OBJECTIVE:To evaluate analytical explanations for the highly reported incidence of antibodies to dsDNA in patients receiving TNF antagonists. METHODS:Sixty serum samples from patients receiving biological anti-TNF medication were assessed for the presence of dsDNA antibodies using three standard diagnostic platforms [ELISA, IIF and multiplex bead array (MBA)], before and after treatment to block heterophile antibodies. Results were compared with those obtained using serum samples from patients with SLE. RESULTS:We identified significant method-specific discrepancies in the estimation of dsDNA antibodies in patients receiving TNF antagonists. dsDNA antibodies were frequent according to ELISA and IIF, but rare according to MBA. Blockade of heterophile antibodies resulted in a significant reduction in titres of dsDNA antibodies detected by IIF. In contrast, there was a much greater consistency for dsDNA antibody results in SLE, especially for those present in high titre, and blockade of heterophile antibodies did not result in a change between the two paired samples by IIF or MBA. CONCLUSION:There is a significant method-specific variation in the detection of dsDNA antibodies in patients receiving TNF antagonists, due in part to the effects of heterophile antibodies.

BACKGROUND:We described a patient who exhibited a gradual increase in carbohydrate antigen 19-9 (CA19-9) concentrations for 4 years at three hospitals, with no associated clinical manifestations; however, we were unable to define the cause of this increase, forcing us to consider whether it was a false-positive result. METHODS:Given the potential for interference, this study used multiple system detection, gradient dilution, Polyethylene glycol (PEG) precipitation and heterophilic antibody blocking assay to evaluate the reliability of CA19-9 concentration increase. RESULTS:Analysis of the patient sample using multiple systems indicated that CA19-9 concentrations showed an obvious increase (154.0, and 889.2 IU/ml, respectively) using the Cobas E602 and Advia Centaur XP systems, and were within the reference ranges (<10 IU/ml) on other modules. PEG precipitation on the Cobas E602 and Advia Centaur XP systems reduced the CA19-9 concentration, as did heterophilic blocking tube (HBT-6, HBT-1) blockade. CONCLUSION:CA19-9 was incorrectly identified to increase due to the presence of heterophilic antibodies. We recommend that heterophilic antibodies should be evaluated in cases with elevated CA19-9 level but no associated clinical manifestations to prevent false positives.

IL-17AA, IL-17FF, and IL-17AF are proinflammatory cytokines that have been implicated in the pathogenesis of autoimmune diseases such as rheumatoid arthritis (RA). In order to measure the levels of these cytokines in synovial fluid and serum samples from RA patients, immunoassays specific for IL-17AA, FF, and AF were developed. Although these assays could tolerate up to 50% pooled normal human serum, false positive reactivity was problematic in patient samples suggesting interference from heterophilic antibodies. We therefore evaluated the ability of several commercially available heterophilic antibody blocking agents to reduce false positive reactivity by testing them against samples that were confirmed as false positives in the IL-17AA, FF, and AF assays. Several of the blockers performed well, including HBR-1, HBR-9, HBR-11, HBR-Plus, Serum Cytokine Assay Diluent, and IIR. We chose to move forward using IIR blocker for sample analysis and verified that IIR had no effect on the assay standard curves and did not affect IL-17 quantitation in plasma from ex vivo stimulated human whole blood. IL-17FF and IL-17AF were below the limits of quantitation of the assays (12.3 and 10.5pg/ml, respectively) in synovial fluid and serum samples from patients with RA and osteoarthritis (OA). For the more sensitive IL-17AA assay (1.6pg/ml limit of quantitation), low levels of IL-17AA were measurable in 48% of RA synovial fluid samples (mean, 7.9pg/ml; median, <1.6pg/ml; range, <1.6-29.7pg/ml; n=23) but not in synovial fluid from patients with OA (n=33). For serum samples, however, IL-17AA was below the limit of detection for both RA and OA patients. When these same serum samples were analyzed in the absence of a heterophilic antibody blocker, false positive reactivity yielded apparent mean IL-17AA levels of 43.3pg/ml (28% positive; n=50) and 14.8pg/ml (12% positive; n=50) for RA and OA patients, respectively, results that could potentially be interpreted as consistent with disease biology. These studies demonstrate the importance of ensuring that HAb interference is well controlled, particularly when measuring low concentrations of cytokines in samples from patients with autoimmune disease.

Immunoassays are currently the methods of choice for the measurement of a large panel of complex and heterogenous molecules owing to full automation, short turnaround time, high specificity and sensitivity. Despite remarkable performances, immunoassays are prone to several types of interferences that may lead to harmful consequences for the patient (e.g., prescription of an inadequate treatment, delayed diagnosis, unnecessary invasive investigations). A systematic search is only performed for some interferences because of its impracticality in clinical laboratories as it would notably impact budget, turnaround time, and human resources. Therefore, a case-by-case approach is generally preferred when facing an aberrant result. Hereby, we review the current knowledge on immunoassay interferences and present an algorithm for interference workup in clinical laboratories, from suspecting their presence to using the appropriate tests to identify them. We propose an approach to rationalize the attitude of laboratory specialists when faced with a potential interference and emphasize the importance of their collaboration with clinicians and manufacturers to ensure future improvements.

OBJECTIVES:The study investigated heterophilic antibodies: the human immunoglobulin classes involved and their specificity for different murine IgG subclasses. DESIGN AND METHODS:Using immunofluorometric assays for human IgA, IgM and IgG binding murine IgG1, we analyzed 173 samples displaying positive interference and 97 negative control samples from a previous study. We also set up assays for heterophilic antibody interference using Mabs from different murine IgG subclasses. Three Mabs each of murine IgG1, IgG2a and IgG2b subclasses, one murine IgG3 Mab and one rat Mab were used. RESULTS:Elevated levels of human murine IgG1-binding immunoglobulins of IgM class only were found in 40% of interference-positive samples, human IgG only in 1.7%, and human IgA only in 2.3% of the samples. Both elevated human IgG and IgM classes were found in 3.5% of the samples, IgA and IgM in 4.0%, and finally, all three immunoglobulin classes in 1.7% of the samples. Eighty percent of interference positive samples showed heterophilic assay interference for at least one murine IgG1 Mab, 35% for IgG2a, 66% for IgG2b, 52% for IgG3a and 17% for the rat Mab. CONCLUSIONS:Heterophilic antibody interference is mainly caused by IgM class human antibodies with a marked murine IgG subclass specificity. Combining assay antibodies from different murine IgG subclasses may reduce interference in immunoassays.

