Archivio Italiano di Urologia e Andrologia - Vol. 91 - n. 1 - 2019 by Edizioni Scripta Manent

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Archivio Italiano di Urologia e Andrologia / Archives of Italian Urology and Andrology - Vol. 91; n. 1 March 2019

Vol. 91; n. 1, March 2019

ORIGINAL PAPERS 1

Transumbilical laparoendoscopic single-site adrenalectomy: A feasible and safe alternative to standard laparoscopy João André Carvalho, Pedro Tiago Nunes, Hugo Antunes, Belmiro Parada, Edson Retroz, Edgar Tavares-da-Silva, Isabel Paiva, Arnaldo José Figueiredo

Posterior muscle-fascial reconstruction and knotless urethro-neo bladder anastomosis during robot-assisted radical cystectomy: Description of the technique and its impact on urinary continence Federico Mineo Bianchi, Daniele Romagnoli, Daniele D’Agostino, Antonio Salvaggio, Marco Giampaoli, Paolo Corsi, Lorenzo Bianchi, Marco Borghesi, Riccardo Schiavina, Eugenio Brunocilla, Peter Wiklund, Angelo Porreca

Factors associated with urinoma accompanied by ureteral calculi Ercan Öğreden, Ural Oğuz, Mehmet Karadayı, Erhan Demirelli, Alptekin Tosun, Mücahit Günaydın

The role of anticholinergic therapy based on the upoint system in the treatment of chronic prostatitis Kamil Fehmi Narter, Utku Can, Alper Coşkun, Kubilay Sabuncu, Fatih Tarhan

Successful treatment with pollen extract of hematospermia in patients with xanthogranolomatous prostatitis Antonio Luigi Pastore, Yazan Al Salhi, Andrea Fuschi, Alessia Martoccia, Gennaro Velotti, Lorenzo Capone, Giorgio Bozzini, Natale Porta, Vincenzo Petrozza, Ester Illiano, Elisabetta Costantini, Antonio Carbone

Subjective and objective results in surgical correction of adult acquired buried penis: A single-centre observational study Andrea Cocci, Gianmartin Cito, Marco Falcone, Marco Capece, Fabrizio Di Maida, Girolamo Morelli, Nim Christopher, David Ralph, Giulio Garaffa

Sutureless laparoscopic partial nephrectomy using fibrin gel reduces ischemia time while preserving renal function Daniele Tiscione, Tommaso Cai, Lorenzo Giuseppe Luciani, Marco Puglisi, Daniele Mattevi, Gabriella Nesi, Mattia Barbareschi, Gianni Malossini

NOTE OF SURGICAL TECHNIQUE 35

The LEST technique: Treatment of prostatic obstruction preserving antegrade ejaculation in patients with benign prostatic hyperplasia Rosario Leonardi

continued on page III

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Official Journal of SIA, SIEUN, UrOP and GUN EDITORIAL BOARD EDITOR IN CHIEF Alberto Trinchieri (Milan, Italy)

ASSOCIATE EDITORS Emanuele Montanari, Department of Urology, IRCCS Foundation Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Italy – Gianpaolo Perletti, Department of Biotechnology and Life Sciences, Section of Medical and Surgical Sciences, University of Insubria, Varese, Italy; Department of Human Structure and Repair, Ghent University, Ghent, Belgium

EDITORIAL BOARD Pier Francesco Bassi, Urology Unit, A. Gemelli Hospital, Catholic University of Rome, Italy – Francesca Boccafoschi, Health Sciences Department, University of Piemonte Orientale in Novara, Italy – Alberto Bossi, Department of Radiotherapy, Gustave Roussy Institute, Villejuif, France – Paolo Caione, Department of Nephrology-Urology, Bambino Gesù Pediatric Hospital, Rome, Italy – Fabio Campodonico, Urology Unit, Galliera Hospitals, Genoa, Italy – Luca Carmignani, Urology Unit, San Donato Hospital, Milan, Italy – Liang Cheng, Department of Urology, Indiana University School of Medicine, Indianapolis, IN; Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN – Luca Cindolo, Department of Urology, S. Pio da Pietrelcina Hospital, Vasto, Italy – Giovanni Colpi, Retired Andrologist, Milan, Italy – Giovanni Corona, Department of Urology, University of Florence, Careggi Hospital, Florence, Italy – Antonella Giannantoni, Department of Surgical and Biomedical Sciences, University of Perugia, Italy – Paolo Gontero, Department of Surgical Sciences, Molinette Hospital, Turin, Italy – Steven Joniau, Organ Systems, Department of Development and Regeneration, KU Leuven, Belgium – Frank Keeley, Bristol Urological Institute, Southmead Hospital, Bristol UK – Laurence Klotz, Division of Urology, Department of Surgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada – Massimo Lazzeri, Department of Urology, Humanitas Research Hospital, Rozzano, Italy – Börje Ljungberg, Urology and Andrology Unit, Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden – Andrea Minervini, Urology and Surgical Andrology Unit, Careggi University Hospital, Florence, Italy – Nicola Mondaini, Uro-Andrology Unit, Santa Maria Annunziata Hospital, Florence, Italy – Gordon Muir, Department of Urology, King's College Hospital, London, UK – Giovanni Muto, Urology Unit, Bio-Medical Campus University, Turin, Italy – Richard Naspro, Urology Unit, Papa Giovanni XXIII Hospital, Bergamo, Italy – Anup Patel, Department of Urology, St. Mary's Hospital, Imperial Healthcare NHS Trust, London, UK – Glenn Preminger, Division of Urologic Surgery, Duke University Medical Center, Durham, NC, USA – David Ralph, St. Peter's Andrology Centre and Institute of Urology, London, UK – Allen Rodgers, Department of Chemistry, University of Cape Town, Cape Town, South Africa – Francisco Sampaio, Urogenital Research Unit, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil – Kemal Sarica, Department of Urology, Kafkas University Medical School, Kars, Turkey – Luigi Schips, Department of Urology, San Pio da Pietrelcina Hospital, Vasto, Italy – Hartwig Schwaibold, Bristol Urological Institute, Southmead Hospital, Bristol, UK – Alchiede Simonato, Department of Urology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy – Salvatore Siracusano, Department of Urology, Trieste University Hospital, Trieste, Italy – Carlo Terrone, Department of Urology, IRCCS S. Martino University Hospital, Genova, Italy – Anthony Timoney, Bristol Urological Institute, Southmead Hospital, Bristol, UK – Andrea Tubaro, Urology Unit, Sant’Andrea Hospital, “La Sapienza” University, Rome, Italy – Richard Zigeuner, Department of Urology, Medical University of Graz, Graz, Austria

SIA EDITORIAL BOARD Massimo Polito, Ospedali Riuniti di Ancona, Ancona, Italy – Paolo Capogrosso, Università Vita-Salute San Raffaele, Milano, Italy – Giuseppe Sidoti, A.O. Garibaldi, Catania, Italy – Nicola Pavan, Azienda Ospedaliero-Universitaria "Ospedali Riuniti" di Trieste, Italy – Enrico Conti, Presidio Ospedaliero Levante Ligure, La Spezia, Italy – Matteo Paradiso, Ospedale Cardinal Massaia-ASL 19, Asti, Italy – Giuseppe Romano, Ospedale Civile S. Donato Arezzo-U.O. Arezzo, Italy – Antonio Vavallo, Ospedale della Murgia, Altamura, Italy – Gianni Paulis, Ospedale Regina Apostolorum, Albano Laziale, Italy – Valeria Randone, Studio privato–Sessuologo Clinico, Catania, Italy – Maria Colucci, Studio privato-Consulente in Sessuologia, Bari, Italy

SIEUN EDITOR Pasquale Martino, Department of Emergency and Organ Transplantation-Urology I, University Aldo Moro, Bari, Italy

SIEUN EDITORIAL BOARD Emanuele Belgrano, Department of Urology, Trieste University Hospital, Trieste, Italy Francesco Micali, Department of Urology, Tor Vergata University Hospital, Rome, Italy - Massimo Porena, Urology Unit, Perugia Hospital, Perugia, Italy – Francesco Paolo Selvaggi, Department of Urology, University of Bari, Italy – Carlo Trombetta, Urology Clinic, Cattinara Hospital, Trieste, Italy – Giuseppe Vespasiani, Department of Urology, Tor Vergata University Hospital, Rome, Italy – Guido Virgili, Department of Urology, Tor Vergata University Hospital, Rome, Italy

UrOP EDITOR Carmelo Boccafoschi, Città di Alessandria Clinic, Alessandria, Italy

UrOP EDITORIAL BOARD Mario Coscione, Department of Urology, Santa Rita New Clinic, Benevento, Italy – Gaspare Fiaccavento, Private Practitioner, San Donà di Piave (VE), Italy – Fabio Galasso, Department of Urology, Casa di Cura Malzoni Villa Platani, Avellino, Italy – Massimo Lazzeri, Department of Urology, Humanitas Research Hospital, Rozzano, Italy – Federico Narcisi, Urologia Casa di Cura Villa Anna, S. Benedetto del Tronto (AP), Italy – Christian Ranno, Catania, Oncological Institute of the Mediterranean (IOM), Viagrande (CT), Italy – Vito Pansadoro, Vincenzo Pansadoro Foundation, Rome, Italy – Manlio Schettini, Urology Unit, Casa di Cura Nuova Villa Claudia, Rome, Italy

GUN EDITOR Arrigo Francesco Giuseppe Cicero, Medical and Surgical Sciences Department, Sant’Orsola-Malpighi University Hospital, Bologna, Italy

GUN EDITORIAL BOARD

Alessandro Palmieri, Department of Urology University Federico II of Naples, Italy

Gianmaria Busetto, Department of Urology, Sapienza University of Rome, Italy – Tommaso Cai, Department of Urology, Santa Chiara Regional Hospital, Trento, Italy – Elisabetta Costantini, Andrology and Urogynecological Clinic, Santa Maria Hospital of Terni, University of Perugia, Terni, Italy – Angelo Antonio Izzo, Department of Pharmacy, University of Naples, Italy – Vittorio Magri, ASST Nord Milano, Milano, Italy – Salvatore Micali, Department of Urology, University of Modena and Reggio Emilia, Modena, Italy – Gianni Paulis, Andrology Center, Villa Benedetta Clinic, Rome, Italy – Francesco Saverio Robustelli della Cuna, University of Pavia, Italy – Giorgio Ivan Russo, Urology Department, University of Catania, Italy – Konstantinos Stamatiou, Urology Department, Tzaneio Hospital, Piraeus, Greece – Annabella Vitalone, Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy

SIA ASSISTANT EDITORS

HONORARY EDITOR

SIA EDITOR

Tommaso Cai, S. Chiara Hospital, Trento, Italy – Vincenzo Favilla, University Hospital Gaspare-Rodolico, Catania, Italy – Paolo Verze, Federico II University, Naples, Italy

Enrico Pisani, Professor Emeritus, Institute of Urology, University of Milan, Italy

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ll ruolo della SIEUN La SIEUN (Società Italiana di Diagnostica Integrata in Urologia, Andrologia, Nefrologia) riunisce diversi medici specialisti e non che si occupano di tutte quelle metodiche in cui gli ultrasuoni vengono utilizzati a scopo diagnostico ed interventistico in ambito uro-nefro-andrologico. La SIEUN organizza un Congresso Nazionale con cadenza biennale e diverse altre iniziative in genere con cadenza annuale (corsi monotematici, sessioni scientifiche in occasione dei congressi nazionali delle più importanti società scientifiche in ambito Uro-Nefro-Andrologico). Dal 2001 la SIEUN è affiliata all’ESUI (European Society of Urological Imaging); pertanto tutti i soci possono partecipare alla iniziative della Società Europea. L’Archivio Italiano di Urologia e Andrologia è l’organo ufficiale della SIEUN. Questa pagina permette una informazione puntuale sulla attività della nostra Società e consente al Consiglio Direttivo della SIEUN di comunicare non solo ai soci, ma ad una platea più ampia, ogni nuova iniziativa.

I PROSSIMI APPUNTAMENTI SIEUN La SIEUN nel 2019 sarà presente con relazioni, moderazioni e letture nei congressi delle più prestigiose Società scientifiche di Urologia, Andrologia ed Ecografia.

EAU Section Meetings-Barcellona Joint meeting of the EAU Sections of Infections in Urology (ESIU) and Urological Imaging (ESUI) Saturday 16th March 2019, 10:15 -14:00 Title: Prepare for the future: Prevent, Detect, Strike back! Chairs:: G. Salomon - Hamburg (DE) F.M.E. Wagenlehner - Giessen (DE)

Società Italiana di Diagnostica Integrata in Urologia, Andrologia, Nefrologia

Decreasing the risk of biopsy related complications by imaging: Time for transrectal biopsy is NOT over! - V. Scattoni, Milan (IT) The difficulties in chronic infections/inflammations of the male genital organs: Does imaging help in any way? - P. Martino, Bari (IT)

La SIEUN sarà coinvolta con un corso ECM educazionale di FUSION BIOPSY a Bologna il 18 Maggio 2019 nell’ambito del 26° Congresso Nazionale AURO. La coordinazione scientifica dello stesso sarà affidata al Prof. Galosi e Dr. Fandella. Tale corso prevederà oltre che ad una parte teorica e una parte pratica (Hands-on).

NUOVO SITO WEB CORSO PRECONGRESSUALE SIA-SIEUN ECOGRAFIA ANDROLOGICA 23 maggio 2019 – Bari Cordinatori: Francesco Mangiapia (SIA), Pasquale Martino (SIEUN)

La SIEUN, con il suo nuovo sito www.sieun.eu, volge lo sguardo all’Europa. Per informazioni ed iscrizioni: www.sieun.eu La segreteria della Società

QUOTE ASSOCIATIVE 2019 Socio ordinario - Euro 100,00 Socio Junior - Euro 50,00 Per la modalità di pagamento della quota sociale collegarsi al sito della Società www.sieun.eu.

I PUNTI SIEUN (una possibilità di incontro tra Soci SIEUN e di contatto con altri specialisti) Presso i punti SIEUN i nostri soci potranno essere continuamente informati su tutte le attività e le iniziative della Società e rinnovare il pagamento della quota associativa.

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CENTRE

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Ed new ok_Cop+Ed+fisse 2006 26/03/19 12:26 Pagina III

CASE REPORTS 43

Management of erosion of inflatable penile prosthesis reservoir into bladder. A different approach Volkan Izol, Mutlu Deger, Bahattin Kizilgok, Ibrahim Atilla Aridogan, Mustafa Zuhtu Tansug

A rare complication of inguinal hernia repair: Total testicular ischemia and necrosis Erhan Ates, Hakan Gorkem Kazici, Akin Soner Amasyali

Blastoid variant of mantle cell lymphoma of the female urethra mimicking a caruncle: A rare but highly aggressive subtype case with literature review Franco Palmisano, Vito Lorusso, Matteo Giulio Spinelli, Paolo Guido Dell’Orto, Emanuele Montanari

Partial cystectomy in young male for a urachal tumor masquerading a bladder leiomyoma Maurizio Sodo, Lorenzo Spirito, Roberto La Rocca, Umberto Bracale, Ciro Imbimbo

Does right-sided varicocele indicate a right-sided kidney tumor? Miguel Bonfitto, Leandro Shogo Matuy Kimura, José Maria Pereira Godoy, Miguel Zerati Filho, Luis Cesar Fava Spessoto, Fernando Nestor Facio Junior

Large primary leiomyosarcoma of the seminal vesicle: A case report and literature revision Emanuele Corongiu, Pietro Grande, Valerio Olivieri, Giorgio Pagliarella, Flavio Forte

Minimally invasive management of a symptomatic case of Zinner’s syndrome: Laparoscopic seminal vesiculectomy and ipsilateral nephroureterectomy Emanuele Corongiu, Pietro Grande, Valerio Olivieri, Giorgio Pagliarella, Flavio Forte

Late urinary bladder metastasis from breast cancer Aldo Franco De Rose, Federica Balzarini, Guglielmo Mantica, Carlo Toncini, Carlo Terrone

Pubis bone osteomyelitys after robotic radical cystectomy with continent intracorporeal urinary diversion: Multidisciplinary approach to a complex situation Daniele Romagnoli, Federico Mineo Bianchi, Paolo Sadini, Andrea Angiolini, Daniele D'Agostino, Marco Giampaoli, Sergio Candiotto, Riccardo Schiavina, Eugenio Brunocilla, Angelo Porreca

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Archivio Italiano di Urologia e Andrologia 2019, 91, 1

III

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Carvalho_Stesura Seveso 25/03/19 17:11 Pagina 1

DOI: 10.4081/aiua.2019.1.1

ORIGINAL PAPER

Transumbilical laparoendoscopic single-site adrenalectomy: A feasible and safe alternative to standard laparoscopy João André Carvalho 1, 2, Pedro Tiago Nunes 1, 2, Hugo Antunes 1, Belmiro Parada 1, 2, Edson Retroz 1, Edgar Tavares-da-Silva 1, 2, Isabel Paiva 3, Arnaldo José Figueiredo 1, 2 1 Urology 2 Faculty

and Renal Transplantation Department, Coimbra University Hospital Center, Portugal; of Medicine, University of Coimbra; 3. Endocrinology Department, Coimbra University Hospital Center, Portugal.

Summary

Objectives: Standard multi-port laparoscopic adrenalectomy (LA) is considered the gold standard for benign adrenal tumors. Single-site LA has been proposed as a feasible and safe alternative because of lower invasiveness, improved cosmetics, less pain and shorter hospital stay. The objective was to evaluate and compare results of single-site transumbilical laparoendoscopic adrenalectomy with standard LA for adrenal tumors. Materials and methods: One hundred consecutive adrenalectomies from 93 patients, performed between March 2009 and June 2017, were laparoscopically excised: 59 by standard multi-port LA (group 1) and 41 by transumbilical laparoendoscopic single-site adrenalectomy (group 2). Data gathered included demographics, comorbidities, preoperative imaging, tumor characteristics, perioperative data, surgical complications, pathology and follow-up. IBM SPSS Statistics 23 software was used and p value < 0.05 was considered significant. Results: Patients of group 2 were younger (48.7 ± 13.9 versus 59.7 ± 15.1 years; p < 0.001) and had fewer comorbidities (p < 0.05). Mean tumor diameter in group 2 was lower than those of group 1 (27.52 ± 14.3 versus 47.9 ± 30.6 mm; p < 0.001). Tumor laterality did not influence the choice of technique nor the surgical morbidity. All procedures were successfully completed, although one standard LA needed conversion to open surgery. Mean operative time, hemorrhagic losses, postoperative opioid analgesic requirement and hospital stay were not statistically different between groups. Most patients in group 2 (31 patients, 85.4%) did not require drainage, compared to 14 (25.4%) patients of group 1 (p < 0.001). Patients who underwent single-site LA resumed normal diet earlier (1.0 ± 0.2 versus 1.6 ± 0.7 days; p < 0.001). There were no reoperations and no perioperative mortality. Overall mean follow-up time was 94.9 ± 3.1 months, not statiscally different between groups (p = 0.7). Conclusions: Our results revealed that transumbilical approach for laparoendoscopic single-site adrenalectomy for adrenal tumors is a feasible and safe alternative to standard laparoscopic adrenalectomy.

KEY WORDS: Standard multi-port laparoscopic adrenalectomy; Laparoendoscopic single-site surgery: Partial adrenalectomy. Submitted 26 August 2018; Accepted 3 September 2018

INTRODUCTION

The first laparoscopic adrenalectomy was performed by Gagner et al. (1) in 1992 and, since then, it has become the gold standard procedure for most adrenal tumors.

Standard multiport laparoscopic adrenalectomy (LA) involves the use of typically three to five ports, depending on the complexity of the procedure. Nowadays, laparo-endoscopic single-site surgery (LESS) is exciting the scientific community because it offers the opportunity to do major laparoscopic surgery with no visible scars and with potential reduced postoperative pain and hospital stay (2). LESS has been used for cholecystectomy (3), appendectomy (4) and several urological surgeries (5), but the high degree of difficulty and the longer learning curve tends to make its widespread difficult. LESS surgery through the umbilicus is the most appealing approach, as it truly avoids any new scar, with the multichannel port being placed through a 1.5 to 2 cmincision at the deep edge of the obliterated embryonic orifice. Partial adrenalectomy has been a promising surgical technique mainly in functioning lesion in a solitary adrenal gland or in bilateral hereditary or sporadic tumors with the goal of reducing endocrinopathy. However, it has a relapse risk that we always have to remember (6). Here, we present our experience with transumbilical LESS adrenalectomy comparing with standard multiport laparoscopic multiport, showing our results with partial adrenalectomy too.

MATERIAL

AND METHODS

Between March 2009 and June 2017, 100 adrenal glands from 93 patients underwent transperitoneal laparoscopic adrenalectomy at the Urology and Renal Transplantation Department of Coimbra University Hospital Center: 59 (59%) underwent standard multi-port laparoscopy (group 1) and 41 (41%) underwent transumbilical laparo-endoscopic single-site adrenalectomy (group 2). Standard multi-port laparoscopy included three to four ports. The multichannel port (Triport) and bent laparoscopic instruments were supplied by Olympus Surgical (KeyMed House, Stock Road, United Kingdom). The multichannel port was placed through a 2-cm incision at the inner edge of the umbilicus and a bent instrument on the left hand was used to create the operative angle. In 30% of cases, it was needed a forceps with no port to move the liver away from the operative field. All transumbilical laparoendoscopic single-site adrenalec-

No conflict of interest declared. Archivio Italiano di Urologia e Andrologia 2019; 91, 1

Carvalho_Stesura Seveso 25/03/19 17:11 Pagina 2

J.A. Carvalho, P. Tiago Nunes, H. Antunes, B. Parada, E. Retroz, E. Tavares-da-Silva, I. Paiva, A. José Figueiredo

tomies were executed by one surgeon while standard LA were performed by more than one surgeon. Data gathered included demographics, comorbidities, preoperative imaging, tumor characteristics, perioperative data, surgical complications, length of stay, need for analgesia, pathology and follow-up. All patients were evaluated by the Endocrinology team with a standard protocol. Written informed consent was obtained from all patients and the study was performed according to the Declaration of Helsinki. Data were collected retrospectively and processed with IBM SPSS Statistics 23 software. Groups were compared using the chi-square test and t Student test for categorical and continuous variables, respectively. Survival analysis was done through Kaplan-Meyer survival curve. Statistical significance was set at p value of < 0.05, and all reported p-values are two-sided.

RESULTS

Patient demographic data are shown in Table 1. Patients elected for transumbilical LESS adrenalectomy were younger and with less comorbidities. Preoperative tumor data are shown at Table 2. The laterality of the lesion didn’t have any impact in the choice of the surgical technique. 52.5% of the cases submitted to standard multi-port LA were incidentally diagnosed nonfunctioning enlarged adrenals. In group 2, arterial hypertension was the main initial symptom and elevated aldosterone was the most common finding. Only 24.4% of the tumors submitted to transumbilical LESS adrenalectomy were non-functioning. Perioperative data are shown in Table 3. There was no difference between groups concerning operative time and estimated blood loss. 29.3% of transumbilical LESS surgeries were partial adrenalectomies: no one was done by standard multi-port laparoscopy. Seven (7%) patients were submitted to bilateral adrenalectomies, two by multi-port LA and five by transumbilical LESS technique. Drainage was placed in a minority of cases submitted to transumbilical LESS technique while the majority of patients submitted to standard multi-port laparoscopy underwent drainage placement. One case of multi-port LA was converted to open surgery due to the Table 1. Demography and comorbities between groups. Group 1: patients submitted to standard multi-port laparoscopy adrenalectomy. Group 2: patients submitted to transumbilical approach for laparoendoscopic single-site adrenalectomy. Demographic data Patients (n) Number of adrenal glands Age at surgery (years) Sex Male Female Cardiovascular disease Diabetes mellitus type 2

Group 1 57 (61.3%) 59 (59%) 59.7 ± 15.1

Group 2 36 (38.7%) 41 (41%) 48.7 ± 13.9

39.0% 61.0% 20.3% 27.1%

36.6% 63.4% 2.4% 7.3%

NS: Non-significant.

Archivio Italiano di Urologia e Andrologia 2019; 91, 1

Table 2. Preoperative tumour data between groups. Group 1: patients submitted to standard multi-port laparoscopy adrenalectomy. Group 2: patients submitted to transumbilical approach for laparoendoscopic single-site adrenalectomy. Tumor data

p: 0.013 p: 0.02

Group 2 (n = 36)

Laterality Left 61.0% 61.0% Right 39.0% 39.0% Presentation Incidental 52.5% 31.7% Arterial hypertension 35.6% 39.0% Cushing disease 5.1% 24.4% Metastasis 0% 2.4% Pain 6.8% 2.4% Functioning adenoma Yes 50.8% 75.6% No 49.2% 24.4% Produced hormone Non-functioning 49.2% 24.4% Aldosterone 11.9% 34.1% Catecholamines 28.8% 14.6% Cortisol 8.5% 26.8% DHEA 1.7% 0% Mean imaging diameter on CT (mm) 47.9 ± 30.6 27.52 ± 14.3 Mean imaging diameter on CT > 40 mm 56.4% 15.2% Maximum diameter (mm) 120 80

P-value NS (p: 0.6)

p: 0.02

p: 0.01

p: 0.002

p < 0.001 p < 0.001

DHEA: Dehydroepiandrosterone; NS: Non-significant.

Table 3. Comparison of perioperative data between groups. Group 1: patients submitted to standard multi-port laparoscopy adrenalectomy. Group 2: patients submitted to transumbilical approach for laparoendoscopic single-site adrenalectomy. Perioperative data Partial adrenalectomy Yes No Bilateral adrenalectomy Yes No Operative time (min) - Unilateral adrenalectomy - Bilateral adrenlaectomy Estimated blood loss (mL) Drainage tube Yes No Need to convert to open surgery Perioperative complications

P-value

p < 0.001 NS (p: 0.8)

Group 1 (n = 57)

Group 2 (n = 36)

0% 100%

29.3% 70.7%

3.6% 96.4%

14.3% 85.7%

93.1 ± 42.1 82.5 ± 17.6 34.9 ± 152.6

87.9 ± 46.4 111 ± 36.8 23.6 ± 87.7

74.6% 25.4% 1.8% 3 diaphragm injuries 1 postoperative retroperitoneal hematoma

14.6% 85.4% 0% 0

44.1% 55.9% 3.2 ± 2.5 1.6 ± 0.7

31.7% 68.3% 2.5 ± 1.4 1.0 ± 0.2

Postoperative opioid analgesic requirement Yes Np Hospital length of stay (days) Time to resume normal diet (days) NS: Non-significant; Postop: Postoperative.

P-value p < 0.001

NS (p: 0.06)

NS (p: 0.9) NS (p: 0.09) NS (p: 0.4) p < 0.001

NS (p: 0.4) NS (p: 0.1)

NS (p:0.2)

NS (p: 0.09) p < 0.001

Carvalho_Stesura Seveso 25/03/19 17:11 Pagina 3

Transumbilical adrenalectomy

Table 4. Pathological data between groups. Group 1: patients submitted to standard multi-port laparoscopy adrenalectomy. Group 2: patients submitted to transumbilical approach for laparoendoscopic single-site adrenalectomy. Tumor data Mean pathological diameter (mm) Adenoma Benign pheochromcytoma Malignant pheochromcytoma Intermediate pheochromcytoma Cortical hyperplasia Carcinoma Myelolipoma Metastatic lesion ab initio Ganglioneuroma Cavernous hemangioma Cyst Undetermined

Figure 1. Survival curves between groups. Group 1: patients submitted to standard multi-port laparoscopy adrenalectomy. Group 2: patients submitted to transumbilical approach for laparoendoscopic single-site adrenalectomy.

Group 1 Group 2 P-value 42.4 ± 27.2 26.50 ± 16.3 p < 0.001 41.4% 48.8% p: 0.04 20.7% 12.2% 6.9% 2.4% 1.7% 2.4% 0% 17.1% 10.3% 4.9% 6.9% 0% 1.7% 4.9% 0% 2.4% 1.7% 0% 3.4% 0% 5.2% 4.9%

Table 5. Characteristics of the tumours submitted to transumbilical partial LESS adrenalectomy. Tumor data N Laterality Left Right Bilateral Yes No Presentation Cushing disease Arterial hypertension Incidental Functioning adenoma Yes No Produced hormone Cortisol Aldosterone Mean Imaging diameter on CT (mm) Mean Imaging diameter on CT > 40 mm Pathological data Adenoma Cortical hyperplasia Unknown cause Operative time (minutes) Hemorragic losses < 200 cc Need of drainage Resume to normal diet (days) Hospital length of stay (days) Reoperation; Perioperative complications; Relapse Improved or normalized arterial pressure Postoperative need for replacement medical therapy Follow-up (months)

Value 9 41.7% 58.3% 55.6% 44.4% 41.7% 33.3% 25% 100% 0% 58.3% 41.7% 21.8 ± 10.3 0% 50% 41.7% 8.3% 100.4 ± 31.3 100% 25% 1 ± 0.1 2.8 ± 1.4 0 88.8% 16.7% 17.4 ± 10.6

absence of surgical plans in a lesion that revealed to be posteriorly a melanoma metastasis. There were four perioperative complications, all of them during or after a standard multi-port laparoscopic adrenalectomy. There was no difference concerning postoperative opioid analgesic requirement and hospital length of stay. The hospi-

tal length of stay was mainly conditioned by medical or hormonal issues more than the surgery itself. However, the time to resume normal diet was lower in group 2. There were neither reoperations nor perioperative mortality and the tumor laterality did not influence surgical morbidity (p > 0.05). Transumbilical LESS technique allowed for a completely hidden scar in all cases, with excellent cosmesis. The final pathology is shown in Table 4. The mean pathological diameter was inferior in the group 2 and, in both groups, benign adenoma was the most common diagnosis. In the next table (Table 5), there is a brief summary on our experience with partial adrenalectomy. All of them were submitted to transumbilical LESS technique and all lesions were hormone producing. More than half were bilateral and presented mostly with symptoms of Cushing disease and arterial hypertension. The pathological data revealed mainly adenoma and cortical hyperplasia. Overall mean follow-up time was 94.9 ± 3.1 months (group 1 = 92.1 ± 5.7 months versus group 2 = 95.6 ± 2.4 months with no statistically difference between groups, p = 0.7), as shown in Figure 1.

DISCUSSION

Laparoendoscopic single-site adrenalectomy is a minimally invasive surgical technique that is being increasingly used. Transumbilical route offers the opportunity to remove the adrenal gland or only the adrenal tumor with only one hidden incision. Therefore, the level of patient with the scar cosmetics is expected to be better. Archivio Italiano di Urologia e Andrologia 2019; 91, 1

Carvalho_Stesura Seveso 25/03/19 17:11 Pagina 4

J.A. Carvalho, P. Tiago Nunes, H. Antunes, B. Parada, E. Retroz, E. Tavares-da-Silva, I. Paiva, A. José Figueiredo

Wang et al. (7) concluded that laparoendoscopic single-site adrenalectomy caused less postoperative pain, albeit, requiring a longer surgical time (55-206 minutes). Other positive factors in favor of laparoendoscopic single-site adrenalectomy are reduced length of hospital stay and improved postoperative aesthetics (8). Jeong et al. (9) compared transumbilical LESS with standard LA to remove a benign adrenal adenoma and concluded that there were no differences concerning operative time, estimated blood loss and hospital stay but the sample was only nine patients. Our results showed that transumbilical approach for laparoendoscopic single-site adrenalectomy for adrenal tumors is a feasible and safe alternative to standard laparoscopic adrenalectomy: operative time, hemorrhagic losses, postoperative opioid analgesic requirement and hospital stay were similar, yet normal diet was resumed earlier. More standard LA cases were drained, but this difference to transumbilical LESS may have been promoted by a stronger focus on cosmetics. The coordination between the surgeon and assistant is vital for this procedure to avoid clashing of instruments with the camera: for that reason, bent instruments were used for the left surgeon hand, along with a flexible camera. Operative time was the same for the two techniques, but patient selection could be a bias to the analysis: patients submitted to laparoendoscopic single-site adrenalectomy were typically younger, with less comorbidities and with lesions of adrenal gland with a smaller diameter. The rate of perioperative complications and the need for conversion to open surgery was zero in the laparoendoscopic single-site adrenalectomy and only one case of the standard multi-port laparoscopic adrenalectomy need conversion due to absence of surgical safer plans. Again, patient selection is extremely important to choose the laparoscopic approach instead of the open approach. The high degree of difficulty and the alleged longer surgical learning curve makes this surgical approach only feasible for experienced laparoscopic surgeons. In our institution, a single urologist performed the transumbilical laparoendoscopic single-site adrenalectomies and standard laparoscopic adrenalectomies were executed by several urologists. The reduced drainage need and the faster recovery of normal diet in transumbilical LESS adrenalectomies could be biased for that reason. LESS approach can be implemented in partial adrenalectomy (10). We started to do partial adrenalectomy and all of them were done by transumbilical LESS technique and all were hormonal active adrenal tumors. During the last years, partial adrenalectomy has been accepted for adrenal tumors in unilateral glands or in patients with hereditary syndromes. Our experience is limited, the follow-up is short to see if there is any relapse and only two patients are not corticoid-free of medical therapy. Partial adrenalectomy is especially done in Conn’s syndrome and in pheochromocytoma. In our series, no pheochromocytoma was submitted to partial adrenalectomy probably because of the multifocal nature of the disease that could explain the relatively high recurrence rate in hereditary pheochromocytoma (10) and for that reason we did not perform partial adrenalectomies in these patients. Nagaraja et al. (6) found that the overall recurrence rate was 8% and 85% of the patients were steroid-free. In our series, no relapse

Archivio Italiano di Urologia e Andrologia 2019; 91, 1

was found and 83.3% of patients did not need any substitutive therapeutic after surgery. More experience and more time are needed to evaluate if this technique could be a good alternative to total adrenalectomy. Although LESS partial adrenalectomy may be a well-tolerated and feasible procedure to reduce endocrinopathy, studies proving long-term outcome and controlled trials are missing: earlier publications suggested that only one-third of one gland is sufficient to avoid hormonal deficiency (6).

CONCLUSIONS

Transumbilical approach for laparoendoscopic single-site adrenalectomy for adrenal tumours could be a good alternative to standard laparoscopic adrenalectomy. Our results showed similar perioperative data, less drainage, quicker return to normal diet and with no reoperations or perioperative mortality.

REFERENCES

1. Gagner M, Lacroix A, Bolté E. Laparoscopic adrenalectomy in Cushing’s syndrome and pheochromocytoma. N Engl J Med. 1992; 327:1033-1033. 2. Miyajima A, Hattori S, Maeda T, et al. Transumbilical approach for laparo-endoscopic single-site adrenalectomy: initial experience and short-term outcome. Int J Urol. 2012; 19:331-5. 3. Piskun G, Rajpal S. Transumbilical laparoscopic cholecystectomy utilizes no incisions outside the umbilicus. J. Laparoendosc. Adv Surg Tech. A 1999; 9:361-4. 4. Esposito C. One-trocar appendectomy in pediatric surgery. Surg Endosc. 1998; 12:177-8. 5. Aron M, Canes D, Desai MM, et al. Transumbilical single-port laparoscopic partial nephrectomy. BJU Int. 2009; 103:516-21. 6. Colleselli D, Janetschek G. Current trends in partial adrenalectomy. Curr Opin Urol. 2015; 25:89-94. 7. Wang L, Wu Z, Li M, et al. Laproendoscopic single-site adrenalectomy versus conventional lapartoscopic surgery: a systematic review and meta-analysis of observational studies. J Endourol. 2013; 27:743-750. 8. Lal G, Duh QY. Laparoscopic Adrenalectomy – Indications and technique. Surg Oncol. 2003; 12:105-123. 9. Jeong BC, Park YH, Han DH, et al. Laparoendoscopic single-site and conventional laparoscopic adrenalectomy: a matched case-control study. J Endourol. 2009; 23:1957-60. 10. Ho CH, Liao PW, Lin VC, et al. Laparoendoscopic single-site (LESS) retroperitoneal partial adrenalectomy using a custom-made single-access platform and standard laparoscopic instruments: technical considerations and surgical outcomes. Asian J Surg. 2015; 38:6-12. Correspondence João André Carvalho, MD (Correspondence Author) joao.andre.mendes.carvalho@gmail.com Rua Paulo Quintela, Lote 6,7ºB, 3030-393 Coimbra (Portugal) Pedro Tiago Nunes, MD - ptnunes@gmail.com Hugo Antunes, MD - hugoantunes4@gmail.com Belmiro Parada, MD - parada.belmiro@gmail.com Edson Retroz, MD - edson.retroz@gmail.com Edgar Tavares-da-Silva, MD - edsilva.elv@gmail.com Isabel Paiva, MD - ipaiva@netcabo.pt Arnaldo José Figueiredo, MD - ajcfigueiredo@gmail.com Praceta Prof. Mota Pinto 3000-075 Coimbra (Portugal)

Bianchi_Stesura Seveso 31/03/19 11:02 Pagina 5

DOI: 10.4081/aiua.2019.1.5

ORIGINAL PAPER

Posterior muscle-fascial reconstruction and knotless urethro-neo bladder anastomosis during robot-assisted radical cystectomy: Description of the technique and its impact on urinary continence Federico Mineo Bianchi 1, 2, Daniele Romagnoli 1, Daniele Dâ&#x20AC;&#x2122;Agostino 1, Antonio Salvaggio 1, Marco Giampaoli 1, Paolo Corsi 1, Lorenzo Bianchi 1, Marco Borghesi 2, Riccardo Schiavina 2, Eugenio Brunocilla 2, Peter Wiklund 3, Angelo Porreca 1 1 Department

of Urology, Policlinic of Abano Terme (Padova), Italy; of Urology, S. Orsola-Malpighi Hospital, University of Bologna, Italy; 3 Department of Urology, Mount Sinai Institution, Icahn School of Medicine, USA. 2 Department

Summary

Objective: The aim of our study is to describe the use of posterior muscle-fascial reconstruction during urethro-ileal anastomosis in bladder cancer (BC) patients submitted to robot-assisted radical cystectomy (RC) with orthotopic neobladder (ON) and its role in facilitating day- and night-time continence recovery during a 12-month follow up. Materials and methods: We prospectively collected data from 42 consecutive patients who underwent RARC with totally intracorporeal ON and extended pelvic lymph node dissection (PLND) at our Institution from June 2014 to October 2017. Prior to the urethro-neobladder anastomosis we reconstructed the Denonvilliers Fascia (DF) as previously described for radical prostatectomy using a bidirectional barbed suture. Day and night-time recovery rates were reported at 3, 6 and 12 months after surgery, with continent patients being those using either no urinary pads or 1 safety pads. Results: Median age at surgery was 63 yrs, 41 (97.6%) patients were male. 28 (66.7%) patients presented a clinical T2 disease. Median operative time and median ON reconstruction time were 450 minutes and 180 minutes respectively. 13 (31%) individuals had non-organ confined disease, with 11 (26.2%) patients with positive lymph nodes (median 3 positive lymph nodes) and 2 (4.8%) with non-urothelial cancer at final pathologic examination. Median hospital stay and median catheterization time were 7 (IQR 7-8) and 21 (IQR 19-22). During first 30 post-operative days we recorded 7 (16.7%) low-grade Clavien and 2 (4.8%) IIIa Clavien complications, whereas between 30 and 90 postoperative days we recorded 4 (9.5%) low-grade, 4 (9.5) IIIa and 1 (2.4%) IIIb complications. Day-time and night-time continence rates were 61.9% vs 52.4%, 73.8% vs 64.3% and 90.5% vs 73.8% at three, six and twelve months follow up. Day-time continence was significantly superior in the younger group (97% vs 57%, p 0.01); night-time continence rates were also superior among < 70 yrs patients, despite not reaching statistical significance (77% vs 57%, p 0.3). Conclusions: Posterior muscle-fascial reconstruction aids continence recovery in BC patients undergoing RARC with ON, with younger and fitter patients most benefitting from ON reconstruction.

