Vimentin over-expression and carbonic anhydrase IX under-expression are independent predictors of recurrence, specific and overall survival in non-metastatic clear-cell renal carcinoma: a validation study.

PURPOSE: Clinical outcomes prognostic markers are awaited in clear-cell renal carcinoma (ccRCC) to improve patient-tailored management and to assess six different markers' influence on clinical outcomes from ccRCC specimen and their incremental value combined with TNM staging. MATERIALS AND METHODS: This is a retrospective, multicenter study. One hundred and forty-three patients with pT1b-pT3N0M0 ccRCC were included. Pathology specimens from surgeries were centrally reviewed, mounted on a tissue micro-array and stained with six markers: CAIX, c-MYC, Ki67, p53, vimentin and PTEN. Images were captured through an Ultra Fast Scanner. Tumor expression was measured with Image Pro Plus. Cytoplasmic markers (PTEN, CAIX, vimentin, c-MYC) were expressed as surface percentage of expression. Nuclear markers (Ki67, p53) were expressed as number of cells/mm2. Clinical data and markers expression were compared with clinical outcomes. Each variable was included in the Cox proportional multivariate analyses if p < 0.10 on univariate analyses. Discrimination of the new marker was calculated with Harrell's concordance index. RESULTS: At median follow-up of 63 months (IQR 35.0-91.8), on multivariate analysis, CAIX under-expression and vimentin over-expression were associated with worse survival (recurrence, specific and overall survival). A categorical marker CAIX-/Vimentin+ with cutoff points for CAIX and vimentin of 30 and 50 %, respectively, was designed. The new CAIX-/Vimentin+ marker presented a good concordance and comparable calibration to the reference model. Limitations are the retrospective design, the need for external validation and the large study period. CONCLUSION: Using an automated technique of measurement, CAIX and vimentin are independent predictors of clinical outcomes in ccRCC.

Multiparametric magnetic resonance imaging and prostate cancer: what's new? / Resonancia magnética multiparamétrica y cáncer de próstata: ¿qué hay de nuevo?

Prostatic multi-parametric magnetic resonance imaging (MP-MRI) has recently had a wide development becoming a key tool in the diagnostic and therapeutic decisions in prostate cancer (Pca). The fast development both in technology and in reading (PIRADS V2) requires a continuous updating of knowledge within this area. The aim of this article is to present an updated revision of technical aspects, reading patterns and prostatic MP-MRI in Pca, with a multidisciplinary approach. Currently guidelines establish the use of the MP-MRI when there is a high PSA and a negative prostatic biopsy; tumor staging; evaluation in candidates to active surveillance; focal treatments plans and tumoral recurrence evaluation. Although it is used in other indications in some centers, like its use in patients suspicious of Pca but with no previous biopsy, there is still the need of a cost/benefit assessment for its use to be wider.

Follow-up after focal therapy in renal masses: an international multidisciplinary Delphi consensus project.

PURPOSE: To establish consensus on follow-up (FU) after focal therapy (FT) in renal masses. To formulate recommendations to aid in clinical practice and research. METHODS: Key topics and questions for consensus were identified from a systematic literature research. A Web-based questionnaire was distributed among participants selected based on their contribution to the literature and/or known expertise. Three rounds according to the Delphi method were performed online. Final discussion was conducted during the "8th International Symposium on Focal Therapy and Imaging in Prostate and Kidney Cancer" among an international multidisciplinary expert panel. RESULTS: Sixty-two participants completed all three rounds of the online questionnaire. The panel recommended a minimum follow-up of 5 years, preferably extended to 10 years. The first FU was recommended at 3 months, with at least two imaging studies in the first year. Imaging was recommended biannually during the second year and annually thereafter. The panel recommended FU by means of CT scan with slice thickness ≤3 mm (at least three phases with excretory phase if suspicion of collecting system involvement) or mpMRI. Annual checkup for pulmonary metastasis by CT thorax was advised. Outside study protocols, biopsy during follow-up should only be performed in case of suspicion of residual/persistent disease or radiological recurrence. CONCLUSIONS: The consensus led to clear FU recommendations after FT of renal masses supported by a multidisciplinary expert panel. In spite of the low level of evidence, these recommendations can guide clinicians and create uniformity in the follow-up practice and for clinical research purposes.

Cumulative morbidity of ureteroscopy for upper tract urothelial carcinoma.

