Ferran Algaba

Publications of Ferran Algaba

• Utility of whole slide imaging and virtual microscopy in prostate pathology.

  Authors: Philippe Camparo, Lars Egevad, Ferran Algaba, Daniel M Berney, Liliane Boccon-Gibod, Eva Compérat, Andrew J Evans, Rainer Grobholz, Glen Kristiansen, Cord Langner, Antonio Lopez-Beltran, Rodolfo Montironi, Pedro Oliveira, Ben Vainer, Murali Varma

  APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. 04/2012; 120(4):298-304.

  Whole slide imaging (WSI) has been used in conjunction with virtual microscopy (VM) for training or proficiency testing purposes, multicentre research, remote frozen section diagnosis and to seekWhole slide imaging (WSI) has been used in conjunction with virtual microscopy (VM) for training or proficiency testing purposes, multicentre research, remote frozen section diagnosis and to seek specialist second opinion in a number of organ systems. The feasibility of using WSI/VM for routine surgical pathology reporting has also been explored. In this review, we discuss the utility and limitations of WSI/VM technology in the histological assessment of specimens from the prostate. Features of WSI/VM that are particularly well suited to assessment of prostate pathology include the ability to examine images at different magnifications as well as to view histology and immunohistochemistry side-by-side on the screen. Use of WSI/VM would also solve the difficulty in obtaining multiple identical copies of small lesions in prostate biopsies for teaching and proficiency testing. It would also permit annotation of the virtual slides, and has been used in a study of inter-observer variation of Gleason grading to facilitate precise identification of the foci on which grading decisions had been based. However, the large number of sections examined from each set of prostate biopsies would greatly increase time required for scanning as well as the size of the digital file, and would also be an issue if digital archiving of prostate biopsies is contemplated. Z-scanning of glass slides, a process that increases scanning time and file size would be required to permit focusing a virtual slide up and down to assess subtle nuclear features such as nucleolar prominence. The common use of large blocks to process prostatectomy specimens would also be an issue, as few currently available scanners can scan such blocks. A major component of proficiency testing of prostate biopsy assessment involves screening of the cores to detect small atypical foci. However, screening virtual slides of wavy fragmented prostate cores using a computer mouse aided by an overview image is very different from screening glass slides using a microscope stage. Hence, it may be more appropriate in this setting to mark the lesional area and focus only on the interpretation component of competency testing. Other issues limiting the use of digital pathology in prostate pathology include the cost of high quality slide scanners for WSI and high resolution monitors for VM as well as the requirement for fast Internet connection as even a subtle delay in presentation of images on the screen may be very disturbing for a pathologist used to the rapid viewing of glass slides under a microscope. However, these problems are likely to be overcome by technological advances in the future.

• Unclassified renal cell carcinoma: a report of 56 cases.

  Authors: Antonio Lopez-Beltran, Ziya Kirkali, Rodolfo Montironi, Ana Blanca, Ferran Algaba, Marina Scarpelli, Kutsal Yorukoglu, Arndt Hartmann, Liang Cheng

  BJU international. 03/2012;

  Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Unclassified RCC represents 0.7-5.7% of renal tumours. Limited reported data from twoStudy Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Unclassified RCC represents 0.7-5.7% of renal tumours. Limited reported data from two series suggests that unclassified RCC is an aggressive form of RCC, mainly because most cases are at an advanced stage at presentation, but overall and cancer-specific survival were not significantly different between unclassified and clear-cell RCC in an additional series of 38 patients. Our study of 56 cases of unclassified RCC describes the pathological features that can be applied to predict prognosis on a daily basis. In particular nuclear grade, TNM classification, tumour coagulative necrosis, tumour size, microvascular invasion and 2004 WHO histotype are independent predictors of disease-free and cancer-specific survival. OBJECTIVE: •  To evaluate the clinicopathological features and outcomes of 56 patients with unclassified renal cell carcinoma (RCC) meeting 2004 World Health Organization diagnostic criteria. PATIENTS AND METHODS: •  Urological pathology files of the participating institutions were reviewed and cases of unclassified RCC that met the inclusion criteria were retrieved. •  Nuclear grade, pT status, tumour size, regional lymph node involvement, distant metastases, coagulative tumour necrosis, mucin and sarcomatoid differentiation were evaluated in radical nephrectomy or nephron-sparing specimens. •  Significant factors in univariate analysis were then assessed by a multivariate analysis of independent prognostic factors using Cox proportional hazard regression analysis. RESULTS: •  Fifty-six cases met the histological criteria for unclassified RCC. Thirty-four (61%) cases were categorized as unrecognizable cell type (mean overall survival 47 months; median 36 months), 20 (36%) as composites of recognized types (mean overall survival 36 months; median 26 months), and two (4%) (mean survival 16 months; median 16 months) as pure sarcomatoid morphology without recognizable epithelial elements. •  Cox multivariate analysis showed nuclear grade (P= 0.020), stage (P < 0.001), tumour coagulative necrosis (P= 0.018), tumour size (P < 0.001), microvascular invasion (P < 0.001) and tumour histotype (P= 0.028) to be independent predictors of disease-free survival, with tumour size being the most significant (hazard ratio [HR] 9.068, 95% confidence interval [CI] 3.231-25.453). •  Nuclear grade (P= 0.026), stage (P < 0.001), tumour coagulative necrosis (P < 0.001), tumour size (P= 0.044), microvascular invasion (P < 0.001), tumour recurrence after surgery (P < 0.001) and tumour histotype (P= 0.056) were independent predictors of cancer-specific survival, with tumour recurrence after surgery being the most significant (HR 14.713, 95% CI 5.329-40.622). CONCLUSION: •  The prognosis of patients with unclassified RCC seems to be related to clinicopathological features known to be relevant in common forms of RCC.

