Risk factors for residual disease at re-TUR in a large cohort of T1G3 patients.

INTRODUCTION AND OBJECTIVES: The goals of transurethral resection of a bladder tumor (TUR) are to completely resect the lesions and to make a correct diagnosis in order to adequately stage the patient. It is well known that the presence of detrusor muscle in the specimen is a prerequisite to minimize the risk of under staging. Persistent disease after resection of bladder tumors is not uncommon and is the reason why the European Guidelines recommended a re-TUR for all T1 tumors. It was recently published that when there is muscle in the specimen, re-TUR does not influence progression or cancer specific survival. We present here the patient and tumor factors that may influence the presence of residual disease at re-TUR. MATERIAL AND METHODS: In our retrospective cohort of 2451 primary T1G3 patients initially treated with BCG, pathology results for 934 patients (38.1%) who underwent re-TUR are available. 74% had multifocal tumors, 20% of tumors were more than 3 cm in diameter and 26% had concomitant CIS. In this subgroup of patients who underwent re-TUR, there was no residual disease in 267 patients (29%) and residual disease in 667 patients (71%): Ta in 378 (40%) and T1 in 289 (31%) patients. Age, gender, tumor status (primary/recurrent), previous intravesical therapy, tumor size, tumor multi-focality, presence of concomitant CIS, and muscle in the specimen were analyzed in order to evaluate risk factors of residual disease at re-TUR, both in univariate analyses and multivariate logistic regressions. RESULTS: The following were not risk factors for residual disease: age, gender, tumor status and previous intravesical chemotherapy. The following were univariate risk factors for presence of residual disease: no muscle in TUR, multiple tumors, tumors > 3 cm, and presence of concomitant CIS. Due to the correlation between tumor multi-focality and tumor size, the multivariate model retained either the number of tumors or the tumor diameter (but not both), p < 0.001. The presence of muscle in the specimen was no longer significant, while the presence of CIS only remained significant in the model with tumor size, p < 0.001. CONCLUSIONS: The most significant factors for a higher risk of residual disease at re-TUR in T1G3 patients are multifocal tumors and tumors more than 3 cm. Patients with concomitant CIS and those without muscle in the specimen also have a higher risk of residual disease.

The significance of calprotectin, CD147, APOA4 and DJ-1 in non-invasive detection of urinary bladder carcinoma.

Aim of the study is to define the diagnostic accuracy of selected urinary protein biomarkers in the non-invasive detection of primary and recurrent urothelial carcinoma of the urinary bladder. The urinary levels of calprotectin, CD147, APOA4 and protein deglycase DJ-1 were examined in 255 individuals, including 60 controls with non-malignant urological disease, 61 patients with a history of urinary bladder cancer with negative cytology and negative cystoscopy and 134 patients with urinary bladder cancer. Urinary concentrations of biomarkers were determined by Enzyme-Linked Immunosorbent Assay (ELISA). During the follow-up of patients with non-muscle invasive bladder cancer (NMIBC), a group of 44 patients with cancer recurrence was compared to the group of 61 patients with a history of NMIBC but with no evidence of disease. Urinary concentrations of the evaluated markers did not reveal any significant difference between these groups. During the primary diagnosis, a group of 90 patients with primary bladder cancer and 60 subjects with benign disease were compared. Urinary levels of CD147 were not significantly higher in patients with tumors. The greatest diagnostic accuracy was observed in APOA4 (sensitivity 55.6, specificity 83.3, AUC 0.75), and lesser in calprotectin (sensitivity 39.4, specificity 87.7, AUC 0.66) and in DJ-1 (sensitivity 61.1, specificity 66.7, AUC 0.64), respectively. Apolipoprotein A4 may be used potentially as a supplemental urinary marker in the diagnosis of primary bladder cancer.

Predictors of oncological outcomes in T1G3 patients treated with BCG who undergo radical cystectomy.