KEY WORDS: RARC; Orthotopic neobladder; Posterior musclefascial reconstruction; Robotic surgery; Radical cystectomy. Submitted 8 January 2019; Accepted February 2019

INTRODUCTION

Radical cystectomy with pelvic lymph node dissection represents the gold standard treatment for muscle-invasive bladder cancer (1). Despite ileal conduit (IC) being the most commonly performed type of urinary derivation (UD), orthotopic neobladder (ON) reconstruction might lead to a better quality of life, mainly due to a better preservation of patientâ&#x20AC;&#x2122;s self-image, especially among younger individuals (2). Robot-assisted radical cystectomy (RARC) was first described more than 10 years ago and is steadily gaining popularity among tertiary care centers, but most cases of ON are performed through a minilaparotomy (3, 4). Totally intracorporeal robot-assisted ON have been shown to be comparable in terms of urodynamic profiles to open ON, as high-volume and lowpressure reservoirs, despite worse continence rates during the first months after surgery (5). Continence rate usually improve throughout follow up, as the ON requires months to reach its full functional capacity, with 75-95% and 50-85% day-time and night-time continence rates at long term follow-up, respectively (6-8). The aim of our study is to describe our novel technique to perform urethra-neobladder anastomosis and to present its functional results through a 12 months follow-up, with particular regard to day-time and night-time continence rates.

MATERIALS

AND METHODS

We prospectively collected data from 42 patients who consecutively underwent RARC with pelvic lymph node dissection (PLND) and totally intracorporeal orthotopic neobladder (ON) reconstruction from June 2014 to October 2017 at our Institution. Every surgical procedure was performed by 2 surgeons (AP and AS) with previous experience of urologic robot-assisted surgery. The first procedures were performed after completing a modular training program under a skilled surgeon (PW) (9). Surgeons from a second Tertiary Center participated as table-assistants, after a week of video sessions, as a part of a structured modular training to gradually master

No conflict of interest declared. Archivio Italiano di Urologia e Andrologia 2019; 91, 1

Bianchi_Stesura Seveso 31/03/19 11:02 Pagina 6

F.M. Bianchi, D. Romagnoli, D. D’Agostino, A. Salvaggio, M. Giampaoli, P. Corsi, L. Bianchi, M. Borghesi, R. Schiavina, E. Brunocilla, P. Wiklund, A. Porreca

the technique. For each patient we prospectively reported intra- and peri-operative data, with complete pathologic data. Complications were stratified as early, during first 30 post-operative days, and late, from 30 to 90 postoperative days, and were graded according to ClavienDindo classification. Day-time and night-time continence were evaluated at 3, 6 and 12-month follow up. Continence was defined as the need for 1 safety pad or urine loss inferior than 10 g at pad test (10). Indications RARC with ON was proposed to patients with either muscle-invasive bladder cancer (MIBC) or non-muscle-invasive bladder cancer (NMIBC) with high risk features, namely high-grade tumour with carcinoma in situ (CIS), recurrent high-grade disease after bladder instillations with Bacillus Calmette-Guerin (BCG), multiple and/or large high-grade tumours, recurrent multifocal large low-grade tumours (11, 12). Previous abdominal surgery wasn’t considered as an absolute contraindication for robotic surgery, albeit it could lead to sometimes long pre-operative laparoscopic lysis of peritoneal adherences. The presence of tumour of the prostatic urethra leads to a higher chance of urethral lesions, although it is not considered as an absolute contraindication for ON reconstruction (13). An intra-operative frozen section was performed to exclude tumour localization of the urethral stump, despite missing 33% of CIS at this site (14). As commonly scheduled to prostate cancer patients undergoing radical prostatectomy (RP), pre-operative mpMRI was performed to determine the extent of nervesparing (NS) surgical plan in younger and sexually active individuals (15). Compromised renal and/or hepatic function were considered as excluding factors for ON reconstruction, as well as severe chronic bowel inflammation. Age and previous abdominal radiotherapy were not considered as absolute contraindications, although elderly patients share a higher risk of enuresis and nighttime incontinence (8, 16-18). Surgical procedure With the patient in steep Trendelenburg position we perform trans-peritoneal approach using Da Vinci Xi® Surgical System (Intuitive Surgical, Sunnyvale, CA, USA). The ureters are isolated from 4-5 cm below the pelvicureteral junction to the Waldeyer’s sheath, where they are clipped using 2 Hemo-Locks®. The left ureter is transposed through the sigmoid mesocolon. The radical cystoprostatectomy with extended pelvic lymph node dissection is performed as previously described (19, 20). For the only female patient included in our study the uterus and the ovaries were removed along with the anterior wall of the vagina, whose identification was eased by manipulating a sponge in the vagina. After proper examination, no signs of tumour invasion of the vaginal walls were detected, thus allowing us to also preserve the autonomic nerves that run through its lateral walls. The vaginal edges were finally closed using a “clam-shell technique” (20). Uni- or bilateral nerve-sparing was performed whenever oncologically safe, according to pre-operative mpMRI results. During the initial part of radical cystectomy, the

Archivio Italiano di Urologia e Andrologia 2019; 91, 1

peritoneum was incised just below the tips of the seminal vesicles to expose the Denonvilliers’ fascia (DF). In case of nerve-sparing procedures the fascia was then opened and a surgical plane between DF and the rectum was developed uni or bi-laterally, as performed during robotic prostatectomy (21). It is essential to spare as much as possible the rhabdosphincter as well as distal urethra, to maintain an adequate closure pressure. After dissection of the prostatic apex, a frozen section of the distal urethra is performed to exclude urethral tumours. Each patient also underwent extended PLND, including external as well as internal and common iliac lymph nodes (LN), obturator fossa and pre-sacral area LN. After removal, the cystoprostatectomy specimen and LN are placed in two different impermeable bags to avoid leakage of neoplastic cells. The Da Vinci Xi® is then un-docked, and patient position is flattened to around 10-15° of Trendelenburg to proceed with the reconstructive phase. Anastomosis technique and totally intracorporeal neobladder reconstruction After further docking of Da Vinci Xi® Surgical System, a distal ileal segment is mobilized to reach down the urethral stump. Using a 35 or 45 cm bidirectional barbed suture 3/0 (Filbloc® Assut, Europe) as a first step we stitch the Denonvilliers Fascia (DF) with both needles, as performed during urethro-vesical anastomosis of radical prostatectomy (RP) (21-23). Using the left needles, the DF is gently transposed to the fibrous part of the sphincter with to bites from left to right. The DF is then firmly attached to the fibrous sphincter using the right end of the suture. In our opinion, this step is as important during ON as for RP. The distribution of tensions will reduce the tractions upon the urethro-ileal anastomosis, limiting urinary leakages and facilitating urinary continence recovery. A 20 F opening is then created on the anti-mesenteric edge of the lower ileal segment using robotic scissors. During the second step, the left end is used to approximate the posterior side of urethral stump to the lower margin of the 20 F opening of the ileal segment using two bites from left to right. With the right end the posterior distal urethra is sutured to the lower margin of the ileal opening. During the third step the urethro-ileal anastomosis is then completed stitching the anastomosis anticlockwise from 5’ to 12’ using the right end and clockwise from 7’ to 12’ using the left end according to Van Velthoven technique. A 20 F tri-lumen catheter is then placed through the anastomosis. The ON is then completed according to the technique described by Hosseini using a 50 cm distal ileal segment with a full intracorporeal approach (20). Statistical analysis Continuous variables were reported as medians with interquartile ranges (IQR) and categorical variables were described as frequencies with percentages. Chi-square was used to compare day- and night-time urinary recovery rates among patients aged < 70 yrs and those ≥ 70 yrs, using a one-tailed 95% confidence interval. Statistical analysis was performed with Statistical Package for Social Science (SPSS) v 21 for Macintosh.

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Posterior muscle-fascial reconstruction before urethro-neobladder anastomosis

RESULTS

Table 1 depicts pre-operative features. 41 out of 42 patients were male, with median age of 63 yrs, median American Society of Anaesthesiology (ASA) score of 2 and median BMI of 26. 28 (66.7%) had MIBC with 11 individuals (26.2%) with associated CIS; 39 BC patients (92.9%) had a high-grade disease, 15 (35.7%) were submitted to intravesical instillations of BCG and 14 (33.3%) underwent a cycle of adjuvant chemotherapy. Median operative time was 450 minutes (Table 2), with median cystectomy time of 120 minutes, median PLND time of 90 minutes and median ON reconstruction time of 180 minutes. Median estimated blood loss (EBL) was 225 ml, 3 (7.1%) patients received intra-operative blood transfusions, 17 (41.5%) and 7 (17.1%) underwent bilateral and unilateral NS preservation, respectively. No patient was converted to laparotomic cystectomy. 2 (4.8%) patients had CIS at final pathology, 8 (19%) had T0 disease and 13 (31%) had non-organconfined BC; 9 (21.4%) patients had concomitant CIS, 1 (2.4%) had positive BC margins and 2 (4.8%) individuals presented a squamous cell carcinoma (SCC). Each patient underwent extended PLND, with a median of 31 lymph node (LN) retrieved. 11 patients had positive lymph nodes at final pathology, with a median of 3 (IQR 1-9) LN involved. 17 (41.4%) patients had concomitant prostatic carcinoma (PC), with 12 (29.3%) Gleason grade 1 and 5 (12.2 %) grade 2 disease, respectively, and just one case (2.4 %) of positive surgical margins for PC. Post-operative data are shown in Table 3. Median hospital stay was 7 days (IQR 7-8). Median catheterization time was 21 days (IQR 19-22). During first 30 postoperative days we recorded 7 (16.7%) low Clavien grade complications and 2 (4.8%) grade IIIa complications, Table 1. Patients’ demographic and pre-operative data. Number of patients (%) Sex (%) Male Female Age at surgery Median IQR ASA score Median IQR BMI Median IQR Pre-operative stage CIS Ta3 T1 T2 T3-T4 Pre-operative grade Low grade G1-G2 (%) Highgrade G3 (%) Concomitant CIS (%) Previous BCG instillation Neo-adjuvant CHT (%)

42 (100) 41 (97.6) 1 (2.4) 63 (59-68) 2 2 2-3 26 23.6-28 3 (7.1) (7.1) 8 (19) 28 (66.7) 0 (0) 3 (7.1) 39 (92.9) 11 (26.2) 15 (35.7) 14 (33.3)

IQR: Interquartile range; ASA: American Society of Anesthesiology; BMI: Body mass index; CIS: Carcinoma in situ; BCG: Bacillus Calmette-Guérin; CHT: Chemotherapy.

Table 2. Patients’ peri-operative data. Total operative time (min) Median IQR Cystectomy time (min) Median IQR PLND time (min) Median IQR ON time (min) Median IQR Estimated blood loss (ml) Median IQR Intraoperative blood transfusions (%) Conversion to open surgery (%) NS procedure (%)* No NS Unilateral NS Bilateral NS Pathologic stage (%) CIS T0 T1 T2 T3 T4 Concomitant CIS (%) Positive surgical margins (%) Hystotype (%) No tumor TCC SCC PLND (%) Number of LN retrieved Median IQR N+ (%) Number of positive LN # Median IQR Incidental PCa (%)* Gleason grade group* 1 2 3-5 Positive PCa margins (%) **

450 410-480 120 80-150 90 80-110 180 120-240 225 127.5-312.5 3 (7.1) 0 (0) 17 (41.5) 7 (17.1) 17 (41.5) 2 (4.8) 8 (19) 9 (21.4) 10 (23.8) 9 (21.4) 4 (9.5) 9 (21.4) 1 (2.4) 8 (19) 32 (76.2) 2 (4.8) 42 (100) 31 24-37 11 (26.2) 3 1-9 17 (41.4) 12 (29.3) 5 (12.2) 0 (0.0) 1 (6%)

IQR: Interquartile range; PLND: Pelvic lymph node dissection; ON: Orthotopic neobladder; NS: Nerve-sparing; CIS: Carcinoma in situ; TCC: Transitional cell carcinoma; SCC: Squamous cell carcinoma; LN: Lymph node; PCa: Prostate cancer. * Among male patients; ** Among male patients with concurrent PCa; # Patients with positive lymph nodesy.

with 4 (9.5%) individuals who were re-admitted at our Institution. Between 30 and 90 post-operative days 4 (9.5%) low grade Clavien complications were registered, with 4 (9.5%) grade IIIa complications and 1 (2.4%) IIIb complication (due to urinary leakage from the ON), with a total of 7 patients re-admitted at our Institution. No patients deceased during first 90 post-operative days. 22 (55.3%) patients reported regular sexual intercourses after 90 post-operative days with oral phosphodiesterase-5 inhibitors (PDE 5). Archivio Italiano di Urologia e Andrologia 2019; 91, 1

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F.M. Bianchi, D. Romagnoli, D. Dâ&#x20AC;&#x2122;Agostino, A. Salvaggio, M. Giampaoli, P. Corsi, L. Bianchi, M. Borghesi, R. Schiavina, E. Brunocilla, P. Wiklund, A. Porreca

Table 3. Post-operative and within-90 post operative days features. Hospital stay (days) Median IQR Catheterization time (days) Median IQR < 30-day Clavien grade complications 0 I II IIIa IIIb IV-V < 30-day complications (%) Lymphocele Ureteral stent displacement UTI Paralytic ileus Uretero-ileal anastomosis stricture > 30-day re-admission rate (%) > 30 and < 90-day Clavien grade complications 0 I II IIIa IIIb IV-V > 30 and < 90-day complications (%) Lymphocele Uretero-ileal anastomosis stricture UTI Acute retention of urine Urinary leakage > 30 and < 90-day re-admission rate (%) 90-day mortality (%) Potency rate*

7 7-8 21 19-22 33 (78.6) 5 (11.9) 2 (4.8) 2 (4.8) 1 (2.4) 1 (2.4) 3 (7.1) 1 (2.4) 3 (7.1) 1 (2.4) 1 (2.4) 4 (9.5) 33 (78.6) 2 (4.8) 2 (4.8) 4 (9.5) 1 (2.4) 0 (0) 2 (4.8) 2 (4.8) 2 (4.8) 2 (4.8) 1 (2.4) 7 (16.7) 0 (0) 22 (53.7)

IQR: Interquartile range; UTI: Urinary tract infection; * Among male patient.

Continence recovery Table 4a depicts overall urinary recovery rate, with 61.9%, 73.8% and 90.5% continent patients during daytime at 3, 6 and 12 months, respectively; night-time continent patients also increased during our 12-month follow-up, with 22 (52.4%), 27 (64.3%) and 31 (73.8%) Table 4a. Overall day- and night-time continence rate at 3, 6 and 12month follow up. 3 months

6 months

12 months

Day-time continence

26 (61.9)

31 (73.8)

38 (90.5)

Night-time continence

22 (52.4)

27 (64.3)

31 (73.8)

Table 4b. Day- and night-time continence rates at 12 months stratified according to age at surgery.

< 70 yrs

â&#x2030;Ľ 70 yrs

p-value

Day-time continence

34 (97.2)

4 (57.1)

0.01

Night-time continence

27 (77.1)

4 (57.1)

0.3

Archivio Italiano di Urologia e Andrologia 2019; 91, 1

continent patients at 3, 6 and 12 months as the ON gradually reached its full functional capacity. After stratifying 12-month continence rates according to age at surgery (namely < 70 yrs vs â&#x2030;Ľ 70 yrs, Table 4b) daytime continence was significantly superior in the younger group (97% vs 57%, p 0.01); night-time continence rates were also superior among < 70 yrs patients, despite not reaching statistical significance (77% vs 57%, p 0.3).

DISCUSSION

In the past decade, many surgeons tried to translate different types of ON, formerly proposed for open radical cystectomy (ORC), for RARC, in order to simplify technique, thus reducing operative times, and to obtain better functional outcomes. The lack of tactile feedback demands a careful manipulation of the bowel down to the deep pelvis, with steep Trendelenburg position. No cases of colonic ON have been described with robotic surgery; each reported technique describe a refluxing uretero-ileal anastomosis (3). Pruthi et al. described a novel technique for robotic neobladder, a U-shaped reservoir without bowel cross-folding and using a stapler device to reduce intraoperative time (24). As evidenced by other authors, also in our series ON reconstruction is the most time-consuming step during RARC, with a median time of 180 minutes, compared to 120 minutes for radical cystectomy and 90 minutes for extended PLND. Although operative times should lower by gaining more experience with this procedure, this phase is indeed a limiting step for a widespread diffusion of this technique. The lack of cross-folding and the use of a stapler device could however translate in a quicker renal impairment due to higher reservoir pressures and a higher rate of neobladder calculi respectively. As recently evidenced by RAZOR randomized controlled trial, RARC is not related to fewer early and late post-operative complications than ORC. Despite longer operative times than ORC, RARC is related to a lower EBL, lower blood transfusion rate and shorter hospital stay, with comparable oncologic outcomes (25). Previously, Bochner and al. reported similar outcomes in terms of comorbidities and mortality between ORC and RARC with extracorporeal ON, with higher costs related to robotic surgery (26). During first 90 post-operative days, we recorded 11 Clavien low-grade complications and 7 grade III complication, of those only one was submitted to a further surgical procedure under general anesthesia to repair a urinary fistula. Ureteral strictures represent the most frequent long-term complications after RC with different types of UD, with subsequent loss of renal functions, upper urinary tract infections and need for further invasive procedures. The exact cause for ureteral strictures is unclear but anastomotic ischemia has been proposed as the main factor contributing to their relatively high incidence.(27) In our series 3 (7%) patients developed ureteral strictures during our 3-month follow up, with available literature reports of 5% to 10% of ureteral strictures after RC with uretero-ileal anastomosis; preoperatively dilated ureters are more likely to develop strictures months after surgery (28, 29). The management of ureteral strictures is mostly endoscopic and laparoscopic/robot-assisted among Tertiary

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Posterior muscle-fascial reconstruction before urethro-neobladder anastomosis

Care centers, thus reserving laparotomic surgery to a small number of patients (30). All-grade Clavien complication rate was 48.9%, which is slightly lower than reported > 60%, with up to 7% of mortality in some series, which could proof a good patient selection for ON reconstruction, as further confirmed by a median hospital stay of 7 days. Moreover, median EBL and intraoperative transfusion rates were exceptionally lower than those reported by other authors for totally intracorporeal ON (31, 32). The choice of ON has to be carefully discussed with the patient, with many variables such as age, pre-operative cognitive function, general health, comorbidities, disease stage, post-operative rehabilitation, that are needed to be taken into account when deciding the most suitable type of UD (33, 34). Indeed, younger and fitter patients with low tumour burden are the most likely to benefit from ON reconstruction, with better continence rates and higher QoL scores during follow-up (2). Urethro-ileal anastomosis is a crucial step during ON reconstruction. A tension-free anastomosis is paramount to prevent strictures and urinary leakages from the urethro-ileal anastomosis. A proper preservation of the external urinary sphincter when dissecting the prostatic apex and the identification of an ileal segment with an adequately long mesentery are crucial to reduce as possible tension when suturing ON to the membranous urethra (3). The length of membranous urethra has been itself identified as a very important parameter to predict good continence recovery rates after RP (35). In this context, posterior musculofascial reconstruction with subsequent urethro-ON anastomosis using a bidirectional barbed suture, as described for RP, limits tension upon the anastomosis, thus reducing urinary leakages and acute urinary retentions related to strictures (21, 22, 36). In our series, despite a relatively short follow-up, we registered only one case of acute urinary retention and only one urinary leakage, which needed a further surgical procedure to repair the fistula. Continence rates at 12 month-follow up were in line with those previously reported for ORC of 75-95% and 5085% continence rates during day-time and night-time, respectively (8). After stratifying 12-month recovery rates according to age at surgery, day-time and night-time continence rates were superior for patients aged < 70 yrs, despite night-time continence couldnâ&#x20AC;&#x2122;t reach statistical significance due to the low number of elderly patients. Many authors indicated urinary leakage to be the main culprit of lower QoL scores for patients submitted to ON versus those with IC (37, 38). A complete recovery of urinary continence after radical cystectomy with ON is deeply connected to the full maturation of the newly created reservoir. The estimated time to reach a 300-500 ml is around 8 months. Elderly patients are more likely to experience incontinence due to apoptosis of rhabdosphincter cells, with reduced urethral closure pressure, lower sphincter length and progressive denervation of the membranous urethra. Furthermore, nerve-sparing techniques have been found to improve continence rates in patients with ON (6, 7, 39). According to the epidemiological studies 5% of individuals newly diagnosed with PCa declared incontinence prior to any surgical procedure regardless of age, with older individuals with other

urinary disturbances reporting even pre-operative higher incontinence rates (40). Hence, an accurate assessment of urinary continence in patients undergoing RC with ON should be explored, as incontinent patients wouldnâ&#x20AC;&#x2122;t benefit from an orthotopic reconstruction. At last, potency rates were exceptionally good, as 22 out of 24 male patients who underwent uni- or bilateral nerve sparing procedures regular sexual intercourses w/o oral medications with PDE5-I, which further confirms a proper patient selection for this kind of procedure. The main limitations of this study are the relatively small cohort of patient, the lack of a control group, a relatively short follow-up especially for long-term complications and perhaps the lack of urodynamic studies.

CONCLUSIONS

Posterior musclefascial reconstruction before performing urethro-ileal anastomosis helps improving urinary continence in patients undergoing RARC with ON, with comparable results to ORC. A proper patient selection is paramount to fully benefit from ON, with younger and fitter patients experiencing better continence and potency rates. Further studies will be needed to assess whether a posterior reconstruction could translate in changes of the urodynamic profile.

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and ileal orthotopic neobladder in a contemporary cohort. J Urol. 2017; 197:210-215. 11. Sylvester RJ, van der Meijden AP, Oosterlinck W, et al. Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur Urol. 2006; 49:466-5. 12. Fernandez-Gomez J, Madero R, Solsona E, et al. Predicting nonmuscle invasive bladder cancer recurrence and progression in patients treated with bacillus Calmette-Guerin: the CUETO scoring model. J Urol. 2009; 182:2195-203. 13. Autmann RE, Abol-Enein H, Davidsson T, et al. ICUD-EAU International Consultation on Bladder Cancer 2012: Urinary diversion. Eur Urol. 2013; 63:67-80. 14. Gordetsky J, Bivalacqua T, Schoenberg M, Epstein JI. Ureteral and urethral frozen sections during radical cystectomy or cystoprostatectomy: an analysis of denudation and atypia. Urology. 2014; 84:619-23. 15. Schiavina R, Bianchi L, Borghesi M, et al. MRI Displays the prostatic cancer anatomy and improves the bundles management before robot-assisted radical prostatectomy. J Endourol. 2018; 32:315-321. 16. Studer UE, Hautmann RE, Hohenfellner M, et al. Indications for continent diversion after cystectomy and factors affecting long-term results. Urol Oncol. 1998; 4:172-82. 17. Mills RD, Studer UE, Metabolic consequences of continent urinary diversion. J Urol. 1999; 161:1057-66.

30. Schiavina R, Zaramella S, Chessa F, et al. Laparoscopic and robotic ureteral stenosis repair: a multi-institutional experience with a long-term follow-up. J Robot Surg. 2016; 10:323-330. 31. Novara G, Catto JW, Wilson T, et al. Systematic review and cumulative analysis of perioperative outcomes and complications after robotassisted radical cystectomy. Eur Urol. 2015; 67:376-401. 32. Moeen AM, Safwat AS, Elderwy AA, et al. Management of neobladder complications: endoscopy comes first. Scand J Urol. 2017; 51:146-151. 33. Ali AS, Hayes MC, Birch B, et al. Health related quality of life (HRQoL) after cystectomy: comparison between orthotopic neobladder and ileal conduit diversion. Eur J Surg Oncol. 2015; 41:295-9. 34. Månsson A, Davidsson T, Hunt S, Månsson W. The quality of life in men after radical cystectomy with a continent cutaneous diversion or orthotopic bladder substitution: is there a difference? BJU Int. 2002; 90:386-90. 35. Paparel P, Akin O, Sandhu JS, et al. Recovery of urinary continence after radical prostatectomy: association with urethral length and urethral fibrosis measured by preoperative and postoperative endorectal magnetic resonance imaging. Eur Urol. 2009; 55:629-37. 36. Porreca A, Salvaggio A, Dandrea M, et al. Robotic-assisted radical prostatectomy with the use of barbed sutures. Surg Technol Int. 2017; 30: p. 39-43.

18. Skinner DG, Studer UE, Okada K, et al. Which patients are suitable for continent diversion or bladder substitution following cystectomy or other definitive local treatment? Int J Urol. 1995; 2 (Suppl 2):105-12.

37. Gilbert SM, Wood DP, Dunn RL, et al. Measuring health-related quality of life outcomes in bladder cancer patients using the Bladder Cancer Index (BCI). Cancer, 2007; 109:1756-62.

19. Desai MM, Berger AK, Brandina RR, et al. Robotic and laparoscopic high extended pelvic lymph node dissection during radical cystectomy: technique and outcomes. Eur Urol. 2012; 61:350-5.

38. Hedgepeth RC, Gilbert SM, He C, et al. Body image and bladder cancer specific quality of life in patients with ileal conduit and neobladder urinary diversions. Urology. 2010; 76: p. 671-5.

20. Hosseini A, Adding C, Nilsson A, et al. Robotic cystectomy: surgical technique. BJU Int. 2011; 108:962-8.

39. Gilpin SA, Gilpin CJ, Dixon JS, et al. The effect of age on the autonomic innervation of the urinary bladder. Br J Urol. 1986; 58:378-81.

21. Porreca A, D'Agostino D, Dandrea M, , et al. Bidirectional barbed suture for posterior musculofascial reconstruction and knotless vesicourethral anastomosis during robot-assisted radical prostatectomy. Minerva Urol Nefrol. 2018; 70:319-325. 22. Ficarra V1, Gan M, Borghesi M, et al. Posterior muscolofascial reconstruction incorporated into urethrovescical anastomosis during robot-assisted radical prostatectomy. J Endourol. 2012; 26:1542-5. 23. Lin YF, Lai SK, Liu QY, et al. Efficacy and safety of barbed suture in minimally invasive radical prostatectomy: A systematic review and meta-analysis. Kaohsiung J Med Sci. 2017; 33:107-115. 24. Pruthi RS, Nix J, McRackan D, et al. Robotic-assisted laparoscopic intracorporeal urinary diversion. Eur Urol. 2010; 57:1013-21. 25. Parekh DJ, Reis IM, Castle EP, et al. Robot-assisted radical cystectomy versus open radical cystectomy in patients with bladder cancer (RAZOR): an open-label, randomised, phase 3, non-inferiority trial. Lancet. 2018; 391:2525-2536.

40. Porreca A, Noale M, Artibani W, et al. Pros-IT CNR study group. Disease-specific and general health-related quality of life in newly diagnosed prostate cancer patients: the Pros-IT CNR study. Health Qual Life Outcomes, 2018; 16:122.

Correspondence Federico Mineo Bianchi, MD (Corresponding Author) federico.mineobianchi@gmail.com Lorenzo Bianchi, MD - lorenzo.bianchi3@gmail.com Marco Borghesi, MD - mark.borghesi1@gmail.com Riccardo Schiavina, MD - rschiavina@yahoo.it Eugenio Brunocilla, MD - eugenio.brunocilla@unibo.it S. Orsola-Malpighi Hospital, University of Bologna, Via Palagi 9, Bologna (Italy)

27. Lobo N, Dupré S, Sahai A, et al. Getting out of a tight spot: an overview of ureteroenteric anastomotic strictures. Nat Rev Urol. 2016; 13:447-55.

Daniele Romagnoli, MD - danieleromagnoli87@gmail.com Daniele D’Agostino, MD - dott.dagostino@gmail.com Antonio Salvaggio, MD - asalvaggio@casacura.it Marco Giampaoli, MD - giampaoli.marco85@gmail.com Paolo Corsi, MD - pcorsi@casacura.it Angelo Porreca, MD - angeloporreca@gmail.com Policlinic of Abano Terme, Piazza Cristoforo Colombo 1, Abano Terme, Padua (Italy)

28. Hosseini A, Dey L, Laurin O, et al. Ureteric stricture rates and management after robot-assisted radical cystectomy: a single-centre observational study. Scand J Urol. 2018; 52:244-248.

Peter Wiklund, MD - peter.wiklund@mountsinai.org Mount Sinai, 625 Madison Avenue, New York City, New York (USA)

26. Bochner BH, Dalbagni G, Sjoberg DD, et al. Comparing open radical cystectomy and robot-assisted laparoscopic radical cystectomy: a randomized clinical trial. Eur Urol. 2015; 67:1042-1050.

29. Hautmann RE, de Petriconi R, Kahlmeyer A, et al. Preoperatively dilated ureters are a specific risk factor for the development of ureteroenteric strictures after open radical cystectomy and ileal neobladder. J Urol. 2017; 198:1098-1106.

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DOI: 10.4081/aiua.2019.1.11

ORIGINAL PAPER

Factors associated with urinoma accompanied by ureteral calculi Ercan Öğreden 1, Ural Oğuz 1, Mehmet Karadayı 1, Erhan Demirelli 1, Alptekin Tosun 2, Mücahit Günaydın 3 1 Giresun

University, Faculty of Medicine, Department of Urology, Giresun, Turkey; University, Faculty of Medicine, Department of Radiology, Giresun, Turkey; 3 Giresun University, Faculty of Medicine, Department of Emergency Medicine, Giresun, Turkey. 2 Giresun

Summary

Objective: Urinoma is a rare entity and mainly occurs due to acute obstruction such as ureteral stone. We aimed to demonstrate factors associated with urinoma accompanied by ureteral calculi. Material and methods: Data of 550 patients who were diagnosed with ureteral stone by computed tomography (CT) were analyzed retrospectively. In 20 patients perirenal urinoma was associated with ureteral calculi (group I), whereas in other 530 patients no urinoma was detected (group II). Gender, age, size, side and localization of the stone, hydronephrosis, fever, sepsis, urinary tract infections (UTIs), hematuria, serum creatinine, blood urea nitrogen (BUN), white blood cell (WBC), C-reactive protein (CRP), presence of diabetes mellitus (DM), hypertension (HT) and cronic kidney disease (CKD) of the two groups were compared. Results: The average age of the patients were 46.2 (20-71) and 44.9 (10-82) years in group I and group II, respectively (p > 0.05). According to our results leukocytosis, microscopic and macroscopic hematuria, UTIs, increase of serum creatinine, BUN and CRP, diagnosis of DM and HT were significantly associated with urinoma (p < 0.05). In addition, patients with distal ureteral stones are more prone to urinoma (p = 0.001). An interesting finding of the study was that the stone size in group I (median 5 mm [range 3-8]) was significantly smaller than in group II (9.3 mm [4-25]; p = 0.001). Conclusions: Small stone size, distal localisation of the stone in ureter, leukocytosis, hematuria, UTIs, increase of serum creatinine, BUN and CRP, presence of DM and HT are associated with perirenal urinoma.

KEY WORDS: Computerized tomography; Factors associated with urinoma; Prevalence; Ureteral calculi; Urinoma. Submitted 26 August 2018; Accepted 11 October 2018

INTRODUCTION

Urinoma is defined as an extravasated urine collection with surrounded fibrous capsule. Urinary stones, surgical ligation of ureters, tumors, posterior urethral valve (PUV) and blunt or penetrating traumas are involved in the etiology of urinoma (1). Spontaneous urinoma is rare and ureteral stones are among the most common causes of spontaneous urinoma. High hydrostatic pressure applied on the ureter wall by the impacted ureteral stone and formation of micro-tears in the mucosa during stone passage play an important role in the mechanism of uri-

noma (2). When the intraluminal pressure exceeds 35 cm/H2O, rupture develops from the fornix, which is the weakest part of the collecting system, resulting in urinoma. In this case, the urine is first spread to the subcapsular area, then to the perirenal region and the retroperitoneal area (3). Urinoma leads to local irritation, inflammatory side effects, fever, malaise, sepsis, acute abdomen and deterioration of general condition (4). Computed Tomography (CT) is adequate for definitive diagnosis of urinoma. At CT, fluid collection around the kidney and imaging of the stone within the ureter is sufficient for the diagnosis of spontaneous urinoma. It may also document the contrast extravasation from the collecting system and determine the location of the rupture (5, 6). Ureterorenoscopic stone surgery and ureteral stent placement are recommended in the current treatment of spontaneous urinoma (7). There is no specific finding of urinoma and this may lead to delayed diagnosis and treatment causing increased morbidity and mortality in patients who have admitted to emergency clinics with colic pain. In this study, it was aimed to identify the risk factors for urinoma, to define parameters that would facilitate the diagnosis and help in choosing appropriate treatment, and to discuss the topic under light of current literature.

MATERIAL

AND METHODS

Between May 2010 and March 2018, 11,000 patients were diagnosed with ureteral stone at our center. The diagnosis of stone was made by direct X-ray, intravenous pyelogram (IVP), ultrasonography (USG), unenhanced CT and contrast-enhanced CT. The data of 2100 patients who underwent ureterorenoscopy (URS) due to ureteral stone were retrospectively reviewed. Electronic and conventional medical records, including demographic information, laboratory data, electronic notes, operative reports and radiological reports, were reviewed for each patient. A total of 550 patients who were diagnosed with ureteral stone by CT and whose data were complete were included in the study. Patients with kidney trauma and patients with a history of kidney surgery were excluded from the study. Vital findings were also queried from the medical records and

No conflict of interest declared. Archivio Italiano di Urologia e Andrologia 2019; 91, 1

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E. Öğreden, U. Oğuz, M. Karadayı, E. Demirelli, A. Tosun, M. Günaydın

presence of UTIs, fever and urosepsis were recorded. Patients' age, gender, stone localization, presence of hydronephrosis, fever, sepsis, UTIs, microscopic and macroscopic hematuria, serum creatinine, BUN, WBC and CRP values were evaluated. Chronic diseases such as diabetes mellitus (DM), hypertension (HT) and chronic kidney disease (CKD) were recorded. Urine cultures were obtained from patients with asymptomatic bacteriuria and appropriate empirical treatment was initiated. Symptomatic UTIs criteria included fever, costovertebral angle sensitivity, pyuria (≥ 10 white blood cells per highpower field), and positive urine culture [≥ 105 colonyforming units (CFU) of uropathogen/mL]. Findings of urosepsis included at least 2 signs of SIRS (Systemic Inflammatory Response Syndrome) in the presence of infection (Fever > 38°C or < 36°C, heart rate > 90 beats/min, respiratory rate > 20/min or PaCO2 < 32 mm/Hg, WBC > 12,000/mm3 or < 4.000/mm3). Appropriate antibiotic therapy was started according to results of antibiotic susceptibility testing in patients who were diagnosed with urosepsis. Patients were classified as group I (n = 20; 3,6%) if were diagnosed with spontaneous urinoma secondary to ureteral stone and group II (n = 530; 96,4%), if without urinoma (Figure 1). Patients diagnosed with urinoma and ureteral stone were treated with ureteroscopy (URS) and lithotripsy and ureteral double J stent placement. The stents were removed after 4 weeks as treatment was completed. Both groups were compared in terms of gender, age, stone size and stone localization, fever, sepsis, UTIs, hematuria,

serum cratinine, BUN, WBC, CKD values as well as presence of DM, HT and CKD. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Statistical Analysis The data obtained in this study were analyzed with the SPSS 20 (IBM SPSS Statistics; Armonk, NY, USA) package program. Results are presented as frequency and percentage (%). The abnormal distribution of data from each group was confirmed with the Kolmogorov-Smirnov test, thus statistical comparisons were performed using Mann Whitney-U Test. Chi-square test was used to examine the dependency between the groups. A P value less than 0.05 was considered statistically significant.

