Advances in Urological Diagnosis and Imaging - AUDI (Vol. 2 - n. 1 - 2019)

ADVANCES IN UROLOGICAL DIAGNOSIS AND IMAGING EDITOR IN CHIEF Andrea B. Galosi CO-EDITOR Pasquale Martino

OFFICIAL JOURNAL of

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Vol. 2 - n. 1 - 2019

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ADVANCES

IN

UROLOGICAL DIAGNOSIS AND IMAGING

Official Journal of S.I.E.U.N. EDITOR in CHIEF Andrea B. Galosi, Ancona (IT)

CO-EDITOR

Pasquale Martino, Bari (IT)

ASSISTANT EDITOR Lucio Dell’Atti, Ancona (IT)

EDITORIAL BOARD Urology

Ahmed Hashim, London (GB), Artibani Walter, Verona (IT) Battaglia Michele, Bari (IT), Bucci Stefano, Trieste (IT) Carini Marco, Firenze (IT), Carrieri Giuseppe, Foggia (IT) De Nunzio Cosimo, Roma (IT), Fandella Andrea, Treviso (IT) Ficarra Vincenzo, Messina (IT), Finazzi Agrò Enrico, Roma (IT) Franzese Corrado, Nola (IT), Gunelli Roberta, Forlì (IT) Kastner Christof, Cambridge (GB), Lapini Alberto, Firenze (IT) Miano Roberto, Roma (IT), Mirone Vincenzo, Napoli (IT) Montorsi Francesco, Milano (IT), Morgia Giuseppe, Catania (IT) Muller Stefan, Bonn (GE), Palazzo Silvano, Bari (IT) Pavlovich Christian, Baltimore, Maryland (USA) Pepe Pietro, Catania (IT), Rocco Bernardo, Modena (IT) Salomon George, Hamburg (GE) Schiavina Riccardo, Bologna (IT), Scattoni Vincenzo, Milano (IT) Volpe Alessandro, Novara (IT), Waltz Joachen, Marseille (FR)

Andrology

Bettocchi Carlo, Bari (IT), Bitelli Marco, Roma (IT) Cai Tommaso, Trento (IT), Cormio Luigi, Foggia (IT) Fusco Ferdinando, Napoli (IT), Gontero Paolo, Torino (IT) Liguori Giovanni, Trieste (IT), Lotti Francesco, Firenze (IT) Pizzocaro Alessandro, Milano (IT), Trombetta Carlo, Trieste (IT)

Nephrology

Boscutti Giuliano, Trieste (IT), D’Amelio Alessandro, Lecce (IT), Fiorini Fulvio, Rovigo (IT), Gesualdo Loreto, Bari (IT), Granata Antonio, Agrigento (IT), Ranghino Andrea, Ancona (IT)

Radiology

Barozzi Libero, Bologna (IT), Bertolotto Michele, Trieste (IT) Giuseppetti Gian Marco, Ancona (IT), Giovagnoni Andrea, Ancona (IT), Valentino Massimo, Tolmezzo (IT)

Pathology

Beltran Antonio Lopez, Lisbon (PT) Fiorentino Michelangelo, Bologna (IT) Liang Cheng, Indianapolis (USA), Montironi Rodolfo, Ancona (IT)

Bio-Medical Engineering Wijkstra Hessel, Eindhoven (NL)

Co-Editor Editor-in-Chief

Official Journal of S.I.E.U.N.

General Information AIMS and SCOPE

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Contents 3

Giuseppe Martorana, Lorenzo Bianchi, Francesco Chessa, Marco Borghesi, Riccardo Schiavina, Eugenio Brunocilla

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Critical analysis of multiparametric RMI before and after radical prostatectomy conducted by the same radiologist: Comparison between pathological and radiological maps Erika Palagonia, Luca Leone, Francesca Sternardi, Alessia Cimadamore, Marco Fogante, Rodolfo Montironi, Andrea Giovagnoni, Lorenzo Montesi, Andrea Benedetto Galosi

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Advances in Urological Diagnosis and Imaging - 2019; 2, 1

REVIEW

Evolution of imaging in prostate cancer: The University of Bologna contribution

Giuseppe Martorana1, 2, Lorenzo Bianchi1, 2, Francesco Chessa1, 2, Marco Borghesi1, 2, Riccardo Schiavina1, 2, Eugenio Brunocilla1, 2 1 Department 2

of Urology, S. Orsola-Malpighi University Hospital, University of Bologna, (Italy); Department of Specialistic, Diagnostic and Sperimental Medicine (DIMES), University of Bologna, (Italy).

The diffusion of transrectal ultrasound (TRUS) has rapidly given rise to ultrasound-guided prostatic biopsy to detect prostate cancer (PCa). It is still considered today as being the gold standard for PCa diagnosis. However, TRUS has several diagnostic limitations. Over the years several methods of performing prostate biopsy have been proposed in order to improve cancer detection. There is a need to standardize the routine clinical practice both concerning the adoption of optimal imaging and the various therapeutic approaches in different phases of PCa history.

SUMMARY

Figure 1. Consensus Conference on prostate biopsy in Bologna (2005).

Hodge, et al.

Norberg, et al.

KEY WORDS: Imaging, prostate cancer, university of Bologna Besides prostate specific antigen (PSA) and digital rectal examination (DRE), the only imaging technique that has allowed the detailed study of the prostatic gland, over the last several years, has been transrectal ultrasound (TRUS).

As a consequence of good diagnostic performance and low economic impact, the worldwide diffusion of TRUS has rapidly given rise to ultrasound-guided prostatic biopsy to detect prostate cancer (PCa), which is still considered today as being the gold standard for PCa diagnosis (1).

However, TRUS has several diagnostic limitations (i.e overall accuracy of 50%) (2) and the PSA value remains the most important predictor of PCa in clinical settings. Of note, TRUS is routinely used as a guide for prostatic biopsy (random biopsy) in case of suspect PSA values. However, we should take into consideration that more than 50% of prostatic biopsies are useless (2). Over the years several methods of performing prostate biopsy have been proposed in order to improve cancer detection.

The Italian group for prostatic biopsy, during a Consensus Conference in 2005, proposed to standardize the techniques for prostatic biopsy (Figure 1). Take into account that random prostatic biopsy has some limitations: low detection rate (50%), low efficacy (high number of cores to diagnose PCa), under-staging and under-grading as compared to radical prostatectomy (RP) specimens.

To overcome these limitations, we proposed a novel ultra-

Eskew, et al.

Biopsia addizionale in prostata di più di 50g

Nava, et al.

Biopsia della zona di transizione diretta medialmente verso l’uretra con un angolo di 10°

Ravery, et al.

Biopsia addizionale in prostata di più di 50g

Babain, et al.

Prestim, et al.

Prostata finale a ottetto di tecnica bioptica della prostata

Naughton, et al.

Gore, et al.

Prelievo bioptico addi‐ zionale della zona di transizione in prostate di grandi dimensioni Schema bioptico con tasso di determinazio‐ ne ottimale

sound platform (F.E.M.M.I.N.A.) (5) that uses a specific software to elaborate different patterns of prostatic ultrasound to generate an algorithm (RULES = Radiofrequency Ultrasonic Local Estimators) to predict the presence of PCa (4) (Figure 2).

Advances in Urological Diagnosis and Imaging - 2019; 2,1

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G. Martorana, L. Bianchi, F. Chessa, M. Borghesi, R. Schiavina, E. Brunocilla Figure 2. FEMMINA algorithm to predict the presence of prostate cancer basing on ultrasound findings (Bertaccini A, Franceschelli A, Schiavina R, et al. A novel spectral ultrasonic differentiation method for marking regions of interest in biological tissues. In vivo preliminary results.

Archivio italiano di urologia, andrologia: organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica. 2007; 79(3):108-110.).

sion tomography (PET). Together with other centers, at the initial stage, the urology department of Bologna firstly defined the future perspectives and the role of these imaging techniques in PCa patients (Figure 3).

Even though both techniques proved to be similar in precision, spectroscopy MRI revealed more accurate (76%) compared to Choline PET/CT (67%) (6) in diagnosis and in local staging of PCa. For this reason, seeing as Choline PET/CT was however more accurate and efficient with respect to clinical nomograms, the Urology Department of Bologna focused its interest on aiming its use more towards detecting nodal or systemic metastases in primary staging and in detecting the site of PCa recurrence after primary treatment (7), which proved to be yet another major achievement for our Centre (Figure 4).

Choline PET/CT revealed to be slightly more accurate in predicting the presence of nodal metastasis in PCa patients submitted to RP with extended pelvic lymph nodedissection (8). However, according to current European guidelines (1), PET is not yet recommended for nodal and systemic staging in patients with intermediate and high risk PCa before radical treatment (1), due to its low accuracy rate, whilst it is recommended to detect nodal metastases before surgery in very high risk PCa patients (9) having a significantly higher accuracy compared to conventional imaging (86% vs 69%) (Figure 5). Contrarily, cross sectional imaging and bone scan are recommended. Recent evidence underlines how CT scan and bone scan have no role for PCa staging proposal, but, nevertheless, these traditional methods continue to be routinely used in patients with intermediate and high risk, as according to international guidelines….despite having a notably low accuracy rate…. it could be said that they are being utilized as “a defensive medicine”.

Concerning spectroscopy MRI, after initial encouraging Figure 3. Conference on prostate cancer imaging in Bologna (2004). results for diagnosis of PCa, after a few years this technique was progressively abandoned, due to elevated costs, time length of examinations and limited diffusion (Figure 6).

However, the knowledge acquired with the experience of spectroscopy MRI has given rise to the modern multiparametric MRI (mpMRI) (10). Moreover, the international definition and standardization of parameters essential to carry out accurate mpMRI exams has progressively given less feasibility to the role of spectroscopy in favour of anatomic phase (T2 weighed) and functional phases (diffusion and perfusion) (11). Thanks to this initial step, nowadays mpMRI represents the most accurate imaging technique to detect PCa. Notably, mpMRI is essential both for diagnostic proposal and for local staging proposal. In fact, mpMRI is able to precisely define the relaThe initial experience of 105 PCa patients submitted both tionship between the tumour and the prostatic capsule: to standard TRUS and this novel F.E.M.M.I.N.A. ultrasound this is essential in planning the correct surgical approach platform, confirmed a better alignment between the with respect to neurovascular bundle preservation. In this RULES algorithm (85%) and PCa revealed from RP specisetting, the use of mpMRI as a viable tool for surgical planmens, compared to standard TRUS (67%) (4). ning was able to significantly reduce positive surgical marFurthermore, since 2004 the contribution of Bologna in gins. Furthermore, in a series of 137 men referred to PCa imaging has been primarily focused on spectroscopy robotic prostatectomy, we found that the preoperative magnetic resonance imaging (MRI) (5) and positron emisuse of mpMRI was able to modify the nerve sparing

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Advances in Urological Diagnosis and Imaging - 2019; 2,1

Evolution of imaging in prostate cancer: The University of Bologna contribution Figure 4. Correlation between PET/CT and final pathology.

(Martorana G1, Schiavina R, Corti B, et al. 11Ccholine positron emission tomography/computerized tomography for tumor localization of primary prostate cancer in comparison with 12-core biopsy.J Urol. 2006; 176(3):954-60; discussion 960.).

Figure 5. Correlation between clinical nomograms and PET/CT for nodal metastases. (Schiavina R, Scattoni V, Castellucci P, et al. 11C-Choline Positron Emission Tomography/Computerized Tomography for Preoperative Lymph-Node Staging in Intermediate-Risk and High-Risk Prostate Cancer: Comparison with Clinical Staging Nomograms. European Urology. 8// 2008; 54(2):392-401.).