PURPOSE: To evaluate the oncological impact of postponing radical cystectomy (RC) to allow further conservative therapies prior to progression in a large multicentre retrospective cohort of T1-HG/G3 patients initially treated with BCG. METHODS: According to the time of RC, the population was divided into 3 groups: patients who did not progress to muscle-invasive disease, patients who progressed before radical cystectomy and patients who experienced progression at the time of radical cystectomy. Clinical and pathological outcomes were compared across the three groups. RESULTS: Of 2451 patients, 509 (20.8%) underwent RC. Patients with tumors > 3 cm or with CIS had earlier cystectomies (HR = 1.79, p = 0.001 and HR = 1.53, p = 0.02, respectively). Patients with tumors > 3 cm, multiple tumors or CIS had earlier T3/T4 or N + cystectomies. In patients who progressed, the timing of cystectomy did not affect the risk of T3/T4 or N + disease at RC. Patients with T3/T4 or N + disease at RC had a shorter disease-specific survival (HR = 4.38, p < 0.001), as did patients with CIS at cystectomy (HR = 2.39, p < 0.001). Patients who progressed prior to cystectomy had a shorter disease-specific survival than patients for whom progression was only detected at cystectomy (HR = 0.58, p = 0.024) CONCLUSIONS: Patients treated with RC before experiencing progression to muscle-invasive disease harbor better oncological and survival outcomes compared to those who progressed before RC and to those upstaged at surgery. Tumor size and concomitant CIS at diagnosis are the main predictors of surgical treatment while tumor size, CIS and tumor multiplicity are associated with extravesical disease at surgery.

The importance of serum osteopontin and stanniocalcin-1 in renal cell carcinoma.

A total of 56 RCC patients with staging ≥ pT1b were enrolled in a prospective study to assess the prognostic importance of serum levels of osteopontin (OP), stanniocalcin-1 (SC), FGF-23, alpha Klotho and 25-OH-D at the time of diagnosis in renal cell carcinoma (RCC) patients. The relationship between the serum level of the analyzed parameters and recurrence-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS) was examined, and our control group consisted of 20 patients without cancer. The levels of osteopontin, stanniocalcin-1, FGF-23 and alpha Klotho were determined by Enzyme-Linked Immunosorbent Assay (ELISA) and 25-OH-D by chemiluminiscence immunoanalysis (CLIA). The follow-up period median was 46 months. Renal cell carcinoma recurred in 9 patients and 20 patients died during follow-up; 12 of them from RCC. The level of osteopontin and stanniocalcin-1 varied between the control group and RCC patients (at p=0.02 and p=0.0003). Higher levels of stanniocalcin-1 were detected in the metastatic RCC group than in the localized RCC group (p=0.003). Only the stanniocalcin-1 level at the time of surgery was associated with RFS (p=0.0004). Both OS and CCS were associated with the osteopontin, stanniocalcin-1 and FGF preoperative level. Patients with stanniocalcin-1 level over 1,277 pg/ml and osteopontin level over 100 ng/ml had 17.8 times higher and 7.9 times higher risk of dying from RCC progression, respectively (p<0.001 and p=0.002). High levels of osteopontin, stanniocalcin-1 and FGF 23 at the time of surgery are important prognostic factors related to CSS and OS. Patients with high stanniocalcin-1 level were at risk of tumor recurrence.

Recurrence, progression and cancer-specific mortality according to stage at re-TUR in T1G3 bladder cancer patients treated with BCG: not as bad as previously thought.

PURPOSE: The goals of transurethral resection of a bladder tumor (TUR) are to completely resect the lesions and to make a correct diagnosis to adequately stage and treat the patient. Persistent disease after TUR is not uncommon and is why re-TUR is recommended in T1G3 patients. When there is T1 tumor in the re-TUR specimen, very high risks of progression (82%) have been reported. We analyze the risks of recurrence, progression to muscle-invasive disease and cancer-specific mortality (CSM) according to tumor stage at re-TUR in T1G3 patients treated with BCG. METHODS: In our retrospective cohort of 2451 T1G3 patients, 934 patients (38.1%) underwent re-TUR. 667 patients had residual disease (71.4%): Ta in 378 (40.5%), T1 in 289 (30.9%) patients. Times to recurrence, progression and CSM in the three groups were estimated using cumulative incidence functions and compared using the Cox regression model. RESULTS: During a median follow-up of 5.2 years, 512 patients recurred. The recurrence rate was significantly higher in patients with a T1 at re-TUR (P < 0.001). Progression rates differed according to the pathology at re-TUR, 25.3% in T1, 14.6% in Ta and 14.2% in case of no residual tumor (P < 0.001). Similar trends were seen in both patients with and without muscle in the original TUR specimen. CONCLUSIONS: Patients with T1G3 tumors and no residual disease or Ta at re-TUR have better recurrence, progression and CSM rates than previously reported, with a CSM rate of 13.1 and a 25.3% progression rate in re-TUR T1 disease.