RESULTS

In this study, we found urinoma in 20 (0.2%) of 11000 patients diagnosed with ureteral stones in our clinic. The mean age of the patients was 46.2 (20-71) years in group I and 44.91 (10-82) years in group II (p > 0.005). Gender distributions of the patients were 16 (80%) male, 4 (20%) female in group I and 339 (63.96%) male and 191 (36.04%) women in group II (p > 0.005). Gender distributions of the patients were similar in both groups. Upper ureter was considered as the segment from renal pelvis to the upper border of the sacrum, middle ureter is as the segment from the upper to the lower border of the sacrum, and lower ureter as the segment which extends from Figure 1. lower border of the sacrum to the The image of spontaneous urinoma. A: Perirenal urinary leak; B: Retroperitoneal bladder. Proximal ureteral stones urinary leakage; C: Stones of millimetric size in the distal ureter; D: Sagittal section were not observed in group I, view of urinoma and distal ureteral stone. while they were present in 345 (65.1%) patients in group II. Middle ureteral stones were found in 5 (25%) patients in group I and 126 (23.8%) patients in group II. Distal ureteral stone distributions in group I and group II were 15 (75%) and 59 (11.1%), respectively (p = 0.001). The difference of distribution of stone localizations between the A. B. groups was statistically significant. Pyuria was found in 5 (25%) patients in group I and in 47 (8.9%) patients in group II (p = 0.032). Microscopic hematuria was detected in 16 patients (80%) in group I and in 42 (7.9%) patients in group II (p = 0.001). Macroscopic hematuria was positive in 9 (45%) and 42 (7.9%) patients, respectively (p = 0.001). Fever was found in 12 (60%) patients in group I and in 30 (5.7%) patients in group II (p = C. D. 0.001) and UTIs were detected in

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Urinoma and ureteral calculi

Table 1. Factors associated with urinoma accompanied by ureteral calculi.

Gender

Pyuria

Microscopik hematuria

Fever

UTI

Urosepsis

CRP WBC

BUN

Creatinin

CKD

Group II n % 339 64.0 191 36.0 530 100 345 65.1 126 23.8 59 11.1 530 100 483 91.1 47 8.9 530 100

Total n % 355 64.6 195 35.4 550 100 345 62.7 131 23.8 74 13.5 550 100 498 90.5 52 9.5 550 100

Absent Exist Total Absent Exist Total Absent Exist Total

4 16 20 11 9 20 8 12 20

20 80 100 55 45 100 40 60 100

488 42 530 488 42 530 500 30 530

92.1 7.9 100 92.1 7.9 100 94.3 5.7 100

492 58 550 499 51 550 508 42 550

Absent Exist Total Absent Exist Total Normal High Normal High Total Normal High Total Normal High Total Absent Exist Total Absent Exist Total Absent Exist Total

15 5 20 18 2 20 6 14 10 10 20 13 7 20 10 10 20 13 7 20 20 0 20 10 10 20

75 25 100 90 10 100 30 70 50 50 100 65 35 100 50 50 100 65 35 100 100 0 100 50 50 100

506 24 530 520 10 530 508 22 506 24 530 492 38 530 505 25 530 507 23 530 523 7 530 506 24 530

95.5 4.5 100 98.1 1.9 100 95.9 4.1 95.5 4.5 100 92.8 7.2 100 95.3 4.7 100 95.7 4.3 100 98.7 1.3 100 95.5 4.5 100

521 29 550 538 12 550 514 36 516 34 550 505 45 550 515 35 550 520 30 550 543 7 550 516 34 550

Male Female Total Proximal Middle Distal Total Absent Exist Total

Localization

Gross hematuria

Group I n % 16 80 4 20 20 100 0 0 5 25 15 75 20 100 15 75 5 25 20 100

Chi Square Test Chi Square p 1.522 0.217

0.001

Fisher's exact

0.032

89.5 10.5 100 90.7 9.3 100 92.4 7.6 100

Fisher's exact

0.001

Fisher's exact

0.001

Fisher's exact

0.001

94.7 5.3 100 97.8 2.2 100 93.5 6.5 93.8 6.2 100 91.8 8.2 100 93.6 6.5 100 94.6 5.5 100 98.7 1.3 100 93.8 6.2 100

Fisher's exact

0.003

Fisher's exact

0.067

Fisher's exact

0.001

Fisher's exact

0.001

Fisher's exact

0.001

Fisher's exact

0.001

Fisher's exact

0.001

Fisher's exact

0.001

UTI: Urinary tract infection; CRP: C-reactive protein; WBC: White blood cell; BUN: Blood urea nitrogen, DM: Diyabetes Mellitus; CKD: Chronic kidney disease; HT: Hypertension.

Table 2. The differences between groups with/without urinoma in terms of age and stone size.

Age

Stone size/mm

Group I Group II Total Group I Group II Total

n 20 530 550 20 530 550

Mean Median Min 46.2 45 20 44.9 44 10 45 44 10 5 4 3 9.3 9 4 9.1 8 3

Max SD 71 13.88 82 13.95 82 13.94 8 1.78 25 3.56 25 3.6

Mann Whitney U Test Rank Avarage z p 274.89 -0.465 0.642 291.73 283.07 74.9

-5.785 0.001

5 (25%) and 24 (4.5%), respectively (p = 0.003). The difference between the two groups was statistically significant in terms of pyuria, hematuria, fever and UTIs. Urosepsis was observed in 2 (10%) patients in group I and in 10 (1.9%) patients group II, however the difference was not statistically significant (p > 0.05). CRP was higher in 14 (70%) patients in group I and in 22 (4.1%) patients in group II (p = 0.001). WBC was high in 10 (50%) patients in group I and in 24 patients (4.53%) in group II (p = 0.001). BUN was high in 7 (35%) patients in group I and in 38 (7.2%) patients in group II (p = 0.001). Creatinine was high in 10 (50%) patients in group I than and in 25 (4.7%) patients in group II (p = 0.001). DM was detected in 7 (35%) and 23 (4.3%) patients in group I and group II, respectively (p = 0.001). CKD was not seen in any patients in group I, whereas 7 (1.3%) patients had CKD in group II (p > 0.05). However, this difference was not statistically significant. HT was found in 10 (50%) patients in group I and in 24 (4.5%) patients in group II (p = 0.001). The difference between the two groups in terms of CRP, WBC, BUN and high serum creatinine values and presence of chronic diseases such as DM and HT was statistically significant. There was no statistically significant difference between the patient groups in term of presence of CKD (Table 1). The mean stone size was 5 (38) mm in group I and 9.3 (425) mm in group II (p = 0.001). The difference in stone size between the two groups was statistically significant (Table 2). According to logistic regression analysis results, 1 mm increase in stone length reduced the risk for urinoma 2.022-fold. The presence of microscopic hematuria and high serum CRP

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E. Öğreden, U. Oğuz, M. Karadayı, E. Demirelli, A. Tosun, M. Günaydın

level were both detected high in patients with urinoma. Logistic regression analysis revealed that distal localization of the stones also increased the risk for urinoma 3.806-fold.

DISCUSSION

As a result of the collecting system disruption at any level from calyces to urethra, the urine that extravasates the urinary system is called urinoma. Urinomas may sometimes, although rare, occur spontaneously. The most common etiological cause of spontaneous urinomas is the ureteral stones (8). Hydronephrosis, UTIs, and increased pressure due to obstruction, provide a basis for rupture. The intraluminal pressure increases on the collecting system as a result of obstruction elsewhere in the system due to a stone and extravasation occurs at the calyceal fornix, the weakest part of the collecting system. The kidneys have mechanisms to protect themselves against increasing pressure in the collecting system. These mechanisms include pyelo-sinus, pyelo-venous, and pyelo-lymphatic backflow. An increase of more than 35 cmH2O in intrapelvic pressure results in the failure of these mechanisms and leads to forniceal rupture (9). Furthermore, small-sized ureteral stones cause microtears during spontaneous passage; this in turn plays a facilitating role in the rupture of collecting system mucosa, resulting in extravasation of urine (10, 11). In their latest study, Gershman et al. (12) reported that 75.7% of distal ureteral stones cause primary urinoma. In the same study, the mean stone size was 4.09 mm with stone size decreasing significantly from proximal ureteral to distal ureteral locations, and urinoma incidence was found to be more frequent in distal ureteral stones. In our present study, 75% of the patients with urinoma had distal ureteral stones and this finding was consistent with the literature. We found that the mean stone size was 5 mm and a 1 mm increase in stone length reduced the urinoma risk of 2.022 fold, whereas the distal localization of stones increased the urinoma risk of 3.806 fold. Apart from obstruction and stasis caused by the stone in the ureteral lumen, in addition UTIs constitute a facilitating factor for development of the urinoma. Spontaneous urinomas that develop due to an ureteral stone may cause side-pain, reno-ureteral pain, renoabdominal pain, as well as vasovagal nausea and vomiting. Ureterovesical junction (UVJ) stones and UTIs can cause urinary urgency, fever, abdominal pain and pain in genital organs. Besides these symptoms, urinomas can result in serious complications. Possible complications include hydronephrosis, paralytic ileus and acute abdomen, electrolyte imbalances, abscess formation, sepsis, and chronic renal failure in delayed cases (11). Gershman et al. (12) reported a UTIs ratio of 5.2% in a retrospective study. The rate of UTIs in our study was 5.3% in accordance with previous reports. UTIs trigger the collecting system rupture and result in the accumulation of infected urine in the retroperitoneal space. This picture sets a ground for urosepsis and retroperitoneal abscess formation in delayed cases (13). In our study, we found that the rate of patients diagnosed with urosepsis was 2.2%, a rate not statistically different from

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that observed in absence of urinoma. Furthermore, retroperitoneal abscess was not observed in any of the patients who were diagnosed with urosepsis. We think that early diagnosis of urinoma along with early surgical and medical treatment were effective in this respect. Sterile urine in contact with the retroperitoneum can trigger an inflammatory response, whereas infected urine may lead to acute abdomen, retroperitoneal abscess formation and retroperitoneal fibrosis in later stages. In patients with urinary infection and pyuria, these complications may be more aggressive and may result in a clinical picture with progression to sepsis by disturbing the general condition in the patients. In many case reports published to this time, it has been reported that urinary infection, pyuria, hematuria and sepsis were present in patients who had diagnosis of urinoma in the emergency room. Blood tests of these cases revealed high WBC, BUN and elevated serum creatinine levels (14). In our study pyuria, hematuria, fever, UTIs and urosepsis were significantly common in the patients with urinoma and CRP and WBC values were also high in these patients. Although urinoma has been reported to play a protective role in renal function, it has been shown an impaired kidney function in several recent case reports. Heikkila et al. (15) demonstrated that urinoma affects renal function and leads to progressive renal damage in 25% of patients. In our study, BUN and plasma creatinine values were significantly higher in the cases with urinoma but CKD did not develop in our patients, probably because of early treatment and early surgical intervention. HT, DM and CKD are common comorbid diseases. Comorbidities are important for the patient in terms of bearing an additional disease to the existing disease and facing an increased morbidity. Especially, the suppression of the current clinical picture by these comorbid diseases may delay the diagnosis and increase the complication rates. Many case reports published in the literature have reported that diagnosis of urinoma might be delayed with accompanied CKD and DM and as a result, the complication rates were increased (11, 15). In our present study, the DM rate was 35% vs 4.3% and the HT rate was 50% vs 4.5% in patients with and without urinoma (p < 0.05). CKD was not seen in any of the patients who had been diagnosed with urinoma. Spontaneous urinoma is a rare disease and most commonly caused by ureteral stones. Until recently, literature about urinoma mainly consisted of case reports only and there was no study on prevalence of urinoma. However, the development of imaging modalities, availability of spiral CT and the widespread use of contrast agents in the clinical settings have led to a relative increase in the number of diagnosed spontaneous urinomas (16, 17). In fact, in the present study, we found urinoma in 0.2% of patients diagnosed with ureteral stones.

CONCLUSIONS

Infection related parameters such as CRP and WBC elevation, pyuria, hematuria, fever, and high creatinine levels were found to be higher in patients with ureteral stones and urinoma. Interestingly, urinomas were more

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Urinoma and ureteral calculi

common in the smaller-sized and distally ureter-located stones. In addition, chronic diseases such as HT and DM have attracted attention as factors that increase urinoma risk in patients with ureteral stones.

Junction Rupture Caused by a Small Distal Ureteral Calculus. Chin Med J (Engl) 2015; 128:3118-19.

REFERENCES

10. Ferri E, Casoni GL, Morabito G, et al. Rupture of the renal pelvis complicating a renal colic: report of a case. Am J Emerg Med. 2006; 24:383-5.

2. Ay D, Yencilek E, Celikmen MF, et al. Spontaneous rupture of ureter: an unusual cause of acute abdominal pain. Am J Emerg Med. 2012, 30:1-2.

11. Gayer G, Zissin R, Apter S, et al. Urinomas caused by ureteral injuries: CT appearance. Abdom Imaging. 2002; 27:88-92.

1. Nouira Y, Ben Younes A, Rekik H, et al. Spontaneous perirenal urinoma during nephritic colic. Ann Urol (Paris) 2000; 34:156-7.

3. Miller NL, Lingeman JE. Management of kidney stones. BMJ. 2007; 334: 468-72. 4. Patil KK, Wilcox DT, Samuel M, et al. Management of urinary extravasation in 18 boys with posterior urethral valves. J Urol. 2003; 169:1508-11. 5. Chen GH, Hsiao PJ, Chang YH, et al. Spontaneous ureteral rupture and review of the literature. Am J Emerg Med. 2014; 32:772-4. 6. Pampana E, Altobelli S, Morini M, et al. Spontaneous ureteral rupture diagnosis and treatment. Case Rep Radiol. 2013; 2013:851859. 7. Stravodimos K, Adamakis I, Koutalellis G, et al. Spontaneous perforation of the ureter: clinical presentation and endourologic management. J Endourol. 2008; 22:479-84. 8. Jeon CH, Kang JH, Min JH, et al. Spontaneous Ureteropelvic

9. Georgieva M, Thieme M, Pernice W, et al. Urinary ascites and perirenal urinoma-a renoprotective "Complication" of posterior urethral valves. Aktuelle Urol. 2003; 34:410-12.

12. Gershman B, Kulkarni N, Sahani DV, et al. Causes of renal forniceal rupture. BJU Int. 2011; 108:1909-12. 13. Titton RL, Gervais DA, Hahn PF, et al. Urine leaks and urinomas: diagnosis and imaging-guided intervention. Radiographics. 2003; 23:1133-47. 14. Pace K, Spiteri K, German K. Spontaneous proximal ureteric rupture secondary to ureterolithiasis. J Surg Case Rep. 2017, 2016. 15. Heikkilä J, Taskinen S, Rintala R. Urinomas associated with posterior urethral valves. J Urol. 2008; 180:1476-78. 16. Murawski M, Gołebiewski A, Komasara L, et al. Rupture of the normal renal pelvis after blunt abdominal trauma. J Pediatr Surg. 2008; 43:e31-33. 17. Ashebu SD, Elshebiny YH, Dahniya MH. Spontaneous rupture of the renal pelvis. Australas Radiol. 2000; 44:125-27.

Correspondence Ercan Öğreden, MD (Corresponding Author) ercanogreden@gmail.com Ural Oğuz, MD Mehmet Karadayı, MD Erhan Demirelli, MD Giresun University, Faculty of Medicine, Department of Urology, Giresun (Turkey) Alptekin Tosun, MD Giresun University, Faculty of Medicine, Department of Radiology, Giresun (Turkey) Mücahit Günaydın, MD Giresun University, Faculty of Medicine, Department of Emergency Medicine, Giresun (Turkey)

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ORIGINAL PAPER

DOI: 10.4081/aiua.2019.1.16

The role of anticholinergic therapy based on the upoint system in the treatment of chronic prostatitis Kamil Fehmi Narter 1, Utku Can 2, Alper Coşkun 2, Kubilay Sabuncu 2, Fatih Tarhan 2 1 Acibadem

Mehmet Ali Aydinlar University, Urology, Istanbul/Turkey; of Urology, University of Health Sciences, Kartal Dr. Lütfi Kırdar Training and Research Hospital, Istanbul/Turkey.

2 Department

Summary

Objective: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common problem and severely impairs the quality of life (QoL). We aimed to investigate the effects of different treatment options on voiding symptoms and QoL in patients with urinary phenotype according to the UPOINT system. Matherial and methods: Ninety-six patients with NIH category II,III CP/CPPS were included in the study prospectively. After the diagnosis, the questionnaires including NIH Chronic prostatitis Symptom Index (NIH-CPSI), International Prostate Symptom Score (IPSS), Overactive Bladder Screening Questionnaire (OAB-V8), and Beck depression inventory were filled by the patients. The patients with urinary phenotype were treated by alpha-blocker, antimuscarinic or both therapy modalities (combined) considering the specific therapy recommendations by UPOINT. The questionnaires applied on the first visit were reapplied after one month and treatment success was evaluated. Results: Seventy-three patients were included in ‘Urinary phenotype’ group (76%) and 23 were included in ‘other phenotypes’ (24%) group of the patients according to the UPOINT classification. Significant improvements of symptoms were observed with the all treatment modalities when the NIH-CPSI, IPSS and OAB-V8 scores were compared before and after treatment in the ‘Urinary phenotype’ group. Significant differences in the percentage of change in values were obtained in the anticholinergic group for pain subdomain of NIH-CPSI and IPSS scores. Conclusion: U-POINT clasification is useful for deciding on the treatment modality in CP/CPSS patients. We showed anticholinergic therapy might be effective option. Addition to the symptomatic recovery, there is need more further studies about effectivity cholinergic system in the prostate tissue.

KEY WORDS: Chronic prostatitis; Anticholinergic therapy, UPOINT system. Submitted 28 August 2018; Accepted 25 September 2018

INTRODUCTION

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disease especially seen in men younger than 50 years old. Its prevalence was reported from 2 to 16% in the male population (1, 2). CP/CPPS has a significant negative impact on quality of life and it may cause depresssion and anxiety due to pyschological effects. This syndrome has not been well described yet and its optimal treatment is not clear. Moreover, there is no standard diagnostic test for CP/CPPS. The diagnosis

of this problematic disease is only on the basis of symptoms such as pain/discomfort in the pelvic area or lower urinary tract symptoms (LUTS) like storage symptoms frequency and urgency (3, 4). Antibiotics, alpha-adrenergic blockers, and anti-inflammatory drugs may be chosen in the treatments for CP/CPSS, but anticholinergic treatment for CP/CPSS has not been preferable yet adequately, and there are few references about this topic (5). According to the National Institutes of Health (NIH), inflammation of the prostate can be classified as acute bacterial prostatis (category I), chronic bacterial prostatitis (category II), chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS, category III) and asymptomatic prostatitis (category IV) (6). CPSS are further subdivided by the presence of inflammation in the extraprostatic secretions or semen (category IIIa) or the absence of it (category IIIb). Although there is no symptoms of disease, chronic prostatitis can be declared histologically on many prostate biopsy reports. The UPOINT system was described in 2008. Patient's symptoms were seperated into six phenotypes as (U)rinary symptoms, (P)sychological dysfunction, (O)rgan specific symptoms, (I)nfectious causes, (N)eurologic dysfunction and (T)enderness of the pelvic floor muscles according to the this system (7). Moreover, comorbidities are often present along with CP/CPSS such as irritable bowel syndrome and fibromyalgia. Recently, a (S)exual dysfunction domain (UPOINT(S)) was described as an additional content to the clinical phenotyping of CP/CPPS (8). Until today, anticholinergic therapy for patients with CP/CPSS has been very few reported as a symptomatic treatment option for voiding problems. Our theory are based on cholinergic system effective on the infectious/inflammation process in the prostate tissue. So that, anticholinergic therapy can be a new alternative and additional therapy option for these patients. Many patients with CP/CPSS may have LUTS and genital/pelvic pain. It depend on this, new individualized treatment modalities for patients with CP/CPPS has been considered as a multimodal therapy based on UPOINT sysytem. For this reason, we aimed to classify patients with CP/CPSS according to the UPOINT system and investigate the effects of different treatment modalities such as anticholinergic treatment on voiding symptoms and quality of life in a prospective clinical trial. No conflict of interest declared.

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Anticholinergic therapy for chronic prostatitis

MATERIALS

AND METHODS

Ninety-six patients with symptoms of CP/CPPS who were referred to our outpatient clinic between March 2014 and May 2015 were enrolled in this prospective study. All patients were evaluated with a detailed medical history, physical examination, and laboratory tests (urine analysis, two glass test, urinary sonographic evaluation, uroflowmetry, and postvoid residual urine volume-PVR). All patients were also asked to fill out National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) (9), International Prostate Symptom Score (IPSS) (10), Overactive Bladder Screening Qustionare version 8 (OABV8) (11), and Beck depression inventory (12). Validated Turkish versions of these all questionnaries are used in the study. NIH categories was designated by the number of leucocytes and culture analysis in the expressed prostate secretion (EPS) examination (modified Meares and Stamey test/two glass test-1968). National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), International Prostate Symptom Score (IPSS), Overactive Bladder Screening Questionnaire version 8 (OABV8), and Beck depression inventory were used to grade the symptoms. Patients aged 20 to 50 years and patients with CP/CPSS (NIH category II, IIIa and IIIb) with pelvic pain/discomfort for 3 or more months, negative urine culture, maximum urinary flow rate of 15 ml/sec or greater were included to study. Patients with medical history of pelvic surgery/previous prostate surgery, benign prostate hyperplasia (BPH), urinary obstruction or high postvoid residual volume (> 100 cc), urinary tract infection, prostatic cancer, urethral stricture, diabetes mellitus, neurogenic lower urinary tract dysfunction and patients who had 5-alpha reductase inhibitors or anticholinergics were excluded from the study. After the NIH-CPSI, IPSS, OAB-V8 and Beck depression inventory evaluations, patients were clinically classified as ‘urinary phenotype’ or ‘other phenotypes’ according to UPOINT system. Alpha blocker (silodosin 8 mg/daily), antimuscarinic (propiverin 30 mg/daily), or combination therapies have been ordered for patients with urinary phenotype, taking into consideration failure of treatments and allergy records in medical history. All patients were classified into the treatment groups as patients with high voiding subdomain of IPSS score were treated with the alpha blocker, patients with high OAB-V8 score were treated with the anticholinergic or patients with both criteries were treated with the alpha blocker and anticholinergic in combined group. Addition to these cut off (IPSS ≥ 8 and OABV8 ≥ 8) values, for the patients with modest and severe depression, cut off value of Beck Depression Inventory was accepted 17 or higher. NIH-CSPI score was evaluated as a succesful with at least a 6-point improvement and experienced improvements in every domain. When similar questionnaire results were obtained, treatment option were selected according to preference of clinician. One month later, all patients were recalled for control, then all questionnaires were applied again and effectiveness of treatment was evaluated. This study was approved by our Instutional Review Board (03.06.2014/8) and was conducted according to the Declaration of Helsinki. All patients gave informed consent. Data were presented as median + standard deviation (SD). Stastical analysis was performed by Mann-Whitney

U, Kruskal-Wallis and Wilcoxon tests with SPSS 12.0 (SPSS Inc. Chicago, IL, USA) and p < 0.05 was considered to indicate significance. The difference in values before and after treatments was defined as ‘∆’ and (∆/value before treatment) x100 was defined as ‘% change’.

RESULTS

Based on the U-POINT scoring system, patients were classified as ‘urinary phenotype’ (n: 73, 76%) and ‘other phenotypes’ (n: 23, 24%). The mean age, duration of symptoms, voiding volume and prostate volume were similar between two groups. LUTS were found to be more frequent in the group of ‘urinary phenotype’. Maximum flow rate at voiding in the ‘urinary phenotype’ group was significant lower than the ‘other phenotypes’. NIH-CPSI, IPSS and OAB-V8 scores were statistically significant higher in the ‘urinary phenotype’ group (p < 0.001). Stastistically difference was obtained in urinary and QoL subdomain of NIH-CPSI, except pain subdomain between urinary and other phenotypes group. Significant differences were also obtained in IPSS subdomain between ‘urinary phenotype’ and ‘other phenotypes’. But Beck depression inventory scores were similar between two groups (Table 1). Three patients with positive prostatic secretion culture (Category II) were treated with antibiotics and the remaining 73 patients with non-bacterial prostatitis (25 patients with category IIIa, 48 patients with category IIIb) were treated with appropriate medical agents. Moreover, alphablockers (n: 19), anticholinergics (n: 16) and combination therapies (n: 38) were initiated to patients in the ‘urinary phenotype’ group, while psychotherapy or physiotheraphy (n: 6) and food supplements contain quercetin (n: 13) were preferred in the group of ‘other phenotypes’. Lifestyle changing and dietery modifications was recommended for all patients (Table 2). Table 1. Evaluation of clinical and demographic data of patients with and without predominant urinary symptoms according to U-POINT score. U-POINT Urinary Other phenotype (n = 73) phenotypes (n = 23) median + SD median + SD Age 37 + 9.6 36.5 + 9 Duration of symptoms (months) 12 + 47 12 + 15.5 Qmax 21 + 8 27 + 6.3 Prostate volume (cc) 22 + 7.5 20 + 8.1 NIH-CPSI 24 + 7.3 19 + 5.8 Pain 10.5 + 4.9 10 + 4.3 Urinary 7 + 2.7 2 + 1.4 QoL 8 + 2.3 6+2 IPSS IPSS 15.5 + 8.1 5.5 + 5.9 QoL 5 + 2.3 3 + 1.3 OAB-V8 18 + 8.4 7 + 5.6 BECK 8.5 + 8.1 9..5 + 7.1

0.708 0.235 0.002 0.860 < 0.001 0.45 < 0.001 0.002 < 0.001 < 0.001 < 0.001 0.968

*Mann-Whitney U.

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K. Fehmi Narter, U. Can, A. Coşkun, K. Sabuncu, F. Tarhan

Table 2. Treatment chart for patients with and without predominant urinary symptoms according to U-POINT score. Treatment Antibiotics Alpha blocker Anticholinergic Combined Quercetin Others Total

U-POINT Urinary phenotype (n = 73) n (%) 0 19 (26) 16 (22) 38 (52) 0 0 73 (100)

Other phenotypes (n = 23) n (%) 3 (13) 0 1 (4) 0 13 (57) 6 (26) 23 (100)

Significant improvements were observed in the three treatment groups (alpha blockers, anticholinergic and combined) when comparing the pre and post treatment values of the NIH-CPSI, IPSS and OAB-V8 scores in the ‘Urinary phenotype’ group. Recovery in all three groups was observed according to Beck depression scale, but it was not statistically significant difference in anticholinergic group (p = 0.387). The best improvement in the pain subdomain of NIH-CPSI and IPSS scores were obtained from the anticholinergic group compared to the others (Table 3).

DISCUSSION

Table 3. Assessment of pre and post treatment NIH-CSPI, IPSS, OAB-V8 and BECK depression inventory scores according to the treatment groups in ‘urinary phenotype’ group.

NIH-CSPI Total Pretreatment Posttreatment Δ* % Change* 1P Pain Pretreatment Posttreatment Δ* % Change* 1P Urinary Pretreatment Posttreatment Δ* % Change* 1P QoL Pretreatment Postreatment Δ* % Change* 1P IPSS Pretreatment Posttreatment Δ* % Change* 1P OAB-V8 Pretreatment Posttreatment Δ* % Change* 1P BECK Pretreatment Posttreatment Δ* % Change* 1P

Alpha blocker n = 19

Antimuscarinic n = 16

Combined n = 37

20.9 + 6.6 15.6 + 5.1 -5.3 + 5 -12.2 + 11.6 < 0.001

27.2 + 7.5 20.1 + 6.3 -7.1 + 5.8 -16.6 + 13.5 0.001

25.1 + 7.3 20 + 7.3 -5.1 + 6.2 -11.8 + 14.3 < 0.001

0.267

8.4 + 5.2 6.3 + 3.8 -2.1 + 2.2 -9.8 + 10.7 0.002

11.8 + 5.2) 8 + 3.6 -3.8 + 3 -18.1 + 14.5 0.001

9.8 + 4.5 8.1 + 3.4 -1.8 + 2.9 -8.5 + 13.7 < 0.001

0.031**

6.2 + 2.9 4.6 + 2.2 -1.5 + 2.2 -15.3 + 22.2 0.012

7.3 + 2.8 5.5 + 2.6 -1.8 + 2 -17.5 + 19.8 0.003

7.1 + 2.6 5.3 + 2.8 -1.9 + 2.2 -18.6 + 22.1 < 0.001

0.894

6.4 + 2.3 4.7 + 2 -1.7 + 2.2 -14 + 18 0.003

8.1 + 1.5 6.6 + 2.1 -1.6 + 2.6 -13 + 21.9 0.008

8.1 + 2.2 6.7 + 2.6 -1.4 + 2.6 -11.7 + 18.8 0.001

0.858

14.8 + 7.2 11.3 + 6.5 -3.6 + 4.2 -10.2 + 11.9 0.003

16.4 + 8.7 10.5 + 6.3 -5.9 + 4.9 -17 + 14 0.001

16.8 + 8.6 13.9 + 7.7 -2.9 + 3.8 -8.3 + 10.9 < 0.001

0.053

13.5 + 8 9.7 + 6 -3.8 + 3.6 -10.5 + 10.1 0.001

20 + 6 14.8 + 6.2 -5.3 + 4.5 -14.6 + 12.5 0.001

19.7 + 8 16.9 + 7.4 -2.8 + 4.1 -7.9 + 11.4 < 0.001

0.190

9.5 + 6.4 6.3 + 4.8 -3.2 + 2.9 -5 + 4.6 0.001

11 + 8.8 9.4 + 8.7 -1.6 + 5.1 -2.5 + 8.1 0.387

11.6 + 8.7 8 + 6.4 -3.7 + 6.1 -5.8 + 9.6 < 0.001

0.223

1 Wilcoxon

2 Kruskal Wallis

*Δ : The difference in values before and after treatments **% Change: Percentage of change in values before and after treatments; (Δ /the maximum score of relevant questionnaire) x100

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The prostate is innervated by rich supply of mixed autonomic postganglionic neurons that arise from the pelvic (inferior hypogastric) and the preganglionic parasympathetic neurons joining the pelvic plexus from the pelvic nerve arising from the sacral spinal cord segment (13). Cholinergic innervation is found in the both stromal and glandular epithelial areas of the human prostate for secretion and contraction (14). The prostate secretes many substances into the seminal plasma that includes PSA (serine protease), zinc, citric acid, magnesium, spermine, prostatic acid phosphatase calcium, and accounts for approximately 15% of volume of the normal human ejaculate. Moreover, in vitro contraction of isolated prostate can be inhibited by muscarinic receptor antagonists in the human (15-17). Recently, anticholinergic (antimuscarinic) treatment has become more actual for treatment of male LUTS because such drugs work not only bladder but also on the prostate (18). Muscarinic receptors are intensely represented, especially those belonging to the M1 subtype, on glandular epithelial cells whereas M2 subtype receptors are more represented on the stromal cells. Animal data suggest that muscarinic receptors may be important in the genesis of prostatic secretions (19), smooth muscle contraction of the prostatic capsule (15, 17) and prostatic growth (18, 20). Cholinergic fibres were found in various regions of the prostate including the anterior capsule, peripheral zone, proximal and distal central zones and their density was more than adrenergic fibers (21). Moreover, muscarinic receptors with binding characteristics of

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Anticholinergic therapy for chronic prostatitis

the M3 subtype are predominant in the rat ventral prostate (22), and M1 subtype is dense in the rabbit vas deferens (23). Despite of the only small acute urinary retention risk, muscarinic antagonists may be helpful in men with LUTS as well as overactive bladder (OAB). The expression of muscarinic receptors can be correlated with CP/CPSS. Recently, a possible etiological pathway has been described. According to this mechanism, an unfavorable event as trauma or infection leads to an injury-response of the tissue. Inflammation and upregulation of cytokines may lead to additional organ damage involving nerves, blood vessels, smooth muscles, and the loss of urothelium integrity. As we well know, urothelium is a whole unit especially in the trigonum and prostatic Ăźrethra, and some muscle fibers in detrusor and sphincter region continue in the prostatic area, so that it is a functional and anatomic whole unit. The resulting pain may produce contraction of pelvic smooth and skeletal muscles, finally leading to LUTS, ejaculatory pain or pain in other regions such as back and abdomen. Prolonged pain may sensitize central and peripheral nervous systems and finally cause hyperalgesia and allodynia. For this reason, the primary symptoms of CP/CPPS can be pelvic pain and frequency and few physicians prefer anticholinergics empirically for treatment, and there are only hints of treatment with anticholinergics in some of the guidelines (9). In our study, anticholinergic therapy improved the pain subdomain score associated with CP/CPSS more than the others (p = 0.031). According to this result, anticholinergic therapy is the best succesful option for treatment of pain subdomain of NIH-CPSI. In some actual studies, muscarinic receptors have also been suggested to be implicated in the control of inflammation, cell growth and proliferation (24, 25). The muscarinic receptors are also present in the urethra, but their function have not been clarified adequately. The urethral sphincter tone is predominantly regulated by adrenergic nerves, but muscarinic receptors also modulate the tone (26). Muscarinic receptor mediates contraction of the proximal urethra whilst mediating relaxation of the distal urethra (27). All muscarinic receptor subtypes (M1-5) are located on the urinary system, especially M2 receptors mostly occur in the circular muscle layers, and muscarinic M3 receptors in the longitudinal layer. During inflammation expression of muscarinic M5 receptors is increased, especially in the epithelium and cholinergic induced production of nitric oxide (NO) increase (28). We chose propiverine as an anticholinergic in this study because of it is a competitive antagonist with similar affinity for all muscarinic receptor subtypes (29). Kim et al. presented their results about efficacy of anticholinergics for CP/CPSS at American Urological Association's (AUA) 2010 Annual Meeting and then confirmed this finding with a prospective study in 2011 (30, 31). In that study, ninety six patients with CP/CPPS were randomly assigned in a single-blind fashion and received either ciprofloxacin or ciprofloxacin and solifenacin (5 mg/d) for 2 months. IPSS, NIH-CPSI, IIEF-5 questionnaires and assessment of QoL were used in that study. According to the results of the study, 67% of

patients had urinary symptoms. Similarly, in our study 76% of patients showed urinary phenotype. On the other hand, the IPSS assessment appears to be a good indicator follow-up in the management of CP/CPPS especially in many patients with severe LUTS. Statistically significant differences in the total score, the pain and sub-domain scores of NIH-CPSI and total score and storage domain score of IPSS were reported according to Kimâ&#x20AC;&#x2122;s research. Moreover, they reported a statistically non significant increase of the total score of IIEF-5 and no statistically significant difference in residual urine. As a result of the study, the efficacy of anticholinergic treatment in CP/CPPS was demonstrated by the improvements in the NIH-CPSI and IPSS total and storage scores. Similar to the results of that study, the NIHCPSI and IPSS total and storage scores improved significantly in the anticholinergic treatment group for patients with CP/CPSS in our study (p = 0.053). More than 90% of cases of CP are not associated with a significant bacteriuria, a condition referred to as chronic pelvic pain syndrome (CPPS) and may not respond to antibiotics or other classical treatment options. Many hypotheses have been suggested for the physiopathology of CP/CPSS including infection, inflammation, autoimmunity, neuromuscular spasm or intraprostatic urinary reflux. CP/CPSS is a syndrome, not a disease and patients may have a wide array of symptoms. For this reason, symptomatic treatment is essential for these patients. Symptom severity should be assessed using the NIH Chronic prostatitis symptom index (CPSI), which is a validated nine question survey that covers the three domains of pain, urinay symptoms and quality of life (32). The UPOINT system was developed to identify clinical phenotypes according to the symptoms and decide for combined multimodal treatment strategies. The UPOINT system (www.upointmd.com) was validated in several clinical trials (33-35). In this system each category has its own treatment. Use of this treatment strategy is starting to become more widespread and is proving its effectiveness. A strong correlation between the number of positive UPOINT domains and the worse total score of the CPSI measured in patients was shown (36). Shoskes et al demostrated that a majority (84%) of patients treated based on the UPOINT phenotype had a clinical improvement of CP/CPSS symptoms measured by an at least a 6-point or greater decrease in NIH-CPSI score (33, 34, 37). Another study about UPOINT clinical phenotyping reported that 75% of patients had at least a 6-point improvement in CPSI and experienced improvements in every domain (38). In our study, many patients with CP/CPSS had LUTS and we evaluated to all patients according to UPOINT classification. In addition to the correlation between the UPOINT and CP/CPSS, sexual dysfunction (ED) was added as a specific domain to create UPOINT(S) (12). In this study, the authors suggested that adding sexual dysfunction to the domain system may be helpful, as a sexual dysfunction is a frequent complaint of patients suffering from CP/CPSS. According to this study, the prevalence of sexual dysfunction is 65% in these patients. Multimodality treatment strategies that provides superior outcomes over other treatment strategies for this disArchivio Italiano di Urologia e Andrologia 2019; 91, 1

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K. Fehmi Narter, U. Can, A. Coşkun, K. Sabuncu, F. Tarhan

ease and it aims to offer a personalized combination therapy. At least combined therapy may show synergistic effects in the management of CP/CPPS. In our study, NIH-CPSI, IPSS and OAB-V8 scoring values were calculated at statistically significant higher level in the ‘urinary phenotype’ group (p < 0.001). We found statistically significant differences between the two groups in the total score and urinary domain of the NIH-CPSI and the total score and storage symptom score of the IPSS. As a result of NIH-CPSI, IPSS and OAB-V8’s data, we can suggest that CP/CPSS is a complex problem and it can effect bladder, prostate and lower urinary tract functions as a whole system. However to prove the effective of anticholinergics in CP/CPPS decrease of absolute values between two groups should be considered during the study. Our data suggest that anticholinergics are effective in the management of CP/CPSS, especially for the treatment of storage symptoms. In our study, total and storage scores of NIH-CPSI and IPSS improved significantly in the anticholinergic treatment group for patients with CP/CPSS (p = 0.053). As we well know, UPOINT system may recommends all treatment options for ‘urinary phenotype’ according to patient’s symptoms and preference of the clinician. According to our results, anticholinergics may be a treatment option for many patients with CP/CPSS who have high IPSS scores with modarate or severe LUTS symptoms. Moreover, this effect of antimuscarinics may be explain by the influence of anticholinergic system on the prostate tissue. Many treatment options for this disease have been used such as alpha blockers, antibiotic therapy, anti-inflammatory drugs and analgesics, antispasmodics, 5-alpha reductase inhibitors (5-ARI), lifestyle changing, psychotherapy, physiotheraphy, local thermotherapy, neuroleptics and anti-anxiolitics, narcotics, acupuncture, extracorporeal shockwave therapy, myofascial trigger point release, biofeedback, food supplements (quercetin, zinc etc), phytotherapy (bioflavonoids), botulinum toxin A injection or occasionally surgical therapy. There have been few studies of the efficacy of anticholinergics for these patients. At least for a symptomatic relief of complaints, anticholinergic treatment may be tried according to the results of our study. But there is a need for a long term, randomized, controlled study to confirm the efficacy of this treatment. The limitations of the our study are the lack of a questionnaire to assess the sexual performance of the patients such as IIEF-5 and of an evaluation of long-term treatment outcomes. Furthermore, our study was not a large scale and long term research. So that, more randomized, controlled, long-term and large-scale clinical trials are needed. On the contrary, our study was the first to include Beck depression scale together with UPOINT system in patients with CP/CPSS. Although there was a decrease in Beck score after treatment in patients treated with anticholinergics, the change was not significant (p = 0.387). This positive but statistically insignificant result can be pioneer for entegration of Beck depression scale and UPOINT system that could be named as UPOINT(D; depression) similarly to UPOINT(S) modification.

