HER-2 immunohistochemical expression as prognostic marker in high-grade T1 bladder cancer (T1G3).

OBJECTIVES: To evaluate if the Human epidermal growth factor receptor 2 (HER-2) expression levels may be used as potential prognostic marker in high grade T1 blad- der cancer (T1G3) METHODS: Specimens from transurethral resection of bladder tumour (TURBT) of 103 patients with high-grade T1 bladder cancer were collected. This pathologic database was reviewed. Four-year follow-up data were matched with pathologic data. Eighty-three patients entered the study. HER-2 staining was performed. Patients were grouped for HER-2 status. Statistical analysis included Kaplan Meier survival analysis and Log-rank test. RESULTS: Pathological review of TURBT specimens confirmed high-grade T1 transitional cell bladder cancer in all patients. Median follow-up was 12 months (mean 23,5; range 3-48). Twenty-one patients (25.4%) present strong HER-2 expression (3+), 28 (33.7%) moderate expression (2+), 26 (33.7%) weak staining (1+) and 8 (9.6%) negative expression (0). Thirty- one patients of 83 (37.4%) had not evidence of disease, 41 (49.4%) recurred, 11 (13.2%) had a progression of disease. Forty-one patients had high grade T1 recurrence. Patients with HER-2 status 0 did not showed progression of disease. Patients with HER-2 status 3+, undergoing cys- tectomy because progression of disease, had a pathological stage > pT2 and a nodal involve- ment. Median Disease-Free Survival (DFS) for all patients was 12 months (DFS probability (pDFS) = 49.3%; 95% CI, -11.1/+10.1). Median DFS in HER-2 groups was 8 (pDFS 37.5%; 95% CI,-28.8/+29.9), 24 (pDFS 46.1%; 95% CI,-19.5/+17.5), 20 (pDFS 46.4%; 95% CI,-18.8/+16.9) and 10 months (pDFS 47.6%; 95% CI,-21.9/+19.1) respectively in HER-2 status 0,1+,2+,3+. Log-Rank test is not statistically significant (p = 0,39). CONCLUSIONS: This study showed that HER-2 expression does not represent a prognostic mark- er of recurrence/progression of disease in high-grade T1 bladder cancer.

Bradeion (SEPT4) as a urinary marker of transitional cell bladder cancer: a real-time polymerase chain reaction study of gene expression.

PURPOSE: We evaluated whether Bradeion/SEPT4 gene expression could be used as a potential urinary marker to diagnose bladder transitional cell carcinoma. MATERIALS AND METHODS: From 2005 to 2007 we collected urine samples from 58 individuals, 17 healthy controls and 41 patients in whom bladder tumors were previously diagnosed by cystoscopy. Urine was collected from all patients before transurethral resection of bladder tumor. We performed real-time reverse transcriptase-polymerase chain reaction to evaluate Bradeion/SEPT4 transcript levels using urine sample mRNA. Statistical analysis was done with the Mann-Whitney test and ROC curves. RESULTS: Pathological examination of bladder tumor specimens revealed transitional cell bladder cancer. According to the 2002 TNM classification stage was Ta in 11 patients, T1 in 18 and T2/T3 in 12. All patients had G2 or G3 tumors according to the 1973 WHO grade classification. Relative quantification analysis of Bradeion transcript showed significantly increased levels compared to controls, namely 21.85 times higher in Ta stage tumors, 7.21 times higher in T1 tumors and 4.36 times higher in grade T2/T3 tumors. We compared each tumor stage group with the control group using the Mann-Whitney test to verify the statistical significance of observed differences. The ROC curve built on the change in threshold cycle revealed that with this method we attained 92.68% sensitivity and 64.71% specificity (AUC 0.798, p=0.0001). CONCLUSIONS: Bradeion/SEPT4 transcript levels are significantly increased in patients with transitional cell bladder cancer compared to healthy controls. Our preliminary study supports the possible usefulness of Bradeion as a urinary marker of urothelial disease.

Postoperative nomogram for invasive bladder cancer: does it really work? A multicenter cohort study.

