Superficial Urothelial Carcinoma Of Bladder Research Articles

Human papilloma virus DNA revelation in the superficial urothelial bladder carcinoma

Human papilloma virus DNA revelation in the superficial urothelial bladder carcinoma

Detection of the recurrence of superficial urothelial carcinoma of urinary bladder by combined urine cytology and cystoscopy

The study was aimed to evaluate the accuracy of combined urine cytology and cystoscopy for the detection of the recurrence of superficial urothelial carcinoma of urinary bladder without bladder biopsy. A total 60 patients [males 48, females 12; age range 41-80 years (mean age- 63.15 years)] were included. Urine cytology as well as cystoscopy were done with a targeted biopsy taken from any apparently visible growth in the bladder. The systematic biopsy was taken where there was no growth. Reports of the cytology and cystoscopy were compared with the histopathology reports. It was found that 18 patients were cytology positive (false positive 2) and 42 patients were cytology negative (false negative 10) with sensitivity 61.5% and specificity 94%. During cystoscopy 24 patients were found recurrent growth in the bladder (false positive 3) and 36 patients were negative (false negative 5) with sensitivity 80.7% and specificity 91%. But when combined urine cytology and cystoscopic findings evaluated, the sensitivity and specificity were found 100% and 91% respectively. In conclusion, combined urine cytology and cystoscopy can be used for the detection of recurrence of superficial urothelial carcinoma of urinary bladder.

Predicting 90-day and long-term mortality in octogenarians undergoing radical cystectomy

BackgroundRadical cystectomy bears a considerable perioperative mortality risk particularly in elderly patients. In this study, we searched for predictors of perioperative and long-term competing (non-bladder cancer) mortality in elderly patients selected for radical cystectomy.MethodsWe stratified 1184 consecutive patients who underwent radical cystectomy for high risk superficial or muscle-invasive urothelial or undifferentiated carcinoma of bladder into two groups (age < 80 years versus 80 years or older). Multivariable and cox proportional hazards models were used for data analysis.ResultsWhereas Charlson score and the American Society of Anesthesiologists (ASA) physical status classification (but not age) were independent predictors of 90-day mortality in younger patients, only age predicted 90-day mortality in patients aged 80 years or older (odds ratio per year 1.24, p = 0.0422). Unlike in their younger counterparts, neither age nor Charlson score or ASA classification were predictors of long-term competing mortality in patients aged 80 years or older (hazard ratios 1.07-1.10, p values 0.21-0.77).ConclusionsThis data suggest that extrapolations of perioperative mortality or long-term mortality risks of younger patients to octogenarians selected for radical cystectomy should be used with caution. Concerning 90-day mortality, chronological age provided prognostic information whereas comorbidity did not.

136 Eyelid Metastasis From Bladder Small Cell Carcinoma

Metastases to the eyelids are rare. The primary neoplasms are more frequently in breast, skin, digestive, and urological systems. There are very few reports related to bladder carcinomas. We present a unique case of small neuroendocrine cell carcinoma of the bladder metastatic to the eyelid. A 83-year-old man was treated for a high-grade superficial urothelial bladder carcinoma in August 2013 with endoscopic resection and intravesical BCG. In November 2014, he had an in situ bladder carcinoma (CIS). In November 2015, he presented a small cell neuroendocrine carcinoma in the bladder with invasion of muscular wall and areas of in situ carcinoma with focal neuroendocrine differentiation (immunostains positive for synaptophysin and partial for chromogranin A). In October 2016, he developed a skin metastasis of the back. In January 2017, a resective biopsy from a left superior eyelid nodule revealed a small cell carcinoma. The immunohistochemical reactions showed that tumor cells were positive for synaptophysin, chromogranin A, and CD56, and negative for cytokeratin 20. Metastases to the eyelids are rare. This is the first reported case of small cell neuroendocrine carcinoma of bladder metastasizing to the eyelid. The patient had a history of high-grade superficial urothelial carcinoma, later a CIS, and then the small cell neuroendocrine carcinoma. In the study, we need to discard Merkel cell carcinoma.

A diagnostic marker for superficial urothelial bladder carcinoma: lack of nuclear ATBF1 (ZFHX3) by immunohistochemistry suggests malignant progression.