BACKGROUND:Heterophilic antibodies are still an important source of interference in immunoassays. We have conducted a screening study for interference in a panel of commercially available assays using two sera known to contain high titer Fc-reactive heterophilic antibodies. METHODS:The sera were distributed to laboratories participating in the Nordic External Quality Assessment cooperation (EQANord). Duplicate samples pre-blocked with aggregated murine monoclonal MAK33 were also supplied. Discrepancies (>50%) between the results for native and blocked samples were used to classify the tested assays as susceptible to interference. A total of 170 different assay kits covering 91 analytes were tested. RESULTS:We found that 21 assays, covering 19 different analytes, were susceptible to interference from the heterophilic antibodies in the two sera. Many of these are clinically and commercially important assays. Some of the false results were grossly elevated and could have been detrimental to patient care in a clinical setting. CONCLUSIONS:Heterophilic antibodies with Fc-reactivity remain a threat. A more widespread use of antibody fragments and aggregated immunoglobulin could potentially improve the heterophilic antibody resistance of assays intended for clinical use.

BACKGROUND:Standard diagnostic testing for HIV infection has traditionally relied on a high sensitivity HIV antibody screening test using an enzyme-linked immunosorbent assay (ELISA) followed by a high specificity antibody confirmatory test such as a Western Blot. Recently several of the screening assays have been enhanced with an ability to identify p24 antigen thereby narrowing the diagnostic window. OBJECTIVES:To explore the implications of enhanced HIV screening methods that may be leading to HIV misdiagnoses. STUDY DESIGN:A patient deemed to be an HIV infected 'elite controller' was found to be misdiagnosed when undergoing detailed investigations prior to initiating antiretroviral therapy. A root cause analysis was performed to identify the causative factors of this misdiagnosis. A retrospective review of all "elite controllers" in Alberta, Canada revealed challenges of current HIV testing algorithms. RESULTS:Technical and human factors were identified as being causative in this HIV misdiagnosis including (i) high rates of false reactive results on the Abbott ARCHITECT HIV-1&2 COMBO EIA, (ii) human error in reading the initial Western blot, (iii) HIV algorithmic directives in which confirmatory (Western blot) testing was not performed on a repeatedly reactive screen test. The outcome of this analysis identified opportunities for improvement, including implementation of a newly approved (automated) confirmatory assay and improved communication between the clinician and laboratory. CONCLUSIONS:HIV testing remains problematic despite significant advances in HIV test performance and algorithm development, presenting new and unexpected issues. Ensuring a high-quality management system including implementation of the latest HIV technologies and algorithms along with human resources and policies are required to minimize the impact of false positive diagnoses, especially in the era of universal screening and 'test and treat' recommendations.

We retrospectively analyzed the performance of the Architect HIV antigen/antibody (Ag/Ab) combination assay in a tertiary health care center with a situation of low HIV prevalence. The specificity and positive predictive value (PPV) were 99.78% and 31.21%, respectively. However, the specificity and PPV could increase to 99.99% and 89.70% using an arbitrary cutoff value.

OBJECTIVE:To investigate the clinical characteristics of patients with false-positive human immunodeficiency virus (HIV) screening test results and provide a theoretical basis to interpret the results of HIV screening tests. METHODS:This retrospective study evaluated the incidence of false-positive results for HIV screening tests and characterized false-positive reactions during HIV screening in a large-scale study at Zhongshan Hospital, Xiamen University. RESULTS:False-positive HIV test results occurred for 264 of 275,263 (0.10%) serum samples. Although the incidence of a false-positive HIV screening result did not differ between male and female patients (screening χ = 1.194; P = 0.275), it increased with age (χ = 25.759; P < 0.01). False-positive reactions were associated with 16 disease categories, including 101 diseases, some of which have never been reported previously to be associated with false-positive HIV screening results. CONCLUSIONS:The occurrence of false-positive HIV screening test results may indicate underlying serious disorders. Characterization of patients with false-positive HIV screening test results can help identify potential diseases unrelated to HIV.

Background:In China, although tremendous efforts has been made, the HIV/AIDS is still not controlled. Objectives:The study was carried out to determine the epidemic of HIV infection in Xi'an, analyse false positives (FP) risk factors and potential utility of sample-to-cutoff index to identify true positives using Architect HIV Ag/Ab Combo. Methods:A retrospective review for HIV screening by Architect HIV Ag/Ab Combo was performed in a teaching hospital in Xi'an between 2015 and 2016. The prevalence of HIV, positive predictive value (PPV) at different cut-off indexices (COI) were calculated. The epidemic of infections and risk factors for FP results were investigated. Results:In the study, the HIV prevalence and FP rate of Architect HIV Ag/Ab Combo were 0.076 and 46.08%, respectively. The Han Chinese, males and people aged < 40 years accounted for the majority of infections (98.29, 76.07 and 73.5%, respectively). 85.47% of the infections were transmitted through sexual contact (35.04% of male homosexual and 50.43% of heterosexual). COI at 1-10, 10-30 and ≥ 30, the PPVs were 0, 50 and 100%, respectively. The independent risk factors for FP, i.e., pregnancy and malignancy had a statistically significant association with FP ( < 0.05), and age had a very strong statistically significant association with FP ( < 0.001). Conclusions:In Xi'an, sexual contact was the most important transmission mode for HIV, and the infections were predominantly identified in Han Chinese, males, young and middle-aged people. For Architect HIV Ag/Ab Combo, it can achieve 100% of PPV with COI ≥30, and the age was strongly statistically associated with FP.

We investigated whether an ordinary centrifuge can achieve the standard centrifugal effect required according to specifications for infectious disease screening using the Abbott i2000. Samples were collected and centrifuged following a standard operating procedure (SOP). They were then divided into three groups according to the results of the initial screening tests: a negative group, weak-positive group, and positive group. Twenty negative samples and all weak-positive and positive samples were re-analyzed. Two tubes for each re-analyzed sample were centrifuged simultaneously, one for 10 min at 10 000 × g, per recommendations, and one for 10 min at 2750 × g. No significant difference was found between the groups using different centrifugal forces. There was a strong correlation in the quantitative values between the two conditions of centrifugation. Consistency analysis showed a Cronbach's alpha > 0.8 for detection of Treponema pallidum, human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B surface antigen in the three groups (negative group, weak-positive group, and positive group) under different centrifugation conditions. Strong consistency was found under different centrifugal conditions, regardless of the initial testing results. In conclusion, we conducted centrifugation steps in duplicate, according to infectious disease screening protocols. Our study showed that all samples should be centrifuged using a recommended relative centrifugal force after a proper clotting time, as in the standard operating procedure of our laboratory. In this way, we were able to obtain the same results using an ordinary centrifuge as those obtained using a high-speed centrifuge, such as the Abbott i2000.

