New insights into antibody levels against SARS-CoV-2 for healthcare personnel vaccinated with tozinameran (Comirnaty).

AIM: The aim of this study is to determine the levels of spike protein IgG and total antibodies in subjects vaccinated against SARS-CoV-2 (both infected and non-infected) and the titer evolution over time. In addition, we also addressed the performance of each of the included platforms in the study, as they are intended to measure antibody levels in naturally infected patients. MATERIALS AND METHODS: An observational study including 288 volunteer healthcare professionals vaccinated against SARS-CoV-2 (Comirnaty™) at the Andújar Alto Guadalquivir Hospital. Serum samples were obtained in September 2020 and 14 and 90 days after administration of the second dose. The following in vitro methods were used: Elecsys Anti-SARS-CoV-2 N and Elecsys Anti-SARS-CoV-2 S (Roche, Germany) and EliA SARS-CoV-2-Sp1 IgG (Thermo Fisher Scientific, Germany). RESULTS: For the Elecsys S method at 1/10 dilution and for the EliA Sp1 IgG method at 1/5 dilution, 54% and 19% of samples were out of range, respectively. The vaccine activated a high humoral response- 0 to 3000 BAU/mL being the "normal titer range" in all volunteers. Patients vaccinated after COVID-19 exhibited higher total S antibody load values than non-vaccinated volunteers while showing the same response for S IgG isotype. Titers decreased up to 86% in the case of S IgG neutralizing antibodies. CONCLUSIONS: The characterization of human response to SARS-CoV-2 vaccines is still far from being completely elucidated. It is important to increase the methods dynamic range to study humoral response evolution in depth and decide whether booster doses or seasonal vaccination plans will be necessary to definitively control the pandemic.

Primary hypolactasia diagnosis: Comparison between the gaxilose test, shortened lactose tolerance test, and clinical parameters corresponding to the C/T-13910 polymorphism.

BACKGROUND & AIMS: There is no consensus on the most accurate method to diagnose primary hypolactasia. We aimed to compare the diagnostic accuracy of the new gaxilose test with 2 traditional tests (lactose tolerance test and clinical criteria) for the diagnosis of primary hypolactasia using the C/T-13910 polymorphism as a reference standard. METHODS: Patients with a clinical suspicion of lactose intolerance were subjected to gaxilose tests, shortened lactose tolerance tests, and symptom questionnaires before and after overload with 50 g lactose and after a lactose-free diet. The diagnostic accuracy and degree of agreement and correlation were assessed using a genetic test (C/T-13910 polymorphism) as a reference standard and their respective 95% confidence intervals. RESULTS: Thirty consecutive patients (70% women) participated in the study. The genetic test confirmed the C/T-13910 polymorphism in 11 patients (36.8%). The presence of diarrhoea and the symptom score after lactose overload, along with the tolerance test, were the variables with the highest degree of agreement (κ > 0.60). Area under the ROC curve was >0.82 (p < 0.05), with sensitivity and specificity values of >0.80. However, the gaxilose test obtained lower values: κ, 0.47; area under curve, 0.75 (0.57-0.94); sensitivity, 0.82 (0.55-1); and specificity, 0.68 (0.45-0.92). The multivariate analysis showed an association between the post-overload symptom questionnaire and the results of the genetic test (odds ratio: 1.17; 1.04-1.31; p < 0.01). CONCLUSIONS: The presence of diarrhoea and the symptom score after overload with 50 g lactose showed a higher degree of agreement and diagnostic accuracy for primary hypolactasia than the gaxilose test when the genetic test is used as a reference standard.

Low positive rate of serum autoantibodies in colorectal cancer patients without systemic rheumatic diseases.

