Vol. 77; n. 2, June 2005 Founded in 1924 by: G. Nicolich U. Gardini G.B. Lasio Indexed in Medline/Index Medicus EMBASE/Excerpta Medica Medbase/Current Opinion SIIC Data Base Urological and Andrological Sciences Echoguided drug infiltration in chronic prostatitis: results of a multi-centre study. Federico Guercini, Cinzia Pajoncini, Robert Bard, Francesco Fiorentino, Vittorio Bini, Elisabetta Costantini, Massimo Porena Official Journal of the SIEUN Vladimir Startsev, Ivan Pouline Ablation of non functioning renal allograft by embolization: a valid alternative to graft nephrectomy? Andrea Solinas, Franco De Giorgi, Mauro Frongia Early surgical repair of penile fractures: our experience. S.I.E.U.N. Società Italiana di Ecografia Urologica Nefrologica e andrologica Gioacchino De Giorgi, Lorenzo G. Luciani, Claudio Valotto, Umberto Moro, Silvio Praturlon, Filiberto Zattoni Still a place for the classical systematic sextant technique? Cancer detection rates and complications in 1025 consecutive prostatic biopsies. Massimo Maffezzini, Lorenzo Gavazzi, Tiziana Calcagno, Giacomo Capponi, Roberto Bandelloni Orbital metastasis as a first indication of prostate cancer: a case report. Riccardo Autorino, Aniello Zito, Ferdinando Di Giacomo, Luca Cosentino, Giuseppe Quarto, Giuseppe Di Lorenzo, Salvatore Mordente, Umberto Pane, Antonio Giordano, Massimo D’Armiento Endoscopic treatment of a large leiomyoma of the bladder. Giuseppe Carrieri, Tommaso Corvasce, Pasquale Annese, Isabella Tolve, Alessandro Caniglia, Giuseppe Di Sabato Bizarre leiomyoma of scrotum. Antonio Celia, Morgan Bruschi, Stefano De Stefani, Beniamino Baisi, Anna Maria Cesinaro, Salvatore Micali, Maria Chiara Sighinolfi, Giampaolo Bianchi Liposarcoma of the spermatic-cord: description of two clinical cases and review of the literature. Michele Malizia, Eugenio Brunocilla, Alessandro Bertaccini, Fabiano Palmieri, Giovanni Vitullo, Giuseppe Martorana A rare case of bladder fibroepithelial polyp in childhood. Athanasios George Zachariou, Ioannis Nikolaos Manoliadis, Paraskevi Antonios Kalogianni, George Konstantinos Karagiannis, Dimitrios Jonh Georgantzis Whither the andrologic pathology of Italian lads with the end of medical check up to conscripts. Nicola Mondaini, Gianluca Giubilei, Michelangelo Rizzo, Marco Carini GOLDEN COMMUNICATIONS 64nd CONVEGNO ASSOCIAZIONE UROLOGI LOMBARDI - ERBUSCO (BS), 3 LUGLIO 2004 Official Journal of the SIUrO SIUrO Poste Italiane S.p.A. - Spedizione in abbonamento postale - D.L. 353/2003 (conv. in L. 27/02/2004 n. 46) Art. 1, comma 1 DCB Milano Adjuvant therapy in different risk-groups of patients with superficial bladder cancer. Società Italiana di Urologia Oncologica Chi intende iscriversi alla SIUrO trova le istruzioni ed i moduli necessari sul sito internet www.siuro.it - La quota associativa annuale è pari a: – Soci ordinari 70 EUR – Medici specializzandi 30 EUR Per ottenere ulteriori informazioni è possibile contattare la segreteria SIUrO È possibile pagare la quota associativa annuale tramite bonifico bancario sul c/c n. 737405, intestato alla Società Italiana di Urologia Oncologica, presso Unicredit Banca Filiale 3357 (via Massarenti) ABI 2008 CAB 02474 o tramite bollettino postale sul c/c n. 28212405 intestato a Società Italiana Urologia Oncologica S.I.Ur.O indicando nella causale “Quota associativa anno 2005”. via P. Palagi, 9 - 40138 Bologna c/o Clinica Urologica, Alma Mater Studiorum Università di Bologna, Policlinico S. Orsola Malpighi, Padiglione Palagi Tel. +39 051 6362421 Fax +39 051 308037 E-mail [email protected] www.siuro.it Urological and Andrological Sciences Founded in 1924 by: G. Nicolich, U. Gardini, G.B. Lasio Official Journal of theEditorial SIEUN -board Official Journal of the SIUrO Editor in chief Enrico Pisani Associate editors G. Martorana (SIUrO), F. Rocco (AUL), A. Trinchieri, G. Virgili (SIEUN) Assistant editor A. Bertaccini (SIUrO) Editorial Board G. Arcangeli (SIUrO), M. Battaglia (SIUrO), E. Belgrano (SIEUN), O. Bertetto (SIUrO), F. Boccardo (SIUrO), E. Bollito (SIUrO), S. Bracarda (SIUrO), G. Conti (SIUrO), J.G. Delinassios (SIUrO), P. Martino (SIEUN), F. Micali (SIEUN), E. Montanari, M. Porena (SIEUN), D. Prezioso (SIUrO), F.P. Selvaggi (SIEUN), G. Sica (SIUrO), C. Trombetta (SIEUN), G. Vespasiani (SIEUN), G. Zanetti Indexed in Medline/Index Medicus - EMBASE/Excerpta Medica - Medbase/Current Opinion - SIIC Data Base Contents Original Paper Echoguided drug infiltration in chronic prostatitis: results of a multi-centre study. Federico Guercini, Cinzia Pajoncini, Robert Bard, Francesco Fiorentino, Vittorio Bini, Elisabetta Costantini, Massimo Porena Pag. 87 Adjuvant therapy in different risk-groups of patients with superficial bladder cancer. Vladimir Startsev, Ivan Pouline Pag. 93 Ablation of non functioning renal allograft by embolization: a valid alternative to graft nephrectomy? Andrea Solinas, Franco De Giorgi, Mauro Frongia Pag. 99 Early surgical repair of penile fractures: our experience. Gioacchino De Giorgi, Lorenzo G. Luciani, Claudio Valotto, Umberto Moro, Silvio Praturlon, Filiberto Zattoni Still a place for the classical systematic sextant technique? Cancer detection rates and complications in 1025 consecutive prostatic biopsies. Massimo Maffezzini, Lorenzo Gavazzi, Tiziana Calcagno, Giacomo Capponi, Roberto Bandelloni Pag. 103 Pag. 106 Case Report Orbital metastasis as a first indication of prostate cancer: a case report. Pag. 109 Riccardo Autorino, Aniello Zito, Ferdinando Di Giacomo, Luca Cosentino, Giuseppe Quarto, Giuseppe Di Lorenzo, Salvatore Mordente, Umberto Pane, Antonio Giordano, Massimo D’Armiento Endoscopic treatment of a large leiomyoma of the bladder. Giuseppe Carrieri, Tommaso Corvasce, Pasquale Annese, Isabella Tolve, Alessandro Caniglia, Giuseppe Di Sabato Pag. 111 Bizarre leiomyoma of scrotum. Antonio Celia, Morgan Bruschi, Stefano De Stefani, Beniamino Baisi, Anna Maria Cesinaro, Salvatore Micali, Maria Chiara Sighinolfi, Giampaolo Bianchi Pag. 113 Liposarcoma of the spermatic-cord: description of two clinical cases and review of the literature. Michele Malizia, Eugenio Brunocilla, Alessandro Bertaccini, Fabiano Palmieri, Giovanni Vitullo, Giuseppe Martorana Pag. 115 A rare case of bladder fibroepithelial polyp in childhood. Athanasios George Zachariou, Ioannis Nikolaos Manoliadis, Paraskevi Antonios Kalogianni, George Konstantinos Karagiannis, Dimitrios Jonh Georgantzis Pag. 118 To the Editor Whither the andrologic pathology of Italian lads with the end of medical check up to conscripts. Nicola Mondaini, Gianluca Giubilei, Michelangelo Rizzo, Marco Carini Pag. 121 64nd CONVEGNO ASSOCIAZIONE UROLOGI LOMBARDI - ERBUSCO (BS), 3 LUGLIO 2004 GOLDEN COMMUNICATIONS The new transperineal-prerectal approach in posterior urethroplasty. Edoardo Austoni, Andrea Guarneri, Fulvio Colombo, Enzo Palminteri Pag. 122 Surgical treatment of metastases from renal cell carcinoma. Alessandro Antonelli, Danilo Zani, Alberto Cozzoli, Sergio Cosciani Cunico Pag. 125 Metastatic retroperitoneal renal cell carcinoma. A case for more aggressive approach. Risk and results. Pietro Tombolini, Michele Ruoppolo, Giuseppe Malagola, Fabrizio Rovera Pag. 129 Dorsal free graft urethroplasty according to Barbagli. Minimum follow-up of 2 years. Paolo Parma, Bruno Dall’Oglio, Lino Schiavon, Marco Luciano, Stefano Guatelli Vincenzo Galletta, Candido Bondavalli Pag. 131 The reconstruction of “complex” ureteral lesions. Pierpaolo Graziotti, Alessandro Piccinelli, Guido Giusti, Mauro Seveso Gianluigi Taverna, Alessio Benetti, Luisa Pasini, Silvia Zandegiacomo Pag. 133 Microscopic and microbiological findings for evaluation of chronic prostatitis. Vittorio Magri, Lisa Cariani, Roberto Bonamore, Antonella Restelli, Maria Cristina Garlaschi, Alberto Trinchieri Pag. 135 The use of vesical irrigation system dual pump Endo FMS Urology in the endoscopic therapy of benign prostatic hyperplasia. Piero Larcher, Giorgio Borroni, Andrea Begani, Paola Franch, Massimo Grisotto Pag. 139 The use of vesical irrigation system dual pump Endo FMS Urology in the endoscopic therapy of the vesical neoplasms. Piero Larcher, Giorgio Borroni, Andrea Begani, Paola Franch, Luca Carmignani Pag. 141 Editorial Dear Readers, just one year ago, as president of SIUrO, I had announced with pleasure that the “Italian Archives of Urology and Andrology” had become the official journal of our Association. This is a fact of great prestige for our members and for all experts on the subject interested in scientific research. As you know, in fact, the “Italian Archives” is the only Italian urological journal on Medline and quoted at the international level. On the basis of an editorial cooperation, the SIUrO Board members have been selected for reviewing all manuscripts focusing on uro-oncology, with respect to each scientific field. We hope that the SIUrO members with theirs scientific contributions, will improve more and more the quality of the journal. For the first time this year, communications and posters that will be awarded in the course of the next National SIUrO Congress (Giardini Naxos, 3-6 November 2005) will be published “in extensor” in the first issue of 2006. Another innovation of this year is that, in few months, it will be possible to download all the issues, updated every three months, of the Italian Archives by the SIUrO web site. This close collaboration with the editorial board will allow us to publish some supplementary issues as it happened for the final program and abstracts related to free communications, posters and videos of the last SIUrO National Congress all included in the supplement to the September issue. In the next months, we are planning to publish a supplement containing the data of the important project carried out at the consensus conference on the guidelines for prostatic biopsy which was held in Bologna last February. I would like to thank our readers and authors of the articles which contribute to the development and growth of this journal and to extend a special invitation to the SIUrO members to carry on their scientific production and to send their contributions to the official journal of our Association. Giuseppe Martorana Archivio Italiano di Urologia e Andrologia 2005, 77, 2 VII ORIGINAL PAPER Echoguided drug infiltration in chronic prostatitis: results of a multi-centre study. Federico Guercini1, Cinzia Pajoncini1, Robert Bard2, Francesco Fiorentino3, Vittorio Bini4, Elisabetta Costantini1, Massimo Porena1 Urologic Department, Perugia University, Italy; 2Radiologic Department, New York University School; Genoma Laboratory of Molecular Biology, Roma; 4Paediatrics and Gynaecologic Department, Perugia University, Italy. 1 3 Summary Objectives: In chronic prostatitis there are many causes that may provoke a therapeutical failure of a systemic antibiotic treatment. At the moment a consensus has not been reached on the efficacy of the many therapeutical options that are available with not one of these approaches being efficacious in all patients. In our view the main causes of treatment failure are the well-known hurdle to antibiotic diffusion inside the glandular parenchyma associated with the so-called intraprostatic bacterial biofilms and the possible presence of local auto-immune reactions. Given this background, we tested ultrasound guided intraprostate infiltration of a cocktail of antibiotics and betamethasone, for a therapeutical options. Material and Methods: 320 patients, referred to us because of symptoms indicative of chronic prostatitis, were enrolled in this study. The inclusion criteria were the severity of the symptoms and the failure of repeated cycles of antibiotics in the previous 12 months. At the initial consultation patients completed the NIH Prostatitis Symptoms Index (NIH-CPSI). All underwent: a) digital rectal examination (DRE), b) transrectal prostatic ultrasound scan (TRUS), c) uroflowmetry, d) cultures of first voiding and after prostatic massage urine and coltures of sperm for saprophytic and pathogen germs, yeasts and protozoa, e) DNA amplification with polymerase chain reaction (PCR) on urine and sperm, for Chlamydia trachomatis, Mycoplasmata (Ureaplasma urealyticum and Mycoplasma hominis), Gonococcus, HPV and HCV. Patients on the basis of laboratory results received a cocktail of antibiotics associated with betamethasone. The cocktail was administered as prostate infiltration. Administration was repeated after 7 and 14 days. Final assessment of the efficacy of therapy included not only the NIH-CPSI scores but also the patient's subjective judgement expressed as a "percentage overall improvement". The percentage judgements were arbitrarily divided into 4 classes: 0-30% no improvement (Class I); 30-50% satisfactory improvement (Class II); 50-80% good improvement (Class III; 80-100% cured (Class IV). Results: Statistical analysis of the results showed 68% of patients were included in the Class IV and 13% were no responders (Class I). Conclusions: In our opinion this is one of the more valid therapeutical approaches to chronic bacterial or abacterial prostatitis also if it requires more studies. KEY WORDS: Prostatitis; Drug prostatic infiltration; Chronic pelvic pain syndrome; Autoimmunity; Cytokines. INTRODUCTION Many urologists loathe to deal with chronic prostatitis even though it is one of the most common and invalidating pathologies of the male uro-genital system. Although the incidence is not as high as the 30-50% Drach and Barbalias originally estimated, prostatitis is still very frequent. 5-10% of the male population is affected, according to European estimates and about 89% according to the National Ambulatory Medical Care Survey (1-3). Despite these figures, a consensus has not been reached on the efficacy of the many therapeutical options that are available (antibiotics, alpha blockers, finasteride, Pentosan polysulphate, saw palmetto, ProstaQ, surgery, etc.) with not one of these approaches being efficacious in all patients (2, 4-6). In our view the main causes of treatment failure are multiple. On the one hand the well-known hurdle to antibiArchivio Italiano di Urologia e Andrologia 2005; 77, 2 87 F. Guercini, C. Pajoncini, R. Bard, F. Fiorentino, V. Bini, E. Costantini, M. Porena Table 1. Perugia Urology Department Symptoms Index (PUD-PSI). Voiding Symptoms During the night I pass water During the day I pass water My urinary flow is Flow properties Dripping 0 never >3 hours strong normal absent 1 once 2 hours impaired abnormal sometimes 2 twice <2 hours thread-like *** always 3 more more often *** *** *** Pain Symptoms Micturition burning Perineal soreness Inguinal soreness Scrotal soreness Coccygeal soreness Suprapubic soreness Ano-rectal soreness absent absent absent absent absent absent absent 0 moderate moderate moderate moderate moderate moderate moderate 1 severe severe severe severe severe severe severe 2 *** *** *** *** *** *** *** Sexual Symptoms Sexual desire Erection Ejaculation time Ejaculation properties Sperm aspect Ejaculation jet energy 0 normal normal normal normal normal normal 1 25% lost 25% lost 25% less hampered insufficient decreased 2 50% lost 50% lost 50% less painful agglutinated dripping 3 absent absent premature absent bloody *** otic diffusion inside the glandular parenchyma associated with the so-called intraprostatic bacterial biofilms and on the other the possible presence of local autoimmune reactions. The bacterial biofilms encapsulate the infected areas and act as a barrier against antibiotics and the immune defence system. The autoimmune reaction releases cytotoxic substances and pro-inflammatory agents and create a vicious circle of infection and inflammation (4, 7-10). The microfilm hypothesis was developed by Nickel in 1994 (4) and later confirmed by direct microscopy observations (7-8). Bacterial microfilms are caused by the adhesin-mediated sticking of plancton microorganisms to a tubular surface such as the walls of a prostatic duct. Microorganisms adhere in groups of 10-12 cells to form adjacent encapsulated micro-colonies which conglomerate and create the mature biofilm. In vitro studies have shown that antibiotics’ concentration needs to be over 100 times the normal MIC in such conditions. Rupture of the biofilms releases the germs and the required antibiotic dosage drops to normal levels. Consequently biofilms formation creates a vicious circle of pathogen survival and proliferation despite treatment with antibiotics; the bacterials’ agglomerates within the ducts obstruct the lumen and facilitate accumulation of infected glandular secretions. The micro-organisms produce a exopolysaccharide slime which, besides providing a habitat for their hibernation, also strongly stimulates a damaging immune response causing chronic inflammation of the prostatic parenchyma. 88 Archivio Italiano di Urologia e Andrologia 2005; 77, 2 The possible cascade of events is as follows: 1) Acute bacterial or abacterial infection (Chlamydia, Mycoplasmata, etc.) starts. 2) The prostate parenchyma is invaded and microbial mucopolysaccharide biofilms form within the prostate ducts and sequester the infectious agents. 3) Prostatitis becomes chronic. 4) Autoimmune process may start, maybe in the presence of a congenital genotype with low interleukine10 production (11) causing tissue auto-reactivity. 5) Chronic inflammation is by now independent of the original infection and can no longer be treated with standard therapy. Hence the need for a different approach. In this study we describe the effects of an innovative intraprostatic infiltration of antibiotics and cortisone, that was designed to overcome the encapsulating barrier and to limit or inhibit local auto-immune reactions. MATERIALS AND METHODS 320 patients with symptoms of chronic prostatitis were enrolled in this study between 1999 and 2002. The study is been submitted to the Ethical Committee of each participant Centre. The inclusion criteria were failure of repeated cycles of antibiotics in the previous 12 months and the severity of the symptoms with a NIH-CPSI ≥ 21. Each patient signed an informed consent and provided a case history, the NIH Chronic Prostatitis Symptoms Index Questionnaire (NIH-CPSI) Is intraprostatic infiltration a new way to treat prostatitis? Table 2. Percentage of pathogens in urine before and after therapy (*as DNA and IGA) *Friedman test for related data Baseline 3 Months 6 Months 12 Months p* Enterococcus sp 10% 0% 1.3% 4% NS Escherichia Coli 12% 1.8% 2% 2.8% NS Klebsiella 3.5% 0% 2.2% 1.5% NS Staphilococcus 9% 0% 2.1% 3.1% NS Streptococcus 1.2% 0% 1.1% 0% 0.000 Others 0% 1.0% 0% 0% NS Yeast 0% 0% 0% 0% NS Chlamydia* 4% 0% 1.3% 1.3% NS Gonococcus 1.7% 0.8% 0% 0% 0.000 HPV 8.8% 5.8% 7.0% 5.6% NS Micoplasmata 3.5% 0% 0% 0% 0.000 and the Perugia Urology Department Prostatitis Symptoms Index (PUD-PSI) (Table 1) (12). All underwent: a) digital rectal examination (DRE), b) transrectal prostatic ultrasound scan (TRUS), c) uroflowmetry, d) cultures of first voiding and after prostatic massage urine and cultures of sperm for saprophytic and pathogen germs, yeasts and protozoa, e) DNA amplification with polymerase chain reaction (PCR-DNA) on urine and sperm, for Chlamydia trachomatis, Mycoplasmata (Ureaplasma urealyticum and Mycoplasma hominis), Gonococcus, HPV and HCV. DNA was extracted according to the phenol-chloroform procedure (21). The PCR reaction was performed in a total volume of 50 ml containing 5 ml of 10X PCR Buffer II (500 mM KCl, 100 mM Tris HCl, pH 8.3 Applied Biosystems), 1.5 mM MgCl2, 200 mM of each dNTP (Roche Diagnostic, Italy), 2.5 IU AmpliTaq Gold Polymerase (Applied Biosystems), 10 pmol of each primer (Table 5). The cycling condition used was 35 cycles of 30 sec at 94°C, 1 min at 55°C, 1 min at 72°C. Each round of PCR was preceded by an initial 10 min denaturation step at 95°C (to activate AmpliTaq Gold) and followed by a final extension step of 10 min at 72°C. A nested PCR approach was used to amplify Neisseria gonorrhoeae. All the reactions were cycled on a GeneAmp® PCR System 9700 (Applied Biosystems, USA). For monitoring PCR amplification, 5 ml of each PCR product was subjected to electrophoresis for 5 min at 150V on 2% agarose gel in 1X Tris-Borate/EDTA buffer stained with 0.5 mg/ml ethidium bromide. Each patient received an intraprostatic infiltration of dexamethasone 12 mg combined with rifampicyn 300 mg and levofloxacine 25 mg. In presence of Gonococcus we replaced levofloxacin with ceftriaxone 1 g in presence of yeasts we add fluconazole 6 mg, and in presence of protozoa we add methronidazole 15 mg. Table 3. Percentage of pathogens in sperm before and after therapy (*as DNA and IGA); *Friedman test for related data. Baseline 3 Months 6 Months 12 Months p* Enterococcus sp 38.3% 2.5% 0% 3.7% 0.05 Escherichia Coli 14.2% 0.7% 0% 0% 0.001 Klebsiella 5.8% 0% 2.4% 5.2% NS Staphilococcus 12.9% 9.9% 5.5% 5.5% NS Streptococcus 3.9% 3.0% 1.1% 0% 0.000 Others 7.7% 1.0% 0% 0.5% 0.001 Yeast 0.2% 0% 0.4% 0.3% NS Chlamydia* 36.3% 12.7% 5.0% 3.3% 0.001 Gonococcus 17.5% 3.2% 0% 0% 0.000 HPV 14.9% 7.5% 8.2% 4.4% 0.05 4.5% 6.4% 4.0% 2.0% 0.05 Micoplasmata Archivio Italiano di Urologia e Andrologia 2005; 77, 2 89 F. Guercini, C. Pajoncini, R. Bard, F. Fiorentino, V. Bini, E. Costantini, M. Porena Table 4. Follow-up results; *Friedman test for related data. Uroflowmetry (F.max) NIH-PSS PUD-PSI (voiding) PUD-PSI (pain) PUD-PSI (sexual) Baseline 6 Months 12 Months p* 19.6±3 21.7±3 21.5±2.7 NS 25±5 20±3 17±3 0.01 3±1 2.5±1 2.5±1.5 NS 4±0.5 3.2±1 3±0.5 0.01 4±1 3.1±0.5 3±0.5 NS The antibiotic cocktail was administered by transperineal echoguided intraprostatic infiltration either in a random way or inside in any fibrous areas with the aim to sterilize them. We used Toshiba PowerVision 6000 ultrasound scanner with transrectal biplanar multifrequency (6-10 MHz) probe equipped with angiodoppler. The injection needle was Echojet® 23 gauge, 200 mm in length. The needle was inserted 1 cm to the left or the right of the median raphe, according to the site of inflammation, and 1 to 3 cm above the anal sphincter, this point corresponding to the projection of the prostate apex. After the needle had been inserted into the subcutaneous layer, 2 cc local boluses of lidocaine were administered again and again as the needle was pushed towards the apex of the prostate. Attention was focused on anaesthetizing the urogenital diaphragm and the prostatic capsule. A complete treatment included three infiltrations, performed the 1st, the 10th and the 20th day. Follow-up Six and twelve months after the last infiltration, all patients underwent uroflowmetry, all microbiological testing, the NIH-CPSI and the PUD-PSI. For an overall evaluation of therapy, each patient was asked to provide a subjective assessment of treatment by quantifying the improvement on a scale of 0-100. The results of this last evaluation were divided into 4 classes: 0-30% “so called” non-responders (Class I); 31-50% moderate improvement (Class II); 51-80% good improvement (Class III); 81-100% marked improvement/cured (Class IV). Statistical Analysis The Friedman test for related data was applied at the basal time, 6 and 12 month check-ups to the uroflowmetry results, the bacteriological examinations, the NIH-CPSI and the PUD-PSI. RESULTS The mean age of patients was 38 years (range: 21-54 years) and the mean time since disease onset was 5.3 years (range: 6 months-22 years). The percentage of pathogens detected in the sperm and urine by cultures and PCR-DNA before and after therapy are reported in Tables 2 and 3. In the follow-up of overall patients, not statistical significant differences emerged in uroflowmetry results and in 90 Archivio Italiano di Urologia e Andrologia 2005; 77, 2 the PUD-PSI regarding voiding and sexual symptoms. Significant differences were observed in the NIH-CPSI (p <0.01) and in the PUD-PSI regarding pain symptoms (p <0.01) (Table 4). The subjective improvement evaluated by each patient demonstrated that 218 patients (68%) were marked improved or cured (Class IV), 15 patients (5%) were improved as good (Class III), 45 patients (14%) as moderate (Class II), while 42 patients (13%) fell into the class of so-called non-responders (Class I). This last class included a sub-group of 29 patients who did not respond at all. The patients of Class IV showed a significant improvement at six and twelve months regarding NIH-CPSI (p <0.001), PUD-PSI voiding (p <0.01), pain (p <0.001) and sexual symptoms (p <0.01). Side effects of treatment a) Immediate: pain during infiltrations was very rare. Somebody referred a mild burning sensation at the tip of the penis. 