Advances in Urological Diagnosis and Imaging - AUDI (Vol. 1 - n. 2 - 2018) by Edizioni Scripta Manent

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

OFFICIAL JOURNAL of

S.I.E.U.N.

Italian Society of Integrated Diagnostic in Urology, Andrology, Nephrology

Vol. 1 - n. 2 - 2018

Istruzioni Autori AUDI.qxp_Stesura Seveso 29/11/18 10:15 Pagina 1

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.

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ADVANCES

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

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

General Information

Contents

AIMS and SCOPE

“Advances in Urological Diagnosis and Imaging” (AUDI) has the purpose of promoting, sharing and favorite technical-scientific research on echography and imaging diagnosis, in diagnostic and terapeutical field of Urology, Andrology and Nefrology. AUDI publishes original articles, reviews, case reports, position papers, guidelines, editorials, abstracts and meeting proceedings. AUDI is Open Access at www.issuu.com Why Open Access? Because it shares science at your finger tips with no payment. It is a new approach to medical literature, offering accessible information to all readers, becoming a fundamental tool, improving innovation, efficiency and interaction among scientists.

Pasquale Martino, Sebastiani Francesco, Silvano Palazzo

BUSINESS INFORMATION

Price for single printed issue: Euro 20,00 Annual subscription rate for the printed version (3 issues) is Euro 52,00. Subscription orders should be sent to: Edizioni Scripta Manent s.n.c. Via Melchiorre Gioia 41/A - 20124 Milano, Italy Tel. +39 0270608060 - e-mail: info@edizioniscriptamanent.eu Payments should be made by Bank transfer to: Edizioni Scripta Manent s.n.c. Unicredit Milano IBAN: IT 23 K 02008 01749 000100472830

Ultrasonographic study of Peyronie’s disease in patients with absence of palpable plaques Lucio Dell’Atti, Simone Scarcella, Matteo Tallè, Massimo Polito, Andrea Benedetto Galosi

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Echoguided treatment of simple renal cysts: Our experience from 1995 to 2018

Ultrasound-guided placement of hemodialysis central venous catheters: Usefulness, methods and training programs SIEUN National Annual Meeting Tutorial Session

Vittorio Di Maso, Francesco Bianco, Giuliano Boscutti

Our experience with MRI/US fusion prostate biopsy after the first 400 consecutive procedures

Vito Lacetera, Matteo Cevenini, Emanuele Cappa, Bernardino Cervelli, Giuliana Gabrielloni, Michele Montesi, Roberto Morcellini, Gianni Parri, Emilio Recanatini, Valerio Beatrici

Uretero-iliac artery fistula: A challenge diagnosis for a life-threatening condition. Monocentric experience and review of the literature Luca Leone, Lucio Dell’Atti, Marco Tiroli, Francesca Sternardi, Andrea Benedetto Galosi

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Advances in Urological Diagnosis and Imaging - 2018; 1, 2

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ORIGINAL

PAPER

Echoguided treatment of simple renal cysts: Our experience from 1995 to 2018

Pasquale Martino1, Sebastiani Francesco1, Silvano Palazzo2 1 Department 2

of Emergency and Organ Transplantation Urology, Andrology and Kidney Transplantation Unit - University of Bari, Bari (Italy); Department of Urology - Presidium of Brindisi "Di Summa - Perrino" Hospital, Brindisi, (Italy).

Introduction: Simple renal cysts are the most frequent lesions of the kidney in adults. Approximately 30% of subjects over the age of 70 years present a simple renal cyst. It is well accepted that a simple asymptomatic renal cyst does not require any treatment. Objective: To evaluate the efficacy of echoguided single sclerotherapy treatment of simple renal cysts. Materials and Methods: Between January 1995 and January 2018, 430 patients underwent percutaneous drainage of simple renal cysts in our centre. A simple aspiration was performed in 73 cases (16.9% of patients), 24 hours' continuous drainage was placed in 90 cases (20.9%) and in 267 cases (62.2%) the lesions were treated by sclerotherapy. After aspiration of the fluid, 99% ethanol, in an amount equal to 30% of the drained volume and never exceeding 60 ml, was injected inside the cyst; 40 minutes later the ethanol was drawn out and the drainage removed. Results: The outcome was considered good if the cyst was less than 50% of the original size. Percutaneous drainage with sclerotherapy showed a success rate of almost 100% using 99% ethanol. However, this method is not completely free from complications. Conclusions: The long-term results and the mini-invasive, ambulatorial treatment modality are the most important advantages of this procedure. Our experience showed a good success rate with a single sclerotherapy session, combining patient benefit and a low cost of the procedure.