Figure 6. Magnetic Resonance Imaging with spectroscopy for prostate cancer (Testa C1, Schiavina R, Lodi R, et al. Prostate cancer: sextant localization with MR imaging, MR spectroscopy, and 11C-choline PET/CT. Radiology. 2007; 244(3):797-806).

Advances in Urological Diagnosis and Imaging - 2019; 2,1

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G. Martorana, L. Bianchi, F. Chessa, M. Borghesi, R. Schiavina, E. Brunocilla Figure 7. Utilization of mpMRI to improve nerve sparing approach during robotic prostatectomy (Schiavina R, Bianchi L, Borghesi M, et al. MRI Displays the Prostatic Cancer Anatomy and Improves the Bundles Management Before Robot-Assisted Radical Prostatectomy.

Journal of endourology/ Endourological Society. 2018; 32(4):315-321.).

Figure 8. Fusion prostate biopsy using Toshiba Aplio 500 system.

Figure 9. Targeted MRI-in bore prostate biopsy (Schiavina R, Vagnoni V, D'Agostino D, et al.

“In-bore” MRI-guided Prostate Biopsy Using an Endorectal Nonmagnetic Device: A Prospective Study of 70 Consecutive Patients. Clinical genitourinary cancer. 2017; 15(3):417-427.).

approach before surgery, in 50% of cases with appropriateness of 75% (12) (Figure 7).

Besides surgical planning, mpMRI is an essential tool for diagnostic proposal, due to significant higher sensitivity and specificity compared to random biopsy (10). In fact, in the near future each man with suspect PCa (even in cases of

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Advances in Urological Diagnosis and Imaging - 2019; 2,1

naïve biopsy) could be referred to mpMRI before prostate biopsy. So, men with negative mpMRI could be spared from potential side effects of random biopsy and potential diagnosis of not clinically significant PCa; while men with positive mpMRI could be referred to targeted biopsy with higher chances of correctly detecting the significant index lesion and an accurate diagnosis (13). In line with interna-

Evolution of imaging in prostate cancer: The University of Bologna contribution

tional literature, in our experience both fusion and in bore targeted biopsy were able to significantly improve detection rate of PCa (overall PCa and clinically significant PCa) compared to random biopsy (14) (Figures 8, 9).

Another important issue in PCa, is how to detect PCa recurrence, since an accurate and early detection of cancer recurrence would result in higher chances of curing patients. In fact, by the time conventional imaging is able to identify the site of recurrence, the PSA levels are already too high, and we risk missing the possibility of taking curable action (15). The main goal of modern imaging is to identify the site of recurrence for low PSA levels (16).

In fact, the main advantage of Choline PET/CT compared to conventional imaging, is to localize PCa relapse even at a low PSA level. Besides PSA levels, we found that the detection rate of Choline PET/CT is influenced by PSA doubling time and PSA velocity (17) (Figure 10).

However, in our experience of more than 4000 Choline PET/CT scans we can conclude that the overall detection rate of Choline PET/CT is suboptimal since it is roughly 50% (18).

Consequently, in collaboration with our local Nuclear Medicine Department, we tested novel tracers for PET

scan, other than Choline. For example, FACBC or fluciclovine revealed similar detection rates but higher sensitivity for PSA < 1 ng/ml, compared to Choline PET/CT in a prospective trial (19, 20) (Figure 11).

Finally, we contributed to the diffusion of the PSMA PET/CT, which nowadays represents the most accurate imaging in identifying the site of PCa recurrence, even in cases of PSA < 1 ng/mL, having a high clinical impact in changing the therapeutic strategy (21) since it is able to Figure 11. Fluciclovine PET/CT in restaging prostate cancer: example of nodal metastasis (Nanni C, Schiavina R, Boschi S, et al.

Comparison of 18F-FACBC and 11C-choline PET/CT in patients with radically treated prostate cancer and biochemical relapse: preliminary results. European journal of nuclear medicine and molecular imaging. 2013; 40 Suppl 1:S11-17).

Figure 10. Multiple nodal metastasis detected at 11C Choline PET/CT (Castellucci P, Fuccio C, Nanni C, et al. Influence of trigger PSA and PSA kinetics on 11C-Choline PET/CT detection rate in patients with biochemical relapse after radical prostatectomy. Journal of nuclear medicine: official publication, Society of Nuclear Medicine.

2009; 50(9):1394-1400.).

Figure 12. PSMA PET/CT in restaging prostate cancer: example of nodal metastasis (Ceci F, Uprimny C, Nilica B, et al.

(68) Ga-PSMA PET/CT for restaging recurrent prostate cancer: which factors are associated with PET/CT detection rate?

European journal of nuclear medicine and molecular imaging.

2015; 42(8):1284-1294.).

Advances in Urological Diagnosis and Imaging - 2019; 2,1

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G. Martorana, L. Bianchi, F. Chessa, M. Borghesi, R. Schiavina, E. Brunocilla

correctly identify even unusual sites of metastases or low volumes of metastatic spread (22-24).

Thus, the advent of PSMA PET/CT has led to the treatment of a consistent proportion of patients, who would have otherwise been referred to palliative androgen deprivation therapy, with metastases directed therapies (such as salvage lymph node dissection and targeted radiotherapy to lymph nodes or to bone lesions) (22, 25) therefore potentially delaying the introduction of hormonal therapy and prolonging survival (26) (Figure 12).

Thus, taking into account such different imaging techniques available for PCa patients, there is a need to standardize the routine clinical practice both concerning the adoption of optimal imaging and the various therapeutic approaches in different phases of PCa history. For this reason, following other international experiences, in 2014 the Prostate Cancer Unit (a multidisciplinary team including urologists, radiation oncologists, medical oncologists, nuclear medicine physicians, radiologists and pathologists) was established in Bologna to discuss weekly the best options for each PCa patient (Figure 13).

Moreover, the continuous exchange of experience and knowledge between different physicians has given rise to several perspectives for clinical studies. For example, some local and multicentric protocols are ongoing: randomized control trial to evaluate the role of mpMRI for the early re-classification of men with low and very low risk PCa during active surveillance protocols, strict PSA surveillance and early salvage radiotherapy vs. adjuvant radiotherapy in men referred to RP with adverse pathologic characteristics, use of GhRN antagonist (JNY-56021927) vs. placebo in high risk PCa patients undergoing primary radiotherapy.

Looking towards the future, in collaboration with the local Bioengineering Laboratory, the prostatic mpMRI imaging can be elaborated with dedicated, specific software and 3D models can be created and printed including prostatic gland, prostatic capsule, neurovascular bundle and the tumour (Figures 14, 15).

This should improve the knowledge of the tumour correlated with the healthy tissue (prostatic capsule and neurovascular bundle) for better surgical planning before RP. Furthermore, we are developing the realization of enhancing robotic surgery: the 3D virtual models elaborated from mpMRI images can be introduced inside the DaVinci surgical system to augment the normal 3D intraoperative vision with the overlapping 3D virtual model of the prostate and the tumour (Figure 16).

This should improve the intraoperative knowledge of the anatomy of prostatic glands related to the tumour, in order to meliorate the surgical dissection with adequate safe dissection in the areas surrounding the tumour and subsequent optimal preservation of neurovascular bundle in order to reduce the positive surgical margins rate and to improve the erectile function recovery.

3. Bertaccini A, Franceschelli A, Schiavina R, et al. A novel spectral ultrasonic differentiation method for marking regions of interest in biological tissues. In vivo preliminary results. Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica. 2007; 79(3):108-110.

4. Bertaccini A, Franceschelli A, Schiavina R, et al. Accuracy of a new echographic method (RULES, radiofrequency ultrasonic local estimators) in prostate cancer diagnosis. Anticancer research. 2008; 28(3B):1883-1886.

5. Testa C, Schiavina R, Lodi R, et al. Accuracy of MRI/MRSI-based transrectal ultrasound biopsy in peripheral and transition zones of the prostate gland in patients with prior negative biopsy. NMR in biomedicine. 2010; 23(9):1017-1026.

6. Martorana G, Schiavina R, Corti B, et al. 11C-choline positron emission tomography/computerized tomography for tumor localization of primary prostate cancer in comparison with 12-core biopsy. J Urol.

2006; 176(3):954-960; discussion 960.

7. Testa C, Schiavina R, Lodi R, et al. Prostate cancer: sextant localization with MR imaging, MR spectroscopy, and 11C-choline PET/CT. Radiology. 2007; 244(3):797-806.

8. Schiavina R, Chessa F, Borghesi M, et al. State-of-the-art imaging techniques in the management of preoperative staging and re-staging of prostate cancer. International journal of urology: official journal of the Japanese Urological Association. 2018.

9. Schiavina R, Scattoni V, Castellucci P, et al. 11C-Choline Positron Emission Tomography/Computerized Tomography for Preoperative Lymph-Node Staging in Intermediate-Risk and High-Risk Prostate Cancer: Comparison with Clinical Staging Nomograms. European Urology. 2008; 54(2):392401.

10. Schiavina R, Bianchi L, Mineo Bianchi F, et al. Preoperative Staging With (11)C-Choline PET/CT Is Adequately Accurate in Patients With Very High-Risk Prostate Cancer. Clinical genitourinary cancer. 2018; 16(4):305-312e301.

11. Thompson J, Lawrentschuk N, Frydenberg M, et al. The role of magnetic resonance imaging in the diagnosis and management of prostate cancer. BJU international. 2013; 112Suppl2:6-20.

12. Vargas HA, Hotker AM, Goldman DA, et al. Updated prostate imaging reporting and data system (PIRADS v2) recommendations for the detection of clinically significant prostate cancer using multiparametric MRI: critical evaluation using whole-mount pathology as standard of reference. European radiology. 2016; 26(6):1606-1612.

13. Schiavina R, Bianchi L, Borghesi M, et al. MRI Displays the Prostatic Cancer Anatomy and Improves the Bundles Management Before Robot-Assisted Radical Prostatectomy. Journal of endourology/ Endourological Society. 2018; 32(4):315-321.

14. Radtke JP, Schwab C, Wolf MB, et al. Multiparametric Magnetic Resonance Imaging (MRI) and MRI-Transrectal Ultrasound Fusion Biopsy for Index Tumor Detection: Correlation with Radical Prostatectomy Specimen. Eur Urol. 2016; 70(5):846-853.

1. <EAU-Guidelines-Prostate-Cancer-2016.pdf>.

15. Schiavina R, Vagnoni V, D'Agostino D, et al. â&#x20AC;&#x153;In-boreâ&#x20AC;? MRI-guided Prostate Biopsy Using an Endorectal Nonmagnetic Device: A Prospective Study of 70 Consecutive Patients. Clinical genitourinary cancer. 2017; 15(3):417-427.

2. Guichard G, Larre S, Gallina A, et al. Extended 21-sample needle

16. Choueiri TK, Dreicer R, Paciorek A, et al. A model that predicts the

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Advances in Urological Diagnosis and Imaging - 2019; 2,1

Evolution of imaging in prostate cancer: The University of Bologna contribution Figure 13. Conference on novel prostate cancer imaging in Bologna (2016).

Figure 16. Prostate cancer unit meeting in Bologna (2017 and 2018).

Figure 14. ExactVuâ&#x201E;˘ Micro-ultrasound system (29MHz) for prostate cancer detection.

probability of positive imaging in prostate cancer cases with biochemical failure after initial definitive local therapy. J Urol. 2008; 179(3):906-910; discussion 910.

17. Castellucci P, Ceci F, Graziani T, et al. Early biochemical relapse after radical prostatectomy: which prostate cancer patients may benefit from a restaging 11C-Choline PET/CT scan before salvage radiation therapy? Journal of nuclear medicine: official publication, Society of Nuclear Medicine. 2014; 55(9):1424-1429.

18. Castellucci P, Fuccio C, Nanni C, et al. Influence of trigger PSA and PSA kinetics on 11C-Choline PET/CT detection rate in patients with biochemical relapse after radical prostatectomy. Journal of nuclear medicine: official publication, Society of Nuclear Medicine. 2009; 50(9):1394-1400.