BACKGROUND: Antinuclear antibody (ANA) testing is useful for screening, diagnosis and follow-up of patients with systemic rheumatic diseases. Indirect immunofluorescence (IIF) on HEp-2 cells is the gold standard for ANA testing. However, ANA have also been detected in patients with different cancer types but without any autoimmune disease. To overcome these shortcomings, different automated solid-phase assays have been developed. AIM: To determine the positive rate of a new ANA detection method (EliA CTD Screen, Phadia, Germany), in CRC patients without systemic rheumatic diseases. Additionally, we compare this method with IIF. MATERIALS AND METHODS: Serum samples were obtained before a colonoscopy procedure in a patient cohort (n = 186) with a high clinical suspicion of CRC. Samples for ANA detection in CRC patients were processed in parallel by IIF on HEp-2 and the solid-phase fluoroenzymeimmunoassay EliA CTD Screen (Phadia, Germany) on the Phadia 250 instrument (Phadia GmbH, Freiburg, Germany). Positive samples by IIF and/or CTD were tested with EliA single ANA assays (Phadia, Germany) on the Phadia 250 instrument (Phadia GmbH, Freiburg, Germany). RESULTS: Forty-five patients diagnosed with CRC were included. Four cases were positive by CTD and 23 by IIF. Of the four positive patients by CTD, two were positive and one indeterminate for anti-dsDNA antibodies. Of the 23 positive by IIF, one patient was positive and another indeterminate for anti-dsDNA antibodies, and a third patient was positive for anti-U1RNP antibodies. CONCLUSIONS: The CTD assay shows a low false positive rate for detecting autoantibodies in a clinical context of CRC.

Correlation Between Capillary and Venous Blood Glucose in the Lactose Tolerance Test.

BACKGROUND: The lactose tolerance test is a classic method for the study of lactose malabsorption. However, the methodology used has not been standardized, and this leads to differences in results. AIM: The aim of this report was to analyze whether capillary blood glucose measurement is in agreement with venous blood glucose when performing lactose tolerance test. METHODS: This is a prospective study of consecutive patients with suspected lactose malabsorption who had lactose tolerance test performed in venous and capillary blood simultaneously, using a load of 50 g lactose. Agreement was measured using the concordance correlation coefficient of Lin (95 % CI) and Bland-Altman plots. The degree of agreement was measured using the Kappa index. A value of p < 0.05 was considered statistically significant. RESULTS: Eighty-four patients (68 % women) were included. The concordance correlation coefficient showed very poor agreement between the two techniques: 0.68 (0.58-0.77), 0.72 (0.62-0.8), and 0.77 (0.69-0.83) for baseline, 30, and 60 min, respectively. The Bland-Altman plots showed that capillary blood glucose measurements result in higher levels than venous blood glucose measurements, with mean differences of 0.39, 0.77, and 1.1 mmol/L at baseline, 30, and 60 min, respectively. The degree of agreement was low, with a Kappa index of 0.59 (p < 0.001). CONCLUSIONS: The test measured in venous blood is not in agreement with the measurement obtained from capillary blood. It is likely that the diagnostic accuracy attributed without distinction to lactose tolerance test in different studies for lactose malabsorption is incorrect, making it necessary to specify the analysis method.

Plasma Tumor M2-Pyruvate Kinase Levels in Different Cancer Types.

BACKGROUND/AIM: Tumor M2-pyruvate kinase (M2-PK) is up-regulated in proliferating tissues. It has been shown that tumor M2-PK is detectable and quantifiable in the stool and plasma of patients with colorectal cancer (CRC). Tumor M2-PK has been extensively studied in gastrointestinal tumors but its role in other cancer types has not yet been deeply evaluated. The aim of the study was to determine and compare plasma tumor M2-PK levels in different cancer types. MATERIALS AND METHODS: All patients undergoing diagnostics for cancer at our Hospital during 2011 were included in the study (n=139). Plasma tumor M2-PK concentration was analyzed by an enzyme-linked immunosorbent assay. RESULTS: The different cancer types found in the study were: 60 colorectal, 43 breast, 8 lung, 5 prostatic, 4 ovarian and the remaining 19 cases were other uncommon tumor types. Most tumors had high concentrations of tumor M2-PK; prostatic, pharyngeal and testicular tumors had levels lower than or near the cut-off. Plasma tumor M2-PK levels were significantly higher in patients with distant metastases and stage IV by TNM. CONCLUSION: Plasma tumor M2-PK is not a specific marker for CRC and is elevated in many other types of cancers, including breast, lung, ovarian, and thyroid. Small amounts are found in prostatic, pharyngeal and testicular tumors.

Lactose tolerance test shortened to 30 minutes: An exploratory study of its feasibility and impact.