SUMMARY

KEY WORDS: Ultrasound, Cyst, Sclerotherapy, Treatment, Outcomes.

INTRODUCTION A simple renal cyst is a non-neoplastic disease of the renal parenchyma. It is quite a common condition in adults, with an incidence of at least 20% at the age of 40 years and 33% at the age of 60 years (1). To date, the etiopathogenic origin of this disease is not entirely clear, but it may be caused by congenital as well as acquired disorders. No conflict of interest declared.

Simple renal cysts are characterized by a thin wall with a clear amber-like liquid inside: this macroscopic appearance is called “blue-domed”. Calcifications can be found inside the cyst. In approximately 5% of simple renal cysts the content is found to be blood, and half of these cases are associated with the presence of a neoplasm inside the cyst (13-15). In most cases, simple renal cysts are asymptomatic. In other circumstances the cyst may increase in volume, causing compression phenomena responsible for tensive pain in the side. In other cases it may become infected or bleed, causing the development of more severe symptoms. Compression of the renal blood vessels or urinary tract by a simple cyst is an infrequent cause of hypertension or renal dysfunction. The diagnosis is frequently incidental, during ultrasound screening of the abdomen performed for other reasons (2). Laboratory tests show no deterioration of renal function and urine analysis is often normal. CT scan may be useful if a tumor is suspected or in cases where a more detailed imaging of the neighboring structures is needed. It is well accepted that a simple renal cyst without clinical symptoms does not require any treatment (2-4). The main indications for treatment are: • Symptoms due to the mass effect; • Compression of the urinary tract; • Hypertension; • Cytological assessment; • Size ≥9 cm; • “Anxiety of the patient”. Contraindications to percutaneous treatment are: • Haemorrhagic diathesis; • Severe respiratory failure; • Severe obesity; • Malformations. Management of a symptomatic renal cyst can be accomplished using several methods: percutaneous aspiration with or without instillation of sclerosing agents, percutaneous marsupialisation, and open, laparoscopic or retroperitoneoscopic cyst unroofing (5-10). Advances in Urological Diagnosis and Imaging - 2018; 1,2

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P. Martino, S. Francesco, S. Palazzo

MATERIALS

AND

METHODS

drainage with sclerotherapy showed a success rate of almost 100% using 99% ethanol. In patients treated with aspiration alone or with the placement of percutaneous drainage we observed a complete relapse rate of 85% and 39%, respectively. Table 1 shows our results. However, this method is not completely free from complications such as burning pain (29%), vagal syndrome (11%), intracystic bleeding (0.5%).

