Pharmacogenetic predictors of severe peripheral neuropathy in colon cancer patients treated with oxaliplatin-based adjuvant chemotherapy: a GEMCAD group study.

BACKGROUND: Oxaliplatin-based chemotherapy (CT), widely used as adjuvant therapy for stage III and selected high-risk stage II colon cancer (CC) patients, is often associated with cumulative peripheral neuropathy. Our aim is to identify single-nucleotide polymorphisms (SNPs) in genes involved in oxaliplatin metabolism, DNA repair mechanisms, cell cycle control, detoxification or excretion pathways to predict severe (grade 2-3) oxaliplatin-induced peripheral neuropathy (OXPN) among CC patients treated with oxaliplatin and fluoropyrimidine-based adjuvant CT. PATIENTS AND METHODS: Genomic DNA was extracted from formalin-fixed-paraffin-embedded peritumoral samples from 206 high-risk stage II and stage III CC patients receiving oxaliplatin-based adjuvant CT from January 2004 to December 2009. Genotyping was carried out for 34 SNPs in 15 genes using MassARRAY (SEQUENOM) technology. A total of 181 stage II-III CC patients treated with the same CT regimens were enrolled as a validation set. RESULTS: The rs2230641 cyclin H (CCNH) rs2230641 C/C [odd ratio (OR)=5.03, 95% confidence interval (CI) 1.061-2.41, P=0.042] and the ATP-binding cassette subfamily G, member 2 (ABCG2) rs3114018 A/A genotypes (OR=2.67; 95% CI 0.95-4.41; P=0.059) were associated with a higher risk of severe OXPN. In addition, patients harboring the combination of CCNH C/C and/or the ABCG2 rs3114018 A/A genotypes had a higher risk of grade 2-3 OXPN than those with the CCNH any T and ABCG2 any C genotypes (37.73% versus 19.42%; OR=2.46; 95% CI 1.19-5.07; P=0.014) in the logistic regression analysis using age, gender, adjuvant CT regimen and cumulative dose of oxaliplatin as covariates. The ability to predict severe OXPN of this combined analysis was independently validated in the second cohort (58% versus 33.33%; OR=2.99; 95% CI 1.45-6.13; P=0.002). CONCLUSIONS: Our results suggest that SNPs in CCNH and ABCG2 can modulate the development of severe OXPN among stage II-III CC patients who received oxaliplatin-based CT, thus enabling the individualization of adjuvant treatment.

Role of PCA3 and SelectMDx in the optimization of active surveillance in prostate cancer.

INTRODUCTION & OBJECTIVES: A not negligible percentage of patients included in active surveillance (AS) for low and very low risk prostate cancer (PCa) are reclassified in the confirmatory biopsy or have disease progression during follow-up. Our aim is to evaluate the role of PCA3 and SelectMDx, in an individual and combined way, in the prediction of pathological progression (PP) in a standard AS program. MATERIALS & METHODS: Prospective and observational study comprised of 86 patients enrolled in an AS program from 2009 to 2019, with results for PCA3 and SelectMDx previous to PCa diagnosis or during their confirmatory period. Univariate and multivariate analysis were performed to correlate PCA3 and SelectMDx scores as well as clinical and pathological variables with PP-free survival (PPFS). The most reliable cut-offs for both biomarkers in the context of AS were defined. RESULTS: SelectMDx showed statistically significant differences related to PPFS (HR 1.035, 95%CI: 1.012-1.057) (p = 0.002) with a C-index of 0.670 (95%CI: 0.529-0.810) and AUC of 0.714 (95%CI: 0.603-0.825) at 5 years. In our series, the most reliable cut-off point for SelectMDx was 5, with a sensitivity and specificity for PP of 69.8% and 67.4%, respectively. Same figure for PCA3 was 65, with a sensitivity and specificity for PP of 51.16% and 74.42%, respectively. The combination of both biomarkers did not improve the prediction of PP, C-index 0.630 (95%CI: 0.455-0.805). CONCLUSIONS: In the context of low or very low risk PCa, SelectMDx > 5 predicted 5 years PP free survival with a moderate discrimination ability outperforming PCA3. The combination of both tests did not improved outcomes.

Long-term oncological results of treatment for high-risk prostate cancer using radical prostatectomy in a cancer hospital. / Resultados oncológicos a largo plazo del tratamiento cáncer de próstata de alto riesgo mediante prostatectomía radical en un hospital oncológico.