11% of patients complained of a drop of blood in the first 2 or 3 micturitions following an accidental perforation of the urethra (0.5% of cases). No therapy was required. b) Delayed: haemospermia in 81% of patients was observed usually at the first post-infiltration ejaculation and 2% required coagulant treatment (tranexamic acid orally). Transient worsening of prostatitis symptoms occurred in 13% of patients, usually on the 2nd day after infiltration and disappeared within 24-36 hours. Nimesulide, as pain-killing was prescribed in these cases and symptoms were resolved quickly. Intra-prostatic hematoma developed in 8 patients (3%) and was associated with perineal soreness for 48-72 hours and blood in the ejaculate for up to 15 days. It resolved spontaneously in 7 cases while 8 required ultrasound guided removal of the collection without any further complications. c) Persistent: only one patient, two years after a single infiltration, complains of abnormal penile sensitivity and erectile disturbances even though NTP Rigiscan and penile Echo-Doppler are normal. DISCUSSION The many theories on the pathogenesis of chronic prostatitis are not necessarily mutually exclusive. Acute urethral infection may rise to the prostate and become Is intraprostatic infiltration a new way to treat prostatitis? chronic because of insufficient therapy or an inadequate immune defence system (13). A sterile uretro-prostatic reflux with intra-parenchymal precipitation of urates may trigger chronic inflammation as may local autoimmune reactions (9). Repeated courses of antibiotics are undoubtedly helpful, particularly in cases of bacterial prostatitis and most urologists agree that even the so-called abacterial forms of prostatitis benefit from prolonged antibiotic treatments (14). To reach a therapeutic concentration in prostatic tissue the ideal antibiotic needs to be liposoluble, with a low grade of plasma ionization (pKa), an acid pH and poor protein binding properties. However, treatment with even these agents often fails apparently because of impenetrable bacterial biofilms within the prostate and serious local auto-immune reactions (9-10). For all these reasons we opted for a cocktail of antibiotics and cortisone. The etiology of prostatitis justifies the use of antibiotics as the resistance of chronic prostatitis is due not only to the difficulty in diffusing the drugs within the prostate but also to the presence of the encapsulating bacterial biofilms. Besides in our previous trial (15) we have doubted, the real existence of abacterial prostatitis. Dexamethasone was associated in an attempt to break up the vicious circle of immune reactions and inflammation which is intrinsically linked to the disease. Several other reasons underlie the decision to infiltrate antibiotics with cortisone into the prostate. When drugs are injected directly into the prostate they reach local concentrations that are about 2,000-2,500 times higher than with systemic administration and they can overcome, if present, the perimicrobial polysaccharide barrier of the biofilms. The quinolonics and the macrolides inhibit cytokine release, particularly IL 2, IL 6 and TNF (16), which coincidentally are the same cytokines that are found in high concentration in the semen and EPS of men with prostatitis (11). Furthermore, cortisone not only inhibits possible allergic reactions to antibiotics, which were not, by the way, observed in any of our patients, but also inhibits cytokine release. Conversely, high antibiotic concentrations counteract the hypothetical risk of steroid-induced intra-prostate abscess or weakening of the host defence system. This study may be criticized on its lack of a control group which, for obvious ethical reasons, could not be recruited as the invasive nature of the infiltration precluded its use to administer placebo. Moreover, in studies without a placebo group it is important to establish that the treatment given did actually cause improvement. This question can be answered by comparing for each patient the incidence and the improving of symptoms before and after the treatment. Besides these patients acted as a control group for themselves as they had already undergone several unsuccessful cycles of systemic antibiotic therapy before being recruited to this study. Another limitation is our use of a subjective assessment of efficacy as the overall percentage of improvement. However, in our experience, the assessment of the overall efficacy of therapy could not be evaluated simply in terms of negative bacteriological results, even though the difference between the pre and post infiltrations tests was significant, or evaluated in a reduction in the symptom scores, because chronic prostatitis has a marked psychological and behavioral impact. In fact, the disappearance or the improvement of some symptoms is not always associated with the patient's awareness of recovery and vice versa. CONCLUSIONS Over the years the results of intra-prostate infiltration of antibiotics have been, on the whole, disappointing. The reasons for the success of our approach appear to be in a depth bacteriological analysis, aimed at detecting Chlamydia and Gonococcus and in the use of a high definition ultrasound probe (7-10 MHz) to visualize and infiltrate areas of inflammation and fibrosis. The fibrotic areas definitively must be infiltrated in order to make them "explode", which is the only way to ensure they are sterilized. REFERENCES 1. McNaughton M, Stafford RS, O’Leary M., Barry MJ. How common is prostatitis? A National Survey of phisicyan visits. J Urol 1998; 159:1224 2. Nickel JC, Nyberg LM, Hennenfent M. Reasearch guidelines for chronic prostatitis: Consensus report from the first National Institutes of Health International Prostatitis Collaborative Network. Urology 1999; 54:229 3. Schaeffer AJ, Landis JR, Knauss JS, Propert KJ, Alexander RB, Litwin MS, Nickel JC, O'Leary MP, Nadler RB, Pontari MA, Shoskes DA, Zeitlin SI, Fowler JE Jr, Mazurick CA, Kishel L, Kusek JW, Nyberg LM. The Chronic Prostatitis Collaborative Research Network Group. Demographic and clinical characteristics of men with chronic prostatitis: the National Institutes of Health chronic prostatitis cohort study. J Urol 2002; 168: 593 4. Nickel JC, Costerton JW, McLean RJ, Olson M. Bacterial biofilms: influence on the pathogenesis, diagnosis and treatment of urinary tract infections. J Antimicrob Chemother 1994; 33 (Suppl A):31 5. Dimitrakov J, Diemer T, Ludwig M, Weidner W. Recent developments in diagnosis and therapy of the prostatitis syndromes. Curr Opin Urol 2001; 11:87 6. Shoskes DA, Katske F, Kim S. Diagnosis and management of acute and chronic prostatitis. Urol Nurs 2001; 21:255 7. Anderson GG, Palermo JJ, Joel D. Schilling JD, Roth R, Heuser J, Scott J, Hultgren SJ. Intracellular Bacterial Biofilm-Like Pods in Urinary Tract Infections Science 2003; 301:105 8. Parsek MR, Singh PK. Bacterial Biofilms: An Emerging Link to Disease Pathogenesis. Annu Rev Microbiol 2003; 57:v677 9. Alexander RB, Brady F, Ponniah S. Autoimmune prostatitis: Evidence of T cell reactivity with normal prostatic proteins. Urology 1997; 50:893 10. Alexander RB. Immunology and prostatitis. Third Annual International Prostatitis Network Meeting 2000 Washington. Rev Urol 2001; 3:94 11. Shoskes DA, Albakri Q, Thomas K, Cook D. Cytokine polymorphisms in men with chronic prostatitis/chronic pelvic pain synArchivio Italiano di Urologia e Andrologia 2005; 77, 2 91 F. Guercini, C. Pajoncini, R. Bard, F. Fiorentino, V. Bini, E. Costantini, M. Porena drome: association with diagnosis and treatment response. J Urol 2001; 168:331 12. Guercini F, Pajoncini C, Bini V, Porena M. Symptoms correlated with prostatitis. Eur Urol (Suppl.) 2002; 1:175 17. Robert R, Prat-Pradal D, Labat JJ, Bensignor M. Anatomic basis of chronic perineal pain: role of pudendal nerve. Sur Radiol Anat 1998; 20:93 13. Lipsky BA. Prostatitis and urinary tract infection in men: What’s new; What’s true. Am J Med 1999; 106:327 18. Nickel JC, Costerton JW. Bacterial localization in antibiotic-refractory chronic bacterial prostatitis. Prostate 1993; 23:107 14. McNaughton Collins M, Fowler FJ Jr., Elliott DB, Albertsen PC, Barry MJ. Diagnosing and treating chronic prostatitis: do urologists use the four-glass test? Urology 2000; 55:403 19. Luzzi GA. Chronic prostatitis and chronic pelvic pain in men: aetiology, diagnosis and management. J Eur Acad Dermatol Venereol 2001; 16:253 15. Guercini F, Mazzoli S, Pajoncini C, Porena M. Does Abacterial Prostatitis really exist?. J Urol 2003; 169:29 20. Batstone GR, Doble A, Gaston JS. Autoimmune T cell responses to seminal plasma in chronic pelvic pain syndrome (CPPS). Clin Exp Immunol 2002; 128:302 16. Galley HF, Nelson SJ, Dubbels AM, Webster NR. Effect of ciprofloxacin on the accumulation of interleukin-6, interleukin-8, and nitrite from a human endothelial cell model of sepsis. Crit Care Med 1997; 25:1392 21. Sambrook J., Russell DW, Inwin N. Molecular Cloning: A laboratory manual. Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 3° ed, 2000 Correspondence: Federico Guercini, MD, Via Archimede 44 - 00197, Rome, Italy; E-mail: [email protected] 92 Archivio Italiano di Urologia e Andrologia 2005; 77, 2 ORIGINAL PAPER Adjuvant therapy in different risk-groups of patients with superficial bladder cancer. Vladimir Startsev, Ivan Pouline Urology Dept., Regional Oncological Hospital, St. Petersburg, Russia. Summary Objectives: We assessed and compared the outcomes of two different courses of adjuvant therapy to patients with superficial bladder TCC. Methods: The study included 142 patients (28 women and 114 men with a median age of 58.5 years) with newly diagnosed bladder transitional cell carcinoma (TCC), who underwent transurethral resection of bladder tumor (TURBT) between October 2002 and October 2003. Before surgery patients underwent routine examination, including measurement of tPSA level and transrectal ultrasound sonography (TRUS). In 26 (18.3%) patients with considerably enlarged prostate and LUTS we simultaneously performed TURBT and transurethral resection of the prostate (TURP). Pathological findings showed pTa stage in 20 (14.1%), pT1G1-2 in 99 (69.7%), pT1G3 in 15 (10.6%) and pTis in 3 (2.1%) cases; we additionally examined prostate specimens after TURP. The main criteria for adjuvant treatment were: grade, number and location of the tumor in the bladder. The group of patients (group A) with G3 and multicentric lesions, localized at the lower third of the bladder, underwent BCG-therapy according the conventional schedule (60 patients, 42.3%). In group B (82 patients, 57.7%) patients underwent local chemotherapy (Thiotepa 80 mg p/week or Doxorubicin 50 mg p/week), started within 24 hours after operation. A second-look TURBT was performed within 6 weeks of treatment course in both groups. The morphological records of surgery were reviewed, compared with the initial findings and analysed statistically. Results: Recurrence rate in groups A and B was 18.3% (11 patients) and 25.6% (21 patients), respectively (with common level 22.5%) (p=0.04). Three (5.0%) patients of group A and five (6.1%) of group B withdrew consent. We observed recurrent low-grade pTa tumours in 4 patients (36.4%) and 8 patients (38.1%) respectively in group A and B (p<0.03) and pT1 G1-2 tumours in 5 patients (45.5%) and 8 patients (38.1%) respectively in group A and B (p<0.005). We observed pT1G3 in two (18.2%) cases of group A, and in two (9.5%) cases of group B. In addition, two (9.5%) patients of B group had T2G2 lesions. Adiuvant therapy was continued in all patients, except four patients with G3 and two patients with T2 stage who underwent more aggressive treatment (4 cystectomies and 2 external beam radiotherapy). We switched 16 patients in group B with recurrent cancer to BCG treatment. Nobody of TURP-operated patients had recurrence in the distal part of urethra, and toxicity level of TURP-operated patients was not worse than in the whole patients cohort (not more than grade II). Conclusion: BCG adjuvant therapy demonstrated good results in the treatment of the recurrence of superficial TCC. However, in patients with low recurrence risk we used chemotherapy successfully. A second-look TURBT within 6 weeks after the initial surgery provided important prognostic information. Patients with T1G3 tumors, being at high risk of residual, or even invasive, cancer, could be offered definitive therapy within a 1-year period. Patients who underwent simultaneous TURP for relief of LUTS did not show cancer recurrences in the operated area or an higher toxicity of adiuvant treatment. KEY WORDS: Bladder Cancer; Chemotherapy; Immunotherapy INTRODUCTION Lower urinary tract tumors account for about 10% of all cancers and for 5% of all cancers in women all over the world. In fact, the incidence and the morbidity of this disease tend to increase. More than 90% of such cancers, both in Europe and USA, are TCC (1). The incidence of bladder cancer in Russia is also very Archivio Italiano di Urologia e Andrologia 2005; 77, 2 93 V. Startsev, I. Pouline high: it was established that from 1990 to 1997 it increased from 4.0% to 4.6% (2). The rate of initial superficial TCC tends to increase from 39.4% in 1990 to 40.8% in 1999 (3). It is well-known that in patients with superficial bladder cancer (Ta, T1 or Tis) about 70% will recur within 5 years after a transurethral resection (TURBT) alone (4). It is crucial to distinguish the small group of lesions that are at serious risk of progression to life-threatening muscle invasion, the vast majority of superficial tumors rarely progress (4, 5). It has been observed that between 5% and 50% of patients with superficial bladder cancer during the observing period of adjuvant treatment have progressed to stage T2 (i.e. muscle-invasive disease) with worsening prognosis (6, 7). The recurrence and progression rate depends on the tumor grade, stage, presence or absence of CIS, and length of follow-up of patients (4, 8). In the National Bladder Cancer Group (NBCG) study (9) the recurrence rate increased when there were associated mucosal abnormalities, positive cytology, four or more tumors, and tumors larger than 5 cm in maximum diameter (1, 9, 10, 11). The highest therapeutic ratio for adjuvant intravesical therapy can be achieved in patients with high-risk superficial TCC of the bladder who demonstrate multiple primary tumors, multiple recurrences, high-grade tumor, T1 tumor, positive urinary cytology post resection, and diffuse CIS (12). The most important objective in treating superficial bladder cancer is to prevent progression to muscle-invasive disease (13). Some authors suggest aggressive treatment options in patients with high-risk superficial T1-bladder cancer, including early cystectomy or radiotherapy (7, 14, 15), others prefer the goal of organ preservation by adjuvant intravesical therapy after transurethral resection (TURB) (16). In the 1980s many investigators suggested adjuvant chemotherapy, as method of choice (17-20). Controlled studies demonstrated that Thiotepa (20, 21), doxorubicin (Adriamycin) (18), mitomycin C (Mutamycin) and ethoglucid (Epodyl) (17, 22, 23) are active against TCC. The reduction in size of residual TCC (after TURBT) was seen in 29% of cases with thiotepa, 38% with doxorubicin and 47% with mitomycin (24). Chemotherapy is an excellent measure, but it is not indicated in every case. Holmgren in Sweden was the first to report the use of BCG to treat cancer in man in 1935 (25). After investigations on animals in 1950s, in 1976 Morales et al. (26) reported their clinical trial of BCG in 9 patients with recurrent tumors. Subsequents investigations showed that the benefits of BCG immunotherapy appeared to be durable (27-31). It was shown an average response rate of 55% and 73% in treatment respectively of residual TCC (32) and CIS (in 663 patients, 15 studies) (33, 34) with BCG instillations. Long-term studies of adjuvant BCG instillations in comparision with mitomycin C in cases with moderate or high-risk cancer showed that the recurrence rate was significantly lower with BCG than with only mitomycin C in patients at high risk (11, 28, 35); there was no difference in disease progression, survival, adverse events and cost (36, 37). 94 Archivio Italiano di Urologia e Andrologia 2005; 77, 2 BCG is the standard intravesical therapy of choice for T1G3 bladder tumors and CIS. In 2000 Brake et al. (38) reported a 19% recurrence rate and a 13% muscle invasive progression in patients with T1G3 after 26-week cycles of BCG. In cases intolerant of BCG, mitomycin C may be a second choice of therapy (39). Despite the risk of recurrence and progression of cancer, several different treatment regimens, sometimes excluding BCG, have been proposed. In Japan, epirubicin, at different doses, (6th Trial of the JUCRG) showed good results, excluding T1G3 cases (40). In China, BCG associated to chemotherapeutic agents (50 mg adriblastin or epirubicin) was administered in highrisk patients during a 15-year follow-up (41) with a recurrence rate of 44.4% at 10-year follow-up and a progression rate of 24.0%, without statistically significant difference between the two chemoterapeutic variants. Interesting results were shown in 2004 by EORTC (42): it has been observed a 30% decrease of recurrence rate with a single immediate instillation of a chemotherapeutic agent (epirubicin, mitomycin C, thiotepa or pirarubicin) in patients with multiple Ta-1 tumors after TURBT in comparision with TURBT alone. At present time many clinicians suggest that chemotherapy instillations immediately after TURBT are “…the treatment of choice in patients with a single, low risk papillary tumor” and may be recommend as initial adjuvant treatment in patients with higher risk tumors ( 16, 31, 37, 42. Alternative treatments are intravesical administration of recombinant human interferon-a2b (43, 44), photodynamic therapy (45, 46), and administration of other immunologically active agents. Additional intravesical immunotherapy can reduce the risk of muscle-invasion as an alternative to cystectomy as method of choice in the treatment of high-risk cancer (47). The most important issue of conservative treatment is the quality of the initial TURBT. Recent papers demonstrated that a routinely “second-look” or “repeat” TUR, performed within 2-6 weeks, is advisable to control noninvasive tumors and to detect residual tumor in a significant percentage of patients (48-51). In an evaluation of 96 patients, Herr (52) showed that only 24.0% of patients were free of tumor at the second TUR, and 28.0% had previously undiagnosed muscle involvement (52, 53). For this reason it is recommended to include in the schedule of conservative treatment of T1 tumors a second TURBT within 2 to 4 weeks after the first one (47, 48, 50). In our study we assessed and compared the outcomes of two different regimens of adjuvant therapy (BCG and chemotherapy) in patients with superficial bladder TCC. MATERIALS AND METHODS Patients. From September 2002 we selected, treated and followed-up 142 consecutive patients with newly diagnosed bladder tumors. Out of them, 28 were women and 114 men (1:4.1) with age ranging from 51 to 69 years (median 58.5 years). Between October 2002 and October 2003 the information about the patients observed in the outpatient clinic for routine surveillance cystoscopy were entered into a database. The criteria of Adjuvant therapy in different risk-groups of patients with superficial bladder cancer. Table 1. Patient characteristics. Group A Group B Males 66 76 Females 15 13 Sex: 0.462 Tumor size (cm): 0.024 Less than 2 cm 82 2-5 cm 36 Greater than 5 24 Tumor grade: 0.549 G1 9 31 G2 32 28 G3 15 – 3 – Ta – 20 T1 57 62 TURP-operated patients 11 15 Stage: Tis p Value (chi-square test) 0.147 0.481 eligibility included untreated papillary and non-papillary transitional cell carcinomas (TCC) of the bladder in absence of other active neoplasms or serious complications. Methods. Before treatment physical examination, urinalysis, blood count, serum creatinine, liver function, chest plain X-rays and intravenous pyelography (IVP) were performed. In all the male subjects serum tPSA level, transrectal ultrasound sonography (TRUS) and IPSStesting were obtained before surgery. The results of preoperative investigations are shown in Table 1. All patients were fully informed about this trial and signed the informed consent form. After routine preparation all patients underwent complete transurethral resection of the bladder tumors (TURBT) and were followed-up for a minimum of 6 month. This period was to observe and eliminate tumor recurrences. A 26 F cystoresectoscope (AVVA-land, St.-Petersburg) was used for the surveillance cystoscopy and for bladder resection. In addition to conventional TURBT we performed TUR-biopsies of suspicious urothelial areas. In 26 (18.3%) patients with considerably enlarged prostate and associated lower urinary tract symptoms (LUTS) with bladder neck obstruction (BNO) we simultaneously performed the transurethral resection of the prostate (TURP). No surgical complication was observed. In case of TURP we irrigated the bladder for a median duration of 2.1 days (1.5-2.5 days). The median duration of irrigation in patients after TURBT in 86 patients (60.6%) was 1.5 days (1-2.5 days). Pathology specimens. All pathology specimens were reviewed by one pathologist, tumor grade was assigned as recommended by Koss. Resected tissue was immediately fixed in 10% buffered formalin and then embedded in paraffin wax; each paraffin section was stained with haematoxylin and eosin. All the patients included in the study had superficial TCC of the bladder. According to morphological investigations, primary cancer was stage pTa in 20 (14.1%), pT1G1-2 in 104 (73.2%), pT1G3 in 15 (10.6%) and pTis in 3 (2.1%) cases. In addition, all prostate specimens after TURP were diagnosed as benign prostatic hyperplasia (BPH) with association of chronic prostatitis. The median resected mass of the prostate was 18.7 g (range 16-24) (Table 1). Classification. We used the grading system described by Epstein et al. in the 1998 WHO International Society of Urologic Pathology Classification (54, 55) in which tumors are dichotomized as either low grade or high grade. Patients considered at high risk for tumor recurrence were defined as those with a history of moderate or high grade papillary tumors, any invasion or associated carcinoma in situ (CIS). Patients at low risk were those with low grade papillary tumors or papilloma with no invasion (stage Ta). Disease progression was defined as any increase in clinical stage or development of metastases. Patients underwent different adjuvant treatment on the basis of the recurrence risk. BCG-treatment Schedule. Criteria for BCG immunotherapy (group A, n=60, 42.3%) were multicentric or highor moderate grade tumors or tumor with size more than 2 cm, located mainly at the base of the bladder. The adjuvant treatment was initiated within 2 weeks after TURBT with the Pasteur strain BCG (80 mg suspended in 50 ml sterile saline held for 90 min in the bladder). The treatment was continued as follows: once per week till the second TURBT or the 6th week, after monthly for 6 months, and finally quarterly for 1 year. Blood count and serum creatinine were obtained every 7 days or more frequently if it was necessary. Patients who underwent TURP were not excluded from the immunotherapy group. Chemotherapy-treatment Schedule. Adjuvant chemotherapy agents were administered in patients (group B, n=82, 57.7%) with solitary, low grade papillary tumors, with tumor size less than 2 cm, located in the upper and middle third of bladder. The treatment began within 24 hours after the operation, after receiving the pathological report of specimen analysis. We used initially Thiotepa 40 mg (with subsequent dose of 80 mg weekly) or Doxorubicin 50 mg (with subsequent dose pf 50 mg weekly). Administration continued up to date of the second TURBT and then, on the basis of pathological report, changed on more aggressive treatment or not. The total dose administered in cases who completed the treatment were: Thiotepa 400 mg and Doxorubicin 300 mg. Follow-up protocol. In both patient groups the secondary TURBT was performed within 6 weeks from the first procedure. Pathology reports of the first and second TURBT were reviewed, compared and analyzed statistically. Patients with recurrences or progression of cancer underwent more aggressive treatment (change of the agent of adjuvant treatment or cystectomy). Archivio Italiano di Urologia e Andrologia 2005; 77, 2 95 V. Startsev, I. Pouline Table 2. Pathological characteristics of recurrences in both groups of patients. Group A Group B Ta 4 8 <0.02 T1G1-2 5 8 <0.051 T1G3 2 2 T2G2 Total p Value (chi-square test) 2 11 20 Patients were analyzed for disease-free and progressionfree survival. For statistical analysis we used SPSS 8.0 for Windows (SPSS Inc., Chicago, Illinois). Chi-square test and Cox proportional hazards models with time dependent covariates were used for evaluation. All p values are 2-sided and considered significant if p<0.05. RESULTS Recurrence rate in groups A and B was 18.3% (11 patients) and 25.6% (21 patients), respectively (with common level 22.5%) (p= 0.04). Fourteen patients with progressive tumor died of the disease and 23 patients died of other causes. Three (5.0%) patients of group A and five (6.1%) of group B withdrew consent. The pathological report results are in the Table 2. As shown in Table 2, we observed recurrence stage pTa in 4 (36.4%) and 8 (38.1%) patients (p<0.03), pT1G12 in 5 (45.5%) and 8 (38.1%) patients (p<0.05) in group A and B, respectively. We observed a few recurrent pT1G3: 2 (18.2%) patients in group A and 2 (9.5%) in group B. Table 3. Local toxicity. 