MicroRNAs in urine supernatant as potential non-invasive markers for bladder cancer detection.

Urinary bladder carcinoma contributes to 4% of newly diagnosed oncological diseases in the Czech Republic. Biomarkers for its early non-invasive detection are therefore highly desirable. Urine seems to be an ideal source of such biomarkers due to the content of cell-free nucleic acids, especially microRNAs (miRNAs).To find potential biomarkers among miRNAs in urine supernatant, we examined in total 109 individuals (36 controls and 73 bladder cancer patients) in three phases. In the first - discovery - phase, microarray cards with 381 miRNAs were used for miRNA analysis of 13 controls and 46 bladder cancer patients. In the second - verification - phase, the results of this first phase were verified on the same groups of subjects by single-target qPCR assays for the selected miRNAs. For the third - validation - phase, new independent samples of urine supernatant (23 controls and 27 bladder cancer patients) were analyzed using single-target qPCR assays for 13 verified in the previous phase. The results of all phases were normalized to miR-191, miR-28-3p, and miR-200b, which were selected as suitable for our study by the qBase+®.We found that miR-125b, miR-30b, miR-204, miR-99a, and miR-532-3p are significantly down-regulated in patients' urine supernatant. In our experiments, the analysis of miR-125 levels provided the highest AUC (0.801) with 95.65% specificity and 59.26% sensitivity, the analysis of miR-99a lead to AUC (0.738) with 82.61% specificity and 74.07% sensitivity. We demonstrate that levels of these miRNAs could potentially serve as promising diagnostic markers for the non-invasive diagnostics of bladder cancer.

The prognostic value of T1 bladder cancer substaging: a single institution retrospective study.

OBJECTIVE: To evaluate the prognostic value of the depth of lamina propria invasion in patients with T1 bladder cancer. SUBJECTS AND METHODS: 200 patients were treated between the years 2002 and 2009. Tumours with depth of invasion above the muscularis mucosae level were categorised as pT1a and those with depth of invasion up to or beyond the muscularis mucosae as pT1b. RESULTS: Categorisation for pT1a and pT1b was performed in 176 of 200 patients (88%). In 10 patients a muscle-invasive tumour was found in re-transurethral resection samples. 131 (79%) of 166 analysed patients had pT1a tumour and 35 (21%) had pT1b tumour. During the follow-up, in 101 (61%) patients the tumour had recurred and in 27 (16.3%) the tumour had progressed. Of all the investigated parameters, T1 substaging (p < 0.0001), grade (p = 0.0003) and the number of bacillus Calmette-Guérin instillations (p = 0.0490) were significant in predicting progression. The only significant factor for disease-specific survival was T1 substaging in univariable (p = 0.0008) and multivariable (hazard ratio 4.407) analysis. T1 substaging (p = 0.0149) and tumour multiplicity (p = 0.0448) have a statistically significant prognostic value with respect to overall survival. CONCLUSIONS: Deep invasion of the lamina propria is a significant adverse prognostic factor for tumour progression, disease-specific survival and overall survival.

Prediction of recurrence in low and intermediate risk non-muscle invasive bladder cancer by real-time quantitative PCR analysis: cDNA microarray results.