OBJECTIVES: To analyse the most relevant oncologic results of treatment using radical prostatectomy (RP) for high-risk prostate cancer (HRPC) in a specialist cancer hospital. MATERIAL AND METHODS: A descriptive retrospective study of RP was conducted at our centre from 1986 to 2017 on HRPC whose primary objective was to determine overall survival (OS) and cancer-specific survival (CSS). The study's secondary objectives were to determine biochemical progression-free survival (BPFS), metastasis-free survival (MFS), rescue therapy-free survival (RTFS), hormone therapy-free survival (HTFS) and the development of castration-resistant prostate cancer. We performed a Cox regression analysis to establish predictive models and to better understand the weight of each variable that defines high risk. RESULTS: A total of 2093 RPs were performed, 480 (22.9%) of which were for HRPC. The median follow-up for the overall series was 79.57 months (P25-75 37.92-135.16). Lymphadenectomy was not performed in 6.5% of the cases. The lymphadenectomy was of the obturator type in 51.2% of the cases and extended in 42.3%. Overall survival at 5, 10 and 15 years was 89.8% (95% CI 86.7-92.9%), 73.3% (95% CI 68-78.6%) and 51.4% (95% CI 43.8-59%), respectively. CSS at 5, 10 and 15 years was 94.8% (95% CI 92.4-97.2%), 84.0% (95% CI 79.3-88.7%) and 75.5% (95% CI 68.8-82.2%), respectively. MFS at 5, 10 and 15 years was 87.4% (95% CI 84.1-90.7%), 72.2% (95% CI 66.7-77.7%) and 61.7% (95% CI 54.3-69.1%), respectively. A total of 120 patients of 477 analysed (25.1%) required rescue radiation therapy, and 293/477 never required hormone therapy (61.4%). Of the 93 pN1 patients, 33 (35.5%) did not require hormone therapy. The time from RP to biochemical progression was the variable with the greatest prognostic weight for MFS, CSS and overall survival. CONCLUSIONS: RP plus extended lymphadenectomy should be the first therapeutic manoeuvre when feasible within a multimodal strategy. A longer follow-up of the series is needed to validate the hypothesis of better oncologic results based on the earlier implementation of rescue radiation therapy, extended lymphadenectomy and drugs that prolong survival in the CRPC phase.

Association between late-onset hypogonadism syndrome plus metabolic syndrome and prostate cancer and its aggressiveness. / Asociación del síndrome de hipogonadismo tardío y síndrome metabólico con el cáncer de próstata y su agresividad.

OBJECTIVE: To assess the relationship between prostate cancer (PC) and the presence of metabolic syndrome and late-onset hypogonadism (LOH) syndrome. MATERIAL AND METHOD: A retrospective study was conducted on 686 patients who underwent prostate biopsy. We analysed the demographic variables, clinical data and biopsy results. To diagnose metabolic syndrome, we employed the criteria of the American Heart Association. For the diagnosis of LOH syndrome, we employed the Androgen Deficiency in the Aging Male questionnaire and testosterone levels (TT). We evaluated the relationship between free testosterone (FT) and bioavailable testosterone (BT) on one hand and PC and its aggressiveness on the other, as well as the usefulness of the TT to prostate specific antigen (TT/PSA) ratio in the PC diagnosis. RESULTS: The patient's median age was 65 years. Metabolic syndrome is not associated with PC (39.4% vs. 35%; P=.1) but is associated with a PC Gleason score >7 (50.4% vs. 29.44%; P=.002). LOH, low FT and low BT are associated with an increased presence of PC (51% vs. 35%, P=.02; 44.86% vs. 33.33%, P=.03; and 46.46% vs. 33.08%, P=.01, respectively) and with an increased probability of a PC Gleason score >7 (61.54% vs. 37.5%, P=.02; 54.17% vs. 34.12%, P=.02; 54.35% vs. 34.48%, P=.02, respectively). Additionally, the median TT/PSA ratio was significantly lower in patients with positive biopsies (P=.022). CONCLUSIONS: Metabolic syndrome was not associated with the probability of having PC but was associated with a PC Gleason score >7. Moreover, LOH syndrome had a higher percentage of PC and a greater presence of PC Gleason scores >7, as did low levels of FT and low levels of BT.

[Update on the diagnosis of PCa in urine. The current role of urine markers]. / Actualización en el diagnóstico del CaP en orina. Papel actual de los marcadores urinarios.

Prostate cancer (PCa) is still a main health issue, in fact it is responsible for 10% of cancer deaths across Europe. The morphology of the prostate gland makes urine an ideal sample, non invasive, for determination both diagnostic and prognostic biomarkers. We use urinary PCA3 levels to indicate a prostate biopsy, and it is the only urinary biomarkers in PCa with FDA approval for clinical use. Many other biomarkers based on the expression of specific genes of PCa are being studied and validated, for instance the fusion gene TMPRSS2-ERG with a commercial kit available, while another approach is to test the expression of a panel of genes. An emerging focus of research, which deserves attention, is miRNAs. Other newer approaches such as epigenetics, proteomics and metabolomics also would be very useful in the future for the development and validation of new biomarkers. In this paper we review the state of the art in the field of urinary biomarkers in PCa.