96 Group A Group B Gross haematuria None Mild Moderate Severe 50 7 2 1 78 3 1 – Micturition pain None Mild Moderate Severe 53 5 1 1 60 7 3 2 Frequency None Mild Moderate Severe 51 6 2 1 Archivio Italiano di Urologia e Andrologia 2005; 77, 2 Two (9.5%) patients of group B had T2G2 lesions. We continued BCG-course in all the patients of group A, except the two with T1G3. Since those patients had highgrade tumors also initially, they underwent radical surgery. We changed adjuvant treatment on more aggressive therapy in the 2 patients of group B with T1G3 and in the two with T2-stage (2 cystectomies and 2 organ-confined treatment with external beam radiotherapy). Treatment was selected on the basis of the co-morbidity status of the patients. Nobody of TURP-operated patients had recurrence in the distal part of the urethra. We did not found statistically significant difference in recurrence rate among patients treated or not with TURP. Side effects. The most common were irritative bladder symptoms (pain and frequency) and hematuria (Table 3). Instillations were never interrupted before the second TURBT. No significant difference in local toxicity rate was observed between the 2 groups. Systemic toxicity was seen in group A consisting in general fatigue and fever. Severe toxicity did not develop in any patients of either group. The toxicity level in TURP-operated patients was not worse than in the whole cohort of patients (not more than grade II). DISCUSSION The effectiveness of BCG in preventing recurrences of superficial bladder carcinoma is well recognized. The question whether intravesical immunotherapy with BCG is superior to intravesical chemotherapy remains actual. There is no doubt about the efficacy of BCG in eradicating CIS or preventing papillary tumors after TURBT. Although series are not large and follow-up is too short, several reports indicate that BCG is capable of preventing muscle-invasive disease (30). The administration of BCG in patients with low-grade or intermediate stage and grade tumors is questionable from the first clinical trials in BCG-therapy, whereas in high-risk patients BCG remains the first choice. BCG will never be the best treatment option for every patient with superficial bladder cancer. In conclusion, BCG-adjuvant therapy demonstrated mainly good results in the treatment of the recurrences of high-risk superficial bladder cancer. On the contrary, in patients with low recurrence risk, chemotherapy is an alternative treatment. A “second look” TURBT within 6 weeks after the initial procedure provided significant prognostic information. Patients with T1G3 tumors, being at high risk of residual, or even invasive, cancer, can be offered definitive therapy with one year follow-up. Patients who underwent simultaneous TURP for relief of LUTS did not show cancer recurrences in the operated area or higher toxicity. REFERENCES 1. Malmstrom P, Busch C, Norlen B. Recurrence, progression and survival in bladder cancer: a retrospective analysis of 232 patients with less than 5 year follow-up. Scand J Urol Nephrol 1987; 21:185 Adjuvant therapy in different risk-groups of patients with superficial bladder cancer. 2. Axel EM, Matveev BP. The presence attitude of onco-urological service in Russia. Clin Oncol 1999; 1 3. Axel EM, Davidov MI. Illness and morbidity cancer statistics for 2000 year. Malignancies in Russia and SNG countries in 2000 year. Moscow, ROSC of Blokhin N.N. RAMS. 2002; p 85 4. Mostofi M, Davis C, Sesterhenn I. Pathology of tumors of the urinary tract. In: Skinner D, Lieskowsky G (Eds). Diagnosis and management of genitourinary cancer. Philadelphia, PA: W.B. Saunders, 1988, p 83 5. Heney N. Natural history of superficial bladder cancer. Urol Clin North Am 1992; 19:429 6. Gattegno B. T1G3 Bladder Cancer: Conservative Management or Cystectomy? Eur Urol 2004; 45:399 7. Lum BL, Torti FM. Adjuvant intravesicular pharmaco-therapy for superficial bladder cancer. J Natl Cancer Inst 1991; 83:681 8. Farrow G, Utz B, Rise C. Morphological and clinical observations of patients with early bladder cancer treated with total cystectomy. Cancer Res 1976; 36: 2495 9. Heney N, Ahmed S, Flanagan MJ, et al. Superficial bladder cancer: progression and recurrence. J Urol 1983; 130:1083 10. Anderstrom C, Johansson C, Nilsson S. The significance of lamina propria invasion on the prognosis of patients with bladder tumors. J Urol 1980; 124:23 11. Malmström PU. Intravesical therapy of superficial bladder cancer. Crit Re Oncol/Hemat 2003; 47:109 12. Lamm D. Long-term results of intravesical therapy for superficial bladder cancer. Urol Clin North Am 1992; 19:573 22. Blinst ICG. Intravesical doxorubicin for the prophylaxis of superficial bladder tumors: a multicenter study C.A. Cancer J Clin 1984; 54:756 23. Garnick M, Schade D, Israel M. et al. Intravesical doxorubicin for prophylaxis in the management of recurrent superficial bladder carcinoma. J Urol 1984; 131:43 24. Kowalkowski T, Lamm D. Intravesical therapy of superficial bladder cancer. In: Resnick M (Eds) Current trends in urology. Baltimore MD: Williams & Wilkins, 1989 25. Crispen R. History of BCG and its substrains. In: Debruyne FMJ, Denis L, van der Meijden APM. (eds.): EORTC Genitourinary Group Monograph 6; BCG in Superficial Bladder Cancer. New York Liss, 1989, p 35 26. Morales A, Eidinger D, Bruce AW. Intracavitary Bacillus Calmette-Guérin on the treatment of superficial bladder tumours. J Urol 1976; 116:180 27. Pinsky CM, Camacho FJ, Kerr D, et al. Treatment of superficial bladder cancer with intravesical BCG. In : Terry WD, Rosenberg SA (Eds), Immunotherapy of Human Cancer. New York: Elsevier 1982, p 310 28. Rubben H, Krege S, Giani G, et al. Prospective randomized study of adjuvant therapy after complete resection of superficial bladder cancer: mitomycin C versus BCG connaught versus TUR alone. In: de Kernion J. (Ed), International Society of Urology reports. New York, NY: Churchill Livingstone; 1990 p 365 29. Herr H, Pinsky CM, Whitmore Jr WF, et al. Experience with intravesical bacillus Calmette-Guérin therapy of superficial bladder tumors. Urology 1985; 25:119 30. Herr HW. Bacillus Calmette-Guerin therapy alters the progression of superficial bladder cancer. J Clin Oncol 1988; 6: 1450 13. Whelan P. Treatment of Superficial Bladder Cancer: A discussion on intravesical immunotherapy and intravesical chemotherapy. Eur Urol Suppl 2004; 3:70 31. Witjes JA. Bladder Carcinoma in Situ in 2003: State of the Art Eur Urol 2004; 45:142 14. Rödel C, Dunst J, Grabenbauer GG, et al. Radiotherapy is an effective treatment for high-risk T1-bladder cancer. Strahlenther Onkol 2001; 177:89 32. Lamm D, et al. A randomized trial of intravesical doxorubicin and immunotherapy with bacillus Calmette-Guérin for transitional cell carcinoma of the bladder. N Engl J Med 1991; 325:1205 15. Malavaud B. T1G3 Bladder Tumours: The Case for Radical Cystectomy. Eur Urol 2004; 45:406 33. Sosnowski J, Lamm D. Immunotherapy of bladder carcinoma. In: Crawford E, Das S (Eds), Current genitourinary cancer surgery. Philadelphia, PA: Lea & Febiger, 1990 p 480 16. Gohji K, Nomi M, Okamoto M, et al. Conservative therapy for stage T1b, grade 3 transitional cell carcinoma of the bladder. Urology 1999; 53:308 34. Lamm D. Results of clinical trials of BCG therapy AUA Today. J Urol 1991; 141:22 17. Heney N. First-line chemotherapy of superficial bladder cancer: mitomycin C vs. thiotepa. Urology 1985; 26:27 18. Horn Y, Eidelman A, Walach N et al. Intravesical chemotherapy in a controlled trial with thiotepa versus doxorubicin. J Urol 1981; 125:652 19. Koontz W, Prout G, Smith W, et al. The use of intravesical thiotepa in the management of noninvasive carcinoma of the bladder. Urology 1984; 131:43 35. Kaasinen E, Wijkström H, Malmström PU, et al. Alternating Mitomycin C and BCG Instillations versus BCG Alone in Treatment of Carcinoma in Situ of the Urinary Bladder: A Nordic Study. Eur Urol 2003; 43:637 36. Bohle A, Bock PR. Intravesical bacille Calmette-Guerin versus mitomycin C in superficial bladder cancer: formal meta-analysis of comparative studies on tumor progression. Urology 2004; 63:682 20. Mori K, Lamm D, Crawford E. A trial of BCG versus Adriamycin in superficial bladder cancer. Urol Int 1986; 41:254 37. Shelley MD, Wilt TJ, Court J, et al. Intravesical bacillus Calmette-Guerin is superior to mitomycin C in reducing tumour recurrence in high-risk superficial bladder cancer: a meta-analysis of randomized trials. BJU Int 2004; 93:485 21. Flanagan R, Ellison M, Butler M. A trial of prophylactic thiotepa or mityomycin C intravesical therapy in patients with recurrent or multiple superficial bladder cancer. J Urol 1986; 136:35 38. Brake M, Loertzer H, Horsch R, Keller H. Recurrence and progression of stage T1, grade 3 transitional cell carcinoma of the bladder following intravesical immunotherapy with bacillus CalmetteGuerin. J Urol 2000;163:1697 Archivio Italiano di Urologia e Andrologia 2005; 77, 2 97 V. Startsev, I. Pouline 39. Tolley DA, Parmar MK, Grigor KM, et al. The effect of intravesical mitomycin C on recurrence of newly diagnosed superficial bladder cancer: a further report with 7 years of follow-up. J Urol 1996; 155:1233 40. Kuroda M, Niijima T, Kotake T, et al. Effect of prophylactic treatment with intravesical epirubicin on recurrence of superficial bladder cancer--The 6th Trial of the Japanese Urological Cancer Research Group (JUCRG): a randomized trial of intravesical epirubicin at dose of 20mg/40ml, 30mg/40ml, 40mg/40ml. 6th Trial of the Japanese Urological Cancer Research Group. Eur Urol 2004; 45:600 41. Cheng CW, Chan SF, Chan LW, et al. 15-Year Experience on Intravesical Therapy of T1G3 Urinary Bladder Cancer: a Conservative Approach. Jpn J Clin Oncol 2004; 34:202 42. Sylvester RJ, Oosterlinck W, Van Der Meijden AP. A single immediate postoperative instillation of chemotherapy decreases the risk of recurrence in patients with stage Ta T1 bladder cancer: a meta-analysis of published results of randomised clinical trials. J Urol 2004; 171:2186 43.Torti F, Shortliffe L, Williams RD et al. Alpha-interferon in superficial bladder cancer: a Northern California Oncology Group Study. J Clin Oncol 1988; 6:476 44. Glashon R. A randomized controlled study of intravesical alpha-2β interferon in carcinoma in situ of the bladder. J Urol 1990; 144:658 45. Ash D, Brown S. Photodynamic therapy achievements and prospects. Br J Cancer 1989; 60:151 46.Jr GP, Lin C, Benson R, et al. Photodynamic therapy with hematoporphyrin derivative in the treatment of superficial transitional-cell carcinoma of the bladder. N Engl J Med 1987; 317:1251 47. Ozen H, Ekici S, Uygur MC, et al. Repeated transurethral resection and intravesical BCG for extensive superficial bladder tumors. J Endourol 2001; 15:863 48. Jakse G, Algaba F, Malmström PU, Oosterlinck W. A SecondLook TUR in T1 Transitional Cell Carcinoma: Why? Eur Urol 2004; 45:539 49. Langenstroer P, See W. The role of a second transurethral resection for high-grade bladder cancer. Curr Urol Rep 2000; 1:204 50. Zurkirchen MA, Sulser T, Gaspert A, et al. Second transurethral resection of superficial transitional cell carcinoma of the bladder: a must even for experienced urologists. Urol Int 2004; 72:99 51. Dalbagni G, Herr H., Reuter VE. Impact of a second transurethral resection on the staging of T1 bladder cancer. Urology 2002; 60:822 52. Herr HW. The value of a second transurethral resection in evaluating patients with bladder tumors. J Urol 1999; 162:74 53.Brauer A, Buettner R, Jakse G. Second resection and prognosis of primary high risk superficial bladder cancer: is cystectomy often too early? J Urol 2001; 165:808 54. Boccon-Gibod L, Algaba F, Hamdy FC. Uropathology. Eur Urol 2003; 43:1 55. Harnden P. Transitional cell tumours of the bladder: classification and diagnostic pitfalls. Curr Diagn Pathol 2002; 8:76 Correspondence: Vladimir Yu Starsev, M.D., Urologi Department, Leningrad Regional Oncological Hospital, St. Petersburg, 191104 Russia; E-mail: [email protected] 98 Archivio Italiano di Urologia e Andrologia 2005; 77, 2 ORIGINAL PAPER Ablation of non functioning renal allograft by embolization: a valid alternative to graft nephrectomy? Andrea Solinas1, Franco De Giorgi2, Mauro Frongia1 Department of Renal Pathology, Unit of Urology; 2Service of Radiology, San Michele Hospital, Cagliari, Italy. 1 Summary Objective: Transplantectomy for the treatment of graft intolerance syndrome (GIS) is an invasive procedure with high risk, often performed in patients with poor general conditions. Renal allograft embolization is a recent alternative treatment to surgical nephrectomy. The aim of this study was to evaluate the efficacy and safety of allograft embolization in a series of patients with GIS. Patients and Methods: The study included 12 patients (9 males and 3 females) with irreversible renal graft rejection and GIS. All patients were in hemodialysis and they have not responded to medical treatment. Infection was ruled out by blood and urine cultures. The embolization was performed using polyvinyl alcohol particles and steel coils. Vascular access was obtained via femoral artery puncture in all the patients. Before starting embolization at the puncture site local anaesthesia was performed. Results: Eleven of the twelve procedures were technically successful, but in one patient a second treatment was necessary, after a month, for the presence of collateral perirenal circulation caused hematuria. There were no major complications and the mean hospital stay was 5 days. Conclusion: The graft embolization is a simple, safe and effective technique that permits non-surgical ablation of a non-functioning renal allograft in a significant number of patients. KEY WORDS: Kidney transplantation; Renal embolization; Vascular graft occlusion. INTRODUCTION The gold standard for the treatment of non functioning renal allograft with graft intolerance syndrome (GIS) has been the graft nephrectomy. This procedure is associated with a high rate of morbidity and mortality (1, 2). Hemorrhage, hematoma, abscess and vascular injury are the most common complications of surgical transplantectomy (3, 4). Renal allograft embolization is a recent alternative treatment to surgical nephrectomy (1). However, the safety and long-term efficacy of this technique has not been established. The graft can be left in situ when there are no additional complications. In some patients graft intolerance occurs when the immunological treatment is completely withdrawn. These patients may develop “flu like symptoms”, fever, malaise, pain or tenderness in the graft zone (5). When graft intolerance appears, the extended maintenance of low-dose immunosuppressive drugs can be effective (6). In the patients not responders to the medical treatment the ablation of non functioning renal allograft is inevitable. The aim of this study was to present the results of our series of renal vascular embolization for the treatment of graft intolerance syndrome in failed allograft kidneys. PATIENTS AND METHODS From January 1988 to December 2004, 504 transplanted kidneys was performed at our center. Until 2000 non functioning renal allograft with GIS were treated with the graft nephrectomy. With the advent and development of new angiography techniques, angio-embolization of these failed grafts is possible. From March 2001 to December 2004 renal graft embolization was performed in 12 patients with non-functioning renal allograft and GIS who have not responded to medical treatment and in the absence of simultaneous infectious disease. All patients were in hemodialysis. Patients were 9 males and 3 female, the mean age was 44 (30-62) years and the mean graft survival 100 (13-174) months. From the beginning of dialysis the graft was left in situ for 5 (3-7) months. The causes of renal failure and starting dialysis were chronic rejection in 11 (91.6%) patients and de novo glomerulonephritis in one (8.3%). Archivio Italiano di Urologia e Andrologia 2005; 77, 2 99 A. Solinas, F. De Giorgi, M. Frongia Figure 1. Intra-arterial angiography of the right iliac region. Renal artery patency with end-to-side anastomosis with the iliac artery. tion. Vascular access was obtained via femoral artery puncture in all the patients. Before starting embolization, we assessed the renal allograft anatomy, renal artery patency and the presence of perirenal collateral supply (Figure 1). We performed selective retrograde catheterisation of the allograft renal artery with a standard angiographic catheter. Additionally, the renal artery branches were selectively catheterised with a microcatheter to achieve occlusion at the most distal point. The distal intrarenal vascular bed was embolized using polyvinyl alcohol particles between 150-350 micron in size and the renal artery with steel coils deposited at the end of the procedure in order to prevent recanalization (Figure 2). After completing renal embolization, intra-arterial angiography of the aorto-iliac sector was performed to confirm occlusion of the renal artery and to check for collateral renal supply. The day after embolization a Doppler sonography was taken to verify the disappearance of arterial flow. Informed consent was obtained from each patient prior to the examination. RESULTS Figure 2. Post- embolization angiography. Total occlusion of the allograft renal artery and the intrarenal branches. Visualization of steel coils in main branch of the renal artery. All patients received cadaveric grafts. In ten patients it was the first renal transplantation, the second in two. Infection was ruled out by blood and urine cultures. Symptoms included fever, graft pain, graft swelling, malaise and anemia. Usually patients presented with more than one symptom. In all cases, attempts to treat the symptoms with steroids or non-steroidal antiinflammatory drugs failed. All the patients received broad spectrum antibiotics intravenously before and after the procedure. Renal embolization was performed using local anaesthesia at the puncture site and no seda- 100 Archivio Italiano di Urologia e Andrologia 2005; 77, 2 The embolization was a clinical success, defined as alleviation of symptoms, in 11 patients. There were no deaths and no major complications in any of the patients. Only one patient, presented hematuria after a month of the graft embolization. A new arteriography, performed in this patient, demonstrated extensive collateral perirenal circulation originated in two circumflex iliac artery (Figure 3). In this patient, Doppler study showed no flow either in the renal artery or the intrarenal arteries, demonstrating that the vascular embolization remained intact. In this case we were able to embolize only one circumflex artery (Figure 4). This partial embolization was sufficient to disappeared hematuria. Post embolization syndrome, characterized mainly by fever, occurred in all the patients and only one patient experienced slight post-embolization pain but there were no technical complications during angiography. The symptoms of GIS ceased within 1-7 days after embolization, but in one patient though most of the symptoms were relieved within 1 week, non-infectious fever remained high for 20 days and the resolution was successful with conservative management. The mean hospital stay was 5 days, while 10 days were required for 1 patient. The long-term results of allograft embolization is good, with absence of clinical intolerance and complications in all the patients. DISCUSSION The kidney embolization, introduced in the 1973 for the treatment of renal cell carcinoma (7) is today commonly accepted as palliative therapeutic option in non operable tumours with serious haemorrhage, pain or manifestations of the paraneoplastic syndrome. It is also used in the treatment of the hemorragic complication of the percutaneous nephrolithotomy (8) and in the iatrogenous kidney bleeding consequent to percutaneous Embolization of non functioning renal allograft Figure 3. Angiography shows total occlusion of the main renal artery, with cortical repatency originating in two circumflex iliac artery. tions. Graft nephrectomy has been the treatment of choice for non-functioning renal allograft with GIS, often performed in patients with poor general conditions, and it is still practised in some hospital, though studies report a morbidity of 6-25% and mortality of 07% (1, 2). The surgical procedure can be very difficult because of the development of fibrosis around the kidney with severe potential complications such as haemorrhage, haematoma, abscess and vascular injury. Ablation of non functioning renal allograft by embolization is a less invasive method of treatment with a shorter hospital stay and a lower complication rate (2, 4). In this study the embolization was a clinical success in majority of the patients with no major complications. The mean hospital stay was 5 days. CONCLUSIONS Figure 4. The same case of Figure 3, angiography shows embolization of only one circumflex artery. In summary our data confirmed, in accord with other authors, that embolization of non functioning renal allograft can be used as treatment of choice for patients with clinical signs of GIS (4, 14). Furthermore, it does not preclude nephrectomy if symptoms of GIS persist, and repeated transplantation is still possible. The allograft nephrectomy is indicated in case of hyperacute rejection, kidney rupture, irreparable urological complications, irreversible arterial or venous thrombosis, neoplasm and when embolization fails (4). In cases of asymptomatic non-functioning grafts, nephrectomy may not be necessary. REFERENCES 1. Lorenzo V, Diaz F, Perez L et al. Ablation of irreversibly rejected renal allograft by embolization with absolute ethanol: a new clinical application. Am J Kidney Dis 1993; 22:592 2. Cofán F, Vilardell J, Gutierrez R et al. Efficacy of renal vascular embolization versus surgical nephrectomy in the treatment of nonfunctioning renal allografts. Transplant Proc 1999; 31: 2244 3. O’Sullivan DC, Murphy DM, Mc Lean P, Donovan MG. Transplant nephrectomy over 20 years: factors involved in associated morbidity and mortality. J Urol 1994; 151:855 4 Cofán F, Real MI, Vilardell J et al. Percutaneous renal artery embolisation of non-functioning renal-allografts with clinical intolerance. Transpl Int 2002; 15:149 5. Silberman H, Fitzgibbons T, Butler J, Berne T. Renal allograft retained in situ after failure. Arch Surg 1980; 115:42 nephrostomy (9). This technique has shown to be a valid alternative to the surgical nephrectomy also for not neoplastic pathologies in patients who are at increased risk for operative complications (10) or in the treatment of non functioning hydronephrotic kidneys (11). In literature few cases are described in which it was used in paediatric patients for the treatment of the pseudoincontinence (12, 13). This approach was first reported by Lorenzo et al. (1) in the treatment of non-functioning kidney graft; the results were good and there were no severe complica- 6. González-Satué C, Riera L, Franco E, Escalante E, Dominguez J, Serrallach N. Percutaneous embolization of the failed allograft in patients with graft intolerance syndrome. BJU International 2000; 86:610 7. Almgard LE, Fernstrom I, Haverling M, Ljungqvist A. Treatment of renal adenocarcinoma by embolic occlusion of the renal circulation. Br J Urol 1973; 45:474 8. Gremmo E, Ballanger P, Dore B, Aubert J. Hemorrhagic complications during percutaneous nephrolithotomy. Retrospective studies of 772 cases. Prog Urol 1999; 9:460 9. Peene P, Wilms G, Baert AL. Embolization of iatrogenic renal Archivio Italiano di Urologia e Andrologia 2005; 77, 2 101 A. Solinas, F. De Giorgi, M. Frongia hemorrhage following percutaneous nephrostomy. Urol Radiol 1990; 12:84 12. De Groote B, Van Laer P, Maurus K, Van Biervliet JP, Meeus L. Embolization of ectopic kidney to control incontinence. Ped 1990; 85:217 10. Hom D, Eiley D, Lumerman JH, Siegel DN, Goldfischer ER, Smith AD. Complete renal embolization as an alternative to nephrectomy. J Urol 1999; 161:24 13. Solinas A, De Giorgi F, Frongia M. Embolization of a hypoplastic kidney with a vaginal ectopic ureter in a case of pseudo-incontinence. Arch Ital Urol Androl 2004; 76:117 11. Hirao Y, Okajima E, Yoshida K et al. Renal ablation with absolute ethanol for non functioning hydronephrosis. Eur Urol 1993; 24:203 14. Delgado P, Diaz F, Gonzalez E et al. Transvascular ethanol embolization: first option for the management of symptomatic nonfunctioning renal allografts left in situ. Transpl Proc 2003; 35:1684 Correspondence: Andrea Solinas, M.D., Azienda Ospedaliera “G. Brotzu, Ospedale San Michele, S.C. di Urologia, Via Peretti 3 - 09134 Cagliari, Italy; E-mail: [email protected] 102 Archivio Italiano di Urologia e Andrologia 2005; 77, 2 ORIGINAL PAPER Early surgical repair of penile fractures: our experience. Gioacchino De Giorgi, Lorenzo G. Luciani, Claudio Valotto, Umberto Moro, Silvio Praturlon, Filiberto Zattoni Dipartimento Interaziendale di