The aim of the study was to define specific genetic profile in Ta and T1 urinary bladder carcinoma patients with and without recurrence by gene expression microarrays. Eleven patients with the time to recurrence shorter than one year (patients with recurrence) and 11 patients with time to recurrence longer than 4 years (patients without recurrence) were enrolled. Data from microarrays were subjected to a panel of statistical analyses to identify bladder cancer recurrence-associated gene signatures. Initial screening using the GeneSpring and Bioconductor software tools revealed a putative set 47 genes differing in gene expression in both groups. After the validation, 33 genes manifested significant differences between both groups. The significant expression was observed in the group of patients without recurrence by 30 genes of which the highest differences were detected by ANXA1, ARHGEF4, FLJ32252, GNE, NINJ1, PRICKLE1, PSAT1, RNASE1, SPTAN1, SYNGR1, TNFSF15, TSPAN1, and WDR34. These genes code for signal transduction, vascular remodeling and vascular endothelial growth inhibition mainly. In the group with recurrence, 3 genes had significant differences, the highest differences were identified by two genes (PLOD2 and WDR72). Loci of genes with significant changes of gene expression were located on characteristic chromosomes for bladder cancer: 7 loci on chromosome 9, 8 loci on chromosomes 1, 2, 3, 12,14,15,16, and 22. We have selected and validated 15 genes that are differentially expressed in superficial bladder cancer. We hope that this cohort of genes will serve as a promising pool of candidate biomarkers for early stage bladder cancer. Our results indicate that it may be possible to identify patients with a low and high risk of disease recurrence at an early stage using a molecular profile.

[Difficulties in routine diagnostics of urothelium lesions]. / Problémy v rutinní diagnostice uroteliálních lézí.

BACKGROUND: Facing the increasing frequency of urothelial neoplasms and stratified therapeutic strategy pathologists have to meet the demands of urologists for constantly increasing preciseness of the histopathology reports influencing the application of tailored therapeutic schemes. The WHO/ISUP consensus conference in 1998 resulted into adoption of a new classification of the urothelial lesions. Its employment requires considering of features that can be difficult to find in the material provided. MATERIAL AND METHODS: parallel typing of more than 200 urothelial neoplasms from the daily routine biopsy samples provided by the faculty of medicine urology clinic according to the previous Mostofi 1973 and the new WHO/ISUP 1998 classification. RESULTS: Realizing the consultation demands we have identified some repetitive problems in the urothelium lesions diagnostics considering typing, grading, and staging of the lesions. Typing was a less frequent source of problems. It appeared in classifying lesions with inverted growth, and mucin producing urothelial neoplasms vs. adenocarcinomas. Less important typing problems are represented by uncommon rare diagnoses, as they manifest from the beginning as a specialty solvable mostly with the help of immunohistochemistry. Grading was experienced as troublesome in the following items: papillary hyperplasia vs. LG papillary ca, PUNLMP vs. LG papillary ca, HG papillary ca with a majority of LG material, monotonous types of HG flat lesions, and combined lesions. Staging difficulties applied mostly in identification of the initial unequivocal invasion and the substaging of pT1 into pT1a and pT1b with learning to find the decisive mucosa structures described in detail as late as 1983 (2). We have implemented reporting the presence/absence of the detrusor muscle in the material as a marker describing the representativness of the sample provided; we consider this approach less confusing than introduction of clinical staging terminology Ta, T1 instead of pTa, pT1. To help the practising pathologists accustomed to the previous classification system we have organized postgraduate courses dealing with the application of the new diagnostic criteria adopted by the new version WHO 2004 urothelial neoplasms classification. A slide collection from the routine biopsy material comparing the previous and the new classification and a reference image database with commented reference images are being developed in the LUCIA Net image archiving system. Free access for study is available at http://www.laboratory-imaging.com. Recently, it includes over 80 images. CONCLUSION: adopting the new system of urothelial lesions classification requires consideration of formerly not employed features. The learning can be simplified with both classical slide collection & e-learning image database.

Does the expression of fascin-1 and tumor subclassification help to assess the risk of recurrence and progression in t1 urothelial urinary bladder carcinoma?

