic lung or lymphatic metastases did not significantly alter the prognosis.

Cancers Screening in an Asymptomatic Population by Using Multiple Tumour Markers.

BACKGROUND: Analytic measurement of serum tumour markers is one of commonly used methods for cancer risk management in certain areas of the world (e.g. Taiwan). Recently, cancer screening based on multiple serum tumour markers has been frequently discussed. However, the risk-benefit outcomes appear to be unfavourable for patients because of the low sensitivity and specificity. In this study, cancer screening models based on multiple serum tumour markers were designed using machine learning methods, namely support vector machine (SVM), k-nearest neighbour (KNN), and logistic regression, to improve the screening performance for multiple cancers in a large asymptomatic population. METHODS: AFP, CEA, CA19-9, CYFRA21-1, and SCC were determined for 20 696 eligible individuals. PSA was measured in men and CA15-3 and CA125 in women. A variable selection process was applied to select robust variables from these serum tumour markers to design cancer detection models. The sensitivity, specificity, positive predictive value (PPV), negative predictive value, area under the curve, and Youden index of the models based on single tumour markers, combined test, and machine learning methods were compared. Moreover, relative risk reduction, absolute risk reduction (ARR), and absolute risk increase (ARI) were evaluated. RESULTS: To design cancer detection models using machine learning methods, CYFRA21-1 and SCC were selected for women, and all tumour markers were selected for men. SVM and KNN models significantly outperformed the single tumour markers and the combined test for men. All 3 studied machine learning methods outperformed single tumour markers and the combined test for women. For either men or women, the ARRs were between 0.003-0.008; the ARIs were between 0.119-0.306. CONCLUSION: Machine learning methods outperformed the combined test in analysing multiple tumour markers for cancer detection. However, cancer screening based solely on the application of multiple tumour markers remains unfavourable because of the inadequate PPV, ARR, and ARI, even when machine learning methods were incorporated into the analysis.

The assessment of serum concentration of adiponectin, leptin and serum carbohydrate antigen-19.9 in patients with pancreatic cancer and chronic pancreatitis.

UNLABELLED: Pancreatic cancer and chronic pancreatitis are still significant diagnostic and clinical problems. The clinical impact of preoperative serum carbohydrate antygen 19-9 (CA 19-9) levels have been disscussed. The aim of this study was a comparative analysis of the concentrations in serum of adipocytokines: adiponectin and leptin and CA 19-9 in patients with pancreatic cancer (PC), chronic pancreatitis (CP) and 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 coincidence of pancreatic cancer in CP group. Group 3 (CG) consisted of 30 persons and were recruited among patients operated for cholelithiasis. The serum samples were taken from patients and the concentration of adiponectin, leptin, CA 19-9 and CEA were evaluated. The revealed concentrations levels of the adiponectin were significantly higher in the PC serum samples compared to the CP and CG. There was no significant correlation between increased adiponectin concentration and body fat mass in the PC group. The concentration of leptin was significantly lower in CP serum samples compared to PC and CG. The concentration of leptin was similar in the PC and CG. The concentration of leptin was mainly dependent on body fat mass and fat distribution. Additionally, measurement of waist circumference and body composition was recorded using bioelectrical impedance analysis. CONCLUSIONS: significantly higher concentration levels of adiponectin in the PC group, independent of body fat mass, may play a potential role as a new tumor marker in PC and might be useful in the differential diagnosis between PC and CP, but this statement needs further investigation. To our knowledge, this was the first study evaluating not only body mass index but also the content and distribution of body fat in patients with PC and CP.

Is a preoperative assessment of the early recurrence of pancreatic cancer possible after complete surgical resection?

BACKGROUND/AIMS: The prognosis of pancreatic adenocarcinoma (PAC) is poor. The serum carbohydrate antigen 19-9 (CA 19-9) level has been identified as a prognostic indicator of recurrence and reduced overall survival. The aim of this study was to identify preoperative prognostic factors and to create a prognostic model able to assess the early recurrence risk for patients with resectable PAC. METHODS: A series of 177 patients with PAC treated surgically at the St. Andrea Hospital of Rome between January 2003 and December 2011 were reviewed retrospectively. Univariate and multivariate analyses were utilized to identify preoperative prognostic indicators. RESULTS: A preoperative CA 19-9 level >228 U/mL, tumor size >3.1 cm, and the presence of pathological preoperative lymph nodes statistically correlated with early recurrence. Together, these three factors predicted the possibility of an early recurrence with 90.4% accuracy. The combination of these three preoperative conditions was identified as an independent parameter for early recurrence based on multivariate analysis (p=0.0314; hazard ratio, 3.9811; 95% confidence interval, 1.1745 to 15.3245). CONCLUSIONS: PAC patient candidates for surgical resection should undergo an assessment of early recurrence risk to avoid unnecessary and ineffective resection and to identify patients for whom palliative or alternative treatment may be the treatment of choice.