BACKGROUND:Circulating heterophilic antibodies interfere with immunological assays in laboratory examinations; however, their rate of incidence is currently questionable. We developed an enzyme-linked immunosorbent assay (ELISA) to detect human anti-mouse antibodies (HAMAs) in routine examinations. METHODS:The study samples were comprised of serum samples obtained from 290 inpatients and outpatients at our hospital. Mouse immunoglobulin G1 (mIgG1), mIgG2a, and mIgG2b were used as the antigens and horseradish peroxidase (HRP)-conjugated anti-human IgG and IgM were used to identify the HAMA isotype. RESULTS:HAMAs were detected in 11.7% (34/290) of the samples. We observed 18 and 20 samples positive for IgG- and IgM-type HAMAs, respectively. Four samples contained both IgG- and IgM-type HAMAs. HAMAs against mIgG1, mIgG2a, and mIgG2b were found in 21, 14, and 13 samples, respectively. Existence of HAMAs was confirmed by western blotting using mIgG's as the antigens and HAMAs as the primary antibodies. Heterophilic blocking reagent (HBR) was also used to block the heterophilic interactions. Unexpectedly, a low HBR concentration rather enhanced the interactions instead of blocking them. CONCLUSIONS:A considerable number of HAMA-positive samples, reacting with the heavy chain of mIg, were found in routine examinations. A sufficient amount of HBR should be used for blocking the heterophilic interactions.

A 51-year-old woman was admitted to the hospital with abdominal pain, jaundice, and transaminitis. The patient's laboratory results showed elevated liver enzymes, high antinuclear antibodies (ANA) titer, positive anti-smooth muscle antibody, and hypergammaglobulinemia. Given risk factors for HIV infection, an ADVIA Centaur® HIV Antigen/Antibody Combo assay was performed showing a reactive sample with a follow up HIV-1 nucleic acid test (NAT) proving to be negative. Following confirmation of autoimmune hepatitis type I via a liver biopsy, steroids were initiated and significant clinical improvement of symptoms as well as resolution in transaminitis were noted. Autoimmunity is the most likely causative factor in inducing a false positive reactive screening assay. It is important to recognize that cross-reactivity with autoimmune conditions and HIV specific proteins is a potential concern for false reactive samples.

The consequences of falsely reactive HIV test results can be significant, for patients and healthcare providers. This case describes a diagnostic investigation of a patient with pronounced discordant HIV serological results, to determine HIV status. The fourth generation serological screening assay (Roche COBAS Elecsys HIV combiPT) had high positive results but confirmatory testing was negative (Abbott HIV Ag/Ab Combo). Five separate samples over 13 days were tested using multiple fourth generation HIV immunoassays and molecular tests for HIV-1 and HIV-2. Potential causes of falsely reactive serological results were investigated. Samples were sent to the manufacturer for analysis. The screening assay was positive on all samples with a very high signal to cut-off ratio (S/CO) of greater than 400. However, multiple serological and molecular assays did not detect HIV-1 or HIV-2 specific antibodies, antigen or nucleic acid. A recombinant immunochromatographic assay had faint reactivity to gp41 peptide and the manufacturer investigation reported cross-reactivity to one of the screening assay's synthetic peptides. Possible causes of the false positive result include cross reactivity to other antigens, including prior schistosomiasis infection, or the patient's previously excised ameloblastoma (a rare germ cell tumor of the jaw). This is a rare case of false high positive results on fourth-generation HIV serology testing due to high level non-specific reactivity to an isolated synthetic peptide component of the assay. It highlights the need for confirmatory testing even in settings with HIV high prevalence and awareness that false-positive serological results may have a high S/CO.

Heterophile antibodies are a well-recognized cause of erroneous results in immunoassays. We describe here a 22-month-old child with heterophile antibodies reactive with bovine serum albumin and caprine proteins causing false-positive results to human immunodeficiency virus type 1 and other infectious serology testing.

We hypothesized that heterophil antibodies reactive with animal proteins used in blot preparation caused nonspecific staining (NSS) on HIV Western blot (WB) studies, causing indeterminate results. We analyzed samples showing NSS on HIV WB using a multiplexed immunoassay to simultaneously measure IgG antibodies to animal IgG (bovine, goat, sheep, mouse) and bovine serum albumin. Heterophil antibodies reactive with IgG from several animal species were detected in 23 (49%) of 47 samples showing NSS on HIV WB; 15 positive samples demonstrated antibodies to all 5 antigens. Similar IgG heterophil antibodies were detected in only 2 (8%) of 24 control samples. Of the HIV WB samples with a positive HIV-1 enzyme-linked immunosorbent assay (ELISA) result at the time of WB testing (11/47), heterophil antibodies were found in 8 (73%) of 11. Preabsorption with bovine, goat, and sheep IgG removed heterophil antibodies detected by the multiplexed assay and, in some cases, eliminated reactivity in ELISA and WB testing. Heterophil antibodies are associated with indeterminate HIV immunoassay results and are an important cause of false-positive HIV ELISA results. Multiplexed immunoassays provide a powerful tool for screening patients for heterophil antibodies and resolving possible false-positive results.

BACKGROUND:The Architect HIV Ag/Ab Combo Assay, a fourth-generation ELISA, has proven to be highly reliable for the diagnosis of HIV infection. However, its high sensitivity may lead to false-positive results. OBJECTIVES:To evaluate the diagnostic performance of Architect in a low-prevalence population and to assess the role of the sample-to-cutoff ratio (S/CO) in reducing the frequency of false-positive results. STUDY DESIGN:We conducted a retrospective study of samples analyzed by Architect between January 2015 and June 2017. Positive samples were confirmed by immunoblot (RIBA) or nucleic acid amplification tests (NAATs). Different S/CO thresholds (1, 2.5, 10, 25, and 100) were analyzed to determine sensitivity, specificity, and negative and positive predictive values (NPV, PPV). ROC analysis was used to determine the optimal S/CO. RESULTS:A total of 69,471 samples were analyzed. 709 (1.02%) were positive by Architect. Of these, 63 (8.89%) were false-positive results. Most of them (93.65%) were in samples with S/CO < 100. However, most confirmations by NAATs (12 out of 19 cases) were also recorded for these samples. The optimal S/CO was 2.5, which provided the highest area under the ROC curve (0.9998) and no false-negative results. With this S/CO, sensitivity and specificity were 100.0%, and PPV and NPV were 95.8% and 100.0%, respectively. In addition, the frequency of false-positive results decreased significantly to 4.15%. CONCLUSIONS:Although Architect generates a relatively high number of false-positive results, raising the S/CO limit too much to increase specificity can lead to false-negative results, especially in newly infected individuals.

