Transrectal ultrasonography for staging tumors of the urinary bladder

Transurethral ultrasonography appears to help the urologist stage transitional cell tumors of the bladder. On the basis of the depth of invasion, one can determine whether transurethral resection of tumors will be adequate or whether segmental resection or cystoprostatectomy is required. The adequacy of transurethral resection of tumors can be monitored by comparing the depth of resection with the initial ultrasound examination. Pelvic lymph nodes cannot be assessed by transurethral ultrasound, and therefore CT, MRI, or lymphangiography must be used as well. Currently, CT scanning is the preferred modality because it is noninvasive, simple, inexpensive, and widely available. Other pelvic disorders, including gynecologic disease and neoplasms of gastrointestinal, neural, or bony origin, also may be assessed by transurethral ultrasonography, although experience with its use for these purposes is limited.     

The muscularis mucosae of the human urinary bladder. Implications for tumor staging on biopsies.

The human urinary bladder wall is traditionally described as being without a muscularis mucosae. A consecutive one year material of 772 bladder biopsies from 171 patients were examined for the proposed presence of lamina muscularis mucosae (MM). MM was observed in 15% of the biopsies and in 35% of the patients and graded into three patterns according to its continuity. Biopsies with transitional cell carcinomas were reviewed in order to find out whether MM-positive biopsies had been staged correctly. The data are discussed in relation to earlier studies on the subject.     

Value of multiparametric magnetic resonance imaging for local staging of invasive urinary bladder tumours.

BackgroundInitial tumour staging in bladder cancer mainly relies on the histo-pathological outcome of the transurethral bladder tumour resection (TURBT) and imaging by means of a CT-scan (CT-intravenous urography; CT-IVU). The reported risk of understaging varies from 24-50%. To further improve the the evaluation of depth of invasion of the bladder tumour the application of magnetic resonance imaging (MRI) may be useful. To substantiate the additional value of this imaging modality the present observational study was designed.Study designThis is a prospective observational study to analyse bladder tumour staging with multiparametric magnetic resonance imaging (mpMRI) in patients with a known bladder tumour, who are planned for radical cystectomy.Study populationPatients with an invasive bladder cancer who are planned for radical cystectomy.InterventionPatients were accrued during their visit to the outpatient department of urology. They underwent routine cystoscopy, laboratory tests (including serum Creatinin) and CT-IVU investigations and subsequently a mpMRI.Main study parameters/endpointsTo demonstrate the value of mpMRI in the initial staging of bladder tumours using radiological bladder tumour stage (T-stage) based on mpMRI and pathological bladder tumour stage based on ‘whole-mount’ histo-pathology after radical cystectomy.ResultsThirty-seven participants with known bladder tumours underwent mpMRI and subsequent cystectomy. After mpMRI 10 participants were diagnosed with non-muscle-invasive bladder cancer (NMIBC) and 27 participants with muscle-invasive bladder cancer (MIBC). In the ‘whole-mount’ pathology results 12 participants had NMIBC and 25 participants had MIBC. We found a sensitivity and specificity of 0.88 en 0.58 respectively, for the evaluation of MIBC. The positive and negative predictive value were 81% and 70% respectively. The diagnostic accuracy of mpMRI to differentiate between NMIBC and MIBC was 78%.ConclusionsWe found a sensitivity of 88% and a specificity of 58% for mpMRI to discriminate NMIBC from MIBC.     

Evidence of progesterone receptors in the mucosa of the urinary bladder.

OBJECTIVE: To investigate whether progesterone receptors are present in the mucosa of the urinary bladder of continent premenopausal women compared with continent postmenopausal women. MATERIALS AND METHODS: Fifty-seven biopsies from the mucosa of the trigone and lateral wall of the urinary bladder were examined by the avidin-biotin-peroxidase immunohistochemical technique for the presence of estrogen and progesterone receptors. The specimens were obtained at cystoscopy performed to investigate hematuria in 42 patients and neoplasia in 15. The study group (n = 29) comprised non-pregnant premenopausal women in the luteal phase of their menstrual cycle and the control group (n = 28) comprised postmenopausal women. None of the subjects had urinary incontinence or was taking medication with hormones. In no case did the primary lesion involve the specimen used for laboratory analysis. RESULTS: There was positive immunostaining with estrogen in 28 patients of the study group (96.5%) and 4 (14.4%) in the control group (p<0.0001). The 28 samples of the study group also showed positive immunostaining for progesterone receptors. There was positive immunostaining with progesterone in 18 samples (64.3%) of the control group (p<0.01). Fourteen samples (50%) of the control group thus showed positive immunostaining for progesterone but no evidence of positive immunostaining with estrogen. Immunostaining for estrogen and progesterone receptors was similar in trigonal and lateral wall samples. CONCLUSION: In continent pre- and post-menopausal women, a direct progestogenic effect on the mucosa of the urinary bladder seems likely in addition to estrogen.     