Clinical assessment and prognostic evaluation of tumor markers in patients with gastric cancer.

AIM: To investigate the relationship between the serum levels of CEA, CA19-9, CA24-2, CA72-4, and AFP in patients with gastric cancer (GC) and their clinicopathological characteristics; to analyze the efficacy of these tumor markers in evaluating the prognosis of GC. METHODS: Overall, 389 patients with GC either located in the gastric cardia (132), the pyloric antrum (112) or the body of the stomach (145) were included in the study. Serum levels of CEA, CA19-9, CA72-4, and AFP were detected with the ECLIA method, while CA24-2 was measured with ELISA. RESULTS: First, the serum level of CEA in GC patients with a cardia-located cancer was significantly higher than in patients with pyloric antrum-located cancer (p=0.050). CA72-4 level in patients with GC located in the gastric body was significantly higher than in patients with cardia and pyloric antrum-located cancers (p=0.042 and p=0.039, respectively). Secondly, serum CA19-9 and CA24-2 levels in females with cardia-located GC were significantly higher than those in males with the same type of tumor (p=0.037 and p=0.033, respectively). Additionally, for females with gastric body-located GC the levels of CEA and CA72-4 were significantly higher than those in male patients with the same type of tumor (p=0.047 and p=0.048, respectively). Conversely, in female GC patients with pyloric antrum-located cancer the serum levels of CA19-9 and CA24-2 were significantly lower than those in male patients with the same type of cancer (p=0.013 and p=0.007, respectively). Moreover, CEA, CA19-9, CA24-2, and CA72-4 levels were strongly related to TNM grade and histological anatomy stage, whereas CEA and CA72-4 levels were strongly related to lymph node stage (p=0.000 and p=0.042, respectively). Patients with vascular embolism had higher serum levels of CEA, CA19-9, CA24-2, and CA72-4 compared with patients without vascular embolism (p=0.005, p=0.031, p=0.007, and p=0.014, respectively). In patients with distant metastases and ascites the levels of CEA, CA19-9, and CA24-2 were higher than in patients without these conditions (p=0.003, p=0.001, p=0.001, p=0.016, p= 0.011, and p=0.030, respectively). Serum CEA, CA19-9, and CA24-2 levels showed correlations with tumor invasive depth and growth types (p=0.001, p=0.040, and p=0.035, respectively). Patients with lump and catheter tumor growth types had significantly higher AFP levels than patients with invasion and anabrosis growth types (p=0.034 and p=0.005, respectively). Tumor size was correlated with the preoperative serum levels of CEA, AFP, and CA72-4 (p=0.007, p=0.020, and p=0.008, respectively). Additionally multiple linear regression analysis showed that preoperative levels of CEA and CA72-4 were correlated to TNM stages, CA19-9 and CA24-2 levels were correlated to both gender and distant metastasis, and AFP was correlated only to ascites. During follow-up there were 115 deaths. Median survival time for GC patients with negative preoperative CEA was 18.07 months, and was 10.97 months for patients with preoperative CEA positive levels (p=0.0005). Similarly, the median survival time for GC patients with negative preoperative CA72-4 was 33.60, and was 16.03 months for patients with preoperative CA72-4 positive levels (p=0.0041). CONCLUSIONS: The preoperative levels of CEA, CA19-9, CA24-2, CA72-4, and AFP were closely related to TNM grade, gender, distant metastasis and ascites. These makers seem to play important roles in predicting recurrence and metastasis, and in evaluating prognosis.

Frequency and intensity of postoperative surveillance after curative treatment of pancreatic cancer: a cost-effectiveness analysis.