BackgroundPathological stage and grade have limited ability to predict the outcomes of superficial urothelial bladder carcinoma at initial transurethral resection (TUR). AT-motif binding factor 1 (ATBF1) is a tumor suppressive transcription factor that is normally localized to the nucleus but has been detected in the cytoplasm in several cancers. Here, we examined the diagnostic value of the intracellular localization of ATBF1 as a marker for the identification of high risk urothelial bladder carcinoma.MethodsSeven anti-ATBF1 antibodies were generated to cover the entire ATBF1 sequence. Four human influenza hemagglutinin-derived amino acid sequence-tagged expression vectors with truncated ATBF1 cDNA were constructed to map the functional domains of nuclear localization signals (NLSs) with the consensus sequence KR[X10-12]K. A total of 117 samples from initial TUR of human bladder carcinomas were analyzed. None of the patients had received chemotherapy or radiotherapy before pathological evaluation.ResultsATBF1 nuclear localization was regulated synergistically by three NLSs on ATBF1. The cytoplasmic fragments of ATBF1 lacked NLSs. Patients were divided into two groups according to positive nuclear staining of ATBF1, and significant differences in overall survival (P = 0.021) and intravesical recurrence-free survival (P = 0.013) were detected between ATBF1+ (n = 110) and ATBF1− (n = 7) cases. Multivariate analysis revealed that ATBF1 staining was an independent prognostic factor for intravesical recurrence-free survival after adjusting for cellular grading and pathological staging (P = 0.008).ConclusionsCleavage of ATBF1 leads to the cytoplasmic localization of ATBF1 fragments and downregulates nuclear ATBF1. Alterations in the subcellular localization of ATBF1 due to fragmentation of the protein are related to the malignant character of urothelial carcinoma. Pathological evaluation using anti-ATBF1 antibodies enabled the identification of highly malignant cases that had been overlooked at initial TUR. Nuclear localization of ATBF1 indicates better prognosis of urothelial carcinoma.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2845-5) contains supplementary material, which is available to authorized users.

Total hip arthroplasty infection due to Mycobacterium bovis, after BCG therapy

The loosening of total joint replacement is a frequent complication after total hip arthroplasty (THA). Septic osteolysis should always be feared. We report here a rare case of hip arthroplasty infection due to Mycobacterium bovis after Bacillus Calmette-Guerin (BCG) therapy in a context of bladder cancer. A 70-year-old man was referred to the department of rheumatology in September 2015, because of a total functional disability of the left lower limb. He underwent an un-cemented left total hip arthroplasty in 2003 for the treatment of osteoarthritis. We noted a bladder carcinoma treated by BCG instillation in 2013. Concerning his lower-limb, the activity-related pain has progressively intensified. No fever, weight loss, night sweat or other constitutional symptoms had been noticed. The medical examination showed an isolated painless mass in the inguinal fold. Initial x-ray showed a large trochanteric bone defect and a medial femoral cortex osteolysis. A CT-scan revealed a mass located between the acetabulum and the femoral vasculo-nervous package. A puncture of the mass yielded a hematic and purulent material. On day 14 of incubation, a BCG Mycobacterium bovis strain developed on a specific mycobacterial culture. Tuberculosis vaccine is an effective intravesical immunotherapy for superficial urothelial bladder carcinoma. Most patients experience irritative voiding. Flu-like symptoms may occur and are resolved with symptomatic treatment. Osteoarticular complications are rare. Only 8 cases of prosthetic infections due to Mycobacterium bovis are reported. There is no predictive factor that could help identify patients at risk for developing BCG infection. Most of patients present sub-acute or chronic joint pain, with a great difficulty and a long delay for clinicians to make the diagnosis. In our case, the pseudo-tumoral aspect associated with the loosening of the THA showed many similarities with polyethylene wear induced osteolysis with a classic inflammatory granuloma. A regimen of antituberculous drugs was essential alongside with the removal of the mass. Peri-prosthetic infection due to Mycobacterium bovis is a very rare complication of BCG therapy but clinicians should be able to evocate this diagnosis.