Stress proteins and cytokines are urinary biomarkers for diagnosis and staging of bladder cancer

Background

Cancer often involves inflammatory processes. We hypothesized that immune mediators in urine may serve as biomarkers for bladder cancer (BCa).

Objective

To investigate whether BCa might be marked by urinary levels of heat shock proteins (HSPs; HSP60, HSP70, or HSP90) or cytokines (interferon [IFN]-γ, tumor necrosis factor [TNF]-α, tumor growth factor [TGF]-β, interleukin [IL]-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, or IL-13).

Design, setting, and participants

This was a case–control study with a discovery and validation phase. We examined urine from 106 consecutive patients: healthy controls (n = 18); hematuria with no evidence of BCa (n = 20); non–muscle-invasive BCa (n = 50); and muscle-invasive BCa (n = 18). The concentrations of HSPs and cytokines were assessed by enzyme-linked immunosorbent assay. In the validation phase, independent urine samples from 40 patients were analyzed (controls [n = 19] and BCa [n = 21]).

Measurements

We used the area under the curve (AUC) of a receiver operating characteristic analysis to determine the ability of HSPs and cytokines to mark BCa and applied a multivariate logistic regression to create a formula able to diagnose BCa. The formula was applied to the validation set without recalculation, and positive and negative predictive values were calculated.

Results and limitations

Urinary concentrations of IL-8, IL-10, and IL-13 were significantly elevated in BCa; IL-13 was the most prominent marker (AUC: 0.93; 95% confidence interval [CI], 0.85–0.99). The multivariate regression analysis highlighted HSP60 (odds ratio [OR]: 1.206; 95% CI, 1.041–1.397, p = 0.003) and IL-13 (OR: 1.020; 95% CI: 1.007–1.033, p = 0.012).The validation assay was performed using HSP60 and IL-13. The overall positive predictive value was 74% (95% CI, 64–84%); and the negative predictive value was 76% (95% CI, 66–86%). Since we examined a small number of patients, the results need to be confirmed in a larger cohort.

Conclusions

These results suggest that it might be possible to develop a urinary biomarker for BCa and raise the possibility that expression of anti-inflammatory cytokines and HSPs might allow BCa to evade immune surveillance.     

Diagnosis and staging of bladder cancer.

The need for prompt diagnosis and accurate staging of bladder cancer cannot be over-emphasized, as delays in diagnosing the tumor are clearly associated with a poor prognosis. Accurate staging using the American Joint Committee system is essential if clinicians are to compare the results of different therapies.     

Gadolinium-enhanced magnetic resonance imaging in the staging of urinary bladder neoplasms

Magnetic resonance imaging (MRI) proved to be an important diagnostic tool in the correct staging of bladder neoplasms. The advantage of multiplane imaging and high soft-tissue contrast may be extended by the use of MRI contrast media such as the gadoliniumdiethylene-triaminepentaacetic acid complex. In 60 patients with suspected or proved bladder tumors, the results of preoperative gadolinium-enhanced MRI were correlated with the histopathologic findings. The staging accuracy of infiltrating tumors was 83% and sensitivity and specificity 86% and 83%, respectively. Three tumors could only be localized after administration of gadolinium. All active tumors demonstrated significant contrast enhancement after intravenously injected gadolinium. Small papillary tumors or carcinoma in situ remain problematic to preoperative staging procedures. The advantages of gadolinium-enhanced MRI will best be employed in the exact pretherapeutic staging of infiltrative bladder neoplasms or in restaging procedures after chemotherapy and radiotherapy.     

Immunophenotypic characterization of the bladder mucosa infiltrating lymphocytes after intravesical BCG treatment for superficial bladder carcinoma.

The lymphocytes infiltrating the bladder mucosa of 28 patients treated with bacillus Calmette-Guérin (BCG) for superficial bladder carcinoma were characterized using an immunohistochemical technique on frozen sections of biopsy specimens obtained during cystoscopy. The inflammatory response induced by BCG consisted mainly of T lymphocytes (CD3+), most of which had the helper/inducer phenotype (CD4+), with a CD4/CD8 ratio greater than 1. A minor subset of lymphocytes were of B phenotype (CD22+). These findings persisted for the whole follow-up period (6-12 months) in spite of a progressive decrease of the inflammatory infiltrate. No difference in the lymphocyte phenotype was observed between nonresponding patients and those who responded to BCG in the short term. It is concluded that, although intravesical BCG therapy does affect the immunocompetent cells of the bladder wall, the BCG-induced antitumor activity is unlikely to depend exclusively on a local immune mechanism.     

Eicosanoid synthesis by human urinary bladder mucosa: pathological implications

Biopsies of human urinary bladder mucosa obtained during cystoscopy were shown to release eicosanoids in the following order: prostacyclin (PGI2), prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha) and thromboxane A2 (TXA2). The total and the relative amounts of eicosanoids released were similar to those reported for the rat urinary bladder. These eicosanoids may play a role in modulating the tone and contractility of the bladder as well as affecting cytoprotection of the mucosa. In view of the abundant release of eicosanoids by the bladder, caution must be exercised when considering urinary eicosanoid excretion as reflecting production by the systemic vasculature and/or the kidneys.     