OBJECTIVES: Nomograms are statistical models designed to maximize predictive accuracy. We have tested the statistical correlation between the predictions of International Bladder Cancer Nomogram Consortium and the clinical outcomes in a multicenter Italian cohort of patients treated with radical cystectomy (RC) and pelvic lymph-nodes dissection. METHODS AND MATERIALS: Two hundred four patients who underwent RC were selected for multiple variable and then enrolled in the study. Patients were tested by the "online tool" based on the nomogram, then stratified and risk grouped for 5-year predicted disease-free survival (pDFS): low risk (67%-100%), intermediate risk (34%-66%), and high risk group (0%-33%). Receiving operating characteristic curve (ROC) quantified the area under curve (AUC) as predictive accuracy. Actual overall survival (aOS) and actual disease-free survival (aDFS) were calculated with Kaplan-Meyer analysis. Median of pDFS was compared with 5-year aDFS. RESULTS: AUC was 0.69 (P < 0.001). The aOS is 50% (95% confidence interval (95% CI, -7.68/+8.23) at 5-years after RC, the aDFS is 65.5% (95% CI, -7.56/+8.98). The 5-year aDFS is 75.3% (-8.82/+12.53) in low risk group; 67.3% (-12/+16.4) in intermediate risk group; 28.3% (-20/+17.2) in high risk group. The 5-year aDFS was well calculated by the nomogram but in all groups the nomogram slightly underestimated the prediction. In intermediate risk group, 5-year aDFS overscored both the nomogram pDFS and the pDFS range of this group (34%-66%). In all patients investigated, the pDFS was 65%, a value close to the 5-year aDFS found (65.6%). CONCLUSION: Statistical correlation between postoperative nomogram prediction and the clinical reality was observed.

Calcium oxalate nephrolithiasis: urinary "medium size peptides"analysis using MALDI-TOF mass spectrometry.

OBJECTIVE: Urinary lithiasis is one of the most common benign urological diseases. The pathogenic mechanisms of renal stone formation are complex and not clearly defined. We have studied the urinary protein composition of patients affected by calcium oxalate (CaOx) nephrolithiasis in a range of molecular weight between 1 and 5 kDa (medium size peptides). These molecules seem to have a double role in limiting the crystal adhesion to renal cells and at the same time in facilitating the degradation of crystals once internalised in cells. Their daily excretion is high, approximately 2-7 mg/die, even if studies have reported higher values. Our aim in surveying the urinary peptides was to look for qualitative difference in the medium size range, possible indication of the presence of a biomarker or any predisposing factors in patients affected by calcium oxalate nephrolithiasis. MATERIALS AND METHODS: The urinary protein composition of 17 patients (11 male, 6 female; mean age 45 yrs +/- 14SD) affected by CaOx nephrolithiasis was assessed in comparison with 17 healthy subjects. It was performed a qualitative assay using MALDI-TOF mass spectrometry (MS) in a range of molecular weight between 1 and 5kDa (medium size peptides). RESULTS: No differences were detected in the mass spectrums between patients and control subjects: all peaks overlapped. In addition, the values of peak intensity were comparable in both patient and control subject mass spectrums. CONCLUSIONS: In the range of molecular weight between 1 and 5 kDa, we have not detected significant differences in the urinary composition between stone former patients and healthy subjects. Our results warrant further research in different molecular size peptides.

Human factors in surgery: from Three Mile Island to the operating room.

Human factors is a definition that includes the science of understanding the properties of human capability, the application of this understanding to the design and development of systems and services, the art of ensuring their successful applications to a program. The field of human factors traces its origins to the Second World War, but Three Mile Island has been the best example of how groups of people react and make decisions under stress: this nuclear accident was exacerbated by wrong decisions made because the operators were overwhelmed with irrelevant, misleading or incorrect information. Errors and their nature are the same in all human activities. The predisposition for error is so intrinsic to human nature that scientifically it is best considered as inherently biologic. The causes of error in medical care may not be easily generalized. Surgery differs in important ways: most errors occur in the operating room and are technical in nature. Commonly, surgical error has been thought of as the consequence of lack of skill or ability, and is the result of thoughtless actions. Moreover the 'operating theatre' has a unique set of team dynamics: professionals from multiple disciplines are required to work in a closely coordinated fashion. This complex environment provides multiple opportunities for unclear communication, clashing motivations, errors arising not from technical incompetence but from poor interpersonal skills. Surgeons have to work closely with human factors specialists in future studies. By improving processes already in place in many operating rooms, safety will be enhanced and quality increased.

Is extracorporeal shock wave lithotripsy in pediatrics a safe procedure?