OBJECTIVE: To assess complications after ureteroscopy (URS) for upper tract urothelial carcinoma (UTUC) management and to assess its postoperative cumulative morbidity burden using the Comprehensive Complication Index (CCI). MATERIALS AND METHODS: Single center retrospective study including patients submitted to URS for UTUC suspicion. URSs were both diagnostic and operative. Postoperative complications were recorded according to the EAU Guidelines and graded according to Clavien-Dindo Classification (CDC). The cumulative postoperative morbidity burden developed by patients experiencing multiple events was assessed using the CCI. Multivariable logistic regression (MLR) analyses identified factors independently associated with the development of any grade and major postoperative complications. RESULTS: Overall, 360 patients with UTUC suspicion were included with a total of 575 URSs performed. The cumulative number of all postoperative complications recorded was 111. In 86 (15%) procedures, patients experienced at least one postoperative complication, while 25 (4.3%) experienced more than one complication. Of these, 16 (14%) were severe (CDC ≥ IIIa). The most frequent type of complications were urinary (34%), bleeding (30%) and infectious (30%). The higher the CDC grade, the higher the median CCI, with a statistically significant increase in median CCI from CDC II to major complications. Patients who experienced intraoperative complications were at higher risk of developing any grade and major postoperative complications at MLR. CONCLUSIONS: Complications after ureteroscopy for UTUC are relatively uncommon events. Patients who experience intraoperative complications are at higher risk of developing postoperative complications. The comprehensive complication index appeared more representative of the cumulative postoperative morbidity rather than the Clavien-Dindo classification.

What is the added value of combined core biopsy and fine needle aspiration in the diagnostic process of renal tumours?

PURPOSE: Non-diagnostic results still hinder the routine use of core biopsy (CB) and fine needle aspiration (FNA) in the diagnostic process of renal tumours. Furthermore, substantial interobserver variability has been reported. We assessed the added value of combining the results of CB and FNA by five pathologists in the ex vivo diagnosis of renal mass. METHODS: Two ex vivo core biopsies were taken followed by two FNA passes from extirpated tumours. All samples were evaluated by five blinded pathologists. A consensus diagnosis of the surgical specimen was the index for comparison. For each pathologist, the number of non-diagnostic (non-conclusive or undetermined biology and failed biopsies), correct and incorrect scored cases of each technique was assessed. When a non-diagnostic CB or FNA had a correct diagnostic counterpart, this was considered as of added value. RESULTS: Of the 57 assessed tumours, 53 were malignant. CB was non-diagnostic in 4-10 cases (7-17.5%). FNA established the correct diagnosis in 1-7 of these cases. FNA was non-diagnostic in 2-6 cases (3.5-10.5%), and the counterpart CB established the correct diagnosis in 1-6 of these cases. For the 5 pathologists, accuracy of CB and FNA varied between 82.5-93% and 89.5-96.5%, respectively. Combination of both types of biopsy resulted in 55-57 correct results (accuracy 96.5-100%), i.e., an increase in accuracy of 3.5-14%. CONCLUSION: Combining the result of CB and FNA in renal mass biopsy leads to a higher diagnostic accuracy. Recommendations on which technique used should be adapted to local expertise and logistic possibilities.

Indications and histology of 489 orchiectomies analyzed by patient age.

OBJECTIVE: To evaluate the indications and histology of our series of orchiectomies, analysing the results by patient's age. METHODS: We included the orchiectomies realized in our hospital between 2005 and 2020 in patients older than 18 years. We estimated demographic data, indications, histology and effectiveness of testicular ultrasound by three groups of age. RESULTS: We included 489 orchiectomies, which 364 (74%) belonged to Group A (patients between 18-50 years), 59 (12%) to Group B (50-70 years) and 66 (14%) to Group C (older than 70 years). In Group A, 284 (78%) orchiectomies were indicated due to malignancy suspect. In 91.9% cases (261) malign neoplasm was confirmed at final histology and 253 (89%) were germinal cells. Testicular ultrasound had a positive predictive value (PPV) of 90% in this group. In Group B, 34 (57%) orchiectomies were indicated because of malignancy suspect. At final histologic analysis, 25/34 (73.5%) confirmed malign neoplasm. Ultrasound had a PPV of 68%. In Group C, orchiepididymitis was the main cause of testicular removal with 30 cases (45,5%). From the 20 cases (30.3%) with suspicion of malignancy, only 6 had confirmed malign histology. Testicular ultrasound PPV for malignancy was 31%. CONCLUSION: In patients younger than 70 years the main orchiectomy's indication was suspect of malignancy and in older than 70, testicular inflammation. The germinal neoplasm was the predominant histology in younger than 70 years. In older than that, malignancy was infrequent. The positive predictive value of testicular ultrasound for malignancy decreased with patient's age. In patients older than 50 years proper image diagnosis to assess malignancy should be considered before orchiectomy is done.