BACKGROUND:False-reactivity in HIV-negative specimens has been detected in HIV fourth-generation antigen/antibody or 'combo' assays which are able to detect both anti-HIV-1/HIV-2 antibodies and HIV-1 antigen. OBJECTIVES:We sought to characterize these specimens and determine the effect of heterophilic interference. STUDY DESIGN:Specimens previously testing as false-reactive on the Abbott ARCHITECT HIV Ag/Ab combo assay and re-tested on a different (Siemens ADVIA Centaur HIV Ag/Ab) assay. A subset of these specimens were also pre-treated with heterophilic blocking agents and re-tested on the Abbott assay. RESULTS:Here we report that 95% (252/264) of clinical specimens that were repeatedly reactive on the Abbott ARCHITECT HIV Ag/Ab combo assay (S/Co range, 0.94-678) were negative when re-tested on a different fourth generation HIV combo assay (Siemens ADVIA Centaur HIV Ag/Ab). All 264 samples were subsequently confirmed to be HIV negative. On a small subset (57) of specimens with available volume, pre-treatment with two different reagents (HBT; Heterophilic Blocking Tube, NABT; Non-Specific Blocking Tube) designed to block heterophilic antibody interference either eliminated (HBT) or reduced (NABT) the false reactivity when re-tested on the ARCHITECT HIV Ag/Ab combo assay. CONCLUSIONS:Our results suggest that the Abbott ARCHITECT HIV Ag/Ab combo assay can be prone to heterophilic antibody interference.

We aimed to develop and validate two novel protein chips, which are based on microarray chemiluminescence immunoassay and can simultaneously detected 11 biomarkers, and then to evaluate their clinical diagnostic value by comparing with the traditional methods. Protein chips were evaluated for limit of detection, specificity, common interferences, linearity, precision and accuracy. 11 biomarkers were simultaneously detected by traditional methods and protein chips in 3683 samples, which included 1723 cancer patients, 1798 benign diseases patients and 162 healthy controls. After assay validation, protein chips demonstrated high sensitivity, high specificity, good linearity, low imprecision and were free of common interferences. Compared with the traditional methods, protein chips have good correlation in the detection of all the 13 kinds of biomarkers (r≥0.935, P<0.001). For specific cancer detection, there were no statistically significant differences between the traditional method and novel protein chips, except that male protein chip showed significantly better diagnostic value on NSE detection (P=0.004) but significantly worse value on pro-GRP detection (P=0.012), female chip showed significantly better diagnostic value on pro-GRP detection (P=0.005). Furthermore, both male and female multivariate diagnostic models had significantly better diagnostic value than single detection of PGI, PG II, pro-GRP, NSE and CA125 (P<0.05). In addition, male models had significantly better diagnostic value than single CA199 and free-PSA (P<0.05), while female models observed significantly better diagnostic value than single CA724 and β-HCG (P<0.05). For total disease or cancer detection, the AUC of multivariate logistic regression for the male and female disease detection was 0.981 (95% CI: 0.975-0.987) and 0.836 (95% CI: 0.798-0.874), respectively. While, that for total cancer detection was 0.691 (95% CI: 0.666-0.717) and 0.753 (95% CI: 0.731-0.775), respectively. The new designed protein chips are simple, multiplex and reliable clinical assays and the multi-parameter diagnostic models based on them could significantly improve their clinical performance.

BACKGROUND/AIMS:A C12 biochip system using 12 tumor markers has been developed in China for serum diagnosis of common cancers. This work is to evaluate this C12 system in the diagnosis of gastric cancer. METHODOLOGY:Sera from 100 gastric carcinoma patients were screened for 12 tumor markers including carcinoembryonic antigen, alpha-fetoprotein, carbohydrate antigen 19-9, carbohydrate antigen 242, cancer antigen 15-3, cancer antigen 125, prostate specific antigen, free-PSA, neuron-specific enolase, human chorionic gonagotropin-beta, human growth hormone, and ferritin, using the C12 biochip system. The most relevant tumor marker and the contribution of the tumor markers to the improvement of diagnosis were determined. RESULTS:The overall diagnostic rate of C12 biochip system was 37%, and 7.8%, 29.4%, 35.5% and 50%, respectively, for stages I, II, III and IV patients. The differences in diagnostic rates between stage I (7.8%) and stage IV (50%) reached statistical significance (chi-square test, Chi2=7.20, p<0.01). Among all the 12 markers, carbohydrate antigen 19-9 had the highest positive rate up to 23%, against which any form of combinations of 5 most relevant tumor markers (2, 3, 4 or 5 markers combined) could not significantly improve the diagnostic rate. CONCLUSIONS:The C12 biochip system has some value in the diagnosis of advanced stage gastric cancer, but less sensitive in early gastric cancer.

OBJECTIVE:To assess the value of multi-tumor markers protein biochip in the diagnosis and therapy of pulmonary carcinoma. METHODS:Twelve tumor markers (CA199, NSE, CEA, CA242, Ferrtin, β-HCG, AFP, f-PSA, PSA, CA125, HGH, and CA153) were detected using protein chip in 308 patients with pulmonary carcinoma, 218 with benign lung lesions and 250 healthy subjects. RESULTS:The positivity rate was 72.4% in pulmonary carcinoma cases, obviously higher than that in the benign cases (22.0%, P<0.01) and healthy subjects (5.6%, P<0.01). The positivity rates differed significantly between the pulmonary carcinoma cases of different pathological types. The positivity rates of CEA, CA125, and CA153 were significantly higher in adenocarcinoma cases than in squamous carcinoma cases (P<0.05), and also higher in cases with lymph node metastasis than in those without (71.9% vs 52.1%, P<0.05). CONCLUSION:Protein biochip containing multiple tumor markers provides valuable assistance in the diagnosis and therapeutic effect monitoring of pulmonary carcinoma.

BACKGROUND & OBJECTIVE:Measurement of blood tumor markers is the most widely used and convenient method for the diagnosis of colorectal cancer(CRC). This study was to evaluate the diagnostic value of a biochip diagnostic system C12 in the diagnosis of CRC. METHODS:Twelve tumor markers were detected in the sera of 130 pathologically confirmed CRC patients, including carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 242 (CA242), cancer antigen 15-3 (CA15-3), cancer antigen 125 (CA125), prostate specific antigen (PSA), free-PSA(f-PSA), neuron-specific enolase (NSE), human chorionic gonagotropin-beta (beta-HCG), human growth hormone (HGH), and ferritin, using the C12 diagnostic biochip system. The most relevant tumor markers and the most useful combinations of tumor markers were determined. RESULTS:The overall diagnostic rate for the 130 patients was 42.3%; and the diagnostic rates were 13.6%, 39.5%, 38.2% and 68.8%, for stages I, II, III and IV patients, respectively. There was significant difference in the diagnostic rates between stage I and stage IV patients. Among all the 12 markers, CEA had the highest diagnostic rate of 35.4%. Any combinations of the 5 most relevant tumor markers did not significantly improve the diagnostic rate. However, the combination of 4 markers (CEA+f-PSA +CA125+CA242 or CEA+CA19-9+CA125+f-PSA) was as good as 12 markers in terms of diagnosis. CONCLUSIONS:The C12 biochip diagnostic system has some value in the diagnosis of advanced CRC, but its sensitivity for the diagnosis of early CRC is not satisfactory.

