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INTRODUCTION: posterior urethral valves represent an important cause of childhood chronic kidney disease. The identification of biomarkers that indicate early kidney damage and even adequate clearance could reduce how many patients head towards kidney failure. OBJECTIVE: this study evaluated how this easy-analysis biomarker (CA 19-9) could help identifying potential renal damage and adequate clearance in obstructive uropathies. METHODS: 46 female Wistar rats were divided into 5 groups, with different patterns of partial urinary tract obstruction: group control; group OIV: infravesical obstruction; group OIVd: infravesical obstruction with reversion, obstruction relief 7 postoperative days later; group OUu: unilateral ureteral obstruction; group OUb: bilateral ureteral obstruction. The CA 19-9s performance was compared to another biomarker: Ngal. Determination of basal CA 19-9 and Ngal in urine and blood and serum creatinine levels was performed in the rats prior to surgery (T0) and after 14 days (T1). Group OIVd underwent intermediate (Ti) collection before clearance. RESULTS: the urinary concentration of CA 19-9 increased in groups OIV, OIVd and OUb; elevation at T1 and Ti, reached statistical significance compared to the T0 value (p<0,05). Changes in urinary CA 19-9 were more expressive in infravesical obstruction groups (AUC 0.81). Obstruction relief in group OIVd promoted significant urinary CA 19-9 reduction (p<0,05) in the final evaluation. CONCLUSIONS: CA 19-9 urinary concentration increased in partial urinary tract obstruction. Its best performance was in the bladder neck obstruction group, in which the elevation was detected early (6 days after infravesical obstruction) and the CA19-9 urinary concentration declined after clearance.

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PURPOSE: To evaluate the predictive role of maternal urinary CA 19-9 as a non-invasive marker for diagnosing antenatal posterior urethral valve (PUV). METHODS: A total of 40 women in the third pregnancy trimester were enrolled. Case group (group A) consisted of 20 women with a diagnosis of antenatal PUV. Twenty women with similar gestational age, fetal sex, normal US, and no history of congenital anomalies were chosen as a control group (group B). Maternal urine samples were collected and urinary CA 19-9 was measured in both groups. The correlations between maternal urinary CA 19-9 and APD (measured during pregnancy and the initial evaluation of the newborn) were assessed. CA 19-9 level in first urine of neonates was also evaluated. RESULTS: The mean ± SD of maternal urine CA 19-9 was higher in PUV group compared to the control group (131.6 ± 23.8 vs. 13 ± 2.7 U/mL). In addition, there was a significant correlation between maternal urinary CA 19-9 and the APD measured at the third trimester (p < 0.001) and the initial evaluation of fetus after birth according to SFU grading system (p < 0.001). However, no significant difference was found between gestational age and urinary CA 19-9 level (p = 0.34). There was also a significant correlation between the CA 19-9 level in first urine of neonates and CA 19-9 level of maternal urine (p < 0.001). CONCLUSIONS: This is the first time that maternal urinary CA 19-9 has been applied as a noninvasive and practical diagnostic marker in antenatal PUV.

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OBJECTIVE: To assess the role of urinary carbohydrate antigen 19-9 (CA19-9) measurement in determining optimal management of ureteropelvic junction obstruction (UPJO) and predicting failure of conservative management. PATIENTS AND METHODS: Children with UPJO diagnosed between December 2012 and April 2015 were included. Depending on clinical and para-clinical findings, patients were divided into three groups: Group 1 consisted of patients who were considered for non-operative management with improvement of the condition during the course of follow-up. Group 2 were suitable for observation; however due to deterioration of condition pyeloplasty was indicated after a period of observation. Group 3 patients required immediate pyeloplasty. Urinary CA19-9 was measured in all patients at baseline and compared between the study groups. RESULTS: A total of 112 children (115 affected kidneys) with UPJO and mean age of 18.6 ±â€¯3.3 months were assessed. Group 1, 2, and 3 consisted of 54(48.2%), 24(21.4%), and 34(30.4%) patients, respectively. Mean baseline urinary CA19-9 was 37.83 ±â€¯5.20, 145.45 ±â€¯18.38 and 244.62 ±â€¯41.42 in groups 1, 2 and 3, respectively. Multivariate analysis showed that both CA19-9 and APD are independent predictors of need for surgery in patients on observation. ROC curve analysis revealed that urinary CA19-9 level at cut off value of 52.6 U/mL had sensitivity of 92.0% and specificity of 70.9% in predicting failure of non-operative management. CONCLUSION: Higher urinary CA19-9 level is associated with failure of non-operative management in patients with UPJO. Such patients may require close follow-up and assessments to prevent irreversible damage to the kidney. TYPE OF STUDY: Study of Diagnostic Test. LEVEL OF EVIDENCE: Level II.