INTRODUCTION: To evaluate the prognostic value of T1 subclassification and fascin-1 expression in T1 human urothelial cell carcinoma of the bladder. MATERIALS AND METHODS: In a prospective study with 105 consecutive patients, T1 tumors were subclassified into 2 groups according to the depth of tumor invasion. The tunica muscularis mucosae was used as a landmark. The expression of fascin-1 was examined by using an anti-fascin-1 mouse monoclonal antibody and was evaluated semiquantitatively for both intensity and distribution. The patients were followed up for 27.3 +/- 13.7 months. RESULTS: The T1 tumor subclassification was feasible in 99 patients (94%). T1a tumor was detected in 77 patients (73%), T1b tumor in 22 patients (21%). An invasive tumor was found in 5 patients (4.8%) during the restaging transurethral resection of the bladder. The risk of understaging in patients with T1b tumor was 18%. There was not a significant difference in time to the recurrence in the T1a and the T1b group. The progression-free survival rates were significantly different between both groups (p = 0.0034). No correlation was found between fascin-1 positivity and the depth of tumor invasion. Fascin-1 positivity did not correlate with recurrence or the progression-free intervals. In the multivariate analysis, only the extent of lamina propria invasion was an independent predictor of the tumor progression. The fascin positivity was not an independent prognostic factor relating to the risk of recurrence or progression. CONCLUSION: The finding of T1b tumor was connected with a significantly higher risk of progression and understaging. The fascin-1 expression did not correlate with the depth of tumor invasion or with the tumor recurrence or progression.

Urinary cytology and quantitative BTA and UBC tests in surveillance of patients with pTapT1 bladder urothelial carcinoma.

OBJECTIVES: To compare results of urinary cytology, quantitative detection of human complement factor H-related protein (BTA TRAK), and urinary fragments of cytokeratins 8 and 18 (UBC IRMA) with the recurrence status in patients with pTapT1 bladder cancer and to define the possible role of these methods in a surveillance protocol. METHODS: We collected urine from 88 consecutive patients with primary pTapT1 tumors before the first transurethral resection (TURB) and before each follow-up cystoscopy. In all samples urinary cytology and quantitative BTA and UBC tests were performed. We compared results with recurrence status and with tumor characteristics in the case of recurrence. We constructed receiver operator characteristic (ROC) curves for quantitative methods. In addition, we evaluated individual cutoffs based on pretreatment levels. RESULTS: During the mean follow-up of 16.96 months, we performed 313 cystoscopies, 93 of which were positive in 51 patients. The sensitivity and specificity of cytology, BTA, and UBC were 19.8% and 99%, 53.8% and 83.9%, and 12.1% and 97.2%, respectively. The sensitivity of pTis detection was 66.6%, 0%, and 100%, respectively. With cutoffs set to a sensitivity of 90%, the specificity of BTA and UBC dropped to 24.8% and 20.4%, respectively. Individually calculated cutoffs did not provide a significant benefit. CONCLUSIONS: Because of high specificity and sensitivity in pTis detection, urinary cytology fulfills requirements for an adjunctive method to cystoscopy. Quantitative BTA and UBC tests have a low sensitivity in the detection of bladder cancer recurrence and cannot be used routinely to reduce the number of cystoscopies during follow-up.

[Cystectomy in the treatment of bladder cancer]. / Cystektomie v léce nádoru mocového mechýre.

Radical cystectomy with pelvic lymphadenectomy and urinary diversion is an important component in the treatment of bladder cancer. It is considered the most important method in the therapy for muscle invasive and selected high-risk non-muscle invasive tumours with excellent local control and high complete remission rate. It consists of complete removal of tumour tissue in the bladder, small pelvis and regional lymph nodes. In males, urinary bladder and prostate are routinely removed; in females, bladder, uterus and anterior vaginal wall are removed. Urethrectomy is indicated only in selected situations. An integral part of the operation is the bilateral pelvic lymphadenectomy. Extravesical disease extension and lymph node positivity are unfavourable prognostic factors. Better prognosis is expected in patients with less than 5 positive nodes. Important prognostic factor is also the number of removed lymph nodes, which is a strong argument for meticulous bilateral pelvic lymphadenectomy. Lymph node density (number of positive nodes/ number of removed nodes) is considered as very important prognostic factor. Better prognosis can be expected in patients with less positive and more removed nodes.

