F. Ramón de Fata

Eficacia y seguridad de fosfomicina-trometamol en la profilaxis de la biopsia transrectal de la próstata: estudio prospectivo aleatorizado comparativo con ciprofloxacino

OBJECTIVE Prostate biopsy is the standardized diagnostic method for prostate cancer. However, although there is not a standardized protocol, there are recommendations in order to reduce the incidence of complications. The objective of the present work is to assess the efficacy and safety of antibiotic prophylaxis in the prostate biopsy by comparing two antibiotic regimes: two doses of fosfomycin-trometamol 3g (FMT) every 48 hours with 10 doses of oral ciprofloxacin 500 mg every 12 hours during 5 days. MATERIAL AND METHODS Randomized prospective study was performed with 671 patients who had undergone to walking transrectal ultrasound guided prostate biopsy. Patients of group A (n=312) were treated with ciprofloxacin, and patients of group B (n=359) with FMT. Efficacy and tolerability of two prophylactic regimes were compared. Urine culture was carried out at 2 weeks after biopsy. Initially, patients with asymptomatic bacteriuria were not treated with antibiotics; urine culture was repeated after 1 month, persistent bacteriuria was treated according to antibiogram. RESULTS No differences between groups were found in age (P=.78), cancer presence (P=.9) or number of biopsy cylinders (P=.93). The mean number of cores obtained was 11.3 ± 3.25 (range 6-20). Digestive intolerance was observed for 9 patients (2.9%) of group A and 10 patients (2.8%) in group B. One patient (.3%) of group A showed severe allergic reaction. In total, 167 patients (24.6%) had complications: 16 (2.4%) fever, 47 (6.9%) hemospermia, 81 (11.9%) hematuria, 7 (1%) rectal bleeding and 16 (2.4%) urinary retention. No statistically differences between groups were observed (27.6% vs. 22.6%; P=.17). However, hemospermia was more frequent in group A (9.9% vs. 4.5%; P=.006). Bacteriuria after biopsy was detected in 44 patients (6.6%), being more frequent in group B patients (4.2% vs. 8.6%; P=.02) although a higher number of second treatment cycles were not needed (53.9% vs. 29%; P=.17). The likelihood of resistance to ciprofloxacin in patients with bacteriuria in A was greater than that of FMT in B (69.2% vs. 41.9%; P=.0004). CONCLUSIONS Antibiotic prophylaxis with FMT (2 doses of 3g) in prostate biopsy is an alternative as effective and safe as ciprofloxacin (10 doses of 500 mg), which carries lower rate of resistance. According to our experience, this drug is a safe, well-tolerated, and easily manageable prophylactic option, facilitating patient compliance. More prospective multicenter studies are necessary to confirm these findings.

Estudio comparativo entre cirugía retrógrada intrarrenal y micro-nefrolitotomía percutánea en el tratamiento de la litiasis renal de tamaño intermedio

OBJECTIVE Retrograde intrarenal surgery (RIRS) has proven efficacy with minimal morbidity in the treatment of intermediate-sized kidney stones. The aim of this study was to examine the feasibility of micropercutaneous nephrolithotomy (microperc) for this indication and evaluate its results compared with those of RIRS. MATERIAL AND METHODS From September to December 2013, we performed a comparative prospective study between RIRS and microperc, with 20 consecutive patients with intermediate-sized (1-3cm) kidney stones. We employed a flexible dual-channel ureteroscope (Cobra, Richard Wolf GmbH) and a Microperc 4.85/8 Fr (with the patient supine) with flexible fiberoptics (0.9mm, 120° and 10,000 pixels) (PolyDiagnost GmbH). The study variables were demographic data, stone characteristics, percentage of stone elimination, complications (Clavien-Dindo), surgical time, hospital stay and need for auxiliary procedures. RESULTS The patients underwent RIRS (n=12) or microperc (n=8). There were no differences in the demographics or stone characteristics between the 2 groups. The percentage of stone elimination with RIRS and microperc was 91.7% and 87.5% (P=1), respectively. One of the patients who underwent RIRS (8.3%) experienced postoperative fever; one of the patients who underwent microperc (12.5%) experienced postoperative colic pain (both cases were classified as Clavien I). The operative times were similar: 120min (111.2-148.7) and 120 (88.7-167.5) min for RIRS and microperc (P=.8), respectively. None of the patients required a blood transfusion. The hospital stays were also equivalent: 1 day (1-2) and 1.5 days (1-3.5) for RIRS and microperc (P=.33), respectively. Two patients treated with microperc (25%) required auxiliary procedures (simultaneous RIRS and flexible nephroscopy after percutaneous trajectory dilation to treat, in both cases, a significant fragment that had migrated to an inaccessible calyx), and 1 patient in the RIRS group (8.3%) required percutaneous nephrolithotomy due to unfavorable infundibular-calyceal anatomy (P=.54). CONCLUSIONS Microperc is a minimally invasive method that is emerging as an effective and safe treatment for intermediate-sized kidney stones. Studies are needed to better evaluate its cost-effectiveness, the need for complementary treatments and its possible complementarity with RIRS when working with patients in the supine position.

