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Jesus Fernandez-Gomez
European urology 09/2011; 60(3):433-4. · 7.67 Impact Factor
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Jesus Fernandez-Gomez,
Rosario Madero,
Eduardo Solsona,
Miguel Unda,
Luis Martinez-Piñeiro,
Antonio Ojea,
Jose Portillo,
Manuel Montesinos,
Marcelino Gonzalez,
Carlos Pertusa,
Jesus Rodriguez-Molina,
Jose Emilio Camacho,
Mariano Rabadan,
Ander Astobieta,
Santiago Isorna,
Pedro Muntañola,
Anabel Gimeno,
Miguel Blas,
Jose Antonio Martinez-Piñeiro
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ABSTRACT: European Organization for Research and Treatment of Cancer (EORTC) risk tables only included 171 patients treated with bacillus Calmette-Guérin (BCG) for non-muscle-invasive bladder cancer (NMIBC).
To evaluate the external validity of the EORTC tables in patients with NMIBC treated with BCG over 5-6 mo.
Data on 1062 patients treated with BCG were analyzed.
Discrimination was assessed using the concordance index (c-index) and the prognostic separation index (PSEP). For calibration, probabilities of recurrence and progression obtained with the EORTC risk tables in our series were compared with those reported by the EORTC.
With respect to the discriminative ability of the EORTC model, c-index was similar to those reported in the EORTC series for recurrence. However, c-indices for progression in our series were lower than c-indices reported by Sylvester et al. [1]. Although PSEP in our series was lower than in the EORTC series for recurrence at 1 yr, similar results were found at 5 yr. Regarding progression, PSEP in our series was lower than in the EORTC series. Whilst a successful stratification of recurrence and progression probability at 1 and 5 yr was achieved using the EORTC tables in our series, model calibration showed lower risks of recurrence than those reported by Sylvester et al. [1] in all groups. For progression, lower risks were found in higher-risk groups. There are some limitations in the present study. A different distribution of patients was found, with higher proportions of primary grade 3 T1 tumors and tumors in situ than in the EORTC series. An additional limitation is that prior recurrence of the EORTC table was not included in our parameters. Consequently, two separate analyses were performed for recurrence.
The EORTC model successfully stratified recurrence and progression risks in our cohort. However, the discriminative ability of the EORTC tables decreased in our patients for progression. Moreover, these tables overestimated risks of recurrence and progression after BCG therapy.
European urology 05/2011; 60(3):423-30. · 7.67 Impact Factor
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ABSTRACT: • To assess the prevalence of peripheral neuropathy in patients with erectile dysfunction (ED). • To evaluate the reliability of clinical tests such as the five-item version of the International Index of Erectile Function (IIEF-5) and the Neuropathy Symptom Score (NSS) classification system in predicting the concurrence of peripheral neuropathy.
• We studied 90 patients who were consecutively recruited from the Department of Andrology of the Central Hospital of Asturias. • Anamnesis included questions about risk factors related to ED. • The severity of ED was classified according to IIEF-5 scores and symptoms of peripheral neuropathy were assessed using the NSS. • Neurophysiological tests included electromyography, nerve conduction studies, evoked potentials from pudendal and tibial nerves as well as bulbocavernosus reflex. • Small fibre function was assessed using quantitative sensory tests and sympathetic skin response. Statistical analysis was performed using the SPSS-11 program.
• Patients with more severe symptoms of peripheral neuropathy showed lower (worse) IIEF-5 scores (P= 0.015) and required more aggressive therapies (P < 0.001). • Neurophysiological exploration confirmed neurological pathology in 68.9% of patients, of whom 7.8% had myelopathy and 61.1% peripheral neuropathy. • Polyneuropathy was found in 37.8% of the patients, of whom 8.9% had pure small fibre polyneuropathy, and pudendal neuropathy was diagnosed in 14.4%. • No association between neurophysiological diagnosis and IIEF-5 score was detected, but a statistical association was found between neuropathy and NSS scores.
• Up to now, the impact of peripheral neuropathy in the pathogenesis of ED has been underestimated. The combination of anamnesis and an ad hoc neurophysiological protocol showed its high prevalence and provided a more accurate prognosis. • In future, clinical practice should optimize the assessment of pelvic small fibre function.