Distension treatment of the urinary bladder

Three patients were treated with hydrostatic pressure therapy (bladder distension) for different pathology, two with success, and one without effect. On the basis of preliminary results authors suggest the procedure in selected cases.     

Radiation treatment of urinary bladder carcinoma

Summary A series of 602 patients with verified urinary bladder cancer have been treated with full irradiation in the period 1957–1970. As expected, the survival rate decreased with increasing stage of the tumour. Another group was randomized and treated according to either of two fractionation schemes. This trial started in 1971 and shows that there is increased survival and tumour clearance rate with superfractionation.     

Surgical treatment of urinary bladder cancer

Ultrasonic transabdominal and transrectal investigations, computed tomography, endoscopic photodynamic studies, polyfocal biopsy of the urinary bladder were used in examination of 1238 patients which were diagnosed to have urinary bladder cancer. 894 patients underwent transurethral resection of the bladder. Morphologically, cancer of the urinary bladder has an inductory effect on intact parts of the bladder mucosa. This means that even most radical resection does not eliminate grounds for a new tumor growth. Radical cystectomy was performed in diffuse papillomatosis, multiple stage T2 tumors of high-grade malignancy, tumors at stage T3, T4, Nx, MO, in rapid recurrent tumors after conservative or operative treatment.     

Percutaneous transabdominal whole layer core needle biopsy for staging the urinary bladder cancer]

Accurate staging is one of the most important determinants necessary in planning an effective treatment for bladder cancer, but at the present time, staging by the conventional clinical methods are not completely reliable. Accordingly, we have newly developed a percutaneous transabdominal core needle biopsy technique capable of obtaining good cylindrical specimens of the entire layer. In order to obtain the core specimen of the bladder wall, which is a vesico-elastic material, the biopsy needle must penetrate the bladder wall at an extremely high speed. We have developed an original automatic biopsy instrument and modified the head of needle for this purpose. With this method, we could obtain good core specimens for pathological staging in about 90% cases. The correlation between the pathological stagings of core specimens and those of cystectomy specimens were in good agreement. This technique is accurate not only for preoperative pathological staging, but also monitoring histopathologically the responsiveness of multi-disciplinary treatment for invasive bladder cancer. This method allows us to determine the optimal therapeutic modality for managing individual patient with invasive bladder cancer.     

Lymph node staging for urinary bladder carcinoma with positron emission tomography (PET)

PET is a new method in nuclear medicine which examines the metabolism and not the morphology. Tumors show a higher rate of glycolysis than benign tissue and hence can be detected by radioactive glucose. This method has proved good for various tumors. In this study the lymph node staging of bladder cancer by PET was investigated. In 64 patients a PET of the pelvis after injection of fluorodeoxyglucose (FDG) was carried out preoperatively; the PET-results were compared with the histology of the OR specimen after classical pelvic lymphadenectomy. For lymph node staging positive nodes were found in 14 patients which was correct; a false-negative result was obtained in 7 patients. In 37 patients the PET-result was true-negative and in 6 patients false-positive resulting in a sensitivity of 67 %, a specificity of 86 % and an accuracy of 80 %. Therefore, our PET results are encouraging and seem to be better than those obtained by classical staging procedures such as CT or MRI.     

Lymph node staging for urinary bladder carcinoma with positron emission tomography (PET)

Summary PET is a new method in nuclear medicine which examines the metabolism and not the morphology. Tumors show a higher rate of glycolysis than benign tissue and hence can be detected by radioactive glucose. This method has proved good for various tumors. In this study the lymph node staging of bladder cancer by PET was investigated. In 64 patients a PET of the pelvis after injection of fluorodeoxyglucose (FDG) was carried out preoperatively; the PET-results were compared with the histology of the OR specimen after classical pelvic lymphadenectomy. For lymph node staging positive nodes were found in 14 patients which was correct; a false-negative result was obtained in 7 patients. In 37 patients the PET-result was true-negative and in 6 patients false-positive resulting in a sensitivity of 67 %, a specificity of 86 % and an accuracy of 80 %. Therefore, our PET results are encouraging and seem to be better than those obtained by classical staging procedures such as CT or MRI.      

Regeneration of the canine urinary bladder mucosa after complete surgical denudation

To study the site of origin of epithelial regeneration in the urinary bladder after surgical denudation, we completely obliterated the bladder mucosa in 17 dogs, using the neodymium: YAG laser. Bladder-mapping studies showed that the regenerating cells arose from the epithelium of the terminal ureters and urethra. Experimental construction of isolated bladder pouches confirmed these findings and demonstrated that urine flow was not essential for reepithelialization. These results are relevant to the treatment of patients with multifocal carcinoma in situ of the bladder. Although the entire bladder can be denuded successfully, the studies demonstrate that the procedure might fail if the sources of epithelial regrowth, the distal ureters and urethra, contain untreated carcinoma in situ.