• Female Gender and Carcinoma In Situ in the Prostatic Urethra Are Prognostic Factors for Recurrence, Progression, and Disease-Specific Mortality in T1G3 Bladder Cancer Patients Treated With Bacillus Calmette-Guérin.

  Authors: Joan Palou, Richard J Sylvester, Oscar Rodríguez Faba, Rubén Parada, Juan A Peña, Ferran Algaba, Humberto Villavicencio

  European urology. 10/2011;

  BACKGROUND: Controversy exists over the most important prognostic factors in T1 high-grade non-muscle-invasive bladder cancer (NMIBC) patients treated with bacillus Calmette-Guérin (BCG). OBJECTIVE:BACKGROUND: Controversy exists over the most important prognostic factors in T1 high-grade non-muscle-invasive bladder cancer (NMIBC) patients treated with bacillus Calmette-Guérin (BCG). OBJECTIVE: Evaluate prognostic factors for recurrence, progression, and disease-specific mortality after adjuvant intravesical BCG immunotherapy in patients with T1G3 NMIBC and long-term follow-up. DESIGN, SETTING, AND PARTICIPANTS: A single-institution retrospective analysis of 146 patients with primary stage T1G3 NMIBC. INTERVENTION: All patients were treated with complete transurethral resection (TUR) plus multiple bladder biopsies that included the prostatic urethra. No second TUR was done. Patients underwent an induction course of intravesical BCG (Connaught strain, 81mg) without maintenance therapy. MEASUREMENTS: The variables analysed for time to recurrence, progression, and death due to bladder cancer (BCa) were gender, age, tumour multiplicity, diameter, aspect, substaging, concomitant carcinoma in situ (CIS), and CIS in the prostatic urethra. Cox regression models were used to assess the univariate and multivariate prognostic importance of these factors and estimate hazard ratios (HRs). Time-to-event distributions were estimated using cumulative incidence functions. RESULTS AND LIMITATIONS: The median follow-up was 8.7 yr. Sixty-five patients (44.5%) had recurrence, 25 patients (17.1%) had progression, and 18 patients (12.3%) died because of BCa. Female gender and presence of CIS in the prostatic urethra were associated with an increased risk of recurrence (p=0.0003, HR: 2.53), progression (p=0.001, HR: 3.59), and death due to BCa (p=0.004, HR: 3.53). CONCLUSIONS: In primary T1G3 bladder tumours treated with induction BCG, female gender or having CIS in the prostatic urethra were the only prognostic factors for time to recurrence, progression, and disease-related mortality. It is very important to perform a biopsy of the prostatic urethra in patients with primary high-grade NMIBC as a first step to obtain this prognostic information.

• Diagnosis, staging, and risk factors: SIU/ICUD Consensus Meeting on Germ Cell Tumors (GCT), Shanghai 2009.

  Authors: Peter Albers, Ferran Algaba, Gabriella Cohn-Cedermark, Maria DeSantis, Sabine Kliesch, Judd W Moul

  Urology. 10/2011; 78(4 Suppl):S427-34.

• Handling and reporting of nephrectomy specimens for adult renal tumours: a survey by the European Network of Uropathology.

  Authors: Ferran Algaba, Brett Delahunt, Daniel M Berney, Philippe Camparo, Eva Compérat, David Griffiths, Glen Kristiansen, Antonio Lopez-Beltran, Guido Martignoni, Holger Moch, Rodolfo Montironi, Murali Varma, Lars Egevad

  Journal of clinical pathology. 09/2011; 65(2):106-13.

  To collect information on current practices of European pathologists for the handling and reporting of nephrectomy specimens with renal tumours. A questionnaire was circulated to the members of theTo collect information on current practices of European pathologists for the handling and reporting of nephrectomy specimens with renal tumours. A questionnaire was circulated to the members of the European Network of Uropathology, which consists of 343 pathologists in 15 European countries. Replies were received from 48% of members. These replies indicated that nephrectomy specimens are most often received in formalin. Lymph nodes are found in less than 5% of nephrectomy specimens. All respondents give an objective measure of tumour size, most commonly in three diameters. The most common method to search for capsule penetration is to slice tissue outside the tumour perpendicularly into the tumour. The most common sampling algorithm from tumours greater than 2 cm is one section for every centimetre of maximum tumour diameter. Most respondents use the 2004 WHO renal tumour classification although only slightly over half consider small papillary tumours malignant if the diameter is greater than 5 mm. The Fuhrman grading system is widely used. Almost all use immunohistochemistry for histological typing in some cases, while only 7% always use it. The most utilised special stains are CK7 (95%), CD10 (93%), vimentin (86%), HMB45 (68%), c-kit (61%) and Hale's colloidal iron (52%). Only 18% use other ancillary techniques for diagnosis in difficult cases. While most pathologists appear to follow published guidelines for reporting renal carcinoma, there is still a need for the development of consensus and further standardisation of practice for contentious areas of specimen handling and reporting.