INTRODUCTION: Lactose malabsorption (LM) is a very common condition with a high prevalence in our setting. Lactose tolerance test (LTT) is a basic, affordable test for diagnosis that requires no complex technology. It has been recently shown that this test can be shortened to 3 measurements (baseline, 30 min, 60 min) with no impact on final results. The purpose of our study was to assess the feasibility and benefits of LTT simplification and shortening to 30 min, as well as the financial impact entailed. MATERIAL AND METHODS: A multicenter, observational study of consecutive patients undergoing LTT for LM suspicion. Patients received 50 g of lactose following a fasting period of 12 h, and had blood collected from a vein at all 3 time points for the measurement of blood glucose (mg/dl). Differences between the shortened and complete test forms were analyzed using McNemar´s test. A comparison of blood glucose levels between patients with normal and abnormal results was performed using Student´s T-test for independent mean values. Consistency was assessed using the kappa index. A p < 0.05 was considered to be statistically significant. RESULTS: A total of 270 patients (69.6 % females) were included, with a mean age of 39.9 ± 16 years. LTT was abnormal for 151 patients (55.9 %). We observed no statistically significant differences in baseline blood glucose levels between patients with normal and abnormal LTT results (p = 0.13); however, as was to be expected, such differences were obvious for the remaining time points (p < 0.01). Deleting blood glucose measurements at 60 minutes only led to overdiagnose LM (false positive results) in 6 patients (2.22 %), with a kappa index of 0.95 (95 % CI: 0.92-0.99) (p < 0.001) versus the complete test. Suppressing measurements at 60 min would have saved at least € 7,726. CONCLUSION: The shortening of LTT to only 2 measurements (baseline and 30-min) hardly leads to any differences in final results, and would entail savings in time, materials, and personnel.

Dhat syndrome, an emergent condition within urology in Spain.

BACKGROUND: Dhat syndrome (DS) consists of vague somatic symptoms and at times sexual dysfunction which the patient falsely attributes to involuntary emissions of semen outside of sexual relations. OBJECTIVE: Describe and analyse the occurrences of DS in patients attending the clinic and clarify the existence of this condition within the Spanish Urological service. MATERIALS AND METHODS: Patients reporting semen loss in urine or involuntarily outside of sexual relations were studied during a period from May 2006 to December 2007. Variables of age, nationality, marital status, family situation, medical history, reasons for the consultation, physical condition and additional tests were studied. All treatments and its effectiveness were also recorded. RESULTS: DS affected predominantly southern Asian continent citizens (n = 32). The average age was 35.44. Seventeen patients reported semen loss during urination; 20 at the end of urination; 11 spontaneously; 5 while sleeping; 4 during defecation; 1 while showering; 1 while eating meat; and 3 produced by noticing stained clothing. In 28 cases, the supposed loss of semen was linked to sex-related symptoms. All examinations and tests ruled out the existence of actual loss of semen. CONCLUSIONS: In urology consultations, we have been witnessing the unusual appearance of DS, a condition known by psychologists and psychiatrists and practically unheard of by urologists. A previously unknown condition in Spain, immigration from Asia, is causing the appearance of this syndrome. Its rapid identification will prevent patients from paying costly and unnecessary tests and provide alternative therapies, within a multidisciplinary approach involving psychologists and psychiatrists.

KiSS-1 methylation and protein expression patterns contribute to diagnostic and prognostic assessments in tissue specimens for colorectal cancer.

KISS1 is a metastasis suppressor lost in several solid malignancies. We evaluated the clinical relevance of KiSS-1 methylation and its protein expression in colorectal cancer. The epigenetic silencing of KiSS-1 by hypermethylation was tested in colon cancer cells (n = 5) before and after azacytidine treatment. KiSS-1 methylation was evaluated by methylation-specific PCR in colorectal cancer cells, and normal, benign, and tumor tissues (n = 352) were grouped in a training set (n = 62) and two independent validation cohorts (n = 100 and n = 190). KiSS-1 protein expression was analyzed by immunohistochemistry on tissue arrays. KiSS-1 hypermethylation correlated with transcript and protein expression loss, being increased in vitro by azacytidine. Methylation rates were 53.1, 70.0, and 80.0 % in the training and validation sets, respectively. In the training set, KiSS-1 methylation rendered a diagnostic accuracy of 72.7 % (p = 0.002). Combination of KiSS-1 methylation and serum CEA (p = 0.001) increased the prognostic utility of CEA alone (p = 0.022). In the first validation set, KiSS-1 methylation correlated with tumor grade (p = 0.011), predicted recurrence (p = 0.009), metastasis (p = 0.004), disease-free (p = 0.034), and overall survival (p = 0.015). In the second validation cohort, KiSS-1 methylation predicted disease-specific survival (p = 0.030). In the training set, cytoplasmic KiSS-1 expression was significantly higher in nonneoplastic biopsies as compared to colorectal tumors (p < 0.0005). In the validation set, loss of cytoplasmic expression correlated with tumor stage (p = 0.007), grade (p = 0.035), recurrence (p = 0.017), and disease-specific survival (p = 0.022). KiSS-1 was revealed epigenetically modified in colorectal cancer. The diagnostic and prognostic utility of KiSS-1 methylation and expression patterns suggests their assessment for the clinical management of colorectal cancer patients.