BACKGROUND:To verify whether serum tumor abnormal protein (TAP) would correlate with the responsiveness of palliative chemotherapy in patients with advanced gastric cancer, and the variation of conventional serum tumor markers e.g., carcinoembryonic antigen (CEA), antigen 125 (CA125),carbohydrate antigen19-9 (CA19-9) of adjuvant chemotherapy in patients with early gastric cancer. MATERIALS AND METHODS:Patients with histologically confirmed gastric cancer and treated with chemotherapy were enrolled into this study. TAP values of these patients were determined by detecting abnormal sugar chain glycoprotein in serum, combined with the area of agglomerated particles. For patients with advanced gastric cancer, responsiveness of palliative chemotherapy was compared with variation of TAP and the relation between variation of TAP and tumor markers in patients with early gastric cancer was analyzed. RESULTS:Totally 82 gastric cancer patients were enrolled into this study. The value of TAP is more closely related to responsiveness of palliative chemotherapy for patients with advanced gastric cancer. The correlation between TAP and responsiveness to palliative chemotherapy is stronger than the correlation between several conventional serum tumor markers (CEA, CA125 and CA199) .The variation of TAP was also positively correlated with the trend of CA125 in adjuvant chemotherapy. CONCLUSIONS:TAP is sensitive in monitoring the responsiveness to palliative chemotherapy in patients with advanced gastric cancer. But this result should be confirmed by randomized clinical trials for patients with gastric cancer.

BACKGROUND:The 12 tumor markers' (TMs) biochip diagnostic (C12) system has been proven useful in some previous studies but its value for colorectal cancer (CRC) only was not systematically investigated. AIMS:To evaluate the value of C12 system for CRC. SETTINGS AND DESIGN:The associations between TMs and clinicopathological characteristics were evaluated. The most relevant TMs, the most useful combinations, and the correlations between TM levels were assessed. MATERIALS AND METHODS:The TMs detected by the C12 system in the sera of 170 pathologically confirmed CRC patients were analyzed. One or more TMs higher than or equal to reference value were defined as positive. STATISTICAL ANALYSIS:Chi-square test, Spearman rank correlation test and Receiver-operating characteristic (ROC) curves were used for the analysis. RESULTS:The overall positive rate was 41.76%, and was low in stage 0-I (12.90%). Carcinoembryonic cantigen (CEA) had the highest positive rate of 36.47%. The positive rates were significantly correlated to clinical stages and lymph node status, but not to age, sex, tumor location and pathological types. Any combinations of the five highest positive TMs did not have significantly improvements. The levels of three most related TMs (CEA, CA19-9, CA242) of CRC had positive correlation with each other. CA242 and beta-HCG levels were associated with lymph node metastasis. CONCLUSIONS:C12 system has some value in advanced CRC, but not in early CRC.

BACKGROUND:To evaluate the diagnostic values of multiple tumor marker protein biochip detective system for lung cancer. METHODS:The serum levels of 12 tumor markers, including CA199, NSE, CEA, CA242, CA125, CA153, AFP, ferritin, free-PSA, PSA, β-HCG and HGH, were measured in 108 lung cancer patients, 48 patients with benign pulmonary lesion and 145 healthy by the detective system. RESULTS:The positive rates were 83.33% (90/108), 52.08% (25/48) and 28.97% (42/145) in lung cancer, benign pulmonary lesion and healthy groups, respectively. The lung cancer group had significantly higher positive rate than that of the controls (Chi-Square=16.75 and 73.32, both P < 0.001); There was significant difference of positive rate in various clinical stages of lung cancer (Chi-Square=7.89, P=0.048), but not in different pathologic classification. Serum CA199, CEA and CA242 levels were closely correlated with clinical staging (F=2.84, P=0.041; F= 3.49, P=0.018; F =5.22, P=0.002). The positive rate of CEA in adenocarcinoma was higher, but no significant difference was observed (Chi-Square=0.71, P=0.07). NSE in small cell lung cancer had the highest positive rate (Chi-Square=19.03, P < 0.001). Combined measurement of the twelve markers had higher sensitivity (Chi-Square= 368.58, P < 0.001), but less specificity (Chi-Square= 369.87, P < 0.001). CONCLUSIONS:Combined measurement of various serum tumor markers using protein biochip can significantly increase the diagnostic sensitivity for lung cancer. Meanwhile, it is also significant for defining clinical stage, identificating pathologic classification, as well as monitoring therapeutic efficacy. As its specificity and positive predictive value are lower, it is more suitable to be used as a surveying tool for symptomless people, especially for high risk people for lung cancer.

BACKGROUND:Various studies assessing the diagnostic value of serum tumor markers in patients with esophageal cancer remain controversial. This study aims to comprehensively and quantitatively summarize the potential diagnostic value of 5 serum tumour markers in esophageal cancer. METHODS:We systematically searched PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI) and Chinese Biomedical Database (CBM), through February 28, 2013, without language restriction. Studies were assessed for quality using QUADAS (quality assessment of studies of diagnostic accuracy). The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were pooled separately and compared with overall accuracy measures using diagnostic odds ratios (DORs) and symmetric summary receiver operating characteristic (SROC) curves. RESULTS:Of 4391 studies initially identified, 44 eligible studies including five tumor markers met the inclusion criteria for the meta-analysis, while meta-analysis could not be conducted for 12 other tumor markers. Approximately 79.55% (35/44) of the included studies were of relatively high quality (QUADAS score≥7). The summary estimates of the positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) for diagnosing EC were as follows: CEA, 5.94/0.76/9.26; Cyfra21-1, 12.110.59/22.27; p53 antibody, 6.71/0.75/9.60; SCC-Ag, 7.66/0.68/12.41; and VEGF-C, 0.74/0.37/8.12. The estimated summary receiver operating characteristic curves showed that the performance of all five tumor markers was reasonable. CONCLUSIONS:The current evidence suggests that CEA, Cyfra21-1, p53, SCC-Ag and VEGF-C have a potential diagnostic value for esophageal carcinoma.

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.

OBJECTIVE:To evaluate the application of the multiple tumor markers's protein chip (C12 chip) in the screen program of the elderly. METHODS:The C12 chip included alpha-fetoprotein (AFP), neuron-specific enolase (NSE), prostate special antigen (PSA), free-PSA (f-PSA), carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), carbohydrate antigen 153 (CA153), carbohydrate antigen 199 (CA199), carbohydrate antigen 242 (CA242), human chorionic gonadotropin-beta (β-HCG), human growth hormone (HGH)and ferritin. The sera of the 399 healthy elderly under the screening program and 1791 adults were detected by the C12 chip. Definition of positive was set as: one or more tumor markers higher than or equal to the reference value. RESULTS:The positive rates of AFP, PSA, f-PSA, CEA, CA125, CA153 and CA199 between the elderly group and the adult group were significantly different (P < 0.05). The normal test value of AFP, PSA, f-PSA, CEA, CA125, CA199, CA242 and ferritin between the elderly group and the adult group were significantly different (P < 0.05). CONCLUSION:AFP, PSA, f-PSA, CEA, CA125, CA153 and CA199 of the C12 chip were useful in the screening program of the elderly to discover the sign of tumor at an early stage.