[The p53 positivity in non-tumor mucosa in patients with superficial urinary bladder cancer]. / P53 pozitivita v nenádorove sliznici u pacientu s povrchovým uroteliiálním karcinomem mocoveho mechyre.

BACKGROUND: The aim of the study is to assess the prognostic value of p53 positivity in the non-tumor mucosa of urinary bladder in patients with superficial urinary bladder carcinoma. METHODS AND RESULTS: In 45 patients cold cup non-tumor mucosa samples were taken at the same time with the TUR of superficial urinary bladder carcinoma prospectively. Monoclonal antibody BP53-12-1 was used for the detection of p53 protein. When identifying positive colouring only the nuclear immunoreactivity was being evaluated. 200 nuclei at minimum were examined in several representative fields. The McCarthy method in Bacus modification was used to analyse the findings. It is a semiquantitative method which detects not only the percentage of p53 positive cells but also the intensity of positivity classified into four degrees (0 - negative, 1 - slightly positive, 2 - distinctly positive, 3 - strongly positive). The intensity of p53 positivity was quantified as HSCORE, where HSCORE = 7Pi (i + 1), in which i is one of the four see above degrees and Pi fluctuates from 0 % to 100 %. The result is a numerical figure from 100-400. A negative finding is of HSCORE 100, HSCORE of 400 is the highest possible. The samples were analysed in the analytical system LUCIA. The borderline value was quantified to HSCORE 200. All patients were carefully followed up and treated using usual schemes. The results were evaluated by the use of SAS system (Cary, USA). Thirty patients recurred during the follow-up and 7 of them progressed. The average HSCORE in those who did not recur was 130.2, in patients with the recurrence of tumor it was 162.5 and in patients with progression it was 169.2. We have found a correlation between the HSCORE and the risk of recurrence, which was statistically significant. CONCLUSIONS: The p53 positivity in non-tumor mucosa of urinary bladder in patients with superficial bladder cancer may bring additional information when predicting the risk of recurrence. More extensive studies need to be carried out.

Association of PAX5 expression with clinical outcome in patients with TaT1 transitional cell carcinoma of the bladder.

OBJECTIVES: To assess the frequency and intensity of PAX5 gene messenger ribonucleic acid (mRNA) expression in TaT1 bladder cancer tissue, as well as its correlation with clinicopathologic variables and patient outcome. METHODS: The RNA expression of PAX5 was evaluated with reverse transcriptase polymerase chain reaction in the tumor tissue of 75 patients with stage TaT1 bladder cancer treated with transurethral resection. Patients were observed with cystoscopy and urinary cytologic evaluation. The association between PAX5 expression and clinicopathologic variables and patient outcome was evaluated. Benign urothelium from 8 patients with benign prostatic hyperplasia was obtained. These patients were used as a control group. RESULTS: PAX5 expression was found in 62 patients with bladder cancer (82.7%) but in no patient from the control group. High PAX5 expression (greater than 0.2) was confirmed in 19 patients (25.3%). No significant relationship was observed between quantity of PAX5 expression and clinicopathologic variables. The 3-year recurrence-free and progression-free survival rates in highly positive patients were 13.2% and 71.6%, compared with 40.6% and 92.8%, respectively, in patients with weak or negative expression (log-rank test, P = 0.0075, P = 0.022). Multivariate Cox proportional hazard model analysis identified PAX5 expression as an independent predictor of tumor recurrence. CONCLUSIONS: PAX5 gene expression is a frequent finding in superficial transitional cell carcinoma of the bladder. High levels of PAX5 are associated with poorer recurrence-free and progression-free survival rates. Moreover, PAX5 expression was found to be an independent prognostic factor for recurrence-free survival by a multivariate analysis.

[Fluorescence cystoscopy in the diagnostics and treatment of superficial urinary bladder tumors]. / Fluorescencní cystoskopie a její místo v diagnostice a lécbe povrchových nádoru mocového mechýre.