BJU International 05/2011; 108(11):1855-9. · 2.84 Impact Factor
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ABSTRACT: The aim of this study was to detect a potential association between clinicopathological factors of prostate cancer aggressiveness and the expression of matrix metalloproteases and their inhibitors in tumour and stromal cells.
A tissue array technique and immunochemistry with specific antibodies against matrix metalloproteinases (MMPs)-1, 2, 7, 9, 11, 13, 14, and their tissue inhibitors (TIMPs)-1, 2 and 3 were used to analyse the surgical specimens of 133 patients treated by radical prostatectomy. For each antibody preparation, the cellular location of immunoreactivity was determined.
The expression of MMP-2 was negatively associated with high tumour grade. With regard to stromal fibroblasts, TIMP-3 expression was positively associated with histological grade. MMP-7 expression was negatively associated with pretreatment serum levels of PSA, whereas MMP-13 was positively associated with higher levels of the antigen. TIMP-2 expression by mononuclear inflammatory cells correlated significantly and negatively with tumour grade.
The expression of TIMP-3 by fibroblasts was associated with a higher Gleason score. An increased expression of MMP-13 by fibroblasts was associated with a greater preoperative level of PSA. In contrast, MMP-2 expression by tumour as well as TIMP-2 expression by peritumoral inflammatory cells was associated with less aggressive prostate carcinoma characteristics.
Scandinavian Journal of Urology and Nephrology 01/2011; 45(3):171-6. · 0.99 Impact Factor
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ABSTRACT: To evaluate the role of the sympathetic skin response (SSR) in men with erectile dysfunction (ED), focusing on detecting SSR in the penis.
We assessed the SSR in 82 patients with ED, as an indicator of abnormalities both in amyelinic C-fibres and in autonomic pathways in these patients. The SSR was carried out according to the to the Technical Standards of the International Federation of Clinical Neurophysiology. Electrical stimulation was applied through superficial electrodes over the contralateral median nerve. Values were recorded with superficial electrodes on the skin in the contralateral hand and foot, as well as in the penis. The percentage of SSR (SSR%) was classified into three groups, i.e. 0-20%, 21-89% and 90-100%. Results of latency were also classified into three groups of normal or abnormal (increased) latency, and response blocking (no response), the last two being considered pathological conditions.
In the penis, the mean (sd) SSR% was 52.8 (43.19)% and significantly lower than responses in hands and feet. There was a significant correlation of the SSR% between the palm of the hand and the sole of the foot (P = 0.01) and between the sole of foot and penis (P = 0.05). Diabetics showed a significant decrease (P = 0.001) in the mean SSR% in the palm of the hand and sole of the foot. Although not statistically different, the mean SSR% in the penis was lower in diabetics than in patients with other risk factors for ED. Likewise, the mean SSR% in hand, foot and penis increased with an increase in the International Index of Erectile Function. In the penis, latency was normal (<1.5 ms) in 14 and abnormal in 37 patients. There was a significant association between pathological chronic re-innervation in the bulbocavernosus muscle and SSR latencies in the foot (P = 0.002) and penis (P = 0.03). Bulbocavernosus muscle electromyography showed a higher frequency of chronic bilateral axonomnesis in patients with abnormal latencies (28%) than in patients with normal SSR latencies in the penis.
These results establish an indication of the SSR in patients with ED, registering responses not only in classic locations like the palm of the hand or sole of the foot, but also in the penis. The SSR% was useful as an indicator of the effect on efferent C fibres. Despite SSR being a polysynaptic potential of long latency and regulated by the cerebral cortex, the present results show that it is advisable to record the latencies of SSR in the three areas registered, and especially in the penis, where it seems be more useful as a marker of lumbosacral and/or pudendal alterations.