The role of p53 immunohistochemical marker in development of superficial urothelial bladder carcinoma

Purpose. Determination the role of the p53 expression as a prognostic factor in the development of superficial urothelial bladder carcinoma. Materials and methods. Medical histories of 72 patients (11 women and 61 men) with diagnosed primary superficial urothelial carcinoma of the bladder I and II grade were retrospectively analyzed. All patients were undergone a repeated transurethral resection was performed in 6 weeks after the first operation. In the case of the absence of residual tumor, cystoscopy was performed every 3 months during the first year then every 3–6 months during next 5 years. The average time of follow-up was 43.2 months. According to the standard protocol an immunohistochemical study with detection of p53 was carried out on 72 sections of formalin-fixed and paraffin-embedded tumor fragments. p53 expression was also determined in 10 histologically unchanged fragments of the bladder mucosa. Results. Depending on the percent of nuclei with p53 expression, two groups were identified. The first group included 40 tumor samples (55.5 %) with p53 expression less than 20 % and 17 tumor samples (23.6 %) without p53 expression. The second group included 15 tumor samples (20.9 %) with p53 expression more than 20 % (4 patients – 20–40 %, 8 patients – 40–60 %, 3 patients – 60–80 %). р53 expression was not determined in the all 10 samples of normal bladder tissue. During follow-up period 1 of 57 patients of the first group has a disease progression comparing with 13 of 15 patients in the second group. Patients of the both group were similar in respect with clinical characteristics. The mean time to disease progression was 17.3 months. Conclusion. Results of the current study shows that p53 immunohistochemical marker is a prognostic factor in the development of superficial urothelial bladder carcinoma.

Lethal BCG-osis, in the context of superficial urothelial bladder carcinoma, diagnosed in autopsy

Intra-vesicular Bacillus Calmette–Guérin (BCG) immuno-therapy is a cornerstone in the treatment of superficial bladder carcinoma. However, it can rarely cause BCG-osis, a systemic infection, potentially fatal. A case of a 73year old man, diagnosed with superficial urothelial bladder carcinoma five months ago, who died with clinical features of septic shock one day after BCG therapeutic maintenance infusion, is presented. The cause of death, BCG-osis, was revealed during autopsy.

Enhanced oxidative stress and the glycolytic switch in superficial urothelial carcinoma of urinary bladder

ObjectiveTo examine whether oxidative stress and the glycolytic switch are correlated to tumor grading, tumor recurrence, and disease progression in urothelial carcinoma (UC) of the urinary bladder (UB). MethodsAll surgical specimens obtained from 27 patients (each containing their UC and normal tissues of UB) were subjected to a pathological examination by computerized tomography, and a portion of each specimen was used for the analysis of molecular biomarkers. The mRNA expression levels of pyruvate dehydrogenase kinase-1 (PDK1), hypoxia-inducible factor 1 alpha (HIF-1α), lactate dehydrogenase A (LDHA), pyruvate dehydrogenase, and glucose transporter protein 1 (Glut-1) were measured using TaqMan-based real-time quantitative polymerase chain reaction. In addition, 8-hydroxy-2-deoxyguanosine (8-OHdG) and the mitochondrial DNA (mtDNA) copy number were also determined. ResultsThe 8-OHdG content and glycolytic genes expression were higher in UC of the UB than those in the normal tissues of UB, whereas the mtDNA copy number was depleted. According to the multivariate analysis, patients with Grade 3 tumors had higher expression levels of HIF-1α, LDHA, and Glut-1 than those with Grades 1 and 2 tumors. In addition, patients with locally recurrent tumors had a higher expression of HIF-1α and LDHA than those with nonrecurrent tumors. Furthermore, patients under disease progression had higher levels of HIF-1α and PDK1 than those not under disease progression. ConclusionsUC of the UB manifested that the glycolytic phenotype would reflect the Warburg effect. We suggest that the molecular mechanism in the regulation of glycolytic switch in UC of the UB might provide a specific biomarker for the future development of cancer diagnosis.

Phase II Trial of Intravesical Gemcitabine and Biomarker Evaluation in Patients with Superficial Urothelial Carcinoma of the Bladder

Phase II Trial of Intravesical Gemcitabine and Biomarker Evaluation in Patients with Superficial Urothelial Carcinoma of the Bladder

Prognostic significance of tumor location and superficial urothelial bladder carcinoma history in patients with ureteral urothelial carcinoma treated with radical nephroureterectomy