BACKGROUND:The clinical stage of the disease at diagnosis often determines the prognosis and survival rate of a patient with pancreatic cancer. Early symptoms of pancreatic cancer are often not obvious on imaging (ultrasound, computed tomography (CT), and so on), and when patients present with weight loss, jaundice and abdominal pain and other symptoms, they are usually already in the advanced stages of pancreatic cancer. However, the examination of combined tumor markers might improve their sensitivity or specificity in aiding diagnosis. METHODS:Twelve tumor markers including AFP, CEA, NSE, CA125, CA15-3, CA242, CA19-9, PSA, f-PSA, FER, β-HCG and HGH were measured by the protein biochip detection in serum in 235 pancreatic cancer patients, 230 benign pancreatic disease patients and 240 healthy people. RESULTS:Positive detection rates of tumor markers were: CA19-9 (49.3%), CA125 (45.1%), FER (44.2%), CA242 (42.5%), CEA (38.6%), CA15-3 (36.7%), β-HCG (29.6%), AFP (24.5%), NSE (18.2%), PSA (19.5%), f-PSA (9.4%) and HGH (8.7%) respectively. There was significant difference in CA19-9, NSE, CEA, CA242 and CA125 by multi-tumor marker protein biochip detection among patients with cancer, benign disease and healthy people (P<0.05). The positive rate of 5 tumor markers was 94.9%, and this was much higher than that of any single marker. CONCLUSION:The detection of CA19-9, NSE, CEA, CA242 and CA125 in the multi-tumor marker protein biochip system is helpful in the diagnosis of pancreatic cancer.

BACKGROUND:The early diagnostic of lung cancer plays an important role in the prognosis of surgical treatment among lung cancer patients. To evaluate the clinical application of multi-tumor markers protein biochip in the diagnosis of lung cancer, 12 tumor markers were detected in patients with different stages of lung cancer. METHODS:Serum CA125, CA19-9, Ferritin, CA15-3, CA242, CEA, AFP, NSE, PSA, f-PSA, HGH, and β-HGH were assessed in 506 patients, with 224 patients with lung cancer (including 123 cases of adenocarcinoma, 30 squamous cell carcinoma, 54 small-cell carcinoma, and 17 non classification), 159 patients with benign lung disease and 90 healthy people control by the C-12 multiple tumor protein-chip detective system. RESULTS:The positive rate of C-12 (77.23%) in lung cancer was significantly higher than that of benign lung disease (13.84%) and healthy people (9.76%) (P < .01). In lung cancer, the positive rate of CA199, NSE, CEA, CA242, Ferritin, f-PSA, and CA125 were significantly higher than that of benign lung disease and healthy people. In adenocarcinoma, the positive rate of CA125 (73.53%) was significantly higher than that of squamous cell carcinoma (36.67%) and small-cell carcinoma (56.62%). CONCLUSION:The C-12 multiple tumor protein-chip detective system has acceptable sensitivity in the diagnostic of lung cancer.

PURPOSE:To assess the value of multi-tumor marker protein chips in the diagnosis and treatment of ovarian cancer. MATERIALS AND METHODS:Twelve tumor markers (CA19-9, NSE, CEA, CA242, CK19, β-HCG, AFP, SCC, c-PSA, CA125, CA724 and CA15-3) were detected by protein biochip in 220 patients with ovarian carcinomas, 205 with benign ovarian tumors and 200 healthy subjects. RESULTS:The positivity rate was obviously higher in ovarian cancer (77.7%), than that in the benign cases (26.3%, p<0.01) and healthy subjects (4.5%, p<0.01). Serum levels of tumor markers were furthermore significantly higher in cases with lymph node metastasis (86.8%) than those without metastasis (44.7%), p<0.01. CONCLUSIONS:Multi-tumor marker protein chips provide important assistance in the diagnosis and treatment evaluation in ovarian cancers.

BACKGROUND/AIMS:Gastrointestinal (GI) cancer remains number one cancer killer in China. Serum tumor markers (TMs) are frequently used in the diagnosis of GI cancer. This study was to assess value of C12 multi-tumor marker protein chip diagnostic system developed in China in GI cancer. METHODOLOGY:Sera from 329 GI cancer patients were detected by the C12 protein chip diagnostic system which consisted of 12 TMs including CEA, AFP, CA19-9, CA242, CA15-3, CA125, PSA, fPSA, NSE, B-HCG, HGH and Ferritin. The contribution of various TMs to the improvement of diagnosis was analyzed. The relationship between its positive rate and clinical stage, pathological type, and gender were explored. RESULTS:The diagnostic rates were 13.73%, 33.33%, 38.30%, 58.03%, respectively, for stage I, II, III and IV patients, and the overall diagnostic rate was 39.21%. There were statistically significant differences in stage I versus stage III, stage I versus stage IV, and stage II versus stage IV (p < 0.01). The other stage comparisons did not reach statistical significance (p > 0.05). Among the 12 TMs of the protein chip, the top 3 positive rates of 27.36%, 19.76% and 19.45% were obtained from CEA, CA242 and CA19-9, respectively, which were correlated with stage of GI cancer. The combinations of 5 most relevant TMs (3, 4 or 5 markers combined) improve the diagnostic rate significantly comparison to CEA (p < 0.05 or p < 0.01)). The combination of CEA+CA19-9+f-PSA (35.71%) for male patients, and CEA+CA19-9+ CA125 (40.95%) for female patients almost got the same diagnostic value as the C12 protein chip diagnostic system did (38.39% for male, 40.95% for female). CONCLUSIONS:The C12 system is of some value in the diagnosis of GI cancer, but new markers are needed to improve the early diagnosis. In GI cancer, the most rational combination way was CEA+CA19-9+f-PSA for male patient and CEA+CA19-9 +CA125 for female patient.