Figure 15. 3D virtual and physic printed model of prostate, prostate cancer and neurovascular bundle to improve anatomical knowledge and nerve sparing dissection.

19. Graziani T, Ceci F, Castellucci P, et al. (11)CCholine PET/CT for restaging prostate cancer. Results from 4,426 scans in a single-centre patient series.

European journal of nuclear medicine and molecular imaging. 2016; 43(11):1971-1979.

20. Nanni C, Schiavina R, Boschi S, et al. Comparison of 18F-FACBC and 11C-choline PET/CT in patients with radically treated prostate cancer and biochemical relapse: preliminary results. European journal of nuclear medicine and molecular imaging. 2013; 40 Suppl 1:S11-17.

21. Schiavina R, Ceci F, Borghesi M, et al.The dilemma of localizing disease relapse after radical treatment for prostate cancer: which is the value of the actual imaging techniques? Current radiopharmaceuticals.

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G. Martorana, L. Bianchi, F. Chessa, M. Borghesi, R. Schiavina, E. Brunocilla 22. Farolfi A, Ceci F, Castellucci P, et al. (68)Ga-PSMA-11 PET/CT in prostate cancer patients with biochemical recurrence after radical prostatectomy and PSA <0.5 ng/ml. Efficacy and impact on treatment strategy. European journal of nuclear medicine and molecular imaging.

2018.

23. Schiavina R, Ceci F, Romagnoli D, et al. (68)Ga-PSMA-PET/CTGuided Salvage Retroperitoneal Lymph Node Dissection for Disease Relapse After Radical Prostatectomy for Prostate Cancer. Clinical genitourinary cancer. 2015; 13(6):e415-417.

24. Maurer T, Weirich G, Schottelius M, et al. Prostate-specific mem-

brane antigen-radioguided surgery for metastatic lymph nodes in prostate cancer. Eur Urol. 2015; 68(3):530-534.

25. Ceci F, Uprimny C, Nilica B, et al. (68)Ga-PSMA PET/CT for restaging recurrent prostate cancer: which factors are associated with PET/CT detection rate? European journal of nuclear medicine and molecular imaging. 2015; 42(8):1284-1294.

26. Ost P, Reynders D, Decaestecker K, et al. Surveillance or Metastasis-Directed Therapy for Oligometastatic Prostate Cancer Recurrence: A Prospective, Randomized, Multicenter Phase II Trial.

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CORRESPONDENCE Lorenzo Bianchi Sant'Orsola-Malpighi Hospital University of Bologna - Bologna (Italy) E-mail: lorenzo.bianchi3@gmail.com Tel. 3392434221

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Advances in Urological Diagnosis and Imaging - 2019; 2,1

ORIGINAL

PAPER

Critical analysis of multiparametric RMI before and after radical prostatectomy conducted by the same radiologist: Comparison between pathological and radiological maps Erika Palagonia1, Luca Leone1, Francesca Sternardi2, Alessia Cimadamore3, Marco Fogante2, Rodolfo Montironi3, Andrea Giovagnoni2, Lorenzo Montesi1, Andrea Benedetto Galosi1 1Azienda

Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Clinica Urologica; Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Radiologia Pediatrica e Specialistica; 3Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Anatomia Patologica.

2Azienda

Introduction: We analysed revision by the same radiologist of the multiparametric magnetic resonance imaging (mpRMI) images after comparison with pathological sections after radical prostatectomy. Our objective is to evaluate the reliability of mpRMI in identification of prostate cancer (PCa) foci through the comparison with pathological report of index and not-index lesions using maps.

Materials and Methods: We evaluated 23 patients underwent radical prostatectomy in a single urological department.

All specimens have been reviewed by a single dedicated uropathologist. All mpRMI (1,5 T, 32 channels external coil) have been evaluated by a single dedicated radiologist. Two maps of cancer lesions have been created based respectively on pathological sections (gold standard) and mpRMI findings. Tumor volume and Prostate cancer grade group (GG) have been evaluated for each single cancer focus. Images have been newly reviewed by the same radiologist comparing the histological map after radical prostatectomy.

Results: In the sections of 23 radical prostatectomies were found 45 neoplastic foci: 23 index lesions (51,1%) and 22 satellite lesions (48,9%). 8 patients presented a monofocal tumor, 15 presented a multifocal tumor. GG1 was in 24 cases (53,3%), GG2 in 12 (26,7%), GG3 in 4 (8,9%), GG4 in 1 (2,2%) and GG5 in 5 (8,9%). 3 foci resulted with extra-prostatic extension (EPE). At mpRMI were found 46 areas (3 PI-RADS

SUMMARY

3, 29 PI-RADS 4 and 14 PI-RADS 5). 32 of these areas corresponded to PCa, 14 did not. The mpRMI identified 32 (71,1%) of 45 neoplastic foci, including 21 index lesions (91,1%) of 23 totals known. 13 tumoral foci (28,9%) were not individuated, including 11 (84,6%) clinically non-significant tumor (GG1, intra-capsular, volume < 0,5 cc) and 2 (15,4%) index lesions (1 GG4 and 1 GG5); no extra-prostatic extension (EPE) was identified in these cases. At the revision of mpRMI with the histological maps, we identified 3 foci more than pre-operative evaluation (respectively of GG 1, 4 and 5) and 2 of these were index lesions. PI-RADS 4 and PI-RADS 5 were assigned respectively in 2 and 1 case. After that the 77% of 45 total lesions found at pathological report and the all amount of tumoral foci not identifiable resulted not clinically significant.

Conclusions: In our experience, mpRMI can individuate the 71,1% of all tumoral foci and the 91,1% of index lesions. The 28.9% of cancer lesions not individuated are mainly clinically not significant, after revision this number drop at 23% with only non-significant tumors. False positives decreased after revision and they were in 78,6% located in the transitional zone and they were found to be inflammation in 71,4% of all cases.

In case of multifocality at mpRMI in different sections on the same side, sagittal sections are useful to characterizing lesions of longitudinal development in the same lobe.

KEY WORDS: mpRMI, prostate, cancer, pathology concordance.

INTRODUCTION Prostate cancer (PCa) is the most frequently diagnosed male malignant disease among men. The manifestation of PCa ranges from indolent to highly aggressive disease and, therefore, the actual challenge is to identify clinically significant cancers, in order to plan the right treatment.

Nowadays, the use of multiparametric Magnetic Resonance Imaging (mpMRI) has spread in the prostate imaging and has become reproducible through the reporting system and prostate imaging data (PI-RADS) (1). mpMRI allows the identification of prostate areas occu-

pied by suspected prostatic cancer and the subsequent target biopsy in those areas. Due to its importance in the non-invasive diagnosis of prostate cancer, mpMRI has become the first test to be offered to a patient with increased prostate specific antigen (PSA) before to submit the patient to the prostate biopsy (2).

Despite its increasing importance and use among urologist offices, mpMRI remains burdened by many errors of interpretation and classification of suspected areas.

Our aim is to compare the preoperative and post-operaAdvances in Urological Diagnosis and Imaging - 2019; 2,1

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tive mpMRI findings with the definitive pathological report after radical prostatectomy. Mainly we focused on the pathological relationship of the index and non-index lesions with subsequent revision, analyzed by the same radiologist, of the preoperative mpRMI images after.

We also microscopically analyzed the false positives highlighted by preoperative magnetic resonance imaging to identify areas that can be more easily confused with prostate cancer.

In our study, patientsâ&#x20AC;&#x2122; preoperative biopsies were not considered, as they were not part of the study design and also because of the variability of the data observed in the prereview collection.

MATERIALS

AND METHODS

We evaluated 23 patients underwent retropubic radical prostatectomy in a single urological institution. All specimens have been reviewed by a single dedicated uropathologist that reported all foci in a graphic map, describing for each focus the volume, the grade group (GG), the stage, the state of margins and the position in the gland.

All mpRMI exams (performed with a 1,5 Tesla machine

with a 32 channels external coil) have been evaluated by a single dedicated radiologist pre and post operation; sequences analysed are T1 and T2 anatomical imaging combined with one or more functional sequences of choice: dynamic contrast-enhanced (DCE), diffusionweighted imaging (DWI), apparent diffusion co-efficient (ADC) and MR spectroscopy (MRS). All identified lesions were registered on an 18-region prostate diagram, reporting the PI-RADS evaluated pre and post prostatectomy (Figure 1a, 1b). The graphic map of pathological exam was considered as gold standard and the mpMRI graphic map was compared (Figure 2).

In our study each focus was considered and evaluated as a single cancer. Foci not identified by the mpMRI were considered as false negative.

Suspected areas at mpMRI not reported by pathological exam were considered as false positives; the pathologist reviewed the specimens to identify the correspondent areas on the prostate, describing the microscopic aspect of those areas.

The histopathological graphic map reports localization and extension of each tumoral focus from apex to base of the prostate, eventually signalling extra-prostatic extension, positive surgical margins or seminal vesicles invasion.

Figure 1a, b. Histological maps, representing sections of prostate with coloured in black prostate cancer, the arrow indicates positive margin and asterisk the extra-prostatic extension of tumor.

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Critical analysis of multiparametric RMI Figure 2. Histological map in red shows the extension and localization of prostate cancer. In black and numbered radiological map from mpMRI imaging shows radiological findings.

PI-RADS 5 were assigned respectively in 2 and 1 case by the same radiologist.

The 10 tumoral foci not identifiable of all 45 were all included in not clinically significant prostate cancer lesion (Grade Group 1, intra-capsular and volume < 0,5 cc). 23% therefore belong to non-aggressive tumors, which can be controlled by active surveillance.

The 14 false positives of 46 suspicious described areas (30%) on mpRMI were classified in 11 PI-RADS 4 and 3 PI-RADS 3, all of these lesions were reviewed by pathologist. In 10 cases was found inflammation (71,4%) and cysts (including 1 haemorrhagic cyst) in 4 cases (28,6%); these lesions were in the transition zone in 11 cases (78,6%).

Where is not common to find an aggressive tumor.

After radiological revision these 14 false positives became 5 cases, all of them classified in PI-RADS 4 and including 2 (40%) located in the posterior base and 3 (60%) in the transitional zone. In 9 of the false positive were recognised after comparison the absent of suspicious cancer area (no PI-RADS 3, 4 or 5).

In 6 cases (18,7%) suspicious areas located in different planes on the same side were identified at mpRMI and described as discontinuous; at pathological report these foci were described as single foci not discontinuous, from base to apex. At radiological revision, through sagittal reconstructions, it was possible identify the continuity of these lesions. This was an important aspect that changes the point of view of the radiologist, placing more on a three-dimensional perspective.

DISCUSSION

RESULTS In the sections of 23 robotic and retropubic radical prostatectomies were found 45 neoplastic foci: 23 index lesions (51,1%) and 22 satellite lesions (48,9%). 8 patients presented a monofocal tumor, 15 presented a multifocal tumor.

We observe for each single focus Prostate cancer grade group: GG1 was in 24 cases (53,3%), GG2 in 12 (26,7%), GG3 in 4 (8,9%), GG4 in 1 (2,2%) and GG5 in 5 (8,9%).

3 foci of 45 resulted with extra-prostatic extension (EPE).

We didn’t find seminal vesicles invasion (Stage T3b).

At mpRMI were found 46 areas divided following PI-RADS classification in: 3 Pi-rads 3, 29 PI-RADS 4 and 14 PI-RADS 5. 32 of these 46 areas corresponded to PCa, 14 did not.