Análisis de los factores implicados en el fracaso de la uretroplastia en el varón

INTRODUCTION Outcome of urethroplasty techniques in our environment and risk factors for recurrence of stenosis in these patients are studied in this paper. MATERIAL AND METHODS Retrospective study on men with urethral strictures treated with urethroplasty in the period 2000-2012. Maximum flow (Qmax), post-void residual (PVR) urine and patient perception of voiding were obtained pre- and postoperatively. Complications were recorded according to the Clavien-Dindo scale. Recurrent stricture was defined according to clinical criteria and endoscopic or imaging confirmation (failure of urethroplasty). Univariate analysis (log-rank) and multivariate (Cox regression) were performed to define the variables implied in the recurrence. RESULTS 82 patients with mean age 55.6 ± 17.4 (19-84 years) underwent surgery for urethroplasty. 28% of patients showed multiple stricture, 73.2% bulbar stricture, 41.54% penile stricture and 14.6% membranous stricture. End-to-end anastomosis was performed in 26 cases (31.7%), flap urethroplasty in 21 (25.6%), urethroplasty with free graft in 31 (37.8%) and two-time urethroplasty in 4 (4.9%). Graft urethroplasty showed a longer operative time (p = 0.02) and shorter hospital stay (P = 0.0035). The results were: mean ΔQmax (mean on baseline) 9.1 ± 7.5 and mean ΔPVR -65.8 ± 136 (both P < 0.0001). Minor early complications occurred in 8 (9.8%) and major in 3 (3.6%). Recurrence occurred at a mean time of 39.8 ± 39.2 months in 18 patients (21.9%). The percentage of recurrence-free patients was: 91.4% (1-year), 82.1% (5-year) and 78.1% (10-year). Univariate analysis assessed technique used (log-rank, P = 0.13), age (P = 0.2), length stricture (P = 0.003), previous Sachse (P = 0.18), associated lichen (P = 0.18), multiplicity (P = 0.36), year of surgery (P = 0.2), Qmax (P = 0.3) and RPM (P = 0.07) preoperative. End to end anastomosis (HR 4.98, P = 0.04) and length > 3 cm (HR 4.6, P = 0.01) were identified by regression analysis as independent variables associated with poor prognosis. CONCLUSION Length stricture is both prognostic factor and criterion on choosing the type of urethroplasty, and it makes more complicated to compare the success rates of each surgical procedure. Whatever the stricture size is, the results of anastomotic urethroplasty are worse than those of urethroplasty with buccal mucosal-free grafts.

Análisis de los factores que influyen en la pérdida hemática en la nefrolitotomía percutánea: registro de la Asociación Española de Urología sobre la posición supina

OBJECTIVE Percutaneous nephrolithotomy (PCNL) is the minimally invasive procedure of choice for removing renal stones larger than 2 cm. This study has aimed to identify the different variables that might influence decrease of hemoglobin during the surgery performed in supine position. MATERIAL AND METHODS A prospective, multicenter, observational study of supine PCNL, based on the Spanish Association of Urology database, was analyzed. The different preoperative and postoperative factors that might affect the decrease of hemoglobin were assessed: demographics and anthropometric data, comorbidities, size and location of the stones, anatomical variants and technical aspects of the procedure. RESULTS From September 2008 to December 2012, 397 supine PCNL procedures performed in 15 Spanish centers were registered. Mean hemoglobin decrease was 2.3±1.5 g/dl and overall blood transfusion rate was 5.5%. No statistically significant differences were found between genders, body mass index (BMI) and age in terms of blood loss. There were also no differences between patients with cardiovascular, hypertensive, diabetic and anticoagulant treatment background. Blood loss was not significantly influenced by stone size and location. Technical aspects of the procedure as operative time (> 120 min ≤), access to the pelvi-caliceal system (ultrasound, fluoroscopy), percutaneous tract dilation technique (Alken, balloon or Amplatz) or placement of nephrostomy (tube versus tubeless) were not associated with differences in pre-op/post-op hemoglobin. Only multiple percutaneous tracts (≥2) and middle calix access were statistically significantly (P=.03 and P=.01) related with less blood loss. CONCLUSIONS PCNL in supine position is a minimally invasive procedure for removal of large (≥2 cm) and multiple renal stones, with a low incidence of blood loss and minimal transfusion rate. Multiple percutaneous tracts and middle calix puncture were the only statistically significant variables associated with decrease in hemoglobin levels.