Urinary tract symptoms and erectile function in patients at risk of prostate cancer.

INTRODUCTION AND OBJECTIVE: We estimate that more tan 63000 prostate biopsies are performed in our country each year. There are no functional status data of those patients and if there is a relationship between biopsy result and functional status. In order to solve that question we have performed this study. MATERIAL AND METHOD: 1,128 prostate biopsies were included. Patients fill in the IPSS, IIEF-5 and ICIQ-SF questionnaires before the prostate biopsy was performed. A prospective data collection of clinical, pathological and questionnaires results was done. A descriptive analysis was carried out. IPSS and IIEF-5 results were categorized. Results were compared depending on the biopsy result. In the subgroup of patients with prostate cancer, questionnaires results were stratify according to the clinical risk group. RESULTS: The mean age of the sample was 65. Prostate cancer detection rate was 32,71%, 52,2% of the sample had mild lower urinary tract symptoms (LUTS) and 13,4% had severe LUTS at the time of the biopsy. Regarding the impact of LUTS on quality of life (QOL), only 12,6% showed a perfect QOL. More than 50 percent of patients suffered from some degree of erectile dysfunction at the time of the biopsy. According to ICIQ-SF, 24% of the sample experienced some kind of urinary incontinence, although it is true that most of them classified it as small amount. Patients with a positive biopsy had a lower IPSS and IIEF-5 average score. There were no differences in the prostate cancer detection rate stratified by the severity of LUTS. CONCLUSIONS: Patients undergoing prostate biopsy have, with a high probability, LUTS. Approximately 50% suffer from some degree of erectile dysfunction and 24% had some kind of urinary leakage.

External validation of FXYD3 and KRT20 as predictive biomarkers for the presence of micrometastasis in muscle invasive bladder cancer lymph nodes.

INTRODUCTION: Recent studies have proposed that FXYD3 and KRT20 mRNA quantified by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in paraffin could be biomarkers to detect lymph nodes with micrometastases that avoid detection by conventional analysis with hematoxylin-eosin (HE). A validation study was conducted on the lymph nodes of patients who underwent radical cystectomy. OBJECTIVE: To classify the adenopathic state of a sample of patients who underwent cystectomy, based on the lymph node expression of FXYD3 and KRT20. The secondary objective was to assess whether there is a differential oncologic evolution for the patients, depending on the lymph node expression of these proteins. MATERIAL AND METHOD: The study included lymph nodes from 64 patients who underwent cystectomy for infiltrating bladder tumor: The model was developed using metastatic lymph nodes from 15 patients and lymph nodes from 4 patients with no known tumor. Genetic expression was measured using real-time qRT-PCR. We calculated (using qRT-PCR) the median expression of FXYD3 and KRT20 mRNA in the lymph node tissue. We then analyzed the receiver operating characteristic (ROC) curves, according to the function y=0.1400+0.250FXYD3-2.532. The cutoff was established using an ROC curve. The formula was applied to the remaining lymph node tissue, based on the previously established cutoff. The sample was classified into 4 subgroups: HE- qRT-PCR-, HE- qRT-PCR+, HE+ qRT-PCR+ y HE+, qRT-PCR-. A descriptive, comparative analysis was performed, as well as a metastatic progression-free survival analysis, calculating the Kaplan and Meyer curves for the 3 established subgroups. The test results were considered statistically significant at P<.05. RESULTS: Using qRT-PCR, we verified that there were differences in the median expression of FXYD3 (P=.05) and KRT20 (P=.009) between the lymph node tissues of patients with benign prostate hyperplasia and those of patients with lymph node metastasis. A cutoff was assigned to 0.377. The sample was classified as follows: 37.5% of the patients were pN0 by HE and pN0 by qRT-PCR (-HE -qRT-PCR), 39.1% were pN0 by HE but metastatic by qRT-PCR (-HE +qRT-PCR), and 15 patients (23.4%) were metastatic by both techniques (+HE +qRT-PCR). The Kaplan and Meyer curves showed poorer metastatic progression-free survival for the patients who were +HE and +qRT-PCR than for the other subgroups, with no significant differences between -HE +qRT-PCR and -HE -qRT-PCR. CONCLUSIONS: According to our results, 39.1% of the patients with infiltrating vesical tumors overexpressed the FXYD3 and KRT20 biomarkers and were N0 by HE. We observed no differential clinical behavior among the patients who underwent cystectomy according to their expression of FXYD3 and KRT20 when they were N0 by HE.

Overexpression of Ki-67 and cyclins A and B1 in JC virus-infected cells of progressive multifocal leukoencephalopathy.