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INTRODUCTION: Ureteropelvic junction obstruction (UPJO) is the most common cause of hydronephrosis in children. One major challenge in the management of UPJO is to select the patients that must be subjected to early obstruction relief. Currently, there is no gold standard for this assessment. Therefore, the aim of the present study was to evaluate the urinary levels of carbohydrate antigen (CA) 19-9 and normalized CA 19-9 (Ca 19-9/Cr ratio) in UPJO patients before and after surgery and compare them with a control group to assess their potential clinical application as an assisting tool in diagnosis of UPJO patients. MATERIAL AND METHODS: From Jan 2013 to Jun 2016, 30 children with history of inguinal hernia, circumcision, hydrocele, and undescended testis as the control group (group 1) and 30 children with unilateral congenital UPJO (group 2) were enrolled in the study. Random CA 19-9 and random creatinine were measured in the voided urine samples of control group and proven congenital UPJO group preoperatively (group 2A) and at 6 months after dismembered pyeloplasty (group 2B). In addition, the random urinary CA 19-9/CR ratio was evaluated as a marker to normalized urinary CA 19-9. DISCUSSION: The urinary CA 19-9/Cr ratio was significantly greater in the UPJO group than in the control group. The urinary CA 19-9 also was more in group 2A than in group 1; however, it was not statistically significant. The urinary CA 19-9/Cr ratio and renal pelvis anteroposterior diameter decreased significantly in the group 2B 6 month after complete relief of obstruction in comparison with group 2A preoperatively. Urinary CA 19-9 also decreased in 2B group though it was not significant. CONCLUSION: Urinary CA 19-9/Cr ratio is suggested as a non-invasive marker that can assist in diagnosis and long-term follow-up of UPJO patients. This ratio is superior to urinary CA 19-9 as it is more strongly correlated with UPJ obstruction.

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

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This study was designed to evaluate the role of urinary and serum carbohydrate antigen 19-9 (CA19-9) as a biomarker in the assessment of patients with ureteral stone. A total of 38 patients with ureteral stone and hydronephrosis who underwent transurethral lithotripsy (TUL) (Group A) and 24 age-matched healthy controls (Group B) were evaluated in this study. Urinary and serum CA19-9 concentrations were measured in group A patients before TUL as well as 4 and 8 weeks following the operation. Urinary and serum CA19-9 concentrations were also measured in group B participants. Median concentration of urinary and serum CA19-9 was 34.0 and 15.0 kU/L in group A patients and 16.1 and 5.3 kU/L in group B, respectively (p < 0.001). Medians of CA19-9 concentration in urine and serum reduced to 12.5 and 4.5 kU/L 8 weeks after TUL (p < 0.001). Following successful TUL and hydronephrosis resolution, a significant decline was detected in serum and urinary CA19-9. We also noted that duration of ureteral obstruction was associated with serum and urinary CA19-9 concentrations, suggesting the potential role of this marker in predicting renal damage associated with urinary tract obstruction and determining the appropriate timing of interventions.