• EAU guidelines on testicular cancer: 2011 update.

  Authors: Peter Albers, Walter Albrecht, Ferran Algaba, Carsten Bokemeyer, Gabriella Cohn-Cedermark, Karim Fizazi, Alan Horwich, Maria Pilar Laguna

  European urology. 08/2011; 60(2):304-19.

  On behalf of the European Association of Urology (EAU), guidelines for the diagnosis, therapy, and follow-up of testicular cancer were established. This article is a short version of the EAUOn behalf of the European Association of Urology (EAU), guidelines for the diagnosis, therapy, and follow-up of testicular cancer were established. This article is a short version of the EAU testicular cancer guidelines and summarises the main conclusions from the guidelines on the management of testicular cancer. Guidelines were compiled by a multidisciplinary guidelines working group. A systematic review was carried out using Medline and Embase, also taking Cochrane evidence and data from the European Germ Cell Cancer Consensus Group into consideration. A panel of experts weighted the references, and a level of evidence and grade of recommendation were assigned. There is a paucity of literature especially regarding longer term follow-up, and results from a number of ongoing trials are awaited. The choice of treatment centre is of the utmost importance, and treatment in reference centres within clinical trials, especially for poor-prognosis nonseminomatous germ cell tumours, provides better outcomes. For patients with clinical stage I seminoma, based on recently published data on long-term toxicity, adjuvant radiotherapy is no longer recommended as first-line adjuvant treatment. The TNM classification 2009 is recommended. These guidelines contain information for the standardised management of patients with testicular cancer based on the latest scientific insights. Cure rates are generally excellent, but because testicular cancer mainly affects men in their third or fourth decade of life, treatment effects on fertility require careful counselling of patients, and treatment must be tailored taking individual circumstances and patient preferences into account.

• Current pathology keys of renal cell carcinoma.

  Authors: Ferran Algaba, Hideyuki Akaza, Antonio López-Beltrán, Guido Martignoni, Holger Moch, Rodolfo Montironi, Victor Reuter

  European urology. 07/2011; 60(4):634-43.

  Renal cell carcinoma (RCC) in adults comprises a heterogeneous group of tumours with variable clinical outcomes that range from indolent to overtly malignant. The application of molecular geneticRenal cell carcinoma (RCC) in adults comprises a heterogeneous group of tumours with variable clinical outcomes that range from indolent to overtly malignant. The application of molecular genetic techniques to the study of renal neoplasms has resulted in an improved classification of these entities and a better understanding of the biologic mechanisms responsible for tumour development and progression. The current 2004 World Health Organisation classification of adult renal epithelial neoplasms has expanded rapidly with new categories recently incorporated. To review and evaluate the evidence implicating pathologic features and classification of RCC in adults as a tool to approach patients' prognosis and modulate current therapy. Members of Committee 3: Pathology, under the auspices of the International Consultation on Urological Diseases and the European Association of Urology (ICUD-EAU) International Consultation on Kidney Cancer, performed a systematic review using PubMed. Participating pathologists discussed pathologic categories and diagnostic features of RCC in adults. We reviewed and discussed articles and the personal experiences of participating uropathologists. The conclusions reached by the ICUD-EAU 2010 International Consultation on Kidney Cancer emphasise the appropriate pathologic diagnosis of RCC in adults as a tool to approach patients' prognosis and modulate current therapy. Further emphasis should be placed on defining risk groups of RCC and diagnostic features of unusual tumours such as familial RCC, translocation RCC, and tubular mucinous and spindle cell carcinoma. A number of recently described entities and morphologic variants of classical categories deserves recognition because they can be important in differential diagnosis and therapy.

• Interactive digital slides with heat maps: a novel method to improve the reproducibility of Gleason grading.

  Authors: Lars Egevad, Ferran Algaba, Daniel M Berney, Liliane Boccon-Gibod, Eva Compérat, Andrew J Evans, Rainer Grobholz, Glen Kristiansen, Cord Langner, Gina Lockwood, Antonio Lopez-Beltran, Rodolfo Montironi, Pedro Oliveira, Matthias Schwenkglenks, Ben Vainer, Murali Varma, Vincent Verger, Philippe Camparo

  Virchows Archiv : an international journal of pathology. 06/2011; 459(2):175-82.