Both SV40 and JC virus (JCV) appropriate the host cell replicative machinery to attend to their own reproductive needs. SV40 large T antigen is able to induce the expression of cyclins A, B1, and E (but not of cylin D1) in transfected diploid cells. Whether JCV infection influences cyclin expression in a similar fashion in the setting of progressive multifocal leukoencephalopathy (PML) remains unknown. Brain lesions from 7 PML cases (4 autopsies and 3 biopsies) were immunohistochemically investigated for the expression of Ki-67 and cyclins A, B1, and D1. All 7 cases showed strong positivity for Ki-67 and cyclins A and B1 in JCV-infected oligodendrocytes and astrocytes, the nuclear immunolocalization of cyclin A being in strong contrast to the cytoplasmic distribution of cyclin B1. No immunostaining for cyclin D1 was obtained in any of the 7 cases. These findings suggest that JCV infection is associated with overexpression of Ki-67 and cyclins A and B1 in PML host glial cells. Since cyclin changes in JCV-infected cells recapitulate SV40 T antigen-associated cyclin fluctuations, it appears reasonable to think that JCV T antigen shares some of the previously described capabilities of SV40 T antigen to alter cyclin expression for the sake of viral replication.

Detection of mycobacterium tuberculosis in paraffin-embedded pleural biopsy specimens by commercial ribosomal RNA and DNA amplification kits.

STUDY OBJECTIVES: To evaluate the utility of two gene amplification systems in historical paraffin-embedded pleural biopsy (PEB) tissues from patients with pleural tuberculosis, and to compare the results to those obtained with conventional histologic and microbiological methods. DESIGN: A retrospective study. PATIENTS AND METHODS: Seventy-four formalin-fixed PEB tissues collected and stored over 12 years (1984 through 1995) were retrieved. Gene amplifications were performed in 57 tissues from patients with diagnoses of pleural tuberculosis and in 17 from patients with carcinoma as controls, using the first version of the Amplified Mycobacterium tuberculosis Direct Test (AMTDT; Gen-Probe; San Diego, CA) and the LCx Mycobacterium tuberculosis Assay (LCxMTB; Abbott Laboratories; Abbott Park, IL). RESULTS: The sensitivities of the AMTDT and LCxMTB were 52.6% and 63.2%, respectively (p = not statistically significant). The specificity of both tests was 100%. Twenty tissue samples (35.1%) were positive by both systems, and 10 tissues (17.5%) were positive only by the AMTDT, while 16 tissues (28.1%) were positive only by the LCxMTB. Both tests gave negative results for 11 specimens (19.3%). When both tests were used, a positive diagnosis was achieved in 80.7% of the samples. Diagnosis of 73.7% of patient conditions had previously been made by smear examination of pleural biopsy and sputum, pleural liquid, or biopsy culture. The overall diagnostic yield with both culture and amplification techniques was 96.5% (55 of 57 patients) for pleural tuberculosis, with amplification techniques adding 22.8% of the diagnoses. CONCLUSIONS: Amplification techniques are useful in archival PEB tissues, providing additional diagnoses beyond culturing, although the sensitivity should be improved, possibly by standardizing protocols.

[Benign metastasizing pulmonary leiomyomatosis. A report of 3 cases]. / Leiomiomatosis pulmonar benigna metastatizante. A propósito de tres casos.

The benign metastasizing leiomyoma is an uncommon variety of leiomyoma, tumor derived from smooth muscular tissue. The benign metastasizing leiomyoma affects a middle age women, with antecedents of uterine leiomyoma, the pulmonary lesions appeared as a multiple nodules, without systemic affectation. We present three cases of benign metastasizing leiomyoma that de diagnosis was made for biopsy by thoracotomy; and in one case the markers from estrogens' receivers were positive.

[Pseudotumorous cardiac infiltration in a patient with acute monoblastic leukemia]. / Infiltración cardíaca seudotumoral en un paciente con leucemia aguda monoblástica.

Although cardiac infiltration is common in advanced stage of acute leukaemia, it is not usually diagnosed at life and it is extremely rare for it to become pseudotumoral. A 25-years-old patient with an acute monoblastic leukaemia who had a leukaemic infiltration which affected the main part of the left ventricle at the time of diagnosis, is referred. The heart infiltration was detected by a two dimension echocardiography. In spite of a massive infiltration, heart failure was not present and the left ventricle's ejection fraction was 50%. Even though chemotherapy was administered, the patient died four days after diagnosis due to septic shock of respiratory origin. The most relevant autopsy finding was a widespread pseudotumoral infiltration of the left ventricle, the back side of the right ventricle and the interventricular wall. The pseudotumoral infiltration of the heart by acute leukaemia is uncommon and must be differentiated from granulocytic sarcoma. The usefulness of the different diagnostic procedures is discussed.