Los polifenoles del vino ejercen su efecto antineoplásico sobre la línea celular PC-3 andrógeno resistente a través de la inhibición de la actividad transcripcional del promotor de COX-2 mediada por NF-kβ

OBJECTIVE Mediterranean diet may play a role in the prevention of prostate cancer (PCa) development and progression. Cyclooxygenase-2 (COX-2) expression is associated with increased cellular proliferation, prevents apoptosis and favors tumor invasion. We intend to clarify whether resveratrol and other polyphenols effectively inhibit COX-2 activity and induce apoptosis in hormone-resistant PC-3 cell line. MATERIAL AND METHOD PC-3 cells were cultured and treated with different concentrations of gallic acid, tannic acid, quercetin, and resveratrol in presence of phorbol myristate acetate (PMA; 50 μg/ml) that induces COX-2 expression. Total RNA was extracted and COX-2 expression was analyzed by relative quantification real-time PCR (ΔΔCt method). COX-2 activity was determined by PGE-2 detection using ELISA. Caspase 3/7 luminescence assay was used to disclose apoptosis. Transitory transfection with short human COX-2 (phPES2 -327/+59) and p5xNF-kβ-Luc plasmids determined COX-2 promoter activity and specifically that dependant of NF-kβ. RESULTS COX-2 expression was not modified in media devoid of PMA. However, under PMA induction tannic acid (2.08 ±.21), gallic acid (2.46 ±.16), quercetin (1.78 ±.14) and resveratrol (1.15 ±.16) significantly inhibited COX-2 mRNA with respect to control (3.14 ±.07), what means a 34%, 23%, 46% and 61% reduction, respectively. The inhibition in the levels of PGE-2 followed a similar pattern. All compounds studied induced apoptosis at 48 h, although at a different rate. PMA caused a rise in activity 7.4 ±.23 times phPES2 -327/+59 and 2.0 ±.1 times p5xNF-kβ-Luc at 6h compared to basal. Resveratrol suppressed these effects 17.1 ±.21 and 32.4 ±.18 times, respectively. Similarly, but to a lesser extent, the rest of evaluated polyphenols diminished PMA inductor effect on the activity of both promoters. CONCLUSIONS Polyphenols inhibit transcriptional activity of COX-2 promoter mediated by NF-kβ. This effect could explain, at least in part, the induction of apoptosis in vitro by these substances in castration resistant PCa.

Estudio comparativo aleatorizado para la evaluación de un nuevo esquema terapéutico de fosfomicina trometamol en mujeres posmenopáusicas con infección no complicada del tracto urinario inferior

OBJECTIVES To compare two therapeutic regimes in terms of bacterial eradication of post-menopausal with uncomplicated acute cystitis who complete antibiotic treatment. MATERIALS AND METHOD A multicenter, randomized, prospective and controlled study between two short antibiotic regimes: fosfomycin trometamol (FMT) 3g, 2 doses separated by 72hours and ciprofloxacin 250mg every 12hours for 3 days. A total of 118 post-menopausal women were enrolled in the study. They underwent an initial urine culture to know the responsible microorganism and susceptibility to treatment. This was repeated 5-7 days and 4 weeks after the treatment to evaluate bacterial eradication. Clinical symptoms and treatment safety were also evaluated. RESULTS There were microbiological data at the onset of the treatment in 82 women (69.49%). Of these, 27 did not have positive culture at the first visit (30.51%), 76 (64.41%) fulfilled all the protocol requirements and adverse effects from the treatment were collected in 113 (95.76%) of the patients enrolled in the study. The germs isolated most frequently were Escherichia coli (E. coli) (76.83%), Klebsiella pneumoniae (K. pneumoniae) (7.32%), Proteus mirabilis (P. mirabilis) (4.89%) and Enterococo sp. (3.66%). In terms of efficacy, no differences were detected in the proportion of patients who achieved bacterial eradication between the two study arms: 62.16% of the patients who received FMT and 58.97% of those treated with ciprofloxacin (chi-square, p=0.78). The proportion of patients who achieved clinical cure was also similar (86.49% for FMT and 82.05% for ciprofloxacin; square, p=0.59). These results indicate similar efficacy of both antibiotics in the treatment of uncomplicated lower tract urinary infection in post-menopausal women. In regards to safety data, the proportion of global adverse effects associated to the treatments was 3.45% for FMT and 9.09% for ciprofloxacin. Treatment compliance was 100% for FMT and 83.64% for ciprofloxacin. CONCLUSIONS The FMT administered at a dose of 3g every 72hours (2 total doses) and ciprofloxacin at a dose of 250mg every 12hours during 3 days (6 total doses) have a comparable efficacy profile in lower tract urinary infection in post-menopausal women who adequately comply with the treatment, also having comparable safety. The FMT has a better antimicrobial susceptibility profile and better rate of treatment compliance.