The mpRMI identified 32 (71,1%) of 45 neoplastic foci recognised in histopathological section, including 21 index lesions (91,1%) of 23 totals known. 13 tumoral foci (28,9%) of 45 were not individuated, including 11 (84,6%) clinically non-significant tumor (GG1, intra-capsular, volume < 0,5 cc) and 2 (15,4%) index lesions (1 GG4 and 1 GG5); no EPE was identified in these cases.

At the revision of mpRMI imaging with the histological maps, we identified 3 foci more than pre-operative evaluation (respectively of Grade group 1, 4 and 5) and 2 of these were index lesions. Exactly the 77% (35 foci) of 45 total lesions found at pathological report. PI-RADS 4 and

The aim of this radiological exam in the clinical practise is actually to maximizing the efficient detection of clinically significant disease, reducing the detection of clinically insignificant disease. Compared to the past decades, mpMRI has increased the diagnosis of prostate cancer, identifying approximately 92% of the index lesions (3).

Our study confirmed this high accuracy, resulting in 100% of significant-cancer detection. Furthermore, the majority of not recognized tumors at preoperative and postoperative mpMRI, is represented by “clinically insignificant” cancers.They are characterized histologically by Gleason Score 6, tumor volume < 0,5 cc and intraprostatic disease (4).

This is an important result because we expect that a negative mpMRI is useful to exclude an aggressive disease and, at the same time, to reduce overdiagnosis and over-treatment.

Another result of our experience is the identification of radiologist’s mistakes, correlated in particular with the location of the focus in the transition zone (5, 6) or in the identification of multiple suspected areas resulted the same cancer. This result in the clinical practise can help us in predict the location of the neoplasm in the gland also without the use of a fusion-software in a setting of cognitive fusion biopsy.

In our study it also appeared that, after the radiologist’s review, many false positives were still recognized as PI-RADS 3 areas. This is the big limit of this exam because many patients underwent prostate biopsy because of these results. We know from the literature that currently Advances in Urological Diagnosis and Imaging - 2019; 2,1

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E. Palagonia, L. Leone, F. Sternardi, A. Cimadamore, M. Fogante, R. Montironi, A. Giovagnoni, L. Montesi, AB. Galosi

the best strategy for managing patients with indeterminate lesions to mpMRI is based on strict surveillance using PSA monitoring and repeated mpMRI, to reduce the number of biopsies and the risk of overdiagnosis (7), but at the preoperative diagnosis with mpMRI the number of false positives is still about 30% than all lesions. Logically this can lead to overdiagnosis and over-treatment, but after revision this number has dropped to 23%, with only non-significant tumors.

The limitation of our study are the small population and the absence of data related to the prostate biopsy of those patients.

The strength of our study is the systematic review of the specimens and of the mpMRI images from the same pathologist and radiologist. In fact, in a review presented in 2018

by Stabile, et al. however, it emerges that the limitations related to the use of the clinical practice of mpMRI are its limited availability, relatively high cost and the presence of interobserver variability among radiologists of different experience (8). So far, the advent of the PI-RADS score v.2 is expected to significantly improve standardization and reduce variability in interpretation and identification (9).

Unfortunately, in the literature there is a lack of data that confirmed the detection rate of magnetic resonance in the graphic comparison with the definitive pathological report, few centers of pathological anatomy report the data graphically. This feature allows the radiologist to have a graphic and three-dimensional map that can represent the tumor and that consequently allows a direct relationship with the preoperative mpRMI. We used this graph primarily to analyze the role of resonance to detect significant tumor lesions.

The future role of mpMRI in the presurgical decision-making process of radical prostatectomy is emerging widely, mpMRI can help to change the initial surgical plan, according to clinical decision-making. Furthermore, as also evidenced by our data, the use of a targeted bioptic approach can lead to a reduction in the probability of diagnosis of a clinically insignificant disease, without however significantly modifying the detection of a disease considered significant.

CONCLUSIONS In our experience, mpRMI can individuate the 71,1% of all cancer foci and the 91,1% of all index lesions. Our results are similar to the current literature (3). The 84% of cancer lesions not individuated are clinically not significant.

The critical analysis of mpRMI led to identify lesions not identified at initial evaluation (2 of 23 index and 1 of 11 not index). 23% of neoplastic foci remains unidentifiable also after revision, in this study they represent in all cases clinically not significant cancer.

We also noticed that in case of multifocality at mpRMI in different sections on the same side, sagittal sections are useful to characterizing lesions of longitudinal development in the same lobe.

False positives were in 78,6% located in the transitional zone and they were found to be inflammation in 71,4% of all cases. They have decreased after radiological revision from 14 to 5, all of them indicated like PI-RADS 4.

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Considering the data analysed before the radiologist's review, we can state that the magnetic resonance imaging confirms its importance in the preoperative phase and that, despite the 28,9% of unidentified lesions that are mainly non-significant tumors, this doesn’t change the sensitivity of the magnetic resonance imaging in significant tumors.

REFERENCES 1. Kumar V, Bora GS, Kumar R, Jagannathan NR. Multiparametric (mp) MRI of Prostate Cancer. Prog Nucl Magn Reson Spectrosc [Internet].

2018; Available from: https://doi.org/10.1016/j.pnmrs.2018.01.001 2. Heidenreich A, Bastian PJ, Bellmunt J, et al. EAU guidelines on prostate cancer. part 1: screening, diagnosis, and local treatment with curative intent-update 2013. Eur Urol. 2014; 65(1):124-37.

3. Shah TT, To WKL, Ahmed HU. Magnetic resonance imaging in the early detection of prostate cancer and review of the literature on magnetic resonance imaging-stratified clinical pathways. Expert Rev Anticancer Ther. 2017; 17(12):1159-68.

4. Galosi AB, Lacetera V. [Small volume (< 0.5 cc) prostate cancer: characteristics and clinical implications]. Urologia. 2009; 76(4):236-41.

5. Noguchi M, Stamey TA, Neal JE,Yemoto CE. An analysis of 148 consecutive transition zone cancers: clinical and histological characteristics.

J Urol. 2000; 163(6):1751-5.

6. Delongchamps NB, Rouanne M, Flam T, et al. Multiparametric magnetic resonance imaging for the detection and localization of prostate cancer: combination of T2-weighted, dynamic contrast-enhanced and diffusion-weighted imaging. BJU Int. 2011; 107(9):1411-8.

7. Gómez Rivas J, Giganti F, Álvarez-Maestro M, et al. Prostate Indeterminate Lesions on Magnetic Resonance Imaging&#x2014; Biopsy Versus Surveillance: A Literature Review. Eur Urol Focus [Internet].

2019; Available from: https://doi.org/10.1016/j.euf.2018.02.012 8. Stabile A, Giganti F, Emberton M, Moore CM. MRI in prostate cancer diagnosis: do we need to add standard sampling? A review of the last 5 years. Prostate Cancer Prostatic Dis [Internet]. 2018; 21(4):473-87.

Available from: https://doi.org/10.1038/s41391-018-0071-8 9. Weinreb JC, Barentsz JO, Choyke PL, et al. PI-RADS Prostate Imaging - Reporting and Data System: 2015, Version 2. Eur Urol. 2016; 69(1):16-40.

Declaration of interest The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.

CORRESPONDENCE Erika Palagonia Clinic of Urology, Polytechnic University of the Marche Region AOU Ospedali Riuniti of Ancona, School of Medicine, United Hospitals, Via Conca 71, I−60126 Ancona erika.palagonia@gmail.com

ORIGINAL

PAPER

Fusion Ultrasound guided prostate biopsy (MRI/US): Our preliminary experience with a rigid software platform Andrea Fabiani1, Alessandra Filosa2, Emanuele Principi3, Lucilla Servi4 1

Section of Urology ASUR Marche Area Vasta 3, Macerata Hospital, (Italy); Section of Pathological Anatomy, Department of Clinical Pathology, Area Vasta 3, ASUR Marche, Macerata Hospital, (Italy); 3 Surgery Dpt, Section of Urology ASUR Marche Area Vasta 3, Macerata Hospital, (Italy); 4 Surgery Dpt, Chief of Section of Urology ASUR Marche Area Vasta 3, Macerata Hospital, (Italy).

2

Introduction and Objective: Definitive diagnosis of prostate cancer is performed using tranrectal or transperineal ultrasound guided biopsy. Recent developments are made in Resonance Imaging (MRI) in the diagnosis.

In particular, MRI demonstrated ability to detect central and anterior prostate cancers that went undetected on random biopsies. The last evolution of MRI-targeted prostate biopsies was to fuse mpMRI to a real time TRUS image. In this way, MRI can be used to localize a tumor and TRUS can be used to guide the needle. Herein, we present our preliminary experience with a rigid system platform for MRI/US fusion prostate biopsy.

Material and methods: 42 consecutive patients with suspected prostate cancer (PCa) underwent prostate biopsy using PercuNav® system (Philips, Bethesda, Maryland, USA). We divided the patients into 2 groups: patients with a previous negative mapping underwent to a MRI/US fusion re-biopsy (Group A); and biopsy-naïve patients who underwent to a first MRI/US fusion prostate biopsy (Group B). Group A (21 patients): mean age 67,8 years (CI 50-85), mean PSA = 9.99 ng/ml (CI 4.6321.76); mean prostate volume 79,7 ml(CI 17-160), Digital Rectal Examination (DRE) positive in 3/21, mean total cores 9 (CI 218). Group B (22 patients): mean age 67,5 years (CI 55-80), mean PSA= 7.61 (1,33- 27.39); mean prostate volume 61,6 ml (18-110), DRE positive in 4/21, mean total cores 9,1 (CI 2-18).

Results: Patients’ mean age was 51.3±16.7. ED was the predominant disorder in 73.2% of patients, followed by penile pain and length loss in 19.5% and 7.3% of patients, respectively.

32(78.1%) patients showed the pattern 1, 6(14.6%) pattern 2, and 3(7.3%) pattern 3. Plaques size varied from 3 to 13 mm. The penile hemodynamic response to CDU reported abnormal findings distally to the septal plaques in 20 patients (< 25 cm/sec).

Median left and right cavernosal artery flows measured a peak systolic velocity of 31 cm/sec and 33 cm/sec, respectively.

Conclusion: We believe that an US study with CDU provides a way to characterize, localize, and deliver treatment choice in patients with Peyronie’s Disease.

SUMMARY

KEY WORDS: Prostate, biopsy, fusion, multiparametric MRI, ultrasound.

No conflict of interest declared.

INTRODUCTION Definitive diagnosis of prostate cancer is performed using core-needle biopsies obtained transrectally or transperineally. The most common means of guiding prostate biopsies is conventional “B-mode” transrectal ultrasound imaging (TRUS). However, TRUS does not reliably distinguish between cancerous and noncancerous tissue in the prostate. However, the systematic prostate biopsy lacks sensitivity as well as grading accuracy. Recent developments are made in Resonance Imaging (MRI) in the diagnosis of prostate cancer (PCa). In particular, MRI demonstrated ability to detect central and anterior prostate cancers that went undetected on random biopsies (1).

The inclusion of two or more MRI parameters-T2 weighted, DWI, MRSI, and DCE MRI-became known as multiparametric MRI (mpMRI), and many studies demonstrated improved detection and localization of prostate cancers when two or more of these parameters were positive.

However, because each individual MR technique has its own shortcomings, the mpMRI combines the benefits of each individual MRI sequence in order to provide the greatest sensitivity and specificity for cancer foci (2).

Three approaches have emerged that utilize MRI information for guiding targeted prostate biopsies. The direct “in bore” MR biopsies, the “so called” cognitive fusion, and the MRI/US fusion via software-based image co-registration without requiring the MRI to be physically present (3).

The last evolution of MRI-targeted prostate biopsies was to fuse mpMRI to a real time TRUS image. In this way, MRI can be used to localize a tumor and TRUS can be used to guide the needle much like the cognitive technique.

Furthermore, because TRUS is already used to guide random biopsies, MRI-US fusion does not alter the normal workflow of urologists who typically perform the biopsy.