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BACKGROUND: Currently pancreatic cancer is the fourth leading cause of cancer-related death worldwide. Because of its late manifestation and consequent dismal prognosis, there is an urgent need to develop highly sensitive and specific marker. Neutrophil Gelatinase-Associated Lipocalin (NGAL) recently emerged as a protein playing an important role in carcinogenesis of various neoplasms. OBJECTIVE: Our aim was to assess the potential of urine and bile concentration of NGAL in differentiating pancreatic adenocarcinoma from chronic pancreatitis. METHODS: Forty-two patients operated on due to pancreatobiliary lesions were enrolled in this study. All enrolled patients had eGFR within reference range. Levels of CEA, CA 125 and Ca19-9 were assessed using standard laboratory protocols. A sample of urine was collected prior to the surgery. Intraoperatively a 5 ml sample of bile was collected directly from the common bile duct. Bile and urine levels of NGAL were measured using a ELISA kit. After standard pathological examination of specimens obtained during surgery, patients were divided into 2 groups: 21 patients with pancreatic adenocarcinoma and 15 patients with focal chronic pancreatitis. RESULTS: NGAL concentration in bile in patients with PDAC vs CP was 75.72 ± 16.05 ng/mL vs 62.62 ± 18.6 ng/mL respectively (p= 0,011). NGAL concentration in urine was 43.26 ± 21.21 ng/mL vs 17.96 ± 14.58 ng/mL (p= 0.002) respectively. In order to compare these markers with routinely used ones, ROC curve was built for Ca125 to establish cutoff point and in case of CA19-9 clinically used cutoff (≥ 37U/mL) was applied. Sensitivity and specificity for NGALurine with cutoff value of 27 ng/mL was 80.95% and 80% respectively, while these values for NGALbile were 71.43% and 80% respectively. Ca19-9 measured in plasma with clinically used cutoff value had sensitivity of 71.43% and specificity of 73.33%. Sensitivity and specificity for Ca 125 measured in plasma with cutoff value of 13 U/mL were 85.71% and 66.67% respectively. CONCLUSIONS: In conclusion, NGAL in urine and bile are remarkably accurate in differentiating pancreatic mass due to chronic pancreatitis from pancreatic adenocarcinoma. Therefore, NGAL concentrations in bile and urine should be further investigated in order to assess their usefulness in early pancreatic adenocarcinoma diagnosis.

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INTRODUCTION: Serum carbohydrate antigen (CA) 19-9 has been clinically applied as a valuable tumor marker for pancreatic and gastrointestinal carcinoma. CA 19-9 is expressed in normal excretory epithelium tissues. Increased CA 19-9 has also been observed in uroepithelial tumors as well as in nonmalignant conditions including hydronephrosis secondary to ureteral stones. OBJECTIVE: The purpose of this article is to evaluate the role of urinary CA 19-9 as a non-invasive biomarker in the postnatal differentiation of obstructive and non-obstructive hydronephrosis in patients with unilateral antenatal hydronephrosis. STUDY DESIGN: Infants with isolated renal pelvic dilatation, defined as the presence of anteroposterior pelvic diameter (APPD) equal to or greater than 7 mm based on antenatal ultrasound after 28 weeks' gestation, underwent systematic investigation for uropathies and were prospectively followed up. The pyeloplasty group consisted of 17 patients with ureteropelvic junction (UPJ) obstruction who had undergone pyeloplasty. The non-obstructive dilatation (NOD) group consisted of 17 patients with non-obstructive hydronephrosis, and the control group consisted of 21 healthy children. Commercial enzyme-linked immunosorbent assay (ELISA) kits were used to measure the urinary and serum CA 19-9 levels. In both hydronephrosis groups (pyeloplasty and non-obstructive dilatation), the correlations between urinary and serum CA 19-9 levels with the anteroposterior pelvic diameter measured at the third trimester and the postnatal initial evaluation and differential renal function were investigated. RESULTS: The initial median urinary CA 19-9 levels were significantly greater in children who underwent pyeloplasty than in both the non-obstructive hydronephrosis (143 ± 38 vs. 68 ± 23, respectively; p = 0.007) and the healthy control groups (143 ± 38 vs. 13 ± 3, respectively; p = 0.001) (Figure). Three months after surgery, the urinary CA 19-9 levels had decreased significantly according to the preoperative levels in the pyeloplasty group (143 ± 38 vs. 55 ± 16, p = 0.039). In both the pyeloplasty and NOD groups, there was a correlation of urinary CA 19-9 levels with differential renal function and a correlation of serum CA 19-9 levels with the initial anteroposterior pelvic diameter. Receiver operator characteristic (ROC) analysis revealed a better diagnostic profile for the urinary CA 19-9 level than for the serum CA 19-9 level in terms of identifying obstruction in the hydronephrosis groups (areas under the curve = 0.8 and 0.7, respectively). The best cut-off value of for urinary CA 19-9 was 85.5 U/mL with 76% sensitivity, 85% specificity. The negative predictive value was 80%. DISCUSSION: The results suggest that voided urine CA 19-9 levels seems to be a more useful marker than serum CA 19-9 in obstructive dilatation. An appropriate decrease in urinary CA 19-9 levels after pyeloplasty may be used as a predictor of surgical outcome. In addition, the results have a number of important diagnostic implications that should be further validated in a larger study population. CONCLUSIONS: Based on these results, we suggest that a high urinary CA 19-9 level is a non-invasive clinically applicable marker for differentiating between obstruction and non-obstructive dilatation.