To investigate the significance of tumor location and superficial urothelial bladder carcinoma (UBC) history on oncological outcomes in patients treated with radical nephroureterectomy (RNU) for ureteral urothelial carcinoma (UC). One hundred and thirty-two patients treated with RNU for ureteral UC between January 1999 and July 2010 were retrospectively analyzed. Recurrence probabilities and survival rates were analyzed, stratified by tumor location and superficial UBC history. Comparison of patients with proximal, middle, and distal ureteral UC showed that percentage of bladder recurrence was 13.3, 14.7, and 25.0 %, respectively (P = 0.285); retroperitoneal (tumor bed or lymph node) recurrence was 26.7, 14.7, and 27.9 % (P = 0.319); and contralateral recurrence was 0, 2.9, and 0 % (P = 0.234). Comparison of patients with and without history of superficial UBC revealed that percentage of bladder recurrence was 15.4 and 20.2 %, respectively (P = 0.681); retroperitoneal recurrence was 15.4 and 25.2 % (P = 0.433); and contralateral recurrence was 0 and 0.84 % (P = 0.740). Using multivariable Cox regression analyses, there were no significant differences of recurrence-free survival (RFS) and cancer-specific survival (CSS) with regard to neither tumor location nor superficial UBC history (RFS: P = 0.282 and 0.762, CSS: P = 0.272 and 0.818, respectively). Tumor location and history of superficial UBC could not be used to predict oncological outcomes of patients who underwent RNU for ureteral UC. Therefore, operative strategies or postoperative surveillance should not be affected by tumor location or history of superficial UBC.

Prosthetic Joint Infection due toMycobacterium bovisafter Intravesical Instillation of Bacillus Calmette-Guerin (BCG)

Intravesical instillation of Bacillus Calmette-Guerin (BCG) is a treatment to prevent recurrence of superficial urothelial bladder carcinoma. Complications after bladder instillation of BCG have been reported including locally invasive and systemic infections due to dissemination of Mycobacterium bovis from the bladder. We present an uncommon case and literature review of prosthetic joint infection due to M. bovis after intravesical BCG treatment of bladder cancer.

Multicystic urothelial carcinoma of the bladder with gland-like lumina and with signet-ring cells. A case report

We present the case of 80-year-old male with superficial papillary urothelial carcinoma of the urinary bladder with striking multicystic architecture with a combination of features of urothelial carcinoma with gland-like lumina, with signet-ring cell differentiation and microcystic pattern. However, the tumor shared the morphologic features of several variants of urothelial carcinoma, the most important differential diagnosis covered so-called florid Brunneriosis, cystitis cystica, and primary adenocarcinomas of the urinary bladder.

BCL-2, TP53 and BAX protein expression in superficial urothelial bladder carcinoma

Whether TP53, BCL-2 and BAX expressions add independent prognostic information in patients with Ta/T1bladder urothelial carcinoma remains unclear. TP53 overexpression correlated with high tumor grade ( p = 0.004), WHO grading categories (0.045), BAX expression ( p = 0.043) and pathologic stage ( p = 0.05). BCL-2 immunostaining was inverse associated with tumor grade ( p = 0.008). Lack of BAX expression was related to reduced patient’s survival ( p = 0.028). Mortality was higher in patients with BCL-2+/TP53+ ( p = 0.023) or TP53+/BAX− ( p = 0.027) phenotype. BAX and pathologic stage were independent predictors of progression-free and overall survival, respectively. Therefore, BAX expression might be relevant in patient’s prognosis.

Association of Cyclooxygenase-2 Immunoreactivity with Tumor Recurrence and Disease Progression in Superficial Urothelial Bladder Cancer

The main characteristic of urothelial bladder cancer is a clear predisposition to recurrence and disease progression. The aim of this study was to assess the possible relationship between cyclooxygenase-2 (COX-2) immunoreactivity in superficial urothelial bladder carcinoma and tumor grade, stage, number of recurrences and clinical disease progression. In this prospective study 70 consecutive patients who underwent transurethral resection for superficial urothelial bladder cancer were included. Tumor slides were immunohistochemically stained for COX-2, and COX-2 immunoreactivity in tumor and inflammatory stromal cells was categorized as negative or mildly, moderately or strongly positive. Patients were followed up for 2 years, and during this period the possible association of COX-2 immunoreactivity with tumor stage and grade, number of recurrences and progression of disease was evaluated. COX-2 immunoreactivity in tumor cells was found in 57 (81.4%) patients and did not correlate with tumor grade, stage of disease, number of recurrences, and progression of disease. COX-2 immunoreactivity in inflammatory cells was found in 16 of the 57 patients with COX-2 positive tumors, and was significantly related to the number of recurrences, time to appearance of the first recurrence, and disease progression. COX-2 immunoreactivity in inflammatory stromal cells adjacent to the COX-2-positive tumor might be useful in clinical practice for selection of patients with a high risk of tumor recurrence and disease progression.