Urologia, Azienda Ospedaliera S.M. Misericordia, Università degli Studi, Udine. Summary Objective: Fracture of the penis is a relatively rare condition, defined as the rupture of the tumescent corpora cavernosa. The fracture is quite easily recognized, whereas its management remains controversial. Our experience regarding the early treatment of penile fractures is herein reported. Materials and Methods: In a 7-year period (1997-2004) 10 patients aged 23 to 42 years, presented with a penile fracture, occurred during coitus. All patients were admitted to the hospital 1 to 10 hours after injury. Diagnosis was made on clinical examination. Six patients referred a snapping sound at the time of injury. Common clinical features included sudden penile pain, detumescence and penile deviation. All patients showed penile haematoma; 3 had scrotal and perineal haematoma as well. None of the patients had urethral bleeding. Results: all patients were surgically treated; at the time of surgery unilateral albugineal rupture was found in all cases. With a mean follow-up of 37 months (range 1-78) all cases were able to achieve an adequate erection. No complications, such as deformations, penile plaque, urethral fistula or erectile dysfunction were reported. Conclusion: Immediate surgical repair in case of penile fracture is recommended in order to obtain better functional outcome and to avoid potential complications. KEY WORDS: Penile fracture; Coital trauma; Penile degloving; Penile surgical repair. INTRODUCTION Penile fracture is a relatively rare urological emergency, defined as a rupture of the tunica albuginea of the corpora cavernosa by blunt trauma. The fracture usually occurs to the erect penis when one or both corpora cavernosa are ruptured. The rupture occurs during sexual intercourse, rolling over in bed, or during sexual manip- Table 1. Patient’ characteristics. Patients S.D. Z.G C.M S.L. S.L. L.A. B.R. N.L. B.O. O.M. Age (yrs) Site of haematoma Time at observation Site of tear of albuginea of corpora Follow-up (months) 25 31 27 27 28 26 39 42 23 23 Penile Scrotal/perineal Scrotal/perineal Scrotal/perineal Penile Penile Penile Penile Penile Penile 1h 10 h 6h 1h 1h 1h 1h 1h 1h 1h right left right left right right right left right left 78 66 60 45 42 41 21 14 2 1 Archivio Italiano di Urologia e Andrologia 2005; 77, 2 103 G. De Giorgi, L.G. Luciani, C. Valotto, U. Moro, S. Praturlon, F. Zattoni Figure 1. Figure 4. Peno-scrotal haematoma following penile fracture occurred during coitus. Outcome after early surgical repair of penile fracture. Figure 2. ulation, because of a sudden increase in intracorporeal pressure that overwhelms the tunica albuginea. The simultaneous involvement of both corpora cavernosa and/or corpus spongiosum and urethra was also reported (1). Penile fracture is easily recognizable, due to its history and presentation. Clinical signs include haematoma, swelling and skin discoloration; haematoma is confined to the penis, scrotum or perineum in case of an undamaged Buck’s fascia. Many patients hear a snapping sound and experience sharp penile pain followed by collapse of the erection. The optimal treatment is still controversial (2), particularly in case of bilateral corporeal involvement or urethral damage. The long-term results of conservative treatment indicated significant complications, such as curved or painful erection, fibrotic plaque or erectile dysfunction. Our experience with early surgical treatment of penile fractures is herein reported. Intraoperative finding: left dorsolateral tear of the tunica albuginea at the proximal third of the penis. Buck’s fascia is open and cavernous tissue is evident. A haemostatic lace is placed at the base of the penis. Figure 3. Intraoperative finding: Buck’s fascia is open, the edges of the tunica albuginea are regularized and sutured with PDS. MATERIALS AND METHODS Between November 1997 and May 2004, ten patients aged 23 to 42 years, were hospitalized with penile fracture at our Department. Patients’ characteristics are reported in Table 1. All patients underwent immediate surgery. Indications were based on clinical examination in all cases (Figure 1). Penile degloving through a circumferential subcoronal approach, evacuation of the haematoma, and primary repair of the tear in the tunica albuginea with a PDS suture were performed in all patients (Figure 2-4). No urethral injury was found. All patients were discharged on postoperative day 2 and checked again one week later. RESULTS The interval time from injury to observation ranged from 1 to 10 hours. All patients reported penile trauma during coitus with sudden pain at the time of 104 Archivio Italiano di Urologia e Andrologia 2005; 77, 2 Early surgical repair of penile fractures: our experience rupture. Six patients heard a “snapping” sound, sharp penile pain followed by collapse of the erection. In 7 cases a penile haematoma was present; in 3 cases the haematoma extended to scrotum and perineum. The penis was curved on the side of rupture in all cases (Figure 1). Urethral discharge has never been reported. Mean follow-up after surgery was 37 months (range 178). All patients presented spontaneous erections early postoperatively. In our experience no early or late complications have been reported at follow-up (infected haematoma, fistulas, penile abscess, penile deformity or induration, painful erection, erectile dysfunction). Erection was adequate for sexual intercourse in all cases. DISCUSSION AND CONCLUSIONS Penile fracture, even if it is a relatively rare condition, represents a true urological emergency. Ultrasonography can be useful in showing the precise site of the tear of the tunica albuginea and defining the extent of the injury. In our experience, however, diagnosis and indication to surgical treatment was based only on history and physical examination, making ultrasound unnecessary. Previous studies advocated a conservative treatment (splitting of the penis, pressure dressing over a Foley catheter, ice packs) (3-5), although complication rates were significantly high. Therefore, more recent studies generally support the need for an early surgical approach in case of penile fracture. This might preserve the collagen function and avoid a fibrotic evolution of the tunica albuginea with potential penile curvature, painful erection or erectile dysfunction (6, 7). With the strategy previously described, no short and long-term complications were reported. We can conclude that immediate surgical repair has to be considered in all cases of penile fracture, as suggested by other Authors (7, 8), in the light of the low invasiveness of the procedure, short hospitalisation and low complication rate. REFERENCES 1. Tsang T, Demby AM. Penile fracture with urethral injury. J Urol 1992; 147:466 2. Kalash SS, Young JD Jr. Fracture of the penis: controversy of surgical versus conservative treatment. Urology 1984; 24:21 3. Dincel C, Caskurlu T, Resim S, Bayraktar Z, Tasci AI, Sevin G. Fracture of the penis. Int Urol Nephrol 1998; 30:761 4. Dever D, Saraf PG, et al. Penile fracture: operative management and cavernosography. Urology 1983; 22:394 5. Farah R, Stiles R, et al. Surgical treatment of deformity and coital difficulty in healed traumatic rupture of the corpora cavernosa. J Urol 1978; 120:118 6. Ishikawa T, et al. Fracture of the penis: nine cases with evaluation of reported cases in Japan. Int J Urol 2003; 10:257 7. Anselmo G, Maccatrozzo L, Merlo F, Fandella A. Le lesioni traumatiche dei genitali esterni. In: Molinatti GM, Fontana D. Andrologia-Fisiopatologia e Clinica. Roma: Verduci Editore, 1997:471 8. Gontero P, Muir GH, Frea B. Pathological findings of penile fractures and their surgical management. Urol Int 2003; 71:77 Correspondence: Dott. Gioacchino De Giorgi, Department of Urology, Azienda Ospedaliera S.M. Misericordia, P.le S.M.Misericordia, 15 33100 Udine; E-mail: [email protected] Archivio Italiano di Urologia e Andrologia 2005; 77, 2 105 ORIGINAL PAPER Still a place for the classical systematic sextant technique? Cancer detection rates and complications in 1025 consecutive prostatic biopsies. Massimo Maffezzini1, Lorenzo Gavazzi1, Tiziana Calcagno1, Giacomo Capponi1, Roberto Bandelloni2 Struttura Complessa di Urologia e 2Servizio di Anatomia Patologica, Ospedali Galliera, Genova, Italy. 1 Summary Objectives: To verify if there might still be an indication to the sextant biopsy technique we reviewed the cancer detection rate obtained and the complications encountered during a five years interval, at our hospital. Methods: From January 1997 to December 2002 we have submitted to prostatic biopsy a total of 1025 consecutive patients with a clinical suspect of prostate cancer. A total of six cores were obtained in all the patients with an additional core at suspect lesions. Results: Overall, prostate cancer was present in the biopsies of 444 of 1025 patients giving a detection rate of 43.3%. In patients with serum PSA levels between 4.1 and 10 ng/ml., 169 of 466 biopsies were positive, for a detection rate of 36.3%. An increase in percentage of positivity was observed with increasing decades of age. Overall complication rate was 1.4%. Conclusions: In patients older than 70 years, and with PSA levels higher than 10 ng/ml, the sextant technique may offer cancer detection rates comparable with techniques using an increased number of cores, and with lower complication rates. KEY WORDS: Prostate cancer diagnosis; Sextant biopsy; Cancer detection rates; Complications. INTRODUCTION The diagnosis of prostate cancer relies upon the results obtained by sampling tissue from the gland. The sextant biopsy technique popularized by Hodge et al. in 1989 (1) that has considered been so far as the gold standard, has been recently recognized to carry a false negative rate of 20 to 30% (2, 3). Therefore, based on the observation that the sextant technique may under estimate cancer diagnosis, several studies have focused on increasing the number of cores, above six, with the purpose to increase the cancer detection rate (3-10). We review herein the cancer detection rate, and the complications encountered with the sextant technique at our center, in order to verify if there might be still an indication for such biopsy strategy. PATIENTS AND METHODS We reviewed the clinical data, and the pathology reports of all men referred to our Hospital, for a clinical suspect of prostate cancer and submitted to prostatic biopsy, from January 1997, to December 2002. The clinical suspect of cancer was based on one, or more, of the fol- 106 Archivio Italiano di Urologia e Andrologia 2005; 77, 2 lowing findings: a positive digital rectal exam (DRE), suspicious imaging at transrectal ultrasound (TRUS), or an elevation on serum prostatic specific antigen (PSA). Patient preparation consisted in a cleansing enema on the night before, and oral administration of prophylactic ciprofloxacin 500 mg on the morning of the biopsy. After DRE, the prostate was imaged with the patient in the lateral knee chest position with a real time, bi-planar or multi-planar multi-frequence, 7.5 MHz endorectal probe, of a B and K ultrasound scanner. Biopsies were taken with a 16 or 18 gauge tru-cut needle and a springloaded biopsy gun (Bard). A total of six cores were obtained in all patients. An additional core was also taken at suspicious ultrasound lesions, as described by Hodges (1). The sampling of the peripheral zone was performed directing the needle more laterally to the midparasagittal line, as proposed by Stamey (11). The specimens were placed in formalin solution, processed with step sectioning and immunohistochemistry techniques, and reviewed by a single pathologist (RB). The procedure was performed without anesthesia and the patients were observed for two hours following the pro- Still a place for the classical systematic sextant technique? Cancer detection rates and complications in 1025 consecutive prostatic biopsies. Table 1. (57.5%). The detection rates for the various serum PSA levels, and age ranges are listed in Table 1. Positivity rate according to serum PSA levels, and age distribution. PSA Range 0-4 ng/ml 4.1-10 ng/ml 10.1-20 ng/ml >20.1 ng/ml Positive/Totals 27/78 169/466 121/283 127/198 % 34.6 36.3 42.7 64.1 Age < 50 y 50-59 y 60-69 y 70-79 y > 80 y Positive/Totals 10/17 25/106 126/358 228/442 65/113 % 58.8 23.5 35.2 51.6 57.5 COMPLICATIONS The procedure was well tolerated. Although a variable of degree of macroscopic hematuria was observed in the majority of patients, complications that required hospital admission were observed in 15 patients (1.4%). The complications are detailed as follows: gross hematuria in 10 patients, hematuria with clots retention in 2 patients, fever and chills in 2, and rectal bleeding in one. DISCUSSION cedure to monitor side effects that were treated, and recorded. RESULTS The population of the study is composed by 1025 patients who were evaluated primarily at our hospital, or referred by other centers or by general practitioners, and accepted to undergo prostatic biopsies. Median age was 69.5 years, range 47 to 91. Overall, prostate cancer was present in the biopsies of 444 of 1025 patients giving a detection rate of 43.3%. In patients with serum PSA levels between 4.1 and 10 ng/ml, 169 of 466 biopsies were positive for carcinoma, for a detection rate of 36.3%. In patients with PSA levels between 10.1 and 20 ng/ml, 121 out of 283 biopsies were positive for cancer, for a detection rate of 42.7%, whereas, for serum PSA levels above 20.1 ng/ml, 127 of 198 patients had positive biopsies for cancer giving a detection rate of 64.1%. An increase in the percentage of positive biopsies was observed with increasing decades of age. Positive biopsies were found in 25 of 106 patients (23.5%) aged 50 to 59 years, in 126 of 358 patient aged 60 to 69 years (35.2%), in 228 of 442 patients aged 70 to 79 years (51.6%), and in 65 of 113 aged 80 years and beyond, The systematic sextant technique has represented the standard for the diagnosis of prostate cancer since its introduction, in 1989 (1). Its validity has recently been challenged by the objection that it under samples the far lateral regions of the gland where a significant number of cancers may reside. Therefore, different biopsy protocols including additional number of cores have been investigated in which the sextant method has been compared concurrently, in the same session of biopsy, with methods including more than 6 cores (3-10) . An overall increase in the cancer detection rate has been reported in the range of 8.1% to 14.8%. Such gain is even higher among patients with PSA levels between 4 and 10 ng/ml, ranging from 20.8% to 53.6%. A summary of the results of such studies is given in Table 2. The only negative trial was reported by Naughton et al (8). The study failed to demonstrate any advantage for the 12 cores over the 6 cores method. However, as the authors recognize, the sub-optimal size of the study population may have influenced the interpretation of their results. Nevertheless, it is of note that 7 out of 33 tumors, that is 21%, were diagnosed in the 12-core biopsy group. In the present study the overall detection rate was 43.3% and, in patients with PSA levels between 4 and 10 ng/ml, the detection rate was 36.3%. Such figures are in the highest range of the literature, for the systematic sextant biopsies. An explanation for this finding may reside in the technique adopted since attention was paid at aiming the gland by driving the needles more laterally respect to the parasagittal plane, as suggested by Stamey (11). It is likely that a higher amount of tissue sampled from the lateral Table 2. Detection rates with the 6 cores technique compared with > 6 cores biopsies. Detection Rate ∆ Improvement ∆ Improvement 6xt PSA 4-10 ng/ml Author Year N° Pts N° Cores Overall Detection Rate Norberg 1997 512 8-10 276/512= 52% 234/512= 37.2% 14.8% n.s. Eskew 1997 119 13-18 48/119= 40% 31/119= 26% 14% 15/28= 53.6% Levine 1998 137 12 43/137= 31% 30/137=21.9% 8.1% 8/21= 38.1% Presti 2000 483 10 202/483= 42% 161/483= 33.3% 9.7% 20.8% Babaian 2000 362 11 110/362= 30% 74/362= 20% 10% 21/58= 36% Naughton 2000 244 6-12 33/122= 27% 32/112= 26% 1% n.d. Archivio Italiano di Urologia e Andrologia 2005; 77, 2 107 M. Maffezzini, L. Gavazzi, T. Calcagno, G. Capponi, R. Bandelloni “horns” of the gland was present in our biopsies, thereby increasing the detection rate. In addition, the sample might reflect an involuntary selection of patients both for age and PSA levels. The median age of the sample is 69.5 years, with almost one half of the patients aged 70 years, or older. Elevated serum PSA, of 10.1 ng/ml and above, was present in almost one half of the study population (namely, 283 patients whose PSA was above 10 ng/ml, and 198 whose PSA was above 20 ng/ml). An ideal biopsy should consist in a number of samples adequate to give a realistic picture of the prostate, and causing no discomfort. More importantly also, since the majority of men will undergo the procedure for a nonmalignant condition, the procedure should cause no complications. Today, the ideal number of cores is still undetermined. Compared to the classical sextant an increased number of cores can sample the gland more adequately, as most of the recent studies point out (3, 10). Patients with large prostate glands, or with PSA levels in the “grey” area, and patients with persistent clinical suspect and negative histology are likely to benefit the most from a more accurate sampling. It seems almost inevitable that increasing the number of samples beyond six will also increase the need of anesthesia as well as the rate of complications. The incidence of complications, although not uniformly reported by all authors, may vary between 3.5% as observed by Norberg (4), to 12% as observed by Stewart (10) and by Borboroglu (9), to 20% as reported by Eskew (5). Gross hematuria and acute urinary retention are the two complications most frequently described. Generally, hematuria heals spontaneously and catheterization is required only for persistent hematuria, or for retention. The increase in complication rates, though, is likely to be outscored by the gain on the information obtained. In the present series of biopsies hematuria and acute urinary retention requiring hospitalization have been observed in 15 out of 1025 patients, that is 1,4%. We conclude that there is a subset of patients, namely those aged 70 years or older, and whose PSA level is greater than 10 ng/ml, in whom the sextant technique can offer detection rates comparable with techniques using an increased number of cores with lower complication rates. REFERENCES 1. Hodge KK, McNeal JE, Terris MK, Stamey TA. Random systematic versus directed ultrasound guided transrectal core biopsies of the prostate. J Urol 1989; 142:71 2. Stroumbakis N, Cookson MS, Reuter VE, Fair WR. Clinical significance of repeat sextant biopsies in prostate cancer patients. Urology 1997; 49:113 3. Levine MA, Ittman M, Melamed J, Lepor H. Two consecutive sets of transrectal ultrasound guided sextant biopsies of the prostate for the detection of prostate cancer. J Urol 1998; 159:471 4. Norberg M, Egevad L, Holmberg L, Sparen P, Norlen BJ, Busch C. The sextant protocol for ultrasound-guided core biopsies of the prostate underestimates the presence of cancer. Urology 1997; 50:562 5. Eskew LA, Bare LR, McCullogh DL. Systematic 5 region prostate biopsy is superior to sextant method for diagnosing carcinoma of the prostate. J Urol 1997; 157:199 6. Presti JC Jr, Chang JJ, Bhargava V, Shinohara K. The optimal systematic prostate biopsy scheme should include 8 rather than 6 biopsies: results of a prospective clinical trial. J Urol 2000; 163:163 7. Babaian RJ, Toi A, Kamoi K, et al. A comparative analysis of sextant and an extended 11-core multisite directed biopsy strategy. J Urol 2000;163: 152 8. Naughton CK, Miller DC, Mager DE, Ornstein DK, Catalona WJ. A prospective randomized trial comparing 6 versus 12 prostate biopsy cores: impact on cancer detection. J Urol 2000; 164:388 9. Borboroglu PG, Comer SW, Riffenburgh RH, Amling CL. Extensive repeat transrectal ultrasound guided prostate biopsy in patients with previous benign sextant biopsies. J Urol 2000; 163:158 10. Stewart CS, Leibovich BC, Weaver AL Lieber MM. Prostate cancer diagnosis using a saturation needle biopsy technique after previous negative sextant biopsies. J Urol 2001; 166: 86. 11. Stamey TA. Making the most out of six systematic sextant biopsies. Urology 1995; 45:2 Correspondence: Massimo Maffezzini, M.D., Head of Urology, Ospedali Galliera, Mura delle Cappuccine, 14 - 16128 Genova,Italy; E-mail: [email protected] 108 Archivio Italiano di Urologia e Andrologia 2005; 77, 2 CASE REPORT Orbital metastasis as a first indication of prostate cancer: a case report. Riccardo Autorino1, Aniello Zito1, Ferdinando Di Giacomo1, Luca Cosentino1, Giuseppe Quarto1, Giuseppe Di Lorenzo2, Salvatore Mordente2, Umberto Pane1, Antonio Giordano2, Massimo D’Armiento1 Clinica Urologica, Seconda Università degli Studi di Napoli, Italy Cattedra di Oncologia, Università Federico II, Napoli, Italy 1 2 Summary Prostatic carcinoma accounts for only 3.6% of orbital metastases encountered in clinical practice. We report the clinical presentation and response to treatment of a patient with metastatic prostatic carcinoma to the sella turcica. A 73-year-old man presented with a three-months history of progressive right proptosis associated with increasing diplopia in downgaze and slightly decreased visual acuity. Gadiolinium-MRI scans of the head revealed a left osteoblastic intrasellar mass, displacing the pituitary gland. Laboratory testing revealed a serum PSA level of 22 ng/ml. Transrectal ultrasound-guided biopsy revealed prostatic adenocarcinoma (Gleason score 4+3) in both lobes of the prostate. A bone scan was performed showing that the patient had multiple secondary bony lesions. Total androgen blockade was initiated. Moreover, he was referred for radiotherapy of this metastatic lesion to the sella turcica. The visual complaints regressed dramatically within the first month of the treatment. A follow-up MRI scan at 6 months showed almost complete involution of the orbital metastatic process. However the disease subsequently progressed and the patient died 22 months after diagnosis. KEY WORDS: Metastatic prostate cancer; Orbital metastases, Sella turcica; Treatment. INTRODUCTION Orbital metastases are uncommon, representing only 2% to 9% of all adult orbital neoplasms (1). The majority of orbital metastases in adults are carcinomas, with lung carcinoma in men and breast carcinoma in women being the most common primary lesion (2). Prostatic carcinoma has a well recognized pattern of metastatic disease, most frequently involving the axial skeleton. It accounts for only 3.6% of orbital metastases encountered in clinical practice. Orbital metastases are more commonly osteoblastic and frequently cause proptosis and diplopia, that can be the presenting features of metastatic disease (3). We report the clinical presentation and response to treatment of a patient with metastatic prostatic carcinoma to the sella turcica. CASE REPORT A 73-year-old man presented with a three-months history of progressive right proptosis associated with increasing diplopia in downgaze and slightly decreased visual acuity. He denied any systemic symptoms and he had no history of urological malignancies. On palpation, the left orbit was tense, with increased resistance to retrodisplacement of the globe. The left conjunctival vessels were hyperemic. Immediately following complete clinical workup, Gadiolinium-MRI scans of the head, encompassing the orbit, middle cranial fossae and temporal fossae, were performed, revealing a left osteoblastic intrasellar mass, displacing the pituitary gland (Figure 1). Laboratory testing revealed normal metabolic, hepatic and throyd panels, an alkaline phosphatase level of 1230 U/l and serum PSA level of 22 ng/ml. He had normal digital rectal examination findings. Transrectal ultrasound-guided biopsy revealed prostatic adenocarcinoma (Gleason score 4+3) in both lobes of the prostate. A bone scan was performed showing that the patient had multiple secondary bony lesions, including the one to the orbit. Therefore, total androgen blockade with gonadotropinreleasing hormone agonist in conjunction with an antiandrogen was initiated. Moreover, he was referred for radiotherapy of this metastatic lesion to the sella turcica. He was treated using Gamma-knife with a total dose of 36 Gy. The visual complaints regressed dramatically within the first month of the treatment. He had no side effects related to the radiotherapy. His PSA nadir was 0.4 ng/ml. Archivio Italiano di Urologia e Andrologia 2005; 77, 2 109 R. Autorino, A. Zito, F. Di Giacomo, L. Cosentino, G. Quarto, G. Di Lorenzo, S. Mordente, U. Pane, A. Giordan, M. D’Armiento Figure 1. MRI scan at presentation showing a left orbital mass. Figure 2. MRI scan at 6 months. A follow-up MRI scan at 6 months showed almost complete involution of the orbital metastatic process (Figure 2). However the