Nowadays, ultrasound-guided percutaneous treatment is a safe technique and offers a valid alternative to open surgery or laparoscopy. The technique is performed under local anaesthesia and may consist of a simple puncture, puncture and drainage or puncture and sclerotherapy. The simple evacuation puncture is used especially when the liquid inside the cyst is blood or corpusculated fluid. It is a diagnostic puncture, and the risk of recurrence ranges DISCUSSION between 30-80% depending on the case. Treatment with percutaneous drainage consists of the Over the years, various authors have reported different positioning of a nephrostomy drain for 24 hours in the opinions about this procedure. The biggest difference is cyst cavity after all the fluid has been drawn out. The aim related to the number of treatments to be carried out. of this technique is to collapse the walls of the cyst. In this A number of substances acting as sclerosing agents have case the risk of recurrence is 65-80%. been used (phenol, lipiodol, alabrina, quinocrina, Surgical access can be posterior or posterolateral. In the methotrexate, 98% ethanol, tetracycline, fibrin glue, etc.). first case the patient is in supine position and the puncture Ethanol 99% is one of the best because contact between is performed below the 12th rib, about 10 cm away from the drug and the cells of the cystic walls induces the death the vertebral spinous process. This access is safe but not of the latter within 1-3 minutes. It takes at least 4-12 hours comfortable for the patient. In the second case, the patient to penetrate the capsule. Porpiglia et al. reported that 98% is in prone-oblique position and the puncture is performed of simple renal cysts disappeared after percutaneous on the mid-axillary line.This access is more comfortable for drainage and three alcohol sclerotherapies at intervals of the patient but poses a higher risk of intestinal perforation. 24 hours (5). For Paananen et al. the outcome was satisfacBetween January 1995 and January 2018, 430 patients in tory in 87% of the patients with a simple renal cyst, treated our clinic underwent percutaneous drainage of simple with a single 99% ethanol infusion (11). Table 2 shows the renal cysts. In 84% of cases we found individual cysts of results for different sclerotherapy techinques. sizes ranging between 84 mm and 191 mm. We found lower polar cysts in 47% of cases, upper polar cysts in 37%, cysts in the middle portion of the kidney in 14% and cysts CONCLUSIONS near the renal pelvis in 2%. Simple aspiration was performed in 73 cases (16.9% of patients), 24 hours' continPercutaneous echoguided treatment of simple renal cysts uous drainage was placed in 90 cases (20.9%) and in 267 with sclerotherapy is not completely free from complicacases (62.2%) the lesions were treated by sclerotherapy. Sclerotherapy was performed with 99% ethanol in 94% of cases and with fibrin glue Table 1. Findings of patients underwent ultrasound-guided percutaneous (Tissucol) in the remaining 6%. treatment for simple renal cysts. After drainage of the fluid from the inside of the cyst, the nephrostomy tube is secured to Simple Percutaneous Sclerotherapy Sclerotherapy the skin. The drained fluid is sent to the labaspiration rainage with tissucol with 99% oratory for cytologic and microbiological ethanol examination. The cystic cavity is then filled 0% 14% 17% 68% Success with saline solution that is immediately drained with a syringe; 99% ethanol is then 22% 3% 32% Relapse <50% of volume 6% injected inside the cyst, in an amount equal 25% 30% 0% to 30% of the original volume of the liquid, Relapse >50% of volume 9% never exceeding 60 ml. The patient is asked 85% 39% 50% 0% Complete relapse to change position frequently, then 40 minutes later, the ethanol is drained from the cyst, the Table 2. Review of the literature on the treatments of simple renal cysts. nephrostomy drainage is removed and the patient is Author Year Patients Treatment Success Volume Disappearance discharged. (complete/partial) reduction of symptoms

RESULTS

Porpiglia

1996

Repeated sclerotherapy

96%/-

Fontana

1999

Repeated sclerotherapy

98%/-

55%

The outcome was considered good if the size of the cyst was 0% or less than 50% of the original size. Percutaneous

Paananen

2001

Repeated sclerotherapy

22%/-

79%

75%

Delakas

2001

Repeated sclerotherapy

83%/11%

Akinci

2005

Single sclerotherapy

18%/-

93%

83%

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Echoguided treatment of simple renal cysts: Our experience from 1995 to 2018

tions such as burning pain, vagal syndrome, intracystic bleeding. Our experience shows that this treatment is a valid alternative to open surgery or laparoscopy. The long term results, and mini-invasive ambulatorial treatment are the most important advantages of this procedure. Furthermore, our experience shows that a good success rate can be obtained with a single sclerotherapy session, combining patient benefit and a low cost of the procedure.

REFERENCES 1. Laucks SP Jr, McLachlan MSF. Aging and simple renal cysts of the kidney. Br J Rad. 1981; 54:12-14. 2. Holmberg G, Hietala SO. Treatment of simple renal cysts by percutaneous puncture and instillation of bismuthphosphate. Scand J Urol Nephrol. 1989; 23:207-212. 3. Hubner W, Pfaf R, Porpaczy P. Renal cysts: percutaneous resection with standard urologic instruments. J Endourol. 1990; 4:61-64. 4. Hanna RM, Dahniya MH. Aspiration and sclerotherapy of symptomatic simple renal cysts: value of two injections of a sclerosing agent. AJR Am J Roentgenol. 1996; 167:781-783. 5. Porpiglia F, Morra I, Rocca A, et al. Percutaneous alcoholization of simple serous cysts of the kidney. Arch Ital Urol Androl. 1996; 65(suppl 5):197-199.