ADJUVANT INTRAVESICAL TREATMENT OF SUPERFICIAL BLADDER CANCER WITH A STANDARDIZED MISTLETOE EXTRACT

Adjuvant intravesical immunotherapy with bacillus Calmette-Guerin (BCG) for noninvasive superficial bladder cancer has been shown to decrease tumor recurrence significantly. However, serious local and systemic side effects of this treatment have promoted the use of other immunoactive substances, which to date have failed to show efficacy equal to that of BCG immunotherapy. In the current phase I/II clinical trial an aqueous mistletoe extract standardized to mistletoe lectin was administered intravesically to 30 patients with superficial urothelial bladder carcinoma. About 4 weeks after transurethral resection each patient received 6 instillations at weekly intervals of 50 ml extract with mistletoe lectin concentrations between 10 and 5,000 ng/ml, which was retained in the bladder for 2 hours. Three patients per group received a dose, which was then doubled in the next group. Clinical followup consisted of examinations with cystoscopy, cytology and random biopsies. To detect cytokines and tumor necrosis factor-p75 receptor venous blood and urine samples were taken before instillation, and 2, 6 and 24 hours thereafter. The tolerability of intravesically administered mistletoe extract was good at all applied concentrations. None of the patients had local or systemic side effects according to WHO classification 1-4. Within the 12-month observation time study patients with pTa G2 and pT1 G2 tumors showed a recurrence rate of 33%, comparable to that in a local historical control group of patients with equal stage and grade who were treated with adjuvant BCG. Comparison of urine cytokine levels before instillation, and 2, 6 and 24 hours thereafter brought about no significant alterations in all measured cytokines. From these results it is concluded that standardized mistletoe extract could be a potential alternative adjuvant therapy for superficial bladder cancer. Nevertheless, the optimal intravesical treatment regimen has yet to be defined.

Evaluation of hypoxia‐inducible factor 1α overexpression as a predictor of tumour recurrence and progression in superficial urothelial bladder carcinoma

To investigate the possible role of hypoxia-inducible factor 1alpha (HIF-1alpha, a transcription factor important in regulating O(2) homeostasis and physiological responses to oxygen deprivation) in the recurrence and progression of superficial urothelial bladder cancer, and to examine its expression in relation to proliferation status, apoptotic activity and intratumoral angiogenesis. Paraffin wax-embedded tissue from 140 patients with superficial primary urothelial bladder carcinoma was immunostained for HIF-1alpha, Ki-67, single-stranded DNA antibody for apoptotic cells, p53, bcl-2, vascular endothelial growth factor and CD31 antigen. We calculated the proliferative rate, the apoptotic index and the microvessel density (MVD). The mean (sem) follow-up was 46 (3.5) months, within which 86 patients relapsed while 18 progressed to a higher tumour stage and/or grade. HIF-1alpha expression was more common in high-grade superficial urothelial carcinomas. The positivity was related to increased proliferative activity (P = 0.012), apoptotic rate (P = 0.006) and MVD (P < 0.001). HIF-1alpha overexpression had a marginal adverse influence on progression-free survival (P = 0.058; univariate analysis), but when combined with p53 overexpression, the unfavourable impact was statistically important (P = 0.028). In multivariate analysis, only grade and the high Ki-67 labelling index were significant predictors of recurrence-free survival, while T-stage and the HIF-1alpha+/p53+ phenotype emerged as the only independent variables of adverse prognostic significance for time to progression. HIF-1alpha overexpression combined with aberrant mutant p53 nuclear protein accumulation seem to indicate an aggressive phenotype, suggesting a potential biological model predictive of future risk of disease progression in patients with superficial urothelial bladder carcinoma. These indicators may be helpful in clinical practice to discriminate superficial bladder cancer worth a more intensive follow-up, or more aggressive treatment.