The patient is in a far more comfortable environment and often only local anesthetic is required. This method is rapidly evolving, with the major technical hurdle involving the “registration” of the MRI to the ultrasound image.

Because the prostate on MRI (with or without an Advances in Urological Diagnosis and Imaging - 2019; 2,1

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endorectal coil) often differs in shape and deformation from the same prostate on TRUS, some method of image registration must take place for successful fusion.

This process can involve the identification of landmarks (e.g. points, curves, surfaces) which can be recognized on both corresponding images, thereby allowing the two images to become aligned through either a “rigid” or “elastic” transformation. Rigid transformations do not change the images themselves, but allow for translation and rotational variations between images, while elastic transformations account for the addition of local deformation, warping, or scale changes as well (3). Below we present our preliminary experience with a rigid system platform for MRI/US fusion prostate biopsy.

MATERIALS

AND

METHODS

From February to June 2018, we prospectively and consecutively collected the clinical and pathological data of the first 90 patients who underwent TRUS prostate biopsy using the PercuNav Philips fusion technique (MRI/US fusion) at the Urology Unit in Macerata Civic Hospital.

Of these, we considered only the 42 cases performed by the same operator so as to characterize the experience both as preliminary and personal.

We then submitted the patient data that comprise the subgroup of the case study to further subdivision. We evaluated two distinct groups. Patients with one or more prostate biopsy mapping (PBm) previously performed and negative for carcinoma and undergoing biopsy with our MRI/US fusion technique were included in group A. Figure 1. The biopsy target plannig.

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Patients never undergoing PBm and who underwent prostate biopsy with MRI/US fusion technique, they were included in group B. The MRI images were obtained from three different diagnostic centers and each suspected area was characterized according to the ESUR-PIRADS v2 global score system (4). A centralized revision of the images was not performed even if the preliminary identification of the regions of interest (ROI) in the mpMRI, if not preliminarily sent in the attached diagram by the radiologist, was carried out through a collegial revision with a local reference Radiologist. As said, the same operator carried out the 42 procedures subject to assessment. All biopsy samples were examined by the same urogenital pathologist and classified according to the 2005 International Society of Urological Pathology Modified Grading System (ISUP 2005) (5).

Prostate cores was obtained by a Tru-cut needle 18G allocated on an end-fire transrectal probe (end-fire needle access). Ultrasound machine was a Philips Affiniti 70.

We have standardized our MRI/US fusion technique using the PercuNav software following some basic steps.

STEP 1: preliminary evaluation also with the help of a Radiologist Colleague of the T2 weighted images of the MRI and identification of lesions; STEP 2: planning of the biopsy target on weighed T2w scans (Figure 1); STEP 3: with the patient in left lateral decubitus, application of the transducer to the patient and calibration of the magnetic field generated externally by the device (Figure 2); STEP 4: execution of TRUS in transversal scan with endfire probe and subsequent “fusion” of ultrasound image to

Fusion Ultrasound guided prostate biopsy (MRI/US): our preliminary experience with a rigid software platform Figure 2. The patient position in left lateral decubitus.The triangle indicates the magnetic field generator and the star indicates the tracking bracket.

Figure 4. The bioptic sampling.

Figure 3. The matching imaging.

MRI in weighted T2w scans, exploiting more frequently the urethra as a point of reference (Figure 3); STEP 5: execution of MRI/US targeted prostate fusion biopsy (Figure 4); STEP 6: possible execution of random biopsy samples where previously planned with the patient.

RESULTS In Table 1 are summarized the characteristics of the population considered. In group A, we included 21 patients already undergoing previous prostate bioptic mapping.

Mean age was 67.8 years (50-85), average PSA 9.99 ng/ml (4.63-21.76 ), average prostatic volume 79.7 ml (17-160).

DRE were positive in 3 of 21 patients. On average, patients underwent 1.3 prostate biopsy mapping (1-3), all with a negative outcome for neoplasm. The lesions iden-

tified by mpMRI were characterized with PIRADS 3 in 7 patients of 21 (33%), PIRADS 4 in 13/21 (62%), PIRADS 5 in 1/21 (5%). Group A patients received an average of 9 samples (2-18). In group B we have similarly included 21 patients, but they never underwent previous prostatic biopsy procedures. The mean age was 67.5 years (55-80), with a mean PSA of 7.61 ng / ml (1.33-27.39), positive DRE in 4 cases (19%), mean prostate volume 61.6 ml (18-110).

On average, each patient underwent 9.1 biopsy samples (2-18). PIRADS 3 lesions were reported in 33% of cases, PIRADS 4 in 57%, PIRADS 5 in 10% of cases.

As showed in Table 2, in the Group A the biopsy procedures lasted an average of 10 minutes (10-12). 9 cases of prostate carcinoma (42.8%) were diagnosed with diseases with significance criteria in 7 of 9 cases (78%). The average Gleason score was 7 (6-8). The percentage of cancers diagnosed on targeted biopsies was 100% (9/9), 3 in Advances in Urological Diagnosis and Imaging - 2019; 2,1

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DISCUSSION

Table 1. Patients characteristics.

RE-BIOPSY

PTS BIOPSY NAIVE

Improvements in imaging technology and screening methods have changed the way clinicians approach 21 21 Patients (n) in prostate cancer. The fact that there are many commercial options for fusion biopsy will drive 67,8 (50-85) 67,5 (55-80) Mean Age (years) future applications and refinement of the technol9,99 (4,63-21,76) 7,61 (1,33-27,39) Mean PSA (ng/ml) ogy. The PercuNav platform was the first office3/21 4/21 based fusion biopsy platform and was developed at DRE positives the National Institutes of Health in Bethesda, 1,3 (1-3) Mean number of previous PBm (n) Maryland, USA in collaboration with Philips Healthcare. Patient recruitment began in 2004 and 9 (2-18) 9,1(2-18) Mean numbers of cores (n) has since continued to undergo clinical testing and 79,7 (17-160) 61,6 (18/110) Mean prostatic Volume (ml) development (6). Biopsy needle localization and tracking data is recorded via an external magnetic 7/21 7/21 PI-RADS 3 field generator but the biopsy uses existing free13/21 12/21 PI-RADS 4 hand ultrasound technology. The biopsies are performed transrectally. Once the mpMRI data is load1/21 2/21 PI-RADS 5 ed onto the software platform and an initial TRUS sweep is performed, rigid image fusion is performed and clinicians are able to see both the MRI Table 2. Results. and US images move in real time. This allows for a lesion to be targeted on MRI but monitored via RE-BIOPSY PTS BIOPSY NAIVE TRUS for the course and depth of the needle to 10 (10-12) 13 (12-16) Mean operative time (min) ensure that it enters the suspicious area. Because biopsy still uses familiar freehand TRUS technology, 9/21 (42,8%) 12/21 (57%) Cancer detection rate training for this platform is primarily software7/9 (78%) 10/12 (83%) Significant tumors based and can be gained after only a few biopsy sessions (3). Initial data for the first 101 men who 7 (6-8) 7 (6-8) Mean Gleason score underwent biopsy on a research-based iteration of UroNav demonstrated that 89.5% of men with 9/9 (100%) 11/12 (92%) Total Tumors in targeted biopsies high suspicion lesions on MR were diagnosed with 0/9 4/12 (33%) Tumors in random biopsies PCa, with targeted cores detecting more PCa than 7/9 (78%) 10/12 (83%) standard 12-core TRUS cores (7). In 582 patients, Significant tumors in targeted Rais-Bahrami and collegues have demonstrated an biopsies (n) increasing correlation between mpMRI suspicion 3/9 2/12 PCa in PIRADS 3 and Gleason score with detection for Gleason ≥ 8 5/9 9/12 PCa in PIRADS 4 PCa showing a 98% sensitivity at the low-moderate cutoff and a 91% negative predictive value at 1/9 1/12 PCa in PIRADS 5 the moderate-high cutoff (8). Overall cancer detection rates are nearly equivalent for targeted versus systematic (80% vs 81%), but the addition of targeted cores to systematic cores markedly increased the detection rates of intermediate-high risk disease with 32% PIRADS 3 lesions, 5 in the case of PIRADS 4 lesion and 1 of patients upgraded after targeted biopsy. Furthermore, in the case of PIRADS 5 lesions. No neoplasia was detecttargeted cores detected clinically significant disease (bioped in the bioptic cores coming from areas of the prostate sy Gleason Score ≥ 4+3) in 18% of patients with negative not characterized by mpMRI lesions and therefore persystematic biopsies, while systematic cores detected 8% of formed randomly, not targeted. Significant tumors were Gleason ≥ 4+3 cases missed by targeted biopsy (9). Thus, 7/9 (78%). In Group B, the average duration of the prostratification of low-risk versus high-risk PCa patients is cedures was 13 minutes (12-16). The detection rate of possible and may help minimize the number of biopsy sescancer was 57% (12/21), with a total of 10 significant sions a patient undergoes while also strengthening confitumors (83%; 10/12) and an average Gleason score of 7 dence in biopsy results, also important for active surveil(6-8). In 11 out of 12 cases (92%) the neoplasm was lance. However, more research is warranted to assess detected in targeted biopsies on injuries reported by patients with low-moderate MR lesion suspicions as well MRI, in 75% of cases with PIRADS 4, in 17% PIRADS 3 as further clarifying whether the improved performance of and in the remaining 8% of cases with PIRADS 5. In 4 targeted biopsy cores in diagnosing PCa is due to cases (33%) a neoplasm was detected even in non-tarimproved sampling techniques or as a result of improved geted biopsies performed in addition to the targeted localization from the imaging findings. ones.

The present case study should be considered as our preNo significant complications were reported in either group liminary experience in the use of one of the various (fever, urine retention, urinary sepsis, hospitalization).

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Fusion Ultrasound guided prostate biopsy (MRI/US): our preliminary experience with a rigid software platform

MRI/US fusion biopsy platforms currently available on the market. The considerations we can make about the results obtained do not have the pretension of proving the superiority of this technique over the others. It is a question of assessing the initial impact of the use of this technology in the field of prostate cancer diagnostics in our Urological Section. The choice in the purchase the PercuNav System was oriented by the need to have a technology that would improve the discrete diagnosis rate of prostate cancer (48.48%), as shown by a recent statistical analysis performed on a sample of the first TRUS prostate biopsy setting with end fire probe (10), looking for the best compromise between accuracy, reproducibility and feasibility in everyday outpatient clinical practice. Our goal was therefore to evaluate the adherence of the first results obtained to the aforementioned expectations and needs. In order to eliminate confounding factors as much as possible, despite the fact that 90 patients underwent MRI/US fusion biopsy during the period under examination, we considered only the 42 procedures performed by the same operator and evaluated by a single pathologist. Patients were classified according to the referred previous PBm. There was no differences in terms of age between the two groups with a mean PSA that is higher for patients who have already undergone biopsy procedures. It is evident that in these cases, the indication to the execution of mpMRI and to the subsequent MRI/US fusion, has been placed on the basis of the finding of a progressive increase in the PSA values. In total, there was 7 patients of the 42 assessed (16%) those in whom the indication to PB could have been placed only on the basis of the clinical finding of a positive DRE. It is surprising that in the group of patients never previously subjected to PB, there have been 4 cases with a positive DRE, that would have represented for itself the absolute indication to a TRUS biopsy, without the need for preliminary mpMRI. Evidently, the diffusion of the mpMRI method and the persistent fears of patients and general practitioners regarding the invasiveness and possible complications of TRUS biopsy have led to a divergence from the current indications to mpMRI in case of prostatic neoplastic pathology. This is the clinical scenario in which our preliminary experience in MRI / US fusion developed. In fact, we continued to perform a number of withdrawals, however high even in definable Biopsy-naive patients (group B), reserving the execution of targeted biopsies where there was a specific request from the patient (especially in case of motivations clinics appropriately discussed with the same) or in the case of a clear overlap between the clinical and instrumental data. The prostatic volume on which the procedures were performed tended to be higher in the group of patients in whom MRI/US fusion represented a re-biopsy. The datum is clearly explainable with the difficulty that the traditional method of prostatic transverse TRUS prostate biopsy, in particular in the first biopsies, it has to sample all the glandular volume extensively (11). Regarding the capacity of the PIRADS v2 system to characterize the suspect of a neoplastic lesion, we must observe that in the case studies of this evaluation there was adherence to the current guidelines with PIRADS values > 3 considered worthy of bioptic correlation. No PIRADS 2 was evidently consid-