6. Hulbert JC, Hunter D,Young AT, et al. Percutaneous intrarenal marsupialization of a perirenal cystic collection endocystolysis. J Urol. 1988; 139:1039-1041. 7. Amar AD, Das S. Surgical management of benign renal cysts causing obstruction of the renal pelvis. Urology. 1984; 14:429-433. 8. Cloix P, Martin X, Pangaud C, et al. Surgical management of complex renal cysts: a series of 32 cases. J Urol. 1996; 156:28-30. 9. Guazzoni G, Montorsi F, Bergamaschi F, et al. Laparoscopic unroofing of simple renal cysts. Urology. 1994; 43:154-159. 10. Rassweiler JJ, Seemann O, Frede T, et al. Retroperitoneoscopy: experience with 200 cases. J Urol. 1998; 160:1265-1269. 11. Paananen I, HellstrĂśm P, Leinonen S, et al. Treatment of renal cysts with single session percutaneous drainage and ethanol sclerotherapy: long term outcome. Urology. 2000; 57:130-33. 12. Blazer S, Zimmer EZ, Blumenfeld Z, et al. Natural history of fetal simple renal cysts detected in early pregnancy. J Urol. 1999; 162:812. 13. Israel GM, Bosniak MA. An update of the Bosniak renal cyst classification system. Urology. 2005; 66:484. 14. Israel GM, Hindman N, Bosniak MA. Evaluation of cystic renal masses: comparison of CT and MR imaging by using the Bosniak classification system. Radiology. 2004; 231:365. 15. Warren KS, McFarlane J. The Bosniak classification of renal cystic masses. BJU Int. 2005; 95:939.

Compliance with ethical standards Ethical statements: All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Informed consent was obtained from all patients for being included in the study. Funding: No funding was received for this study.

CORRESPONDENCE Pasquale Martino, MD, Prof. Department of Emergency and Organ Transplantation Urology, Andrology and Kidney Transplantation Unit, University of Bari â&#x20AC;&#x201C; (Italy) pasqualeluciomartino@libero.it

Advances in Urological Diagnosis and Imaging - 2018; 1,2

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ORIGINAL

PAPER

Ultrasonographic study of Peyronie’s disease in patients with absence of palpable plaques

Lucio Dell’Atti, Simone Scarcella, Matteo Tallè, Massimo Polito, Andrea Benedetto Galosi Department of Urology, University Hospital “Ospedali Riuniti”, Polytechnic University of Marche Region Ancona, (Italy).

Aim: Non-palpable isolated septal plaques (ISP) without deformity of the penis are not usually diagnosed with the physical examination. An accurate ultrasonographic (US) study of the penis can show in a significant number of patients affected by erectile dysfunction (ED) and penile pain without deformity or curvature the presence of nonpalpable ISP. The aim of this study was to evaluate the US patterns observed in patients investigated for ED or penile pain without curvature.We reviewed the medical records of 386 patients who underwent an initial color-Doppler ultrasonography (CDU) of the penis for DE and/or penile pain without curvature. After satisfying inclusion criteria, 41 patients were individualized. All patients had a non-palpable plaque with involvement of the penile septum. Three US patterns were identified: focal hyperecoic thickening of the intercavernosus septum (IS) with acoustic shadow (pattern 1), non-calcified thickening (isoechoic or slightly hyperechoic (pattern 2), and microcalcifications in the IS without associated acoustic shadow (pattern 3). 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: Peyronie’s Disease; Ultrasound; Intercavernosus Septum; Erectile Dysfunction; Penile Pain.

INTRODUCTION Peyronie’s Disease (PD) is defined as an acquired fibrosis within the tunica albuginea, usually causing deformity, pain No conflict of interest declared.

Advances in Urological Diagnosis and Imaging - 2018; 1,2

and erectile dysfunction (ED) (1). The prevalence of PD in the general male population range between 3 and 9% (2). Non-palpable isolated septal plaques (ISP) without deformity of the penis are not usually diagnosed with the physical examination (3). The role of ultrasound in the diagnosis of PD is well proved due to the high resolution grayscale imaging, alone or in combination with color-Doppler (4). Non-palpable ISP of the penis showed by ultrasonographic (US) study are likely present in a significant number of patients affected by ED and penile pain without deformity or curvature (3,4). In this study, we wished to define the US patterns observed in patients investigated for ED or penile pain without curvature.