BACKGROUND: Few data exist to guide oncologic surveillance following curative treatment of pancreatic cancer. We sought to identify a rational, cost-effective postoperative surveillance strategy. METHODS: We constructed a Markov model to compare the cost-effectiveness of 5 postoperative surveillance strategies. No scheduled surveillance served as the baseline strategy. Clinical evaluation and carbohydrate antigen (CA) 19-9 testing without/with routine computed tomography and chest X-ray at either 6- or 3-month intervals served as the 4 comparison strategies of increasing intensity. We populated the model with symptom, recurrence, treatment, and survival data from patients who had received intensive surveillance after multimodality treatment at our institution between 1998 and 2008. Costs were based on Medicare payments (2011 US dollars). RESULTS: The baseline strategy of no scheduled surveillance was associated with a postoperative overall survival (OS) of 24.6 months and a cost of $3837/patient. Clinical evaluation and CA 19-9 assay every 6 months until recurrence was associated with a 32.8-month OS and a cost of $7496/patient, with an incremental cost-effectiveness ratio (ICER) of $5364/life-year (LY). Additional routine imaging every 6 months incrementally increased total cost by $3465 without increasing OS. ICERs associated with clinic visits every 3 months without/with routine imaging were $127,680 and $294,696/LY, respectively. Sensitivity analyses changed the strategies' absolute costs but not the relative ranks of their ICERs. CONCLUSIONS: Increasing the frequency and intensity of postoperative surveillance of patients after curative therapy for pancreatic cancer beyond clinical evaluation and CA 19-9 testing every 6 months increases cost but confers no clinically significant survival benefit.

Comparison of risk of malignancy index (RMI), CA125, CA 19-9, ultrasound score, and menopausal status in borderline ovarian tumor.

OBJECTIVE: The aim of this study was to assess the prognostic values of risk of malignancy index (RMI IV), ultrasound score, menopausal status, and serum CA125 and CA19-9 level in patients with borderline ovarian tumor (BOT). METHODS: Fifty women having borderline ovarian tumor (BOT) and 5O individuals with benign adnexal mass were enrolled in this retrospective study. The sensitivity, specificity, positive predictive values, negative predictive values and diagnostic accuracy of preoperative serum levels of the CA125 and CA19-9, ultrasound findings and menopausal status, and RMI IV were calculated for prediction of discrimination between BOTs and benign adnexal masses and the results were compared. RESULTS: The RMI IV was the best method for discrimination between BOTs and benign adnexal masses and was more accurate than the other parameters. When Receiver Operator Characteristic area under the curves for menopausal status was analyzed, serum CA 125 and CA19-9 level, ultrasound score, RMI IV(CA125), and RMI IV(CA19-9) were, 0.580, 0.625, 0.548, 0.694, 0.734 and 0.711, respectively. The best RMI IV cut-off was found to be 200 for discrimination of benign and BOT lesions. In the RMI formulation, replacing CA125 with CA19-9 didn't affect RMI IV sensitivity and specificity for discrimination. CONCLUSION: Compared to ultrasound, menopausal status, CA-125, CA19-9, the RMI IV was found to be the best predictive method for differentiation of BOTs from benign adnexal masses. RMI IV cut-off value of 200 is suitable for differentiation of benign and BOT's.

Stool DNA testing for the detection of pancreatic cancer: assessment of methylation marker candidates.

BACKGROUND: Pancreatic cancer (PanC) presents at late stage with high mortality. Effective early detection methods are needed. Aberrantly methylated genes are unexplored as markers for noninvasive detection by stool testing. The authors aimed to select discriminant methylated genes and to assess accuracy of these and mutant KRAS in stool to detect PanC. METHODS: Nine target genes were assayed by real-time methylation-specific polymerase chain reaction (MSP) in bisulfite-treated DNA from microdissected frozen specimens of 24 PanC cases and 30 normal colon controls. Archived stools from 58 PanC cases and 65 controls matched on sex, age, and smoking were analyzed. Target genes from fecal supernatants were enriched by hybrid capture, bisulfite-treated, and assayed by MSP. KRAS mutations were assayed using the QuARTS technique. RESULTS: Areas under the receiver operating characteristics curves (AUCs) for tissue BMP3, NDRG4, EYA4, UCHL1, MDFI, Vimentin, CNTNAP2, SFRP2, and TFPI2 were 0.90, 0.79, 0.78, 0.78, 0.77, 0.77, 0.69, 0.67, and 0.66, respectively. The top 4 markers and mutant KRAS were evaluated in stool. BMP3 was the most discriminant methylation marker in stool. At 90% specificity, methylated BMP3 alone detected 51% of PanCs, mutant KRAS detected 50%, and combination detected 67%. AUCs for methylated BMP3, mutant KRAS, and combination in stool were 0.73, 0.75, and 0.85, respectively. CONCLUSIONS: This study demonstrates that stool assay of a methylated gene marker can detect PanC. Among candidate methylated markers discriminant in tissue, BMP3 alone performed well in stool. Combining methylated BMP3 and mutant KRAS increased stool detection over either marker alone.