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OBJECTIVES: Although the glycoprotein group tumor marker CA 19-9 has been detected in both serum and urine of bladder cancer patients, information about their comparative role in screening of low grade transitional cell carcinoma (LGTCC) and high grade transitional cell carcinoma (HGTCC) is rare. MATERIALS AND METHODS: In this study we measured both the urinary and serum levels of CA 19-9 in 35 LGTCC and 20 HGTCC patients by ELISA and determined the cut off value of both urinary and serum CA 19-9 levels by receiver operator characteristic curve (ROC) for both patient groups. Odds ratio (OR) for CA 19-9 was analyzed with its range at 95% confidence interval to analyze the role of this tumor marker as a screening parameter for both of these cancer types. RESULTS: For urinary CA 19-9 the OR was 20.16 with an interval of 4.91-82.71 whereas for the serum CA 19-9 it was 7.5 with an interval of 2.28-24.62. CONCLUSIONS: From these data we suggest that urinary CA 19-9 is a better screening parameter with optimum sensitivity and specificity than its serum counterpart for diagnosis of low grade and early stages of transitional cell carcinoma of urinary bladder. Furthermore, it can be suggested that urinary CA 19-9 can be used as better prognostic marker for LGTCC than its serum counterpart.

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PURPOSE: To diagnose the urothelial carcinoma of the bladder by measuring CA19-9 level in the urine. MATERIALS AND METHODS: This study was conducted on 47 patients with histopathologically confirmed urothelial cancer and 50 control subjects. The urinary level of CA19-9 was measured in both groups by enzyme-linked immunosorbent assay after concentration of urine with Bio-Gel dry beads. Urine cytology was also done in both controls and patients. RESULTS: The mean urinary level of CA19-9 was 194.59 ± 110.56 u/mL in patients and 11.67 ± 8.42 u/mL in controls (P = .0001). The mean urinary level of CA19-9 in patients with low-grade and high-grade bladder cancer was 206.56 ± 114.56 u/mL and 174.80 ± 94.06 u/mL, respectively (P = .56). Urine cytology by Papanicolaou stain was mostly negative. CONCLUSION: It can be concluded that CA19-9 may be a useful non-invasive test to diagnose the urothelial carcinoma of the bladder.