MATERIALS

AND

METHODS

Between March 2008 and September 2016, we retrospectively reviewed the medical records of 386 patients who underwent an initial color-Doppler ultrasonography (CDU) of the penis for DE and/or non-resolving penile pain without curvature. The criteria used to enrol patients were: inability to obtain or maintain sufficient penile erection < 1 year; an International Index of Erectile Function 5 score (IIEF5) < 21; penile pain without curvature or deformity < 6 months. For a standardization of the clinical data, patients with a history of traumatic penile injury, mental disorder, abnormal blood levels of sex hormones and history of penile deformity were excluded from our study. All patients were evaluated through their detailed history, whole blood counts, blood levels of sex hormones (testosterone, prolactin, luteinizing hormone and folliclestimulating hormone) and IIEF5 questionnaires. During genital examination, the penis was inspected for presence/absence of plaques. Any penile deviation was observed in all patients enrolled. US study was performed with the patient in the supine position using a machine equipped with a 7-12 MHz multi-frequency linear probe. All patients provided written informed consent before the procedure. With the penis placed toward the abdomen and transducer placed at the ventral surface of the root of

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Ultrasonographic study of Peyronie’s disease in patients with absence of palpable plaques

excluded from the study: 331 patients did not present the penis, a first B-mode US study was performed in transversal and longitudinal planes starting at the level of plaques, 5 patients presented plaques also in other posithe glans and moving down to the base of the penis. Using tions, and 9 patients presented plaques confined only to a 25 gauge insulin injector, 10 micrograms of prostaglandin the IS, but their data were not complete, or images were E1 (PGE1) was injected into the left corpus cavernosum. not available for review. Patients’ age ranged from 29 to 68 After the intra-corporal injection, diameters of right and years with mean age of 51.3±16.7. The baseline demoleft cavernosal arteries were measured, and the peak sysgraphics and clinical characteristics of the 41 patients tolic velocity (PSV) were estimated every 5 minutes for 25 included in the study are shown in Table 1. The interval minutes (5). Less than 10% of patients required additional from onset of symptoms to clinical presentation was 6.8 doses. The values used for different vascular status defini(range 2-9) months. ED was the predominant disorder in tions were PSV less than 25 cm/sec for arterial insufficien73.2% (30/41) of patients, followed by penile pain and cy and end-diastolic velocity (EDV) greater than 5 cm/sec length loss in 19.5% (8/41) and 7.3% (3/41) of patients, for corporal veno-occlusive dysfunction. CDU was perrespectively. Only 12.2% (5/41) of patients reported a susformed by an experienced sonographer who has been performing CDU studies on patients with ED for more 15 years (LD). US evaluation of size, location, Table 1. Distribution of clinical characteristics and ultrasonography and morphological patterns of the plaques were patterns in patients affected by Peyronie’s Disease with plaques confined to recorded. Measurement of plaques length and intercavernosus septum. width were made in the longitudinal and transverse axes to calculate the total area. In gray-scale ultraUS patterns sonography, the two corpora cavernosa are homoHyperechoic Isoechoic Hyperechoic P Patients characteristics geneous in echo structure and identified as two thickening thickening thickening hypoechoic circular structures. The tunica albuginea with AS without AS is visualized as a linear hyperechoic structure cover(n: 32) (n: 6) (n: 3) ing the corpora cavernosa (6). The echoes from the tunica albuginea are specular reflections and thus 55.5 (45-63) 54.3 (29-68) 54.5 (48-61) NS Age (years), median (range) are showed with efficacy only when the ultrasound 7.9 (3-13) 8 (5-12) 7.6 (6-10) NS Plaques size (mm), beam is perpendicular to them. Calcified penile median (range) plaques are usually seen as focal hyperechoic thickening of the tunica albuginea, showing strong 25.7 ± 4.3 24.7 ± 3.9 25.4 ± 4.9 NS BMI (kg/m2), mean ± SD echogenicity with attenuation of the acoustic beam. NS Tobacco, n (%) However, non-calcified plaques are isoechoic or 19 (59.4) 4 (66.7) 2 (66.7) Never slightly hyperechoic compared with the surround5 (15.6) 0 1 (33.3) Former ing tunica albuginea (3, 5). Peyronie’s plaques are 8 (25) 2 (33.3) 0 Current more often located on the dorsal side of the penis, but they can also be found ventrally or, less in other positions (7). A central plaque confined to intercav12 (37.5) 3 (50) 1 (33.3) <0.001 Hypertension, n (%) ernosus septum (IS) could contribute to loss of 0 0 <0.001 Cardiovascular diseases, n (%) 7 (21.9) rigidity distally to the lesion, penile length loss or pain, and changing of the blood flow without evi4 (12.5) 0 0 <0.001 Diabetes, n (%) dence of deformity (8). Statistical analysis Descriptive statistics for variables with a normal distribution, non-normal distribution, and categorical variables were evaluated using mean and standard deviation or median and interquartile range, according to their distribution. The association between US patterns and the factors associated were evaluated using the Student’s t-test or the Mann Whitney U test, depending or their distribution. Statistical analyses were performed using Microsoft Excel 2010 platform. A p < 0.05 was considered to indicate statistical significance.