BACKGROUND: 5-aminolevulinic acid induced fluorescence cystoscopy can detect more tumour lesions comparing to standard cystoscopy. The goal of our study was to assess the influence of fluorescence cystoscopy used during transurethral resection on the recurrence rate and the length of tumor-free interval in stage Ta, Tl transitional cell carcinoma of the urinary bladder. METHODS AND RESULTS: In prospective randomized study 109 patients with primary or recurrent stage Ta Tl bladder transitional cell carcinoma treated with transurethral resection were enrolled. 17 patients with high grade tumors were evaluated separately. In group A the transurethral resection was performed with standard white light endoscopy, in group B with fluorescence cystoscopy. The patients were followed using standard cystoscopy and urinary cytology. Recurrence free interval was evaluated in whole groups and also for single and multiple and for primary and recurrent tumors separately. The median time to recurrence was 8.05 months in group A and was significantly shorter than 13.54 months in group B (p = 0.04, log-rank test). In separate analyses the median time to recurrence was significantly shorter using fluorescence cystoscopy in multiple (p = 0.004) and in recurrent (p = 0.02) tumors, but not in solitary and primary tumors. CONCLUSIONS: 5-aminolevulinic acid induced fluorescence cystoscopy used during transurethral resection reduces the early recurrence rate in stage Ta Tl bladder transitional cell carcinoma.

[A case of a patient with solitary prostate metastasis of the colorectal carcinoma three years after abdominoperineal amputation of the rectum]. / Prípad pacienta se solitární metastázou kolorektálního karcinomu v prostate tri roky po abdominoperineální amputaci rekta.

AIM: The aim of this study is to present a case-review of a patient with an extremely rare finding of a solitary metastasis of the colorectal carcinoma in his prostate. METHODOLOGY: A Case-Review. RESULTS: The study describes a case of a 42-year-old patient who underwent abdominoperineal amputation for the rectal carcinoma pT3 N1 M0 with complementary actinotherapy and chemotherapy. Three years after his rectum amputation, a CT scan disclosed a hypodense focus in his prostate of unknown origin. Elevation of the CEA was found upon laboratory examination, other tumor markers including the PSA were not abnormal. The positron emission tomography (PET) did not disclose other distant foci. The patient was administered 4 courses of chemotherapy with, basically, no signs of regression in the prostate foci. Biopsy from the suspicious focus was conducted transperitoneally, followed by its histological examination which confirmed cribriform adenocarcinoma. Our team decided on salvage cystoprostatectomy, securing urine derivation by the ilium conduit. 6 months later, the CT examination showed a massive local relapse and two metastatic foci in the liver, further oncological therapy was not indicated. The patient died 7 moths after the radical cystoprostatectomy. CONCLUSION: This case-review points out a possibility of metastatic prostate affections connected to the colorectal carcinoma disorder, as well as its treatment procedures.

The expression of PAX5, p53 immunohistochemistry and p53 mutation analysis in superficial bladder carcinoma tissue. Correlation with pathological findings and clinical outcome.

OBJECTIVES: The expression pattern of PAX5 in the tissue of superficial bladder transitional cell carcinoma (TCC), its prognostic value and its correlation with p53 immunohistochemistry and p53 mutation analysis were evaluated. METHODS: Study comprised 61 patients with histologically confirmed superficial bladder TCC. Expression level of PAX5 mRNA was investigated using reverse transcriptase-polymerase chain reaction (RT-PCR) and determined semiquantitatively. The presence of p53 mutations was determined by SSCP and confirmed by direct sequencing. The p53 immunohistochemistry was performed with DO1 antibody and semiquantitatively evaluated using HSCORE (HS) method. As the control group for the evaluation of the PAX5 expression served 8 men with benign prostatic hyperplasia. RESULTS: PAX5 expression was found in 50 patients with bladder TCC but in no patient from the control group. Its quantity however correlated neither with the stage nor with the grade of the tumor. P53 mutation was confirmed only in 1 patient with pTaG2 tumor in exon 5 (deletion of proline 128). On the contrary, positive immunohistochemical staining of p53 was detected in most patients. Using the cutoff value of HS 200, 56.9% of patients showed p53 overexpression. Quantity of p53 immunochistochemical positivity did not correlate with the quantity of PAX5 expression. Using the cutoff values of HS 200 for p53 and of 0.2 for PAX5, 7 of 8 patients with future progression had p53 and 4 had PAX5 overexpression respectively. CONCLUSION: The expression of gene PAX5 is a frequent event in superficial TCC of the bladder.