BJU International 09/2009; 104(11):1709-12. · 2.84 Impact Factor
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Jesus Fernandez-Gomez,
Rosario Madero,
Eduardo Solsona,
Miguel Unda,
Luis Martinez-Piñeiro,
Marcelino Gonzalez,
Jose Portillo,
Antonio Ojea,
Carlos Pertusa,
Jesus Rodriguez-Molina,
Jose Emilio Camacho,
Mariano Rabadan,
Ander Astobieta,
Manuel Montesinos,
Santiago Isorna,
Pedro Muntañola,
Anabel Gimeno,
Miguel Blas,
Jose Antonio Martinez-Piñeiro
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ABSTRACT: Bacillus Calmette-Guerin is the most effective therapy for nonmuscle invasive bladder cancer. Recently to calculate the risks of recurrence and progression based on data from 7 European Organisation for Research and Treatment of Cancer trials a scoring system was reported. However, in that series only 171 patients were treated with bacillus Calmette-Guerin. We developed a risk stratification model to provide accurate estimates of recurrence and progression probability after bacillus Calmette-Guerin.
Data were analyzed on 1,062 patients treated with bacillus Calmette-Guerin and included in 4 Spanish Urological Club for Oncological Treatment trials. Stepwise multivariate Cox models were used to determine the effect of prognostic factors. In each patient the weight of all factors was summed to a total score. Patients were then divided into groups, and cumulative recurrence and progression rates were calculated.
A scoring system was calculated with a score of 0 to 16 for recurrence and 0 to 14 for progression. Patients were categorized into 4 groups by score, and recurrence and progression probabilities were calculated in each group. For recurrence the variables were gender, age, grade, tumor status, multiplicity and associated Tis. For progression the variables were age, grade, tumor status, T category, multiplicity and associated Tis. For recurrence calculated risks using Spanish Urological Club for Oncological Treatment tables were lower than those obtained with Sylvester tables. For progression probabilities were lower in our model only in patients with high risk tumors.
We propose a scoring model to stratify the risk of recurrence and progression in patients treated with bacillus Calmette-Guerin.
The Journal of urology 09/2009; 182(5):2195-203. · 4.02 Impact Factor
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Jesus Fernandez-Gomez,
Eduardo Solsona,
Miguel Unda,
Luis Martinez-Piñeiro,
Marcelino Gonzalez,
Rafael Hernandez,
Rosario Madero,
Antonio Ojea,
Carlos Pertusa,
Jesus Rodriguez-Molina,
Jose Emilio Camacho,
Santiago Isorna,
Mariano Rabadan,
Ander Astobieta,
Manuel Montesinos,
Pedro Muntañola,
Anabel Gimeno,
Miguel Blas,
Jose Antonio Martinez-Piñeiro
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ABSTRACT: To evaluate the prognostic factors of recurrence and progression after intravesical adjuvant bacillus Calmette-Guérin (BCG) immunotherapy in patients with non-muscle-invasive bladder tumors.
From February 1990 to May 1999, the Spanish Club Urológico Español de Tratamiento Oncológico (CUETO) group has performed four randomized phase 3 studies comparing different intravesical treatments in patients with noninvasive bladder cancer. Data from 1062 evaluable patients treated only with BCG were analyzed. Most patients received BCG once weekly for 6 consecutive weeks and a short-term BCG maintenance (once every 2 wk 6 times more). Associated tumor in situ (TIS) was found in 7.5% (n=80) of cases. There were 22.1% (n=235) patients with T1G3 tumors, 22.9% of whom (n=54) were associated with TIS. Stepwise multivariate Cox regression models with stratification by study and dose were used to assess the independent effect of predictive factors and hazard ratios (HRs) were estimated from the Cox model.
Multivariate analysis demonstrated that female gender (HR=1.71) compared to male gender, recurrent tumors (HR=1.9) compared to primary tumors, multiplicity, and presence of associated TIS (HR=1.54) increased the risk of recurrence. Recurrent tumors (HR=1.62) compared to primary tumors, high-grade tumors (HR=5.64) compared to G1 tumors, T1 tumors (HR=2.15) compared to Ta tumors, and recurrence at 3-mo cystoscopy (HR=4.6) increased the risk of progression.
Significant independent predictors for recurrence were female gender, history of recurrence, multiplicity, and presence of associated TIS. Age, history of recurrence, high grade, T1 stage, and recurrence at first cystoscopy were independent predictors of progression by multivariate Cox analysis.