BACKGROUND:Carbohydrate antigen 19-9 (CA19-9) is usually synthesized by pancreatic and bile duct cells and is present in small amounts in serum. During the period of tumor disease, its serum level significantly increases, and it is the most widely used serum tumor marker for diagnosis and monitoring therapy of pancreatic cancer. METHODS:We reported a case of abnormal elevation of serum CA19-9. Considering the possibility of detection interference, we used heterophilic antibody blocking analysis, detection by different analysis systems, and polyethylene glycol (PEG) precipitation to evaluate the reliability of abnormally elevated CA19-9 concentration. RESULTS:Repeated measurements on the Roche Cobas 8000 system of another hospital significantly reduced the CA19-9 concentration, as did PEG precipitation. Therefore, the abnormally elevated level of CA19-9 in this patient is considered to be pseudoelevation caused by interferences. CONCLUSIONS:We suggest considering the presence of detection interference in cases with elevated CA19-9 levels but no related clinical manifestations to prevent false positives. PEG precipitation may be a simple and feasible solution to eliminate interference.

In the differential diagnosis of pancreatic cancer, CA19-9 appears to be the most sensitive and specific marker currently in use. In the absence of jaundice and at levels greater than 1000 U/ml, the specificity is almost 100%. Levels higher than 1000 U/ml are very uncommon for benign diseases. We report a case of obstructive jaundice due to an impacted stone in the common bile duct with cholangitis, where a CA19-9 level of 61,800 U/ml prompted suspicion of a malignant cause. After treatment the CA19-9 returned to a normal level. One year postoperatively neither abdominal ultrasound nor CT-scan showed any sign of intraabdominal malignancy. Reviewing the literature, we conclude that even very high levels of CA19-9 in cases with obstructive jaundice can be caused by benign diseases. Unlike other tumour markers (alpha-foetoprotein, carcinoembryonic antigen), where exceedingly high levels are definitely caused by malignancy, high levels of CA19-9 can be caused by benign obstructive jaundice. In such cases CA19-9 is useless as a tumour marker. The biliary obstruction must be treated successfully and more diagnostic procedures or even laparotomy performed, to exclude malignancy or treat a benign disease.

OBJECTIVE:To investigate the effect of hemoglobin A1c (HbA1c) and glycated albumin (GA) on serum CA199 in diabetic patients. METHODS:29 NGT matched control subjects and 371 hospitalized diabetic patients were enrolled. Diabetic patients were divided into satisfactory group (< 6.5%), general group (6.5%-7.5%) and dissatisfactory group (> 7.5%) by the level of HbA1c. The levels of serum CA199 among three groups were compared. The relationship between HbA1c and CA199, GA and CA199 was analysed. Multiple stepwise regression analysis was performed to compare the effect of different variables on CA199 as the independent variables were sex, age, duration, TC, TG, HDL, LDL, FBG, PBG, HbA1c and GA. RESULTS:(1) CA199 level of the group of HbA1c above 7.5% was significantly higher than the group of HbA1c between 6.5% and 7.5% and the group of HbA1c less than 6.5%. (2) The coefficient of correlation between HbA1c and CA199 was 0.394 (P = 0.000), and that was 0.381 between GA and CA199 (P = 0.000). (3) Multiple stepwise regression analysis show standard regression coefficient of HbA1c is 0.364 (P = 0.000). CONCLUSION:(1) CA199 level of diabetic patient in poor glucose control was significantly higher than the patient in good control. (2) CA199 was positively correlated with FBG, PBG, HbA1c and GA. (3) HbA1c is the independent risk factor of CA199. The elevated CA199 in diabetic patient has close relationship with poor glucose control in a long period.

BACKGROUND:This study aimed to determine the underlying pathophysiologic mechanism of elevated carbohydrate antigen 19-9 (CA19-9) in pulmonary sequestration (PS) patients. MATERIALS AND METHODS:Four pulmonary sequestration patients, 12 pneumonia patients and 12 healthy adult volunteers were prospectively studied. Specimens from another 34 pulmonary sequestration patients were retrospectively analyzed. Serum CA19-9 levels of 4 patients were tested before and 1 week, 1 month and 3 months after surgery. The CA19-9 levels of 12 pneumonia patients and 12 healthy adult volunteers were tested as controls. The expression and localization of CA19-9 in diseased lesions and corresponding normal lung tissues were analyzed by Immunohistochemical (IHC). Hematoxylin-eosin (HE) staining was performed to observe the pathological changes in pulmonary sequestration tissues. RESULTS:Serum CA19-9 levels were significantly higher in the 4 patients (797.3 ± 316 IU/ml) than in the pneumonia patients (10.07 ± 5.01 IU/ml) and healthy volunteers (9.85 ± 4.12 IU/ml). In addition, serum CA19-9 levels decreased dramatically after the focus was removed. Positive staining of CA19-9 was found in 70% (24/34) of pulmonary sequestration tissues, and CA19-9 was mainly expressed in the bronchial mucus. In the 4 diseased lesions, deformed alveolar structure and inflammatory cell infiltration were observed, and the degree of damage was positively correlated with serum CA19-9 levels. CONCLUSIONS:CA19-9 could be generated by abnormal columnar epithelia in pulmonary sequestration tissues and was transported into circulation after alveoli damage. CA19-9 could serve as an adjuvant diagnostic marker in pulmonary sequestration.

BACKGROUND:Gastric cancer (GC) is a common malignant tumor of the digestive system with a high degree of malignancy. It usually develops insidiously without any specific symptoms in the early stages. As one of the diseases caused by abnormal gene changes, GC has abnormal expression of various oncogenes and products during its development. Tumor markers such as carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199) and carbohydrate antigen 724 (CA724) are not expressed or lowly expressed in normal people, but significantly increased after carcinogenesis. Monitoring the changes in the levels of tumor markers such as CEA, CA199 and CA724 is conducive to early diagnosis and evaluation of the occurrence of some solid tumors. AIM:To investigate the expression of CEA, CA199 and CA724 in GC and their correlation with clinical features, hoping to provide more effective markers for the early preventive diagnosis of GC. METHODS:Of 87 patients with GC admitted to our hospital from September 2020 to December 2021 were included in the GC group, and another 80 healthy people who came to our hospital for physical examination with normal results during the same period were selected as the control group. The serum CEA, CA199, and CA724 levels were compared between the two groups, and the serum CEA, CA199, and CA724 levels were compared in patients with GC at different TNM stages, and the differences in the positive rates of CEA, CA199, and CA724 alone and in combination in detecting TNM stages of GC and GC were compared. In addition, the relationship between the levels of tumor markers CEA, CA199 and CA724 and the clinicopathological characteristics of GC patients was also analyzed. The relationship between the serum levels of CEA, CA199 and CA724 and the survival period of GC patients was analyzed by Pearson. RESULTS:The serum levels of CEA, CA199 and CA724 in GC group were significantly higher than those in control group ( < 0.05). With the increase of TNM stage, the serum CEA, CA199 and CA724 expression levels in GC patients increased significantly, and the differences between groups were statistically significant ( < 0.05). The positive rate of the CA724 single test was higher than that of CEA and CA199 single test ( < 0.05). The positive rate of the three combined tests was 95.40% (83/87), which was higher than that of CEA, CA199 and CA724 single tests. The difference was statistically significant ( < 0.05). The combined detection positive rates of CEA, CA199, and CA724 in stages I, II, III, and IV of GC were 89.66%, 93.10%, 98.85%, and 100.00% respectively, all of which were higher than the individual detection rates of CEA, CA199, and CA724. The differences were statistically significant ( < 0.05). There was no significant difference in serum CEA, CA199 and CA724 levels between GC patients with different genders, smoking history and alcohol history ( > 0.05). However, the serum CEA, CA199 and CA724 levels were significantly higher in GC patients aged ≥ 45 years, TNM stage III-IV, with lymph node metastasis and tumor diameter ≥ 5 cm than in GC patients aged < 45 years, TNM stage I-II, without lymph node metastasis and tumor diameter < 5 cm ( < 0.05). CONCLUSION:The expression levels of serum tumor markers CEA, CA199 and CA724 in patients with GC are high and rise with the increase of TNM stage. The levels of CEA, CA199 and CA724 are related to age, TNM stage, lymph node metastasis and tumor diameter. The combined detection of CEA, CA199 and CA724 is helpful to improve the diagnostic accuracy of GC with high clinical guidance value.