El papel de la metaloproteinasa de la matriz MMP-9 y del inhibidor tisular de metaloproteinasa TIMP-2 como marcadores séricos de cáncer vesical

INTRODUCTION The diagnosis and molecular staging of bladder cancer based on the detection of gelatinases mRNA (MMP-2 and MMP-9) in peripheral blood circulating and mononuclear cells have shown promising results. We analyze if the determination of the corresponding protein synthesis products makes it possible to diagnose and characterize patients with bladder cancer. MATERIAL AND METHOD Quantification of the serum levels of MMP-2, MMP-9 and TIMP-2 in a series of 42 individuals (31 patients with bladder cancer in different stages and 11 healthy controls) using the ELISA technique was carried out. The determinations were compared between cases and controls (Mann-Whitney U) and between different groups of tumors (Mann-Whitney U or Kruskal-Wallis), according to the clinical-pathological characteristics (age, gender, T category, M category or grade). Diagnostic yield of these markers was evaluated by analysis of the ROC curves. RESULTS There is a correlation between the determinations of MMP-2 and TIMP-2 (R=.699; P>.0001) and MMP-9 and TIMP-2 (R=.305; P=.049). Patients with bladder cancer have higher levels of MMP-9 (p<0.0001) and TIMP-2 (P=.047) than the controls. Furthermore, the MMP-9/TIMP-2 ratio is also superior in cancer patients (P<.001). Differences were not detected between cancer and controls regarding age (P=.64) or gender (P=.64). Differences were also not detected regarding MMP-2 (P=.35) or MMP-2/TIMP-2 rate (P=.45). Within the cancer patient population, the MMP-2 and MMP-9 values differ according to T category (P=.022 and P=.038, respectively) and those of the TIMP-2 according to M category (P=.036). ROC curve analysis showed that both MMP-9 and the MMP-9/TIMP-2 ratio discriminate patients with cancer and controls, with equivalent diagnostic accuracy (ABC 0.953) and cut offs of 3.93 ng/mL (S 90%; Sp 81%) and 0.053 ng/mL (S 96%; Sp 84%), respectively. CONCLUSIONS The results obtained suggest that both serum MMP-9 and TIMP-2 would have an application in the prediction of the development and progression of bladder cancer, and a potential utility as clinical markers of the disease. Multicenter, prospective studies that confirm their preliminary results are necessary.

Linfadenectomía retroperitoneal laparoendoscópica por puerto único en tumor germinal no seminomatoso

INTRODUCTION Umbilical laparoendoscopic single-site (LESS) surgery represents an excellent alternative to laparoscopic or robotic multiport surgery. LESS surgery offers faster recovery, less postoperative pain and optimal cosmetic results. LESS is possible in virtually any urologic surgery. PATIENT AND METHOD We present a 38-year-old male with BMI 31.2 and with history of stage I nonseminomatous mixed germ cell tumor showing interaortocaval lymph node recurrence without elevation of tumor markers. Patient was undergone to right laparoendoscopic single-site retroperitoneal lymph node dissection (LDRP-LESS) by umbilical approach using a single-site multichannel KeyPort (Richard Wolf GmbH, Knittlingen, Germany). RESULTS After the placement of the device and triangulation of the clips, we proceeded to operate on posterior parietal peritoneum. The descending colon was mobilized to access the retroperitoneum. Complete retroperitoneal lymph node dissection on the right side from iliac vessels to renal vessels, including the paracaval and interaortocaval space, was performed. The specimen was inserted into a laparoscopic bag and was removed together with multichannel system. Abdominal drainage was not employed. Surgical time was 85 min and estimated bleeding 50 cc. The patient was very satisfied with the cosmetic results and was discharged the following day without needing analgesia. The pathology report revealed metastatic seminoma in 5 of 11 lymph nodes receiving systemic chemotherapy (VP16-CDDPs) for 4 cycles with good tolerance. A year later, the patient was disease-free and had no complications. CONCLUSIONS Umbilical primary LDRP-LESS, with excellent oncologic and cosmetic results, is feasible in selected cases. This approach could be considered the least invasive surgical option economically advantageous due to the reusable nature of the instruments used.