RESULTS Of the 386 patients retrospectively analysed using our ultrasound database, we stored images of 41 patients that presented penile plaques confined only to the IS and complete clinical data. Among patients

Hypercholesterolemia, n (%)

9 (28.1)

3 (50)

2 (66.7)

Clinical symptoms, n (%) Erectile dysfunction Penile pain Penile length loss

26 (81.3) 4 (12.5) 2 (6.2)

2 (33.3) 4 (66.7) 0

2 (66.7) 0 1 (33.3)

Penile CDU findings, n (%) Mean PSV > 25 cm/sec Mean PSV < 25 cm/sec Mean EDV > 5 cm/sec Mean EDV < 5 cm/sec

14 (43.8) 18 (56.2) 2 (6.2) 30 (93.8)

4 (66.7) 2 (33.3) 0 6 (100)

3 (100) 0 0 3 (100)

Treatments for PD, n (%) Phosphodiesterase-5 inhibitor Vitamin E Pentoxyfilline I.I. with steroids I.I. with verapamil

14 (43.8) 2 (6.2) 2 (6.2) 6 (18.8) 8 (25)

0 4 (66.7) 0 0 2 (33.3)

0 3 (100) 0 0 0

<0.002 <0.001

<0.001

US = ultrasonography; AS = acoustic shadow; BMI = body mass index; NS = not significant; CDU = color-Doppler ultrasound; PD = Peyronie’s disease; I.I. = intralesional injections. Advances in Urological Diagnosis and Imaging - 2018; 1,2

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L. Dellâ&#x20AC;&#x2122;Atti, S. Scarcella, M. TallĂ¨, M. Polito, AB. Galosi Figure 1. Longitudinal (A) and transverse (B) US images obtained along the ventral aspect of the penis show a hyperechoic thickening of the intercavernosus septum with acoustic shadow (white arrows).

Figure 2. Longitudinal US image obtained along the ventral aspect of the penis shows a slightly hyperechoic thickening of the intercavernosus septum without acoustic shadow (white arrow).

Figure 3. Transverse US image obtained along the ventral aspect of the penis shows microcalcifications of the intercavernosus septum without associated acoustic shadow (white arrow).

picious of penile trauma during sexual activity. Medical history revealed presence of risk factors for ED: hypertension (39%), cardiovascular diseases (17.1%), diabetes (9.8%), hypercholesterolemia (34.2%), and smoking history (39.1%). All patients had a non-palpable plaque and Bmode US allowed the recognition of plaque with involvement the penile septum. Thirty two (78.1%) patients showed hyperechoic thickening of the IS with acoustic shadow (Figure 1), 6 (14.6%) patients non-calcified plaques (isoechoic or slightly hyperechoic compared with the surrounding tunica albuginea; Figure 2), and 3 (7.3%) patients microcalcifications in the IS without associated acoustic shadow (Figure 3). Plaques size varied from 3 to 13 mm in maximum diameter. The penile hemodynamic response to intracavernosal PGE1 injection reported abnormal findings distally to the ISP in 20 patients (< 25 cm/sec). Median left and right cavernosal artery flows measured a PSV of 31 cm/sec (range 17-80) and 33 cm/sec (range 15-80), respectively. The management of twenty-five patients included a conservative treatment with oral medication: phosphodiesterase-5 inhibitor (34.2%), vitamin E (22%) and pentoxifylline (4.9%). The other sixteen patients underwent intralesional injections with steroids (14.7%) and verapamil (24.4%). None of the patients has been subjected to surgical treatment.