ered as deserving of histological correlation. PIRADS 4 was by far the predominant figure (25/42; 59%). Positive biopsies were highlighted in 36% of PIRADS 3 (5/14); in 56% of PIRADS 4 lesions (14/25); and in 66% of the PIRADS 5 (2/3). Even in our preliminary and limited experience, therefore, there would seem to be a correlation between the probability of a positive biopsy outcome aimed at increasing PIRADS. However, it should be emphasized that the mpMRI investigations were not carried out in the same center but in three different structures which, although of known experience, still represent an element probably confusing the results, considering the inevitable subjectivity of the criteria considered in the PIRADS v2 system. We did not perform a centralization in the assessment of ROI but only an identification, preliminary to the procedure and guided by a local radiologist, of the images provided by the patients on compact disk, especially where the reporting radiologist did not provide a summary scheme. What has been, from the results obtained, the diagnostic accuracy of the method in the two groups under evaluation? The detection rate in the group of patients already undergoing biopsy procedures, was 42.8%, lower than the figure of our previous diagnostic experience (48.48%). However, these are not comparable percentages. In fact, in the 21 patients of group A, the diagnosis evidently had difficulties, likely related to the size and location of the lesions, so much so that previous mapping had failed to correlate the increase in PSA or the clinical data of a DRE. positive, with a prostate tumor pathology. This is indirectly shown by the fact that in 100% of cases the targeted biopsy in this group of patients has shown a neoplasm, which is more significant in 78% of cases. Therefore, the data of the global detection rate in this area loses its weight and cannot be compared with that related to the experience of our group in the first TRUS biopsies. On the other hand, an interesting result is that of the detection rate in the â&#x20AC;&#x153;biopsy-naiveâ&#x20AC;? group of patients, that is to say those subjects that have never before been subjected to prostate biopsy procedures. The detection rate was 57%, a much higher value than the aforementioned 48.48%. However, the existence of 4 cases with positive DRE should be considered, which could probably have been successful regardless of the fusion technique. By eliminating these cases from the calculation, we would have a global detection rate of 47% which, although lower than the standard of our previous experience, in the absence of fusion, must take into account 33% of diagnosis performed in non-targeted biopsies and 83% of histological significance of diseases, always in targeted biopsies. The overdiagnosis in group B occurs only in 1 case out of 12 total (8%). The overdiagnosis in group A was instead of 22% (2/9). A recent systematic review (12) found that targeted MRI/US fusion biopsies are able to detect more clinically significant cancers than standard techniques. The median detection rate for any type of cancer was 50.5% compared to 43.4% of the standard bioptic strategy. Our results show performances in line with these data (57% fusion vs. 48.48% standard), albeit with a notable superiority in terms of significance of the diseases diagnosed on targeted samples, with our 78% decidedly higher compared to 33.3 % of the

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A. Fabiani, A. Filosa, E. Principi, L. Servi

systematic review, in which, however, there are differences between the populations studied, especially in terms of the number of “naive biopsy” patient groups compared to those in which MRI / US fusion was a re- biopsy.

The use of the Philips PercuNav system, in this preliminary and personal experience, was reproducible. The end fire probe reproduces the methodological aspects of traditional TRUS biopsy with the need of only a few technical measures, mainly related to the implementation of the external magnetic field generator and the overlap of MRI and ultrasound images.The average execution time ranged from 10 to 16 minutes, remaining substantially constant during all the cases performed, characterizing the biopsy as fast and safe. The procedure is still a “free- hand” technique, so the operator’s experience remains crucial, especially to limit the image artifacts that could hinder the fusion, especially as regards the pressure of the probe on the rectal wall that could distort images and alter the location of the lens.

The present study presents some certain limitations.

The first is related to the number of patients taken into consideration, limited by the preliminary character of the experience. A protocol that standardizes the number of samples in the areas indicated by mpRMI has not been defined. Further limitation must be found in the failure to centralize the execution of the multi-parametric magnetic resonance, with relative lack of systematic reporting.

CONCLUSIONS In our preliminary experience, the use of the Philips UroNav system has shown encouraging results especially in the group of patients with persistent clinical and laboratory suspicion of carcinoma, representing a useful tool for overcoming the limitations inherent in the standard technique of systematic re-biopsy, allowing the reduction of false negatives, a better risk stratification, the reduction of the number of prostatic biopsy mapping and the lowering of over detection.

The technique, reproducible and feasible, also allows a high detection rate in case of first diagnostic approach.

We are not able to define the possibility that this technique ensures an accurate diagnosis of significant disease with a reduced number of samples so as to be able to omit the random mapping of the prostate.

Future studies are therefore indispensable, even comparative among the different software available on the market, which also identify the appropriate standards to be followed in clinical practice.

REFERENCES

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3. Logan JK, Rais-Baharami S, Turkbey B, et al. Current Status of MRI and Ultrasound Fusion Software Platforms for Guidance of Prostate Biopsies BJU Int. 2014; 114(5):641-652.

4. Greer MD, Brown AM, Shih JH, et al. Accuracy and agreement of PIRADSv2 for prostate cancer mpMRI: A multireader study. J Magn Reson Imaging. 2017; 45(2):579-585.

5. John S, Cooper S, Breau RH, et al. Multiparametric magnetic resonance imaging - Transrectal ultrasound-guided cognitive fusion biopsy of the prostate: Clinically significant cancer detection rates stratified by the Prostate Imaging and Data Reporting System version 2 assessment category. Can Urol Assoc J. 2018. doi: 10.5489/cuaj.5254. [Epub ahead of print] 6. Stamatakis L, Siddiqui MM, Nix JW, et al. Accuracy of multiparametric magnetic resonance imaging in confirming eligibility for active surveillance for men with prostate cancer. Cancer. 2013; 119(18):3359-66.

7. Pinto PA, Chung PH, Rastinehad AR, et al. Magnetic resonance imaging/ultrasound fusion guided prostate biopsy improves cancer detection following transrectal ultrasound biopsy and correlates with multiparametric magnetic resonance imaging. J Urol. 2011; 186:1281-5.

8. Rais-Bahrami S, Siddiqui MM, Turkbey B, et al. Usefulness of Multiparametric Magnetic Resonance Imaging Suspicion Levels in Detecting Prostate Cancer. J Urol. 2013; 190(5):1721-27.

9. Siddiqui MM, Rais-Bahrami S, Truong H, et al. Magnetic Resonance Imaging/Ultrasound-Fusion Biopsy Significantly Upgrades Prostate Cancer Versus Systematic 12-core Transrectal Ultrasound Biopsy. Eur Urol. 2013; 64(5):713-19.

10. Fabiani A, Principi E, Filosa A, Servi L.The eternal enigma in prostatic biopsy access route. Arch Ital Urol Androl. 2017; 89(3):245-246.

11. Galosi AB, Tiroli M, Cantoro D, et al. Biopsy of the anterior prostate gland: technique with end-fire transrectal ultrasound. Arch Ital Urol Androl. 2010; 82(4):248-252.

12. Valerio M, Donaldson I, Emberton M, et al. Detection of clinically significant prostate cancer using magnetic Resonance imaging ultrasound fusion targeted biopsy: a systematic review. Eur Urol. 2015; 68:8-19.

Authors’ contributions All authors participated in the design and conduct of the study. All authors reviewed and approved the final version of the manuscript.

CORRESPONDENCE Andrea Fabiani, MD, Surgery Dpt Section of Urology ASUR Marche Area Vasta 3

1. Komai Y, Numao N, Yoshida S, et al. High diagnostic ability of multiparametric magnetic resonance imaging to detect anterior prostate cancer missed by transrectal 12-core biopsy. J Urol. 2013; 190:867-73.

Macerata Hospital - Italy

2. Hegde JV, Mulkern RV, Panych LP, et al. Multiparametric MRI of prostate cancer: an update on state-of-the-art techniques and their performance in detecting and localizing prostate cancer. J Magn Reson Imaging. 2013; 37:1035-54.

Mobile: +393474865381

Advances in Urological Diagnosis and Imaging - 2019; 2,1

E-mail: andreadoc1@libero.it Phone: +3907332572507

ORIGINAL

PAPER

Ultrasound in dermatologic pathology of penile shaft: Unusual cystic lesions in the dorsal surface Andrea Fabiani1, Alessandra Filosa2, Giorgio Filosa3, Lucilla Servi4 1 2 3 4

Surgery Dpt, Section of Urology, ASUR Marche Area Vasta 3, Macerata Hospital, (Italy); Section of Pathological Anatomy, Department of Clinical Pathology, Area Vasta 3, ASUR Marche, Macerata Hospital, (Italy); Dermatologist, Past Chief of Dermatology Unit, Area Vasta 2 ASUR Marche, Carlo Urbani Hospital, Jesi (AN), (Italy); Surgery Dpt, Chief of Section of Urology, ASUR Marche Area Vasta 3, Macerata Hospital, (Italy).

There is a growing number of reports in the literature about the use of sonography to assess anatomic changes in different dermatologic entities. Skin diseases of male genitalia are fairly common and can mostly affect the psychological well being of males patients in all ages.

Elsewhere, male patients complaining of genital conditions initially may consult with urologists. We report four cases of unusual cystic lesions involving coronal sulcus and the internal foreskin in the penile dorsal surface. With these clinical cases presentation, we want to underline how the clinical and ultrasonographic evaluation are mandatory for the differential diagnosis. Especially in case of symptomatic lesion, a precise disease definition can be obtained only with excision and hysto-pathological examination.

Ultrasound may be considered as a first level of lesion typing, allowing to reassure the patient about the benignity or malignancy. Circumcision is mandatory in case of recurrence or when clinical findings are predictive for neoplasm. The close collaboration with dermatologist and pathologist may allow to a right management of these benign conditions.

SUMMARY

KEY WORDS: Penile lesions, epidermoid cyst, dermatologic ultrasound, circumcision.

a malignant lesion (1). We report four cases of unusual cystic lesion of penile dorsal surface and we discuss the diagnostic, ultrasound patterns and the therapeutic work-up.

MATERIALS

AND METHODS

We collected over the time the cases of unusual cystic lesions of the dorsal surface of the penile shaft. The patients referred to our clinical Department of Urology in the first instance. In each case, the diagnostic and therapeutic work up was conducted using close cooperation with a consultant Dermatologist (FG) and then, after surgical treatment, with a dedicated pathologist (FiA).

All ultrasound evaluation of skin lesions was performed with a linear probe, 12 Mhz frequency, ecocolordoppler machine BK Medical, by a single Urologist. Experienced in ultrasound (FA). All patient underwent to a physical examination. Whenever a careful proximal and remote pathological anamnesis was collected (LS, FA).

RESULTS CASE 1

INTRODUCTION Several different dermatologic conditions may affect the penis. In daily clinical practice, rashes and red patches, ulcers or problems with the foreskin can worry patients who often turn to the urologist in the first instance. The majority of penile dermatoses are benign. They can be managed conservatively. However, a small number of patients may present with pre malignant or even early malignant lesions of the penis. An ulcerated or keratinized aspect may mimic penile cancer. In order to allow early prompt curative treatment, it is important in these cases the immediate differential diagnosis between a benign and No conflict of interest declared.