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PURPOSE: We evaluated the predictive role of serum and urinary carbohydrate antigen 19-9 in the diagnosis and followup of pediatric ureteropelvic junction obstruction. MATERIALS AND METHODS: The study included 27 children with ureteropelvic junction obstruction who underwent pyeloplasty (group 1), and 41 controls consisting of 27 healthy children (group 2) and 14 children with hydrocele/renal cyst (group 3). Serum and voided urine were evaluated for carbohydrate antigen 19-9 in each group. Additionally urine from the affected pelvis and fluid in hydrocele/renal cyst were collected at surgery in groups 1 and 3. Serum and voided urine samples were obtained at 3, 6 and 9 months after pyeloplasty for carbohydrate antigen 19-9 assessment, and were correlated with clinical factors. RESULTS: Preoperative carbohydrate antigen 19-9 level was significantly greater in group 1 than in controls. The best cutoff values for serum and urinary carbohydrate antigen 19-9 were 13.21 U/ml and 30.6 U/ml, respectively, with significantly higher sensitivity and specificity for urinary values. Obstruction release was followed by improvement of renal function together with significant reduction in urinary and serum carbohydrate antigen 19-9 at 3 months. Initial pelvis diameter and renographic function significantly correlated with urinary carbohydrate antigen 19-9. No significant correlation was found regarding serum carbohydrate antigen 19-9. CONCLUSIONS: Voided urine carbohydrate antigen 19-9 is a noninvasive, clinically applicable marker in congenital obstructive nephropathy. The practical implications of these data for diagnosis and long-term followup in ureteropelvic junction obstruction are significant. Our findings suggest that proper decrease in urinary carbohydrate antigen 19-9 after pyeloplasty is predictive of excellent surgical outcomes and resolution of renal damage.

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OBJECTIVES: This study evaluated the clinical significance of urinary CA19-9 levels in bladder cancer patients classified according to various combinations of Lewis (Le) and Secretor (Se) genotypes. METHODS: Urinary CA19-9 and DU-PAN-2 levels were measured as units per mg creatinine (U/mg Cr) in 121 patients with bladder cancer and in 31 patients with other urologic diseases. Genotyping was carried out using polymerase chain reaction-based methods. RESULTS: Urinary CA19-9-values in patients with both Le and Se alleles (Le/Le, Se/Se; Le/Le, Se/se; Le/le, Se/Se; Le/le, Se/se) were significantly higher (P < 0.0001) in bladder cancer cases compared to the other urologic diseases. The cut-off value determined using receiver operating characteristics analyses was 37.6 U/mg Cr. Approximately 70% (57/87) of bladder cancer patients with both Le and Se alleles demonstrated urinary CA19-9 levels over the cut-off value. In contrast, only 16% (4/24) of patients with other urologic diseases were over the cut-off value. CONCLUSIONS: The urinary CA19-9 level can be a new effective diagnostic tool in bladder cancer patients with both Le and Se alleles.

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OBJECTIVE: The aim of this study was to find out the predictive role of serum and urinary carbohydrate antigen 19-9 levels in benign hydronephrosis and whether these levels are helpful for differentiation of complete or partial urinary obstruction. MATERIALS AND METHODS: Fifty-four patients with, and 23 without, benign hydronephrosis were enrolled in this study. Serum and urinary carbohydrate antigen 19-9 were determined by the chemiluminescence enzyme immunometric assay method and these levels were correlated with clinical factors. RESULTS: The mean serum (P < 0.0001) and urinary (P < 0.0001) carbohydrate antigen 19-9 and serum creatinine (P < 0.008) levels were significantly higher in the hydronephrosis group than the control group. There was significant correlation between serum and urinary carbohydrate antigen 19-9 levels in the hydronephrosis group (r = 0.639, P < 0.0001). In the hydronephrosis group, there were no significant differences between the serum creatinine, serum or urinary carbohydrate antigen 19-9 levels and the clinical features except symptom duration. The best cut-off value for the serum and urinary carbohydrate antigen 19-9 were found to be 4.84 U/mL and 29.35 U/mL, respectively. CONCLUSION: Serum and urinary carbohydrate antigen 19-9 levels correlated with each other, were significantly elevated in patients with hydronephrosis and did not predict complete urinary obstruction. Benign hydronephrosis should be considered in the differential diagnosis of carbohydrate antigen 19-9 increments, as this is what is of most importance in clinical practice.