Removal of urinary calculi is an essential element in the successful treatment of patients with urinary stone disease. The new generation of lithotriptors allows the treatment without the need for general anesthesia. The patients, often outpatients, have a faster discharge from the hospital with a reduction of hospitalization time and operating costs. Shock wave lithotripsy (SWL) is currently considered a safe technique for treatment of pediatric urinary lithiasias, with a low percentage of complications and subsequent surgical retreatments. But can we define SWL as a safe procedure in pediatrics? Herein, we will review the literature to justify SWL safety in children, focusing on important parameters as the insertion of preoperative stenting, side effects, and complications after the procedure.

Extracorporeal shockwave lithotripsy in pediatrics.

Since its introduction in 1980, extracorporeal shockwave lithotripsy (SWL) has become the first therapeutic option in most cases of upper-tract urolithiasis, and the technique has been used for pediatric renal stones since the first report of success in 1986. Lithotripter effectiveness depends on the power expressed at the focal point. Closely correlated with the power is the pain produced by the shockwaves. By reducing the dimensions of the focus, it becomes possible to treat the patient without anesthesia or analgesia but at the cost of a higher re-treatment rate. Older children often tolerate SWL under intravenous sedation, and minimal anesthesia is applicable for most patients treated with second- and third-generation lithotripters. Ureteral stenting before SWL has been controversial. Current data suggest that preoperative stent placement should be reserved for a few specific cases. Stone-free rates in pediatric SWL exceed 70% at 3 months, with the rate reaching 100% in many series. Even the low-birth-weight infant can be treated with a stone-free as high as 100%. How can one explain the good results? Possible explanations include the lesser length of the child's ureter, which partially compensates for the narrower lumen. Moreover, the pediatric ureter is more elastic and distensible, which facilitates passage of stone fragments and prevents impaction. Another factor is shockwave reproduction in the body: there is a 10% to 20% damping of shockwave energy as it travels through 6 cm of body tissue, so the small body volume of the child allows the shockwaves to be transmitted with little loss of energy. There are several concerns regarding the possible detrimental effect of shockwaves on growing kidneys. Various renal injures have been documented with all type of lithotripters. On the other hand, several studies have not shown adverse effects. In general, SWL is considered to be the method of choice for managing the majority of urinary stones in children of all ages. Re-treatments improve the stone-free rate, often raising it to 100%. Among the predictors of success, stone size seems to be the most important. In the absence of guidelines, selecting the appropriate treatment modality for each child requires planning and depends on instrument availability and local expertise.

New therapeutical approaches for non muscle invasive bladder cancer.

Non muscle invasive bladder cancer, given its high tendency to recur, coupled with an ever-present possibility to progress to potentially life-threatening muscle-invasive disease, remains a challenging clinical problem. Optimal management begins with early detection and accurate risk assessment through careful attention to clinical and histology features. Prevention of recurrence requires the sequential application of tools to completely remove all visible disease, avert reimplantation during surgical resection, ablate microscopic foci and prevent the emergence of new primary tumors amidst a field of carcinogen-exposed urothelium. Previously standard adjunctive intravesical chemo-immunotherapies are obtaining new vitality as optimization strategies, while new drugs and rational drug combinations provide the potential for improved efficacy with reduced toxicity. Novel therapeutic modalities under investigation include activation of the host immune system and enhancement of the cytotoxic effects of chemotherapeutic agents. New technological advances such as microwave chemothermotherapy offer further hope for better outcomes even for disease previously refractory to conservative measures. While much of this research is in the preclinical phase, the encouraging results of many of the studies discussed here suggest that testing in human trials should follow in the coming years. Yet despite these advances, aggressive surgical management involving bladder removal continues to be an indispensable life-saving maneuver that must be considered in all high-risk cases that fail to promptly respond to other measures. Although great strides continue to be made each year in the diagnosis and management of bladder cancer considerably more work needs to be done in order to improve the lives of our patients with this disease.

Could be ureteral endometriosis considered a symptomatic and severe urological disease?

Ureteral endometriosis is a rare localization of gynecological disease. We presented a case of left ureteral endometriosis in a 30-year-old woman with left abdominal pain and a radiological nonfunctioning kidney. Surgical treatment with ureteral resection and uretero-uretero anastomosys was conducted. Pathological examination of surgical specimen revealed endometriosis. The diagnosis of ureteral endometriosis should be considered in women with renal symptoms of noncalculous obstruction, particularly in premenopausal women with an anamnesys of polycistic ovary disease (POD) or severe menstrual related symptoms, although the disease is often strictly associated with silent renal obstruction. Only a high index of suspicion and the radiological support may help the urologist to obtain a early diagnosis. Early detection and prompt treatment strategy, surgical too, are extremely important to relieve symptoms and preserve renal function. The literature was reviewed.