BACKGROUND:Our aim of was to compare importance of the tumor markers (TMs) serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 in prediction of recurrence after curative gastrectomy for gastric cancer. METHODS:We reviewed retrospectively the clinical records of 149 patients who underwent curative gastrectomy for stage I-III gastric cancer and whose CEA and CA19-9 levels were determined once preoperatively and for more than 3 years postoperatively. We investigated whether the clinicopathological characteristics of patients including age, sex, pathological disease stage, operative approach, type of gastrectomy, and degree of lymph node dissection as well as preoperative positivity of CEA and CA19-9 were risk factors for recurrence in univariate and multivariate analyses. Rate of recurrence was compared between patients positive and negative for postoperative CEA or CA19-9. We also calculated sensitivity, specificity, positive and negative predictable values of postoperative positivity of CEA and CA19-9 for recurrence. The lead time was compared between CEA and CA19-9 that was defined as the time of the first detection of increases in tumor markers and confirmation of recurrence on imaging modalities. RESULTS:The number of patients positive for preoperative CEA was 25 (17%) and for CA19-9 was 11 (7%). Recurrence was confirmed in 29 (19%) patients. Stage III disease, preoperative positivity for CA19-9 but not CEA, and total gastrectomy were risk factors for recurrence in univariate analysis, but stage III disease was the only risk factor for recurrence in multivariate analysis. Forty and 15 patients were positive for postoperative CEA and CA19-9, respectively. The recurrence rate of 47% (7/15) in patients positive for postoperative CA19-9 was greater than that in negative patients (22/134 = 16%), but it did not differ between patients who were positive or negative for postoperative CEA. Specificity for CA19-9 was greater than that for CEA (P < 0.05). The lead time of CEA (3.9 ± 4.7 months) was not different from that of CA19-9 (6.1 ± 7.1 months). CONCLUSIONS:These results indicate that CA19-9 rather than CEA is likely to be more useful for the detection of recurrence after curative gastrectomy for gastric cancer.

BACKGROUND:Glucose and lipid metabolic disorder in patients with type 2 diabetes mellitus (T2DM) is associated with the levels of serum tumor markers of the digestive tract, such as cancer antigen (CA)199. Therefore, tumor markers in T2DM are important. AIM:To evaluate the expression of serum tumor markers [CA199, CA242, and car-cinoembryonic antigen (CEA)] and the clinical implications of the expression in T2DM. METHODS:For this observational study conducted at Hefei BOE Hospital, China, we enrolled 82 patients with first-onset T2DM and 51 controls between April 2019 and December 2020. Levels of fasting blood glucose (FBG), tumor markers (CA199, CEA, and CA242), glycosylated hemoglobin (HbA1c), . were measured and group index levels were compared. Moreover, FBG and HbA1c levels were correlated with tumor marker levels. Tumor markers were tested for diagnostic accuracy in patients with > 9% HbA1c using the receiver operating curve (ROC) curve. RESULTS:The T2DM group had high serum FBG, HbA1c, CA199, and CEA levels ( < 0.05). A comparative analysis of the two groups based on HbA1c levels (Group A: HbA1c ≤ 9%; Group B: HbA1c > 9%) revealed significant differences in CEA and CA199 levels ( < 0.05). The areas under the ROC curve for CEA and CA199 were 0.853 and 0.809, respectively. CA199, CEA, and CA242 levels positively correlated with HbA1c ( = 0.308, 0.426, and 0.551, respectively) and FBG levels ( = 0.236, 0.231, and 0.298, respectively). CONCLUSION:As compared to controls, serum CEA and CA199 levels were higher in patients with T2DM. HbA1c and FBG levels correlated with CA199, CEA, and CA242 levels. Patients with poorly controlled blood sugar must be screened for tumor markers.

OBJECTIVE:To develop a new scoring system based on platelet-to-lymphocyte ratio (PLR) and CA199 to predict the prognosis of gastric cancer. METHODS:PLR-CA199 was identified in a retrospective study that was conducted in a training cohort of 990 gastric cancer patients who underwent curable resection from 2012 to 2014 and validated in a validation cohort of 625 patients between 2015 and 2016. RESULTS:In the training cohort, PLR-CA199 was related to gender (P = 0.041), age (P = 0.014), tumor location (P = 0.015), tumor size (P < 0.001), Bormann type (P < 0.001), vascular invasion (P < 0.001), perineural invasion (P < 0.001), and TNM staging (P < 0.001). In the validation cohort, PLR-CA199 was related to tumor size (P < 0.001), Bormann type (P = 0.007), vascular invasion (P < 0.001), perineural invasion (P < 0.001), and TNM staging (P < 0.001). Survival analysis showed that in the training cohort the mean disease-free survival (DFS) was 70.699 months for patients PLR-CA199 = 0, 51.223 months for patients PLR-CA199 = 1, and 32.152 months for patients PLR-CA199 = 2 (P < 0.001). The correlation between PLR-CA199 and DFS was further confirmed in the validation cohort (50.640 vs. 41.842 vs. 22.382, P < 0.001). Survival analysis showed that the mean disease special survival (DSS) was 76.668 months for patients PLR-CA199 = 0, 61.218 months for patients PLR-CA199 = 1, and 44.665 months for patients PLR-CA199 = 2 in the training cohort (P < 0.001). The correlation between PLR-CA199 and DSS was further confirmed in the validation cohort (53.858 vs. 46.385 vs. 44.665, P < 0.001). Furthermore, univariate and multivariate analyses showed that PLR-CA199 was an independent prognostic factor for DFS and DSS. CONCLUSIONS:Preoperative PLR-CA199 may be a useful prognostic indicator, and is a promising tool for predicting the prognosis for gastric cancer.