The 1973 WHO and 2004 WHO grading systems are not equal in prediction of survival among stage T1 bladder cancer patients. / Los sistemas de clasificación de la OMS de 1973 y 2004 difieren en la predicción de supervivencia entre los pacientes con cáncer de vejiga en estadio T1.

INTRODUCTION AND OBJECTIVES: The aim of this study was to analyse prognostic impact of tumour histological grade on survival differences between primary G2 and G3 WHO1973 stage T1 tumours which were graded as HG according to WHO2004 grading system. MATERIALS AND METHODS: Data from 481 patients with primary T1HG bladder cancer who were treated between 1986 and 2016 in 2university centres were retrospectively reviewed. Log-rank test and Cox regression analysis was performed to compare the groups. RESULTS: 95 (19,8%) tumours were classified as G2 and 386 (80,2%) were G3. Median follow-up was 68 months. The recurrence was observed in 228 (47,5%), and progression in 109 patients (22,7%). Radical cystectomy was performed in 114 pts (23,7%) and there were 64 (13,3%) cancer specific deaths. Recurrence-free rates at 5-years follow-up for G2, G3 and all patients were 68,7%, 51,2% and 56,3% and progression-free rates were 89,3%, 73,2% and 78,1% respectively. For total observation period patients with G3 tumours presented also worse recurrence-free, and progression-free survival levels than patients with G2 tumours. In multivariate analysis, after adjustment for clinical features, the risk of recurrence and progression for G3 tumours was 1,65 and 2,42 fold higher than for G2 tumours. CONCLUSIONS: It was shown that G3 T1 tumours are characterized by worse recurrence free and progression free survivals when compared to G2 cancers.

Handling and reporting of radical prostatectomy specimens in Europe: a web-based survey by the European Network of Uropathology (ENUP).

AIMS: To survey current European practices in handling and reporting of radical prostatectomy (RP) specimens. METHODS AND RESULTS: A European Network of Uropathology (ENUP) was organized for the dissemination of information, survey studies and research collaborations. Contact data of uropathologists were collected from 321 pathology laboratories in 15 West European countries. In the first ENUP survey, 67.6% (217/321) of the members replied to a web-based questionnaire. Some practices were adopted by a large majority, e.g. inking of the specimen (96.6%), Gleason grading (99.5%), stratifying extraprostatic extension (EPE) according to extent (88.2%), reporting TNM stage (88.6%) and reporting location of positive margins (98%). As many as 71.6% of respondents always embedded the entire prostate and only 10.8% always practised partial embedding. Whole mounts were routinely used by 37.5% and standard blocks by 55.5%. Among areas with variable routines were methods to define focal versus extensive EPE and methods to quantify margin positivity, probably reflecting that the optimal method has yet to be determined. CONCLUSIONS: Some practices are almost universally adopted in Europe, whereas others still need to be standardized. The results of the study may be helpful when judging what recommendations are reasonable to issue.

Preservation of renal function in a patient with Fabry nephropathy on enzyme replacement therapy.

Fabry disease is an X-linked recessive inborn error of glycosphingolipid metabolism caused by the deficient activity of the lysosomal enzyme, alpha-galactosidase A. Enzyme replacement therapy (ERT) for this disorder has been available in Europe since 2001. However, its effect on advanced renal failure remains controversial. We report the case of a patient whose decline in renal function was reduced by the administration of ERT (agalsidase-alpha). This reduction was more pronounced after doubling the dose of the enzyme. The rate of deterioration of eGFR went from 6.3 ml/min/year prior to the start of ERT (0.2 mg/kg) to 2 ml/min/year (0.4 mg/kg). To our knowledge, this is the first reported case of a patient with moderately impaired renal function treated with high doses of ERT and follow-up of 6 years. The data shown here suggest that ERT may have a very positive impact on renal function even in advanced stages. The role of proteinuria and its control seem to have a clear responsibility for this favorable outcome.

Pseudoneoplastic lesions of the testis and paratesticular structures.