  Our aims were to analyze reporting of Gleason pattern (GP) 3 and 4 prostate cancer with the ISUP 2005 Gleason grading and to collect consensus cases for standardization. We scanned 25 prostate biopsyOur aims were to analyze reporting of Gleason pattern (GP) 3 and 4 prostate cancer with the ISUP 2005 Gleason grading and to collect consensus cases for standardization. We scanned 25 prostate biopsy cores diagnosed as Gleason score (GS) 6-7. Fifteen genitourinary pathologists graded the digital slides and circled GP 4 and 5 in a slide viewer. Grading difficulty was scored as 1-3. GP 4 components were classified as type 1 (cribriform), 2 (fused), or 3 (poorly formed glands). A GS of 5-6, 7 (3 + 4), 7 (4 + 3), and 8-9 was given in 29%, 41%, 19%, and 10% (mean GS 6.84, range 6.44-7.36). In 15 cases, at least 67% of observers agreed on GS groups (consensus cases). Mean interobserver weighted kappa for GS groups was 0.43. Mean difficulty scores in consensus and non-consensus cases were 1.44 and 1.66 (p = 0.003). Pattern 4 types 1, 2, and 3 were seen in 28%, 86%, and 67% of GP 4. All three coexisted in 16% (11% and 23% in consensus and non-consensus cases, p = 0.03). Average estimated and calculated %GP 4/5 were 29% and 16%. After individual review, the experts met to analyze diagnostic difficulties. Areas of GP 4 and 5 were displayed as heat maps, which were helpful for identifying contentious areas. A key problem was to agree on minimal criteria for small foci of GP 4. In summary, the detection threshold for GP 4 in NBX needs to be better defined. This set of consensus cases may be useful for standardization.

• KISS1 methylation and expression as tumor stratification biomarkers and clinical outcome prognosticators for bladder cancer patients.

  Authors: Virginia Cebrian, Marta Fierro, Esteban Orenes-Piñero, Laura Grau, Patricia Moya, Thorsten Ecke, Miguel Alvarez, Marta Gil, Ferran Algaba, Joaquin Bellmunt, Carlos Cordon-Cardo, James Catto, Antonio López-Beltrán, Marta Sánchez-Carbayo

  The American journal of pathology. 06/2011; 179(2):540-6.

  KISS1 is a metastasis suppressor gene that is lost in several malignancies, including bladder cancer. We tested the epigenetic silencing hypothesis and evaluated the biological influence of KISS1KISS1 is a metastasis suppressor gene that is lost in several malignancies, including bladder cancer. We tested the epigenetic silencing hypothesis and evaluated the biological influence of KISS1 methylation on its expression and clinical relevance in bladder cancer. KISS1 hypermethylation was frequent in bladder cancer cells analyzed by methylation-specific PCR and bisulfite sequencing and was associated with low gene expression, being restored in vitro by demethylating azacytidine. Hypermethylation was also frequently observed in a large series of bladder tumors (83.1%, n = 804). KISS1 methylation was associated with increasing stage (P = 0.001) and tumor grade (P = 0.010). KISS1 methylation was associated with low KISS1 transcript expression by quantitative RT-PCR (P = 0.037). KISS1 transcript expression was also associated with histopathological tumor stage (P < 0.0005). Low transcript expression alone (P = 0.003) or combined with methylation (P = 0.019) was associated with poor disease-specific survival (n = 205). KISS1 transcript expression remained an independent prognosticator in multivariate analyses (P = 0.017). KISS1 hypermethylation was identified in bladder cancer, providing a potential mechanistic explanation (epigenetic silencing) for the observed loss of KISS1 in uroepithelial malignancies. Associations of KISS1 methylation and its expression with histopathological variables and poor survival suggest the utility of incorporating KISS1 measurement using paraffin-embedded material for tumor stratification and clinical outcome prognosis of patients with uroepithelial neoplasias.

• Clinical predictive factors of poor outcome in patients with stage pT0 disease at radical cystectomy.

  Authors: Oscar Rodriguez Faba, Juan Palou, Antonio Rosales, Alberto Breda, Ferran Algaba, Guillermo Urdaneta, Humberto Villavicencio

  The Journal of urology. 06/2011; 186(2):442-7.

  We evaluated new pre-cystectomy predictive factors for outcomes in patients with no evidence of residual tumor at cystectomy (pT0). A total of 1,114 patients underwent radical cystectomy at ourWe evaluated new pre-cystectomy predictive factors for outcomes in patients with no evidence of residual tumor at cystectomy (pT0). A total of 1,114 patients underwent radical cystectomy at our institution between August 1978 and June 2002, of whom 141 (12.66%) had stage pT0. We analyzed overall and disease specific survival in relation to pre-cystectomy predictive factors, such as clinical stage, grade, size, previous nonmuscle invasive disease, number of previous recurrences, associated carcinoma in situ and lymphovascular invasion in the transurethral resection. Other factors analyzed were lymph node (N+) at cystectomy and induction chemotherapy. Clinical stage was cTa in 10 patients, cT1 in 34, cT2 in 55, cT3 in 30 and cTis in 12. At a median followup of 42.5 months overall survival was 62.53% and disease specific survival was 79.14%. Metastatic disease developed in 17 cases (12.1%). Univariate analysis revealed worse disease specific survival in patients in whom muscle invasive tumor developed after nonmuscle invasive disease (p<0.05), and in those who presented with 5 or more previous recurrences (p<0.05), lymphovascular invasion in the transurethral resection (p<0.05) and N+ at cystectomy (p<0.05). Multivariate analysis confirmed a statistically significant association between disease specific survival and 5 or more previous recurrences (HR 1.5, 95% CI 1.07-2.10, p=0.018), muscle invasive tumor after nonmuscle invasive disease (HR 4.4, 95% CI 1.20-16.5, p=0.026) and lymphovascular invasion in the transurethral resection (HR 1.7, 95% CI 1.12-2.30, p=0.04). Although clinical outcomes in patients with stage pT0 disease are often excellent, metastatic disease develops in a percentage of them. Muscle invasive tumor after primary nonmuscle invasive disease, 5 or more previous recurrences and lymphovascular invasion in the transurethral resection predict poor survival.