Optimizing management of pancreatic cysts--prospective re-assessment for 157 cases.

BACKGROUND/AIMS: Ongoing debate continues regarding the appropriate management of pancreatic cysts (PCs). Disagreement prevails regarding frequency of needed follow-up, if and when to perform any PC needle biopsy and indications for surgical resection. EUS is increasingly used to help determine management of PCs. METHODOLOGY: One hundred and fifty seven consecutive patients with PCs were identified out of 5000 patients who underwent EUS between 1995-2007. In 2008, these patients were then prospectively provided clinical follow-up, and CEA, CA19-9 and CRP. RESULTS: No symptoms could be definitively related to the PCs. Twenty four of 157 patients with suspected malignant cysts, mucinous cysts or IPMN had undergone surgical treatment. Whipple's operation was performed in 14 patients and distal pancreatectomy in 10 patients. Fifty PCs were located in the head of pancreas. In 89 patients prospective blood tests were performed; in 6 of them elevated levels of CA-19-9 were detected, 3 of these also had elevated serum CEA. Twelve patients had increased CRP values. No complication (requiring hospitalization) and no mortality related to EUS had occurred. CONCLUSIONS: Elements identified as important for assessment of PCs included: size, serum and fluid markers, imaging characteristics and clinical follow-up. These factors should be included in the recommended guidelines.

Screening the gastric cancer related tumor markers from multi-tumor markers protein chip with kappa coefficient and cost-effectiveness analysis.

BACKGROUND/AIMS: To retrospectively evaluate the clinical values of C12 multi-tumor markers protein chip system in gastric cancer (GC) and screen for GC related tumor markers so as to provide a theoretical base for the establishment of GC diagnostic biochips. METHODOLOGY: The sera of 156 GC patients were detected for 12 common tumor markers using the C12 tumor markers protein chip. GC related parameters were analyzed by Kappa test and cost-effectiveness analysis to find the most optimal tumor marker combination. RESULTS: Carbohydrate antigen (CA) 19-9 (20.5%), CA242 (19.9%), carcinoembryonic antigen (CEA, 17.3%), CA125 (7.1%) were major tumor markers increased among the 156 GC patients. Kappa test revealed 6 tumor marker combinations having strong consistency with the detection results of C12 tumor markers proteinchip, and CA19-9 plus CEA proved to be the best combination by cost-effectiveness analysis. CONCLUSIONS: C12 tumor markers protein chip system had limited value in the diagnosis of GC, and the design of chip was too complicated and costly for widespread screening among the high risk populations. Searching for new GC biomarkers and designing small diagnostic chip could significantly enhance the clinical value of tumor markers in terms of diagnostic rate and practical utility.

[National external quality assessment and comparability of assays for tumor markers measurements].

OBJECTIVE: To evaluate the performance of tumor markers (TM) measurements in clinical laboratories by external quality assessment (EQA) and investigate the comparability of assays for TM. METHODS: Ten quality control sera specimens were distributed to 586 laboratories by global Express Mail Services (EMS) in March 2008 and tested twice with 5 specimens each time. Analytes were total prostate specific antigen (PSA), free PSA, carcinoembryonic antigen (CEA), alpha fetoprotein (AFP), human chorionic gonadotrophin (HCG), beta-HCG, carbohydrate antigen 19-9 (CA19-9), cancer antigen 15-3 (CA 15-3), cancer antigen 125 (CA125), beta-2-microglobulin and ferritin. The collected data were divided into peer groups according to analyzers or methods and the median of peer group was adopted as the target value (TV) separately after outlier removal. Two standard deviations of the median were set as the limit of difference. RESULTS: The first TM EQA results of 2008 showed that the pass percentage of all participating laboratories ranged from 87.3% (CA125) to 95.5% (beta-2-microglobulin). And the second batch ranged from 83.5% (HCG) to 94.0% (beta-2-microglobulin). The coefficient variances (CVs) of intra-group values determined by automatic analyzers were lesser than 15% for each test of every specimen. The CVs of radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) were over 20% and 50% respectively. The inter-group medians of 9 tests showed CVs>20% with HCG 13.4% and ferritin 15.7%. The CV of paired medians of some automatic analyzers was small and showed no statistical significance (all Z<1.890, all P>0.05). CONCLUSION: The analytical performance of automatic analyzers is superior to RIA and ELISA. There is an excellent comparability within automatic analyzers for TM measurements and a lack of comparability within RIA and ELISA. Noncomparability is found in over 80% of TM assays.