Prognostic value of plasmatic tumor M2 pyruvate kinase and carcinoembryonic antigen in the survival of colorectal cancer patients.

Colorectal cancer (CRC) can be cured in most cases if diagnosed at an early stage. Carcinoembryonic antigen (CEA) remains the most widely used cancer marker for determining prognosis of CRC. Previous studies have shown that plasmatic tumor M2 pyruvate kinase (Tu M2-PK) is highly sensitive in CRC detection at an early stage and equally as good as the results for established tumor markers with clinical potential for cancer prognosis and monitoring. The aim of this study was to assess the prognostic value of Tu M2-PK in plasma using a survival analysis in combination with CEA in serum in patients newly diagnosed with CRC. The initial study included 183 patients who had a complete diagnostic colonoscopy. This cohort study was designed to evaluate the survival in patients with histologically confirmed gastrointestinal cancers (n = 41). Tu M2-PK concentrations in EDTA plasma were determined immunologically using an ELISA assay. Plasma Tu M2-PK levels were significantly higher in patients with distant metastases, stage IV for TNM score, and advanced stage (C+D) subgroups of Dukes than other subgroups. The univariate Cox's analysis showed that CEA and Tu M2-PK gave high hazard ratios for risk of death (odds ratio CEA = 3.57 and odds ratioTu M2-PK = 2.23) and comparable values in average survival time. The results for both biomarkers did not overlap. These findings suggest that plasmatic Tu M2-PK levels of more than 20 U/mL may be a predictor of death risk.

Diagnostic and prognostic utility of methylation and protein expression patterns of myopodin in colon cancer.

Myopodin is an actin-binding protein believed to play a tumor suppressor role in several solid neoplasias. We evaluated the potential differential myopodin methylation and expression and their clinical relevance in colon cancer. The epigenetic silencing of myopodin by hypermethylation was tested in colon cancer cells (n = 5) before and after azacitidine treatment. Myopodin methylation status was evaluated by methylation-specific PCR in colon cancer cells and colorectal tissues (n = 210) grouped in a training set (n = 62) and two independent validation series (n = 100 and n = 48) collected at independent clinical settings. Myopodin expression patterns were analyzed by immunohistochemistry on tissue arrays. Myopodin hypermethylation correlated with gene and protein expression loss, being increased in vitro by azacitidine. Myopodin was frequently methylated in colon cancer cells (four out of five). Methylation rates were 90.3%, 70.0%, and 47.8% in the training and validation sets, respectively. Myopodin methylation rendered a diagnostic accuracy of 83.9% (p < 0.0005). Cytoplasmic myopodin expression was significantly higher in non-neoplastic biopsies compared to colon tumors (p < 0.0005). Loss of myopodin expression correlated with increasing tumor stage (p = 0.011), methylation (p = 0.005), and poor overall survival (p = 0.003). In the first validation set (n = 100), myopodin methylation predicted disease-free (p = 0.046) and overall survival (p = 0.031). In the second validation cohort, myopodin methylation and protein expression patterns predicted disease-specific (p = 0.012 and p = 0.001, respectively) and overall survival (p = 0.009 and p = 0.043, respectively). Thus, myopodin was revealed to be epigenetically modified in colon cancer. The diagnostic and prognostic clinical utility of myopodin methylation and expression patterns suggest considering their assessment for the clinical management of colon cancer patients.

The contribution of four immunogenetic markers for predicting persistent activity in patients with recent-onset rheumatoid arthritis or undifferentiated arthritis.