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We investigated the use of genotype-interpreted measurements of the tumor marker Ca 19-9 in the urine of bladder cancer patients as a marker of the extent of urothelial disease. Ca 19-9 in urine (sialyl-Le(a)/creatinine ratio) was measured in 81 bladder cancer patients and correlated to T-category, histologic grade, and presence of urothelial dysplasia. As reference group, Ca 19-9 ratio was measured in urine from 21 apparently healthy individuals. The amount of sialyl-Le(a) expressed is influenced by the Lewis genotype and secretor status. Accordingly, secretor status was determined in urine by a novel ELISA method, and the Lewis genotypes of all of the individuals were determined by PCR cleavage methods. Ca 19-9 concentrations in urine were higher (P < 0.01) in bladder cancer patients than in healthy individuals and significantly (P = 0.02) higher in cancer patients with concomitant urothelial dysplasia than in those with normal urothelium. For individuals Lewis-genotyped as homozygous wild-type, Ca 19-9 concentrations in urine were higher, both in cancer patients (P = 0.06) and in healthy individuals (P = 0.004), than in the heterozygous individuals. Furthermore, nonsecretor cancer patients had higher (P < 0.01) Ca 19-9 concentrations in urine. Attention is drawn to the possibility of a general genotype interpretation of a result in clinical chemistry.

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BACKGROUND: Although Carbohydrate antigen19-9 (CA19-9) is known to be high of its positive rate in blood in pancreatic cancer, etc., recently there have been scattered of cases of urothelial carcinoma in which elevated CA19-9 levels have been detected in both serum and urine. In this study we determined both urine and serum levels of CA19-9 in order to evaluate their diagnostic role of urinary CA19-9. MATERIALS: A total 82 patients, i.e., 32 with bladder cancer, 4 with renal pelvic/ureteral cancer, 5 with renal cancer, 13 with prostatic cancer, 5 with other malignancies, 10 with prostatic hyperplasia, 6 with urolithiasis, 7 with other benign diseases, served as the subjects of this study. METHODS: CA19-9 was determined by EIA method in first-morning urine and serum using a CA19-9 measurement kit (Centocor). Urinary values corrected for the creatinine level in the same sample have been used and are shown as U/mg creatinine (Cr). Urinary CA19-9 and urinary cytology were evaluated in some cases. An immunohistochemical study of CA19-9 for surgical specimens was conducted by the ABC method, using a Histo 19-9 kit (COMPAGNIE ORIS INDUSTRIES S.A.). RESULTS: The cut-off value for serum levels was 37 U/ml, and urine levels were determined in U/mg Cr with a cut-off value of 100 U/mg Cr. The urinary CA19-9 levels was significantly higher (390.9 +/- 934.1 U/mg Cr) in urothelial cancer than in the control group (91.48 +/- 20.0 U/ mg Cr). In urothelial cancer, grade 1 and grade 2 cases were more sensitive than grade 3 cases and they also tended to be high level, although only 27.8% of urothelial cancer patients showed an elevation of serum CA19-9. CA19-9 was detected in all urothelial cancers which could be studied immunohistochemically. In 8 out of 16 superficial cancers CA19-9 was detected in more than 90% of cancer cells, though there were few CA19-9 positive cells in infiltrating cancers. Urinary CA19-9 was more sensitive than urinary cytology, especially in low grade cancers. CONCLUSION: The determination of urinary CA19-9 may be a useful tumor marker of urothelial cancer, and especially in low grade cancer it may be useful in diagnosing of them because its urinary level is high and it is more sensitive than urinary cytology.

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