Archivio Italiano di Urologia e Andrologia 2019; 91, 1

CONCLUSIONS

As we well know, CP/CPPS is a common, worrisome problem especially for the young men population. Until today, anticholinergic therapy is not a choice for the treatment of this problem according to classical treatment algorithms, but after the introduction of UPOINT system this option has been considered, especially for patients belong urinary phenotype based on UPOINT system. If patients with CP/CPSS according to subgroup of the NIH categorization have lower urinary symptoms (LUTS) such as urgency, frequency, nocturia, increased postvoid residual urine, dysuria, they have to be evaluated with UPOINT system and they are best candidate for anticholinergic treatment. In this study, we showed that anticholinergic therapy was an effective and preferable option for these patients. In the near future anticholinergic treatment of patients with CP/CPSS will be accepted and take a place in classical treatment algorithms. In addition to the symptomatic recovery in this disease, we believe that it is possible a physiopathological improvement in the tissue of prostate due to anticholinergic effect, because cholinergic system is well reprsented in the whole prostate tissue. There is need for more randomised prospective clinical trials and histological/molecular researches to evaluate tissue receptors in the prostate.

REFERENCES

1. Krieger JN, Lee SW, Jeon J, et al. Epidemiology of prostatitis. Int J Antimicrob Agents. 2008; 31(Suppl 1):S85-90. 2. Marszalek M, Wehrberger C, Hochreiter W, et al. Symptoms suggestive of chronic pelvic pain syndrome in an urban population: prevalence and associations with lower urinary tract symptoms and erectile function.J Urol. 2007; 177:1815-9. 3. Luzzi GA. Chronic prostatitis and chronic pelvic pain in men: aetiology, diagnosis and management.J Eur Acad Dermatol Venereol. 2002; 16:253-6. 4. Liang CZ, Zhang XJ, Hao ZY, et al. An epidemiological study of patients with chronic prostatitis. BJU Int. 2004; 94:568-70. 5. Fall M, Baranowski AP, Elneil S, et al. European Association of Urology. Eur Urol. 2010; 57:35-48. 6. Krieger JN, Nyberg L Jr, Nickel JC. NIH consensus definition and classification of prostatitis. JAMA. 1999; 282:236-7. 7. Shoskes DA, Nickel JC, Dolinga R, et al. Clinical phenotyping of patients with chronic prostatitis/chronic pelvic pain syndrome and correlation with symptom severity. Urology. 2009; 73:538-42. 8. Magri V, Wagenlehner F, Perletti G, et al. Use of the UPOINT chronic prostatitis/chronic pelvic pain syndrome classification in European patient cohorts: sexual function domain improves correlations. J Urol. 2010; 184:2339-45. 9. Litwin MS, McNaughton-Collins M, Fowler FJ Jr, et al. The National Institutes of Health chronic prostatitis symptom index: development and validation of a new outcome measure. Chronic Prostatitis Collaborative Research Network. J Urol. 1999; 162:369-75. 10. Barry MJ, Fowler FJ Jr, O'Leary MP, et al. The American Urological Association symptom index for benign prostatic hyperplasia. The Measurement Committee of the American Urological Association. J Urol. 1992; 148:1549-57.

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11. Acquadro C, Kopp Z, Coyne KS, et al. Translating overactive bladder questionnaires in 14 languages. Urology. 2006; 67:536-40. 12. Beck AT, Ward CH, Mendelson Met al. An inventory for measuring depression. Arch Gen Psychiatry. 1961; 4: 561-71. 13. Vaalasti A, Hervonen A. Autonomic innervation of the human prostate. Invest Urol. 1980; 17:293-7. 14. Chapple CR, Crowe R, Gilpin SA, et al. The innervation of the human prostate gland-the changes associated with benign enlargement. J Urol. 1991; 146:1637-44. 15. Caine M, Raz S, Zeigler M. Adrenergic and cholinergic receptors in the human prostate, prostatic capsule and bladder neck. Br J Urol. 1975; 47:193-202. 16. Hedlund H, Andersson KE, Larsson B. Alpha-adrenoceptors and muscarinic receptors in the isolated human prostate.J Urol. 1985; 134:1291-8. 17. Gup DI, Shapiro E, Baumann M, et al. Contractile properties of human prostate adenomas and the development of infravesical obstruction. Prostate. 1989; 15:105-14. 18. Ventura S, Pennefather J, Mitchelson F. Cholinergic innervation and function in the prostate gland.Pharmacol Ther. 2002;94:93-112. 19. Bruschini H, Schmidt RA, Tanagho EA. Neurologic control of prostatic secretion in the dog.Invest Urol. 1978; 15:288-90. 20. Witte LP, Chapple CR, de la Rosette JJ, et al. Cholinergic innervation and muscarinic receptors in the human prostate.Eur Urol. 2008; 54:326-34. 21. Crowe R, Chapple CR, Burnstock G. The human prostate gland: a histochemical and immunohistochemical study of neuropeptides, serotonin, dopamine beta-hydroxylase and acetylcholinesterase in autonomic nerves and ganglia.Br J Urol. 1991; 68:53-61.

31. Kim DS, Kyung YS, Woo SH, et al. Efficacy of anticholinergics for chronic prostatitis/chronic pelvic pain syndrome in young and middle-aged patients: a single-blinded, prospective, multi-center study.Int Neurourol J. 2011; 15:172-5. 32. Litwin MS, McNaughton-Collins M, Fowler FJ Jr, et al. The National Institutes of Health chronic prostatitis symptom index: development and validation of a new outcome measure. Chronic Prostatitis Collaborative Research Network. J Urol. 1999; 162:369-75. 33. Shoskes DA, Hakim L, Ghoniem G, et al.Long-term results of multimodal therapy for chronic prostatitis/chronic pelvic pain syndrome. J Urol. 2003; 169:1406-10. 34. Magri V, Marras E, Restelli A, et al. Multimodal therapy for category III chronic prostatitis/chronic pelvic pain syndrome in UPOINTS phenotyped patients. Exp Ther Med. 2015; 9:658-666. 35. Polackwich AS, Shoskes DA. Chronic prostatitis/chronic pelvic pain syndrome: a review of evaluation and therapy.Prostate Cancer Prostatic Dis. 2016; 19:132-8. 36. Zhao Z, Zhang J, He J, et al. Clinical utility of the UPOINT phenotype system in Chinese males with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS): a prospective study. PLoS One. 2013; 8:e52044. 37. Shoskes DA, Nickel JC, Kattan MW. Phenotypically directed multimodal therapy for chronic prostatitis/chronic pelvic pain syndrome: a prospective study using UPOINT. Urology. 2010; 75:1249-53. 38. Guan X, Zhao C, Ou ZY, et al. Use of the UPOINT phenotype system in treating Chinese patients with chronic prostatitis/ chronic pelvic pain syndrome: a prospective study. Asian J Androl. 2015; 17:120-3.

22. Latifpour J, Gousse A, Yoshida M, et al. Muscarinic receptors in diabetic rat prostate.Biochem Pharmacol. 1991; 42 Suppl:S113-9. 23. Levey AI, Kitt CA, Simonds WF, et al. Identification and localization of muscarinic acetylcholine receptor proteins in brain with subtype-specific antibodies. J Neurosci. 1991; 11:3218-26. 24. Profita M, Giorgi RD, Sala A, et al. Muscarinic receptors, leukotriene B4 production and neutrophilic inflammation in COPD patients.Allergy. 2005; 60:1361-9. 25. Kawashima K, Fujii T. Expression of non-neuronal acetylcholine in lymphocytes and its contribution to the regulation of immune function.Front Biosci. 2004; 9:2063-85. 26. Mattiasson A, Andersson KE, Andersson PO, et al. Nerve-mediated functions in the circular and longitudinal muscle layers of the proximal female rabbit urethra.J Urol. 1990; 143:155-60. 27. Nagahama K, Tsujii T, Morita T, et al. Differences between proximal and distal portions of the male rabbit posterior urethra in the physiological role of muscarinic cholinergic receptors. Br J Pharmacol. 1998; 124:1175-80. 28. Giglio D, Tobin G. Muscarinic receptor subtypes in the lower urinary tract. Pharmacology. 2009; 83:259-69. 29. Maruyama S, Oki T, Otsuka A, et al. Human muscarinic receptor binding characteristics of antimuscarinic agents to treat overactive bladder. J Urol. 2006; 175: 365-9. 30. Kim HJ, Kyung YS, Woo SH, et al. The efficacy of anticholinergics for chronic prostatitis/chronic pelvic pain syndrome in young and middle aged patients -single-blinded, prospective, multi-center study - AUA Annual Meeting Program Abstracts 796, 2010, Volume 183, Issue 4, Supplement, page e311.

Correspondence Fehmi Narter, MD, PhD, Assoc Prof (Corresponding Author) fehminarter66@gmail.com Acibadem Mehmet Ali Aydinlar University, Urology Kızıltoprak Istasyon cad. Murat apt. 24/15 Kadikoy 34724 Istanbul (Turkey) Utku Can, MD utkucan99@yahoo.com Alper Coşkun, MD dr.alper05@gmail.com Kubilay Sabuncu, MD kubilaysabuncu@yahoo.com Fatih Tarhan, MD, Assoc Prof tarhanf@yahoo.com Department of Urology, University of Health Sciences, Kartal Dr. Lütfi Kırdar Training and Research Hospital, Istanbul (Turkey)

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DOI: 10.4081/aiua.2019.1.22

ORIGINAL PAPER

Successful treatment with pollen extract of hematospermia in patients with xanthogranolomatous prostatitis Antonio Luigi Pastore 1, 2, Yazan Al Salhi 1, Andrea Fuschi 1, Alessia Martoccia 1, Gennaro Velotti 1, Lorenzo Capone 1, Giorgio Bozzini 3, Natale Porta 4, Vincenzo Petrozza 4, Ester Illiano 5, Elisabetta Costantini 5, Antonio Carbone 1, 2 1 Sapienza

University of Rome, Faculty of Pharmacy and Medicine, Department of Medico-Surgical Sciences and Biotechnologies, Urology Unit, Latina Italy; 2 Uroresearch, no profit Association for Research in Urology, Latina, Italy; 3 Department of Urology Mater Domini Humanitas Castellanza (VA), Italy; 4 Sapienza University of Rome, Faculty of Pharmacy and Medicine, Department of Medico-Surgical Sciences and Biotechnologies, Pathology Unit, Latina Italy; 5 Department of Urology and Andrology, University of Perugia, Terni Italy.

Summary

Introduction: The aim of this study was to report our experience in the management of hematospermia observed in 16 patients suffering from xanthogranulomatous prostatitis. Methods: Recurrent episodes of hematospermia were the onset symptom in all patients, and in 25% of patients it was combined with fever. All patients reported PSA value elevation and the digital rectal examination (DRE) revealed an increase of the gland size and of its consistency in all cases. In all patients, the hematospermia was treated with the oral administration of two tablets of pollen extract in a single (1 g) dose daily for 30 days. Results: Sixteen patients were observed between 2008 and 2016, referring hematospermia, progressive lower urinary tract symptoms (LUTS), and serum PSA level increase. To exclude the prostate cancer presence all patients were submitted to transperineal TRUS guided biopsy. In all the patients complete resolution of hematospermia was achieved treatment with pollen extract. All patients were subsequently treated for LUTS (alpha-adrenergic blockers), but none reported any significant improvement of symptoms. Basing on these pieces of evidence, after 90 days of alpha-blockers therapy, all patients underwent bipolar TURP. Histological examination of resected prostatic tissue revealed in all patients the diagnosis of xanthogranulomatous prostatitis. Conclusions: Patients with xanthogranulomatous prostatitis especially experience irritative symptoms, sometimes combined with fever or hematospermia. Hematospermia as the onset symptom has not been reported so far. The administration of the pollen extract for 30 days was associated with a complete resolution of hematospermia.

KEY WORDS: Hematospermia; Lower urinary tract symptoms; Pollen extract; Xanthogranulomatous prostatitis. Submitted 6 October 2018; Accepted 26 January 2019

INTRODUCTION

Granulomatous prostatitis is a non-specific inflammatory process of the prostate gland, characterized by the presence of granuloma as the main histological feature (1). It is classified as: infectious granuloma, nonspecific gran-

ulomatous prostatitis, post-biopsy granuloma, and systemic granulomatous prostatitis. Rare forms of granulomatous prostatitis include sarcoidosis and xanthogranulomatous prostatitis (2). This form is histologically similar to granulomatous prostatitis, with the prominence of foamy histiocytes, which constitute the xanthomatous component. Non-specific granulomatous prostatitis and xanthogranulomatous prostatitis are likely caused by a blockage of prostatic ducts and stasis of gland secretions. The resulting epithelial disruption leads to the escape of cellular debris, bacterial toxins, prostatic secretions, including corpora amylacea, sperm and semen into the stroma, determining an intense localized inflammatory response. The most reported onset symptom is represented by irritative lower urinary tract symptoms and a raise of serum prostate-specific antigen (PSA) (3) that mimics adenocarcinoma (4). In this study we report our experience on xanthogranulomatous prostatitis observed in 16 patients. All patients were complaining hematospermia, progressive lower urinary tract symptoms (LUTS), and increasing PSA levels. Aim of the study is to describe our successful therapeutic management of this bothering onset symptom, hematospermia, related to this rare form of prostatitis.

PATIENTS

AND METHODS

All patients came to our attention complaining recurrent episodes of hematospermia (associated with fever in 25% of patients), that represented the onset symptom of all cases. All men suffered also from irritative LUTS, mostly characterized by urinary frequency, burning, hesitancy, and nocturia. All patients provided written informed consent. The study was conducted in accordance with the Declaration of Helsinki and was approved by the local Medical Ethical Committee (ASL LT CE approval n.08/1636/42 UROUNIV). In all patients, a PSA elevation was observed (range: 4.99.7 ng/mL), with a free/total ratio always greater than 20% (range: 22-36%). Digital rectal examination (DRE) revealed an increase in the gland volume and a consistency change No conflict of interest declared.

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Pollen extract for hematospermia

with an irregular surface in all cases. The palpatory findings (peripheral nodule of hard consistency) and the serum total PSA level > 4 ng/mL lead us to suspect malignancy in all cases. All patients underwent an ultrasoundguided transperineal prostatic biopsy (12 cores) to exclude the presence of prostate cancer. All patients were investigated for Chlamydia trachomatis (Ct), Ureaplasma urealyticum, Neisseria gonorrhoeae, herpes viruses (HSV 1/2) and human papillomavirus (HPV). In all cases the hematospermia was treated with the oral administration of two tablets of DEPROX 500® in a single dose daily, in line with previous studies 5,6 and according with the manufacturer’s instructions (IDI® Integratori Dietetici Italiani S.r.l, Catania, Italy). Each administration contained 1 g pollen extract (500 mg per tablet), and vitamins B1, B2, B6, B9, B12 and PP. Statistical analysis (Student t-test for paired samples) was performed to compare the outcomes before and after medical therapy and pre- and post-operative. The statistical analysis was done using SPSS software (version 21.0; SPSS Inc., Chicago, IL). P values < 0.05 were considered as statistically significant.

RESULTS

Sixteen patients were observed between 2008 and 2016, referring hematospermia, progressive lower urinary tract symptoms (LUTS), and serum PSA level increase. In all patients the hematospermia was treated with Pollen Extract (2 tabs - 1 g daily) for 30 days with complete resolution of this symptom. The DEPROX 500® treatment was well tolerated in all the analyzed patients, and no significant drug-related side-effect was reported. In all 16 cases the results of infection tests, and the prostate biopsy to detect cancer resulted negative. The prostatic biopsy did not allow the histological diagnosis of xanthogranulomatous prostatitis due to the poor biopsy material that did not enable the histotyping of prostatitis. Thereafter, all patients were treated for LUTS (alpha-adrenergic blockers), but none reported any significant improvement of symptoms, as revealed by IPSS questionnaire and the Qmax registered 30 days post treatment. For this reason, all the subjects were evaluated by transrectal ultrasound examination (TRUS) and urodynamics. TRUS showed a marked inhomogeneity of prostate tissue, with several hypo-echoic and hyper-vascularized areas and calcifications along the peripheral surface of the adenoma, while pressure/flow studies showed the presence of a severe bladder outlet obstruction (BOO). Basing on these evidences, after 90 days of alpha blockers therapy, all patients underwent transurethral bipolar endoscopic resection of the prostate (TURP). Mean catheterization time was 2.8 days (range: 2-4 days); in only one patient acute urinary retention 48 hours after catheter removal due to inflammatory condition (as revealed by DRE) occurred. PSA levels significantly decreased (below 2.0 ng/mL) in all patients. Functional outcomes before and after alpha blockers, pre and post TURP were evaluated by IPSS, IPSS-QoL, maximum flow rate (Qmax expressed in mL/sec), and post void residual urine volume (mL). All patients achieved normal IPSS scores and normal uroflowmetry parameters 5 weeks after surgery. The data are summarized in Table 1.

Table 1. Functional outcomes before and after alpha blocker’s therapy, and preoperative and 3 months after TURP. Before therapy

After therapy

p value

IPSS (SD)

23.65 (0.12)

23.51 (0.11)

0.486

IPSS - QoL (SD)

4.45 (0.04)

4.54 (0.03)

0.115

Qmax (SD)

9.81 (0.13)

9.69 (0.12)

0.553

PVR (SD)

112.95 (0.2)

113.09 (0.18)

0.610

Preoperative

3 months after TURP

p value

IPSS (SD)

23.51 (0.11)

7.41 (0.11)

< 0.0001

IPSS QoL (SD)

4.54 (0.03)

1.54 (0.05)

< 0.0001

Qmax (SD)

9.69 (0.12)

20.74 (0.11)

< 0.0001

PVR (SD)

113.09 (0.18)

21.12 (0.19)

< 0.0001

PSA (SD)

6.24 (0.33)

1.32 (0.27)

< 0.0001

SD: Standard Deviation; IPSS: International Prostate Symptom Score; QoL: Quality of life; Qmax; maximum flow rate (mL/sec); PVR; post-void residual urine volume (mL); PSA; prostate specific antigen (ng/mL).

All patients submitted to TURP reported significant outcomes at the 3 months’ follow-up visit (p < 0.0001). Histological examination of resected prostatic tissue revealed in all patients the diagnosis of xanthogranulomatous prostatitis.

DISCUSSION

The histopathological examination of resected prostatic tissue in all our patients revealed xanthogranulomatous prostatitis with no evidence of malignancy. A non-specific granulomatous inflammation was found, the granulomas were composed of multinucleated giant cells and “xanthogranulomatous cells” (diffusely in 13 cases, focally in one patient; Figure 1). Xanthomatous histiocytes presented a small dark nuclei and abundant clear to foamy cytoplasm due to fat droplets and could be confused with prostate carcinoma. As confirmed by our case series, the final diagnosis of xanthogranulomatous prostatitis can only be achieved by histopathological examination of the prostate (7, 8). The histological feature of xanthogranulomatous prostatitis is the presence of macrophages with foamy cytoplasm “xanthomatous cells” (CD68+) in the mixed inflammatory infiltrate with multinucleated giant cells. Major study limitation was the small number of patients, and the absence of a placebo group of treatment. However, the low number of patients to be enrolled was not sufficient to design a placebo controlled study. In the present study the administration of DEPROX 500® was able to achieve the complete resolution of hematospermia with a disappearance of this onset symptom in all patients within 15 days of treatment assumption, without severe side-effects. To the best of our knowledge this was the first study to evaluate this treatment for this symptom. Furthermore, hematospermia as the onset symptom has not been reported so far. Hematospermia has been sporadically reported as an accompanying symptom in very few cases (9), but only in our case series it represented the uncommon symptom of the disease onset. In 40% of all cases reporting hematospermia, an infectious condition is revealed. Other etiologic factors are inflamArchivio Italiano di Urologia e Andrologia 2019; 91, 1

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A.L. Pastore, Y. Al Salhi, A. Fuschi, A. Martoccia, G. Velotti, L. Capone, G. Bozzini, N. Porta, V. Petrozza, E. Illiano, E. Costantini, A. Carbone

Figure 1. A. Low-power photomicrograph showing intense inflammatory infiltrate composed of lymphocytes, plasma cells, neutrophils and xanthogranulomatous cells in prostatic tissue (magnification 10×); B. High-power photomicrograph showing xanthomatous component of inflammatory infiltrate, composed of histiocytes with small dark nuclei and abundant clear to foamy cytoplasm (magnification 40×); C. CD68 stain showing the presence of xanthomatous histiocytes in the prostatic stroma (magnification 40×). A.

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1. Epstein JI, Hutchins GM. Granulomatous prostatitis: Distinction among allergic, nonspecific, and post-transurethral resection lesions. Hum Pathol. 1984; 15:818-25. 2. Shanggar K, Zulkinfli MZ, Razack AH, et al. Granulomatous prostatitis: A reminder to clinicians. Med J Malaysia. 2010; 65:21-2. 3. Speights VO, Jr, Brawn PN. Serum prostatespecific antigen levels in non-specific granulomatous prostatitis. Br J Urol. 1996; 77:408-10. 4. Srigley JR. Benign mimickers of prostatic adenocarcinoma. Mod Pathol 2004; 17:328-33 5. Cai T, Luciani LG, Caola I, et al. Effects of pollen extract in association with vitamins (DEPROX 500®) for pain relief in patients affected by chronic prostatitis/chronic pelvic pain syndrome: results from a pilot study. Urologia. 2013; 80(Suppl 22):5-10.

6. Cai T, Wagenlehner FM, Luciani LG,et al. Pollen extract in association with vitamins provides early pain relief in patients affected by chronic prostatitis/chronic pelvic pain syndrome. Exp Ther Med. 2014; 8:1032-1038. 7. Uzoh CC, Uff JS, Okeke AA. Granulomatous prostatitis. BJU Int. 2007; 99:510-2.

matory conditions, neoplasms and iatrogenic factors. After confirming the presence of hematospermia, physicians should perform a clinical evaluation, including clinical history and physical examination with DRE. Several previous studies evaluated the pollen extract early pain relief in patients suffering from chronic prostatitis/chronic pelvic pain syndrome (5, 6). In 2006, Elist in a double-blind randomized placebo controlled study, reported the superiority of pollen extract versus placebo in terms of pain score improvement and treatment of LUTS during six months of therapy (10). Additionally, in 2009, Wagenlehner et al. showed that pollen extract improved LUTS, pain and quality of life after 12 weeks of treatment in patients when compared with placebo (11). In our study, 2 weeks of treatment with DEPROX 500® provided significant results in terms of hematospermia disappearance. This effect is possibly due to the association between the pollen extract and vitamins B6 and B12 that improve the antioxidant activity of pollen extract. In the study by Cai et al., DEPROX 500® resulted able to provide improved results in terms of early pain reduction in patients with non-inflammatory chronic prostatitis/chronic pelvic pain syndrome (6).

CONCLUSIONS

The administration of DEPROX 500® was able to achieve the complete resolution of hematospermia with a disappearance of this onset symptom in all patients within 15 days of treatment assumption, without side-effects. Nevertheless, to completely resolve the bothering symptoms of xanthogranulomatous prostatitis surgery was mandatory in all patients.

Archivio Italiano di Urologia e Andrologia 2019; 91, 1

8. Pastore AL, Palleschi G, Fuschi A, et al. Hematospermia and xanthogranulomatous prostatitis: an unusual onset of a rare diagnosis. Can Urol Assoc J. 2013; 7:E820-E822. 9. Stillwell TJ, Engen DE, Farrow GM. The clinical spectrum of granulomatous prostatitis: a report of 200 cases. J Urol. 1987; 138:320-3. 10. Wagenlehner FM, Schneider H, Ludwig M, et al. A pollen extract (Cernilton) in patients with inflammatory chronic prostatitis-chronic pelvic pain syndrome: a multicentre, randomised, prospective, double-blind, placebo-controlled phase 3 study. Eur Urol. 2009; 56:544-551. 11. Elist J. Effects of pollen extract preparation Prostat/Poltit on lower urinary tract symptoms in patients with chronic nonbacterial prostatitis/chronic pelvic pain syndrome: a randomized, double blind, placebo-controlled study. Urology. 2006; 67:60-63. Correspondence Antonio Luigi Pastore, MD, PhD (Corresponding Author) - antopast@hotmail.com Yazan Al Salhi, MD Andrea Fuschi, MD Alessia Martoccia, MD Gennaro Velotti, MD Lorenzo Capone, MD Antonio Carbone, MD - antonio.carbone@uniroma1.it Sapienza University of Rome, Faculty of Pharmacy and Medicine, Department of Medico-Surgical Scienes and Biotechonologies, Urology Unit, ICOT, Latina (Italy) Natale Porta, MD Vincenzo Petrozza, MD Sapienza University of Rome, Faculty of Pharmacy and Medicine, Department of Medico-Surgical Sciences and Biotechnologies, Pathology Unit, Latina Italy Giorgio Bozzini, MD Department of Urology Mater Domini Humanitas Castellanza (Italy) Ester Illiano, MD Elisabetta Costantini, MD Department of Urology and Andrology, University of Perugia, Terni (Italy)

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DOI: 10.4081/aiua.2019.1.25

ORIGINAL PAPER

Subjective and objective results in surgical correction of adult acquired buried penis: A single-centre observational study Andrea Cocci 1, Gianmartin Cito 1, Marco Falcone 2, Marco Capece 3, Fabrizio Di Maida 1, Girolamo Morelli 4, Nim Christopher 5, David Ralph 5, Giulio Garaffa 5 1 Careggi

Hospital, Department of Urology, University of Florence, Florence, Italy; Hospital, Department of Urology, University of Turin, Turin, Italy; 3 Department of Urology, University of Naples, Naples, Italy; 4 Department of Urology, University of Pisa, Pisa, Italy; 5 The Institute of Urology, UCLH, and International Andrology, London, UK. 2 Molinette

Summary

Objective: The purpose of this study was to provide a detailed analysis of surgical and functional outcomes after correction of acquired buried penis in the adult. Materials and Methods: From 2006 to 2016, we retrospectively reviewed 47 patients undergoing surgical treatment for the correction of buried penis. Functional and surgical outcomes, as well as patients’ satisfaction were the main endpoints. Results: The most common complains at presentation were recurrent uro-genital infections, sexual dysfunction, voiding dysfunction and Lichen Sclerosus (LS). Surgical management steps included: circumcision (27.66%), scrotoplasty (19.14%), V-Y skin plasty (4.25%), split thickness skin graft (STSG) 12.76%, full thickness skin graft (FTSG) 36.17%, suprapubic fat pad excision (57.44%), abdominoplasty (25.53%), division of the suspensory ligament (36.17%). Postoperative complications were recorded in 15% of patients. Vaginal penetration and erectile function ended up being more effective in 97.87% (46/47) and 42.55% (20/47) of patients. Improvement in penile erogenous sensation was in 6.38% (3/47). Aesthetic appearance of genitalia fully satisfied 36.17% of patients (17/47). Overall patients’ satisfaction rate resulted 76.59% (36/47). Conclusion: Management of adult acquired buried penis still remains a challenging task to achieve, however excellent cosmetic results can be obtained by surgical reconstruction.

KEY WORDS: Buried penis; Erectile dysfunction; Circumcision; Scrotoplasty. Submitted 4 September 2018; Accepted 26 October 2018

INTRODUCTION

Buried penis is a congenital or acquired condition, in which the phallus is partially or totally hidden below the surface of the skin. Keyes in 1919 first stated that “absence of the penis exists when the penis, lacking its proper sheath of skin, lies buried beneath the integument of the abdomen, thigh or scrotum” (1). Concealed penis (2), webbed penis (3) and inconspicuous penis (4) are sometimes used as synonyms (5). In most cases adult acquired buried penis is secondary to morbid obesity (6), diffuse lymphedema and skin contracture due to scarring of degenerative conditions like

Lichen Sclerosus (LS) (7); in the majority of patients more conditions coexist. The development of buried penis occurs thanks to the elasticity of penile skin and dartos, which can slide and migrate distally while the corpora remain firmly attached to the pubic branches (8). In obese patients as well as in case of diffuse lymphoedema, the pre-pubic tissue progressively envelopes the penis rendering local hygiene impossible (9). Similarly, excessive removal of penile shaft skin during circumcision, either due to surgical error or because all penile shaft skin was affected by LS, may trap the penile shaft in the pre-pubic adiposity. Moreover, diabetes mellitus, which is a relatively common finding on obese patients, may impair immunity response to local and systemic infections and therefore worsen patients’ prognosis (10). Buried penis profoundly impacts patients’ quality of life, as sexual and voiding function are severely compromised. In particular, during micturition, the pooling of urine and the lack of hygiene leads to skin maceration and to recurrent urinary tract infections. Moreover, the maceration of skin, which is not meant to be in contact with urine for prolonged time, may be responsible of the development of permanent degenerative changes such as LS and Carcinoma of the Penis (CP). Substantial quality of life improvement has been consistently reported after definitive surgical management (11). The rationale of the current study was to provide a detailed analysis of surgical and functional outcomes after surgical management of acquired buried penis in the adult, in order to describe the better choice of treatment.

MATERIALS

AND METHODS

After Institutional Review Board approval, we retrospectively identified in this single-centre observational study all patients who have undergone surgical management of acquired buried penis between January 2006 and December 2016. Demographic characteristics of patients, comorbidities, surgical procedures carried out, intra- and postoperative complications and functional outcomes after penile reconstruction were retrospectively reviewed.

No conflict of interest declared. Archivio Italiano di Urologia e Andrologia 2019; 91, 1

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A. Cocci, G. Cito, M. Falcone, M. Capece, F. Di Maida, G. Morelli, N. Christopher, D. Ralph, G. Garaffa

The type of surgical procedure was decided according to the extent of the suprapubic adiposity and the availability and quality of penile skin. Overall, abdominal and scrotal skin quality was determined preoperatively, while the characteristics of penile skin were assessed intraoperatively after surgical exposure of the penis. Each patient signed a written fully informed consent statement to the surgical procedure. In case of phimosis, surgery always began with a dorsal incision of the phimotic ring, in order to guarantee adequate exposure of the penis and to assess the quality of the glans penis mucosa. A circumcising incision was then performed around the corona to free the penile shaft from the surrounding tissues. Apronectomy was carried out through a transverse abdominal incision including a lozenge of skin, in order to remove the excess of skin and adipose tissue in the prepubic region. Following apronectomy, a suction drain was left in the cavity to reduce the risk of haematoma formation. A thick split thickness skin graft (STSG) harvested from a relatively non-hair bearing area of the abdomen was applied on the denuded dartos to reconstruct the shaft skin. When affected by LS, the mucosa of corona and glans were reconstructed with a thin STSG (0.016 inch) harvested from the inner thigh with air dermatome, as previously described by Garaffa et al. (12). Postoperatively, a compressive penile dressing and an indwelling urethral catheter were left in place for 1 week to optimize graft take. Patients were routinely discharged after removal of dressing and urethral catheter. From 2 weeks postoperatively, patients undergoing skin grafting were advised to introduce Phosphodiesterase Type 5inhibitors (PDE5-i) therapy, in order to encourage nocturnal erections and to promote the stretching of the graft. In this way, the scar contracture that would naturally occur during the graft healing, was minimized. Upon discharge, patients were routinely reviewed in the follow-up period at the fourth and eighth week after surgery. Surgical outcomes were assessed at the postoperative follow-up visits using the Patient Global Impression of Improvement (PGI-I) questionnaire, in order to evaluate the functional outcomes and their satisfaction rate after surgery (13). PGI-I estimated the score that best described the postoperative condition, from 1 (very much better) to 7 (very much worse). Moreover, the International Index of Erectile Function (IIEF-5) was used to assess preoperative and postoperative sexual function (14). We used the abbreviated version, also known as IIEF-5 in the validated Italian version (15). The scale considered the presence of the erectile dysfunction, classified as follow: severe (IIEF-5 ≤ 10), moderate (IIEF-5 between 11 and 16) and mild (IIEF-5 between 17 and 25). The Hospital Anxiety and Depression Scale (HADS) questionnaire determined the levels of anxiety and depression that a patient was experiencing pre and postoperatively, with a score from 0 to 21, categorized as follow: normal (0-7), borderline abnormal (8-10), abnormal (11-21) (16). The differences between pre- and postoperative IIEF-15 and HADS score were compared using a paired samples Student t test. All tests were two-sided with a significance set at p ≤ 0.05.

Archivio Italiano di Urologia e Andrologia 2019; 91, 1

RESULTS

Overall, 47 patients were eligible in the study. The mean age at the time of surgery was 51.8 ± 18.38 years (range 43-69 years). Patients’ demographics are reported in Table 1. The average BMI was 30 ± 2.32. 16/47 (34.0%) patients were diabetics. The most frequent reported complaints included recurrent genital infections (8.51%), sexual dysfunction (27.66%), voiding dysfunction (27.66%), LS (10.63%) and a combination of both sexual and urinary dysfunction (25.54%) (Figure 1). The type of surgical approach was tailored on the individual characteristics of each patient. Surgical procedures included circumcision (27.66%), scrotoplasty (19.14%), V-Y plasty of the pre-pubic region (4.25%), skin grafting of the penile shaft (thin STSG 12.76% - thick STSG 36.17%), suprapubic fat pad excision (57.44%), abdominoplasty (25.53%) and division of the suspensory ligament (36.17%) (Figures 2-6). The average hospital stay was 7 ± 2 days (range 2-14 days). No intraoperative complications were recorded. Postoperative surgical complications occurred in 14.9% (7/47) of cases. Complications were managed conserva-

Table 1. Patient’s characteristics (n = 47). Parameter Mean age, years (SD) Mean BMI, Kg/m2 (SD) DM type I, n (%) DM type II, n (%) Hypertension, n (%) Cardiovascular diseases, n (%) Mean operative time, minutes (SD) Mean blood loss, ml (SD) Mean hospital stay, days (SD) Intraoperative complications, n (%) Postoperative complications, n (%)

Value 51.8 (± 18.38) 30 (± 2.32) 10 (21.27) 6 (12.76) 18 (38.29) 8 (17.0) 185 (± 91.12) 180 (± 240.2) 7 (± 6.36) 0 (0) 7 (14.89)

DM: Diabetes mellitus; BMI: Body max index; SD: Standard deviation.

Figure 1. The most frequent symptoms reported by patients with clinical presentation of buried penis.

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Surgical correction of buried penis in adults

Figure 2. One case showing the starting clinical presentation of buried penis.

Figure 5. Immediate post-operative period.

Figure 3. One case showing the starting clinical presentation of buried penis. Figure 6. Clinical presentation three months after surgery.

Figure 4. Skin grafting of the penile shaft.

surgery (17 fully satisfied and 19 partially satisfied) while 8.51% (4/47) declared to be dissatisfied, due to the small size of the discovered penis.

Table 2. Postoperative complications and treatment (n = 47).

tively in 5 patients while surgical intervention was necessary in the remainder, as summarized in Table 2. Functional results after reconstructive surgery are reported in Table 3. Comparing pre- and postoperative HADS score we found a statistically significant difference (p = 0.03). Equally, comparing pre- and postoperative IIEF-5 score, a trend of significance (p = 0.09) was detected. Vaginal penetration became possible in 97.87% of patients (46/47), while erectile function improved in almost half of them (42.55%). 23 patients (48.93%) needed to take PDE5i to enhance their nocturnal erections. Improvement in penile erogenous sensation was recorded in 6.38% (3/47) of patients. Overall, 36 patients were satisfied with the outcome of

Complication Wound infection Apronectomy site dehiscence Myocardial infarction Respiratory failure

Patient (n) 3 2 1 1

Treatment Antibiotics Surgical repair Angioplasty Re-intubation

Table 3. Functional outcomes after surgery (n = 47). Questionnaire Preoperative IIEF-5 Postoperative IIEF -5 Preoperative HADS score Postoperative HADS score Postoperative PGI-I score

Value (SD) 15 (±12.72) 18 (± 12.02) 18 (± 8.48) 8 (± 7.77) 2 (± 2.12)

P value p = 0.09 p = 0.03

SD: Standard deviation; IIEF: International Index of Erectile Function; HADS: Hospital Anxiety and Depression Scale; PGI-I: Patient Global Impression of Improvement.