We assessed the contribution of four baseline markers-HLA-DRB1 shared epitope (SE), -308 tumor necrosis factor α gene promoter polymorphism, rheumatoid factor, and anticitrullinated peptide antibodies-for predicting persistent activity (DAS28 score ≥2.6) after one year of followup in a cohort of 201 patients with recent-onset rheumatoid arthritis (RA) or undifferentiated arthritis (UA) aged 16 years or older who had a 4-week to 12-month history of swelling of at least two joints. Patients had not been previously treated with corticosteroids or disease-modifying antirheumatic drugs (DMARD). In the best logistic regression model, only two variables were retained: SE positivity and number of DMARD administered (area under the curve = 76.4%; 95% CI: 69.2%, 84.4%; P < 0.001). The best linear regression model also included these two variables, explaining only 22.5% of the variability of DAS28 score. In this study, given an equal number of DMARD administered, the probability of persistent activity in patients with recent-onset RA or UA was significantly influenced by SE presence.

[Urology care demand analysis in a specialty centre with a high percentage of immigrant patients]. / Análisis de la demanda de asistencia urológica en un centro de especialidades con una tasa elevada de inmigración.

OBJECTIVE: The objective of this study is to describe patients referred for urological examination by their primary health care centres according to ethnicity and the disorders in question. The area selected for this study is the Raval Sur neighborhood in the city of Barcelona which has a high immigrant population. This will enable us to understand the health needs of an emerging population which is gaining considerable importance in many Spanish cities, at least where the specialty of urology is concerned. PATIENTS AND METHODS: Prospective study of all patients who visited the urology division at Barcelona's Raval Sur Specialty Centre during 2007. The chosen population consisted of all patients visiting the urology division for the first time. RESULTS: We studied 247 patients, of whom 124 were Spanish, 75 South Asian, 27 Americans, 11 Africans and 10 from other countries. The average age was higher in Spanish patients: 57.86 +/- 17.85 years compared with 37.54 +/- 11.07 years for other nationalities. Both groups were predominantly male. Statistical differences for prostate symptoms were observed between patient groups:, these symptoms were present in 32.4% of Spanish patients, 7.95% of South Asians,17.2% of Americans and 9.1% of Africans. Significant differences were also seen in the PSA increase, affecting 15.2% of Spaniards, with no cases in other groups. Sexual functional pathology was only a motive for examination in the South Asian group, with 56.8% of patients. Phymosis and vasectomy surgery were the reasons for consultation in 9.8% of Spaniards, 2.7% of South Asians, 25% of Americans and were not required by any patient of African origin. Lower back pain was also observed in 0.7% of Spaniards, 1.35% of South Asians and 18.2% of Africans, but in none of the American patients. Gross haematuria was present in 5.1% of Spaniards, 3.4% of Americans, 18.2% of Africans and in no South Asian patients. CONCLUSIONS: The most common reason for consultation in the Spanish patient group was prostatic hypertrophy, American patients requested phymosis surgery or surgical sterilization, and South Asians visited for different sexual pathologies, which affected 56.8% of patients in this group. There were no significant differences in the number ofadditional examinations or in in the number of visits required for diagnosis between the different ethnic groups. One problem that we noted was the missed appointment rate for some patients, which is twice as high in the immigrant group as among Spanish patients and highest in the African and South Asian groups.

Lemierre's syndrome and septicaemia caused solely by Arcanobacterium haemolyticum in a young immunocompetent patient.

We present a case of septicaemia caused by Arcanobacterium haemolyticum in a previously healthy 23-year-old man suffering from acute pharyngotonsillitis, who developed complicated Lemierre's syndrome. Three blood cultures (both aerobic and anaerobic) revealed the exclusive presence of A. haemolyticum. The presence of Fusobacterium necroforum was not essential for the development of this pathology. To our knowledge, this is the first reported case of Lemierre's syndrome caused solely by A. haemolyticum. We confirm that this organism must be considered a potential pathogen in immunocompetent patients.

The value of HLA-DRB1 shared epitope, -308 tumor necrosis factor-alpha gene promoter polymorphism, rheumatoid factor, anti-citrullinated peptide antibodies, and early erosions for predicting radiological outcome in recent-onset rheumatoid arthritis.

OBJECTIVE: To study the value of HLA-DRB1 shared epitope (SE), -308 tumor necrosis factor-alpha (TNF-alpha) gene promoter polymorphism, rheumatoid factor (RF), anti-citrullinated peptide antibodies (anti-CCP), and baseline erosions for predicting radiological outcome at 1 year in patients with recent-onset rheumatoid arthritis (RA). METHODS: Radiological damage was assessed by radiographs at baseline and at 1 year in an inception cohort of 134 RA patients with disease duration

Diagnostic usefulness of a third-generation anti-cyclic citrulline antibody test in patients with recent-onset polyarthritis.