Obligatory information that a patient diagnosed of prostate cancer and candidate for an active surveillance protocol must know.

OBJECTIVES: To know the necessary information to reproduce the results found in the literature on active surveillance (AS) in prostate cancer (PCa) in our own center so that the information would be objective and correctly given to the patients. We have aimed to study the percentage of candidates for AS chosen in our setting, and the data on infrastaging, subgrading and prediction of insignificant PCa, debugging the predictive value of clinical variables to improve our selection criteria and finally to analyze the results of our patients enrolled in AS. MATERIALS AND METHODS: A retro- and prospective review of our data bases was performed. A one-year period was analyzed to know AS candidates. Analysis of our radical prostatectomy specimens for infrastaging, subgrading and prediction of insignificant PCa (Epstein's criteria) was made as well as a uni/multivariate analysis of clinical variables in patients with insignificant PCa in the specimen. A prospective validation was performed with overall survival and survival free of active treatment (SFAT) as endpoints in patients enrolled in AS. RESULTS: Between October-2010/October-2011, 44.7% of our PCa were candidates for AS, but only 11.2% choose it. The percentages found for infrastaging, subgrading and prediction of insignificant PCa were 14%, 31.4% and 55.7%, respectively. However, only just 6 patients (6.97%) had≥pT3a+Gleason≥7+volume>0.5cc PCa. The multivariate analysis showed that PSA density and number of affected cores were independent predictors of insignificant PCa. With a mean follow-up of 36±39months, 63 out of 232 patients enrolled in AS went on to active treatment (27.1%), with only 13 due to anxiety without pathologic progression. Median time of SFAT was 72.7 months (CI 95% 30.9-114.4). SFAT at 24 months was 76.4% (69.7-83.1%) and at 48 months 58.1% (48.8-67.4%). Only 10 patients died (4.3%), 9 due to causes different of PCa. Estimated overall survival at 5 years was 92.8% (CI 95% 86.7-98.9%). CONCLUSIONS: It should be mandatory to have the exact knowledge of the local data of each Center in order to objectively inform patients about prostate biopsy efficiency, and if percentages of infrastaging, subgrading and prediction of insignificant PCa are in accordance with the literature. At 3 years, we reproduced the results of the longest series of AS, so we have ascertained that our AS protocol can be implemented with increasingly more patients.

Molecular characterization and clinical impact of TMPRSS2-ERG rearrangement on prostate cancer: comparison between FISH and RT-PCR.

Prostate cancer (PCa) is a very heterogeneous disease, and there are constraints in its current diagnosis. Serum PSA levels, digital rectal examination (DRE), and histopathologic analysis often drive to overdiagnosis and overtreatment. Since 2005, the presence of the genetic rearrangement between transmembrane-serine protease gene (TMPRSS2) and the erythroblast transformation-specific (ETS) member ERG (v-ets erythroblastosis virus E26 oncogene homolog avian) has been demonstrated in almost half of PCa cases. Both FISH and RT-PCR are useful tools for detecting these rearrangements, but very few comparatives between both techniques have been published. In this study, we included FFPE tumors from 294 PCa patients treated with radical prostatectomy with more than 5 years of followup. We constructed a total of 20 tissue microarrays in order to perform break-apart and tricolor probe FISH approaches that were compared with RT-PCR, showing a concordance of 80.6% (P < 0.001). The presence of TMPRSS2-ERG rearrangement was observed in 56.6% of cases. No association between TMPRSS2-ERG status and clinicopathological parameters nor biochemical progression and clinical progression free survival was found. In conclusion, this study demonstrates that both FISH and RT-PCR are useful tools in the assessment of the TMPRSS2-ERG fusion gene status in PCa patients and that this genetic feature per se lacks prognostic value.

Papel de PCA3 y SelectMDx en la optimización de la vigilancia activa en el cáncer de próstata / Role of PCA3 and SelectMDx in the optimization of active surveillance in prostate cancer