A young man presented to our department with an asymptomatic ulcerated lesion on the dorsal surface of the penile coronal sulcus with a largest one side of 1 cm.

At the anamnesis he has no history of trauma, systematic diseases, phimosis, balanoposthitis or condilomatosis. His voiding and sexual functions were both normal. On physical examination, the lesion was a single, raised, no painfull reddish nodule, with an ulcerated surface and poorly defined borders. It was elastic and freely movable within the dermis; and was on the dorsal surface of the coronal sulcus of the penis (Figure 1). Superficial penile ultrasonography showed an anechoic subcutaneous structure separated from the erectile tissue with a connecting tract to the epidermal surface of the penis. On sonography the wall was intact and well-defined without inflammatory aspects (Figure 2).

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A. Fabiani, A. Filosa, G. Filosa, L. Servi.

Figure 1. The asymptomatic ulcerated lesion on the dorsal surface of the penile coronal sulcus with a largest one side of 1 cm in patient case 1.

Figure 2. Anechoic subcutaneous structure with a wall intact and well-defined, without inflammatory aspects; ultrasound features of Fig. 1. The arrow indicates the connecting tract to the epidermal surface, called â&#x20AC;&#x153;punctumâ&#x20AC;?.

Figure 3. The single squamous nodule with an ulcerated surface in case 2.

Figure 4. The dysomogeneous intradermal lesion of 15 mm in major diameter, with an hypo-anechoic central core containing an hyperechoic linear lesion (case 2).

Figure 5. The surgical excision of the cystic lesion in case 2.

CASE 2

A man aged 42 years presented complaining a lesion on the dorsal surface of the coronal sulcus of his penis onset from several years. The anamnesis was silent for any pathological event. On physical examination, the lesion was a single squamous nodule with an ulcerated surface.

It was no painfull, elastic and freely movable within the dermis and was on the dorsal surface of the coronal sulcus of the penis (Figure 3). Ultrasound evaluation with a linear probe 12 Mhz reveal a dysomogeneous intradermal lesion of 15 mm in major diameter, with an hypo-anechoic central core containing an hyperechoic linear lesion (Figure 4).

The patient undergone a surgical excision under local anesthesia (Figure 5).

The histological examination revealed an epidermoid cyst with the typical stratified squamous ephitelium and laminated keratin without skin appendages or germ cells

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(Figure 6). After three months, there is a recurrence of the lesion managed by circumcision with a sleeve technique (Figure 7). Hystopathological report was of a residual cystic lesion.

Ultrasound in dermatologic pathology of penile shaft: Unusual cystic lesions in the dorsal surface Figure 6. The hystopathological features of cystic lesion removed in patient 2.

CASE 3

A 18 years old man referred to our attention for an acute swelling of the penile shaft. On clinical examination prepuce and penile skin were reddish and aedematous. The prepuce was no retractable behind the glans. The penile ultrasound performed revealed a subcoronal dysomogeneous intradermal lesion with a multiple hyperecoic linear images (Figure 8). After antibiotics and anti-inflammatory therapy, the patient undergone circumcision with complete excision of a cystic lesion surrounded by chronic inflammatory infiltrate. After six months follow up, no relapses were diagnosed.

Figure 8. The subcoronal dysomogeneous intradermal lesion with a multiple hyperecoic linear images in case 3.

Figure 7. The preliminary dermographic definition of proximal excisional surgical margin in sleeve circumcision (case 2).

CASE 4

In the fourth case, a 75 years old man was admitted at our department to evaluate a painfull nodular lesion in the left dorsolateral surface of balano-preputial sulcus. The clinical examination revealed an erytematous nodule with hair protruding from (Figures 9a, 9b). Ultrasound study perFigure 9a, b. A nodule with hair protruding from (case 4).

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A. Fabiani, A. Filosa, G. Filosa, L. Servi.

Figure 10a, b. A cystic dermal lesion with a definition of an hair complex arising from cyst core (case 4).

formed confirm the classical features of a cystic dermal lesion with a definition of an hair complex arising from cyst core (Figures 10a, 10b). The patient refused a surgical lesion excision.

DISCUSSION Skin disease of male genitalia are fairly common and can affect patients of all ages. Yet, diagnosis and treatment can be challenging and unsatisfactory, particularly when dealing with non-venereal conditions. In developed countries, dermatologists and genitourinary physicians are the medical specialists that usually treat these disorders, but, elsewhere, male patients complaining of genital conditions initially may consult an urologist. However, due to a number of reasons, but mostly because of a paucity of reliable, comprehensive and easily accessible source of information, non dermatology specialists tend to overlook the genital and systemic signs and symptoms presented by these patients, potentially exposing them to the clinical consequences of suboptimal management of their conditions (2). In particular, the penis may be involved by several dermatological conditions. The majority of these are benign and harmless but they need a mandatory differential diagnosis with malignant or pre-malignant penile lesions. The prepuce may be an unusual location of pilonidal cysts (3-4) and, occasionally, hair may be seen protruding from the sinus tract orifice (Figure 10).

Cystic lesions are quite common in genital skin.The majority represent non neoplastic conditions, such as epidermal inclusion cyst (sebaceous cyst) and pilar cyst (5).

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The neoplastic cysts mostly correspond to benign appendage tumors, such as hydrocystomas, syringocystadenoma papilliferum, and trichofolliculoma. The cysts develop more frequently in the ventral surface of the coronal sulcus (6, 8), near to frenulum.

The aetiology is not clear.

Some authors have adduced that it may develop from abnormal closure of the median raphe during embryogenesis (5, 9). Some reports have suggested an acquired origin after mechanical implantation such as that involving an obstruction of eccrine ducts (10) or an injection of epidermal fragments (7). In these cases the coronal sulcus may act as a cleft where hairs may collect and are forced to penetrate into the penile shaft and foreskin by the natural movement that occurs between these two surfaces (6). The retention and inclusion of follicular products may be the first step for the development of the epidermoid cyst.Theoretically any surgical procedure may produce an epidermoid cyst, examples in literature are rhinoplasty, reduction mammoplasty, myocutaneous flaps where the cutaneous portion is buried, hypospadias repair, penil girth enanchement surgery and circumcision (5-7). Also the use of dermal grafts or needles for biopsy may result in this lesion (7); but fortunately acquired epidermoid cysts are not a common occurrence.

Macroscopically the cyst appeared to be full of a cheesy material (10) with negative cytology and culture results (5).

Histological examination revealed a lined wall with a layer of stratified squamous ephitelium and laminated keratin; it did not contain either skin appendages or germ cells (5).

Urothelium origin of such cysts can be documented by immunohistochemistry for cytokeratin 13 (7). Malignant aspect or transformation are rare. All reported cases of penile epidermoid cyst occurred on the ventral side of the penis. In our cases they was on the dorsal surface.

Cysts can have different length and size, they are usually solitary and painless, well-delimited, slow-growing, non tender and asymptomatic lesions (5); they rarely caused alteration in sexual or voiding functions. Cysts may be complicated by infection or trauma with pain (8). Penile epidermoid cysts can be diagnosed by a careful examination with evaluation by ultrasonography or computerized tomography (10). On sonography, if the cyst is intact, it can appear as a round anechoic structure in the subcutaneous tissue and in the dermis, separated from erectile struc-

Ultrasound in dermatologic pathology of penile shaft: Unusual cystic lesions in the dorsal surface

tures, with a connecting tract to the epidermal surface, called “punctum” (11) (Figure 2). Usually the wall is welldescribed. Occasionally they can be giant structures with brighter echoes and anechoic filiform areas inside, probably caused by accumulated keratin, calcium and colesterole crystals. When cysts are ruptured or ulcerated, they may have more different shapes; as irregular wall, inflammatory signs and infiltration of the surrounding tissues by cheesy material. Epidermoid cysts preserve the posterior acoustic enhancement artifact. On color-Doppler sonography peripherical tissues from the cyst can be characterized by an increased blood flow, often if they are inflammed or after cyst ruptured (11). Computerized tomography is rarely used. The differential diagnosis in this region included: carcinoma, urethrocutaneous fistula, pilonidal cyst, urethral diverticula, dermoid cyst, steatocystoma, teratoma (5, 6, 10, 12). Hystological examination, after excision, remain the only means of obtaining a precise disease definition. No cases of malignancy in cystic disease of the penis have been reported in literature. The indication for the surgical treatment are: secondary cystic infection, pain upon intercourse, cosmetic reasons, or obstruction of the urinary tract (5). The best treatment is complete excision, while aspiration, drainage or an incomplete surgery with residual tissue may carry a risk of recurrence and re-excision (9). Circumcision may be the best treatment especially in case of recurrence due to an incomplete excision.

If there is not a sign of malignancy, a simple observation could be a valid treatment option.

Circumcision is mandatory in case of recurrence or when clinical findings are predictive for neoplasm. The close collaboration with dermatologist and pathologist may allow to a right management of these benign conditions.

REFERENCES 1. Alnajjar HM, Shabbir Majiid, Watkin NA. Penile ulcer Problem based urology. Chapter 8 in Problem Based Urology. Springer. 2013. Gontero P, Kirby RS, Carson CC. Editors.

2. Rosenblatt A, De Campos Guidi HG, Belda W Jr. Male genital lesions The urological perspective Springer Heidelberg New York Dordrecht London. Preface page Vii e-book.

3. Rao AR, Sharma M, Thyveetil M, Karim OM. Penis: an unusual site for pilonidal sinus. Int Urol Nephrol. 2006; 38:607-608.

4. Sion-Vardy N, Osyntsov L, Cagnano E, et al. Unexpected location of pilonidal sinuses. Clin Exp Dermatol. 2009; 34:e599-e601.

5. Aslan Y, Balci M, Atan A. Idiopathic Penile Epidermoid Cyst in a Young Patient Eur J Surg Sci. 2011; 2(1):16-18.

6. Cormio L, Mancini V, Sanguedolce F, et al. Epidermoid cyst of the coronal sulcus mimicking penile cancer: a case report. J Med Case Rep. 2014; 8:179.

7. Saini P, Mansoor MN, Jalali S, et al. Penile Epidermal Inclusion Cyst.

Indian J Pediatr. 2010; 77(7):815-6.

8. De Mendonça RR, Silva JL, Wroclawski ML, et al. Mucoid cyst of the penis: Case report and literature review. Can Urol Assoc J., 2010; 4(6):E155-7.

CONCLUSIONS

9. Suwa M,Takeda M, Bilim V, et al. Epidermoid cyst of the penis: A case report and review of the literature. Int J Urol. 2000; 7(11):431-3.

This report describes four cases of unusual cystic lesions involving coronal sulcus and the internal foreskin in the penile dorsal surface. In our experience we consider clinical and ultrasonographic evaluation mandatory for the differential diagnosis. Excision and hysto-pathological examination remain the only means of obtaining a precise disease definition, especially in case of symptomatic lesion.

10. Yahya T. Case report: Epidermoid cyst of the penis. doi;10.1002/BJUIW-2011:140-web.

11. Ulrich J, Schwürzer- Voit M, Jenderka KV, et al. Sonographic diagnostics in dermatology Journal of German Society of Dermatology. 2014; 1083-1099.

12. Kalkan M., Şahin C, Özyılmaz S, Uçmakl E. Multiple Epidermoid Cysts of Penis. Eur J Gen Med. 2012; 9(Suppl 1):60-62.

Authors’ contributions All authors participated in the design and conduct of the study.

All authors reviewed and approved the final version of the manuscript.