• Flat urothelial carcinoma in situ of the bladder with glandular differentiation.

  Authors: Antonio Lopez-Beltran, Rafael E Jimenez, Rodolfo Montironi, Carlo Patriarca, Ana Blanca, Carmen L Menendez, Ferran Algaba, Liang Cheng

  Human pathology. 04/2011; 42(11):1653-9.

  We present the clinicopathologic and immunonohistochemical features of 25 cases of flat urothelial carcinoma in situ with glandular differentiation. Previously, cases on this category have beenWe present the clinicopathologic and immunonohistochemical features of 25 cases of flat urothelial carcinoma in situ with glandular differentiation. Previously, cases on this category have been reported as in situ adenocarcinoma (a term not currently preferred). Fourteen of 25 cases had concurrent conventional urothelial carcinoma in situ. Five of the cases were primary carcinoma in situ with glandular differentiation; twenty cases of secondary carcinoma in situ with glandular differentiation were associated with urothelial carcinoma alone (n = 11) or with glandular differentiation (n = 7), discohesive (n = 1) or micropapillary carcinoma (n = 1). The individual tumor cells were columnar. The architectural pattern of the carcinoma in situ with glandular differentiation consisted of 1 or more papillary, flat or cribriform glandular patterns. Univariate statistical analysis showed no survival differences between urothelial carcinoma in situ with glandular differentiation and conventional urothelial carcinoma in situ (log-rank 0.810; P = .368). Carcinoma in situ with glandular differentiation showed high ki-67 index and p53 accumulation, high nuclear and cytoplasmic p16 expression and diffuse PTEN expression, a phenotype that also characterized concurrent conventional carcinoma in situ. MUC5A, MUC2, CK20, and c-erbB2 were positive in all 25 cases of urothelial carcinoma in situ with glandular differentiation, and CDX-2 was present in 19 cases; MUC1, CK7, or 34βE12 was focally present in 21, 19, and 18 cases, respectively. MUC1core was negative in all cases. We concluded that urothelial carcinoma in situ with glandular differentiation is a variant of carcinoma in situ that follows the natural history of conventional urothelial carcinoma in situ. The immunophenotype suggests urothelial origin with the expression of MUC5A and CDX2 as signature for glandular differentiation.

• Laparoscopic management of spontaneous retroperitoneal hemorrhage.

  Authors: Juan A Peña, Miriam Serrano, Marco Cosentino, Antonio Rosales, Ferran Algaba, Juan Palou, Humberto Villavicencio

  Urologia internationalis. 04/2011; 87(1):114-6.

  Wünderlich's syndrome is a spontaneous nontraumatic massive retroperitoneal hemorrhage. It is usually secondary to a renal neoplasm, with angiomyolipoma being the most frequent followed by renal cellWünderlich's syndrome is a spontaneous nontraumatic massive retroperitoneal hemorrhage. It is usually secondary to a renal neoplasm, with angiomyolipoma being the most frequent followed by renal cell carcinoma. The management of spontaneous retroperitoneal bleeding varies depending on the hemodynamic status of the patient. We present the first report of a transperitoneal laparoscopic nephrectomy in a patient with spontaneous retroperitoneal active bleeding secondary to a right renal mass.

• Handling and reporting of transurethral resection specimens of the bladder in Europe: a web-based survey by the European Network of Uropathology (ENUP).

  Authors: Antonio Lopez-Beltran, Ferran Algaba, Daniel M Berney, Liliane Boccon-Gibod, Philippe Camparo, David Griffiths, Gregor Mikuz, Rodolfo Montironi, Murali Varma, Lars Egevad

  Histopathology. 02/2011; 58(4):579-85.