Introducción y objetivos: Un porcentaje no despreciable de pacientes incluidos en programas de vigilancia activa (VA) para el cáncer de próstata (CaP) de bajo y muy bajo riesgo son reclasificados en la biopsia confirmatoria o desarrollan progresión de la enfermedad durante el seguimiento. Nuestro objetivo es evaluar el papel del PCA3 y el SelectMDx, de manera individual y combinada, para predecir la progresión patológica (PP) en un programa habitual de VA.Materiales y métodosEstudio prospectivo y observacional que incluyó 86 pacientes inscritos en un protocolo de VA desde 2009 hasta 2019, con resultados de PCA3 y SelectMDx previos al diagnóstico de CaP o durante su periodo de confirmación. Se realizaron análisis univariantes y multivariantes para la correlación de las puntuaciones de PCA3 y SelectMDx, así como de las variables clinicopatológicas con la supervivencia libre de progresión patológica (SLPP). Se definieron los puntos de corte más fiables para ambos biomarcadores en el contexto de VA.ResultadosSelectMDx mostró diferencias estadísticamente significativas en relación con la SLPP (HR: 1,035; IC95%: 1,012-1,057) (p=0,002) con un índiceC de 0,670 (IC95%: 0,529-0,810) y un AUC de 0,714 (IC95%: 0,603-0,825) a 5años. En nuestra serie, el punto de corte más fiable para el SelectMDx fue 5, con una sensibilidad y una especificidad para la PP del 69,8 y del 67,4%, respectivamente. El punto de corte del test PCA3 fue de 65, con una sensibilidad y una especificidad para la PP del 51,16 y del 74,42%, respectivamente. La combinación de ambos biomarcadores no mejoró la predicción de la PP, con un índiceC de 0,630 (IC95%: 0,455-0,805).ConclusionesEn el contexto del CaP de bajo o muy bajo riesgo, SelectMDx >5 predijo una supervivencia libre de PP de 5años con una capacidad de discriminación moderada, superando al PCA3. La combinación de ambos no mejoró los resultados. (AU)

Introduction and objectives: A not negligible percentage of patients included in active surveillance (AS) for low and very low risk prostate cancer (PCa) are reclassified in the confirmatory biopsy or have disease progression during follow-up. Our aim is to evaluate the role of PCA3 and SelectMDx, in an individual and combined way, in the prediction of pathological progression (PP) in a standard AS program.Materials and methodsProspective and observational study comprised of 86 patients enrolled in an AS program from 2009 to 2019, with results for PCA3 and SelectMDx previous to PCa diagnosis or during their confirmatory period. Univariate and multivariate analysis were performed to correlate PCA3 and SelectMDx scores as well as clinical and pathological variables with PP-free survival (PPFS). The most reliable cut-offs for both biomarkers in the context of AS were defined.ResultsSelectMDx showed statistically significant differences related to PPFS (HR: 1.035; 95%CI: 1.012-1.057) (P=.002) with a C-index of 0.670 (95%CI: 0.529-0.810) and AUC of 0.714 (95%CI: 0.603-0.825) at 5years. In our series, the most reliable cut-off point for SelectMDx was 5, with a sensitivity and specificity for PP of 69.8% and 67.4%, respectively. Same figure for PCA3 was 65, with a sensitivity and specificity for PP of 51.16% and 74.42%, respectively. The combination of both biomarkers did not improve the prediction of PP, C-index 0.630 (95%CI: 0.455-0.805).ConclusionsIn the context of low or very low risk PCa, SelectMDx >5 predicted 5years PP free survival with a moderate discrimination ability outperforming PCA3. The combination of both tests did not improved outcomes. (AU)

[Immunohistochemical expression of microvascular density and carbonic anhidrase IX in renal carcinoma. Relation to histological type and tumoral progression]. / Expresión inmunohistoquímica de la densidad microvascular y de la anhidrasa carbónica IX en carcinoma renal. Relación con el tipo histológico y con la progresión tumoral.

PURPOSE: to correlate the immunohistochemical expression of microvascular density (MVD) and the carbonic anhydrase IX (CAIX) with the different histological subtypes of renal carcinoma and its progression. MATERIAL AND METHODS: we studied 93 patients with renal cell carcinoma operated between 1990 and 2008. Antibodies employed for immunohistochemistry (IHC); CD31 (1: 40, Dako) and CD34 (1: 50, Dako) for MVD and CAIX (1: 100, Santa Cruz). CAIX was validated semiquantitatively as: strongly positive (>85%); weakly positive (10% -85%); and negative (< 10%), independently of the intensity of the stain. MVD was validated with both anti-CD31 and anti-CD34 by means of a whole section, to select the microscopic field (x100) with highest density of stained vessels, counting the number of vessels in a photographic field of 0.53 mm(2). Results are expressed as the maximal number of vessels by mm(2) of tumour tissue. RESULTS: median follow up was 40 months (1-160). We found no differences of expression with any of the 3 IHC markers between tumours that progressed (49) and tumours that did not progress (44). The IHC expression of CAIX was strongly related to MVD, measured for both CD31 and CD34 (p<0.0001). MVD with both antibodies was inversely related to tumour size and Fuhrman grade and was also stronger in clear cell carcinomas compared to the rest of histological subtypes, measured by CD31 (p = 0.001) and CD34 (p = 0.003). CONCLUSIONS: neither MVD nor CAIX expressions were related to tumour progression, but were related to histological subtypes. This fact, added to their co-expression, could prompt the use of the CAIX expression, which is far more reproducible, as a quick and easy approximation to MVD. More research should be done to use it as marker for targeted therapy.