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A. Cocci, G. Cito, M. Falcone, M. Capece, F. Di Maida, G. Morelli, N. Christopher, D. Ralph, G. Garaffa

DISCUSSION

Buried penis is a non-specific term indicating both a pediatric and adult morbid condition characterized by the complete entrapment of phallus secondary to congenital or acquired etiologies. Acquired buried penis is becoming increasingly common, in concurrence with the prevalence of obesity (17). Nonetheless, no reliable data about the exact incidence of buried penis in adults are available. In fact, this condition can significantly affect patientsâ&#x20AC;&#x2122; quality of life as it compromises sexual and urinary function and renders urogenital hygiene almost impossible (10, 18). Furthermore, buried penis can be secondary to excessive pre-pubic adiposity or lymphoedematous tissue or to excessive penile shaft skin removal during circumcision (6). During micturition, urine from the buried urethral meatus drips over the scrotum and the thigh resulting in tissue maceration, infection, inflammation, scarring and chronic skin changes (19). The main proposal for the management of adult buried penis is surgical correction. Several surgical techniques have been described, depending on the etiology of the buried penis. When insufficient penile skin is available, either due to previous overzealous circumcision or because all skin is affected by LS and therefore needs to be removed at the time of surgery, adequate cover can be achieved with a STSG (20). In case of excessive penoscrotal lymphoedema, all the lymphoedematous tissue has to be excised down to Buckâ&#x20AC;&#x2122;s fascia on the penis and spermatic fascia on the testicles. Genital skin cover of the penis is achieved with preputial flaps, as they are never affected by lymphoedema, and STSG while scrotal reconstruction is achieved with craniodorsal flaps (21). If excessive suprapubic adiposity is the cause of the buried penis, the excessive adipose tissue has to be completely removed, either through an open suprapubic fat pad excision or liposuction. If excessive abdominal skin is present, the patient needs also to undergo an apronectomy to allow adequate exposure of the genitalia. Suspensory ligament division can be performed in combination with suprapubic fat pad excision in order to gain some extra penile length (17). Donatucci et al. described a treatment algorithm ranging from release of scar contracture and primary closure (10). If insufficient release of the phallus through scar release occurs, then panniculectomy is justified. Depending on the adequacy of skin or soft tissue for closure, the next step would be to use primary skin closure versus Z-plasty. If native skin is not available and/or of poor quality, then split thickness skin grafts or flaps may be necessary. Skin flaps should only be used when an inadequate graft bed exists (14). As a common rule, in case of LS, genital skin should not be used for repair, as it can potentially develop LS in the future and STSG are the solution of choice (12). Generally, thick STSG tend to heal with less contracture and dyschromia than their thin counterparts and therefore are ideal for penile shaft cover in patients who are keen to resume sexual activity. On the other hand, thin

Archivio Italiano di Urologia e Andrologia 2019; 91, 1

STSG tend to have a better take and are therefore the solution of choice for coronal and glans reconstruction (9, 22). The current series confirms the importance of surgically addressing buried penis in order to improve sexual and urinary function, which translates in a significant improvement in overall quality of life. In particular, according to literature, sexual penetration became possible in about 98% of cases and more than 90% of patients were satisfied with the outcome of surgery (9, 23). However, the main limitation of the current study was represented by the small number of the study cohort.

CONCLUSIONS

Surgical management of acquired adult buried penis is necessary as this condition can have a profound negative impact on quality of life. In expert hands, excision of excessive adipose/lymphoedematous tissue and of genital skin affected by LS followed by reconstruction with STSG yields satisfactory functional results and allows restoration of sexual and urinary function in most patients.

REFERENCES

1. Keyes EL. Phimosis-paraphimosis-tumors of the penis. Appleton & Co, New York, NY, USA 1919. 2. Wollin M, Duffy PG, Malone PS, Ransley PG. Buried penis. A novel approach. Br J Urol. 1990; 65:97-100. 3. Crawford BS. Buried penis. Br J Plast Surg. 1977; 30:96-99. 4. Maizels M, Zaontz M, Donovan J, et al. Surgical correction of the buried penis: description of a classification system and a technique to correct the disorder. J Urol. 1986; 136:268-271. 5. Cromie WJ, Ritchey ML, Smith RC, Zagaja GP. Anatomical alignment for the correction of buried penis. J Urol. 1998; 160:14821484. 6. Mattsson B, Vollmer C, Schwab C, et al. Complications of a buried penis in an extremely obese patient. Andrologi.a 2012; 44(Suppl 1): 826-828. 7. Tausch TJ, Tachibana I, Siegel JA, et al Classification system for individualized treatment of adult buried penis syndrome. Plast Reconstr Surg. 2016; 138:703-711. 8. Frenkl TL, Agarwal S, Caldamone AA. Results of a simplified technique for buried penis repair. J Urol. 2004; 171:826-828. 9. Fuller TW, Theisen K, Rusilko P. Surgical management of adult acquired buried penis: escutcheonectomy, scrotectomy, and penile split-thickness skin graft. Urology. 2017; 108:237-238. 10. Donatucci CF, Ritter EF. Management of the buried penis in adults. J Urol. 1998; 159:420-424. 11. Rybak J, Larsen S, Yu M, Levine LA. Single center outcomes after reconstructive surgical correction of adult acquired buried penis: measurements of erectile function, depression, and quality of life. J Sex Med. 2014; 11:1086-1091. 12. Garaffa G, Shabbir M, Christopher N, et al. The surgical management of lichen sclerosus of the glans penis: our experience and review of the literature. J Sex Med. 2011; 8:1246-1253. 13. Yalcin I, Bump RC. Validation of two global impression ques-

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tionnaires for incontinence. Am J Obstet. Gynecol. 2003; 189:98101. 14. Rosen RC, Cappelleri JC, Gendrano N, 3rd. The International Index of Erectile Function (IIEF): a state-of-the-science review. Int J Impot Res 2002; 14:226-244. 15. D'Elia C, Cerruto MA, Cavicchioli FM, et al. Critical points in understanding the Italian version of the IIEF 5 questionnaire. Arch Ital Urol Androl. 2012; 84:197-201. 16. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983; 67:361-370. 17. Adham MN, Teimourian B, Mosca P. Buried penis release in adults with suction lipectomy and abdominoplasty. Plast Reconstr Surg. 2000; 106:840-844. 18. Tang SH, Kamat D, Santucci RA. Modern management of adultacquired buried penis. Urology. 2008; 72:124-127.

19. Burns H, Gunn JS, Chowdhry S, et al. Comprehensive review and case study on the management of buried penis syndrome and related panniculectomy. Eplasty. 2018; 18:e5. 20. Triana Junco P, Dore M, Nunez Cerezo V, et al. Penile reconstruction with skin grafts and dermal matrices: indications and management. European J Pediatr Surg Rep. 2017; 5:e47-e50. 21. Garaffa G, Christopher N, Ralph DJ. The management of genital lymphoedema. BJU Int. 2008; 102:480-484. 22. White N, Hettiaratchy S, Papini RP. The choice of split-thickness skin graft donor site: patients' and surgeons' preferences. Plast Reconstr Surg. 2003; 112:933-934. 23. Hughes DB, Perez E, Garcia RM, et al. Sexual and overall quality of life improvements after surgical correction of "buried penis". Ann Plast Surg. 2016; 76:532-535.

Correspondence Andrea Cocci, MD, Ph.D (Corresponding Author) cocci.andrea@gmail.com Gianmartin Cito, MD Fabrizio Di Maida, MD Careggi Hospital, Department of Urology, University of Florence Largo Brambilla 3 â&#x20AC;&#x201C; 50139 Florence (Italy) Marco Falcone, MD Molinette Hospital, Department of Urology, University of Turin, Turin (Italy) Marco Capece, MD Department of Urology, University of Naples, Naples (Italy) Girolamo Morelli, MD Department of Urology, University of Pisa, Pisa (Italy) Nim Christopher, MD David Ralph, MD Giulio Garaffa, MD The Institute of Urology, UCLH, and International Andrology, London (UK) Archivio Italiano di Urologia e Andrologia 2019; 91, 1

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DOI: 10.4081/aiua.2019.1.30

ORIGINAL PAPER

Sutureless laparoscopic partial nephrectomy using fibrin gel reduces ischemia time while preserving renal function Daniele Tiscione 1, Tommaso Cai 1, Lorenzo Giuseppe Luciani 1, Marco Puglisi 1, Daniele Mattevi 1, Gabriella Nesi 2, Mattia Barbareschi 3, Gianni Malossini 1 1 Department

of Urology, Santa Chiara Regional Hospital, Trento, Italy; of Pathological Anatomy, University of Florence, Italy; 3 Division of Pathological Anatomy, Santa Chiara Regional Hospital, Trento, Italy. 2 Division

Summary

Objectives: We evaluated the efficacy of sutureless laparoscopic partial nephrectomy (LPN), using a fibrin gel in order to minimize renal ischemia time and preserve kidney function. Materials and Methods: Nineteen patients (mean age 58.3 ± 7.1) undergoing sutureless LPN using a fbrin gel were compared with a control group consisting of 21 patients (mean age 57.9 ± 7.5) subjected to LPN with standard suturing. Intraand post-operative data for the two groups were compared. The following parameters were recorded: patient demographics, Charlson Comorbidity Index, tumor characteristics according to the RENAL score, warm ischemia and operative times, estimated blood loss, mean hospital stay, post-operative complications referring to the Clavien-Dindo classification, renal function parameters pathologic and follow-up data. The main outcome measure was renal ischemia time and maintenance of kidney function. Results: Median warm ischemia time was 13 minutes (range 11-19) in the group treated with fibrin gel and 19 (range 1729) in the control group, with a statistically significant difference (p < 0.001). The two groups were homogeneous in terms of the Charlson Comorbidity Index (4.6 vs 4.8) and RENAL score (9.6 vs 9.4). Median operative time differed significantly in the two groups, 183 minutes (range 145-218) in the group treated with fibrin gel and 201 (range 197-231) in the control group (p < 0.001). A negative surgical margin was reported in 18 patients (94.7%) in the group treated with fibrin gel and in 21 patients (100%) in the control group. No difference in renal function was found between the two groups. Conclusions: Sutureless LPN with fibrin gel can reduce warm ischemia and total operative time while preserving kidney function.

KEY WORDS: Laparoscopic partial nephrectomy; Renal cell carcinoma; Haemostatic agent; Fibrin sealant; Complication. Submitted 10 August 2018; Accepted 5 November 2018

INTRODUCTION

Laparoscopic partial nephrectomy (LPN) is the “first-choice treatment” for patients with small renal masses (≤ 4 cm). Oncological outcomes are similar to those observed after a radical procedure, with well demonstrated benefits such as a lower risk of long-term renal insufficiency and consequently better prospects for the quality of life (1-4). However, LPN remains a technically complex procedure

because of the difficulties in hemostasis and management of collecting-system injuries (4). Various techniques, instruments and agents have been proposed to minimize intracorporeal suturing and warm ischemia time, but there is no consensus regarding the best approach when dealing with these issues (5). A wide variety of hemostatic agents (HA) and tissue sealants have been employed, the majority approved for use in urology (6). Levinson et al. described the first series of 7 partial nephrectomies with these agents, highlighting the safety of the procedure, its contribution to lowering warm ischemia time and the absence of any reported complications (7). Hidas compared changes in renal function after Nephron-Sparing Surgery (NSS) using HAs alone versus standard suturing; and reported renal functional loss of 11% versus 20%, respectively, highlighting how the surgeon should aim for shorter warm ischemia times (8). The present study assessed the efficacy of sutureless LPN using a fibrin gel (Tissucol®) in order to minimize renal ischemia time and preserve kidney function, when compared with LPN standard suturing.

MATERIALS

AND METHODS

Study design Data from 19 patients (mean age 58.3 ± 7.1) who had undergone sutureless LPN using Tissucol® between October 2008 and July 2009 were compared with those from a control group of 21 patients (mean age 57.9 ± 7.5) subjected to LPN with standard suturing during the same period. All patients underwent standard laboratory examinations and radiologic evaluations before tumour staging and surgical planning. Demographic and tumor characteristics following the RENAL score were recorded and the Charlson Comorbidity Index was calculated. All procedures were carried out by a single dedicated uro-oncologic surgeon (G.M.). The following variables were also recorded: operative time, warm ischemia time, estimated blood loss, intra-operative transfusion and complications (intra-operative data); post-operative complications using the Clavien-Dindo classification and any subsequent treatment, post-operative hospital stay, renal function, pathologic and follow-up findings (post-operative data). Renal function was evaluated through a change in serum creatiNo conflict of interest declared.

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Sutureless laparascopic partial nephrectomy using fibrin gel

nine or estimated glomerular filtration rate (eGFR) from the baseline according to Gill et al. (9). Percent change in serum creatinine and eGFR was determined by calculating the difference between pre-operative and follow-up data. Follow-up visits were scheduled every 6 months after surgery. Here, we present the long-term follow-up (12 months) results of renal function preservation.

Figure 1. The figure shows renal vein (V) and artery (A) isolation (above) and the subsequent renal artery clamping (below).

Ethical consideration The retrospective nature of the study did not require the Ethical Committee approval. The study was, however, conducted in line with Good Clinical Practice guidelines, with ethical principles laid down in the latest version of the Declaration of Helsinki. Inclusion and exclusion criteria Requirements for inclusion were the presence of a single, solid, contrast-enhanced parenchymal renal mass (attenuation increase > 15 H on contrast-enhanced CT or > 15% on gadolinium-enhanced MRI) consistent with renal cell carcinoma on pre-operative imaging and scheduled for LPN (10). Patients with severe medical or psychiatric illness barring adequate informed consent, under 18 or over 85years, with major concomitant diseases precluding surgical treatment or who had had radiation therapy to the retroperitoneum or previous abdominal major surgery, with an ASA score ≥ 3, poor performance status (ECOG 3-4), known anatomical abnormalities of the uro-genital tract, renal vein involvement, lymphadenopathy, extrarenal tumor extension or preoperative CT scan documenting invasion of the collecting system were all excluded. Patients with positive cytologic urine analysis or with a previous history of urothelial carcinoma were also excluded.

Figure 2. The figure shows the renal mass resection with an electrocautery device and cold-cut endosheares. T: tumour.

RENAL score and Charlson comorbidity index The R.E.N.A.L.-Nephrometry score (NS) was calculated according to Kutikov et al. (11). In brief, standardized points (1-3 points per descriptor) are assigned based on tumour size, endophytic/exophytic properties, proximity to the collecting system and lesion location relative to the polar lines. The Charlson Comorbidity Index was calculated using the specific software available on the Institute for Algorithmic Medicine website (A Texas Non-profi Corporation) (http://www.medal.org/OnlineCalculators/ch1/ ch1.13/ch1.13.01.php) (12). Surgical technique description (TISSUCOL® group) Patients were positioned in strict lateral decubitus and four trocars were routinely inserted. LPN was performed via a transperitoneal approach. No pre-operative ureteral stent was routinely placed. Gerota’s fascia was opened, the ureter identified and the renal artery isolated (Figure 1). Vascular control was achieved by clamping the renal artery before tumour resection (Figure 1) (warm ischemia time included tumour resection, evaluation of bleeding and application of sealant). During warm ischemia, resection was performed with an electrocautery device and cold-cut endo-shears (Figure 2). The perinephric fat was dissected from the kidney at the level of the renal capsule, leaving only the fat overlying the tumour. In all cases, fibrin glue (Tissucol® Baxter AG) was used as the sealant (Figure 3). No addi-

tional methods of hemostasis (including suturing) were applied. Fibrin glue was spread on the tumour bed using a specific device that allowed the two major components to be applied simultaneously. We used a dual chamber delivery system, in which fibrinogen and factor XIII contained in one chamber were admixed with thrombin in the other directly at the application site. Clot formation required 3 minutes and final elimination by macrophages occurred within 2-4 weeks without inducing fibrosis or foreign body reactions (13). The surgical specimen with the tumour and any detached perinephric fat was immediately placed in an Endo-catch® bag which was removed at the end of the procedure through the 12-mm port site, extending the incision if necessary (Figure 4). Biopsy and frozen sections of the resection bed were only performed when tumour infilArchivio Italiano di Urologia e Andrologia 2019; 91, 1

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D. Tiscione, T. Cai, L.G. Luciani, M. Puglisi, D. Mattevi, G. Nesi, M. Barbareschi, G. Malossini

Figure 3. The figure shows the intraoperative TISSUCOL® application on the bed of resection.

Preoperative complication evaluation Perioperative complications were classified according to the Clavien-Dindo system (18). Statistical analyses Data were entered into a Microsoft Excel database and transferred to SPSS 11.0 for Apple-Macintosh (SPSS, Inc., Chicago, Illinois). Descriptive analysis was used to evaluate all the variables considered. Qualitative analyses were compared using the Chi-2 or Fisher exact tests where applicable, and quantitative analyses with Student’s t-test. Data are presented as the mean ± standard deviation (SD) or percentage. Correlations were assessed by Pearson or Spearman test. Statistical significance was achieved if p was less than 0.05. All reported p-values were two-sided.

RESULTS Patient characteristics at baseline In the TISSUCOL® group, the mean age-adjusted Charlson comorbidity index was 4.6 (range 4-7) and mean RENAL score 9.6 (range 8-12), and in the control group 4.8 (range 4-7) and 9.4 (range 8-11), respectively. Table 1 gives the clinical, laboratory and pathologic characteristics of the enrolled patients.

ptF

Figure 4. The figure shows the resected tumour (T) with the overlying fat (ptF).

tration was suspected, as suggested by Porpiglia (14). In the case of a positive biopsy, radical nephrectomy or deeper resection depended on the individual case. All patients in the control group underwent standard suturing LPN, as described by Porpiglia (14). Histological analysis Histopathology was reviewed according to the 2004 WHO classification (15). All renal cell carcinomas were classified according to the TNM staging system (16), while nuclear grade was assigned according to the criteria proposed by Fuhrman et al. (17).

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Intra-operative and peri-operative data TISSUCOL® group After 2-3 minutes of applying the fibrin glue to the resection site, hemostasis was immediate in all cases. All surgery was performed intracorporeally and without hand assistance. Median vascular clamping time was 13 minutes (range 11-19) and median operative time 183 minutes (range 145-218). Median blood loss was 300 ml (range 150-600). No open conversions were required. Five patients (26.3%) presented low-grade complications (Clavien II). Four patients (21%) needed blood transfusions, while one patient showed intraoperative invasion of the collecting system that had not been documented pre-operatively by CT scan. This patient was treated with ureteral stenting for 7 days. Control group All surgery was carried out intracorporeally without hand assistance. Median vascular clamping time was 19 minutes (range 17-29) and median operative time was 201 minutes (range 197-231). Median blood loss was 290 ml (range 150-550). There were no open conversions. Eight patients (38%) showed low-grade complications (Clavien II), while five patients (23.8%) required blood transfusions. Statistically significant differences were found between the two groups for mean ischemia time (p < 0.001), median operative time (p < 0.001) and mean blood loss (p < 0.02). All intra and peri-operative data are summarized in Table 2. Histological results In the TISSUCOL® group, 18 cases were classified as conventional RCC and 1 as angiomyolipoma, while in the control group 19 were diagnosed as conventional RCC

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Sutureless laparascopic partial nephrectomy using fibrin gel

Table 1. Patient anamnestic and clinical characteristics at enrolment time. Group No. of patients Mean age (years) (± SD*) Gender Male Female Mean tumor size at CT scan (cm) (± SD*) Charlson CI§ R.E.N.A.L score Side of lesion R° L† Location of lesion Superior pole Inferior pole Central Location of lesion in renal parenchyma Exophytic Deep Pathological results Renal cell carcinoma Angiomyolipoma Oncocytoma Fuhrman grade in malignant tumors G1 G2 G3 G4 Stage according to UICC classification in malignant tumour pT1b pT2

TISSUCOL® Control 19 21 58.3 ± 7.1 57.9 ± 7.5 13 6 3.1 ± 0.9 4.6 9.6

16 5 2.9 ± 0.8 4.8 9.4

6 13

8 13

5 7 7

4 9 8

13 6

16 5

0.78 0.74

0.68

Kidney function preservation Post-operative renal function remained stable in all patients. No statistically significant differences were found between the two groups in terms of eGFR results at the follow-up visit. In the TISSUCOL® group mean eGFR was 78.3 (range 42-127) and in the control group 79.4 (range 55-130). Table 2 shows laboratory data at the time of enrolment and follow-up visit.

0.72

18 1 -

19 2

6 (33.3) 7 (38.9) 5 (27.8) 0

7 (36.9) 9 (47.4) 3 (15.7) 0

16 (88.8) 2 (11.2)

15 (78.9) 4 (21.1)

Table 2. Peri-operative parameters, complications and renal function. Group Mean operative time (min) (± SD*) Median ischemia time (min) (± SD*) Mean blood loss (mL) (± SD*) Rate of intra-operative transfusion (%) Conversion to open nephrectomy Mean hospital stay (days) (± SD*) Post-operative acute hemorrhagic event Post-operative hematoma with transfusion (%) Post-operative urinary leakage with uretheral stenting eGFR (mL/min/1.73 m2) pre-operative (± SD*) post-operative (± SD*)

P 0.86 0.72

short-term bleedings from the draining tubes, which were removed before patient discharge. No adverse events were observed during hospitalization or at long-term follow-up (79.6 ± 8.9 months). As regards post-operative hospitalization times or complications, no significant differences were found between the two groups.

TISSUCOL® 183 ± 25.9 13 ± 2.3 359 ± 142.8 4/19 (21) 0/19 5.8 ± 1.6 0/19 1/19 (5.2) 1/19 (5.2)

Control 201 ± 27.8 19 ± 3.5 460 ± 126.7 5/21 (23.8) 3/21 (14.2) 6.0 ± 1.5 1/21 (4.7) 3/21 (14.2) 2/21 (9.5)

80.5 ± 10.9 78.3 ± 11.3

81.2 ± 9.8 79.4 ± 13.3

and 2 as oncocytoma. There was no sign of residual tumor on frozen section examination of the resection bed in either group. All pathologic data are detailed in Table 1. Clinical outcome results Post-operative hospitalization times were normal for all patients in the TISSUCOL® group (median 5 days, range 4-7) with no relevant complications as regards wound healing or laboratory analyses. There were no significant

DISCUSSION

LPN is increasingly performed all over the world and constitutes a valid procedure for the management of small renal tumours, but some technical aspects still need to be improved. 0.80 Even in expert hands, rates of urine leakage and hemorrhage are not negligible (19). Despite the development of adjunctive hemostatic agents, none have proved to offer complete hemostasis by themselves (19). In this 0.65 paper, we demonstrated that sutureless LPN with TISSUCOL® can reduce warm ischemia and total operative times as well as preserve kidney function, without severe complications when compared with standard suturing LPN. In particular, renal suturing during LPN is a difficult step, which increases operative and P warm ischemia time. The use of HAs may well < 0.001 simplify the hemostatic procedure, providing < 0.001 similar results to those observed after suture 0.02 renorrhaphy. Our results highlight some important points. The mean ischemia time of 13.8 minutes is sig0.23 nificantly shorter than that reported by Lifshitz et al. (31 min) (20). Thus, the mean total operative time (183 minutes) is also significantly 0.23 shorter than described by other Authors (14, 21). These results can be explained by the fact that a sutureless technique reduces both total ischemia and operative times. Concerning renal function maintenance, our results are promising when compared with the standard technique, probably due to the shorter mean ischemia time in the TISSUCOL® group. Breda et al., in a comprehensive review of the practice patterns of urologists performing LPN and the relevant use of hemostatic agents, underlined that although these agents appear to offer some advantage, they should be limited to controlling minor bleeding and as an adjunct to sutured bolsters (22). In describing an alternative technique of LPN for central tumours, Weight et al, concluded that in selected patients with a tumor extending Archivio Italiano di Urologia e Andrologia 2019; 91, 1

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D. Tiscione, T. Cai, L.G. Luciani, M. Puglisi, D. Mattevi, G. Nesi, M. Barbareschi, G. Malossini

to the collecting system, the LPN defect can be safely reconstructed with a running intraparenchymal hemostatic suture and thrombin sealant with no bolstered renorrhaphy (23). We observed two post-operative complications (bleeding in one case and urine leak in the other), while no open conversion was necessary. In both cases the renal tumour was described as “deep”. Several authors have demonstrated the association between depth of tumour invasion and rate of hemorrhage or urine leakage (21-22, 24). The present study shows some limitations that should be taken into account, such as the small number of patients and the lack of a control group. Further prospective studies in larger series are mandatory to validate the role of HAs during LPN.

CONCLUSIONS

In our experience, sutureless LPN using TISSUCOL® can reduce warm ischemia and total operative time whilst preserving kidney function with no severe complications when compared with standard suturing LPN.

ACKNOWLEDGEMENTS

12. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987; 40.373-83. 13. Dalpiaz O, Neururer R, Bartsch G, Peschel R. Hemostatic sealants in nephron-sparing surgery: what surgeons need to know. BJU Int. 2008; 102:1502-08. 14. Porpiglia F, Volpe A, Billia M, Scarpa RM. Laparoscopic versus open partial nephrectomy: analysis of the current literature. Eur Urol. 2008; 53:732-43. 15. Eble JN, Sauter G, Epstein JI, et al. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. Lyon, France: IARC, 2004. 16. Edge SB, Byrd DR, Compton CC, et al. AJCC Cancer Staging Manual. Springer-Verlag ed, New York, 2010. 17. Fuhrman SA, Lasky LC, Limas C. Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg. Pathol. 1982; 6:655-63. 18. Clavien PA, Barkun J, de Oliveira ML, et al. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009; 250:187-96.

We are grateful to all members of the Department of Urology (Santa Chiara Regional Hospital) for their help in patient data collection and to Professor John Denton for manuscript language revision.

19. Louie MK, Gamboa AJ, Kaplan AG, et al. Bovine serum albumin glutaraldehyde for completely sutureless laparoscopic heminephrectomy in a survival porcine model. J Endourol. 2010; 24:451-55.

REFERENCES

21. Ramani AP, Desai MM, Steinberg AP, et al. Complications of laparoscopic partial nephrectomy in 200 cases. J Urol. 2005; 173:42-7.

1. Porpiglia F, Fiori C, Piechaud T, et al. Laparoscopic partial nephrectomy for large renal masses: results of a European survey. World J Urol. 2010; 28:525-29. 2. Lee CT, Katz J, Shi W, Thaler HT, et al. Surgical management of renal tumors 4 cm or less in a contemporary cohort. J Urol. 2000; 163:730-36. 3. Uzzo RG, Novick AC. Nephron-sparing surgery for renal tumors: indications, techniques and outcomes. J. Urol 2001; 166:6-18. 4. MacLennan S, Imamura M, Lapitan MC, et al. Systematic review of oncological outcomes following surgical management of localised renal cancer. Eur Urol. 2012; 61:972-93. 5. Msezane LP, Katz MH, Gofrit ON, et al. Hemostatic agents and instruments in laparoscopic renal surgery. J Endourol. 2008; 22:403-8. 6. Hong YM, Loughlin KR. The use of hemostatic agents and sealants in urology. J Urol. 2006; 176:2367-74. 7. Levinson AK, Swanson DA, Johnson DE, et al. Fibrin glue for partial nephrectomy. Urology. 1991; 38:314-16. 8. Hidas G, Lupinsky L, Kastin A, et al. Functional significance of using tissue adhesive substance in nephron-sparing surgery: assessment by quantitative SPECT of 99m Tc-Dimercaptosuccinic acid scintigraphy. Eur Urol. 2007; 52:785-89. 9. Gill IS, Eisenberg MS, Aron M, et al. "Zero ischemia" partial nephrectomy: novel laparoscopic and robotic technique. Eur Urol. 2011; 59:128-34. 10. Clark PE, Woodruff RD, Zagoria RJ, Hall MC. Microwave ablation of renal parenchymal tumors before nephrectomy: phase I study. Am J Roentgenol. 2007; 188:1212-14.

11. Kutikov A, Uzzo RG. The R.E.N.A.L. nephrometry score: a comprehensive standardized system for quantitating renal tumor size, location and depth. J Urol. 2009; 182:844-53.

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20. Lifshitz DA, Shikanov SA, Deklaj T, et al. Laparoscopic partial nephrectomy: a single-center evolving experience. Urology. 2010; 75:282-87.

22. Breda A, Stepanian SV, Lam JS, et al. Use of hemostatic agents and glues during laparoscopic partial nephrectomy: a multi-institutional survey from the United States and Europe of 1347 cases. Eur Urol. 2007; 52:798-803. 23. Weight CJ, Lane BR, Gill IS. Laparoscopic partial nephrectomy for selected central tumours: omitting the bolster. BJU Int. 2007; 100:375-78. 24. Venkatesh R, Weld K, Ames CD, et al. Laparoscopic partial nephrectomy for renal masses: effect of tumor location. Urology. 2006; 67:1169-74.

Correspondence Daniele Tiscione, MD Tommaso Cai, MD (Corresponding Author) ktommy@libero.it Lorenzo Giuseppe Luciani, MD Marco Puglisi, MD Daniele Mattevi, MD Gianni Malossini, MD Department of Urology, Santa Chiara Regional Hospital, Trento (Italy) Largo Medaglie d'Oro 9, Trento (Italy) Gabriella Nesi, MD Department of Pathology, University of Florence, Florence (Italy) Mattia Barbareschi, MD Department of Pathology, Santa Chiara Regional Hospital, Trento (Italy)

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NOTE OF SURGICAL TECHNIQUE

DOI: 10.4081/aiua.2019.1.35

The LEST technique: Treatment of prostatic obstruction preserving antegrade ejaculation in patients with benign prostatic hyperplasia Rosario Leonardi Department of Urology and Andrological Surgery, Musumeci GECAS Clinic Gravina of Catania, Catania, Italy.

Summary

The objective of this study was to search for an alternative technique to relieve prostatic obstruction due to benign prostatic hyperplasia without affecting the ejaculatory function. The technical requirements are a laser with a wavelength well absorbed by water (good vaporizing effect) and at the same time by hemoglobin (good hemostatic effect) and laser fibers very resistant at high emission power allowing perfect vaporization in a contact mode. The aim of the technique is to avoid damage of the structures that allow the peripheral region of the prostate and the seminal vesicles to discharge their secretions into the posterior urethra. The orifices of the ejaculatory ducts must therefore be identified and preserved, damage of the ejaculatory ducts along their path inside the prostate must be avoided and the so called “genital sphincter” must be saved. The steps of the Leonardi Ejaculation Sparing Technique (LEST) procedure are as follow: Step 1 - ejaculatory duct orifices must be identified and the limits of the vaporization section must be marked. Step 2 - bladder neck is cleaned of the prostate hypertrophic tissue saving, as much as possible, the smooth muscle fibers of the bladder neck. Step 3 - vapo-resection of the lateral lobe (or enucleation of the adenoma) is performed. Step 4 - cautious and meticulous preparation of the prostatic apexes is obtained with saving of the orifices of the ejaculatory ducts. An antegrade ejaculation is maintained in about 80% of cases in patients without a middle lobe, although in the presence of a middle lobe this rate drops to about 50%.

KEY WORDS: Benign prostatic hyperplasia; Prostatic obstruction; Antegrade ejaculation; Laser. Submitted 25 January 2019; Accepted 8 February 2019

INTRODUCTION

There is a growing interest to maintain a normal sexual function, after surgical management of bladder outflow obstruction due to benign prostatic hyperplasia (BPO). It is well known, that transurethral resection of the prostate (TURP) strongly impacts on sexual function, not so much in terms of erection but, of course, in terms of antegrade emission of seminal fluid. This has led, in recent years, to the search for alternative techniques to relieve obstruction capable of preserving the ejaculatory function. Unfortunately, most of these techniques had a limited diffusion due to both restricted indications (1) and reduced efficacy of obstruction removal.

In this paper we will describe the technique developed by our team, starting from the anatomical and functional premises that support it. Furthermore, the process of the development of the technique over time will be reviewed and finally the surgical procedure aiming to achieve a complete removal of bladder neck obstruction with preservation of ejaculatory function will be described “step by step”. Anatomy of the prostate The prostate is a glandular and stromal organ, single and median, located in the small pelvis between the base of the bladder and the urogenital diaphragm, behind the pubic symphysis and in front of the rectum. The first tract of the urethra, namely the prostate urethra, passes through the prostate from the base to its apex. The secretions of the prostate glands, seminal vesicles and testicles (corpuscular part of the seminal fluid) are voided into the lumen of the prostate urethra. The seminal fluid is made up for about 15-30% from prostate secretion, for about 50-70% from the fluids of the seminal vesicles and for less than 5% from the product of the testicles, deferential ampules, glands of Cowper and urethral glands (2). The prostate is typically described as a chestnut shape with the base facing the bladder and the apex at the bottom, resting on the external urethral sphincter (3). Histologically, it is composed of tubulo-alveolar glands whose ducts open into the prostate urethra. The gland can be clinically divided into the anterior lobe, the middle lobe, if present, and two lateral lobes. McNeal observed that the urethra separates the prostate into two regions, the ventral (fibromuscular) and the dorsal (glandular) one. Approximately halfway between the apex and the base, the posterior wall of the urethra undergoes an acute angle (ventral angle of 35 degrees), which separates the urethra into a proximal segment and a distal segment. The orifices of the ejaculatory ducts and the verum montanum are located in the context of the distal segment. The glandular prostate can be divided into four distinct regions: peripheral zone, central zone, transition zone, and periurethral region (4) (Figures 1, 2). In absence of prostatic hyperplasia (BPH), the peripheral zone makes up about 70% of the gland. The transition

No conflict of interest declared. Archivio Italiano di Urologia e Andrologia 2019; 91, 1

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R. Leonardi

Figure 1. The figure shows schematically a sagittal section of prostate .

Figure 2. 3D reconstruction of different zones of prostate.

zone represents about 5-10% of the glandular tissue and is located at the angle that divides the tract of the urethra above and below the veru montanum. The central area surrounds and protects the ejaculatory ducts and constitutes about 25% of the glandular tissue. The fibromuscular zone that does not contain glandular tissue may, in some subjects, constitute about one third of the glandular volume (5). Functional anatomy of the ejaculation Ejaculation consists of three physiological phases. The first phase, also known as the preparation phase, is under the prevalent influence of the parasympathetic system with an increase in the secretory activity of the prostate glands and seminal vesicles. This is followed by a second phase, called emission phase, which culminates with a coordinated and peristaltic contraction of the smooth musculature of the vasa, ampoules, seminal vesicles and acinar prostatic glands. This results in the emission and accumulation of seminal fluid in the posterior

Archivio Italiano di Urologia e Andrologia 2019; 91, 1

urethra. This phenomenon creates the unstoppable sensation of ejaculation. The seminal fluid injected into the posterior urethra would drain into the bladder if an "anti-reflux" system was not activated by the alpha sympathetic system. Initially, this anti-reflux system was exclusively identified with the bladder neck, but subsequently the histochemical studies of Gosling et Thompson identified this sphincter area in the pre-prostatic segment of the posterior urethra above the veru (6). Bruschini et Tanagho confirmed, by pharmacological and manometric studies, the presence of this area called "genital sphincter" (7) (Figures 3, 4). This functional sphincter with mainly genital function begins in the bladder neck, continues with the smooth muscle fibers intrinsic to the urethra and is added to the urinary sphincter fibers incorporated in the prostate stroma and to the smooth muscle of prostate glandular elements (8). To summarize, it is a smooth muscle complex located in the area proximal to the opening of the ejaculatory ducts in the urethra. These muscles, in the phase in which the action of the sympathetic nervous system prevails, contracts preventing the reflux of the seminal fluid into the bladder (9). In case of BPH, the transition zone is larger than in the normal prostate. The transitional zone compresses the peripheral zone moving it down its apical portion. In addition, in 36 to 70% of patients with BPH there is a reduction or absence of ejaculate, which etiopathogenesis is still unclear. Some authors argue that there may be a compression of the ejaculatory ducts, others that there may be an increase in the angle of the ducts in the terminal portion near their outlet into the urethra. The fact is that the glandular structure of the hypertrophic prostate (transition zone) loses its physiological structure, and the glands, overcrowded and newly formed, often do not produce an adequate volume of secretion compared to a normal gland (Figure 5). Histological studies with quantitative imaging analysis of prostate sections of symptomatic BPH subjects stained with double enzyme immunoassay showed that, for each area examined, the percentage density of smooth muscle and connective tissue was significantly higher than those of glandular epithelium and glandular lumen area (medium SEM) (10). From this finding it can be deducted that the prostate component of the seminal fluid, in the subject with BPH, is significantly reduced.

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The LEST technique

Figure 3. Glandular section along the urinary axis F Anterior fibromuscular layer; BN Bladder Neck; PZ Peripheral zone; GS Genital Sphincter surrounding the premontanal urethra, ensuring with its contraction, during ejaculation, the orthodromic direction of the seminal flow. Modified from F. Basile et al. Manual of Semeiotics and Surgical Methodology. Edra Publisher 15 Jan 2014.

Figure 4. Intraoperative image depicting the Genital Sphincter (SG).