Pseudotumors or tumor-like proliferations (non-neoplastic masses) and benign mimickers (non-neoplastic cellular proliferations) are rare in the testis and paratesticular structures. Clinically, these lesions (cysts, ectopic tissues, and vascular, inflammatory, or hyperplastic lesions) are of great interest for the reason that, because of the topography, they may be relevant as differential diagnoses. The purpose of this paper is to present an overview of the pseudoneoplasic entities arising in the testis and paratesticular structures; emphasis is placed on how the practicing pathologist may distinguish benign mimickers and pseudotumors from true neoplasia. These lesions can be classified as macroscopic or microscopic mimickers of neoplasia.

[Frozen section in urological oncology]. / La biopsia intraoperatoria en patología oncológica urológica.

The indications of Frozen section diagnosis (FS) in surgery due to urologic neoplasia are quite specific, and this explains the fact that they amount to a mere 7.3% of the FSs performed in general hospitals. This also makes the knowledge of their usefulness necessary, and thus we are submitting the present review. Generally speaking, FS is not warranted to identify the nature of a tumoral mass, with the following exceptions: (1) Renal masses of a doubtf ul parenchymal origin, or in the urinary tract: (2) Intesticular neoplasias,when the possibility of a conservative treatment arises; (3) Determination of the presence of a prostate adenocarcinoma in an organ donor with high serum PSA; but even in these circumstances its need is widely controversial. Intraoperative determination of surgical margins is particularly useful in: (1) Partial nephrectomies (it may be limited to inspection after dyeing the margin with Indian ink--bed freezing is very seldom needed); (2) Urethral margins in women with total cystectomies and orthotopic substitution; (3) In partial penectomies (always studying the urethral margin and the cavernosal and spongIosal corpora margins). The study of the nodes is a widely debated issue, and except for those cases in which unexpectedly increased node size is found, systematic FS is indicated neither of the bladder nor of the prostate. The situation regarding penis carcinoma is different, as in the groups with intermediate and high risk of node metastasis, even though there is around 16%-18% of false negatives FS is recommended, particularly of radioisotope-marked sentinel nodes.

[Urothelial carcinoma in a woman with autosomal dominant polycystic kidney disease: description of a case and review of the literature]. / Carcinoma urotelial renal en una paciente con enfermedad renal poliquística autosómico dominante: presentación de un caso y revisión de la literatura.

We describe a case of urothelial carcinoma of renal pelvis in a 48 years old woman affected of autosomal dominant polycystic kidney disease (ADPKD). We discuss the difficulty of the radiological diagnostic and we revise the incidence of renal tumors in this entity. Association between urothelial carcinoma and ADPKD is highly infrequent and without apparently causal relation.

Adipocyte accumulation in corpus cavernosum: First clinical evidence and pathophysiological implications in erectile dysfunction. / Acumulación de adipocitos en el cuerpo cavernoso: primera evidencia clínica e implicaciones fisiopatológicas en la disfunción eréctil.

OBJECTIVES: Animal models have shown that erectile dysfunction is associated with adipocyte accumulation under tunica albugínea, which could be involved in venous leakage and loss of penile rigidity. In the current sudy, we compared the histology of the penile sub-albuginean region of drug-refractory erectile dysfunction patients undergoing penile prosthesis implantation with potent patients with Peyronie's disease undergoing curvature correction procedures. MATERIALS AND METHODS: Seventeen refractory erectile dysfunction patients and fourteen potent patients with Peyronie's disease were recruited. Sub-albuginean tissue samples were taken in each surgery. An expert uropathologist analysed each section. A bivariate analysis was performed. Multivariate logistic regression was used to calculate adjusted odds ratios; P value<.05 was considered significant. RESULTS: Eleven patients (11/17) in the case group presented cavernous fat cell accumulation, while only one patient (1/14) in the control group presented this finding (P<.05). Adjusted odds ratio for erectile dysfunction was 40.72; 95% CI 2.28-727.29 (P=.012). CONCLUSIONS: Different studies have shown that androgen disruption could be involved in penile structural changes, leading to trabecular smooth muscle apoptosis and trans or de-differentiation into adipocytes. This is the first prospective study in humans to report an association between erectile dysfunction and sub-albuginean adipocyte accumulation. Venous leakage secondary to this phenomenon could be a factor in the pathophysiology of erectile dysfunction, especially in patients that do not respond to medical therapy.

HIF pathway and c-Myc as biomarkers for response to sunitinib in metastatic clear-cell renal cell carcinoma.