disease subsequently progressed and the patient died 22 months after diagnosis. carcinoma is important because certain metastases can cause profound morbidity but may be treated effectively in the palliation of advanced disease (3). This case was presented to remind both the urologists and ophtalmologists of the diagnosis of metastatic prostate carcinoma to the orbit and particularly to the sellar region. DISCUSSION The most comprehensive estimates of the prevalence of orbital metastases are from large retrospective series of unilateral proptosis or orbital biopsy specimens in the ophthalmic literature (1, 2). The small number of published cases may not reflect the true incidence of orbital occurrence. Case reports of widely disseminated tumors that happen to include orbital metastases are unlikely to be published. The tumor is likely to be reported only if it appears to be an initial manifestation of previously undetected primary. There are some unusual aspects of this case. Firstly, the metastatic site. To our knowledge this is the sixth case of prostate carcinoma metastatic to the sella turcica and two of them were not localized to the bone (4-8). Secondly, in our case, prior to the discovery of multiple bony lesions after a bone scan was done, the patient denied any systemic manifestations other than those attributable to the ophthalmic system. Thus, ocular complaints were the initial presenting symptoms that led to the diagnosis of prostate cancer. We did not perform any biopsy to the orbit for an histologic confirmation of our diagnosis. Regarding the radiation therapy given to this patient, such irradiation is generally effective in the treatment of distant metastases from carcinoma of the prostate. Marked relief of symptoms occurs in more than 80% of patients treated with adequate doses (9). Nevertheless, the survival after documentation of ocular metastasis is poor as confirmed in the present case. Recognition of unusual metastases from prostate adeno- REFERENCES 1. Boldt HC, Naird JA. Orbital metastases from prostate carcinoma. Arch Ophtalmol 1988; 106:1403 2. Bullock J, Yanes B. Metastatic tumors of the orbit. Ann Ophthalomol 1980; 12:1392 3. Long MA and Husband JES. Features of unusual metastases from prostate cancer. Br J Radiol 1999; 72:933 4. Matsumoto I, Furusato M, Inomata I et al. Prostatic cancer presenting as metastatic adenocarcinoma of sphenoid sinus. Acta Pathol Jpn 1986; 36:1753 5. Perloff JJ, Lemar HJ, Reddy BVV et al. Metastatic adenocarcinoma of the prostate manifested as a sellar tumor. South Med J 1992; 85:1140 6. Losa M, Grasso M, Giugni E et al. Metastatic prostatic adenocarcinoma presenting as a pituitary mass: shrinkage of the lesion and clinical improvement with medical treatment. Prostate 1997; 32:241 7. Couldwell WT, Chandrasoma PT and Weiss MH. Pituitary gland metastasis from adenocarcinoma of the prostate. J Neurosurg 1989; 71:138 8. Patel N, Teh BS, Powell S et al. Rare case of metastatic prostate adenocarcinoma to the pituitary. Urology 2003; 62:352 9. Di Lorenzo G, Autorino R, Ciardiello F et al. External beam radiotherapy in bone metastatic prostate cancer: impact on patients' pain relief and quality of life. Oncol Rep 2003; 10:399 Correspondence: Riccardo Autorino, MD, Vico S. Spirito 54 – 80132 Napoli, Italy; E-mail: [email protected] 110 Archivio Italiano di Urologia e Andrologia 2005; 77, 2 CASE REPORT Endoscopic treatment of a large leiomyoma of the bladder. Giuseppe Carrieri1, Tommaso Corvasce2, Pasquale Annese2, Isabella Tolve2, Alessandro Caniglia3, Giuseppe Di Sabato2 Division of Urology, University of Foggia, Italy Departments of Urology and 3Pathology, Madonna delle Grazie Hospital, Matera, Italy 1 2 Summary Leiomyoma is a benign neoplasm rarely found in the bladder. We present a case of a large leiomyoma of the bladder treated successfully by endoscopic transurethral resection. KEY WORDS: Leiomyoma; Bladder; Mesenchymal tumours. CASE DISCUSSION A 47-year-old female patient was examined for irritative symptoms. Bladder ultrasonography and CT showed a voluminous mass, approximately 6 cm in diameter, in the left hemitrigonum (Figure 1). Endoscopically the lesion had a solid appearance and was covered by an apparently normal mucosa. The patient underwent transuretral resection of the mass, weighing about 100 g, reaching the fat layer of the bladder (Figure 2). The histological examination revealed a leiomyoma of the bladder wall (Figure 3). In the following 3 years of follow-up no relapse was found. Benign mesenchymal tumours constitute 1% of all bladder neoplasms; of these 35% are represented by leiomyomas (1). These tumours have a higher incidence in females, developing prevalently in the third - sixth decade of life. Ovarian hormones seem to play an important role in their pathogenesis as analogously occurs for uterine leiomyomas. Furuhashi (2) has recently demonstrated the presence of estradiol and progesterone receptors in bladder leiomyomas. However, according to other authors, the occurrence of this neoplasm in the post-menopausal period would discredit the role of the ovarian hormones in the etiology and pathogenesis of bladder leiomyomas. Figure 1. CT: gross button-like formation, 6 cm in diameter, in the left hemitrigonum. Figure 2. Complete resection of the lesion reaching the fatty tissue layer surrounding the bladder. Archivio Italiano di Urologia e Andrologia 2005; 77, 2 111 G. Carrieri, T. Corvasce, P. Annese, I. Tolve, A. Caniglia, G. Di Sabato Figure 3. Histological characteristics of bladder leiomyoma: the classical disorderly band disposition of spindle-shaped cells with vesicular nuclei. H & E Reduced from x 200. toms caused by the growth of the neoplasm near the bladder neck have been reported (3) as well as hydronephrosis caused by ureteral obstruction (4). Lesions which prevalently develop outside the bladder may remain asymptomatic until they reach very large dimensions. For large neoplasms and/or in cases with a prevalent extra-vesical development the treatment of choice still today is partial cystectomy. Trans-urethral resection is generally indicated for small tumours. In the case we have reported we opted for an endoscopic procedure even in the presence of a large lesion, resecting the leiomyoma completely, reaching the extravesical fat; the radical procedure represents the key to success in these cases. REFERENCES 1. Knoll LD, Segura J, Scheithauer BW. Leiomyoma of the Bladder. J Urol 1986; 136:906 The leiomyoma presents singularly in 90% of cases and 65% develop endoluminally (3). The lesions, more often peduncular than sessile, are highly vascularized, covered by epithelium with either a normal or necroticgranular appearance. The symptoms in cases that prevalently develop within the bladder are characterized by urinary irritation and occasionally by episodes of macroematuria; in some cases obstructive urinary symp- 2. Furuhaschi M, Suganuma N. Recurrent bladder leiomyoma with ovarian steroid hormone receptors. J Urol 2002; 167:1399 3. Cortellini P. Manifestazioni Anatomo-Cliniche inconsuete di malattie urologiche. 1 ed. Mantova: Corraini Editore, 1996 4. Kirsh EJ, Sudakoff G, Steinberg GD, et al. Leiomyoma of the bladder causing ureteral and bladder outlet obstruction. J Urol 1997; 157:1843 Correspondence: Giuseppe Carrieri, MD, Division of Urolgy and Renal Transplantation, Università degli Studi di Foggia, Viale Luigi Pinto, 71100 Foggia, Italy; E-mail: [email protected] 112 Archivio Italiano di Urologia e Andrologia 2005; 77, 2 CASE REPORT Bizarre leiomyoma of scrotum. Antonio Celia, Morgan Bruschi, Stefano De Stefani, Beniamino Baisi, Anna Maria Cesinaro, Salvatore Micali, Maria Chiara Sighinolfi, Giampaolo Bianchi Chair of Urology, University of Modena and Reggio Emilia, Italy Summary Genital leiomyomas of the scrotal skin are extremely rare benign tumors, originating from the tunica dartos of the scrotum. We report our experience with one patients with schrotal bizarre leiomyoma. KEY WORDS: Mesothelial tumors; Leiomyoma; Scrotum. INTRODUCTION DISCUSSION Scrotal mesothelial tumors, and in particular the leiomyoma are very rare. The leiomyoma is a benign tumor arising from smooth muscle and in the scrotum it arises from vascular smooth muscles, from pila erector muscles or from the dartos. In literature we found 54 cases described. The leiomyoma arise at any age, they are often asymptomatic, but sometimes they seem like an aching bulk. Generally, the mass is mobile, small, unilateral, and sometimes it is pedicle, with smooth surface and with slow growth. The tumor diagnosis is histological and the surgery ablation permits the recovery. We report our experience with one patients with scrotal bizarre leiomyoma. The first case of scrotal leiomyoma was described by Foster in 1858; since then 54 cases have been reported in literature. The leiomyoma of the scrotum arises could occur at any age (min. 1.5 years; max. 78 years), usually appear like a round mass, and they are rarely bilateral (1). They are occasionally pedunculated or ulcerated and the size is variable (raging from 0.5 cm to 8 cm). Six of 54 cases of scrotal leiomyoma reported in literature, at histological examination, show the presence of bizarre nuclei, that is characterized by the presence of nuclear pleomorphism, with big and vesicular nuclei, intranuclear invagination of cytoplasmic globules that produces pseudonuclei (2), like of our experience. The presence of pleomorphic nuclei and internuclear invagination of cytoplasmic glunules (pseudonuclei), CASE REPORT A 52 year-old man presented with acute pain at right scrotal, and he complained 1-year history of right scrotal pain, where it was a small mass. Physical examination disclosed a superficial, regular mass with a smooth surface in the right scrotal. The mass was excised through a right scrotal approach. Macroscopically, the tumor was like a nodular pedicle formation of 1.7 cm in diameter, with smooth surface and yellowish. Histology revealed that the tumor was composed from interlacing fascicles of spindle-shaped cells, with abundant eosinophilic cytoplasm. The cells showed nuclear pleomorphism, that it’s called “bizarre nuclei” with big and vescicular nuclei, intranuclear invagination of cytoplasmic globules that produces pseudonuclei. Without mitotic figures and areas of necrosis (Figure 1). Immunohistochemically, the smooth muscle boundless stained positively for actin and desmin (Figure 2). Figure 1. Spindle-shaped smooth-muscle cells with pseudonuclei (H & E reduced from x200). Archivio Italiano di Urologia e Andrologia 2005; 77, 2 113 A. Celia, M. Bruschi, S. De Stefani, B. Baisi, A.M. Cesinaro, S. Micali, M.C. Sighinolfi, G. Bianchi Figure 2. Immunohistochemistry: the neoplastic cells are positive for desmine antigens, showing muscular origin of the lesion. Reduced from X100. have relevant importance because this histological pattern is similar to malignancy (leiomyosarcoma). The leiomyomas with bizarre nuclei are also called symplastic and they are similar to uterine symplastic leiomyoma (3). The absence of mitotic figures and necrosis leans towards a benign lesion and the surgery ablation permits the correct diagnosis and the recovery. REFERENCES 1. Slone S, O'Connor D. Scrotal leiomyoma with bizaue nuclei: a report of tree cases. Mod. Pathol. 1998; 11:282 2. Sanchez Merino JM, Gomez Cisneros SC, Fernandez-Flores A, Parra Munter L, Lopez Pacius JC, Garcia Alonso J Scrotal Leiomyoma. Actas Urol Esp 2001; 25:233 3. De Rosa G, Boscalino A, Giordano G, Donofrio V, Staibano S, Maio C, et at. Symp1astic leiomyoma of the scrotum: a case report. Pathologica 1996; 88:55 Correspondence: Antonio Celia, MD, Urologist, University of Modena and Reggio Emilia, Policlinico di Modena, via del Pozzo 72 - 41100 Modena, Italy; E-mail: [email protected] 114 Archivio Italiano di Urologia e Andrologia 2005; 77, 2 CASE REPORT Liposarcoma of the spermatic-cord: description of two clinical cases and review of the literature. Michele Malizia, Eugenio Brunocilla, Alessandro Bertaccini, Fabiano Palmieri, Giovanni Vitullo, Giuseppe Martorana Department of Urology, University of Bologna, Policlinico S. Orsola-Malpighi General Hospital, Bologna, Italy. Summary Spermatic cord liposarcoma is a rare tumor; currently only 161 cases are described in literature. Natural history of these tumors is marked by the high local recurrence rate. Radical surgery represents the therapy of choice whilst uncertain is the role of regional and retroperitoneal lymphadenectomy as well as the usefulness of adjuvant radiotherapy or chemotherapy. In this paper we describe our experience of two cases treated at our Department between 1995 and 2002 and discuss about the clinical management of this misleading tumor in the light of the several experiences reported in literature. KEY WORDS: Liposarcoma; Spermatic-cord; Orchiectomy; Lipoma-like; Lymphadenectomy. FIRST CASE A 73-year-old man underwent urological consultation in January 1995 for a right scrotal mass lasting for several months and diagnosed by family doctor as inguinoscrotal hernia. Physical examination confirmed the presence of a painless and irreducible soft scrotal mass. The patient was admitted for a hernia repair. Surgery resulted technically difficult because the spermatic cord was enveloped by a sort of capsulated adipose tissue, extending through the internal inguinal ring, that prevented any attempt of dissection of the funicle from peritoneal-bag. Therefore a radical orchiectomy was performed. Macroscopically, the lesion was a capsulated mass (15 x 10 x 4 cm) composed mostly of adipose tissue infiltranting the spermatic structures. Histological examination revealed well differentiated liposarcoma. The patient was discharged on the 3rd post-operative day. No adjuvant therapy was planned. After 8 years he is well and free from local recurrence and distant metastases. increased epididymis volume and a painless mass involving the spermatic cord. Scrotal echography revealed a regular testis structure while the distal portion of epididymis showed an irregular outline without anomalous echostructures. Utrasounds of the lower abdomen as well as the testicular cancer markers turned out negative. The patient underwent an explorative surgery which revealed a mass of adipose tissue well capsulated, multiloculated, involving the epididymis and the vas deferens (Figure 1), extending until 3 cm from the internal inguinal ring. Figure 1. Surgical specimen: a mass of adipose tissue, well capsulated, that involves the epididymis and the vas deferens. SECOND CASE A 47-years old man came to our Department in February 2002 for a painless lump of the right emiscrotum. He denied any injury or infection in the testis involved. Physical examination revealed a normal testis, a slightly Archivio Italiano di Urologia e Andrologia 2005; 77, 2 115 M. Malizia, E. Brunocilla, A. Bertaccini, F. Palmieri, G. Vitullo, G. Martorana The patient underwent right radical orchiectomy and the histopathological diagnosis was a well differentiated liposarcoma, lipoma-like, involving the structures of spermatic cord. The patient was discharged without any adjuvant therapy and at 20 months follow-up he is disease-free. DISCUSSION Paratesticular liposarcomas are rare tumors (1). They may arise from the epididymis, the mesenchimal layers surrounding the testis and the appendages or the spermatic cord (2). In adults more than 75% of these lesions arise from SC (3). The wall of the spermatic funicle is composed by: 1) an external fascia, wich is an extension of the external oblique aponeurosis; 2) the cremasteric layer; 3) an internal fascia, wich is an extension of the trasversalis fascia. Often it is difficult to localize the precise origin of the tumor. Most of the spermatic cord tumours are benign (7080%) and include primarily lipomas (4, 6). Malignant lesions of spermatic cord are usually sarcomas. Rabdomyosarcomas are the most aggressive and predominate in young people. The other histological forms of sarcomas (leiomyosarcomas, fibrosarcomas and liposarcomas) are most frequently observed in the adult population. Liposarcomas account approximately for 3 to 7% of all spermatic cord tumors (7). Liposarcoma of the spermatic cord usually presents as a painless, irregular mass clearly distinct from the testis, usually negative on transillumination or lightly positive. Liposarcomas of little dimension can be quite easy differentiated but the increased in size may be misleading (3). The clinical diagnosis in these conditions may be difficult, since the tumour can easily be mistaken for an inguinal hernia, hydrocele, funiculocele, spermatocele, hematocele as well as tumours of the testis and epididymis (7-9). Some authors reported that the incidence of liposarcoma is approximately less than 0,1% of the inguinal hernia (10). The ultrasounds can evidentiate a mass with different echo-densities but usually is not specific and decisive. The computed tomographic scan (CT) may make the diagnosis in the half of the cases and may have an important role in defining the involvement of the anterior abdominal wall and/or retroperitoneum. Also magnetic resonance (MR) produces excellent images. Conversely, lymphangiogram should be avoided because it did not yield any positive findings. Due to the high rate of local recurrence (55-70%) and considering the advanced age of the patients involved, a radical surgery with a wide local excision of the tumor is appropriate. Occasionally, the inguinal tumor may extend to lower abdomen and retroperitoneum. Three cases have been reported in the literature. In one, the mass originated from the spermatic cord and extended through the internal inguinal ring to lower abdominal region (11, 12). In another case, a large retroperitoneal mass arising from spermatic left behind was found on CT scan, one month post-operatively 116 Archivio Italiano di Urologia e Andrologia 2005; 77, 2 (13). Liposarcomas tend to spread primarily by local extension. No therapeutic advantage has been attributed to superficial inguinal or retroperitoneal lymphadenectomy because liposarcomas tend to metastasize hematogenously rather than lymphatics (10). In only one case of paratesticular liposarcoma a retroperitoneal lymph node dissection was performed after radiotherapy (14). Radiation therapy seems to have a role in the control of some liposarcomas, especially those at high risk for local failure (15, 16) but the results are controversial. Likewise, a beneficial effect of adjuvant chemotherapy has been reported in two cases, but the follow-up has been too short (8). Doxorubicin has been used occasionally (15). Liposarcoma of the spermatic cord is a rare lesion that should be considered in the differential diagnosis of any non-cystic scrotal mass. Ultrasounds and, more specifically, CT scan and MR may help in the diagnosis. Patients with tumors extending to the inguinal ring should be assessed for intra-abdominal extension of neoplastic lesion. The ideal treatment is radical orchiectomy. Adjuvant radiotherapy should be considered in tumors of intermediate or high histological grade and in recurrent liposarcoma. Retroperitoneal lymphadenectomy does not seem to offer any additional therapeutic benefit. The role of chemotherapy is not well defined. REFERENCES 1. Soler JL, Zulavaga Gomez A, Hidalgo Dominguez MR. Liposarcoma of the spermatic cord: a report of a new case and review of the literature. Acta Urol Esp 1999; 23:447 2. Gowing NF. Paratesticular tumors of connective tissue and muscles. In: Pathology of the Testis. In: Pugh RC. Oxford: Blackwell Scientific Publications (ed), 1976 3. Sogani PC, Grabstald H and Whitmore WF Jr. Spermatic cord sarcoma in adults. J Urol 1978; 120:301 4. Banowsky LH and Schultz GN. Sarcoma of the spermatic cord and tunics: review of the literature, case report and discussion of the role of retroperitoneal lymphnode dissection. J Urol 1970; 103:628 5. El-Badawi AA and Al-Ghorab MM. Tumors of the spermatic cord: review of the literature and report of a case of lymphangioma. J Urol 1965; 94:445 6. Pack GT and Pierson JC. Liposarcoma: study of 105 cases. Surgery 1954; 36:687 7. Certo LM, Avetta L, Hanlon JT, Jacobs D. Liposarcoma of spermatic cord. Urology 1988; 31:168 8. Johnson DE, Harris JD, Ayala AG. Liposarcoma of spermatic cord. Urology 1978; 11:190 9. Vorstman B, Block NL, Politano VA. The management of spermatic cord liposarcomas. J Urol 1984; 131:66 10. Montgomery E, Buras R. Incidental liposarcomas identified during hernia repair operations. J Surg Oncol 1999; 71:50 11. Treadwell T, Treadwell MA, Owen M, McConnel TH, Ashworth CT. Giant liposarcoma of the spermatic cord. South Med J 1981; 74:753 Liposarcoma of the spermatic-cord: description of two clinical cases and review of the literature 12. Chan YF, Yuen MY, Ma LT and Li MK. Recurrent dedifferentiated liposarcoma of the spermatic cord simulating malignant fibrous histiocytoma: an immunohistochemical and ultrasturctural study. Phatology 1987; 19:99 13. Russo P, Brady MS, Conlon K, et al. Adult urological sarcoma. J Urol 1992; 147:1034 14. Blitzer PH, Dosoretz E, Proppe KH and Shipley WU. Treatment of malignant tumors of the spermatic cord: a study of 10 cases and review of the literature. J Urol 1981; 126:611 15. Reitan JB and Kaalhus O. Radiotherapy of liposarcomas. Br J Radiol 1980; 53:969 16. Ballo MT, Zagars GK, Pisters PW, et al. J Urol 2001; 166: 1306 Correspondence: Michele Malizia, MD, Department of Urology, University of Bologna, S. Orsola-Malpighi General Hospital, Via P. Palagi 9 40138 Bologna, Italy; E-mail: [email protected] Archivio Italiano di Urologia e Andrologia 2005; 77, 2 117 CASE REPORT A rare case of bladder fibroepithelial polyp in childhood. Athanasios George Zachariou1, Ioannis Nikolaos Manoliadis2, Paraskevi Antonios Kalogianni1, George Konstantinos Karagiannis1, Dimitrios Jonh Georgantzis1 Elpis Hospital, Volos, Greece; 2Interbalkan Medical Centre, Thessaloniki, Greece 1 Summary Objective: To present a rare case of a benign polyp in a child. Very few cases of urinary tract fibroepithelial polyps in the bladder are reported in the international literarature and they are even less common in children. Material and Methods: A 14-yearold boy presented at the Urology Department of “Elpis” Hospital complaining of painless macroscopic hematuria during the last six months. The patient did not report previous urinary tract disorders. After a thorough laboratory investigation, which included urinalysis, urine culture, ultrasonography, intravenous pyelography and cystoscopy the presence of an exophytic papillary tumor in the bladder was identified. The lesion was removed transurethrally. Results: The biopsy set the diagnosis of fibroepithilial polyp, which is a rare benign neoplasm and occurs in patients of nearly all ages. Polyps are located usually in the ureteropelvic junction, the upper third of the ureter and the posterior urethra. They are rarely found in the bladder, especially in the childhood. KEY WORDS: Fibroepithelial polyp; Bladder; Childhood. INTRODUCTION Fibroepithelial polyps are rare benign neoplasms. They have mesodermal origin like fibroma, leiomyoma, neurofibroma and hemangioma. They are usually located in the upper part of the ureter, the ureteropelvic junction in adults and in the posterior urethra in children (1). In the international literature there are very few cases of fibroepithelial polyps localised in the urinary bladder of children (2). MATERIAL AND METHODS A 14-year-old male patient presented in the Urology Department complaining of painless macroscopic hematuria during the last six months. The patient did not report urinary tract infections, injuries or other diseases (congenital or acquired) which could possibly cause hematuria. A complete blood cell count, levels of serum electrolytes and creatinine, and results of cytologic evaluation of voided urine were normal. Urine examination showed 0 to 2 white blood cells and 18-20 red blood cells per optical field. Urine culture was sterile. Ultrasonography of the kidneys gave no abnormal findings, ultrasonography of the bladder displayed a papillary lesion in the posterior surface (Figure 1). The intravenous 118 Archivio Italiano di Urologia e Andrologia 2005; 77, 2 pyelography that followed did not reveal anything pathological neither from the upper nor from the lower urinary tract. In the bladder there were no filling defects. Cystoscopy revealed a whitish exophytic papillary tumor in the left posterior surface of the bladder, behind the trigone, 1.5 in height and 1.5 cm in width (Figure 2). There were no inflammatory lesions or other pathological structures somewhere else in the bladder. Figure 1. Ultrasonography of the bladder. A papillary lesion is located in the posterior surface. A rare case of bladder fibroepithelial polyp in childhood Figure 2. Cystoscopic view of the lesion. Figure 3. The fibroepithelial polyp is characterized by normal or hyperplastic urothelium overlying an intact basement membrane with extensive submucosal edema, dilated blood vessels, chronic inflammatory cells, and fibrous stroma (hematoxylin-eosin, x40). RESULTS The patient underwent transurethral resection without postoperative complications. The histopathological evaluation revealed a papillary lesion with fine fibrovascular stalk supporting epithelial layers of normal transitional cells. The epithelium in places was either absent or formed intraepithelial nests. These findings suggested the diagnosis of fibroepithelial polyp of the bladder (Figure 3). The patient did not have any more attacks of hematuria and 4 months later had a cystoscopy which revealed a normal bladder with no evidence of tumors. Two years later the patient is free of any symptoms of the urinary tract. DISCUSSION The fibroepithelial polyps of urinary tract are rare benign neoplasms and occur in patients of nearly all ages. They are located usually in the ureteropelvic junction, the upper third of the ureter and the posterior urethra (1, 3). Bolton et al. reviewed the literature on fibroepithelial polyps of the ureter (2). They estimated that approximately 140 cases had been reported in the English literature at the time of their review, but only 120 were evaluable. Thirty of the patients were 0.1 to 15 years old (mean age, 9 years; 80% males), and 90 patients were 17- to 76-years old (mean age, 37 years; 56% males). For unexplained reasons, males were affected more often in the younger age group, while there was a near equal distribution of males to females in the older age group. In the international English literature there are very few reports about bladder polyps. One was about a bladder hamartoma in a 4-year-old girl with amartomatous intestinal polyps contained mucinous glands, smooth muscle and fibrous tissue (4). A bladder polyp was reported in an 8-month-old boy with BeckwithWeidemann syndrome contained myxoid fibrous tissue and smooth muscle bundles only (5). However, there are many studies which concern polyps of the posterior urethra (6, 7). When the polyp is located in the upper urinary tract, hematuria gross or microscopic, intermittent or constant, is the presenting symptom in 85% to 88% of reported cases, regardless of age at presentation. Other less frequent symptoms are pain, voiding problems, infection and mass (8). When the lesion is located in the lower urinary tract, hematuria coexists with mild obstructive symptoms, which in middle aged patients usually suggest benign prostatic hyperplasia (1). Macroscopically, the polyps were characteristically solid and firm with smooth branching mucosal surfaces. Microscopically, normal or hyperplastic urothelium enveloped an edematous loose fibrovascular stroma (7). The diagnosis in the majority of patients is based on clinical and laboratory findings (urine examination, urinary cytology, intravenous urography, computed tomography and cystourethroscopy). Cystourethroscopy is accepted as the most specific examination for the diagnosis of polyps. However, it is difficult for the doctor to collaborate with the child and anaesthesia is a necessity. The most widely used examination for the diagnosis of polyps in childhood is ultrasonography of the bladder, where polyps appear as echogenic foci projecting into the lumen.