European Urology 06/2008; 53(5):992-1001. · 8.49 Impact Factor
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ABSTRACT: The objective of this prospective study is to establish an appropriate cutoff value of urinary CYFRA 21.1 assay and to assess its utility combined with voided cytology and/or haemoglobin dipstick in the follow-up of patients with superficial bladder cancer.
From December 2000 to November 2003, 446 patients in follow-up for superficial bladder cancer (Ta-T1) after transurethral resection of the bladder (TURB) were included in a prospective study. Voided urine specimens were collected 7-14 d before cystoscopy and/or TURB for CYFRA 21.1 (one sample), haemoglobin dipstick (one sample), and cytology (three samples). All samples were processed for CYFRA 21.1 and haemoglobin dipstick according to manufacturer instructions. A control group (n=185) was obtained from patients in follow-up after transurethral resection of superficial disease (without recurrences within the following 6 mo). There were 125 recurrent transitional tumours detected by cystoscopy (34 TaG1; 53 TaG2/T1G1-2; 23 Ta-1G3/Tis, and 15 T2-4). Receiver operator characteristic (ROC) curves were constructed and cutoff values were chosen. Sensitivity, specificity, PPV (positive predictive value), NPV (negative predictive value), and their 95% confidence intervals were calculated.
ROC curve analysis based on the previously reported cutoff value of 4ng/ml for CYFRA 21.1 demonstrated a sensitivity and specificity of 43% and 68%, respectively. At a cutoff value of 1.5ng/ml, sensitivity was 73.8% with a low specificity (41%). Further lowering of the cutoff point below 1.5ng/ml did not demonstrate a significant increase in sensitivity. Therefore, this value was chosen as the most sensitive CYFRA 21.1 cutoff point during the rest of the study. Specificity increased when all the patients treated with pelvic radiotherapy or with UTI, urethral catheterisation, and intravesical instillations within 3 previous months were not included in our analysis. CYFRA 21.1 plus cytology and the combination of CYFRA 21.1, cytology, and haemoglobin dipstick demonstrated the highest overall sensitivities, and detected 91.3% of Ta-1G3 tumours and 93.3% of T2-4 tumours. However, there were one muscle-invasive tumour, two T1G3/Tis, three T1G2, and nine T1G1 neoplasms with negative combination of cytology and CYFRA 21.1 (1,5ng/ml). All these tumours were smaller than 2cm in size; most were single tumours. Nevertheless, there were 16 tumours larger than 0.5cm (0.5-2cm), and multiple neoplasms were endoscopically detected in 14 patients. Similar results were obtained through the combination of CYFRA 21.1 (cutoff: 1.5ng/ml), cytology, and haemoglobin dipstick.
In our experience the low sensitivity of urinary CYFRA 21.1, even using lower cutoff values and/or a combination with cytology and/or haemoglobin dipstick, makes its application not very useful as a surveillance tool for superficial bladder carcinoma.
European Urology 06/2007; 51(5):1267-74. · 8.49 Impact Factor
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ABSTRACT: The purpose of the present study was to evaluate the length of telomeres in patients with bladder cancer using a quantitative flow cytometry (flow-FISH) technique.
Bladder washing samples from 51 patients with bladder cancer were obtained immediately before transurethral resection. The average length of telomere repeats was measured by flow-FISH, as previously reported. Results were expressed in molecular equivalents of soluble fluorochrome (MESF) units.
Bladder washing specimens provided adequate cell numbers for flow-FISH in 49 cases. The TEL means were 1014.71, 2343.36, 5567 and 18267.57 for Ta, T1, T2 and T3/4 tumors, respectively. Regarding grade it was obtained a mean MESF value of 1379.46, 3391.29 and 15925.11 for G1, G2 and G3, respectively. ANOVA demonstrated statistically significant differences in stage (p: 0.014) and tumor grades (p: 0.012). In relation to ploidy, we found a mean MESF value of 2701.37 and 16085.44 MESF units for diploid and aneuploid cells, respectively. Significant difference (p: 0.003) was observed between both groups.
To date, this is the first report wherein telomere length was measured using flow-FISH method in exfoliated cells in urine from patients with bladder cancer. Further investigations are required to demonstrate whether flow-FISH technique might be considered as a tumor marker of bladder cancer.
European Urology 10/2005; 48(3):432-7. · 8.49 Impact Factor