CORRESPONDENCE Andrea Fabiani, MD Surgery Dpt, Section of Urology ASUR Marche Area Vasta 3 Macerata Hospital, Italy E-mail: andreadoc1@libero.it Phone: +39 07332572507 Mobile: +39 3474865381

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Ed _Cop+Ed+fisse 2006 04/10/18 11:28 Pagina IV

C ASE

REPORT

Evaluation and management of a renal sinus angiomyolipoma Simone Scarcella, Lucio Dell’Atti, Andrea Benedetto Galosi Department of Urology, Polytechnic University of Marche Region, University Hospital “Ospedali Riuniti”, Ancona, (Italy).

Angiomyolipoma (AML) is a tumour derived from three components: blood vessels, smooth muscle, and fat. Even though benign in most cases, it can present difficult management decisions. An AML originating from the renal sinus is extremely rare and difficult to differentiate from other fat containing masses. We present a case of a 56year-old woman referred to our department for a right kidney renal mass, originating from the renal sinus, diagnosed as an AML on the basis of the radiologic features consistent with fat tissue characterised by contrast enhancement. The patient was symptomatic for recurrent flank pain and considering the rapid growth of the mass, a surgical resection was planned.

Lesion margins were carefully identified with intra-operative ultrasonography and the mass removed without the need of vascular clamping. No post-operative complications occurred, the definitive histopathological examination confirmed a diagnosis of renal angiomyolipoma and during follow-up no local or metastatic recurrence occurred.

SUMMARY

KEY WORDS: Angiomyolipoma, renal sinus, management, surgery, treatment.

cal checkup with no previous personal or family history of tuberous sclerosis (TS). The CT scan showed a 4.2 x 3.4 x 4.6 cm mass originating from the right renal sinus, mainly composed of fat with contrast enhancement, and was subsequently diagnosed as an AML of the renal sinus.

In May 2017, she was referred to our department for follow-up of the mass. CT revealed a 6.4 x 5.1 x 6.2 cm mass originating from the right renal sinus that appeared to extend into the perinephric soft tissues (Figure 1).

Considering the rapid growth of the mass that was significantly pushing aside the duodenum and the right intermittent flank pain referred by the patient in the previous month, a surgical resection was planned. Intra-operative ultrasonography was used to identify intrarenal lesions margins and the mass removed without vascular clamping and renal warm ischemia. The patient was discharged after 4 days without post-operative complications and the definitive histopathological examination confirmed the radiologic diagnosis of renal angiomyolipoma. At six months CT scan follow-up, no local or metastatic recurrence was documented, preserving a renal function unchanged.

INTRODUCTION

DISCUSSION

Angiomyolipoma (AML) is an uncommon tumor derived from three components: blood vessels, smooth muscle, and fat. Even though benign in most cases it can present difficult management decisions. An AML originating from the renal sinus rather than the renal parenchyma is extremely rare and difficult to differentiate from other fat containing masses, such as lipomatosis, lipoma, and liposarcoma (1).

Only 14 cases of AML involving or originating in the renal sinus have been previously reported in literature (2).

AML has an incidence of 0.1-0.22% in the general population and is four times more frequent in women than in men (1). The lesions may present as sporadic cases or in association with TS, an autosomal dominant neurocutaneous disorder that may affect several organs, e.g. brain, skin, eyes, heart, kidney and lungs. Patients are usually asymptomatic and the diagnosis of AML is often incidental: only lesions greater than 4 cm in diameter can be symptomatic and associated with lumbar pain, anaemia and haematuria (2). Retroperitoneal haemorrhage and/or bleeding into the renal collecting system are the major complications, both conditions may put the patient’s life at risk. The therapeutic strategy varies from selective embolization of the renal artery, surgical removal or active surveillance (1, 2). The first cases of AML involving renal sinus reported in literature was in 1972 by Cass and

CASE REPORT A 56-year-old woman in April 2016 underwent Computed tomography (CT) for diagnostic evaluation of a right kidney renal mass detected during a routine medi-

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S. Scarcella, L. Dell’Atti, AB. Galosi Figure 1. Abdomen CT scan showed a 6.4x5.1x6.2 cm endophytic mass originating from the right renal sinus.

Ireland (3) who described 2 patients with renal angiomyolipoma that presented as renal pelvic masses. All 14 cases, reported in literature, were treated with nephrectomy and microscopically involvement of the kidney parenchyma was detected, suggesting that these masses were not of a true renal sinus origin. On ultrasound (US), AMLs are almost always hyperechoic compared to renal parenchyma due to the presence of macroscopic fat.

However, renal cell carcinoma also appears hyperechoic on US in approximately one third of cases. CT and MRI can detect small quantities of fat and reliably diagnose the usual parenchymal AML, but their ability to definitively diagnose renal sinus AMLs has not been established. The diagnosis of angiomyolipoma originating in the renal sinus, although exceedingly rare, should be considered when

imaging studies demonstrate a fat-containing renal sinus mass with characteristics of an AML. The management of AMLs remains complex and challenging, especially for cases originating from the renal sinus and those without TS.

REFERENCES 1. Shirotake S1,Yoshimura I, Kosaka T, Matsuzaki S. A case of angiomyolipoma of the renal sinus. Clin Exp Nephrol. 2011; 15:953-6.

2. Flum AS, Hamoui N, Said MA, et al. Update on the Diagnosis and Management of Renal Angiomyolipoma. J Urol. 2016; 195:834-46.

3. Cass AS, Ireland GW. Angiomyolipoma of the kidney. Report of 2 cases presenting as pelvic masses. Br J Urol. 1972; 44:129-132.

CORRESPONDENCE Scarcella Simone, MD Department of Urology, Polytechnic University of Marche Region University Hospital “Ospedali Riuniti” Via Conca, 71 - 60126 Ancona - Italy Mail: simoscarc@gmail.com Tel.+39 3924677442 Fax: +39 071/5963367

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Instructions to Authors AIMS AND SCOPE

REFERENCES

Advances in Urological Diagnosis and Imaging is a free open access journal. The Journal has the purpose of promote, spread and favorite the scientific knowledge and research in diagnosis and imaging in Urology, Andrology and Nephrology.

Advances in Urological Diagnosis and Imaging publishes every 4 months original articles, reviews, case reports, position papers, guidelines, editorials, abstracts and congress proceedings.

References must be sorted in order of quotation and numbered with arabic digits between parentheses. Only the references quoted in the text can be listed. Journal titles must be abbreviated as in the Index Medicus.

Only studies published on easily retrieved sources can be quoted.

Unpublished studies cannot be quoted, however articles “in press” can be listed with the proper indication of the journal title, year and possibly volume. References must be listed as follows:

To publish in Advances in Urological Diagnosis and Imaging is completely free.

All accepted paper will be published after a peer reviewed process.

• Journal articles All Authors if there are six or fewer, otherwise the first three, followed by “et al.”. Complete names for Work Groups or Committees.

Complete title in the original language. Title of the journal following Index Medicus rules. Year of publication; Volume number: First page.

Example: Starzl T, Iwatsuki S, Shaw BW, et al. Left hepatic trisegmentectomy. Surg Gynecol Obstet. 1982; 155:21.

• Books Authors - Complete title in the original language. Edition number (if later than the first). City of publication: Publisher, Year of publication.

Example: Bergel DIA. Cardiovascular dynamics. 2nd ed. London: Academic Press Inc., 1974.

• Book chapters Authors of the chapters - Complete chapter title. In: Book Editor, complete Book Title, Edition number. City of publication: Publisher, Publication year: first page of chapter in the book.

Example: Sagawa K. The use of central theory and system analysis. In: Bergel DH (Ed), Cardiovascular dynamics. 2nd ed. London: Academic Press Inc., 1964; 115.

AUTHORS’

RESPONSIBILITIES Manuscripts are accepted with the understanding that they have not been published or submitted for publication in any other journal.

Authors must submit the results of clinical and experimental studies conducted according to the Helsinki Declaration on clinical research and to the Ethical Code on animal research set forth by WHO (WHO Chronicle 1985; 39:51).

The Authors must obtain permission to reproduce figures, tables and text from previously published material. Written permission must be obtained from the original copyright holder (generally the Publisher).

Manuscripts must be written in English language in accordance with the “Uniform Requirements for Manuscripts submitted to biomedical journals” defined by The International Committee of Medical Journal Editors (http://www.ICMJE.org). Manuscripts in Italian language can be published only after translation (expenses will be charged to the Authors).

Manuscripts should be typed double spaced with wide margins.

They must be subdivided into the following sections: Title page - It must contain: a) title; b) a short (no more than 40 characters) running head title; c) first, middle and last name of each Author without abbreviations; d) University or Hospital, and Department of each Author; e) last name, address and e-mail of all the Authors; f) corresponding Author; g) phone and/or fax number to facilitate communication; h) acknowledgement of financial support; i) list of abbreviations.

SUMMARY

The Authors must submit a long English summary (300 words, 2000 characters).

Subheadings are needed as follows: Objective(s), Material and method(s), Result(s), Conclusion(s). After the Summary, three to ten key words must appear, taken from the standard Index Medicus terminology.

TEXT

For original articles concerning experimental or clinical studies, the following standard scheme must be followed: Summary - Key Words Introduction - Material and Methods - Results - Discussion - Conclusions - References - Tables - Legends - Figures.

Case Report should be divided into: Summary - Introduction (optional) Case report(s) - Conclusions - References (Discussion and Supplementary Figures, Tables and References can be submitted for publication in Supplementary Materials).

SIZE

OF MANUSCRIPTS

Literature reviews, Editorials and Original articles concerning experimental or clinical studies should not exceed 3500 words with 3-5 figures or tables, and no more than 30 references.

Case reports, Notes on surgical technique, and Letters to the Editors should not exceed 1000 words (Summary included) with only one table or figure, and no more than three references. No more than five Authors are permitted.

TABLES

Tables must be aimed to make comprehension of the written text easier.

They must be numbered in Arabic digits and referred to in the text by progressive numbers. Every table must be accompanied by a brief title.

The meaning of any abbreviations must be explained at the bottom of the table itself.

FIGURES

Figures are also graphics, algorithms, photographs, drawings. Figures must be numbered and quoted in the text by number. The meaning of all symbols, abbreviations or letters must be indicated. Histology photograph legends must include the enlargement ratio and the staining method.

Legends must be collected in one or more separate pages.

Please follow these instructions when preparing files: • Do not include any illustrations as part of your text file.

• Do not prepare any figures in Word as they are not workable.

• Line illustrations must be submitted at 600 DPI. • Halftones and color photos should be submitted at a minimum of 300 DPI.

MANUSCRIPT

REVIEW Only manuscript written according to the above mentioned rules will be considered. All submitted manuscripts are evaluated by the Editorial Board and/or by two referees designated by the Editors. The Authors are informed in a time as short as possible on whether the paper has been accepted, rejected or if a revision is deemed necessary.

The Editors reserve the right to make editorial and literary corrections with the goal of making the article clearer or more concise, without altering its contents.

Submission of a manuscript implies acceptation of all above rules.

MANUSCRIPT

PRESENTATION Authors must submit their manuscripts (MAC and WINDOWS Microsoft Word are accepted) to the Assistant Editor (dellatti@hotmail.com).

PROOFS

Authors are responsible for ensuring that all manuscripts are accurately typed before final submission. Galley proofs will be sent to the Corresponding Author. Proofs should be returned within seven days from receipt.

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TRATTATO ITALIANO DI

NUTRACEUTICA CLINICA a cura di

Arrigo F. G. Cicero Società Italiana di Nutraceutica

coadiutori

Alessandro Colletti e Francesco Di Pierro 61 Autori e Co-Autori 616 Pagine, 38 Capitoli Bibliografia ricca ed attuale Immagini, tabelle e figure originali Highlights riassuntivi Prezzo: € 100,00 (IVA inclusa)

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Per informazioni su costi e condizioni di acquisto, inviare un’e-mail a: trattato.nutraceutica@gmail.com o chiamare i numeri: 02 70608060 - 377 1785150.