(9) Intravenous urography is rarely used because of radiation. In that case, polyps appear as pedunculated, radiolucent filling defects projecting into the lumen. The treatment of these lesions is transurethral resection with very good results. Reports of fibroepithelial polyps with malignant transformation are found in the literature but are rare (10). Rare instances of fibroepithelial polyps in association with calculi (11), Peutz-Jeghers syndrome (12), ureteral intussusception (13), and retrocaval ureter (14) have also been reported. REFERENCES 1. De Castro R, Campobasso B, Belloli G, Pavanello P. Solitary polyp of posterior urethra in children: report on seventeen cases. Eur J Pediatr Surg 1993; 3:2 2. Bolton D, Stoller ML, Irby P III. Fibroepithelial ureteral polyps and urolithiasis. Urology 1994; 44:582 Archivio Italiano di Urologia e Andrologia 2005; 77, 2 119 A. G. Zachariou, I. N. Manoliadis, P. A. Kalogianni, G. K. Karagiannis, D. J.Georgantzis 3. Fein AB, Mc Clennan BL. Solitary filling defect of the ureter. Semin Roentgenol 1989; 24:201 4. Keating MA, Young RH, Lillihei CW, Retig AB. Hamartoma of the bladder in a four year old girl with hamartomatous polyps of the gastrointestinal tract. J Urol 1987; 138:366 5. Williams MP, Imprahim SK, Rickwood AM. Hamartoma of the urinary bladder in an infant with Beckwith-Wiedemann syndrome Br J Urol 1990; 65:106 6. Goldberg SD, Sugar L. Giant fibroepithelial polyps of the female urethra: two case reports and review of the literature. Can J Surg 1989; 32:6 9. Hikmat, Gomez, Trane, Bove Giant Botryoid Fibroepithelial Polyp of Bladder with Myofibroplastic Stroma and Cystitis Cystica et Glandularis. Ped Devel Pathol 2003; 6:179 10. Zervas A, Rassidakis G, Nakopoulou L, et al. Transitional cell carcinoma arising from a fibroepithelial polyp in a patient with duplicated upper urinary tract. J Urol 1997; 157:2252 11. Oesterling JE, Lui HY, Fishman EK. Real-time multiplanar computerized tomography: a new diagnostic modality used in the detection and endoscopic removal of a distal ureteral fibroepithelial polyp and adjacent calculus. J Urol 1989; 142:1563 12. Sommerhaug RG, Mason T. Peutz-Jeghers syndrome and ureteral polyposis. JAMA 1970; 211:120 7. Blank C, Lissmer L, Kaneti J. Fibroepithelial polyp of the renal pelvis. J Urol 1987; 137:962 13. Fukushi Y, Orikasa S, Takeuchi M. A case of ureteral intussusception associated with ureteral polyp. J Urol 1983; 129:1043 8. Young RH. Pseudoneoplastic lesions of the urinary bladder and urethra: a selective review with emphasis on recent information. Semin Diagn Pathol 1997; 14:1333 14. Clements JC, McLeod DG, Greene WR, Stutzman RE. A case report: duplicated vena cava with right retrocaval ureter and ureteral tumor. J Urol 1978; 119:284 Correspondence: Athanasios G. Zachariou, MD, Spiridi 3, Volos - PC 38221 Greece; E mail: [email protected] 120 Archivio Italiano di Urologia e Andrologia 2005; 77, 2 TO THE EDITOR Whither the andrologic pathology of italian lads with the end of medical check up to conscripts. Nicola Mondaini, Gianluca Giubilei, Michelangelo Rizzo, Marco Carini Department of Urology, University of Florence, Italy. Whither the health of Italian lads with the end of conscription (1) as per January 1, 2005. It’s hard to envisage the aftermath. In Italy, medical check up at time of conscription was a valid tool for epidemiological research, especially for the study of incidence of andrological diseases among males 18 years of age. For the record, conscription begun in 1861, with the Unity of Italy (Unità d’Italia). Since then, all males when they reached the age of 18 had to join the Arm Forces, if they were eligible, of course. In the last 10 years, many studies (2) have been made, involving 80,000 young males, such studies have proved that andrological disorder is present in about 30-40% of youngsters who underwent examination performed by military medical doctors, and only the 10-20% of them were aware of carrying the disease (2-3). With such reports and figures in our hands, we could not ignore the matter, but had to ponder over: Whither the health of Italian lads, now that conscription has come to the end. Bearing in mind that for the majority of these boys, check up of genitalia apparatus was their first and most likely their last. In view of this situation, we urge General Practitioners and Paediatricians alike to pay extra care when performing check up. We strongly believe and must emphasize that if the matter is not dealt with extreme care, the issue could soon become serious, and the Public Health (in general) will have to face the appropiate consequences. Resolute actions must be taken at once. Italian Authorities, meanwhile, have promoted a congress in December 2004 (4), for the occasion a committee has been appointed in order to find a solution to solve the problem. One solution that has been thought of is to perform medical check up to all male students up to Grammar School, viz. up to 14 years old. This solution would help to prevent present and future sexual and fertility failure, as reproductive pathologies are characterized at this point by a considerable valence for their negative reflexes on birth rate as well. REFERENCES 1. http://www.altalex.com/index.php?idstr=6&idnot=7675 2. Mondaini N, Bonafe’ M, Di Loro F, Biscioni S, Masieri L, Ponchietti R. Andrologic disease in a population of 18 years old young men during conscription screening: how many were a first diagnosis? Minerva Urol Nefrol 2000; 52:63 3. Campodonico F, Michelazzi A, Capurro A, Carmignani G. Andrologic disease detected during army medical visit. Arch Ital Urol Androl 2003; 75:205 4. http://w3.uniroma1.it/MEDICFISIO/prev_andr_progr.ppt Correspondence: Nicola Mondaini, MD, Via Colleramole, 8 - 50029 Impruneta (Firenze), Italy; E-mail: [email protected] Archivio Italiano di Urologia e Andrologia 2005; 77, 2 121 64° CONVEGNO ASSOCIAZIONE UROLOGI LOMBARDI - ERBUSCO (BS), 3 LUGLIO 2004 GOLDEN COMMUNICATIONS The new transperineal-prerectal approach in posterior urethroplasty. Edoardo Austoni1, Andrea Guarneri1, Fulvio Colombo1, Enzo Palminteri2 Department and Chair of Urology, University of Milan, San Giuseppe Hospital, Milan, Italy Center for Urethral and Genitalia Reconstructive Surgery, Arezzo, Italy 1 2 Summary Objective: A new posterior urethroplasty is suggested for patients with pelvic fracture urethral distraction defect (PFUDD). Methods: 12 men, with PFUDD were treated with an anastomotic urethroplasty, using a transperineal-prerectal approach. All patients had a suprapubic tube in place and were impotent after pelvic trauma. The goal of this approach was to facilitate an extensive removal of the scar tissues around the prostatic apex to promote successful bulbo-prostatic anastomosis. Results: No patients had intraoperative, perioperative or postoperative complications. Urinary incontinence or rectourethral fistula was never observed. In 11 patients the postoperative mean peak flow was 20 ml/sec. The recurrence of the stricture occurred in 1 patient. Conclusions: The transperinealprerectal approach to the posterior urethra facilitated a free tension posterior end-to-end anastomosis, as an alternative to the transpubic anastomotic procedure. KEY WORDS: Pelvic fracture urethral distraction defect (PFUDD); Perineal prostatectomy; Posterior urethroplasty; Prerectal approach; Transperineal approach. INTRODUCTION The pelvic fracture urethral distraction defects (PFUDD) are currently managed by using a simple or elaborated perineal approach (1). The elaborated approach is combined with inferior pubectomy, and rerouting the bulbar urethra around the corporal bodies (1). The abdominal transpubic approach could be suggested for complex cases requiring a good exposure of the bladder neck (2). We describe a surgical technique for posterior urethroplasty, that uses the anatomical knowledge’s and facilities achieved for radical perineal prostatectomy. The perineum and the prostate are approached by using a transperinealprerectal approach, the prostatic apex is freed from the fibrous tissue due to the pelvic trauma, and pulled down on the perineum. The bulbar urethra is mobilized, and a free tension anastomotic repair is performed. MATERIALS AND METHODS From 1996 to December 2002, 12 men 39-to 64-years old (mean age 48), with PFUDD (Figure 1), underwent a posterior urethroplasty using transperineal-prerectal approach. All patients had a suprapubic cystostomy in place. Seven patients underwent previous attempt to repair by urethrotomy (4 cases) or urethroplasty (3 cases). 122 Archivio Italiano di Urologia e Andrologia 2005; 77, 2 Figure 1. Preoperative retrograde urethrography. The new transperineal-prerectal approach in posterior urethroplasty Figure 2. A: the prostate is fully mobilized, by using a Foley catheter inside the bladder neck; B: the prostatic urethral mucosa is opened and spatuled; C: the bulbar urethra is sutured to the prostate; D: the bulbo-prostatic anastomosis is completed. A B C D All patients were impotent after the pelvic trauma. The patient is placed in exaggerated lithotomy position, and a perineal U-shaped inverted incision is made at 1 cm from the anus towards to the ischial tuberositas. The superficial perineal fascia is incised and the ischiorectal fossae are exposed. The central tendon of perineum is identified and divided. The intrasphineteric access is developed along the rectal wall, and the recto-urethralis muscles are dissected. The posterior layer of the Denonvillier’s fascia is opened allowing the exposure of the membranous urethra and prostatic apex. A perineal midline incision is made and the bulbar urethra is freed, and transected at the bulbo-membranous junction. All the scar tissue is removed, and by using a Foley catheter inserted into the bladder neck, the prostate is fully mobilized, and pulled down (Figure 2 A). The prostatic apex is spatuled for the anastomosis (Figure 2 B). The corpora cavernosa are divided on the midline, and the bulbar urethra is sutured to the prostatic urethra (Figure 2 C). The bulbo-prostatic anastomosis is made without tension (Figure 2 D). A Foley silastic catheter 20 Ch. is left in place, and a suction drain is left in place for 2 days. Three weeks after surgery, a voiding cystourethrography is obtained, and the suprapubic tube is removed. RESULTS None of patients had intraoperative complications. There were no associated perioperative morbidities of bleeding or infection. No fistula or incontinence was observed. Clinical outcome was considered a failure anytime postoperative instrumentation was needed, including dilation. Follow-up of the entire series ranged between 12 to 60 months (mean 32). There were 11 successes (92%), and 1 failure (8%). In 11 patients the urethrography after 1 month, 6 months, and 12 months showed a wide lumen of the anastomosis without obstruction (Figure 3), and the patients have continued to void without difficulty or further instrumentation. In all patients the urofloumetry was repeated any 6 months and the peak flow ranged between 16 to 28 ml/sec (mean 20). The recurrence of the stricture occurred, 6 months after repair, in 1 patient, and a successful management was accomplished by endoscopy. The intracavernous injection of prostaglandins was an efficacious remedy to impotence in all patients. DISCUSSION One-stage perineal anastomotic repair can be accomplished in most instances using a stepwise approach of urethral mobilization, corporal separation, inferior pubectomy and supracrural urethral rerouting to accomplish urethral reanastomosis (1). Some authors sees no reason why urethral mobilization, crural separation, and urethral rerouting should be considered as risk factors in experienced hands and under usual circumArchivio Italiano di Urologia e Andrologia 2005; 77, 2 123 E. Austoni, A. Guarneri, E. Colombo., E. Palminteri Figure 3. Voiding urethrography 1 year after surgery. cumstances, a combined complex abdomino-perineal transpubic anastomotic procedure is required (1, 2). After a wedge pubectomy made during the transpubic urethroplasty, there is a tendency for the penis to drop back into the gap and cause erectile difficulties (2). This problem is compounded by the fairly frequent development of a hernia at this site, which can be difficult to repair (2, 5). In our technique, the inferior pubectomy and supracrural urethral rerouting are unnecessary steps, and the bulbar urethra do not require an extensive mobilization, thus reducing the risk of penile chordee, and ischemic damage to the distal urethral. Moreover, by using a wide dissection along the rectal wall, the scar tissues are more extensively removed, and the prostatic apex is easier mobilized, and pulled down on the perineum, thus reducing the gap for a free tension anastomosis. The vascular preservation of the distal bulbar urethra, the extensive removal of scar tissues, and the free tension anastomosis are all factors reducing the risk of failure over time. The transperineal-prerectal approach to the posterior urethra is not advisable when the patient is potent after the trauma, because the erection’s neural and vascular structures are fully compromised by the surgical steps around the prostatic apex. CONCLUSIONS stances (2). The prostatic apex should be cleared of fibrotic tissue, so that there is a clear channel through to the apex of the prostate, a widely opened prostatic urethra at the apex, and healthy prostatic urothelium clearly exposed (2). Failure to remove enough of the fibrotic tissue in the anastomotic area makes it difficult to approximate the mobilized bulbar urethra to the prostatic apex, and it is a cause of anastomotic failure (3). In the hands of inexperienced surgeon an inferior pubectomy is the step that is most likely to cause vascular or neural damage, and it is difficult to manoeuvre sutures within the depths of the perineum, particularly if the prostate is higher than usual and the inferior pubic arch is narrow (2). However, elaborated perineal anastomotic repair provided a successful outcome in 92% of patients (4). Most restrictures occur within 3 months after surgery or immediately after catheter removal, in prepubescent male and in redo cases (4), and are due to technical failure or ischemia (2). About 5% of posterior urethral distraction defects have complicating factors that preclude a perineal anastomotic repair (1). In these cir- The wide use of the perineal radical prostatectomy allowed us to improve our anatomical knowledge of the male perineum. In patients with complex PFUDD, in which the perineal approach is not advisable, the urologist familiar with the radical perineal prostatectomy may perform the bulbo-prostatic anastomosis by using a transperineal-prerectal approach. In experienced hands, the technique is safe and sure, and may represent an alternative to the complex combined abdomino-perineal approach, including transpubic urethroplasty. REFERENCES 1.Carr LK, Webster GD. Posterior urethral reconstruction. Perineal approach. Atlas Urol Clin North Am 1997; 5:125 2. Mundy AR. Reconstruction of posterior urethral distraction defects. Atlas Urol Clin North Am 1997; 5:139 3. Dixon CM, Torre P. Complications of urethral reconstruction. In Taneja SS, Smith RB, Ehrlich RM. (Eds), Complications of Urologic Surgery, Ed 3. Philadelphia, WB Saunders Company, 2001, p 509 4. Flynn BJ, Delvecchio FC, Webster GD. Perineal repair of posterior urethral stricture and defect: experience in 79 cases in the last 5-years. J Urol 2002; 167:15 5.Lenzi R, Selli C, Stomaci N, Barbagli G. Bladder herniation after transpubic urethroplasty. J Urol 1983; 130:778 Correspondence: Andrea Guarneri, M.D., Department and Chair of Urology, University of Milan, San Giuseppe Hospital, via S. Vittore 12 - 20123 Milan, Italy; E-mail: [email protected] 124 Archivio Italiano di Urologia e Andrologia 2005; 77, 2 64° CONVEGNO ASSOCIAZIONE UROLOGI LOMBARDI - ERBUSCO (BS), 3 LUGLIO 2004 GOLDEN COMMUNICATIONS Surgical treatment of metastases from renal cell carcinoma. Alessandro Antonelli, Danilo Zani, Alberto Cozzoli, Sergio Cosciani Cunico Department of Urology, University of Brescia, Brescia, Italy. Summary Introduction: Even if the number of curable renal cancers increased during the last decades, there is still a considerable amount of patients with distant metastases, evidenced at diagnosis or during the follow-up, without real curative therapeutic options. Materials and Methods: In the period between January 1983 and December 2003 we observed 252 metastatic patients among the 1187 surgically treated for renal cancer (21.2%). The metastatic disease was evidenced at the diagnosis of renal tumour in 118 patients (9.9%), during the follow up at a mean distance of 18.6 months in 134 (11.3%) and was in a single organ in 200 patients, in multiple sites in 52. A metastasectomy was performed in 113 cases, associated with chemo-immunotherapy in 16. Conversely, 44 patients received chemo-immunotherapy alone, 18 radiotherapy, and in the remaining 77 cases no curative therapies were applied. Results: The patients with a single-site metastasis who underwent metastasectomy, especially when pulmonary or adrenal, showed a better prognosis than the ones otherwise treated, while in the patients with bony metastases, multiple-site metastases and the ones who did not receive any curative therapies an extremely dismal prognosis was evidenced. However, a large amount of the patients with a single-site metastasis (79% on 159 treated patients) had a relapse of the disease, even when surgically treated (69%). Conclusions: At present, in the lack of any effective systemic therapies for metastatic renal cancer, surgery offers better survival rates than other choices (chemo-immunotherapy or radiotherapy). Thus, even if the initial bias in the selection of patients is surely significant, in our opinion, each patient with good performance status and a resectable metastatic lesion, better if pulmonary or adrenal, should undergo metastasectomy, that could provide long-term survival in a small part of the patients.The high rate of relapses remarks the actual need of an effective systemic therapy both for the patients who can and cannot undergo surgery for their metastatic disease. KEY WORDS: Renal cancer; Metastasis; Surgical treatment; Metastasectomy. INTRODUCTION MATERIALS The diagnosis of asymptomatic, small in diameter, lowstage and surgically curable renal neoplasms increased during the last years due to the wide diffusion of imaging diagnostic tools. Nevertheless there is still a remarkable amount of patients with distant metastases evidenced at diagnosis or during the follow-up who cannot benefit trom any curative therapies (1). We present our experience on 252 patients with distant metastases from renal cell carcinoma. At our department, between January 1983 and December 2003, among the 1187 patients that underwent surgery for renal cell carcinoma, distant metastases were evidenced in 252 cases (21.2%), discovered at diagnosis in 118 (synchronous metastasis, incidence 9.9%) and during follow-up in 134 (metachronous metastasis, incidence 11.3%) at a mean distance of 18.6 months (range 6-179 months) from the operation for renal tumour. AND METHODS Archivio Italiano di Urologia e Andrologia 2005; 77, 2 125 A. Antonelli, D. Zani, A. Cozzoli, S. Cosciani Cunico Table 1. Involved organ and adopted therapy in the 200 patients with a single-site metastasis (*pleura, vagina, thyroid, breast, pancreas, peritoneum, skin). Surgery Chemo-immunotherapy Radiotherapy No curative treatments Total Lung 35 33 1 24 94 Bone 16 2 14 8 40 Adrenal 28 - - - 28 Liver 3 3 - 6 12 Brain 3 1 - 1 5 Others* 11 5 3 3 21 Total 97 44 18 41 200 In 200 patients (79.3% of 252 metastatic patients) there was a single-site metastasis, while in the remaining 52 cases two or more organs were involved. In 97 patients with a single-site metastasis, a good performance status and a resectable mass, the metastatic disease was approached by the sole surgical treatment, while in 16 patients with a multiple-site metastatic disease, chemo-immunotherapy with interleukine-2 (IL-2) and/or interferon-alfa (IFN-α) was applied to treat the metastatic disease residuated after metastasectomy for a resectable lesion. No major surgical complications occurred following the overall 113 metastasectomies. A medical treatment with IL-2 and/or IFN-α was applied to the 44 patients with a single-site metastasis, a good performance status but an unresectable metastatic mass. A radiant therapy was adopted in 18 patients with single-site metastases, 14 of whom were affected by bone metastasis. The remaining 77 patients (30.5%, 41 with single-site and 36 with multiple-site metastases) received only palliative therapies with no curative aims. The Table 1 reports the involved organ and the adopted therapy in the cases with a single-site metastasis. Survival time was computed for all the patients starting from the time of the diagnosis of metastasis, delayed from the time of surgery for the renal tumour in the cases with metachronous metastases. Survival curves were estimated according to Kaplan-Meier method and differences were evaluated using the log rank test. stasectomy, 2 with chemo-immunotherapy and 2 by radiotherapy. Nine patients (4.5%, 8 patients treated by surgery, 1 with chemo-immunotherapy) are dead for other causes without evidence of relapses at 76.3 months (range 3-163 months); 51 (24.5%) are alive with a progression of the disease at 18.1 months (range 0-125 months); the remaining 106 cases (53%) died at a mean distance of 21.5 months (range 0-98 months). Altogether, at a mean distance of 21.2 months (range 3114 months) 126 on 159 (79%) patients affected by a metastasis in a single organ and treated with a curative aim, and, among them, 67 on the 97 surgically treated (69%), showed a further relapse of the disease. The estimated 3 and 5-years overall survival rates in the cases with a single-site metastasis were 55% and 45% respectively (Figure 1). Computing survival times from the diagnosis of metastasis, no significant differences in survival were evidenced between the patients with synchronous or metachronous metastasis. Concerning the cases with metastasis in a single site, the patients treated by surgery showed cause-specific surviFigure 1. Overall survival curves in patients with single-site or multiple-site metastases. 