BACKGROUND: Clear-cell renal cell carcinoma (ccRCC) is a heterogeneous disease with a different clinical behavior and response to targeted therapies. Differences in hypoxia-inducible factor (HIF) expression have been used to classify von Hippel-Lindau gene (VHL)-deficient ccRCC tumors. c-Myc may be driving proliferation in HIF-2α-expressing tumors in a growth factor-independent manner. OBJECTIVE: To explore the HIF-1α, HIF-2α and c-Myc baseline expression as potential predictors of sunitinib outcome as well as the effectiveness and safety with sunitinib in patients with metastatic ccRCC in routine clinical practice. METHODS: This was an observational and prospective study involving 10 Spanish hospitals. Formalin-fixed, paraffin-embedded primary tumor samples from metastatic ccRCC patients who received sunitinib as first-line treatment were analyzed. Association between biomarker expression and sunitinib treatment outcomes was evaluated. Kaplan-Meier method was applied to measure progression-free survival (PFS) and overall survival. RESULTS: Eighty-one patients were included: median PFS was 10.8 months (95% CI: 7.4-13.5 months), median overall survival was 21.8 months (95% CI: 14.7-29.8 months) and objective response rate was 40.7%, with 7.4% of patients achieving a complete response. Molecular marker staining was performed in the 69 available tumor samples. Significant association with lower PFS was identified for double c-Myc/HIF-2α-positive staining tumors (median 4.3 vs 11.5 months, hazard ratio =2.64, 95% CI: 1.03-6.80, P=0.036). A trend toward a lower PFS was found in positive c-Myc tumors (median 5.9 vs 10.9 months, P=0.263). HIF-1α and HIF-2α expression levels were not associated with clinical outcome. CONCLUSION: These preliminary results suggest that predictive subgroups might be defined based on biomarkers such as c-Myc/HIF-2α. Further validation with more patients will be needed in order to confirm it. Outcomes with sunitinib in metastatic ccRCC in daily clinical practice resemble those obtained in clinical trials.

Molecular staging of bladder cancer with RT-PCR assay for CK20 in peripheral blood, bone marrow and lymph nodes: comparison with standard histological staging.

BACKGROUND: The aim of this study was to analyze whether the CK20 reverse transcriptase polymerase chain reaction (RT-PCR) is suitable for detecting circulating tumor cells and residual tumor cells in lymph nodes, in patients with muscle invasive transitional cell carcinoma (TCC) of the bladder, and to compare these results with standard histological staging. PATIENTS AND METHODS: The nested RT-PCR assay was used to analyze the CK20 transcript in the peripheral blood, bone marrow, lymph nodes, the tumor and normal biopsies of bladder from 57 patients with invasive TCC of the bladder, who underwent radical cystectomy, and from 9 patients with noninvasive TCC. RESULTS: Lymph node pathological status was positive in 24 out of the 57 patients studied and all of them except I showed expression of CK20, with a correlation between histological technique and RT-PCR of 95.8%. A statistically significant correlation of lymph node CK20 RT-PCR with the standard risk factor of pathological stage (p = 0.04) was observed Blood and bone marrow CK20 RT-PCR showed no correlation with pathological stage. CONCLUSION: Lymph node CK 20 RT-PCR correlates with pathological stage in bladder cancer. The CK20 RT-PCR assay appears to be a highly sensitive and specific method for detecting circulating tumor cells and residual disease in lymph nodes in patients with invasive bladder cancer. Further evaluation of the significance of CK20 as a molecular marker for staging and follow-up in these patients is necessary.

[Usefulness of the present renal cell carcinoma classifications]. / Aplicación clínica de las actuales clasificaciones del cáncer renal.

The purpose of classifying neoplasias is to recognize groups with similar progress and prognosis and, if possible, receiving the same treatment. This is why those classifications are systematically being submitted to review and improvement through the new technologies. Differentiation of various entities in renal cancer has been comparatively fast, as the new genetic and molecular discoveries have confirmed the morphologic criteria of the different cell types, thus making it possible to open new therapeutic pathways. Using the current WHO classification we recognize subtypes with excellent prognosis (Multilocular cystic renal carcinoma, Type I renal papillary carcinoma, Tubular and fusocellular mucinous carcinoma), other very aggressive ones (Bellini's collecting duct carcinoma, Medullary carcinoma), and also that the sarcomatoid transformation, even in small areas, impacts the prognosis negatively. Childhood-characteristic renal carcinomas associated with chromosome translocations have been recognized (genetic fusion TFE3 or TFEB), as well as the family forms of renal carcinoma. Regarding the UICC (International Union Against Cancer) classification, there are a series of aspects under argument (size, venous invasion, microvascular invasion, invasion of the adipous tissue of the renal sinus) that shall be discussed too, since it is possible that some modifications of the TNM might occur in the near future.