Resultados oncológicos a largo plazo del tratamiento cáncer de próstata de alto riesgo mediante prostatectomía radical en un hospital oncológico / Long-term oncological results of treatment for high-risk prostate cancer using radical prostatectomy in a cancer hospital

Objetivos: Analizar los resultados oncológicos más relevantes en el tratamiento mediante prostatectomía radical (PR) en el cáncer de próstata de alto riesgo (CPAR) en un hospital oncológico. Material y métodos: Estudio retrospectivo descriptivo de las PR realizadas en nuestro centro desde 1986 a 2017 en CPAR para conocer como objetivo primario las supervivencia global (SG) y cáncer específica (SCE), y como objetivos secundarios las supervivencias libre de progresión bioquímica (SLPB), libre de progresión metastática (SLPM), la necesidad de tratamiento de rescate (SLTR), la necesidad de hormonoterapia (SLHT) y finalmente el desarrollo de cáncer de próstata resistente a la castración. Se realizan análisis de regresión de Cox para establecer modelos predictivos y conocer el peso de cada variable definitoria de alto riesgo. Resultados: Se realizaron 2.093 PR de las cuales 480 (22,9%) fueron en CPAR. La mediana de seguimiento de la serie global fue 79,57 meses (P25-75 37,92-135,16). No se realizó linfadenectomía (LDN) en el 6,5% de los casos, mientras que fue LDN obturatriz en 51,2% y extensa en 42,3%. La SG a 5, 10 y 15 años fue de 89,8% (IC 95%: 86,7-92,9%), 73,3% (IC 95%: 68-78,6%) y 51,4% (IC 95%: 43,8-59%). La SCE a 5, 10 y 15 años fue de 94,8% (IC 95%: 92,4-97,2%), 84,0% (IC 95%: 79,3-88,7%) y 75,5% (IC 95%: 68,8-82,2%) La SLPM a 5, 10 y 15 años fue de 87,4% (IC 95%: 84,1-90,7%), 72,2% (IC 95%: 66,7-77,7%) y 61,7% (IC 95%: 54,3-69,1%) respectivamente. Se requirió radioterapia de rescate en 120 pacientes de 477 analizados (25,1%) y 293/477 nunca han requerido hormonoterapia (61,4%). En relación con el uso de HT en los 93 pacientes pN1, 33 (35,5%) no la han necesitado. El tiempo desde la PR a la progresión bioquímica es la variable de mayor peso pronóstico para la SLPM, la SCE y la SG. Conclusiones: La PR más LDN extensa debería ser la primera maniobra terapéutica cuando es factible dentro de una estrategia multimodal. Es necesario un seguimiento mayor de la serie para validar la hipótesis de unos mejores resultados oncológicos basándose en una aplicación más precoz de la RT de rescate, una LDN extensa y los fármacos prolongadores de supervivencia en la fase de CPRC

Objectives: To analyse the most relevant oncologic results of treatment using radical prostatectomy (RP) for high-risk prostate cancer (HRPC) in a specialist cancer hospital. Material and methods: A descriptive retrospective study of RP was conducted at our centre from 1986 to 2017 on HRPC whose primary objective was to determine overall survival (OS) and cancer-specific survival (CSS). The study's secondary objectives were to determine biochemical progression-free survival (BPFS), metastasis-free survival (MFS), rescue therapy-free survival (RTFS), hormone therapy-free survival (HTFS) and the development of castration-resistant prostate cancer. We performed a Cox regression analysis to establish predictive models and to better understand the weight of each variable that defines high risk. Results: A total of 2093 RPs were performed, 480 (22.9%) of which were for HRPC. The median follow-up for the overall series was 79.57 months (P25-75 37.92-135.16). Lymphadenectomy was not performed in 6.5% of the cases. The lymphadenectomy was of the obturator type in 51.2% of the cases and extended in 42.3%. Overall survival at 5, 10 and 15 years was 89.8% (95% CI 86.7-92.9%), 73.3% (95% CI 68-78.6%) and 51.4% (95% CI 43.8-59%), respectively. CSS at 5, 10 and 15 years was 94.8% (95% CI 92.4-97.2%), 84.0% (95% CI 79.3-88.7%) and 75.5% (95% CI 68.8-82.2%), respectively. MFS at 5, 10 and 15 years was 87.4% (95% CI 84.1-90.7%), 72.2% (95% CI 66.7-77.7%) and 61.7% (95% CI 54.3-69.1%), respectively. A total of 120 patients of 477 analysed (25.1%) required rescue radiation therapy, and 293/477 never required hormone therapy (61.4%). Of the 93 pN1 patients, 33 (35.5%) did not require hormone therapy. The time from RP to biochemical progression was the variable with the greatest prognostic weight for MFS, CSS and overall survival. Conclusions: RP plus extended lymphadenectomy should be the first therapeutic manoeuvre when feasible within a multimodal strategy. A longer follow-up of the series is needed to validate the hypothesis of better oncologic results based on the earlier implementation of rescue radiation therapy, extended lymphadenectomy and drugs that prolong survival in the CRPC phase