10 Bg-rank test p<0.0001 8 Among the 52 patients with multiple-site metastatic disease, 39 (75%) died for the disease at a mean distance of 12.8 months from the diagnosis of the metastasis, while the remaining 13 cases are alive with a progression of the disease at a mean interval of 14.2 months. The 3 and 5-years overall survival rates were less than 20% and 10%, respectively (Figure 1), and no differences were noted in dependence on the adopted therapies. Indeed, among the 200 patients with a single-site metastasis, 34 (17%) are free of disease at mean interval time of 56.6 months (range 6-184 months) from the diagnosis of the metastasis: 30 of them were treated by meta- 126 Archivio Italiano di Urologia e Andrologia 2005; 77, 2 Cum. survival RESULTS 6 4 Single-site 2 Multiple-site 0 0 25 50 75 100 Time 125 150 175 200 Surgical treatment of metastases from renal cell carcinoma Figure 2. Cause-specific survival curves depending on the adopted treatment in patients with single-site metastasis. 10 Log-rank test p<0.0001 Cum. survival 8 6 4 Surgery Radiotherapy 2 0 Chemo-immunotherapy No therapies 0 25 50 75 100 125 150 175 200 Time Figure 3. Cause-specific survival curves depending on the site of metastasis in patients with single-site metastasis treated by metastasectomy. 10 Log-rank test p<0.0028 Cum. survival 8 6 4 Lung 2 Adrenal Other sites Bone 0 0 25 50 75 100 125 150 175 200 Time val rates better than the ones of the patients treated by other curative therapeutic choices (chemo-immunotherapy or radiotherapy), while the prognosis of the patients who received only palliative therapies was markedly dismal (Figure 2). In regard to the sole surgically-treated cases and comparing different metastatic sites, the adrenal (28 patients) and the lung (36 patients) sites yielded the best survival rates, whereas the bone site (16 patients) showed the worse results (Figure 3). DISCUSSION The clinical evidence of a distant metastasis represents the visible presentation of an underlying undetectable systemic metastatic disease that cannot be cured by the sole surgical removal of the macroscopic lesions. However, at the present time the surgical treatment of metastasis from renal cell carcinoma finds its rationale in the lack of any other effective alternative options, even if achieving a complete cancer debulking could also improve the autologus immune responses against renal cancer. As a matter of fact some literature reports cautiously confirm that in a small and hardly selectable part of the patients affected by a metastatic renal cancer, the surgical treatment can offer curative results (2-6). In our opinion metastasectomy for renal cancer is thereby advisable in all the patients with good performance status and surgically resectable metastatic disease. In these conditions the procedure is usually affected by a minimum morbidity (“easy and safe”) and allows the certainty of the diagnosis of metastasis, giving at the same time a considerable psychological help to the patient. Even if it is quite obvious that the selection to indicate or not a surgical treatment constitutes a bias which is a matter of relevance and surely influences the better results of metastasectomy evidenced in our and other’s experiences (7), for these patients a correct prospectic study to test different treatments is not feasible at present. Confirming some literature data (8), also in our experience a multiple-site metastatic disease is burdened with a dismal prognosis in spite of the adopted therapy, while a single-site metastasis, especially if pulmonary or adrenal, synchronous or even metachronous, in a patient with good general conditions, constitutes the best indication for metastasectomy which offers better outcomes than other options. With these settings in a smoll number of cases we obtained long survival times without relapses of the disease after the metastasectomy, while with the other curative therapeutic options (medical or radiant) the results have been less favourable. The evidence of a bony metastasis carries a bad prognosis and any treatment should not be expected to be curative. Finally, we observed a high rate of relapses, even after the radical surgical withdrawn of all the detectable metastatic tissue, and this fact remarks the pressing need of a systemic therapy to treat patients with metastatic renal cancer (9). An effective chemotherapy should be applied when the metastasectomy is not feasible but should also be required after surgery to treat the microscopic metastatic disease and to lower the rate of relapses. CONCLUSIONS In our experience, about 20% of patients with renal cancer shows distant metastases, detected at diagnosis or during the follow-up. In the case of a single-site metastasis, moreover if pulmonary or adrenal, a resectable mass and a good performance status the surgical therapy shows better results than other choices and could give a curative result for a small amount of patients. Nevertheless an effective systemic way of treatment is absolutely necessary to treat metastatic renal cell carcinoma. Archivio Italiano di Urologia e Andrologia 2005; 77, 2 127 A. Antonelli, D. Zani, A. Cozzoli, S. Cosciani Cunico REFERENCES 1. Russo P. Seeking the solution to the problem of metastatic renal carcinoma. Cancer 2003; 97:2941 renal cell carcinoma who responded to interleukin-2-based immunotherapy. Cancer J Sci Am 1998; 4:86 2. Cozzoli A, Milano S, Cancarini G et al. Surgery of lung metastasis in renal cell carcinoma. Br J Urol 1995; 7:445 6. Janzen NK, Kim HL, Figlin RA, et al. Surveillance after radical or partial nephrectomy for localized renal cell carcinoma and management of recurrent disease. Urol Clin North Am 2003; 30:843 3. Kavolius JP, Mastorakos DP, Pavolvich C, et al. Resection of metastatic renal cell carcinoma. J Clin Oncol 1998; 16:2261 7. Mickisch GH. Multimodality treatment of metastatic renal cell carcinoma. Exp Rev Anticancer Ther 2002; 2:681 4. van der Poel HG, Roukema JA, Horenblas S et al. Metastasectomy in renal cell carcinoma: a multicenter retrospective analysis. Eur Urol 1999; 35:197 8. Han K-R, Pantuck AJ, Bui MHT et al. Number of metastatic sites than location dictates overall survival of patients with node-negative renal cell carcinoma. Urology 2003; 61:314 5. Lee DS, White DE, Hurst R et al. Patterns of relapse and response to retreatment in patients with metastatic melanoma or 9. Huland E, Heinzer H. Renal cell carcinoma: novel treatments for advanced disease. Curr Opin Urol 2003;13:451 Correspondence: Alessandro Antonelli, M.D., Clinica Urologica, Piazzale Spedali Civili, 1 - 25123 Brescia; E-mail: [email protected] 128 Archivio Italiano di Urologia e Andrologia 2005; 77, 2 64° CONVEGNO ASSOCIAZIONE UROLOGI LOMBARDI - ERBUSCO (BS), 3 LUGLIO 2004 GOLDEN COMMUNICATIONS Metastatic retroperitoneal renal cell carcinoma. A case for more aggressive approach. Risk and results. Pietro Tombolini, Michele Ruoppolo, Giuseppe Malagola, Fabrizio Rovera Department of Surgery, Operative Unit of Urology, S. Carlo Borromeo Hospital, Milan, Italy. Summary Our point of view in selected cases of bulky renal neoplastic disease was shown. A 43year-old white man was referred for large disseminated retroperitoneal mass after right radical nephrectomy and hilar lymphoadenectomy for locally advanced PT3 N3 M0 G3 renal cell carcinoma followed by interleukin-2 based immunotherapy. We attemped aggressive resection of visible disease with curative intent. Complete resection was technically very difficult with intragorative bleeding representing the major risk. Accidental injuries of aortic wall and vena cava were repaired. A partial incision of the right external iliac vein was performed. Complete removal of the large adenopathic masses was obtained. At 9 month follow-up the patient was free of disease. In conclusion, aggressive surgical approach with complete resection of disseminated retroperitoneal renal cell carcinoma may prolong disease-free survival. KEY WORDS: Renal cell carcinoma; Retroperitoneal; Metastases. INTRODUCTION SURGICAL TREATMENT Locally advanced renal cell carcinoma is a complex problem for both the physician and the patient. Although there is no standard treatment for locally advanced renal carcinoma, an aggressive surgical approach has been recommended. In patients, with no evidence of distant metastases and when the disease is confined in the retroperitoneum, surgical resection in combination with biological therapy should be considered. This paper shows our point of view in selected cases of enlarged neoplastic renal disease. On day 10 of March 2004 the patient underwent an aggressive attempt to resect visibile disease with curative intent, at our department. An abdominal midline incision was performed and then we removed extensive adhesion between liver and gross bowel. After mesenteric inferior arteria closure, retroperitoneum was widely exposed. Adenopathic mass removal started from left renal vein and had proceeded towards right edge. Complete surgical resection was technically very difficult, as intraoperative bleeding represent the major risk. In this patient a large accidental injury of aortic wall occurred. The massive hemorrhage was controlled with vascular clamps placed proximal and distal to the injury on the iliac arteries, and the lesion was repaired with a continuous 5-0 polypropylene suture. During the retro-caval resection, a sudden tear of the vena cava happened; because the impossibility of positioning a Satinsky clamp, we performed the suture after the application of two Allis clamps. Profound hypotension, nevertheless, occurred. The vena cava was reconstructed with the folding of its wall. Another, deliberate, vascular lesion was caused to completely remove a large mass involving the right external iliac vein. In this case, we performed a partial excision of the vein’s wall. CASE REPORT A 43-year-old white man was referred to us on February 2003, for large disseminated retroperitoneal mass. On September 2003 the patient was managed, elsewhere, by right radical nephrectomy and only hilar limphadenectomy for renal cell carcinoma locally advanced pT3N3M0G3, and then treated by interleukin-2 based immunotherapy according to Azpodien. CT scan shows enlarged adenopathic running from renal vessels to iliac bifurcation and moreover at iliac right vessel, both common and external. A bulky disease surrounded vena cava and another mass involved contralateral renal pedicle. The tumour had been estimated unresectable elsewhere. Archivio Italiano di Urologia e Andrologia 2005; 77, 2 129 P. Tombolini, M. Ruoppolo, G. Malagola, F. Rovera RESULT The patient was discharged by Hospital in 11th postoperative day. He only reported superficial disaesthesia in his right leg, because of injury of femoral nerve. At 9-month follow-up, the patient is free of disease. He is still receiving adjuvant therapy with alpha-interferon and vinblastin. DISCUSSION Retroperitoneal disseminated renal cell carcinoma represent a complex problem for the physician and patient. The 1-year survival rate ranging from 10 to 30%. Although there is no standard treatment for advanced or recurrent neoplastic disease, an aggressive surgical approach has been recommended. A large review of patients treated with an aggressive surgical approach as a single modality for locally recurrent renal cell carcinoma shows that 30 to 40% of patients had no evidence of disease at a median follow-up of 36-48 months. Many previous reports have supported the importance of an aggressive debulking surgical approach before starting biological therapy. The combination of immunotherapy and surgery was well tolerated and did not increase morbidity above that of surgery alone. Our experience demonstrates that some patients with disseminated retroperitoneal renal cell carcinoma treated with an aggressive surgical approach may have prolonged disease-free survival. It is mandatory to obtain complete resection off all masses to achieve long-term control and decrease the risk of local or at-distant progression. However, this approach is associated with potential risk of intraoperative complications, particularly massive hemorrhage. REFERENCES 1. Tanguay S, Pisters L, Lawrence D, Dinney C. Therapy of locally recurrent renal cell carcinoma after nephrectomy. J Urol 1996; 155:26 2. Esrig D, Ahlering TE, Lieskovsky G, Skinner D. Experience with fossa recurrence of renal cell carcinoma. J Urol 1992; 147:1491 Corrispondence: Pietro Tombolini, M.D., U.O. Urologia, Ospedale S. Carlo Borromeo, Via Pio XI, Milano. Italy 130 Archivio Italiano di Urologia e Andrologia 2005; 77, 2 64° CONVEGNO ASSOCIAZIONE UROLOGI LOMBARDI - ERBUSCO (BS), 3 LUGLIO 2004 GOLDEN COMMUNICATIONS Dorsal free graft urethroplasty according to Barbagli. Minimum follow-up of 2 years. Paolo Parma, Bruno Dall’Oglio, Lino Schiavon, Marco Luciano, Stefano Guatelli Vincenzo Galletta, Candido Bondavalli Urologic Department C. Poma Hospital, Mantova, Italy. Summary Series of free graft methroplasties for structure of the urethra according to Barbagli. Fifteen men underwent dorsal free graft methroplasty for structures situated in the penile urethra in 6 cases, in the bulbous urethra in 7 and in the urethra geno bulbaris in 2. The length of the structures ranged from 1.5 to 13 cm. In all the patients but one uroflow was satisfactory at a mean follow-up of 40 months. In one patient a reument structure occured 8 months after treatment and was successfully treated with cold urethrotomy. In conclusion, dorsal free graft urethroplasty is a safe and fairly simple procedure in long bulbous stenosis and penile multi stenosis. KEY WORDS: Urethra; Urethral stricture. INTRODUCTION the patch graft (1). Two weeks later a voiding urethroIn 1996, Barbagli developed a new technique of urethgraphy is done and if fistuals are not present the catheroplasty with the use of a free graft positioned on the ter is removed. dorsal part of the urethra (1). This procedure consists of: isolating the urethra from the corpora cavernosa; urethral rotation; longitudinal opening along its dorsal MATERIALS AND METHODS surface. A free skin graft or a buccal mucosa graft is From Jannuary 1997 to April 1999, 15 men aged 26 to sutured to the albuginea of the corpora cavernosa and 82 underwent dorsal free graft urethroplasty. The stricthen the margins of the open urethra are sutured to the tures were situated in the penile urethra in 6 cases, in the margins of the graft (1, 2). bulbous urethra in 7 and in In the close strictures of the the urethra peno bulbaris in proximal bulbar urethra Figure 1. 2 cases. Stricture etiology with spongiofibrosis assoPreoperative retrograde urethrography shows multiple was iatrogenic in 8 patients, ciated, it is easier to dissect strictures of the anterior urethra for length of 13 cm. traumatic in 4, inflammatory completely the urethra at in 1, unknown in 2. The the level of the stricture, to length of the strictures ransuture the free graft to the ged from 1.5 to 13 cm albuginea of the corpora (Figure 1). 14 patients were cavernosa and to the proxiuncircumcised and the foremal edge of the urethral skin provided a graft of suffimucosa. The distal urethra cient size and length. In the is opened along its dorsal case of the circumcised surface and the left mucosal patient a free graft buccal margin of the opened distal mucosa was used. All urethra is sutured to the left patients were evaluated side of the patch graft. The preoperatively with retrograurethra is rotated back to its de and voiding urethrooriginal position and the graphy to define stricture right urethral margin is location and length, and sutured to the right side of Archivio Italiano di Urologia e Andrologia 2005; 77, 2 131 P. Parma, B. Dall’Oglio, L. Schiavon, M. Luciano, S. Guatelli, V. Galletta, C. Bondavalli Figure 2. Retrograde urethrography after dorsal preputial free graft urethroplasty. ultrasonography was performed to evaluate the extent of spongiofibrosis. The follow-up of the patients consists in performing a uroflowmetry every 4 months and a cystourethrography yearly or when urine flow is less than 13 ml per second. RESULTS In all patients but one, uroflow has mantained satisfactory at a mean follow-up of 40 months (range 27-52). In 1 patient a recurrent stricture occurred 8 months after intervention and was succesfully treated with cold urethrotomy. In 1 case of urethral stricture of 13 cm of length a slight ventral recurvatum of the penis occurred. The urethroplasty with dorsal graft of buccal mucosa did not present recurrent stricture at a mean follow-up of 32 months. Diverticulas, fistulas and graft necrosis did not occur in any patients. DISCUSSION The primary indication for the use of dorsal free patch urethroplasty is a lesion longer than 1 cm for strictures of the penile urethra, and a lesion longer than 2 cm for strictures of the bulbous urethra. Contraindications are the presence of an extensive spongiofibrosis causing almost complete obliteration of the urethral lumen and the presence of chronic infection (associated urethral stones, urethral pseudodiverticulus, fistulas or paraurethral abscesses) (1-3). Dorsal free graft urethroplasty is easier to perform than pedicle graft urethroplasty. The free patch dorsally placed receives a good mechanical support and an adequate vascular supply, so it has a low incidence of necrosis and of urethrocele. With this approach, bleeding from the corpus spongiosum is considerably reduced as the urethral lumen is dorsally located (4). Even if the graft should necrose, the urethral mucosa regenerates according to the principles of Browne and Monseur, provided that a catheter is left indwelling for sufficient time. CONCLUSIONS In large bulbous stenosis and penile multi stenosis, dorsal free graft urethroplasty is a safe surgery (bleeding is reduced and the degloving of the penis is not extensive), fairly simple, with few complications and not influenced by stenosis length. We need a longer follow-up to test the efficacy of these procedure as the strictures can also recurr 10 or 15 years after surgery. REFERENCES 1. Barbagli G, Selli C, Tosto A, Palminteri E. Dorsal free graft urethroplasty. J Urol 1996; 155:123 2. Barbagli G, Selli C, Tosto A. Reoperative surgery for recurrent structures of the penile and bulbous urethra. J Urol 156:76 3. Barbagli G, Selli C, Di Cello V, Mottola A. A one stage dorsal free-graft urethroplasty for bulbar urethral strictures. B J Urol 1996; 78:929 4. Andrich DE, Leach CJ, Mundy AR. The Barbagli procedure gives the best results for patch urethroplasty of the bulbar urethra. BJU International 2001; 88:385 Corrispondence: Paolo Parma, M.D., U.O. Urologia, Ospedale C. Parma, Mantova 132 Archivio Italiano di Urologia e Andrologia 2005; 77, 2 64° CONVEGNO ASSOCIAZIONE UROLOGI LOMBARDI - ERBUSCO (BS), 3 LUGLIO 2004 GOLDEN COMMUNICATIONS The reconstruction of “complex” ureteral lesions. Pierpaolo Graziotti, Alessandro Piccinelli, Guido Giusti, Mauro Seveso Gianluigi Taverna, Alessio Benetti, Luisa Pasini, Silvia Zandegiacomo Department of Urology, Istituto Clinico Humanitas, Rozzano, Italy. Summary A total of 13 patients with ureteral lesions wider than 12 cm in length and/or previous radiation treatment have been submitted to reconstructive treatment. Four patients with lesions after radiation therapy were treated with ileal ureter and contemporary bladder augmentation, one with ureteroneocistostomy combined with psoas hitch procedure and one combining psoas hitch and Boori Plap technique. The association of psoas hitch with Boari Flap technique were also used to treat two patients with the undesired outcome of vascular procedure. A patient after complete ureteral stripping following ureteroscopy was submitted to ileal bladder substitution. Two renal autotransplantations were performed in a patient with extensive stricture of the ureter following multiple endourological procedure and in a patient with negative outcome of previous attempt of open ureteral defect reconstrucion following abdominal trauma. KEY WORDS: Ureter; Radiation treatment. INTRODUCTION With this arbitrary term we mean ureteral lesions, ensuing from any etiological event, sharing at least one of the following two conditions: extension wider than 12 cm in length and/or previous radiation treatment. As it is well known, these are the most difficult ureteral defects to repair either for the clinical strategy, or surgical technique or the post-operative complications. MATERIAL AND METHODS In our hospital from January 1998 to December 2002 a total of 13 patients have been submitted to a reconstruction of this kind of ureteral defects. Seven were female and six male, with age ranging between 30 and 71 years (mean 47). Six patients came to us for the complications following pelvic surgery combined with subsequent radiation treatment, two following a vascular surgery procedure, four after endourologic manoeuvre and one after the failure of ureteral reconstructive operation for major abdominal trauma. In all cases the ureteral defect was unilateral and a percutaneous nephrostomy drainage was always positioned before surgical repair attempt. Four patients with lesions after radiation therapy were treated with ileal ureter and contemporary bladder augmentation, one with ureteroneocistostomy combined with psoas hitch procedure and one combining psoas hitch and Boari flap technique. The association of psoas hitch with Boari flap technique were also used to treat two patients with the undesired outcome of vascular procedure and for two lesions following endourological procedure. The extent of the defects allowed only a direct anastomosis between upper ureter and the bladder flap, without antireflux technique (Figures 1a and 1b). A patient after a complete ureteral stripping following ureteroscopy, were submitted to ileal ureter substitution. Two renal autotranspantations were performed, one in a patient with extensive stricture of the upper ureter following multiple endourological procedures, and one after the negative outcome of previous attempt of open ureteral defect reconstruction following abdominal trauma. RESULTS Post-operative complications were limited. Major bleeding requiring a second look and a subsequent laparocele was observed in a case of renal autotransplantation. A patient, operated with the psoas bladder hitch + Boari flap combined procedures, complained a pyeloArchivio Italiano di Urologia e Andrologia 2005; 77, 2 133 P. Graziotti, A. Piccinelli,G. Giusti, M. Seveso,G. Taverna, A.Benetti, L. Pasini, S. Zandegiacomo nephritis after ureteral stent removal, promptly solved with antibiotic therapy. With a mean follow-up of 26 months (range 4-52) all patients present a regular ureteral urine transit without upper tract dilatation. A temporary flank pain during micturition, spontaneously disappeared after few weeks, was reported by all patients treated with psoas bladder hitch+Boari flap procedure. In a case of solitary kidney with preoperative impairment of renal function (serum creatinine 5.2 mg/dl), despite the regular appearance of the reconstructed urinary system, creatinine value did not return to normal (3.2 mg/dl), probably because of permanent parenchymal renal damage. Two patients treated with ileal ureter and bladder augmentation, complain episodes of nocturnal urine incontinence and recurrent asymptomatic urinary tract infection. In one of these patients a significant silent dilatation of controlateral ureter was also evident due to a progression of retroperitoneal fibrosis following radiation therapy. Figure 1. A: Permanent lesion of lumbar ureter following vascular surgery operation; B: IVP two years after surgery. A CONCLUSIONS Long ureteral defects are lesions not commonly observed in daily practice and this is the main reason of our limited experience in number of cases even if it is quite wide for the type of lesions and the surgical solutions adopted. On the base of our data we can assert that with a very precise therapeutic strategy and adequate experience in reconstructive surgery, good results can be obtained in the treatment of “complex” ureteral lesions. B REFERENCES 1. Pagano F, Graziotti P. Le grandi perdite di sostanza dell’uretere. Riv. Radiologia 1980; 20:9 2. Passerini Glazel G, Meneghini A, Aragona F, Oliva G, Milani C, Pagano F. Technical options in complex ureteral lesions: “ureter sparing” surgery. Eur Urol 1994; 25:273 3. Goodwin WE, Winter CC, Turner RD. Replacement of the ureter by small intestine: clinical application of the ileal ureter.. J Urol 1959; 81:406 4. Novick AC, Jackson CL, Straffon RA. The role of renal autotransplantation in complex urological reconstruction. J Urol 1990; 143:406 Correspondence: Pierpaolo Graziotti, M.D., Istituto Clinico Humanitas, Rozzano, Milano, Italy 