HER2/neu expression in bladder cancer: relationship to cell cycle kinetics.

BACKGROUND AND OBJECTIVES: The incidence of overexpression of HER2/neu in bladder cancer is one of the highest among all human malignancies tested; such overexpression is thought to play a role in the aberrant proliferation of cancer cells. This study was conducted to evaluate the quantitative assessment of HER2/neu expression by enzyme immunoassay (EIA) and its prognostic significance in differentiating between high and low proliferating tumors. PATIENTS AND METHODS: Tissue samples were collected from 35 patients with benign bladder lesions, 28 with bilharzial bladder cancer, and 25 with nonbilharzial bladder cancer. Twenty normal samples were obtained from normal safety margin areas in nonbilharzial bladder cancer patients. Out of the malignant samples, 22 were found to be squamous cell carcinoma and 31 were transitional cell carcinoma. All samples were examined for HER2/neu expression by EIA and Western blot (WB). Flow cytometric (FCM) analysis was also performed in all the samples provided. RESULTS: HER2/neu was found to be significantly overexpressed in the malignant group compared to the benign and normal groups (P < 0.001) and no significant difference was found between the bilharzial and nonbilharzial cancer groups or between the transitional and squamous cell carcinoma groups. HER2/neu was significantly correlated to ploidy (P = 0.001), synthetic phase fraction, SPF (P = 0.012), and DNA index (P = 0.002). No significant correlation was found between HER2/neu and stage or grade while it was significantly associated with lymph node status of the tumour (P = 0.02). CONCLUSION: HER2/neu can be measured reliably by the EIA method as confirmed by WB. The quantitative assessment of HER2/neu expression in malignant tumors aided by other proliferation markers such as SPF, DI, and ploidy could be useful in selecting patients for more aggressive treatment or for predicting outcome.

Diagnostic value of urinary molecular markers in bladder cancer.

OBJECTIVES: In an attempt to find a more sensitive and specific non-invasive diagnostic assay for the detection of bladder cancer cells, the authors assayed the exfoliated cells from patient's voided urine and bladder washing fluids for the presence of telomerase, an enzyme that maintains a cell's chromosomal length, metalloproteinase-9 (MMP-9), which has been associated with tumor cell invasion and metastasis. Their results were compared with both voided urine cytology (VUC) and bladder wash cytology (BWC) for the detection of bladder cancer cells. MATERIALS AND METHODS: The authors used preoperative voided morning urine samples from 110 subjects for telomerase, matrix metalloproteinase-9 (MMP-9) and cytology. Bladder wash samples were obtained for telomerase and cytology. Of 110 cases 73 were histologically diagnosed as bladder cancer, whereas the remaining 16 had benign urological disorders. A group of 21 healthy volunteers were also enrolled in this study. Cystoscopy was done for all patients as the reference standard for the identification of bladder cancer. Biopsy of any suspicious lesion was performed for histopathological examination. RESULTS: Receiver-operator characteristics (ROC) curves were used to determine the optimal threshold values for telomerase activity in urine, bladder wash and MMP-9 [0.05, 0.088 and 0.51 (ng/ml), respectively]. The levels and the positivity rates of telomerase activity and MMP-9 were significantly higher in the malignant group compared to either the benign group or normal controls. Bladder cancer patients with positive cytology revealed positive telomerase activity in urine, bladder wash, and MMP-9 in 92%, 87% and 61%, respectively. Also, these positive rates were significantly higher in bilharzial bladder cancer cases (88%, 89%, 69%, respectively) compared to non-bilharzial cases (50%, 62.5%, 50%). The overall sensitivity and specificity were 83% and 88.6%, 86.3% and 78.3% for telomerase activity in urine, and in bladder wash, respectively. 66.6% and 80% for MMP-9, 58.5% and 100% for voided urine cytology and 64.4% and 100% for bladder wash cytology. Combined sensitivity of VUC with the 2 biomarkers together was higher than either combined sensitivity of VUC with one of the biomarkers or than that of the biomarker alone. CONCLUSION: Urinary telomerase and MMP-9 had superior sensitivities over VUC; moreover, combined use of these markers increased the sensitivity of cytology from 58.46% to 95%. The higher sensitivities of markers in bilharzial bladder cancer than non-bilharzial type highlight their clinical utility in screening patients with urinary bilharziasis.

Perioperative renal protection in patients with obstructive jaundice using drug combinations.

BACKGROUND/AIMS: The effectiveness of dopamine alone or in combination with mannitol or furosemide in preventing postoperative renal dysfunction in patients with obstructive jaundice was assessed in this study. METHODOLOGY: Forty patients having obstructive jaundice were randomly allocated into 4 equal groups. Preoperative hydration was performed by infusing all patients 1L of 5% dextrose the night before surgery and another 1L in the morning before surgery. Intra- and postoperative maintenance of adequate intravascular volume was assured by fluid and blood replacement guided by the monitoring of central venous pressure urine output and blood pressure. The 1st group was kept as a control. The other 3 groups received dopamine 2.5 micrograms/kg/min for 2 postoperative days starting before surgery. The 2nd group was maintained on dopamine alone, while mannitol (0.25 g/kg), every 12 hours for 2 postoperative days, was added to the 3rd group. Similarly furosemide (1 mg/kg) every 12 hours for 2 postoperative days, was infused to the patients of the 4th group. Postoperative renal functions were assessed by 24-hour urine output, serum creatinine, creatinine clearance and urine to plasma osmolality ratio. RESULTS: All these tests did not show significant changes in the 1st, 2nd and 7th postoperative days. Only transient decreased creatinine clearance and elevated serum creatinine were observed in the patients of the 4th group in the 1st and 2nd postoperative days. This may be attributed to fluid imbalance induced by furosemide in these patients who were older than the other groups. CONCLUSIONS: The study showed that careful attention to perioperative hydration is the cornerstone in preserving adequate renal function following surgery in patients with obstructive jaundice. Administration of dopamine alone or in combination with mannitol or furosemide did not confer more renal protection.