El PSA basal en una población de varones españoles de 40-49 años anticipa la detección de cáncer de próstata

INTRODUCTION We researched the usefulness of optimizing prostate cancer (PC) screening in our community using baseline PSA readings in men between 40-49 years of age. MATERIAL AND METHOD A retrospective study was performed that analyzed baseline PSA in the fifth decade of life and its ability to predict the development of PC in a population of Madrid (Spain). An ROC curve was created and a cutoff was proposed. We compared the evolution of PSA from baseline in patients with consecutive readings using the Friedman test. We established baseline PSA ranges with different risks of developing cancer and assessed the diagnostic utility of the annual PSA velocity (PSAV) in this population. RESULTS Some 4,304 men aged 40-49 years underwent opportunistic screening over the course of 17 years, with at least one serum PSA reading (6,001 readings) and a mean follow-up of 57.1±36.8 months. Of these, 768 underwent biopsy of some organ, and 104 underwent prostate biopsy. Fourteen patients (.33%) were diagnosed with prostate cancer. The median baseline PSA was .74 (.01-58.5) ng/mL for patients without PC and 4.21 (.76-47.4) ng/mL for those with PC. The median time from the reading to diagnosis was 26.8 (1.5-143.8) months. The optimal cutoff for detecting PC was 1.9ng/mL (sensitivity, 92.86%; specificity, 92.54%; PPV, 3.9%; NPV, 99.97%), and the area under the curve was 92.8%. In terms of the repeated reading, the evolution of the PSA showed no statistically significant differences between the patients without cancer (p=.56) and those with cancer (P=.64). However, a PSAV value >.3ng/mL/year revealed high specificity for detecting cancer in this population. CONCLUSIONS A baseline PSA level ≥1.9ng/mL in Spanish men aged 40-49 years predicted the development of PC. This value could therefore be of use for opportunistic screening at an early age. An appropriate follow-up adapted to the risk of this population needs to be defined, but an annual PSAV ≥.3ng/mL/year appears of use for reaching an early diagnosis.

Estudio comparativo entre abordaje abierto y laparoscópico en la cistectomía radical con reservorio ortotópico ileal continente

OBJECTIVE Probably, laparoscopic radical cystectomy with ileal neobladder and neovesicourethral anastomosis is one of the most complex procedures in minimally invasive surgery. MATERIAL AND METHODS Prospective study carried out in 72 patients surgically treated for invasive bladder neoplasia between January 2008 and October 2013. Patients were undergone to radical cystectomy with ileal neobladder (open approach in 33 patients and laparoscopic approach in 39). The study assessed comparatively surgical outcomes, continence rate and postoperative complications. RESULTS Mean age was 63.5±9 years (64.3 open vs. 62.7 laparoscopic, P=.46) mean surgery time 323.6±78.7 minutes (321.3 vs. 326.5, P=.77), average hospital stay 14.8 days±8,1 (16.2 vs. 13.6, P=.2), transfusion rate 40.3% (66.7% vs. 17.9%, P<.0001) and complications rate 47.2% (63.6% vs. 33.3%, P=.01). Major complications were reported in 29.1% of cases (39.4% open vs. 20,5% laparoscopic, P=.07). With a mean follow-up rate of 42.5±19.2 months (range 15-70), 50 (69.4%) patients remain alive and free of disease. Continence was evaluated in these patients: total continence rate was 38% (50% vs. 27%, P=.09) and diurnal continence rate 58% (70.8% vs. 46.1%, P=.07). Self-catheterization rate was 8% (4.2% vs. 11.5%, P=.67). Total incontinence rate was 34% (25% vs. 42.3%, P=.19). CONCLUSION According to our experience, transfusion rate, number and severity of complications are lower in laparoscopic cystectomy with ileal neobladder. No statistically significant impact on operative time and on hospital stay was observed. In patients undergone to laparoscopic approach, continence rate is lower but not statistically significant.