  To collect of information about European practices on handling and reporting of transurethral resection specimens of the bladder. The European Network of Uropathology is a communication network thatTo collect of information about European practices on handling and reporting of transurethral resection specimens of the bladder. The European Network of Uropathology is a communication network that includes 335 pathology laboratories in 15 western European countries. A web-based questionnaire was answered by 52.2% of members. Some routines were adopted by a majority: formalin fixation (92.5%), separate containers for tumour and resection base (72%) and embedding of the entire specimen (60%). Cancer along/in adipose tissue would be reported as pT3a by 19.5% and non-invasive urothelial carcinoma in prostatic ducts/glands as pT4a by 16.1%. Papillary urothelial neoplasia of low malignant potential is recognized by 72.6% but rarely reported. Immunohistochemistry is rarely or sometimes used for diagnosing bladder cancer by 91.7%, and the most frequently used markers are CK20 (76.9%), CK7 (66.7%) and Ki67 (38.8%). Only 24.8% report prognostic markers, with Ki67 (84.4%) and p53 (64.4%) being most common. Only 50.9% use the International Society of Urological Pathology 1998/World Health Organization (WHO) 2004 grading system, followed by WHO 1973 (43.4%) and WHO 1999 (31.4%). There is still variability in routine practice and a need for standardization of methodologies. These results may be helpful when judging what recommendations are reasonable to issue.

• Sequential intravesical chemoimmunotherapy with mitomycin C and bacillus Calmette-Guérin and with bacillus Calmette-Guérin alone in patients with carcinoma in situ of the urinary bladder: results of an EORTC genito-urinary group randomized phase 2 trial (30993).

  Authors: Willem Oosterlinck, Ziya Kirkali, Richard Sylvester, Fernando Calais da Silva, Christer Busch, Ferran Algaba, Sandra Collette, Aldo Bono

  European urology. 12/2010; 59(3):438-46.

  Bacillus Calmette-Guérin (BCG) is the intravesical treatment of choice for carcinoma in situ (CIS). Our aim was to assess if sequential mitomycin C (MMC) plus BCG after transurethral resection (TUR)Bacillus Calmette-Guérin (BCG) is the intravesical treatment of choice for carcinoma in situ (CIS). Our aim was to assess if sequential mitomycin C (MMC) plus BCG after transurethral resection (TUR) is worthy of further study in non-muscle-invasive bladder cancer patients with CIS. In a noncomparative phase 2 study, 96 patients with primary/secondary/concurrent CIS of the urinary bladder were randomized to sequential MMC plus BCG or to BCG alone after TUR. Patients received six weekly instillations of MMC followed by six weekly instillations of BCG or six weekly instillations of BCG, 3 wk rest, and three further weekly instillations of BCG. Complete responders received three weekly maintenance instillations at 6, 12, 18, 24, 30, and 36 mo in accordance with the initial randomization. End points were complete response (CR) rate at the first control cystoscopy 16-18 wk after start of treatment, disease-free interval, overall survival, and side effects. Ninety-six patients were randomized, 48 to each treatment group. Ten patients were ineligible, and three did not start treatment. In all randomized patients, CR rates on MMC plus BCG and BCG alone were 70.8% and 66.7%, respectively. In 83 eligible patients who started treatment, CR rates were 75.6% and 73.8%, respectively. Based on a median follow-up of 4.7 yr, 25 patients (52.1%) on MMC plus BCG and 22 patients (45.8%) on BCG alone were disease free. Twelve patients stopped treatment due to toxicity: three during induction (two MMC plus BCG, one BCG) and nine during maintenance (three MMC plus BCG, six BCG). In the treatment of patients with CIS, sequential chemoimmunotherapy with MMC plus BCG had acceptable toxicity. CR and disease-free rates were similar to those on BCG alone and to previous publications on sequential chemoimmunotherapy. This study was registered with the US National Cancer Institute clinical trials database (protocol ID: EORTC-30993). http://www.cancer.gov/search/ViewClinicalTrials.aspx?cdrid=68869&version=HealthProfessional&protocolsearchid=7920643.

• The case for conservative management in the treatment of patients with non-muscle-invasive micropapillary bladder carcinoma without carcinoma in situ.

  Authors: Josep M Gaya, Joan Palou, Ferran Algaba, Jacobo Arce, Oscar Rodríguez-Faba, Humberto Villavicencio

  The Canadian journal of urology. 10/2010; 17(5):5370-6.

  Micropapillary carcinoma is a rare pathologic variant of urothelial cell carcinoma. Intravesical bacillus Calmette-Guérin (BCG) has been reported to be ineffective and to entail an increased risk ofMicropapillary carcinoma is a rare pathologic variant of urothelial cell carcinoma. Intravesical bacillus Calmette-Guérin (BCG) has been reported to be ineffective and to entail an increased risk of development of non-organ-confined, metastatic disease. We assess the treatment response and disease progression in patients with micropapillary carcinoma of the bladder. The study comprised 18 patients with micropapillary carcinoma of the bladder who underwent transurethral resection of a bladder tumor and multiple random biopsies between 1997 and 2003. We retrospectively analyzed treatment response and clinical and pathological cancer evolution related to cancer stage and the percentage of the micropapillary component of the cancer. Seven of the 18 patients (38.8%) had carcinoma in situ. At diagnosis, 8 of the 18 patients had non-muscle-invasive bladder cancer; 6 of these patients were treated with intravesical BCG therapy and were alive and free of disease at a median follow up of more than 5 years. Ten of the 18 patients had muscle-invasive bladder cancer; 8 of these patients underwent radical cystectomy, and 7 of the 8 patients (87.5%) had non-organ-confined disease in cystectomy specimens. Seventy percent of patients with muscle-invasive disease at diagnosis had a micropapillary carcinoma component of more than 50% in transurethral resection of the bladder specimens, compared with only 25% of patients with non-muscle-invasive disease. Patients treated successfully with intravesical BCG therapy had a low micropapillary carcinoma component. The 5-year disease-specific survival rate was significantly lower in patients with muscle-invasive disease (30%) than in patients with non-muscle-invasive disease (87.5%) after a median follow up of 52 months (p = 0.001), and it was also significantly lower in patients with a high percentage of the micropapillary component of the carcinoma. This retrospective study of 18 patients with micropapillary carcinoma of the bladder suggests that tumor stage and patient outcome may be related to the percentage of the micropapillary component of the carcinoma. Radical surgery is mandatory in muscle-invasive disease, even though patients with lymph node involvement die from the disease. In non-muscle-invasive disease and in the absence of associated carcinoma in situ, intravesical BCG treatment may be offered when the micropapillary component of the carcinoma component is a small percentage.