Figure 5. Histological appearance of prostate glandular tissue in a normal subject and in a subject with benign prostatic hyperplasia. Histology

Normal prostate

Benign prostatic hyperplasia

LEST procedure (Leonardi Ejaculation Sparing Technique) As mentioned in the introduction, the development of the LEST technique originates from the growing demand from the male population to be able to maintain an intact sexual function (erection and ejaculation) after an efficacious

procedure of removal of bladder neck obstruction (11). Although the gold standard of endoscopic surgical treatment for benign prostatic hyperplasia (BPH) has been, until now, the transurethral resection of the prostate (TURP), in recent years the supremacy of this procedure has been challenged by the introduction of new surgical devices and, above all, of endoscopic lasers capable of removing the prostate adenoma, that is the cause of cervical-urethral obstruction. These techniques have, in fact, reduced hospitalization times and the complications associated with TURP (hemorrhage, incontinence) (12). Until now, little attention was given to the maintenance of ejaculatory function, considering retrograde ejaculation as a minor side effect for the quality of life of the patient, if not as a tangible sign of a successful removal of obstruction. However, patients, if accurately interviewed, do not tolerate retrograde ejaculation, and, for many of them, this risk is the only reason that leads them to delay the procedure, even when mandatory, for fear of incurring this post-operative outcome (13, 14). We have therefore decided, on the basis of the anatomical-functional premises described above, to develop the LEST technique, whose preliminary data have already been published in 2009 (15). We believed that a complete removal of obstruction, overlapping to that achievable by a successful TURP, should not necessarily result in a retrograde ejaculation. This could be possible because the removal of hypertrophic tissue, as mentioned above, will reduce the volume of semen only by a small amount, since hypertrophic tissue produces a reduced amount of secretions. In fact the most volume of semen, especially in subjects with BPH, comes from the glands of the peripheral zone and seminal vesicles. It was therefore necessary: 1. To conceive a technique that would not damage the structures that allow these anatomical regions to introduce their secretions into the posterior urethra. Secretions of the peripheral region of the prostate and the seminal vesicles discharge their secretions at the base of the prostatic urethra above the veru (pre-montonal) through the orifices located in the region surrounding the veru montanum. The orifices of the ejaculatory ducts must therefore be identified and preserved. 2. To avoid damaging the ejaculatory ducts along their path inside the prostate, remembering that they are surrounded by the central part of the prostate and that they get closer and closer to the floor of the prostate urethra, as they approach their openings. 3. To save what Tanagho, and after him other authors, called "genital sphincter", as previously described in the anatomical-functional premises. 4. To have the equipment adequate to develop an unobstructed prostatic lodge without damaging all the structures above described. Lasers In relation to this latter point we had to exclude the devices used for traditional resection, aiming to find a laser with a suitable wavelength to be well absorbed by water (good vaporizing effect), and at the same time by hemoglobin (good hemostatic effect) (Figure 6). It was also necessary to Archivio Italiano di Urologia e Andrologia 2019; 91, 1

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R. Leonardi

Figure 6. The figure shows at the left the absorption spectrum at wavelength 980 nm in water and hemoglobin, at the right the depth of penetration in the prostate tissue of 980 and other types of laser.

choose a wavelength that did not have a significant effect of deep penetration into the tissues producing only a surface vaporization. This is to avoid the very annoying irritative symptoms due to the reabsorption of the coagulative necrosis produced in depth of the unremoved prostate tissue that was associated with the use of lasers already present on the market. The first laser we tried, able to have all the requirements above described, was a laser with 980 mm wavelength working at the power of 100 watts. Since 2010 a significant improvement was achieved by the use of the new HPD 180 watts high power laser, and, by the production of fibers designed and built to work in contact and at high power. Another improvement was done in 2016 with a new laser that is able to mix freely two wave lengths (980 nm and 1470 nm). This diode laser is capable of emitting two wavelengths of 980 nm and 1470 nm simultaneously along the same fiber. In practice it is possible to mix, according to the structure of the tissue to be vaporized, a prevalence of 980 nm with a stronger affinity for hemoglobin or 1470 nm with a higher absorption in water for less vascularized tissues. The low penetration of both wavelengths into the vaporized tissue (350 microns) (18) allows not only to reduce post-operative irritative symptoms but, at the same time, to safeguard the ejaculatory ducts. Fibers From the very first attempts we realized the importance of using contact vaporization. The vaporization for irradiation, produced by the "side-firing fibers", is not able to sculpt the prostatic lodge with millimetric precision. The beam of light emitted by the fiber can create a more or less extended vaporization margin, depending on the distance of the emitting fiber from the prostate tissue. With the "side-firing fiber" a good vaporization is obtained keeping, theoretically, the fiber at a constant distance of 0.5 cm from the tissue to be vaporized. If this distance is not maintained, the radiation power on the tissue is reduced, creating coagulative necrosis instead of vaporization. In our previously published study we did not dispose of “contact” vaporizing fibers, so we had to use a trick that allowed us to use the side fibers in a contact mode. We set the laser to pulsed mode in order to reduce the stress on the fiber by allowing some cooling in the refractory phase

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of emission. The results obtained in the previous study were satisfactory in terms of removal of obstruction and maintaining the anterograde ejaculation (Table 1). Now we are using new fibers called Twister of three sizes (Normal, Large and Extra Large) (16) (Figure 7). The Twister fiber is a special fiber with a quartz tip, with a 15° curvature at the tip, which allows perfect vaporizaTable 1. Results of “side-firing” laser. Modified by Leonardi R.: Preliminary results on selective light vaporization with the sidefiring 980 nm diode laser in benign prostatic hyperplasia: an ejaculation sparing technique. Prostate Cancer Prostatic Dis. 2009; 12:277-80. Parameter IPSS IPSS improvement % Qmax ml/sec Qmax improvement % PVR ml PVR improvement % IPSS-QoL

Baseline n = 52 3-month n = 52 18.4+/-5.8 7.5+/-5.9 - 59% 7.5+/-4.1 20.9+/-8.4 + 179% 160+/-140 3.5+/-1.2

24+/-22 - 85% 1.3+/-1.2 - 63%

12-month n = 22 6.0+/-0.6 - 67% 19.7+/-1.4 + 163% 20.3+/-4.4 - 87% 1.2+/-0.4 - 66%

IPSS = International Prostate Symptom Score PVR = Postvoidal residual urine Qmax = Maximum flow rate QoL = Quality of Life Change from baseline for all parameters P < 0.0001

Figure 7. Twister Fiber XL.

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The LEST technique

Figure 8. Ejaculatory triangle.

tion and/or engraving of the tissue, in a contact mode. The three measures are distinguished by the volume of the quartz tip and the measure has to be chosen according to the prostate volume that must be vaporized. The Twister Fiber is very resistant even when used at high emission powers, and allow, in almost all of cases, to conclude the procedure with a single fiber (17). These technological innovations have allowed us to be much faster in prostate vaporization, reaching a real speed of tissue removal of about 1.5 grams per minute. The indications have been extended to the treatment of increasingly voluminous prostates, but also allowed us to precisely sculpt the new prostate loggia with excellent control of the vaporization margins and, therefore, with a saving of the structures responsible for the anterograde ejaculation, that was crucial for developing the LEST technique. The area to be preserved has been named by us as the “ejaculatory triangle” (Figures 8, 9). Figure 9. Ejaculatory triangle at the end of the procedure.

a middle lobe, the rate drops to about 50%. The ideal feature of the patient for LEST surgery is a bilobed prostate with a good percentage of peripheral prostate, well visible ejaculatory duct orifices (ODEs) and normal seminal vesicles. For this reason, we always practice a trans-rectal prostate ultrasound and flexible urethroscopy on our patients before surgery. The worst results are in prostate with voluminous medium lobe, non-visible ODEs and hypotrophic seminal vesicles. Why most suitable prostates for LEST should not have a middle lobe? We previously described which anatomical structures are responsible for the persistence of antegrade ejaculation, namely the smooth muscles that extends from the bladder neck along the first tract of the posterior urethra to the veru montanum. As we know, in the trilobal prostates, the middle lobe plays an important role in generating a severe obstruction and therefore, for a successful removal of obstruction, it is necessary to remove all the medium lobe from its origin, near to the veru montanum. This involves the removal of most of the ejaculatory triangle and a weakening of the bladder neck. This is the reason, in our opinion, why the presence of a voluminous middle lobe lowers the success rate of the intervention to about 50%. Why is a good presence of peripheral prostate important? By removing most of the transition zone (reaching the surgical capsule), after the procedure prostate secretion is limited to the peripheral region, which pours its secretion on the floor of the prostate urethra (ejaculatory triangle). As far as seminal vesicles are concerned, we know that, under normal conditions, these structures contribute to producing about 65% of the volume of seminal fluid. Having, therefore, two normotrophic seminal vesicles at ultrasound examination and two ODE clearly visible at endoscopic examination, we can predict a good result in term of volume of liquid produced in the post-operative.

PROCEDURE

STEP BY STEP

Step 1: Identification of anatomical structures Introduced the laser cystoscope with a 30° optic, the ODEs are identified and the limits of the vaporization section are marked (Figure 10). Figure 10. Markers of the lower limit of the vaporesection.

Surgical technique The patient who requires a LEST procedure must be well informed about the technique that we are going to do, knowing well which are the success rates of the “ejaculation sparing” technique, in order not to feed false expectations. Studies conducted by us have shown the possibility of maintaining an anterograde ejaculation in about 80% of cases in patients without a middle lobe. In the presence of Archivio Italiano di Urologia e Andrologia 2019; 91, 1

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R. Leonardi

Figure 11. Start of vapo-resection from the bladder neck.

Figure 12. Bladder neck after surgery. Note the bloodless field, the well defined margin of vapo-resection with sparing of the neck and bladder mucosa that, when washing is stopped, prolapses inside the prostate neo lodge.

Step 2: Bladder neck preparation The vaporization starts with a power lower than the maximum usable for the type of fiber used, in order to avoid thermal shocks to the fiber itself. The bladder neck is cleaned of the prostate hypertrophic tissue that caused the obstruction, saving, as much as possible, the smooth muscle fibers of the neck and ensuring that the neck does not remain rigid after vaporization. We proceed with small incisions at 5 and 7 o'clock, taking care not to destroy the muscle fibers completely. It is always important to identify and preserve the bladder neck fibers . At the end of the vaporization, a clean cut is observed between the bladder mucosa and the prostate lodge (Figures 11, 12). Step 3: Vapo-resection of the lateral lobes Contact vaporization must always meet the criteria of symmetry. The prostatic lodge after removal of obstruction must be large and symmetrical. We start vapo-resection at the base of the lateral lobes so that the edges of the ejaculatory triangle are clearly defined. It should be noted that, in larger prostates, and if it is considered necessary to obtain abundant tissue to be subjected to histological examination, instead of carrying out a vapo-resection, a real enucleation of the adenoma (DiLEP) can be used. In these cases, enucleation is performed sparing the structures considered crucial to obtain an antegrade ejaculation (Figure 13). This last step is perhaps the most delicate and important for the success of the procedure (Figures 14, 15). The prostate apexes with the traditional TURP are completely removed, believing that, in this way, the maximum removal of obstruction will be obtained. In fact, anatomical studies have shown that the prostate apex is only partly constituted by the transitional tissue causing the obstruction. Part of the apexes are constituted by the peripheral area of the gland that has been moved down by the hypertrophy of transitional zone. A proof of this is that, at times, some prostate tumors, which are known to develop more frequently in the

Figure 13. Final result after DiLEP with LEST technique. On the left trans-rectal ultrasound examination showing the large lodge with preservation of the neck. In the small box, endoscopic image of preservation of part of the apexes belonging to the peripheral zone of the gland. On the right endoscopic image showing preservation of the floor of the prostate urethra where the peripheral gland flow into. Transitional zone Anterior fiber-muscular area Bladder Urethra

Seminal vesicles

Central zone

Peripheral zone

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The LEST technique

Figure 14. Start of the vapo-resection of the apexes.

Figure 15. Trans-rectal ultrasound image after DiLEP with LEST technique.

Bladder neck

Ejaculatory triangle

REFERENCES

1. Hoepffner JL, Fontaine E, Benfadel S, et al. A modified cervicoprostatic incision technique in hypertrophic adenoma in young subjects desiring to preserve ejaculation. Prog Urol. 1994; 4:371-7.

Apexes

Bla dd er

Se mi na lv es icl es Ce ntr al

peripheral zone but not in the transition zone, are found in the biopsies of the apex. The peripheral part of the prostate tissue does not have a structure that could obstruct the urinary flow. Its preservation guarantees the integrity of the genital sphincter and protects the outlets of the ejaculatory ducts during the vaporization phase of this area. Another fundamental step for the success of the procedure is the preservation of the orifices of the ejaculatory ducts. In doing so, we ensure that the secretions from the seminal vesicles are introduced into the posterior urethra (Figure 16). At this point the intervention can be considered completed. We administer an alpha-blocker in the first 20 days of the post-operative. The choice to administer the alphablocker is to avoid spasms of the smooth muscles of the bladder neck which, with the LEST technique, is spared. We do not administer cortisone or painkillers because treatment with the above technique and with wavelengths 980/1470 does not produce significant irritative symptoms. The patient can resume normal sexual intercourse 20 days after surgery.

Tra ns itio na lz on e An ter ior

2. Segawa A. Studies on secretory function of male sexual organs and their accessory glands. Jap J Urol. 1957; 48:869. 3. Seisen T, RouprĂŞt M, Faix A, Droupy S. The prostate gland: a crossroad between the urinary and the seminal tracts. Prog Urol. 2012; 22(Suppl 1):S2-6. 4. Selman SH. The McNeal prostate: a review. Urology. 2011; 78:1224-8. fib ermu sc ula ra rea

zo ne

Pe rip he ral zo ne

EJACULATORY DUCTS OUTLETS

Ur eth ra

5. Basile F, Bellantone R, Biondi A, et al. Manuale di Semeiotica e Metodologia Chirurgica, EDRA, 2014; ISBN: 9788821434365. 6. Gosling JA, Thompson SA. A neurohistochemical and histological study of peripheral autonomic neurons of the human bladder neck and prostate. Urol Int. 1977; 32:269-76. 7. Bruschini H, Schmidt RA, Tanagho EA. The male genitourinary sphincter mechanism in the dog. Invest Urol. 1978; 15:284-7. 8. Belgrano E, et al. I disturbi dellâ&#x20AC;&#x2122;eiaculazione Edizioni Medico Scientifiche, Pavia 1995. Figure 16. Pre- and post-surgery orifices of the learned ejaculators.

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R. Leonardi

9. Stockamp K, Schreiter F. Proceedings: Function of the posterior urethra in ejaculation and its importance for urine control. Urol Int. 1974; 29:226-30. 10. Shapiro E, Hartano V, Lepor V. Anti-desmin vs. anti-actin for quantifying the area density of prostate smooth muscle. Prostate. 1992; 20:259-67.

15. Leonardi R. Preliminary results on selective light vaporization with the side- firing 980 nm diode laser in benign prostatic hyperplasia: an ejaculation sparing technique. Prostate Cancer Prostatic Dis. 2009; 12:277-80.

11. Chung A, Woo HH. Preservation of sexual function when relieving benign prostatic obstruction surgically: can a trade-off be considered? Curr Opin Urol. 2016; 26:42-8.

16. Shaker HS, Shoeb MS, Yassin MM, Shaker SH. Quartz head contact laser fiber: a novel fiber for laser ablation of the prostate using the 980 nm high power diode laser. J Urol. 2012; 187:575-9.

12. Wang L, Yu QY, Liu Y, et al. Efficacy and safety of laser surgery and transurethral resection of the prostate for treating benign prostate hyperplasia: a network meta-analysis.Asian Pac J Cancer Prev. 2016; 17:4281-4288.

17. Shaker H, Alokda A, Mahmoud H. The Twister laser fiber degradation and tissue ablation capability during 980-nm highpower diode laser ablation of the prostate. A randomized study versus the standard side-firing fiber. Lasers Med Sci. 2012; 27:959-63.

13. Alwaal A, Breyer BN, Lue TF. Normal male sexual function: emphasis on orgasm and ejaculation. Fertil Steril. 2015; 104:1051-60.

18. Leonardi R, Caltabiano R, Lanzafame S. Histological evaluation of prostatic tissue following transurethral laser resection (TULaR) using the 980 nm diode laser. Arch Ital Urol Androl. 2010; 82:1-4.

14. Lue T, et al. Sexual dysfunctions in men health clinical.

Correspondence Rosario Leonardi, MD (Corresponding Author) leonardi.r@tiscali.it Department of Urology and Andrological Surgery, Musumeci GECAS Clinic Gravina of Catania, Catania (Italy)

Manual of Sexual Medicine Health Publications Ltd. 2004 ISBN 09546956-1-5.

Archivio Italiano di Urologia e Andrologia 2019; 91, 1

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DOI: 10.4081/aiua.2019.1.43

CASE REPORT

Management of erosion of inflatable penile prosthesis reservoir into bladder. A different approach Volkan Izol, Mutlu Deger, Bahattin Kizilgok, Ibrahim Atilla Aridogan, Mustafa Zuhtu Tansug Department of Urology, Faculty of Medicine, University of Ă&#x2021;ukurova, Adana, Turkey.

Summary

We report a rare case of erosion of an inflatable penile prosthesis reservoir into the bladder that was managed with a different approach from the literature by preserving the existing reservoir. Inflatable penile implant was applied to a 54-year-old male patient who had undergone with a robot-assisted radical prostatectomy operation due to localized prostate cancer 2 years before. Two months after the operation, the patient referred to our clinic with predominant symptoms of lower urinary tract system associated with scrotal pain and swelling. The urinary system ultrasonography (USG) and the lower abdomen magnetic resonance imaging (MRI) demonstrated that the reservoir of the penile prosthesis was in the bladder. Cystoscopy confirmed that the reservoir was in the bladder. According to literature the reservoir was surgically removed from bladder. After bladder repair, the rectus muscles were repaired creating a space between the rectus muscle and the skin, where the reservoir was placed. After postoperative observation, the patient was discharged without any infection and regression of the lower urinary tract symptoms. No problem was referred by using the penile prosthesis when at 1-month and 3-month follow up and the patient was not uncomfortable in this regard. In conclusion no drawback occurred by using the old reservoir.

KEY WORDS: Penile prosthesis; Reservoir; Erosion; Bladder. Submitted 31 December 2018; Accepted 26 January 2019

INTRODUCTION

Erectile dysfunction (ED) is defined as the inability to achieve and or maintain a penile erection sufficient for satisfactory sexual performance (1). Surgical implantation of penile prosthesis can be recommended as a third-line treatment in patients who have failed pharmacotherapy or require a permanent solution (2). Complications of penile prostethesis include postoperative infection, bleeding, hematoma and device malfunction. In the literature, complications of reservoir of inflatable penile prosthesis are rarely reported, such as reservoir herniation, migration, erosion into the adjacent structure (e.g. bladder, bowel), ectopic reservoir location, hematoma, bowel obstruction and vascular compression with arterial or venous thrombosis (3). We report a rare case of erosion of the reservoir of inflatable penile prosthesis into bladder. In the present case, the reservoir was not removed as in other cases in the literature and differently from published cases it was placed in

an area under the skin above the rectus muscles. The relevance of this case report is the demonstration of a different approach for the treatment of this condition.

CASE

REPORT

A 54-year-old male patient underwent a robot-assisted radical prostatectomy operation due to localized prostate cancer two years before our observation, Because of erectile dysfunction after operation, the patient received sildenafil therapy without benefit from the treatment, so inflatable penile implant was placed in another center. Two months after the operation, the patient referred to our clinic with predominant symptoms of lower urinary tract system associated with scrotal pain and swelling. On physical examination, the right testicle was normal at palpation with minimal hydrocele and penile prosthesis was detected. Left testicle was normal and minimal hydrocele was observed. Scrotal ultrasonography reported a bilateral complicated chronic hydrocele. Laboratory findings showed at urinalysis the presence of 1605 leukocytes, with positive leukocyte esterase (++) and nitrite (+); blood count showed WBC 6900/mm3; serum procalcitonin level was 0.09 n/ml and erythrocytes sedimentation rate (ESR) 59 mm/h; urine culture was negative. Meropenem 500 mg ter in die treatment was started after consultation with Infectious Diseases and Clinical Microbiology clinic. In addition to antibiotic therapy, diclofenac sodium, scrotal elevation and cold application were also provided. Despite the treatment, due to the persistence of the patient's complaints, urinary system ultrasonography (USG) and lower abdomen magnetic resonance imaging (MRI) were performed and it was demonstrated that the reservoir of the penile prosthesis was in the bladder (Figure 1). Cystoscopy confirmed the presence of the reservoir in the bladder. Surgical procedure A Pfannenstiel incision was made to expose the bladder and perivesical space and the bladder anterior wall was released, to reach where the reservoir entered in the bladder. The bladder wall was opened to remove the reservoir and afterthat bladder repair was performed. After bladder repair, the rectus muscles were repaired and a space was created between the rectus muscle and the skin (Figure 2A). The reservoir was kept in saline

No conflict of interest declared. Archivio Italiano di Urologia e Andrologia 2019; 91, 1

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V. Izol, M. Deger, B. Kizilgok, I. Atilla Aridogan, M. Zuhtu Tansug

Figure 1. MR scan showing erosion of the reservoir into bladder.

Figure 4. CT scan at 3 months after operation showing the reservoir in the area formed without problem.

with diluted 180 mg of gentamicin for 10 minutes. Then the reservoir was placed in the space formed (Figures 2B3). After the operation, the patient was treated with vancomycin and meropenem for 2 weeks. After postoperative observation, the patient was discharged without any infection and regression of symptoms of lower urinary tract. No problem in using the penile prosthesis was reported by the patient at 1-month and 3-month follow up. The patient was not uncomfortable in this regard because the patient's reservoir was not visible under the skin and computed tomography (CT) at 3 months did not show any infection status or abscess around the reservoir (Figure 4).

DISCUSSION

Figure 2. A. Space was created between the rectus muscle and the skin. B: The reservoir was placed in the space formed. A.

Figure 3. The reservoir was placed in the space formed and semirigid penile erection was obtained.

Archivio Italiano di Urologia e Andrologia 2019; 91, 1

Surgical implantation of penile prosthesis can be recommended as a third-line treatment in patients who have failed pharmacotherapy or require a permanent solution (2). There are two types of penile prosthesis used by urologists for erectile dysfunction: malleable (semi-rigid, non-inflatable) and inflatable. The first penile implant was introduced by Lash et al. in 1964 and Scott et al. introduced the first inflatable penile prosthesis (IPP) in 1973 (4). Inflatable penile prostheses (IPPs) consist of 3 pieces (two intracorporal cylinders, a scrotal pump and a fluid reservoir). These reservoirs may be placed in the space of Retzius, However, scarring after pelvic surgeries (such as radical prostatectomy, cystectomy, renal transplantation) destroys this space. In the literature, erosions of reservoir of inflatable penile prostheses into bladder have been reported. Possibly the first published case of IPP reservoir erosion into the bladder was described by Leach et al. in 1984. The patients were treated with complete explantation (5). In 1986, Fitch reported a case of reservoir erosion into bladder, but differently of Leach et al., he removed the old reservoir and placed a new reservoir with a successful outcome (6). In 1988, Dupont et al. reported an erosion of reservoir of IPP into the bladder after 4 years from initial implantation with formation of bladder calculi on the reservoir: a complete explantation was carried out (7). Park et al. reported a case of erosion of penile prosthesis reservoir into the bladder due to shortened tubing by multiple revision surgeries and suggested, as rescue surgery, the reposition of a new reservoir on the contralateral side to the erosion (8). In 2009, Kramer et al. report two cases of intravesical reservoir displacement presenting with gross hematuria in the recovery room following repair of a cylinder to pump tubing break of their inflatable penile prostheses (IPPs): they removed reservoirs and a new reservoir was placed in the contra-lateral space of Retzius (9). In 2012 Garber et al. report a case of erosion of a penile prosthesis reservoir into the bladder in a patient undergone four prior IPP surgeries and reported a literature review of intravesical erosions of penile implant reservoirs reporting that all penile implant reservoirs in the bladder mentioned in

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Erosion of penile prosthesis reservoir into bladder

the literature were treated with complete explantation or placement of a new reservoir (10). In 2013, Tran et al. present the case of a 75-year-old male with history of bladder cancer requiring radical cystoprostatectomy who had erosion of the inflatable penile prosthesis reservoir into the neobladder: the patient underwent removal of the IPP reservoir (11). We report the case of the erosion of IPP reservoir into the bladder in a patient who had undergone robot assisted radical prostatectomy due to localized prostate cancer. Unlike other cases in the literature, we put the same reservoir in a space we had prepared after previous treatment of the infection without removal of the reservoir. The reservoir was placed in a space under the skin above the rectus muscle. This case is relevant because it offers a different new approach.

CONCLUSIONS

sexual dysfunction: erectile dysfunction and premature ejaculation. Eur Urol. 2010; 57:804-14. 3. Hartman RP, Kawashima A, Takahashi N, et al. Inflatable penile prosthesis (IPP): diagnosis of complications. Abdom Radiol (NY). 2016; 41:1187-96. 4. O'Rourke TKJr, Erbella A, Zhang Y, Wosnitzer MS. 'Prevention, identification and management of postoperative penile implant complications of infection, hematoma, and device malfunction. Transl Androl Urol. 2017; 6(Suppl 5):S832-S848. 5. Leach GE, Shapiro CE, Hadley R, Raz S. Erosion of inflatable penile prosthesis reservoir into bladder and bowel. J Urol. 1984; 131:1177 8. 6. Fitch WP 3rd, Roddy T. Erosion of inflatable penile prosthesis reservoir into bladder. J Urol. 1986; 136:1080. 7. Dupont MC, Hochman HI. Erosion of an inflatable penile prosthesis reservoir into the bladder, presenting as bladder calculi. J Urol. 1988; 139:367-8. 8. Park JK, Jang SW, Lee SW, Cui Y. Rare complication of multiple revision surgeries of penile prosthesis. J Sex Med. 2005; 2:735-6.

In conclusion the use of the old reservoir was safe. In addition, due to destruction of Retzius in pelvic surgery of some patients, such as those submitted to radical prostatectomy, we demonstrated that the reservoir could be placed in a safer area.

9. Kramer AC, Chason J, Kusakabe A. Report of two cases of bladder perforation caused by reservoir of inflatable penile prosthesis. J Sex Med. 2009; 6:2064-2067.

REFERENCES

10. Garber BB, Morris A. Intravesical penile implant reservoir: report, literature review, and strategiesfor prevention. Int J Impot Res. 2013; 25:41-4.

2. Hatzimouratidis K, Amar E, Eardley I, et al. Guidelines on male

11. Tran CN, Boncher N, Montague DK, Angermeier KW. Erosion of inflatable penile prosthesis reservoir into neobladder. J Sex Med. 2013; 10: 2343-6.

1. NIH Consensus Development Panel of Impotence. JAMA. 1993; 270:83-90.

Correspondence Volkan Izol, MD Mutlu Deger, MD, FEBU (Corresponding Author) drmutludeger@gmail.com Bahattin Kizilgok, MD Ibrahim Atilla Aridogan, MD Mustafa Zuhtu Tansug, MD Department of Urology, Faculty of Medicine, University of Ă&#x2021;ukurova, Adana 01330 (Turkey)

Archivio Italiano di Urologia e Andrologia 2019; 91, 1

Ates_Stesura Seveso 26/03/19 09:22 Pagina 46

DOI: 10.4081/aiua.2019.1.46

CASE REPORT

A rare complication of inguinal hernia repair: Total testicular ischemia and necrosis Erhan Ates, Hakan Gorkem Kazici, Akin Soner Amasyali Department of Urology Aydin Adnan Menderes University School of Medicine, Aydin, Turkey.

Summary

Testicular ischemia and necrosis are quite rare complications following inguinal hernia repair. There is still no consensus on the mechanism of infarction and necrosis in the literature. We present a case with total testicular ischemia and necrosis in the early period following the inguinal hernia repair with prolene mesh, ending up with orchiectomy.

KEY WORDS: Testis; Ischemia; Necrosis; Hernia repair. Submitted 2 January 2018; Accepted 20 January 2018

INTRODUCTION

Currently, prosthetic meshes are used commonly in inguinal hernia repair procedures as the duration of hospital stays are shorter, postoperative pain is less intense, and relapse rates are lower compared to the direct tissue to tissue repair surgeries (1). However, the direct contact of the mesh with the vessels in the inguinal canal or perimesh fibrosis can cause adverse effects on the testicular blood flow. These may result in some troublesome complications such as testicular atrophy, ischemic orchitis, a partial or total testicular ischemia and necrosis. Testicular atrophies are observed at a rate of 0.5% after open inguinal hernioplasties, and the rate increases to 5% after recurrent hernioplasty surgeries, although the rates may vary depending on the experience level of surgeons (2). We present a case with total testicular ischemia and necrosis in the early period following the inguinal hernia repair with prolene mesh, ending up with orchiectomy.

CASE

CRP was 93.4 mg/L. The laboratory examination of the total urine revealed results within normal levels. During the ultrasound examination of scrotums, it was observed that the right testis was 29 x 25 x 44 mm in size with a normal blood supply, however, the left testis was larger (40 x 35 x 52 mm) with a decreased echogenicity compared to the right one. Doppler examination revealed that there is no blood supply to the left testis (Figure 1). In addition, there was some free fluid of about 2 mm height around the left testis. Upon these findings, on the same day, the patient underwent left inguinal exploration in the region of the former incision scar. Following the exposure through the suture line towards the inguinal canal, a 100 cc serous and hemorrhagic fluid was drained. The left spermatic cord was edematous. The left testis was dissected, reaching the level of the internal ring. The left spermatic cord was strangulated at the level of the internal ring by the mesh. At this level, an intracordal necrosis was present. Then, the tunica vaginalis was opened. The testis was necrotic (Figure 2). The incision of the tunica albuginea did not result in arterial bleeding. Spermatic cord was clamped and a left orchiectomy was performed. The operation was finalized by placing a hemovac drain after revision of the mesh graft by a general surgeon. The hemovac drain was removed on the 2nd day following the operation and the patient was discharged without any complications. Figure 1. Image of scrotal doppler ultrasonography. There is no blood flow to the left testis.

PRESENTATION

A 30-years-old male patient presented with pain and swelling in the left testis on the 5th day following a herniorrhaphy with a prolene patch, in another healthcare facility, due to a strangulated hernia in the groin. Upon the consultation request of the emergency department, the patient was examined. The physical examination revealed that the left testis was slightly hard and tender and the spermatic cord was coarse on palpation. There was mild edema cutaneously and subcutaneously. The phren's sign was negative. Laboratory investigation results were 14.1 gr/dL for hemoglobin, 12700 mcL for leukocytes, the platelet count was 288 000 mcL, and

No conflict of interest declared. Archivio Italiano di Urologia e Andrologia 2019; 91, 1

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Testicular necrosis after hernia repair

Figure 2. Intraoperative images. Left testis and spermatic cord (A). Mechanical effect of prolene mesh (black arrow) on left spermatic cord (B), left necrotic testis (C). A.

The patient presented with normal findings on the follow-up visit in the second postoperative week. The pathological examination reported some testis tissue with disseminated ischemic necrosis and bleeding. Informed consent was taken from the patient.

DISCUSSION

Testicular atrophy, ischemia, and necrosis are rare complications after inguinal hernia operations. While testicular atrophy is observed at a rate of 0.5% after primary open inguinal hernioplasty, the incidences may reach up to rates of 5% following open recurrent hernioplasties (2). This is considered to be due to an acute thrombosis

of the pampiniform venous plexus rather than an acute artrial injury because of the collateral blood supply to the testis via the inferior epigastric, vesical, prostatic and scrotal arterial (3). Furthermore, there are studies reporting that testicular ischemia will not develop even, in onethird of the cases, in which the spermatic cord is ligated intentionally (4). In a study, evaluating a total of 6500 patients, it has been determined that, following surgical traumas to the spermatic cord during inguinal hernioplasties, venous congestions develop, leading to thrombosis, which was considered to be the cause of consequent ischemic orchitis and testicular atrophies (5). Especially in large hernias extending to the scrotum and in recurrent hernias, wider dissections of the spermatic cord or dislocation of the testis from the scrotum during surgery increase the rates of ischemic orchitis and testicular atrophy. Therefore, it is argued that medial and inferior dissections extending beyond the pubic tubercle should be avoided during open repair surgeries (6). The testicular veins may be affected mechanically as well as by inflammatory reactions due to prosthetic meshes. Peiper et al. (7), demonstrated inflammatory changes and testicular venous congestion following mesh implementations in animal studies. Inflammation was considered to be due to a fibrotic reaction, triggered by the mesh. In Peiperâ&#x20AC;&#x2122;s study, thrombosis in the spermatic cord was identified, additionally. However, there is no consensus in the literature on the relation of the factors including the spermatic cord structures, testicular volumes, and changes in the arterial blood flow; to the direct contact of the prosthetic mesh or to perimesh fibrosis. Uzzo et al. (8) observed decreases in the arterial perfusion of the testis and in its temperature. The ultrasonographic examination demonstrates decreases in the systolic blood flow and increases in the resistive index in testicular ischemia (9). On the contrary, there are other studies arguing that testicular blood flow and perfusion does not change after hernia surgeries like the study by Zieren et al. (10). Ischemic orchitis in the testis manifests on the 2nd or 3rd day following an inguinal hernia surgery and progresses to the develop an infarction. The physical examination and Doppler ultrasonography are the initial diagnostic methods in cases, of which testicular ischemia is suspected (9). The testicular arterial blood flow and the testicular perfusion should be evaluated by a scrotal Doppler ultrasonography. In these cases, the possibility of a torsioned testis should be considered as well, despite the history of recent inguinal hernioplasty. In our case, the decision of exploration was made when it was determined that there was no blood supply to the testis. The method of treatment is an emergency surgical intervention. Surgical methods vary depending on the observation of testicles during the surgery and on the duration of ischemia. The necrotic regions of the testis are excised and repaired by earlier surgical interventions, however, orchiectomy is inevitable when the early stage ischemia, following inguinal surgeries, is recognized later as it was in our case. Archivio Italiano di Urologia e Andrologia 2019; 91, 1

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E. Ates, H. Gorkem Kazici, A. Soner Amasyali

CONCLUSIONS

All kinds of symptoms such as scrotal pain, redness, and swelling should be evaluated immediately and with care after inguinal surgeries. In addition, it must be considered that this type of complications may develop in any surgery adjacent to the spermatic cord.

6. Wantz GE. Open repair of hernias of the abdominal wall, surgical techniques. Sci Am Surg. 1995; 2:1-19. 7. Peiper C, Junge K, Klinge U, et al. Is there a risk of infertility after inguinal mesh repair? Experimental studies in the pig and rabbit. Hernia. 2006; 10:7-12.

REFERENCES

8. Uzzo RG, Lemack GE, Morrissey KP, Goldstein M. The effects of mesh bioprothesis on the spermatic cord structures: A preliminary report in a canine model. J Urol. 1999; 161:1344-9.

2. Reid I, Devlin HB. Testicular atrophy as a consequence of inguinal hernia repair. The British journal of surgery 1994; 81:91-3.

9. Kupczyk-Joeris D, Kalb A, Hofer M, et al. Doppler sonography of testicular circulation following reconstruction of inguinal hernia. Chirurg. 1989; 60:536-40.

1. Huang CS, Huang CC, Lien HH. Prolene hernia system compared with mesh plug technique: a prospective study of short- to mid-term outcomes in primary groin hernia repair. Hernia 2005; 9:167-71.

3. Fong Y, Wantz GE. Prevention of ischemic orchitis during inguinal hernioplasty. Surg Gynecol Obstet, 1992; 174:399-402. 4. Heifetz CJ. Resection of the spermatic cord in selected inguinal hernias. Twenty years of experience. Arch Surg. 1971; 102:36-9.

Correspondence Erhan Ates, MD drerhanates@yahoo.com Hakan Gorkem Kazici, MD hgkazici@yahoo.com Akin Soner Amasyali, MD drakinsoner@gmail.com Department of Urology Aydin Adnan Menderes University School of Medicine, 09010 Aydin (Turkey)

5. Wantz GE. Testicular atrophy. A risk of inguinal hernioplasty. Chirurgie. 1991; 117:645-51.

Archivio Italiano di Urologia e Andrologia 2019; 91, 1

10. Zieren J, Beyersdorff D, Beier KM, MĂźller JM. Sexual function and testicular perfusion after inguinal hernia repair with mesh. Am J Surg. 2001; 181:204-6.

Palmisano_Stesura Seveso 25/03/19 17:22 Pagina 49

DOI: 10.4081/aiua.2019.1.49

CASE REPORT

Blastoid variant of mantle cell lymphoma of the female urethra mimicking a caruncle: A rare but highly aggressive subtype case with literature review Franco Palmisano 1, 2, Vito Lorusso 1, 2, Matteo Giulio Spinelli 1, Paolo Guido Dell’Orto 1, Emanuele Montanari 1, 2 1 Fondazione 2 University

IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Department of Urology, Milan, Italy; of Milan, Milan, Italy.

Summary

Primary urethral lymphoma is a rare entity without a standardized treatment protocol. We report a case of an elderly woman presenting with a caruncle associated with vaginal spotting and intermittent dysuria. She underwent surgical excision of the lesion. Histological analysis revealed a blastoid variant of mantle cell lymphoma, a previously unreported subtype. The patient received chlorambucil assisting a rapid local disease progression. She died of disseminated disease 6 months after diagnosis. A review of the lymphomas of the urethra is included.

KEY WORDS: Caruncle; Lymphoma; Urethra; Genitourinary; Mantle cell lymphoma; Blastic variant. Submitted 10 September 2018; Accepted 27 September 2018

INTRODUCTION

Non-Hodgkin’s genitourinary lymphoma as a primary extra nodal invasion is a rare condition, with few reported cases affecting the urethra (1). The most common subtypes described are mucosa-associated lymphoid tissue-type (MALT) lymphoma and diffuse large B-cell lymphoma. Herein, we report the first documented case of a blastoid variant of mantle cell lymphoma resembling a caruncle. Furthermore, to shed light on clinical features of primary urethral lymphoma, we reviewed previously reported cases.

CASE

REPORT

A 84-year-old woman presented with a recent onset, fastgrowing genital nodule associated with vaginal spotting and intermittent dysuria. Her medical history was noncontributory, lacking fever, weight loss or any other systemic manifestations. There were no enlarged lymph nodes or organomegaly upon physical examination. Pelvic examination revealed a urethral caruncle arising from the posterior wall of the urethral meatus (Figure 1a, b). It was characterized by an erythematous appearance, firm at palpation, measuring approximately 4 cm at its maximum diameter. The patient underwent cystourethroscopy with a 21F cystoscope revealing no bladder involvement, and surgical excision of the urethral caruncle. Histologic exam-

ination revealed a urethral mucosa characterized by squamous metaplasia, subjugated by a widespread growth pattern of lymphoid proliferation, consisting of mediumsized, blastic-shaped, B-cell phenotype elements. Immunohistochemically, these cells were positive for CD20, CD5, Cyclin D1 and BcL-2, negative for CD23, CD10, BCL6, MUM1, CD3, CD30, TdT and cytokeratin. The Ki-67 index was approximately 90%. A diagnosis of a primary blastoid variant of mantle cell urethral lymphoma was made. A chest, abdomen and pelvis contrast enhanced computed tomography (CT) was performed for the staging workup and revealed non-mediastinal lymphadenopathy, no focal lung lesions, a 2.5-mm angioma located at the right lobe of the liver, normal spleen, pancreas and kidneys, and no abdominal or pelvic lymphadenophaty. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) showed abnormal FDG uptake present in the external genitalia and vagina. The patient was then referred to the Oncohematology Department and underwent two cycles of chlorambucil, despite this a rapid local disease progression was seen (Figire 1c). The patient died of disseminated disease six months after diagnosis.