[Protocol proposal for the histological report of the primary tumor in patients with cutaneous melanoma from the Task Force for Cutaneous Melanoma of the Valencian Community]. / Propuesta de protocolo para el informe histológico del tumor primario de los pacientes con un melanoma cutáneo del Grupo de Trabajo para el Melanoma Cutáneo de la Comunidad Valenciana.

This text compiles a histological protocol proposal for cutaneous melanoma agreed by the Task Force for Cutaneous Melanoma of the Valencian Community. It brings together the protocol itself and, in addition, includes a description of each of the proposed variables that has shown to have a greater prognostic impact in previous works.

Expresión inmunohistoquímica de la densidad microvascular y de la anhidrasa carbónica IX en carcinoma renal. Relación con el tipo histológico y con la progresión tumoral / Immunohistochemical expression of microvascular density and carbonic anhidrase IX in renal carcinoma. Relation to histological type and tumoral progression

Objetivos: relacionar la expresión inmunohistoquímica (IHQ) de la densidad microvascular (DMV) y de la anhidrasa carbónica IX (ACIX) con los tipos histológicos de carcinoma renal (CR) y con su progresión. Material y métodos: se estudiaron 93 pacientes operados por CR entre 1990-2008. Anticuerpos: CD31 (1: 40, Dako) y CD34 (1: 50, Dako) para DMV y ACIX (1: 100, Santa Cruz). ACIX se valoró semicuantitativamente; intensamente positivos (>85%), débilmente positivos (10-85%) y negativos (< 10%), independientemente de la intensidad de la tinción. La DMV se valoró independientemente con anti-CD31 y anti-CD34. Campo de bajo aumento (x100) con mayor densidad de vasos teñidos; se contabilizó el número de vasos en un campo fotográfico de 0,53mm2. Resultados expresados como número máximo de vasos/ mm2 de tejido tumoral. Resultados: mediana seguimiento; 40 meses (1-160). No encontramos diferencias IHQ para ninguno de los 3 marcadores entre tumores que progresan (49) y no progresan (44). La expresión de ACIX estaba relacionada con la DMV (p<0,0001). La DMV se relacionó inversamente con el tamaño tumoral y con el grado de Fuhrman de forma significativa. Así mismo, fue significativamente mayor en los CR de células claras, tanto medida con CD31 (p=0,001) como con CD34 (p=0,003) frente al resto de subtipos histológicos. Conclusiones: la DMV y la expresión de ACIX no se relacionan con la progresión, pero sí con el tipo tumoral. Ello y su coexpresividad permitiría usar la expresión de ACIX como medida orientativa rápida y fácil para medir DMV y su posible relación con la respuesta a antiangiogénicos (AU)

Purpose: to correlate the immunohistochemical expression of microvascular density (MVD) and the carbonic anhydrase IX (CAIX) with the different histological subtypes of renal carcinoma and its progression. Material and methods: we studied 93 patients with renal cell carcinoma operated between 1990 and 2008. Antibodies employed for immunohistochemistry (IHC); CD31 (1: 40, Dako) and CD34 (1: 50, Dako) for MVD and CAIX (1: 100, Santa Cruz). CAIX was validated semiquantitatively as: strongly positive (>85%); weakly positive (10% -85%); and negative (< 10%), independently of the intensity of the stain. MVD was validated with both anti-CD31 and anti-CD34 by means of a whole section, to select the microscopic field (x100) with highest density of stained vessels, counting the number of vessels in a photographic field of 0.53mm2. Results are expressed as the maximal number of vessels by mm2 of tumour tissue. Results: median follow up was 40 months (1-160). We found no differences of expression with any of the 3 IHC markers between tumours that progressed (49) and tumours that did not progress (44). The IHC expression of CAIX was strongly related to MVD, measured for both CD31 and CD34 (p<0.0001). MVD with both antibodies was inversely related to tumour size and Fuhrman grade and was also stronger in clear cell carcinomas compared to the rest of histological subtypes, measured by CD31 (p=0.001) and CD34 (p=0.003). Conclusions: neither MVD nor CAIX expressions were related to tumour progression, but were related to histological subtypes. This fact, added to their co-expression, could prompt the use of the CAIX expression, which is far more reproducible, as a quick and easy approximation to MVD. More research should be done to use it as marker for targeted therapy (AU)