• Neoadjuvant temsirolimus effectiveness in downstaging advanced non-clear cell renal cell carcinoma.

  Authors: Oscar Rodríguez Faba, Alberto Breda, Antonio Rosales, Joan Palou, Ferran Algaba, Pablo Maroto Rey, Humberto Villavicencio

  European urology. 03/2010; 58(2):307-10.

  A 35-year-old woman presented with a 12-cm right renal mass with retroperitoneal lymph node involvement and pulmonary and bone metastases. Renal mass biopsy revealed an unclassified high-gradeA 35-year-old woman presented with a 12-cm right renal mass with retroperitoneal lymph node involvement and pulmonary and bone metastases. Renal mass biopsy revealed an unclassified high-grade non-clear cell renal cell carcinoma (RCC) with eosinophilic cells. Due to the extent of the disease, neoadjuvant temsirolimus was initiated. After 6 wk of treatment, a significant downstaging of the disease and complete disappearance of the metastases were noticed on computed tomography scan. Three months later, a laparoscopic radical nephrectomy and lymphadenectomy was performed. Final pathology confirmed a high-grade non-clear cell RCC, with necrotic changes on lymph node specimens, pT1bN0Mx.

• Impact of prostate cancer multifocality on its biology and treatment.

  Authors: Ferran Algaba, Rodolfo Montironi

  Journal of endourology / Endourological Society. 03/2010; 24(5):799-804.

  Any focal therapy requires correct localization of the lesion; consequently, much effort is now devoted to accurate characterization of the spatial distribution of the tumor within the prostate. OneAny focal therapy requires correct localization of the lesion; consequently, much effort is now devoted to accurate characterization of the spatial distribution of the tumor within the prostate. One of the greatest difficulties in the localization of prostate cancer is its frequent multifocality, but prostate cancer is unifocal in 13% to 43.7% of cases and unilateral in 19.2%. In cases of multifocality, it seems that the index tumor is the biologic driving force behind the malignant potential of prostate cancer. Not only is the Gleason score of the secondary nodes lower than that of the index node, but 80% of the secondary nodes are smaller than 0.5 cc and almost all extraprostatic extensions are associated with the largest cancers. While current evaluation with 12 to 18 core biopsies may be adequate to determine the index lesion, transperineal three-dimensional mapping biopsy of the prostate should be undertaken if greater accuracy is needed.

• EAU penile cancer guidelines 2009.

  Authors: Giorgio Pizzocaro, Ferran Algaba, Simon Horenblas, Eduard Solsona, Silvia Tana, Hein Van Der Poel, Nicholas A Watkin

  European urology. 02/2010; 57(6):1002-12.

  Squamous cell carcinoma (SCC) of the penis is a relatively rare but ominous disease. To present a condensed version of the updated 2009 European Association of Urology (EAU) guidelines on penileSquamous cell carcinoma (SCC) of the penis is a relatively rare but ominous disease. To present a condensed version of the updated 2009 European Association of Urology (EAU) guidelines on penile SCC. We performed a literature search of new data available up to December 2009. No randomized study was found; consequently, level of evidence (LE) and grade of recommendations (GR) are low. More insight was gained into the etiology of SCC of the penis, together with improved staging and treatment: Human papillomavirus 16 plays an etiologic role in approximately 40-50% of cases. Similarities in etiology with SCC of the head and neck, the female genitalia, and the anal canal have been found. Improved diagnostics allowed earlier diagnosis, leading to more conservative treatments. Adjuvant and neoadjuvant chemotherapy showed promising results in patients with advanced or recurrent disease. Centralization of the disease contributed to standardization and rapid diffusion of new treatments with improved results and increased organ preservation. Improvements in the management of SCC of the penis are reflected in changes in the guidelines, but the rarity of the disease precluded randomized studies, leading to low level of evidence and grade of recommendation.

• Bladder preservation strategy based on combined therapy in patients with muscle-invasive bladder cancer: management and results at long-term follow-up.

  Authors: Humberto Villavicencio, Oscar Rodriguez Faba, Joan Palou, Luis Gausa, Ferran Algaba, Eugenio Marcuello

  Urologia internationalis. 01/2010; 85(3):281-6.