BACKGROUND: The high specificity of anti-cyclic citrullinated peptide antibodies (anti-CCP) helps substantially in the diagnosis of rheumatoid arthritis (RA), combined with classical markers such as rheumatoid factor (RF). The recent introduction of third-generation methods (anti-CCP3) for anti-CCP detection could further improve diagnostic efficiency. The aim of this study was to determinate the diagnostic efficiency (sensitivity and specificity) of anti-CCP using a new anti-CCP3 method and to compare it with the previous second-generation method (anti-CCP2). METHODS: Anti-CCP were studied in sera of 234 patients with recent-onset polyarthritis (ROP) (age > or =16 years; evolution time > or =4 weeks < or =1 year; 2 or more inflamed joints, without drug therapy). After 1 year, 124 patients were diagnosed with RA (American College of Rheumatology criteria). Two ELISAs, an anti-CCP2 and an anti-CCP3, were performed. RESULTS: The best sensitivity according to receiver operating characteristic curves was 51.5% and 54.8% for anti-CCP3 and anti-CCP2, with a specificity of 96.2% and 98.1%, respectively (optimal cutoffs 14.2 and 18.7 U/mL). Significant correlations were obtained (p<0.001) when the methods were compared to each other and to RF. CONCLUSIONS: Testing with both types of anti-CCP kit is highly specific for the presence of RA. In our ROP group, anti-CCP2 and anti-CCP3 exhibited similar diagnostic efficiency.

Efficacy of three ELISA measurements of anti-cyclic citrullinated peptide antibodies in the early diagnosis of rheumatoid arthritis.

The objective of the present study was to determine the efficacy of anti-cyclic citrullinated peptide (anti-CCP) antibody detection in the early diagnosis of rheumatoid arthritis (RA), as well as to compare three commercially available enzyme-linked immunosorbent assay (ELISA) kits used to detect such antibodies. We analysed the presence of anti-CCP antibodies in the sera of 78 patients who had been newly referred from primary healthcare centres to the Early Polyarthritis Unit. We also included in the study a group of 50 healthy controls. None of the patients had previously received treatment for the disease. After 1-year follow-up, the diagnosis of RA was confirmed in 53 of these patients. The ELISA kits under study were IMMUNOSCAN RA (Euro-Diagnostica AB), QUANTA Lite CCP IgG ELISA (INOVA Diagnostic) and DIA-STAT Anti-CCP (Axis-Shield Diagnostics); the sensitivity obtained was 52.8%, 58.5% and 52.8%, respectively, with 100% specificity for all three kits. Anti-CCP antibodies detected the presence of RA in 26% of patients without positive rheumatoid factor (RF). The sum of anti-CCP antibodies or the presence of RF gave a sensitivity of up to 67%, with specificity ranging between 94 and 97%. Anti-CCP antibodies show high specificity for the diagnosis of RA. The three ELISAs analysed offer the same degree of diagnostic accuracy.

Low utility of CYFRA 21-1 serum levels for diagnosis and follow-up in bladder cancer patients.

We evaluated serum levels of soluble fragments of cytokeratin 19 (CYFRA 21-1) by immunoassay (ES-700; Roche Diagnostics, Mannheim, Germany) to assess its usefulness in the diagnosis and follow-up of bladder cancer. The study included 39 patients with a diagnosis of transitional cell carcinoma (group 1) and 190 patients (group 2) with no evidence of tumor. In group 2, 180 patients had a history of bladder cancer, and 10 had benign prostatic hyperplasia. Significant differences in CYFRA 21-1 concentrations between groups 1 and 2 (P<0.01) were noted. However, CYFRA 21-1 levels did not significantly differ between the patients with benign prostatic hyperplasia and those with bladder cancer (P=0.274). CYFRA 21-1 values were higher in invasive bladder cancer compared to that detected in superficial stages (P=0.011). Setting the optimal cutoff value at 2.5 ng/mL resulted in a sensitivity of 43.6% and a specificity of 82.1%. No statistical differences were found when we compared disease-free time among the 66 patients with recurrences (30.7 months with levels <2.5 ng/mL vs. 41.2 months with levels >2.5 ng/mL; P=0.248). The risk of recurrence in patients with levels lower than 2.5 ng/mL (0.79) was no different (P=0.097) from that found in patients with higher levels (1.69). CYFRA 21-1 serum levels do not provide enough sensitivity to justify its application in routine protocols for the detection and follow-up of bladder cancer.