DISCUSSION

Caruncles commonly affect the postmenopausal female urethra, appearing as erythematous nodules at the posterior lip of the urethral meatus. This lesion is considered to be neither neoplastic nor preneoplastic, being composed of chronic inflammatory cells, dilated vessels and hyperplastic epithelium. In light of this, an incorrect diagnosis of lymphoma or sarcoma may occasionally be made based on the presence of bizarre stromal cells or lymphoid infiltrate (2). On the other hand, 2.3% of the caruncles were found to be malignant tumors upon histopathological analysis, usually a carcinoma or a Bowen's disease (2). In this context, a caruncle-like primary lymphoma is exceptionally rare. Since 1949, only 29 patients with urethral lymphoma have been reported (1-2), including the present case, with an age distribution ranging from 31 to 90 years old. Of these, a female

No conflict of interest declared. Archivio Italiano di Urologia e Andrologia 2019; 91, 1

Palmisano_Stesura Seveso 25/03/19 17:22 Pagina 50

F. Palmisano, V. Lorusso, M.G. Spinelli, P.G. Dell’Orto, E. Montanari

Figure 1. A, B. Polypoid, caruncle-like, flesh-colored lesion (Images taken during cystoscopy). C. Clinical presentation showing disease progression 3 months after diagnosis. A.

The overall mortality rate is 66% with a 14.5month median survival time. Reported frontline therapy includes CHOP-like regimen or chlorambucil. The blastic variant of mantle cell lymphoma is usually diagnosed upon initial presentation and more rarely in the course of common forms. Patients are predominantly male, over 60 years of age, and one third have B symptoms. The majority of patients have an Ann Arbor stage IV disease (85%), lymphadenopathy (82%) and extranodal involvement (66%), especially in the lung and pleural cavities, more rarely with a gastro-intestinal infiltration. Neither Ann Arbor staging nor bone marrow or blood involvement have been found to influence clinical outcome and there is currently no standard therapy for this disease.

CONCLUSIONS

predominance has been shown, with 75.9% of cases affecting woman. When the female urethra is involved, a caruncle like aspect is the most common presentation, having been reported in 9 cases. Other associated symptoms include spotting, hematuria, dysuria and vulvar pruritis. Cancer-specific mortality is usually relegated to a disseminate disease at diagnosis, whereas the overall 4year survival rate of caruncle-like tumors is 55.5%. Each of the previously reported 29 cases involved nonHodgkin’s lymphoma, with the most common subtypes being mucosa-associated lymphoid tissue-type lymphoma and diffuse large B-cell lymphoma. Treatments include excision, radiotherapy and chemotherapy. To our knowledge, this is the first blastoid variant of mantle cell caruncle-like lymphoma to be reported. According to Bernard et al. (3), the blastic variant form of mantle cell lymphoma is considered to be a very aggressive subtype of non-Hodgkin's lymphoma with 46% of patients who do not respond to treatment dying quickly due to disseminated disease.

Correspondence Franco Palmisano, MD (Corresponding Author) franco.palmisano@hotmail.it Vito Lorusso, MD Matteo Giulio Spinelli, MD Paolo Guido Dell’Orto, MD Emanuele Montanari, MD Department of Urology, IRCCS Ca’ Granda Ospedale Maggiore Policlinico via della Commenda 15, 20122 Milan, Italy

Archivio Italiano di Urologia e Andrologia 2019; 91, 1

In conclusion, the correct recognition of a primary lymphoma of the urethra is of clinical importance and should be considered in the differential diagnosis of a caruncle. Being the extranodal lymphoid infiltrate a diagnostic dilemma, it is of utmost importance that the pathologist has expertise concerning these tumors. An universally accepted treatment scheme is needed, and for subtypes of lymphoma with a less favorable prognosis an aggressive treatment strategy is strongly recommended.

REFERENCES

1. Al Zahrani A, Abdelsalam M, Al Fiaar A, et al. Diffuse large Bcell lymphoma transformed from mucosa-associated lymphoid tissue lymphoma arising in a female urethra treated with rituximab for the first time. Case Rep Oncol. 2012; 5:238-245. 2. Chen YR, Hung LY, Chang KC. Mucosa-associated lymphoid tissue-type lymphoma presenting as a urethral caruncle with urinary bladder involvement. Int J Urol. 2014; 21:1073-4. 3. Bernard M, Gressin R, Lefrère F, et al. Blastic variant of mantle cell lymphoma: a rare but highly aggressive subtype. Leukemia. 2001; 15:1785-91.

Sodo_Stesura Seveso 26/03/19 09:49 Pagina 51

DOI: 10.4081/aiua.2019.1.51

CASE REPORT

Partial cystectomy in young male for a urachal tumor masquerading a bladder leiomyoma Maurizio Sodo 1, Lorenzo Spirito 2, Roberto La Rocca 2, Umberto Bracale 1, Ciro Imbimbo 2 1 Department 2 Department

of Surgery, University of Naples Federico II, Naples, Italy; of Urology, University of Naples Federico II, Naples, Italy.

Summary

Leiomyoma of the bladder is a very rare disorder that accounts for 0.43% of all bladder neoplasms. Although the pathophysiology of the bladder leiomyoma is unknown, there are some theories on it. The patients can be asymptomatic; when present, clinical symptoms (lower urinary tract symptoms and\or hematuria), are associated with tumor size and location. For diagnosis, imaging plays an important role: ultrasound, computed tomography (CT) scan and magnetic resonance imaging (MRI) are the examinations most frequently performed. Treatment consists of surgical removal of the tumor, and the prognosis is excellent.

KEY WORDS: Bladder; Leiomyoma; Partial cystectomy.

Protein S 100 (Figure 2A-B). We performed follow up with ultrasonography and CT scan and at 3 and 9 months. CT scans were negative. We evaluated bladder capacity with flowmetry at 3 and 9 months. Peak and average flows were 21 ml/min and 10 mil/min. Voided volume was 198 ml at 3 months and at 9 months was increased at 296 ml. Figure 1. A. Large, hard tissue density mass arising from the urachus. The mass is not dissociable by the bladder wall at computed tomography. B. High signal intensity mass on T1 magnetic resonance image.

Submitted 10 September 2018; Accepted 27 September 2018

CASE

REPORT

Herein we present a case of leiomyoma of the bladder in young male patient who has been successfully managed with a partial cystectomy using a laparoscopic approach. A 33 year old male with a history of persistent thymus gland was referred to our urology clinic for pelvic pain, urgency and dysuria. No hematuria nor history of weight loss were noticed. His physical examination was unremarkable. Blood work and urine test were within normal limits. An ultrasound of the abdomen and pelvis revealed no hydronephrosis nor masses of the upper tract. Although only partially filled, the bladder revealed a mass. A Computed Tomography (CT) scan and Magnetic Resonance Imaging (MRI) confirmed the presence of an upper side bladder tumor (60 mm x 58 mm x 47 mm) located along the urachus course without any evidence of distant metastasis but with an increased fat density around the mass (Figure 1A-B). The lesion appeared undissociated from the bladder wall. The patient underwent a laparoscopic partial cystectomy and urachus removal with a margin of normal tissue by a 3 trocars technique. The bladder was closed in 2 layers and the peritoneum was then closed. The patient had an uneventful post operative period and a Foley’s catheter was left for 7 days. The mass measured grossly 6 × 5 × 4 cm in its greatest dimensions with a smooth surface and hard consistency. A microscopic description revealed typical features of a leiomyoma tumour: positive for Actina and negative for CD117 and

Figure 2. A. Microscopic description revealed typical features of leiomyoma, positive for Actina. B. Microscopic description revealed typical features of leiomyoma, negative for CD117 and Protein S 100. A.

DISCUSSION

In our case, ultrasonography showed a well-defined, encapsulated, lobulated mass of the bladder with a homogeneous and solid aspect, findings that were also supported by CT. While CT scans can identify the accu-

No conflict of interest declared. Archivio Italiano di Urologia e Andrologia 2019; 91, 1

Sodo_Stesura Seveso 26/03/19 09:49 Pagina 52

M. Sodo, L. Spirito, R. La Rocca, U. Bracale, C. Imbimbo

rate location of leiomyoma tumors, they are not adequate to distinguish the solidity of the lesion. Therefore, ultrasonography should be performed in indeterminate lesions (as seen in CT) (2). Magnetic resonance imaging (MRI) can distinguish between mesenchymal and transitional cell tumors (3). Leiomyomas have intermediate signal intensity on T1weighted images, while T2- weighted images show a low signal intensity (4) but a definitive diagnosis is ultimately made by the histopathological examination. Management of leiomyomas is mainly guided by the size and location of the tumor (5). Treatment options have ranged from enucleation, partial cystectomy and even, though rarely, radical cystectomy. Leiomyomas occur throughout the genitourinary tract, which are most commonly found in the renal capsule. Most bladder tumors are derived from urothelial cells, while non-epithelial tumors of the bladder, particularly leiomyomas, are relatively rare, comprising of about 0.43% of all bladder tumors. In their review of 37 patients Goluboff et al. reported a preponderance of leiomyoma tumours in women (76%) in their third through sixth decades (59%) with a mean age of 44 years (5). In another series (6) all patients were women, with a mean age of 43.6 years, consistent with the report of Guluboff et al. Bladder leiomyomas are known to produce symptoms, dependent primarily on their location and secondarily on their size. Goluboff et al. demonstrated that patients most commonly presented with obstructive urinary symptoms (49%), irritative symptoms (38%), hematuria (11%) or flank pain (13%), while 19% were asymptomatic. In another large series published by Park et al. (6), irritative symptoms occurred most frequently (37.7%), followed by obstructive urinary symptoms (31.1%), hematuria (24.6%) and abdominal bulge or pain (14.8%). Bladder leiomyoma are classified into three groups according to the histological location of tumor: endovesical, intramural and extravesical; which account for 63%, 7%, and 30%, respectively (6). Traditionally, bladder leiomyomas have been treated by surgical resection. The tumor size, extent, and location and the involvement of the sphincter or ureter determine the route of resection. Small endovesical tumors can be managed with transurethral resection (TUR) and fulguration. Larger endovesical, intramural or extravesical tumors can best be managed with segmental resection or partial cystectomy (7). Transvaginal excision and laparoscopic partial cystectomy excision have all been successfully used for bladder leiomyoma removal (8, 9). Some investigators have suggested that surgical removal should be reserved for symptomatic tumors. They assert that asymptomatic patients with a high probability of a leiomyoma as detected from the imaging, biopsy and cystoscopy evaluations can be followed up without invasive surgery due to the histologic similarities of bladder and uterine leiomyomas and no reported malignant transformation of bladder leiomyoma. However, bladder leiomyomas often mimic malignant lesions and, depending on the location, can often be diagnosed only after surgical removal. Furthermore, surgeons are familiar

Archivio Italiano di Urologia e Andrologia 2019; 91, 1

with performing TUR or partial cystectomy and therefore surgical resection is thought to be necessary for both confirmation of the diagnosis and definitive treatment. Because the prognosis of patients with a leiomyoma tumor after surgical treatment is excellent and no malignant transformation has been reported to-date, a followup is not considered necessary unless urinary tract symptoms occur.

CONCLUSIONS Leiomyoma of the urinary bladder is a rare disorder, comprising of about 0.43% of all bladder tumors. The tumor size, rather than the location, appears to affect the nature of symptoms. Successful treatment is up to surgeon, using varying surgical approaches, and the prognosis is good after complete resection.

REFERENCES

1. Cornella JL, Larson TR, Lee RA, et al. Leiomyoma of the female urethra and bladder: report of twenty-three patients and review of the literature. Am. J. Obstet. Gynecol. 1997; 176:1278-1285. 2. Illescas FF, Baker ME, Weinerth JL Bladder leiomyoma: advantages of sonography over computed tomography. Urol Radiol. 1986; 8:216-218. 3. Sundaram CP, Rawal A., Saltzman B. Characteristics of bladder leiomyoma as noted on magnetic resonance imaging. Urology. 1998; 52:1142-1143. 4. Maya MM, Slywotzky C. Urinary bladder leiomyoma: magnetic resonance imaging findings. Urol Radiol. 1992; 14:197-199. 5. Goluboff ET, O'Toole K, Sawczuk IS. Leiomyoma of bladder: report of case and review of literature. Urology. 1994; 43:238-41. 6. Park JW, Jeong BC, Seo SI, et al. Leiomyoma of the urinary bladder: a series of nine cases and review of the literature. Urology. 2010; 76:1425-9. 8. Kanno K, Andou M, Yanai S, et al. Total laparoscopic treatment with cystotomy for intramural bladder leiomyoma. J Minim Invasive Gynecol. 2018; 25:14-15. 9. Yin FF, Wang N, Wang YL, et al. Transvaginal resection of a bladder leiomyoma misdiagnosed with a vaginal mass: a case report and literature review. Case Rep Obstet Gynecol. 2015; 2015:981843.

Correspondence Maurizio Sodo, MD maurizio Sodo sodo@unina.it Umberto Bracale, MD bracale@unina.it Department of Surgery, University of Naples Federico II, Naples (Italy) Lorenzo Spirito, MD (Corresponding Author) lorenzospirito@msn.com Roberto La Rocca, MF robertolarocca87@gmail.com Ciro Imbimbo, MD cimbimbo@unina.it Department of Urology, University of Naples Federico II Via S. Pansini 5, 80131 Naples (Italy)

Bonfitto_Stesura Seveso 25/03/19 17:22 Pagina 53

DOI: 10.4081/aiua.2019.1.53

CASE REPORT

Does right-sided varicocele indicate a right-sided kidney tumor? Miguel Bonfitto 1, Leandro Shogo Matuy Kimura 2, José Maria Pereira Godoy 3, Miguel Zerati Filho 4, Luis Cesar Fava Spessoto 4, Fernando Nestor Facio Junior 4 1 Urology,

Hospital de Base de São José do Rio Preto/Famerp/Funfarme, Brazil; Surgery, Hospital de Base de São José do Rio Preto/Famerp/Funfarme, Brazil; 3 Vascular Surgery Division, São José do Rio Preto School of Medicine, Famerp/Funfarme, Brazil; 4 Urology Division, São José do Rio Preto School of Medicine, Famerp/Funfarme, Brazil. 2 General

Summary

Varicocele is a dilation of the pampiniform venous plexus, mainly affecting the left side of the scrotum. In rare cases, however, the right side is affected. When this occurs, a retroperitoneal disease should be suspected, such as right-sided renal neoplasm. The present case report highlights the importance of right-sided varicocele in the diagnostic investigation of neoplasm of the right kidney.

KEY WORDS: Acute right-sided varicocele; Right-sided renal neoplasm; Renal tumor. Submitted 11 September 2018; Accepted 25 September 2018

INTRODUCTION

Varicocele is defined as a dilation of the pampiniform venous plexus, affecting 10 to 15% of urology patients (1-6). The left side of the scrotum is affected in up to 85% of cases (6). In rare cases of presentation on the right side, a neoplasm or a retroperitoneal mass in the right kidney should be the diagnostic hypothesis (3, 6). A physical examination is the gold standard for the diagnosis of varicocele, which is characterized by the dilation of veins in the spermatic cord (7). Currently, Doppler ultrasound is the main complementary exam (7). Right-sided varicocele may be explained by an increase in hydrostatic pressure due to compression of the renal or spermatic vein caused by a tumor or the formation of thrombi (1, 8). This condition is scored as Grade I when the varicose cord is palpated only during the Valsalva maneuver, Grade II when it is palpable in the standing position and Grade III when it is visible without palpation (1, 4). In this paper, we report a rare case of right-sided varicocele associated with a neoplasm in the right kidney and highlight the importance of this finding in the investigation of kidney tumors.

CASE

REPORT

A 49-year-old male patient with no previous comorbidities sought care due to a varicose cord on the right testicle that had appeared 40 days earlier. The patient reported no pain, local swelling, weight loss, abdominal pain or urinary problems. During the physical examination, the patient presented a good general health state and

flaccid, depressible, painless abdomen with no palpable masses. The scrotal veins on the right side were dilated and an increase in caliber was observed during the Valsalva maneuver (Figure 1). Doppler ultrasound of the scrotum confirmed accentuated right-sided varicocele. The complementary examination of the abdomen revealed a mass in the right kidney. The patient was submitted to computed tomography of the abdomen and pelvis, which revealed a solid, heterogeneous, expansive formation with circumscribed and lobulated contours, occupying nearly the entire right kidney, measuring 14.6 x 10.9 cm, with invasion of the right renal vein causing ectasia of the gonadal vein and accentuated varicocele (Figure 2). The patient was submitted to right nephrectomy with lymphadenectomy. The anatomo-pathological analysis confirmed the occurrence of kidney cell carcinoma (stage pT2 Nx Mx). Following good clinical evolution, the patient was discharged from hospital on the fourth day of the postoperative period and is currently in outpatient follow up.

DISCUSSION

We report a rare case of a right kidney neoplasm associated with right-sided varicocele. This is an uncommon finding and documented little in the literature. Approximately 0.2% of patients present right-sided varicocele, which should lead to the hypothesis of ipsilateral kidney tumor (1, 5-10). In the present report, the diagnostic investigation initiated with the observation of varicose veins in the right side of the scrotum. Subsequent Doppler ultrasound and computed tomography of the abdomen confirmed the diagnosis of right kidney neoplasm and the patient was submitted to nephrectomy. Cases of renal cell carcinoma in patients with right-sided varicocele are rare in the literature. We found only two case reports (11, 12). Ates et al. (13) reported an association between right-sided varicocele and retroperitoneal paraganglioma exerting extrinsic pressure on the inferior vena cava and causing grade 3 dilation of the right pampiniform plexus. DeWitt et al. (6) performed a retrospective investigation of 337 cases of right-sided varicocele, but found no statistically significant association with the diagnosis of a malignancy. These studies con-

No conflict of interest declared. Archivio Italiano di Urologia e Andrologia 2019; 91, 1

Bonfitto_Stesura Seveso 25/03/19 17:22 Pagina 54

M. Bonfitto, L. Shogo Matuy Kimura, J.M. Pereira Godoy, M. Zerati Filho, L.C. Fava Spessoto, F. Nestor Facio Junior

Figure 1. Physical examination revealing grade 3 right-sided varicocele.

REFERENCES

1. Clavijo RI, Carrasquillo R, Ramasamy R. Varicoceles: prevalence and pathogenesis in adult men. Fertility and Sterility. 2017; 108:364-369. 2. Marte A. The history of varicocele: from antiquity to the modern ERA. 2017; 44:563-576. 3. Vanlangenhove P, Dhondt E, Everaert K, Defreyne L. Pathophysiology, diagnosis and treatment of varicoceles: a review. Min Urol Nefrol. 2014; 66:257-82. 4. Molly A, Dewitt E, Greene DJ, et al. Isolated right varicocele and incidence of associated cancer. Urology. 2018; 117:82-85. 5. Baden LR. Acute Varicocele Revealing Renal Cancer. N Engl J Med. 2016; 374:21. 6. Woldu S, Nees S, Batavia JV, et al. Physical exam and ultrasound characteristics of right varicocoeles in adolescents with left varicocoeles. Andrology. 2013; 1; 936-942. 7. Belay RE, Huang GO, Ken J, et al. Diagnosis of clinical and subclinical varicocele: how has it evolved? Asian J Androl. 2016; 18:182-185. 8. Georgiades F, Stylianides A, Grange P, Kouriefs C. Images in Clinical Urology Point to Sinister Causes. Urology. 2016; 97:e23-e24.

Figure 2. Computed tomography of abdomen revealing tumor in right kidney.

9. Robson J, Wolstenhulme S, Knapp P. Is There a Co-Association Between Renal or Retroperitoneal Tumours and Scrotal Varicoceles? A Systematic Review. Ultrasound. 2012; 20:182-191. 10. Hanna GB, Byrne D, Townell N. Right-sided varicocele as a presentation of right renal tumours. Br J Urol. 1995; 75:798-799. 11. Hadad Z, Norup K, Petersen C. Right-sided varicocele testis as the only sign of right-sided renal tumour. Ugeskr Læger. 2016; 178:2-3. 12. Fernández-Pello S, González I, Pérez-Carral JR, et al. Right varicocele as finding of right renal mass. Arch Esp Urol. 2015; 68:641-2. 13. Ates N, Habibi M, Ipekci T. Retroperitoneal paraganglioma presenting as right-sided varicocele: case report. Ann Saudi Med. 2016; 36:148-151. 14. Cheungpasitporn W, Horne JM, Howarth CB. Adrenocortical carcinoma presenting as varicocele and renal vein thrombosis: a case report. J Med Case Rep. 2011; 5:337-41. 15. Roy CR, Wilson T, Raife M, Horne D. Varicocele as the presenting sign of an abdominal mass. J Urol. 1989; 141:597-599. 16. Thompson JN, Abraham K, Jantet H. Metastasis to pampiniform plexus from left renal adenocarcinoma presenting with acute varicocele. Urology. 1984; 24:621-622.

firm the initial aim of the present report of describing a rare association and highlighting the importance of the diagnostic investigation of an abdominal disease following the confirmation of right-sided varicocele. Right-sided varicocele is rare and should alert physicians to the possibility of compression of the inferior vena cava (14). Varicocele in the left side of the scrotum is more frequent due to the anatomic relationship between the left spermatic vein and left renal vein. Therefore, rightsided varicocele should be seen as a possible indicator of neoplasm in the right kidney (14-17).

CONCLUSIONS

As the majority of cases of varicocele occur on the left side, right-sided varicocele is a potential indicator for the clinical investigation of a concomitant abdominal disease. The present report underscores the need for a discerning investigation of right kidney neoplasm following the diagnosis of right-sided varicocele.

Archivio Italiano di Urologia e Andrologia 2019; 91, 1

17. Shinsaka H, Fujimoto N, Matsumoto T. A rare case report of right varicocele testis caused by a renal cell carcinoma thrombus in the spermatic vein. Int J Urol. 2006; 13:844-845. Correspondence Miguel Bonfitto, Resident Physician of Urology, Hospital de Base de São José do Rio Preto/Famerp/Funfarme, (Brazil) Leandro Shogo Matuy Kimura, Resident Physician of General Surgery, Hospital de Base de São José do Rio Preto/Famerp/Funfarme (Brazil) José Maria Pereira Godoy, Professor, Vascular Surgery Division, São José do Rio Preto School of Medicine, Famerp/Funfarme (Brazil) 5416 Brig. Faria Lima Ave. 15090-000 São José do Rio Preto, SP, Brazil Miguel Zerati Filho, Luis Cesar Fava Spessoto, Fernando Nestor Facio Junior, MD, PhD (Corresponding Author) fnfacio@yahoo.com.br Professor, Urology Division, São José do Rio Preto School of Medicine, Famerp/Funfarme (Brazil)

Corongiu1_Stesura Seveso 26/03/19 09:48 Pagina 55

DOI: 10.4081/aiua.2019.1.55

CASE REPORT

Large primary leiomyosarcoma of the seminal vesicle: A case report and literature revision Emanuele Corongiu 1, Pietro Grande 2, Valerio Olivieri 3, Giorgio Pagliarella 1, Flavio Forte 1 1 Department

of Urology, M.G. Vannini Hospital, Rome, Italy; Université, Assistance Publique-Hôpitaux de Paris, Pitié Salpétière, Urology Department, Paris, France; 3 Department of Urology, Ivrea Hospital - ASL TO 4, Ivrea, Italy. 2 Sorbonne

Summary

Primary Leiomyosarcoma of the seminal vesicle is a very rare condition. We report a case of a 74-year-old man with a tumour detected by rectal symptoms with pelvic pain and dysuria at ultrasonography. Computed tomography and magnetic resonance imaging suggest an origin in the left seminal vesicle and did not show a clear cleavage plan with the rectum and a right hydroureteronephrosis was also present. A radical vesiculo-cystoprostatectomy with ileal conduit and bilateral pelvic lymphadenectomy was performed, a sigmoidectomy with end colostomy was performed also. Pathological examination showed a high grade (G3) leiomyosarcoma of the seminal vesicle.

KEY WORDS: Seminal vesicle; Leiomyosarcoma; Oncology; Rare tumors. Submitted 25 October 2018; Accepted 4 November 2018

INTRODUCTION

The localization in the genitourinary tract of soft tissue sarcoma (STS) is a very rare condition (less than 5% of these neoplasms) (7), among these a localization at the level of the seminal vesicles is even more rare (7). To our knowledge, only few cases have been reported to date in the literature but no one with large dimension as in our case (1-7). The diagnosis of the real anatomical origin of this type of neoplasia is made difficult by invasive and compressive phenomena on adjacent organs, so for a correct diagnosis the use of CT-scan and MRI are fundamental. Considering the rarity of these conditions, the role of radiotherapy and chemotherapy seems to remain uncertain, and the treatment of choice remains a radical surgical removal.

revealed no specific findings, and rectal examination was totally negative for rectal or prostatic bulging masses. Ultrasonography (US) discovered a bulky mass located in the right portion of the pelvis compressing the urinary bladder and causing omolateral hydronephrosis. Serum prostate-specific antigen (PSA) levels were normal. A Computed Tomography (CT) confirmed a massive abdominal mass (14 x 13 x 12 cm) with considerable contrast enhancement, determining a compression on the distal part of the right ureter with omolateral hydroureteronephrosis (Figure 1). There was no evidence of a clear cleavage plan between mass and surrounding organs (sigma, bladder and prostate). Furthermore, a nodal involvement at level of the right iliac and obturator lymph nodes was reported. Magnetic Resonance (MRI) confirmed the findings of the CT scan (Figure 2), giving no supplemental information. Based on these data, a surgical approach was decided.

Figure 1. CT scan of the patient.

Figure 2. MRI scan of the patient.

CASE REPORT

A 74-year old Caucasian man, with previous history of hypertension showed up at the emergency department of our hospital in May 2018 due to the acute onset of pelvic pain, dysuria, and partial occlusion of the intestine. Physical examination No conflict of interest declared. Archivio Italiano di Urologia e Andrologia 2019; 91, 1

Corongiu1_Stesura Seveso 26/03/19 09:48 Pagina 56

E. Corongiu, P. Grande, V. Olivieri, G. Pagliarella, F. Forte

Figure 3. Surgical specimen.

The treatment consisted of a radical vesiculo-cystoprostatectomy with ileal conduit and bilateral pelvic lymph node dissection (iliac, obturator and hypogastric nodes). During the surgery the dissection of the mass from the sigma resulted unfeasible, so a sigmoid colon resection with end colostomy was performed (Figure 3). The patient was transferred to intensive care unit for 24 hours after surgery, the post-operative course was without complications and the patient was discharged on the 7th post-operative day.

RESULTS

The final pathological analysis showed a small prostate (5 x 4 x 5 cm) with outbreaks of bilateral adenocarcinoma [pT2c, Gleason 6 (3 + 3)]. No neoplastic invasion of bladder or sigmoid colon and no nodal involvement were found and both ureteral margins were free of tumor. The right seminal vesicle was unscathed, while the left vesicle was not recognizable, as it was included in a large mass with a polylobate appearance measuring of 14 cm on the longest axe and having a hard-elastic consistency and yellowish-white color. Microscopically, the mass consisted of fused cellular elements, organized in short bundles with marked cell polymorphism and foci of necrosis. Neoplastic cells were positive for the histochemical reaction for smooth muscle actin, Desmin and Vimentin, negative for immunohistochemically reaction for s100, determining the final diagnosis of leiomyosarcoma of the seminal vesicle.

DISCUSSION/CONCLUSION

Primary tumors of the seminal vesicle are a very rare condition. Among them, carcinomas are much more frequent than sarcomas (8). At present only 8 cases of primary leiomyosarcoma of seminal vesicles have been described in the literature (1-7). Our case represents the ninth patient, and one with the largest dimensions and the last one described since 2011. No specific risk factor has been identified. The clinical detection of tumors of the seminal vesicles is very difficult, both for the extreme

Archivio Italiano di Urologia e Andrologia 2019; 91, 1

rarity of this neoplasm and for the extreme variability of the symptoms: in some cases the patient is totally asymptomatic, in other cases it has non-specific symptoms (pelvic-abdominal pain, dysuria, rectal symptoms) depending on the size of the tumor and the relationships it contracts with the adjacent organs (7). Radiological imaging is essential for a correct diagnosis, usually the first step is represented by an ultrasound (abdominal or trans-rectal) but it is undoubtedly crucial the use of CT scan and we have seen that in our case as in the last two cases described in literature (6, 7). Further investigation with MRI is very useful to identify the organ of origin of the neoplasm. The histological diagnosis of Sarcoma is obtained on the anatomical specimens. In some of the previously reported cases it was preferred to proceed first to a tissue biopsy, but in our case we preferred to perform the surgery immediately considering the poor results obtained from chemotherapy on soft tissue sarcomas (STS) (7) and consequently the improbability of any reduction in the mass following neoadjuvant chemotherapy. The differential diagnosis should be made with leiomyosarcomas originating from the neighbouring organs (prostate, bladder, rectum) and which secondarily invade the seminal vesicles. The prognosis of leiomyosarcoma of seminal vesicles is negative, less favorable than other urogenital sarcomatoid lesions from the bladder or paratesticular areas (4), this is probably partly due to the delay in diagnosis and the difficulty to perform a radical excision of the neoplasm. Given the rarity of this condition the treatment of choice is uncertain, but the only therapeutic option that offers a chance of cure in STS is radical surgery, in all reported cases the surgical approach consisted in a cystoprostatectomy with a pelvic lymphadenectomy, except in the last case where prostatectomy with removal of seminal vesicles was done. The role of adjuvant radiation therapy in visceral STS is not clear (9), and only two out of 8 reported cases (two with positive margins and one with very close margins) received such treatment. Also, the role of adjuvant chemotherapy is discussed (10), in literature only one patient received adjuvant combination of doxorubicin, fosfamide and dacarbazine (MAID) (7). Concluding our case of primary leiomyosarcoma of the seminal vesicles is only the ninth described, at the time, in the literature and the first in which the extension and compression of the neoplasm has also necessitated a resection of the sigmoid and the creation of a colostomy. Considering the exceptional nature of these neoplasm, the sharing of knowledge and a multimodal approach are fundamental to improve the prognosis that is still poor.

REFERENCES

1. Agrawal V, Kumar S, Sharma D, et al. Primary leiomyosarcoma of the seminal vesicle. Int J Urol. 2004, 11:253-255. 2. Amirkhan RH, Molberg KH, Wiley EL, et al. Primary leiomyosarcoma of the seminal vesicle. Urology. 1994, 44:132-135. 3. Muentener M, Hailemariam S, Dubs M, et al. Primary leiomyosarcoma of the seminal vesicle. J Urol. 2000, 164:2027.

Corongiu1_Stesura Seveso 26/03/19 09:48 Pagina 57

Large seminal vesicle leiomyosarcoma

4. Russo P, Brady MS, Conlon K, et al. Adult urological sarcoma. J Urol 1992, 147:1032-1036, discussion 1036-1037.

leiomyosarcoma of the seminal vesicle: case report and review of the literature.BMC Cancer. 2011; 11:323.

5. Schned AR, Ledbetter JS, Selikowitz SM. Primary leiomyosarcoma of the seminal vesicle. Cancer. 1986; 57:2202-2206.

8. Thiel R, Effert P. Primary adenocarcinoma of the seminal vesicles. J Urol. 2002; 168:1891-1896.

6. Upreti L, Bhargava SK, Kumar A. Imaging of primary leiomyosarcoma of the seminal vesicle. Australas Radiol. 2003; 47:70-72.

9. Swallow CJ, Catton CN. Local management of adult soft tissue sarcomas. Semin Oncol. 2007; 34:256-269.

7. Cauvin C, Moureau-Zabotto L, Chetaille B, et al. Primary

10. Blay JY, Le Cesne A. Adjuvant chemotherapy in localized soft tissue sarcomas: still not proven. Oncologist. 2009; 14:1013-1020.

Correspondence Emanuele Corongiu, MD Giorgio Pagliarella, MD Flavio Forte, MD PhD flavioforte@hotmail.com G.M. Vannini Hospital, Department of Urology Via di Acqua Bullicante 4, 00177, Rome (Italy) Pietro Grande, MD Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Pitié Salpétière, Urology Department, Paris (France) Valerio Olivieri, MD Dept. of Urology, Ivrea Hospital - ASL TO 4, Ivrea (Italy)

Archivio Italiano di Urologia e Andrologia 2019; 91, 1

Corongiu2_Stesura Seveso 25/03/19 17:24 Pagina 58

CASE REPORT

DOI: 10.4081/aiua.2019.1.58

Minimally invasive management of a symptomatic case of Zinner’s syndrome: Laparoscopic seminal vesiculectomy and ipsilateral nephroureterectomy Emanuele Corongiu 1, Pietro Grande 2, Valerio Olivieri 3, Giorgio Pagliarella 1, Flavio Forte 1 1 Department

Summary

Introduction: Zinner syndrome is a rare developmental anomaly of the Wolffian (mesonephric) duct which is characterized by a triad of obstruction of the ejaculatory duct, the ipsilateral seminal vesicle cyst, and the ipsilateral renal agenesis. Usually is totally asymptomatic, however it can also determine symptoms such as lower urinary tract symptoms, perineal pain, ejaculatory disorders such as painful ejaculation or hematospermia, and infertility. Case report: We present a case of a 51 years old men with a 3-year history of lower urinary tract symptoms, perineal pain, obstructed defecation, recurrent urinary tract infections and infertility. CT scan showed a voluminous cystic neoformation of the left seminal vesicle, hypoplasia of the left kidney and ipsilateral ureteronephrosis. The mass was removed using laparoscopic “en block” seminal vesiculectomy with associated ipsilateral nephroureterectomy. No post-operative complications occurred. At 2-month post-operative control the patient reported an improvement of urinary and rectal symptoms..

KEY WORDS: Seminal vesicle cyst; Zinner’s syndrome; Nephroureterectomy; Seminal vesciculectomy; Laparoscopy. Submitted 2018; Accepted 2019

INTRODUCTION

Zinner syndrome is a very rare condition, first described in 1914 (1), with less than 200 cases reported worldwide, characterized by unilateral renal agenesis, ipsilateral seminal vesicle cyst and ejaculatory duct obstruction. The association between upper urinary tract abnormalities and seminal vesicle malformation are based on the shared origin of the ureteral buds and seminal vesicles from the mesonephric (Wolffian) duct (2). In most cases, these anomalies are completely asymptomatic and the diagnosis is often incidental. However, the association with lower urinary tract symptoms, perineal pain, ejaculatory disorders such as painful ejaculation or hematospermia, and infertility may help unveil the syndrome.

CASE

REPORT

We report the case of a 51-year old Caucasian man, presenting with lower urinary tract symptoms (LUTS), perineal pain, obstructed defecation, recurrent urinary tract

infections and infertility. Uroflowmetry, showed reduced maximal flow (9 ml/s), irregular flow pattern and a consistent postvoid residue (150 ml). The evaluation was completed by an abdominal ultrasound which showed a voluminous cystic formation of the left seminal vesicles together with agenesis of the left kidney. Accordingly, CT scan with excretory phase, revealed a small pelvis completely occupied by a voluminous cystic formation dislocating the rectum and the urinary bladder and causing right ureteronephrosis, with ureteral outlet at the level of the cystic mass (Figure 1). Additionally, hypoplasia of the left kidney was noticed (Figure 1). Based on these data, a minimally-invasive surgical approach was planned, as previously reported as a safe and feasible option (3). A laparoscopic left nefroureterectomy and cystic mass ablation was subsequently planned. The patient was placed in Trendelenburg position: a 12 mm optical Trocar was inserted 1 cm above the umbilical fold. Pneumoperitoneum was obtained and three other trocars (two of 5 and one of 10 mm) were placed. The Douglas fold was completely obliterated by the engorged left seminal vesicle underlying the parietal pelvic peritoneum. The extra-peritoneal space was accessed and the seminal tangle carefully dissected, taking care to avoid direct damages to rectal walls and moreover to the Hovealque plexus located at both lateral rectal sides. Special attention was taken to retract laterally the sacro-recto-genito-pubic ligaments (Delbet bands) in which prostatic and vesical vessels roots are contained. The right ductus deferens was identified and spared, while the left one was necessarily transacted at the point in which it seemed to fuse with the left ureter on the engorged dome of the seminal vesicle, configuring a disturbance of the paramesonephric Wolffian duct development. Once the seminal vesicle removed, the patient was moved in right flank position to perform nephroureterectomy. One more 5 mm Trocar was inserted at the cross between the pararectal and infracostal left lines. Via detaching the mesosigma and gaining the Jonnesco space, 3-5 cm above the left common iliac vessels, the aplastic kidney with its small vascular pedicle was found and it was possible to remove the left kidney, the dilated ureter and the cystic mass "en block", with an No conflict of interest declared.

Archivio Italiano di Urologia e Andrologia 2019; 91, 1

Corongiu2_Stesura Seveso 25/03/19 17:24 Pagina 59

Nephroureterectomy e seminal vesciculectomy in Zinner’s syndrome

Figure 1. CT scan.

Figure 2. Hypoplasia of the left kidney and voluminous seminal cystic formation.

Ta D

Approximately 60 days after the surgical procedure, the patient underwent a new uroflowmetric check which showed a more regular pattern and significantly improved urinary indices (Qmax 15 ml/S) and a reduction of post-void volume (60 cc).

REFERENCES 1. Zinner A. Ein fall von intravesikaler samenblasenzyste. Wein Med Wochenschr. 1914; 64:605-609. 2. Kao CC, Wu CJ, Sun GH, et al. Congenital seminal vesicle cyst associated with ipsilateral renal agenesis mimicking bladder outlet obstruction: a case report and review of the literature. Kaohsiung J Med Sci. 2010; 26:30-4. 3. Kiremit MC, Acar O, Sag AA, et al. Minimally invasive management of Zinner’s syndrome with same-session robot-assisted seminal vesiculectomy and ipsilateral nephroureterectomy using a single geometry of trocars, J Endourol Case Rep. 4: 1, 186-189.

operative time of about 2 hours (Figure 2). The postoperative course was without complications and the patient was discharged on the 4th post-operative day.

CONCLUSIONS

Final pathological analysis revealed a small polycystic left kidney in the absence of residual parenchyma. The cystic mass (measured at 33 cm in diameter) was compatible with a polycystic and ectopic seminal vesicle (Figure 2). The patient was subsequently followed-up in outpatient setting, reporting a progressive and continuous improvement LUTS and rectal symptoms.