  To evaluate a bladder preservation strategy in patients with either muscle-invasive bladder cancer (MIBC) or development of MIBC cancer due to progression of non-muscle-invasive bladder cancerTo evaluate a bladder preservation strategy in patients with either muscle-invasive bladder cancer (MIBC) or development of MIBC cancer due to progression of non-muscle-invasive bladder cancer (NMIBC). Between October 1982 and March 1998, 48 patients (mean age 61 years, range 45-75) with MIBC (T2a-b and T3a) were treated using transurethral resection followed by three cycles of systemic chemotherapy. 42 patients (87.5%) had primary MIBC and 6 (12.5%) had MIBC subsequent to NMIBC. After chemotherapy, 39 patients (81.25%) achieved complete remission and 4 (8.3%) partial remission. With a median follow-up of 98.5 months (13-246), the overall survival of the 48 patients was 62.6%. The cancer-specific survival (CSS) of the 39 patients with complete remission was 80.8%. Among the 39 patients with complete remission, 19 had invasive recurrence during follow-up with a CSS of 53.2%; by comparison, among patients with preserved bladders, CSS was 72.1% (p = 0.046). Predictive factors analysed were age, sex, tumour size >3 cm, grade, associated carcinoma in situ (CIS), number of tumours and number of previous recurrences. In multivariate analysis only tumour size and CIS were significant predictive factors for progression after preservation. Of the 6 patients with MIBC after NMIBC, 3 (50%) had no remission and underwent cystectomy and 15 patients (38.6%) had NMIBC recurrences during follow-up. CIS and high-grade tumours were treated with bacillus Calmette-Guérin. A bladder preservation rate of 81% and a CSS rate of 89% were obtained in the group with NMIBC recurrences. Conservative management of MIBC cancer is a feasible alternative to cystectomy in selected cases. Patients with MIBC after progression of primary NMIBC are not good candidates for a bladder preservation approach. NMIBC recurrences after bladder preservation in patients with MIBC respond to transurethral resection and bacillus Calmette-Guérin instillations.

• Urothelial carcinoma of the bladder, lipid cell variant: clinicopathologic findings and LOH analysis.

  Authors: Antonio Lopez-Beltran, Mahul B Amin, Pedro S Oliveira, Rodolfo Montironi, Ferran Algaba, Jesse K McKenney, Ines de Torres, Catherine Mazerolles, Mingsheng Wang, Liang Cheng

  The American journal of surgical pathology. 01/2010; 34(3):371-6.

  In this report, we present the clinicopathologic features of 27 cases of the lipid cell variant of urothelial bladder carcinoma. This is a rare variant of bladder cancer recognized by the current WHOIn this report, we present the clinicopathologic features of 27 cases of the lipid cell variant of urothelial bladder carcinoma. This is a rare variant of bladder cancer recognized by the current WHO classification of urologic tumors. The lipid cell component varied from 10% to 50% of the tumor specimen; in 11 cases the lipid cell component composed greater than 30% of the tumor. The architectural pattern of the tumor varied from solid expansile to infiltrative nests. The large epithelial tumor cells had an eccentrically placed nucleus and abundant vacuolated cytoplasm resembling signetring lipoblasts. Mucin stains were negative in all the cases. Typical features of high grade conventional urothelial carcinoma were present in all the cases with micropapillary or plasmacytoid carcinoma in 2 and 1 cases, respectively; extensive squamous or glandular differentiation was present in 2 additional cases. Most neoplastic cells had nuclei of intermediate nuclear grade with occasional nuclear pleomorphism. Immunohistochemical staining showed that the lipid cell component was positive for cytokeratins 7, 20, CAM 5.2, high molecular weight (34ssE12) and AE1/AE3, epithelial membrane antigen, and thrombomodulin; vimentin and S100 protein were negative. The loss of heterozygosity (LOH) analysis was done on 8 cases using 4 polymorphic microsatellite markers (D9S171, D9S177, IFNA, and TP 53); LOH at least in 1 marker was present in 6 cases. The LOH results were the same for lipid variant and conventional urothelial carcinoma. Pathologic stage was Ta (n=1), T1 (=2), T2, at least (n=7), T3a (n=4), T3b (n=8), and T4a (n=5). Electron microcopy analysis based on 2 cases supported lipid content in tumor cells. Follow-up information was available in all the cases, ranging from 6 to 58 months (mean, 28 mo). Sixteen of the patients died of disease at 16 to 58 months (mean, 33 mo) and 8 patients were alive with disease at 8 to 25 months (mean, 22 mo). Another 3 patients died of other causes at 6 to 15 months (mean, 10 mo). In summary, lipid cell urothelial bladder carcinoma is typically associated with advanced stage high-grade urothelial carcinoma, in which the prognosis is poor and clonally related to the concurrent conventional urothelial carcinoma. In limited samples, it may be misdiagnosed as liposarcoma, sarcomatoid carcinoma (carcinosarcoma), or signetring cell carcinoma. Morphologic distinction from other malignant neoplasms with lipid cell phenotype is critical for its clinical management.