Punctate midline myelotomy for the relief of visceral cancer pain.

OBJECT: This study offers clinical support for the concept that neurosurgical interruption of a midline posterior column pathway by performing a punctate midline myelotomy (PMM) provides significant pain relief without causing adverse neurological sequelae in cancer patients with visceral pain refractory to other therapies. METHODS: A PMM of the posterior columns was performed in six cancer patients in whom visceral pain had been refractory to other therapies. The cause of the visceral pain was related to residual, progressive, or recurrent local cancer or postirradiation effects. Clinical efficacy of the procedure was examined by comparing patient pain ratings and narcotic usage pre- and post-PMM. Follow-up periods ranged from 3 to 31 months. Examination of the results indicates a significant reduction in pain ratings as well as a significant reduction in daily narcotic use. No adverse neurological effects were observed. One spinal cord has been recovered for postmortem examination. CONCLUSIONS: These findings provide corroborating clinical evidence for the existence of a newly recognized midline posterior column pathway that mediates the perception of visceral pelvic and abdominal pain. Preliminary data indicate that significant pain relief can be obtained following PMM with minimal neurological morbidity and suggest that the procedure may provide an alternative treatment modality for cancer-related pain in patients in whom adequate pain control with narcotics cannot be achieved or narcotic side effects cannot be tolerated.

Cognitive improvement despite minimal arachnoid cyst decompression.

There are relatively few reports that evaluate the cognitive functions of patients with arachnoid cysts. Presumably, these 'silent cysts' are regarded as incidental findings with no functional significance. Although postoperative clinical improvement is well documented in patients with significant reduction in cystic volume, the current report describes a patient who underwent cystoperitoneal shunting due to mass effect, with minimal postoperative decompression. Neuropsychological testing indicated significant cognitive improvement in verbal learning, memory, visual-perceptual abilities, constructional skills, conceptual shifting, and psychomotor speed after shunt placement, despite marginal evidence of decompression. These findings suggest that (1) significant cognitive changes can occur in these patients, despite minimal postoperative regression of the lesion, (2) cognitive measures may provide an alternative, functional index of outcome efficacy, and (3) reliance on traditional outcome measures (i.e. anatomical decompression or resolution of clinical symptoms) may underestimate the efficacy of surgical intervention for these patients.

Cognitive sequelae of unilateral posteroventral pallidotomy.

OBJECTIVE: To examine the cognitive sequelae of unilateral posteroventral pallidotomy. DESIGN: Single-group pretest and posttest methodologic assessment with baseline evaluation performed 1 to 2 days prior to surgery and follow-up conducted 3 months after pallidotomy. SETTING: Movement disorder clinic at a university medical center. PATIENTS: Fourteen patients (age range, 43-82 years) with Parkinson disease (average disease duration, 7.4 years). INTERVENTION: Unilateral posteroventral pallidotomy procedures were performed on the right (n=8) and left (n=6) side of the brain. MAIN OUTCOME MEASURES: The protocol consisted of a range of neuropsychological instruments sensitive to subcortical dysfunction, including measures of bi-manual coordination, simple-complex reaction time, visual attention, naming, verbal fluency, learning, recognition memory, and problem solving. RESULTS: No significant deterioration in specific cognitive abilities was observed as a function of the procedure. Patients showed a significant improvement in motor coordination speed for both contralateral and ipsilateral upper extremities. CONCLUSIONS: Stereotactic unilateral posteroventral pallidotomy is associated with minimal risk of adverse neuropsychological effects or cognitive decline. Additional research is warranted, with an increased sample size and extended follow-up, to assess any potential lateralized effects of the procedure.