134 Archivio Italiano di Urologia e Andrologia 2005; 77, 2 64° CONVEGNO ASSOCIAZIONE UROLOGI LOMBARDI - ERBUSCO (BS), 3 LUGLIO 2004 GOLDEN COMMUNICATIONS Microscopic and microbiological findings for evaluation of chronic prostatitis. Vittorio Magri1, Lisa Cariani2, Roberto Bonamore2, Antonella Restelli2, Maria Cristina Garlaschi2, Alberto Trinchieri3 Urology and Sonography 1Outpatient Clinic; 2Microbiology Unit, ICP Milano; 3 Urology Unit, Ospedale di Lecco, Italy. Summary Objective: The aim of this study was to assess the significance of different diagnostic methods for detecting prostatic inflammation/infection. Materials and Methods: :A group of 233 with symptoms suggesting prostatitis without urethral discharge attending an outpatient Prostatitis Clinic was considered. All were evaluated by the same urologist according to a protocol comprising medical history, physical and transrectal ultrasound examination. Patients had a urethral swab for bacterial culture and additional swabs for identification of C. trachomatis, T. vaginalis, U. urealyticum, M. hominis and Candida spp. Patients also underwent a four-specimen study according to Meares and Stamey (first voided urine VB1, midstream urine VB2, expressed prostatic secretion EPS and urine after prostatic massage VB3) and culture of the seminal fluid. Results: Of 233 patients evaluated, 47% had a positive urethral culture, 35% a positive culture of the seminal fluid and only 13% a positive culture of one or more samples of the four-specimen localization test. A positive culture of VB1 or VB2 was very rarely associated with a negative swab culture respectively in 1% and 0.9%; on the contrary, a positive swab culture was frequently associated with negative VB1 and VB2 culture respectively in 90% and 91%. Of the patients with positive urethral culture only 8% and 2% had more than 10 leukocytes respectively in VB1 and VB2. A positive seminal culture was associated with negative EPS and VB3 culture respectively in 89% and 83% cases; on the contrary, a positive culture of EPS or VB3 was associated with a negative seminal fluid culture respectively in 67% and 27% cases. In 49% patients with positive culture of the seminal fluid, more than 10 leukocytes in VB3 were observed. Only in 9 of the 47 patients with positive culture of the seminal fluid EPS can be obtained and 3 of them (33%) had more than 10 leukocytes in EPS. Conclusions: Culture and determination of leukocytes in first voided and midstream urine showed a low sensitivity in detection of urethral infection/inflammation compared to urethral swab culture. On the contrary, microscopic examination of urine after prostatic massage was confirmed as a useful indirect indicator in the diagnosis of prostatic inflammation and showed to be more feasible compared with the analysis of expressed prostatic secretion. In conclusion, urethral swab culture and post-massage urine culture and microscopic examination could be proposed as an alternative standard protocol in order to simplify the evaluation of prostatitis-like syndrome in the clinical practice. KEY WORDS: Chronic prostatitis; Seminal fluid; Urethral swab. INTRODUCTION MATERIALS Accurate diagnosis of urethral and prostatic inflammation and/or infection represents a diagnostic challenge. The reference standard remains the “four-glasses” procedure for the lower urinary tract localization, although additional information could be obtained by urethral swabs and culture of the seminal fluid. The aim of this study was to assess the significance of different diagnostic methods for detecting inflammation/infection of the prostate. A group of 233 with symptoms suggesting prostatitis without urethral discharge attending an outpatient Prostatitis Clinic was considered. All were evaluated by the same urologist according to a protocol comprising a thorough history, including standard symptom evaluation and sexual history and physical and transrectal ultrasound examination. Patients had a urethral swab for bacterial culture and addi- AND METHODS Archivio Italiano di Urologia e Andrologia 2005; 77, 2 135 V. Magri, L. Cariani, R. Bonamore, A. Restelli, M.C. Garlaschi, A.Trinchieri Table 1. Microbiological findings in VB1, VB2, EPS and VB3. VB1 1 Chlamydia VB2 1 Ureaplasma u VB3 6 Chlamydia, Candida, E. coli, H. para, Streptococcus beta-hemolyticus (2) EPS 10 Chlamydia (2), Streptococcus beta hemoliticus (3), E. coli (1), Proteus (1), Morganella (1), Irl haem (1), E. coli+Streptococcus beta hemoliticus (1) VB1+VB2+VB3 4 E. coli (3), Klebsiella (1) VB2+VB3 (non eseguito VB1) 3 E. coli (2), Streptococcus beta hemoliticus (1) VB1+VB3 2 E. coli (1), Enterobacter (1) VB1+VB2 2 E. coli (2) 1 Streptococcus beta hemoliticus (1) EPS+VB3 Total 30 tional swabs for identification of C. trachomatis, T. vaginalis, U. urealyticum, M. hominis and Candida spp. Patients underwent a four-specimen study according to Meares and Stamey (first voided urine VB1, midstream urine VB2, expressed prostatic secretion EPS and urine after prostatic massage VB3) and culture of the seminal fluid. RESULTS Of 233 patients evaluated, 101/214 (47%) had a positive urethral culture, 47/135 (35%) a positive culture of the seminal fluid and 30/233 (13%) a positive culture of the four-specimen localization test (VB1 alone 1 pt, VB2 alone 1 pt, VB1+2 two pts, VB1+3 two pts, VB2+3 three pts, VB1+2+3 four pts, EPS alone 10 pts, VB3 alone 6 pts, EPS+VB3 one pt). Positive cultures of VB1 and VB2 were associated to positive culture of VB3 in 9/13 cases (6/9 cases for VB1 and 7/10 for VB2). When VB1 and VB2 were positive in absence of positive VB3, the isolated were Chlamydia t. (VB1 positive alone), Ureaplasma u. (VB2 positive alone) and E. coli (in 2 cases with VB1+VB2 positive). Table 2. Results of VB1 and VB2 cultures in relation to the result of urethral swab culture. VB1 positive VB1 negative Total 1 95 96 Urethral swab negative Urethral swab positive 8 77 85 Total 9 172 181 VB2 positive VB2 negative Total 1 113 114 Urethral swab negative Urethral swab positive Total 9 92 101 10 205 215 Table 3. Results of VB3 and EPS cultures in relation to the result of seminal fluid culture. VB3 positive VB3 negative Total 3 84 87 8 39 47 Seminal culture negative Seminal culture positive Total 136 11 123 134 EPS positive EPS negative Total Seminal culture negative 2 9 11 Seminal culture positive 1 8 9 Total 3 17 20 Archivio Italiano di Urologia e Andrologia 2005; 77, 2 microscopic and microbiological findings for evaluation of chronic prostatitis Table 4. Presence of 10 or more leukocytes in VB1 and VB2 in relation to the result of culture of urethral swab. Urethral Swab Negative Urethral swab Positive Total VB1 < 10 WBC VB1 > 10 WBC Total 87 9 96 78 7 85 165 16 181 VB2 < 10 WBC VB2 > 10 WBC Total Urethral Swab Negative 111 3 114 Urethral swab Positive 99 2 101 210 5 215 Total Table 5. Presence of 10 or more leukocytes in VB3 and EPS in relation to the result of culture of urethral swab. Seminal culture Negative VB3 < 10 WBC VB3 > 10 WBC Total 51 36 87 24 23 47 Seminal culture Positive Total Seminal culture Negative Seminal culture Positive Total 75 59 134 EPS < 10 WBC EPS > 10 WBC Total 5 4 9 6 3 9 11 7 18 Culture of EPS was positive in 11 out of 20 cases in which it was possible to obtain the sample: in 10 out of these 11 cases the positive culture was not associated to positive cultures of other samples (VB1, VB2 or VB3). VB3 cultures were positive alone in 6/17 cases (Chlamidia t. in 1, Candida sp. in 1, E.coli in 1, Haemophylus parainfluenzae in 1, Streptococcus beta haemoliticus in 2). In 11 cases cultures were positive in more than one sample (E. coli in 8, Klebsiella in 1, Enterobacter in 1, Streptococcus beta-haemolyticus in 1). In 181 cases in which we were able to obtain both urethral swab and VB1 culture, a positive VB1 culture was associated to a negative urethral swab culture in only 1 out 96 cases. Similarly in 215 cases in which we were able to obtain both urethral swab and VB2 culture, a positive VB2 culture was associated to a negative urethral swab culture in only 1 out 114 cases. On the contrary, a positive swab culture was associated with negative VB1 and VB2 culture respectively in 77/85 (90%) and 92/101 (91%) cases. On the other hand in patients with positive urethral culture respectively only 7 out of 85 (8%) and 2 and 101 (2%) had more than 10 leukocytes in VB1 and VB2. A positive seminal culture was associated with negative EPS and VB3 culture respectively in 8/9 (89%) and 39/47 (83%) cases; on the contrary a positive culture of EPS or VB3 was associated with a negative seminal fluid culture respectively in 2/3 (67%) and 3/11(27%) cases. In 23 out 47 (49%) patients with positive culture of the seminal fluid more than 10 leukocytes in VB3 were observed. Only in 9 of the 47 patients with positive culture of the seminal fluid EPS can be obtained and 3 of them (33%) had more than 10 leukocytes in EPS. CONCLUSIONS In the early 1960’s a diagnostic method was developed in order to allow bacteriological assessment of the urethra and prostate by segmenting the voided urine into 3 sequential aliquots: VB1 (voided bladder one) collected as the patient initiate the urinary stream, VB2 collected when the patient has voided approximately 200 ml, and VB3 obtained after EPS (expressed prostatic secretion) collection by prostatic massage (1). Associated to the performance of quantitative bacteriologic cultures, the microscopic appearance of the prostatic expressa together with the sediment of first voided urine, the midstream urine and urine collected after prostatic massage was evaluated considering as pathologic leukocytosis a white blood cells (WBC) count per high power field (HPF) greater than 10 WBC. This technique has been considered the most accurate way to distinguish bacterial prostatitis from nonbacterial types of prostatitis and to estabilish the diagnosis of chronic bacterial prostatitis and has served as the basis of considerable investigative work in prostatitis during the past several years. Archivio Italiano di Urologia e Andrologia 2005; 77, 2 137 V. Magri, L. Cariani, R. Bonamore, A. Restelli, M.C. Garlaschi, A.Trinchieri In more recent years the cost/efficacy of this diagnostic method has been questioned (2-4). In our experience culture and determination of leukocytes in first voided and midstream urine showed a low sensitivity in detection of urethral infection/inflammation compared to urethral swab culture. On the contrary microscopic examination of urine after prostatic massage was confirmed as a useful indirect indicator in the diagnosis of prostatic inflammation and showed to be more feasible compared with the analysis of expressed prostatic secretion. In conclusion urethral swab colture and post-massage urine culture and microscopic examination could be proposed as an alternative standard protocol in order to simplify the evaluation of prostatitislike syndrome in the clinical practice. REFERENCES 1. Meares EM, Stamey TA. Bacteriologic localization patterns in bacterial prostatitis and urethritis. Invest Urol 1968; 5:492 2. McNaughton M, Fowler FJ, Elliott DB, Albertsen PC, Barry MJ. Diagnosing and treating chronic prostatitis: do urologists use the four-glass test? Urology 2000; 55:403 3. Ludwig M, Schroeder-Printzen I, Ludecke G, Woeidner W. Comparision of expressed prostatic secretions with urine after prostatic massage – a means to diagnose chronic prostatitis/inflammatory chronic pelvic pain syndrome. Urology 2000; 55:175 4. Krieger JN, Jacobs R, Ross SO. Detecting urethral and prostatic inflammation in patients with chronic prostatitis. Urology 2000; 55:186 Correspondence: Dott.Vittorio Magri, Presidio dei Poliambulatori ICP, via Andrea Doria 52, Milano; E-mail: [email protected] 138 Archivio Italiano di Urologia e Andrologia 2005; 77, 2 64° CONVEGNO ASSOCIAZIONE UROLOGI LOMBARDI - ERBUSCO (BS), 3 LUGLIO 2004 GOLDEN COMMUNICATIONS The use of vesical irrigation system dual pump Endo FMS Urology in the endoscopic therapy of benign prostatic hyperplasia. Piero Larcher, Giorgio Borroni, Andrea Begani, Paola Franch, Massimo Grisotto Urology Unit, Casa di Cura Igea, Milano, Italy. Summary Objective: Transurethral resection of the prostate (TURO) remains the reference standard treatment in the management of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). The objective of this study was to determine whether vesical irrigation during TURP with the dual pump system Endo FMS Urology is more efficient than standard gravity irrigation. Methods: A group of 30 patients who underwent TURP using the Endo FMS Urology was compared to a group of 30 patients treated with standard vesical irrigation. Results: A 40% decrease of fluid irrigated, a 10% decrease of time for procedure and a 10% increase in the volume of the resected tissue was observed in patients treated with the Endo FMS Urology compared to controls treated with standard vesical irrigation. KEY WORDS: Transurethral resection; Prostate; Vesical irrigation. INTRODUCTION From June 2003, in the Urology Unit of the Casa di Cura Igea of Milan, the dual pump system for intracavitary irrigation ENDO FMS Urology was adopted. The system is used for the endoscopic therapy of BPH, for the endoscopic therapy of the vesical neoplasm, for urethroscopy, and for diagnostic and therapeutic ureteroscopy too. MATERIALS AND METHODS From June 2003 to March 2004 we submitted to TURP 30 patients suffering from BPH using the Endo FMS Urology. We compared these patients to the previous 30 patients treated endoscopically for BPH with standard endovesical irrigation. The volume of adenomas ranged 30-45 cc, total PSA was <4 ng/ml, I.P.S.S. (International Prostate Symptoms Score) 12-30 (medium and severe grade). The two pumps of this system provide both constant programmed irrigation at constant pressure and suction mataining an intracavitary low pressure (20 cm H2O). The possibility of increasing the irrigation flow by a microcomputer allows a faster and more careful haemostasis. The endoscopic vision of prostatic cavity is greatly improved. There is no risk of vesical overfilling. The time of resection has decreased because there is no need to extract the rectoscope to evacuate the bladder during resection. RESULTS No cases of T.U.R. Syndrome were observed. No patient has been submitted to haemo-transfusion. A 40% decrease of fluid irrigated, a 10% decrease of time for procedure and a 10% increase in volume of the resected tissue was observed. No difference in terms of post-operative acute urine retention epysodes was observed. Intra-operative bleeding and post-operative consume of packed red cell decreased in patients treated with the Endo FMS Urology compared with patients treated with the standard procedure. CONCLUSIONS The vesical irrigation dual pump system Endo FMS Urology allows for a faster and safer resection of prostatic tissue because of the optimal view; it allows also a reduction of the amount of irrigated fluid and the maintenance of a low intracavitary pressure during prostatic resection, thus preventing the T.U.R. syndrome. Archivio Italiano di Urologia e Andrologia 2005; 77, 2 139 P. Larcher, G. Borroni, A. Begani, P. Franch, M. Grisotto REFERENCES 1. Interventional therapy for benign prostatic hyperplasia. In Chatelain C, Denis L, Foo KT, Khoury S, Mc Connell J (Eds). Benign Prostatic Hyperplasia. 5th International Consultation on Benign Prostatic Hyperplasia (BPH) June 25 – 28, 2000 Paris. Plymouth (UK), Plymbridge Distributors Ltd, 2001 2. Madsen PO, Nielsen KT. Devices for monitoring intravesical pressure during transurethral resection of the prostate. Med Instrum 1988; 22:69 3. Schulman C. Benign hypertrophy of the prostate: which treatment, for whom? Rev Med Brux 1999; 20:A212 4. Hahn RG. Intravesical pressure during irrigating fluid absorption in transurethral resection of the prostate. Scand J Urol Nephrol 2000; 34:102 Correspondence: : Piero Larcher, M.D, UO Urologia, Casa di Cura Igea, Milano, Italy 140 Archivio Italiano di Urologia e Andrologia 2005; 77, 2 64° CONVEGNO ASSOCIAZIONE UROLOGI LOMBARDI - ERBUSCO (BS), 3 LUGLIO 2004 GOLDEN COMMUNICATIONS The use of vesical irrigation system dual pump Endo FMS Urology in the endoscopic therapy of the vesical neoplasms. Piero Larcher1, Giorgio Borroni1, Andrea Begani1, Paola Franch1, Luca Carmignani2 Urology Unit, Casa di Cura Igea; 2Urology Unit, San Paolo Hospital, Milano, Italy 1 Summary Objective: The objective of this study was to determine whether vesical irrigation during transurethral resection of bladder tumours (TURBT) with the dual pump system for the intracavitary irrigation Endo FMS Urology is more efficient than the standard gravity technique. Methods: One hundred patients suffering from vesical neoplasms underwent TURBT using the Endo FMS Urology (group A). They were compared to 100 patients previously (2002-2003) treated endoscopically for vesical tumours with the standard endovesical irrigation method (group B). Results: We demonstrad a reduction of the average time of resection of 10% in favour of patients of group A, a reduction of 39% of the amount of fluid of vesical irrigated in favour of patients of group A. No differences were observed in the recurrence rate of tumours at 3 months and in need of endoscopic revision in the 48 hours following TURBT. Two patients required blood transfusion after TURBT in group B, none in group A. The average time of hospitalisation in group A was less than one day. Conclusions: On the basis of this experience the use of Endo FMS Urology Irrigation System in TURBT is strongly recommended. KEY WORDS: Vesical irrigation; Vesical neoplasms.. INTRODUCTION The gold-standard in the treatment of superficial bladder tumours is transurethral resection (TURBT). In the presence of a suspect vesical lesion TURBT is the main diagnostic step and it is often the definitive treatment if the lesion is completely resecatable. In consideration of the well known recurrence rate of superficial bladder tumours, endoscopic treatment is advisable because it is less invasive and can be easily repeated. The cleanness of the operating field and the possibility of increasing/reducing the flow of the washing is essential for a correct procedure of resection. Bulking tumours not infiltrating deeply the bladder wall are susceptible of endoscopic conservative treatment if the irrigation and washing system allows an optimal view also in case of massive bleeding. The accuracy of resection allows a radical removal of the tumour reducing the risk of recurrence. Resection with low pressure and constant washing flow allows, after resection of the esophytic mass, to perform deep biopsies and, if necessary, to perform planned perforations of the vesical wall to obtain a complete radical resection or at least to exactly stadiate the tumour in order to correctly plan a radical surgery. In order to perform a planned perforation of the vesical wall, it is necessary to obtain an optimal control of the endovesical washing flow and of the endovesical gradient pressure. The conventional endovesical irrigation system, that works by the force of gravity, allows for a reduced modulation with limited possibility to increase pressure and/or flow speed by means of artifices such as the squeezing or the elevation of the fluid sack. The dual pump system Endo FMS Urology, managed by a computer, is equipped with a precise sensors that allow to maintain the required filling of the bladder. Any difference of endovesical filling and pressure from the selected values causes the pump to stop or to start until the correct value of pressure is achieved again. The constantly reduced endovesical pressure inhibits the overfilling of the bladder reducing to the minimum the risk of re-absoption of the irrigation fluid. The Endo FMS Urology is provided with two pedals that allow an immediate increase in vesical pressure (red Archivio Italiano di Urologia e Andrologia 2005; 77, 2 141 P. Larcher, G. Borroni, A. Begani, P. Franch, L. Carmignani pedal) and an increase in the filling (blue pedal). This new system allows an optimal consume of the irrigation fluid, not requiring to extract the resectoscope to evacuate the bladder and allows an optimal view of the operating field. The increase in flow allows to easily identify the arterial bleedings and a more careful and selective haemostasis. MATERIALS AND METHODS The Endo FMS Urology is a complete fluid management system which provides a constant programmed irrigation pressure together with a suction flow. While a suction pump (master) removes fluid from the cavity through the tubing connected to the resectoscope outer sheat, an irrigation pump (slave), with pressure setting, supplies fluid through the tubing connected to the resectoscope inlet port and maintains the programmed pressure. This provides two independent functions: irrigation pressure and suction flow. Pre-programmed values of these parameters are linked by a microcomputer to maintain a low intravesical pressure of 10 to 20 cm H2O. During TURBT the 2 stopcocks of the resectoscope must be permanently opened. An audiovisual alarm warns if programmed pressure is exceeded. Disposable tubing is installed on the system to feed the continuous flow resectoscope. PATIENTS From June 1st 2003 to March 31th 2004 100 unselected patients have been submitted to TURBT. These procedures were performed by using the endovesical washing system, operated by pumps and computers, called Endo FMS Urology. Characteristics of the patients who underwent TURBT using Endo FMS were: male to female ratio 73/27, mean age 64 years (range: 35-87). Tumour stage and grade were T1 G1-G2 in 77; T2 G1 in 13; T2 G2 in 7; T3 G3 in 3 patients. As control group we considered 100 consecutive patients treated endoscopically from March 2002 to June 2003 for vesical tumours with the standard endovesical irrigation method. The mean time of resection was significantly reduced in patients of group A compared to the patients of group B (- 10%). The recurrence rate was equal in the two groups. The need of re-surgery for serious bleeding in the 48 hours following TURBT was 2% in both groups.Two patients of group B requested haemo-transfusion, whereas no patients in group A was submitted to haemotransfusion. The post TURBT mean hospitalisation period was one day less for patients of group A compared to group B. CONCLUSIONS Using the Endo FMS Urology instead of the standard irrigation system we obtained a reduction of surgery time; a reduction of the amount of fluid for irrigation; a reduction of intra-operative bleeding owing to a more selective haemostasia; the possibility to maintain a low irrigation flow maintaining an optimal view when bleeding is moderate; a reduction of the mean period of hospitalisation. During the procedure, the entrance and exit taps of the Iglesias resector were always completely opened, so there is no need to manually settle them and there is no risk of an accidental vesical over stretching. With reference to the cost, in addition to the Endo FMS Urology purchase cost or its mortgaging, you have to consider the cost of the disposable sets of connection of the pump to the resector. These costs are compensated by the reduced use of irrigation fluid, from the reduced time of use of the endoscopic room and from the shorter hospitalisation. The resection of bulking tumours bodies is easier, more safe and precise to the operator. The definitive haemostasis is more precise and so more reliable. Our study could be criticisable because of the lack of randomisation between the two groups, but in our opinion a randomised comparison between the dual pump and the standard procedure was not ethic, due to the obvious superiority of the dual pump system; for that reason we preferred to refer to historical controls. REFERENCES RESULTS The amount of fluids used for vesical irrigation during the bladder resection was 39% less for the patients of group A (treated with Endo FMS Urology) compared to patients of group B (treated with standard irrigation). 1. Widman J. Controlled continuous flow method fro transurethral resections. Urol 1983; 21:130 2. Briggs TP, Parker C, Connolly AA, Miller R. Fluid delivery system: high flow, low pressure, the key of safe resection. Eur Urol 1991; 19:277 Correspondence: Piero Larcher, M.D., UO Urologia, Casa di Cura Igea, Milano, Italy 142 Archivio Italiano di Urologia e Andrologia 2005; 77, 2 GENERAL INFORMATION Aims and Scope BUSINESS INFORMATION Subscription details “Archivio Italiano di Urologia e Andrologia” publishes papers dealing with the urological, nephrological and andrological sciences. Original articles on both clinical and research fields, reviews, editorials, case reports, abstracts from papers published elsewhere, book rewiews, congress proceedings can be published. Papers submitted for publication and all other editorial correspondence should be addressed to: Annual subscription rate (4 issues) is Euro 52 for Italy and US $130 for all other Countries. Price for single issue: Euro 13 for Italy US $32,5 for all other Countries. 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