Correspondence Emanuele Corongiu, MD (Corresponding Author) emanuele.corongiu@libero.it Giorgio Pagliarella, MD Flavio Forte, MD G.M. Vannini Hospital, Department of Urology Via di Acqua Bullicante 4, 00177, Rome (Italy) Pietro Grande, MD Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Pitié Salpétière, Urology Department, Paris (France) Valerio Olivieri, MD Department of Urology, Ivrea Hospital - ASL TO 4, Ivrea (Italy) Archivio Italiano di Urologia e Andrologia 2019; 91, 1

De Rose_Stesura Seveso 26/03/19 09:32 Pagina 60

DOI: 10.4081/aiua.2019.1.60

CASE REPORT

Late urinary bladder metastasis from breast cancer Aldo Franco De Rose 1, Federica Balzarini 1, Guglielmo Mantica 2, Carlo Toncini 3, Carlo Terrone 1 1 Department

of Urology, Policlinico San Martino Hospital, University of Genoa, Italy; of Urology, San Raffaele Turro Hospital, San Raffaele University, Milan, Italy; 3 Department of Pathology, Policlinico San Martino Hospital, University of Genoa, Italy. 2 Department

Summary

Introduction: Breast cancer (BrC) is the most common non-dermatologic cancer in women. It frequently metastasizes to lung, liver and bone, while the urinary bladder is considered as an unusual site for BrC metastases. Materials and methods: Four years after her first oncologic surgical approach, a known BrC patient complained of a left flank pain, dysuria and urgency. Computed tomography (CT scan) imaging showed an irregular thickening of the left bladder wall and bilateral hydronephrosis. Results: A bladder metastases from BrC was diagnosed based on a histological examination of a transurethral resection of the bladder (TURB-T) specimen. Conclusions: In patients with a history of BrC, urinary bladder screening is not needful. However, if low urinary symptoms persist, an evaluation of the bladder should be considered to rule out metastatic involvement.

KEY WORDS: Bladder cancer, Breast cancer; Bladder metastasis; Breast cancer metastasis. Submitted 5 January 2019; Accepted 25 January 2019

INTRODUCTION

Breast adenocarcinoma is the most frequently diagnosed malignancy in women, with more than 1.6 million new cancer cases diagnosed worldwide (25% of all cancers). BrC remains the leading cause of death for cancer in women, despite increased screening programs and advanced therapies, and its mortality is mainly due to metastatic disease. Common sites of BrC metastasis are lung, liver, bone, lymph nodes and skin while other organs are less frequently involved. Bladder metastasis from solid tumours are rare, accounting for up 4.5% of all bladder neoplasms (1). Most bladder metastasis are due to direct infiltration from peripheral organs, such as colon and rectum, prostate and cervix. Metastasis from distant organs are extremely rare and reported sporadically. The most common are related to stomach and lung tumours as well as melanomas. BrC accounts for about 2.4% cases of all bladder metastasis (1). In most instances, bladder metastases from BrC are associated with other metastatic involvement of pelvic organ with a very poor survival (2, 3).

CASE

REPORT

We present the clinical case of a 57 years-old woman with a negative family history regarding BrC. At the end

of 2013 she presented with painless right breast mass. A mammogram demonstrated a large high dense soft mass lesion in the upper outer quadrant of the right breast (maximum diameter 16 cm). A Tru-cut needle biopsy showed 2 foci of invasive ductal carcinoma of 10 and 6 mm (immunohistochemistry was estrogen receptor (ER) 95% - progesterone receptor (PgR) 40% - Ki67 40% - human epidermal growth factor receptor 2 (HER2) negative and ER 95% - PgR 10% - Ki67 15% HER2 negative, respectively). Tumour clinical stage was T1cN1M0. Neoadjuvant chemotherapy was started (FEC-75 q21 x4 + Paclitaxel 80 mg q7x12) and a right mastectomy with ipsilateral axillary lymph node dissection was done in August 2014. Pathology revealed invasive ductal carcinoma (IDC) with some elements of atypical ductal hyperplasia (ADH-DIN1b) and negative margins. All six removed lymph nodes were involved, one of which presented perineural invasion. Tumour pathological stage was pT1c(m)/G2/N2a(6+/6)/M0 - luminal B (stage IIIA). ER and PgR were positive (ER 95%, PgR 50%), Ki67 1% and HER2 were negative. The patient underwent adjuvant radiotherapy from November to December 2014 and hormonal adjuvant treatment with Letrozole was administrated from September 2014 to August 2016. She had been on regular follow-up every 6 months until November 2016, when the patient suffered from left subcutaneous inguinal mass. Excisional biopsy showed a metastasis from the primary BrC with negative margins. Immunohistochemistry showed ER positive (100%), PgR negative, Ki67 40% and HER2 negative. In January 2017, a follow-up total-body CT scan displayed left enlarged inguinal lymph nodes. Bone scintigraphy was negative. From February 2017, Letrozole was substituted with Fulvestrant, which was continued until April 2018. At the end of April 2018 a new CT scan showed increasing of lymph node disease (left common iliac lymph nodes, internal obturator lymph nodes and left inguinal lymph nodes). The patient took part in the phase II trial of the CDK4/6 inhibitor Palbociclib as single agent or in combination with the same endocrine therapy (ET) received prior to disease progression, in patients with hormone receptor positive (HR+) HER2 negative metastatic breast cancer (mBrC) (TREnd trial). At the end of the first cycle she presented to our attention with left flank pain, dysuria, urge incontinence and No conflict of interest declared.

Archivio Italiano di Urologia e Andrologia 2019; 91, 1

De Rose_Stesura Seveso 26/03/19 09:32 Pagina 61

Late bladder metastasis from breast cancer

Figure 1.

The submucosal layer of the urinary bladder is expanded by medium and large size atypical cells, poorly differentiated, that diffusely infiltrate the muscularis propria. The transitional epithelium is intact, without any dysplastic and neoplastic changes or relation/connection to the neoplastic elements. Hematoxylin-eosin stain (20x).

last few years, probably due to better imaging techniques. Most cases are diagnosed after the diagnosis of primary BrC and are usually associated with other metastatic sites. Although routine screening of the lower urinary tract is not mandatory for all patients, women presenting with urinary symptoms should be evaluated in order to exclude a bladder metastasis. The imaging should include ultrasound, CT and/or MRI scan. Once imaging and/or cystoscopy show a bladder neoplasm in a patient with a BrC history, a TURB-T is mandatory. Chemotherapy and/or hormonal therapy, if not already ongoing, should started as soon as a diagnosis is confirmed. Generally, the prognosis is poor unless bladder metastases represents the only metastatic site (3). Our reported case confirm that bladder metastases may occur late after the diagnosis of the primary tumours. Such data support the need for accurate urological follow-up and early intervention if such clinical state is suspected.

Figure 2.

DISCUSSION

Immunohistochemistry staining is diffusely positive for estrogen receptor in neoplastic cells, otherwise the transitional epithelium of urinary bladder is completely negative (20x).

increasing creatinine. Abdominal CT scan displayed thickening of the posterior-left bladder wall with bilateral grade I-II hydronephrosis. Cystoscopy showed inflammatory changes and suspicious bladder wall thickening. Transurethral resection of bladder tumour (TURB-T) was performed. Pathology revealed muscular invasive anaplastic cells consistent with the known primary breast adenocarcinoma. Microscopically, the bladder layers showed a diffuse infiltration by large size carcinomatous cells displaying round nuclei, distinct nucleoli with a diffuse pattern, without obvious ductal or glandular structure. The urinary transitional epithelium was intact and ulcerated, without dysplastic or neoplastic changes. (Figures 1, 2) The muscular layer was deeply involved. Neoplastic cells were ER and PgR positive, Cytocheratin 7 positive, GCDFP 15 positive and Mammoglobin positive. Ki67 immunostaining was markedly increased. Nowadays, the patient is continuing the therapy with Palbociclib and Fulvestrant. A 3months follow-up cystoscopy and urine cytology didnâ&#x20AC;&#x2122;t show any bladder recurrence.

CONCLUSIONS

Bladder metastases from BrC are uncommon. However, literature reveals an increase of such occurrence over the

Secondary tumours of the urinary bladder are rare and the majority of them are due to the direct extension of another pelvic neoplasm (4). The minority are metastases originating from lymphoma or from solid tumour such as lung, breast cancers and melanoma. Possible mechanisms are through vascular and lymphatic dissemination or direct retroperitoneal invasion (5). To date, approximately 55 cases of urinary bladder metastasis from BrC have been reported in literature (3). In the majority of reported cases, the urinary bladder lesions from BrC were part of a systemic dissemination and multiple organ involvement. This indicates that bladder metastases are usually late complications of primary disease (6). However, a solitary metastasis to the urinary bladder had also been reported (7, 8). Metastases start from the outer layer of bladder wall and advance towards the bladder lumen (9). Urinary symptoms correlate with the advancement of this growth. Early stages of BrC bladder metastases might be asymptomatic, while the most common presenting symptoms are low urinary tract symptoms (LUTS), flank or abdominal pain, hydronephrosis, and haematuria (9). Our patient did not present with macroscopic haematuria. Instead, she complained from recurrent dysuria, urge incontinence and progressive renal failure. Flank pain was later the major weakening symptom that allowed the investigation through CT scan imaging. Diagnostic workshop needs imaging (ultrasound and CT scan), direct visualisation of the bladder mucosa by cystoscopy, and histological confirmation of a specimen obtained by biopsy or TURB-T. Cystoscopy findings vary and comprehend solid tumour, inflammatory patches, and thickened bladder wall with intact overlying mucosa. In our patient cystoscopy revealed suspicious bladder wall thickening and non-specific inflammatory areas. Feldman et al. affirm that assessment should also include further imaging evaluation, citing a case with negative cystoscopy despite strong evidence of bladder wall involvement from the patientâ&#x20AC;&#x2122;s symptoms, ultrasound and CT scan (10). Magnetic resonance imaging Archivio Italiano di Urologia e Andrologia 2019; 91, 1

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A.F. De Rose, F. Balzarini, G. Mantica, C. Toncini, C. Terrone

(MRI) scan would help in definitive confirmation of neoplastic bladder infiltration and it would help in precise local cancer staging. PET-CT scan may reveal other metastases. Patient assessment should incorporate check of blood serum CA 15-3 level which remains the most sensitive tumour marker in BrC follow-up (11). The metastatic pattern of BrC may be related to the histologic type of cancer (10). It has been suggested that infiltrating lobular carcinoma (ILC) has a higher bladder metastatic rate in comparison with infiltrating ductal carcinoma (IDC) representing approximately 90% of BrC (3). Some reports have related the likelihood of developing bladder metastases with the presence of positive lymph nodes at first diagnosis of BrC or with steroid treatment (11). Patients who have been administrated prolonged steroid therapy may develop unusual metastases due to the possible influence of immune-suppressive effects on carcinoma spreading routes. Immunohistochemistry is an indispensable adjunct in the correct diagnosis of metastatic tumours in all sites. Common markers for suspected breast tumours include the expression of cytokeratin, CK-7, CK-18, CK-19, CK20, GCDFP-15 and ER/PgR (8). In the present case, positive CK-7 and CD-138, and negative CD-20 helped the pathologist in confirming the diagnosis of metastatic BrC. Some authors reported differences in hormonal (ER and PgR) and HER2 expression between primary and metastatic tissue, with discordance rates ranging from 24 to 39% (6, 12). Bladder metastases from BrC usually occurs a few months after the initial diagnosis of the primary tumour, but they might also occur years later (3, 10). However, it is possible of bladder metastases being present at the time of first diagnosis of BrC, like in the case reported by Shah et al. (8), whereby acute renal failure due to the ureteral obstruction was the presenting sign. In our patient the bladder metastasis was identified 4 years after the initial diagnosis of BcR. The standard treatment of urinary bladder metastases from BrC involves chemotherapy and hormonal therapy. Radiotherapy might be used only to control bladder

Correspondence Aldo Franco De Rose, MD Federica Balzarini, MD Carlo Terrone, MD Department of Urology, Policlinico San Martino Hospital, University of Genoa, Genoa, Italy Guglielmo Mantica, MD (Corresponding Author) guglielmo.mantica@gmail.com Department of Urology, San Raffaele Turro Hospital, San Raffaele University Via Stamira d’Ancona 20, 20127 Milano (Italy) Carlo Toncini, MD Department of Pathology, Policlinico San Martino Hospital, University of Genoa, Genoa, Italy

Archivio Italiano di Urologia e Andrologia 2019; 91, 1

bleeding. In case of obstructive uropathy, percutaneous drainage or ureteric catheterization should be performed to optimise renal function before starting chemotherapy.

REFERENCES

1. Bates AW, Baithun SI. The significance of secondary neoplasms of the urinary and male genital tract. Virchows Arch. 2002; 440:640-647. 2. Velcheti V, Govindan R. Metastatic cancer involving bladder: a review. Can J Urol. 2007; 14:3443-3448. 3. Sanguedolce F, Landriscina M, Ambrosi A, et al. Bladder metastases from breast cancer: managing the unexpected. A systematic review. Urol Int. 2018; 101:125-131. 4. Cormio L, Sanguedolce F, Di Fino G, et al. Asymptomatic bladder metastasis from breast cancer. Case Rep Urol. 2014; 2014:672591. 5. Pontes JE, Oldford JR. Metastatic breast carcinoma to the bladder. J Urol. 1970; 104:839-42. 6. Zagha RM, Hamawy KJ. Solitary breast cancer metastasis to the bladder: an unusual occurrence. Urol Oncol. 2007; 25:236-239. 7. Ghaida RA, Ayoub H, Nasr R, et al. Bladder metastasis from primary breast cancer: a case report and literature review. Cent European J Urol. 2013; 66:177-84. 8. Shah KG, Modi PR, Rizvi J. Breast carcinoma metastasizing to the urinary bladder and retroperitoneum presenting as acute renal failure. J Urol. 2011; 27:135-136. 9. Ramsey J, Beckman EN, Winters JC. Breast cancer metastatic to the urinary bladder. Ochsner Journal Information. 2008; 8:208212. 10. Feldman PA, Madeb R, Naroditsky I, et al. Metastatic breast cancer to the bladder: a diagnostic challenge and review of the literature. Urology. 2002; 59:138. 11. Łuczyñska E, Pawlik T, Chwalibóg A, et al. Metastatic breast cancer to the bladder case report and review of literature. J Radiol Case Rep. 2010; 4:19-26. 12. Lin WC, Chen JH. Urinary bladder metastasis from breast cancer with heterogeneic expression of estrogen and progesterone receptors. J Clin Oncol. 2007; 25:4308-4310.

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DOI: 10.4081/aiua.2019.1.63

CASE REPORT

Pubis bone osteomyelitys after robotic radical cystectomy with continent intracorporeal urinary diversion: Multidisciplinary approach to a complex situation Daniele Romagnoli 1, Federico Mineo Bianchi 2, Paolo Sadini 2, Andrea Angiolini 2, Daniele D'Agostino 1, Marco Giampaoli 1, Sergio Candiotto 3, Riccardo Schiavina 2, Eugenio Brunocilla 2, Angelo Porreca 1 1 Robotic

Urology and Mini Invasive Urologic Surgery Unit, Abano Terme Hospital, Abano Terme (PD), Italy; Unit, S. Orsola Malpighi University Hospital - Alma Mater Studiorum, Bologna (BO), Italy; 3 Orthopaedic Unit, Abano Terme Hospital, Abano Terme (PD), Italy. 2 Urology

Summary

Pubic bone osteomyelitis is a rare infectious condition which is characterized by a complex diagnostic and therapeutic workup, due to its various clinical manifestations. Among the many causes of this condition, urinary fistula is the most common in case of previous urological procedures. In order to solve this complication, it is crucial to treat both the fistula and (moreover) the infectious locus arising from it, because treating the fistula alone does not provide any control on the infectious noxa. We present the first case of pubic bone osteomyelitis arising from a urinary fistula after a robotic radical cystectomy with intra corporeal continent neobladder, which has been successfully treated through a multidisciplinary approach.

KEY WORDS: Osteomyelitis; Cystectomy; Urinary fistula; Robotic; Multidisciplinary. Submitted 28 December 2018; Accepted 8 February 2019

INTRODUCTION

Pubic bone osteomyelitis (PBO) is a rare complication that may occur after either radical prostatectomy, radical radiotherapy of the prostatic bed or other ablative techniques for the treatment of prostate cancer or benign hyperplasia (1-4). Due to its extremely low incidence, its initial cause is still uncertain. This clinical syndrome is characterized by pelvic and thigh pain, difficulty with ambulation, and recurrent urinary tract and pelvic infection. The pain associated with this condition can significantly impact the quality of life of patients and impede participation in the activities of daily living. Several authors reported urinary fistulation (UF) into the bone symphysis to be the main culprit of this condition (5-7). Common presentation includes chronic and debilitating suprapubic pain, fever, voiding disorders, recurrent urinary tract infections and sometimes impairment and pain during ambulation. Our aim is to present a case of PBO which arose from a urinary fistula after robotic assisted radical cystectomy with continent urinary diversion, and how we managed it in order to solve the chronic inflammatory process.

CASE

DESCRIPTION

We describe the case of a male patient, aged 69, who had undergone a robot-assisted radical cystectomy (RARC) with extended pelvic lymph node dissection (PLND) and intracorporeal orthotopic neobladder substitution (ONS) according to the Studer-Wiklund technique, due to a pT2 High Grade bladder carcinoma. Local staging was performed either with CT scan and MRI in order to plan a better approach to a safe nerve sparing cystectomy, as described for prostate cancer clinical T staging (8). The operation was performed at our institution in March 2018, and no early postoperative complication was documented. Barbed sutures were used for neo-bladder reconstruction and muscle-fascial-reconstruction as described in prostatic surgery for bladder neck-urethral anastomosis (9). Patient was discharged in 7th post-operative day (POD), catheter was removed after 30 postoperative days, and 3 months later, during the scheduled control visit at one month, he described persistent suprapubic pain and recent presentation of 38Â°C fever. Oral empiric antibiotic therapy (prulifloxacin 600 mg daily for seven days) was administered, but neither fever nor suprapubic pain resolved. Thus, patient was hospitalized at our Institution, to rule out a diagnostic work-up. Abdominal ultra sound (US) was negative for abdominal free fluid (suggestive for lymphocele or pelvic haematoma), and neobladder voiding was confirmed complete at ultrasound. Under the suspicion of an infection supported by neovescico-ureteric reflux (para-physiological in case of neobladder), we started intravenous antibiotic therapy (Cefotaxime 1 g twice a day for 7 days) and 3-way urinary catheter was inserted. Patient experienced a quick symptom relief and was discharged after 3 days. A week later catheter was removed, but after two more weeks the patient reported the recurrence of the afore mentioned symptoms. Moreover, the suprapubic pain was described as intensifying during ambulation, and was in some cases associated with mixed urinary incontinence. Patient was readmitted at our Institution, where we performed a contrast enhanced computed tomography (CT), which revealed the presence of a fili-

No conflict of interest declared. Archivio Italiano di Urologia e Andrologia 2019; 91, 1

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D. Romagnoli, F. Mineo Bianchi, P. Sadini, A. Angiolini, D. D'Agostino, M. Giampaoli, S. Candiotto, R. Schiavina, E. Brunocilla, A. Porreca

form fistula between the neobladder anastomosis (at 11 oâ&#x20AC;&#x2122;clock) and the pubic bone. Considering the thin length (1.5 cm) and width (0.5 cm) of the fistula, and the unwillingness of the patient to be submitted to another surgical operation, conservative management was adopted. A neobladder catheter was inserted, in order to grant an adequate drainage of the neobladder, and oral empiric antibiotic therapy (Ciprofloxacin 500 mg twice a day for 1 week every month) was administered. A follow up CT scan was performed two months later, and no residual fistula was apparently documented, thus the catheter was removed. Two weeks later a flexible neo-cystoscopy was performed, and none remnant of the fistula was documented, except for an area of edematous tissue in a location correspondent to the previous leakage. The absence of any residual fistula was confirmed also by a subsequent retrograde uretrography. However, six months after RARC, the patient was admitted at the Emergency Department of our Institution, reporting persisting strong inguinal pain, particularly focused in the pubic symphysis. Pain was reported to have begun one month before, with a subsequent constant increase, associated with a significant impairment in the ambulation of the medial side of the right leg. Moreover, the patient reported to suffer from a significant worsening of urinary continence, using about 3 pads/day, with a steep decrease of

his whole quality of life. A third uro-CT was performed showing the recurrence of the fistula, which resulted to be larger than before (Figures 1-4). Physical examination confirmed intense pain at the palpation of the inguinal region, bilaterally. Due to the intense pain, the patient refused consent to the urinary catheter, so bilateral percutaneous nephrostomies were placed with combined ultrasonographic and radiologic technique, to reduce the urinary leakage from the fistula. Multidisciplinary evaluation was carried out, by a team made up by the members of the Urology unit and Orthopedic unit. We agreed that the clinical situation was the result of a chronic pubic osteomyelitis, which had originally been started by the urinary fistula. The recurrence of the urinary fistula appeared to be the result of the reactivation of the bone chronic inflammatory process, and the extirpation of the tissue involved was planned. Intravenous administration of meropenem 1 g twice a day was administered 3 days before the surgical operation, in order to reduce the septic load. The operation began with a semicircle incision of the skin from pubis to the groin, and subsequent section of the rectus abdominis muscle. The pubic symphysis was Figure 3. MRI scan (T1w) showing focus of pubis osteomyelitis.

Figure 1. CT scan showing fistulous tract in the context of the pubis symphysis.

Figure 2. Pre-operative CT urographic phase highlighting pubo-vesical fistula.

Archivio Italiano di Urologia e Andrologia 2019; 91, 1

Figure 4. MRI scan (T2w) documenting pubis osteomyelitis focus.

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Pubis bone osteomyelitys after robotic radical cystectomy

Figure 5. Intra-operative image of the combined orthopaedic and urologic surgical procedure with removal of the osteomyelitis focus.

isolated, and aggressive scarring of the inflammatory tissue surrounding the fistula was performed (Figure 5). The pubic tissue was deeply removed until obtaining vital, well vascularized and bleeding tissue. Moreover, we noted the involvement of the origin of the right longus adductor muscle by the inflammatory process, thus explaining ambulation impairment. Then retrograde removal of the fistulous path was performed. Neobladder filling with a solution made up of saline and methylene blue was performed, in order to check the presence of any residual fistula. The check resulted negative, as confirmed by a flexible cystoscopy. Then the rectus abdominis muscle was fixed to the remnant part of the symphysis. Double laminar drainages were positioned at the level of the symphysis, and the surgical incision was closed. Operative time was 120 minutes, with estimated blood loss less than 100 mL. Drainages were removed on first and third postoperative day, and length of hospital stay (LOS) was 7 days. The patient experienced a quick relief from the symptoms previously reported, also due to an adequate antalgic therapy made up by nonsteroidal-anti-inflammatory drugs (NSAIDs). One month after surgery a retrograde and anterograde radiological study was performed and resulted negative for any recurrence of the fistula. The patient reported to be fine, thus catheter was removed, and nephrostomies were closed. The patient was revaluated two weeks later and was confirmed symptoms free. Retrograde uretrography was performed resulting negative for any urinary leakage, so both nephrostomies were removed. At 3 and 6 months post-operative control visits, the patient confirmed full continence and no further symptoms.

DISCUSSION

Osteomyelitis of the symphysis pubis is a rare entity, accounting for less than 1% of all cases of osteomyelitis (10). The presenting signs and symptoms are mainly pubic pain, antalgic gait, pain with hip motion, and occasional presence of fever. Postoperative pain after radical cystectomy is expected; nevertheless, pain lasting for

more than 6 months is not usual and may suggest other etiologies (11, 12). Osteomyelitis of the symphysis pubis has been reported after renal transplantation (13), inguinal herniorraphy (14), procedures for urinary stress incontinence such as tension free vaginal/transobturator taping (15), and ablative treatments for prostate cancer, such as high intensity focused ultrasound treatment for prostate cancer (16), pelvic radiation therapy and radical prostatectomy (1). Several theories lie behind the pathogenesis of PBO. This includes infection, trauma secondary to haematogenous spread or complex regional pain syndrome (17). The most common pathogen causing pubic symphysis osteomyelitis is Staphylococcus aureus. However, other organisms such as Pseudomonas aeruginosa, Escherichia coli, Enterococcus species, Mycobacterium tuberculosis, and Salmonella species have also been reported in the literature (18). There have been several reports of pubic bone osteomyelitis secondary to pubosymphyseal fistula, in patients who underwent radical prostatectomy, followed by adjuvant radiation therapy. Matsushita et al. reported 12 patients, from two centers over an 11-year period, who developed a pubovesical fistula, following treatment of prostate cancer (19). All those patients had radiation therapy either as the primary treatment or as salvage therapy and subsequently developed bladder neck contracture. The median interval to develop pubovesical fistula was 37 months after treatment for bladder neck contracture. Broad-spectrum antibiotics were initiated in all patients, and only one patient had resolution of his osteomyelitis. The remaining patients either needed diversion of their urinary tract or insertion of bilateral percutaneous nephrostomies, to achieve resolution of symptoms. Despite such a small sample size, the longtime frame, extending over 11 years, reflects the rarity of this disease and as such the absence of any existing guidelines, for treating those fistulas. Pelvic bone pain and gait instability, after radical prostatectomy, reflect multiple bone etiologies, to contemplate in our differential diagnosis (20-22). Other than osteomyelitis of the pubic symphysis, pelvic insufficiency fracture (PIF), osteonecrosis (ON), and osteitis pubis (OP) are among the others to consider (14). OP is usually mistaken by osteomyelitis. It is defined by a painful inflammatory process resulting in bone destruction of the margins of the symphysis pubis. Nevertheless, OP is a self-limiting process, treated conservatively by anti-inflammatory drugs. The main difference between osteitis pubis and osteomyelitis is the negative culture on biopsy (7). Noteworthy here is that delay in diagnosis or treatment of symphysis pubis osteomyelitis can further manifest as bilateral thigh pain and adductor muscle abscesses, necessitating percutaneous drainage (23, 24). As part of pain relief, pubic bone resection has been shown to provide immediate and sustained improvement in pain, along with the long course of antibiotics administered (25). In a cohort of 16 patients, a statistically significant decrease in the median pain intensity score was noted, over a median follow-up of 9.4 months, after performing pubic bone resection (5.5 versus 0; p = 0.0005). Suturing of the dorsal venous complex (DVC), during the robotic radical prostatectomy procedure, using a type of Archivio Italiano di Urologia e Andrologia 2019; 91, 1

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D. Romagnoli, F. Mineo Bianchi, P. Sadini, A. Angiolini, D. D'Agostino, M. Giampaoli, S. Candiotto, R. Schiavina, E. Brunocilla, A. Porreca

needle called V-lock suture needle, and then fixing it at the level of the pubic bone, has been postulated to be the cause for osteomyelitis. Indeed, the use of barbed suture for urethral anastomosis in safe and efficacious but repeated needle injury to the pubic symphysis, during the urethral vesical anastomosis, may as well inadvertently cause contiguous-focus osteomyelitis (26). Yet, the possibility of an even rarer etiology of the pubic bone osteomyelitis cannot be excluded, given the negative urine culture at time of surgery. In our experience we count only 3 cases of pubo-urinary fistula in over 15 years of high volume surgery, but the one we reported was the first after RARC (2 cases of UF were recorded after open radical prostatectomy). This is the first surgical complication of our series of RARC (27) whose control have been achieved through an open approach, having adopted a less invasive approach in the remaining cases (28). In our opinion, UF and PBO have mutual cause-effect relation. PBO originally arose from a urinary leakage from the neo-bladder, with urinary extravasation as the main responsible for the subsequent bacterial colonization of the pubic bone. Despite long-term antibiotic therapy along with bladder catheter placement to drain urine, with further negative CT that excluded any residual urinary fistula, the patient was nonetheless readmitted in hospital 3 months later due to further recurrence of intense suprapubic pain and ambulation impairment. Despite resolution of systemic infection, antibiotic therapy could not reach and fully turn off the primary osteomyelitis focus, thus impairing tissue repairing processes and causing an additional urinary leakage. An early diagnosis of pubic osteomyelitis is often difficult: the lack of typical acute osteomyelitis symptoms due to the deep position of pelvic bone and the limitation of its motion, along with unspecific symptoms and hematologic findings often lead to a late acknowledgement of this serious condition (29, 30). X-Rays have been used for early diagnosis though appearance of bone destruction and periosteal reaction occur typically 7-14 days after onset, thus limiting their role in the early phase of disease (25). A definitive diagnosis of pubic osteomyelitis is usually made through MRI and CT examination. MRI displays a 94% sensitivity and 97% specificity in detecting this clinical condition, as it represents the most suitable imaging technique to distinguish between infected and normal bone marrow and to detect edematous changes and abscess formation. MRI should be in fact considered as PBO is suspected (29, 30). The treatment for PBO is based on antibiotic therapy and surgical debridement. When recognized early, antibiotic therapy alone could guarantee a complete resolution of this clinical condition, due to the rich vascularization of the pelvis. Del Busto et al. reviewed 7 patients diagnosed with PBO, who didnâ&#x20AC;&#x2122;t require any surgical debridement after complete response to 3-to-12 weeks of antibiotic therapy (31). Surgical debridement is nonetheless recommended after primary antibiotic therapy and consists in a wide removal of necrotic and infected tissues until vital and bleeding ones are reached. Intravenous antibiotics

Archivio Italiano di Urologia e Andrologia 2019; 91, 1

should be prolonged for 6 more weeks after surgery, with 3 additional weeks of oral antibiotics in case of haematogenous origin of PBO (29, 32). In our case direct and prolonged urinary leakage from the orthotopic neobladder resulted in a chronic infection with a slowly increasing inflammatory process that could be identified only when osteomyelitis had already destroyed pubic bone and the abscess was already formed. Uro-CT and MRI imaging were decisive to correctly identifying PBO, as symptoms reported by the patient and hematologic findings were inconclusive. Antibiotic therapy alone was not enough to resolve PBO. Despite complete resolution of urinary fistula and apparent symptom relief, the inflammatory process recurred 2 months later. Persistence of chronic inflammation caused an impairment of tissue reparation, that translated in a recurrent urinary fistula from the neobladder. Multi-disciplinary management was critic for choosing the proper management of this peculiar clinical condition: extensive surgical debridement of the necrotic and infected tissues along with prolonged antibiotic therapy led to a definitive resolution of the chronic inflammation. No signs of recurrence were identified at 3 and 6 months follow up visits, with a complete continence recover and any additional symptoms were reported.

CONCLUSIONS Osteomyelitis of the symphysis pubis is a rare condition, quite uncommon to occur after radical cystectomy. It can be often missed due to vague non-specific symptoms. Its clinical presentation might be confused by the presence of concurrent urinary fistula, which might be its origin, but also its effect. In case of urinary fistula, it is very important to rule out, via MRI, the presence of any concurrent PBO focus, because curative goal might be achieved only if both conditions are treated, preferably through a multidisciplinary approach.

REFEREMCES

1. Gupta S. et al., Pubic symphysis osteomyelitis in the prostate cancer survivor: clinical presentation, evaluation, and management. Urology, 2015; 85:684. 2. Moore DC, et al. A 57-year-old man with a history of prostatectomy and pelvic irradiation presents with recurrent urinary tract infections, hematuria, and pelvic pain. Urology. 2013; 81:221. 3. Kats E, et al. Diagnosis and treatment of osteitis pubis caused by a prostate-symphysis fistula: a rare complication after transurethral resection of the prostate. Br J Urol. 1998; 81:927. 4. Hutchinson RC, et al. Magnetic resonance imaging to detect vesico-symphyseal fistula following robotic prostatectomy. Int Braz J Urol. 2013; 1:288. 5. Bugeja S, et al. Fistulation into the Pubic Symphysis after Treatment of Prostate Cancer: An Important and Surgically Correctable Complication. J Urol, 2016; 195:391. 6. Matsushita K, et al. Pubovesical fistula: a rare complication after treatment of prostate cancer. Urology, 2012; 80: 46. 7. Knoeller, et al. Osteitis or osteomyelitis of the pubis? A diagnostic

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and therapeutic challenge: report of 9 cases and review of the literature, Acta Orthop Belg, 2006; 72:541.

A rare complication after treatment of prostate cancer. Urology, 2012; 80:446.

8. Schiavina R, et al. MRI Displays the Prostatic Cancer Anatomy and Improves the Bundles Management Before Robot-Assisted Radical Prostatectomy. J Endourol. 2018; 32:315.

20. Pauli S, Willemsen P, Declerck K, et al. Osteomyelitis pubis versus osteitis pubis: a case presentation and review of the literature. Br J Sports Med. 2002; 36:71-3.

9. Porreca A, et al. Bidirectional barbed suture for posterior musculofascial reconstruction and knotless vesicourethral anastomosis during robot-assisted radical prostatectomy, Minerva Urol Nefrol. 2018; 70:319

21. Trubiano JA, Yang N, Mahony AA. Bilateral thigh pain after treatment for prostate cancer. BMJ Case Rep. 2013; 2013 pii: bcr2013008784.

10. Lavien G, et al, Pubic Bone Resection Provides Objective Pain Control in the Prostate Cancer Survivor with Pubic Bone Osteomyelitis with an Associated Urinary Tract to Pubic Symphysis Fistula, Reconstructive Urology. 2017; 100:234. 11. McHenry MC, Alfidi RJ, Wilde AH, Hawk WA. Hematogenous osteomyelitis: A changing disease, Cleve Clin Q. 1975; 42:125-53. 12. Moore DC1, Keegan KA, Resnick MJ, et al. A 57-year-old man with a history of prostatectomy and pelvic irradiation presents with recurrent urinary tract infections, hematuria, and pelvic pain, Urology. 2013; 81:221. 13. Jindal RM, Idelson B, Bernard D, Cho SI.R. M. Osteomyelitis of symphysis pubis following renal transplantation, Postgrad Med J. 1993; 69:742. 14. Mader R, Yeromenco E. Pseudomonas osteomyelitis of the symphysis pubis after inguinal hernia repair, Clini Rheumatol. 1999; 18:167. 15. Goldberg RP, Tchetgen MB, Sand PK, et al. Incidence of pubic osteomyelitis after bladder neck suspension using bone anchors, Urology, 2004; 63:704. 16. Robison CM, Gor RA, Metro MJ. Pubic bone osteomyelitis after salvage high-intensity focused ultrasound for prostate cancer. Curr Urol. 2013; 7:149-51. 17. Sexton DJ, Heskestad L, Lambeth WR, et al. Postoperative pubic osteomyelitis misdiagnosed as osteitis pubis: report of four cases and review. Clin Infect Dis. 1993; 17:695-700. 18. Alqahtani SM, Jiang F, Barimani B, Gdalevitch M. Symphysis pubis osteomyelitis with bilateral adductor muscles abscess. Case Rep Orthop. 2014; 2014:982171. 19. Matsushita K, Ginsburg L, Mian BM, et al. Pubovesical fistula:

22. Lavien G, Chery G, Zaid UB, Peterson AC. Pubic bone resection provides objective pain control in the prostate cancer survivor with pubic bone osteomyelitis with an associated urinary tract to pubic symphysis fistula. Urology. 2017; 100:234-239. 23. Kitaguchi D, et al. Pubic osteomyelitis after surgery for perforated colonic diverticulitis with fecal peritonitis: A case report. Int J Surg Case Rep. 2017; 38:50. 24. Rosenthal RE, et al. Osteomyelitis of the symphysis pubis: a separate disease from osteitis pubis. Report of three cases and review of the literature. J Bone Joint Surg Am. 1982; 64:123. 25. Kozlowski K, Hochberger O, Povysil B. Swollen ischiopubic synchondrosis: a dilemma for the radiologist. Australas. Radiol. 1995; 39:224. 26. Porreca A, et al. Robotic-Assisted Radical Prostatectomy with the Use of Barbed Sutures. Surg Technol Int. 2017; 30:39. 27. Porreca A, et al. Robot assisted radical cystectomy with totally intracorporeal urinary diversion: initial, single-surgeon's experience after a modified modular training, Minerva Urol Nefrol. 2018; 70:193. 28. Schiavina R, et al. Laparoscopic and robotic ureteral stenosis repair: a multi-institutional experience with a long-term follow-up. J Robot Surg. 2016; 10:323. 29. Carek PJ, et al. Diagnosis and management of osteomyelitis. Am Fam Phys. 2001; 63:2413. 30. Sammak B, et al. Osteomyelitis: a review of currently used imaging techniques. Eur. Radiol. 1999; 9:894. 31. Del Busto R, et al. Osteomyelitis of the pubis. Report of seven cases. JAMA. 1982; 248:1498. 32. Wilmes D, et al. Osteomyelitis pubis caused by Kingella kingae in an adult patient: report of the first case, BMC Infect. Dis. 2012; 12:236.

Correspondence Daniele Romagnoli, MD (Corresponding Author) danieleromagnoli87@gmail.com Daniele D'Agostino, MD Marco Giampaoli, MD Angelo Porreca, MD Robotic Urology and Mini Invasive Urologic Surgery Unit, Abano Terme Hospital Piazza Cristoforo Colombo, 2 Abano Terme (PD) (Italy) Federico Mineo Bianchi, MD Paolo Sadini, MD Riccardo Schiavina, MD Eugenio Brunocilla, MD Andrea Angiolini, MD Urology Unit, S. Orsola Malpighi University Hospital - Alma Mater Studiorum Via Pelagio Palagi, 9 Bologna (Italy) Sergio Candiotto, MD Orthopaedic Unit, Abano Terme Hospital Piazza Cristoforo Colombo, 2 Abano Terme (PD) (Italy)

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Archivio Italiano di Urologia e Andrologia / Archives of Italian Urology and Andrology - Vol. 91; n. 1 March 2019

Vol. 91; n. 1, March 2019

ORIGINAL PAPERS 1

Factors associated with urinoma accompanied by ureteral calculi Ercan Öğreden, Ural Oğuz, Mehmet Karadayı, Erhan Demirelli, Alptekin Tosun, Mücahit Günaydın

The role of anticholinergic therapy based on the upoint system in the treatment of chronic prostatitis Kamil Fehmi Narter, Utku Can, Alper Coşkun, Kubilay Sabuncu, Fatih Tarhan

NOTE OF SURGICAL TECHNIQUE 35

The LEST technique: Treatment of prostatic obstruction preserving antegrade ejaculation in patients with benign prostatic hyperplasia Rosario Leonardi

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