The prognostic value of MDM2 overexpression in superficial urothelial bladder carcinoma

The prognostic significance of p53 accumulation and MDM2 overexpression in superficial and papillary urothelial cell carcinoma (UCC) of the bladder has not yet been established. Therefore, MDM2 and p53 protein were investigated focusing on tumour grade and muscularis mucosae invasion in order to identify their prognostic significance. Thirty-five archival UCC were studied by immunohistochemistry using monoclonal antibodies DO7 against p53, and IB10 against MDM2. MDM2 overexpression was observed in 51.4% of the cases. The recurrence rate for patients with MDM2 overexpression was 7.09 fold higher than for those without MDM2 overexpression. p53 accumulation was not related to prognosis. There was no significant difference between low and high grade tumours in regard to MDM2 overexpression and p53 accumulation. pTa cases presented the higher frequency of MDM2 positive cases (66.7%) and a lower frequency of p53 accumulation (33.3%). MDM2 overexpression does not seem to be related to muscular mucosae invasion. Thus, MDM2 status may well be a prognostic marker in superficial urothelial bladder carcinomas.

Evaluation of cellular tumour rejection mechanisms in the peritumoral bladder wall after bacillus Calmette-Guérin treatment.

To compare the immunological status of normal and peritumoral bladder walls, and to characterize immunocompetent cells before and during intravesical instillations of bacillus Calmette-Guérin (BCG). Twenty-three patients with superficial urothelial bladder carcinoma (stages pTa to pT1, grades 1-3) were treated with six weekly instillations of 150 mg of BCG (Pasteur strain). Biopsies of cystoscopically normal bladder wall were taken before, 3 weeks and 3 months after BCG instillation. The controls comprised bladder biopsy specimens from 13 brain-dead ventilated kidney donors. Local infiltrating cell types, i.e. lymphocyte infiltrates (CD4, CD8, CD20, CD3, interleukin-2-receptor-positive, natural killer, gammadelta), macrophages and dendritic cells, adhesion and costimulatory molecules (ICAM-1 and B7-BB1) and major histocompatibility complex (MHC) class I and class II antigens were assessed using semi-quantitative immunohistochemical analysis. Before BCG the peritumoral bladder wall had fewer macrophages than control bladder wall. BCG treatment restored normal numbers of macrophages and enhanced T helper lymphocytes, B lymphocytes, natural killer cells, activated lymphocytes, dendritic cells, normal MHC class I, adhesion (ICAM-1) and costimulatory (B7-BB1) expression. The enhancement of these immunological variables was transient, with a return to baseline 3 months after BCG instillation. These results support the concept that there is a host-immune escape associated with bladder cancer. BCG therapy may temporarily restore impaired tumour rejection mechanisms in the peritumoral bladder wall, suggesting a need for maintenance therapy after the first course of BCG.

Il carcinoma uroteliale della vescica pT1G3. Studio clinico-patologico e morfometrico di 26 casi trattati con BCG:Urothelial bladder carcinoma pT1G3. Clinico-pathological and morphometric study of 26 cases treated with BCG

From 1987 to 1993, 26 patients with superficial urothelial bladder carcinoma pT1G3 were observed consecutively at the Dept. of Urology of Pordenone City Hospital and the Division of Pathology of the Centro di Riferimento Oncologico di Aviano (Italy). All patients were treated with TUR and then with a course of BCG-intravesical instillations. The complete immunoprophylaxis treatment consisted of a weekly instillation of BCG for 6 weeks; then cystoscopy and urinary cytologies or random biopsies were performed. An additional 1-monthly BCG treatment for 3 months was administered to 10 disease-free patients. In 6 cases of pT1G3 recurrences, a new complete cycle of BCG was performed whereas in 10 patients with local progression, defined as muscular infiltration, a cystoprostatectomy or RT therapy was advised. Follow-up examinations, planned every 3 months for 2 years and then every 6 months for 3 years, included cystoscopy and urinary cytologies in 19 patients and cystoscopy with randomized biopsies and washing in the remaining 7 patients. Ten patients were disease-free at a mean of 34 months follow-up (range 13-65 months); 6 patients experienced recurrence at a mean of 7 months follow-up (range 3-40 months) and 10 patients local progression at a mean of 13 months follow-up (range 3-44 months). The morphometric study demonstrated that cases with average nuclear area, in the deepest part of the histological section, more or equal to 40 μm2have a threefold progression rate, compared to cases with average nuclear area less than 40 μm2(p = 0.10). Our results would indicate the possible role of morphometric evaluation of prognostically important parameters, in the clinical management of patients with pT1G3 tumours.