DISCUSSION

Advances in Urological Diagnosis and Imaging - 2018; 1,2

As connective tissue disorder of penile tunica albuginea PD commonly causes deformity and shortening of the penis often associated with ED (9). Moreover, it is the most frequent cause of penile painful (6). Although first observed in 1561 by Fallopius and Vesalius, it was not until 1743 that the disease was fully described by Francois Gigot de la Peyronie (10). Over 270 years after the first description, the exact pathophysiology remains still uncertain (1-3). PD is thought to arise from microvascular trauma during sexual intercourse. In response to such trauma, inflammatory cells (macrophages, neutrophilis, mast cells) release inflammatory mediators and collagenases. In this early phase of PD, inflammation and edema irritate nerve endings, thereby producing pain. Subsequently, in the chronic phase of PD, the process of plaque formation impairs the erectile tissue often resulting in ED, length loss and deformity of the penis (11, 12). The diagnosis of PD is based on: medical history, physical examination, photographic images as well as US imaging modalities with or without CDU, computed tomography (CT) and nuclear magnetic resonance (MRI) (13). Recently, a validated questionnaire was developed to help the diagnosis and evaluation of the grav-

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Ultrasonographic study of Peyronie’s disease in patients with absence of palpable plaques

ity of PD, known as the Peyronie’s Disease Questionnaire (PDQ). The PDQ is a 15-question tool to assess the presence, progression, and severity of symptoms in patients with PD (14). The role of imaging is to detect impalpable plaques and determine their dimensions. MRI is superior to US for superior contrast resolution in assessing non-calcified plaques. On MRI the plaques appear as hypointense areas of thickening in the tunica albuginea on both T1weighted and T2-weighted sequences (5, 15, 16). Hauck E et al. (17) observed that MRI provides a detailed evaluation of penile anatomy, an accurate presentation of irregularities of tunica albuginea, as well as deformities of corporal bodies. On US, plaques calcification are better showed than on MRI with a detection rate of 100% (6). Calcifications are signal-free on MRI, but the use of gadolinium perifocal contrast enhancement can make inflammatory reactions in and around the calcified plaques (16). However, penile calcifications are not uncommon incidental finding on CT of the pelvis (18). Ultrasonography has been observed to be the method of choice because it is cost-effective and can define both morphological patterns and hemodynamic status of the corpora cavernosa (19). This study shows that non-palpable ISP of the penis identified by US are likely present in a significant number of patients who experience ED, pain or length loss of the penis without evidence of penile deformity or curvature. We evaluated the US patterns in attempt to identify the different stages of the disease and the lesions’ characteristics. Three distinct US patterns were observed, which correspond to different stages of PD. Penile plaques have usually been demonstrated as hyperechoic thickening of the IS with acoustic shadow (76.2%). Detection of plaque calcifications is associated with stabilization of the disease and provides information useful to select patients for lithotripsy therapy. Acoustic shadowing produced by extensive calcification of the plaques can reduce visibility of associated pathological changes of the corpora cavernosa (20). In accordance with several authors we showed that isoechoic plaques are rare and characterized by focal thickening of the IS tissue (11). This form of presentation is found in the initial stages of the disease when the fibrosis is confined and the interstitial edema predominant (12).The isolated thickening and fibrosis of the septum represent the most challenging aspect of the disease, because it is more difficult to be identified with US study. The differential diagnosis includes the following conditions: cavernosal fibrosis secondary to local trauma, chronic inflammation, benign or malignant tumors (21). In particular, the epithelioid sarcoma of the penis is a rare disease that may express as focal lesion and can mimic PD (22). Finally, we described the US pattern of hyperchoic lesions in the IS without associated thickening and acoustic shadow. This pattern is reflective of a calcification process before solid plaque formation. However, microcalcifications can be occasionally identified also in regions in which the tunica albuginea does not present thickened (6). Correlation between plaque enhancement characteristics and natural history of PD has been demonstrated by Bekos, et al. (23). They observed that the density of echogenic areas and presence of acoustic shadows are predictors of disease’s stability. Other authors don’t confirm these results and to date, the natural history and

mechanism of ISP remains undefined (8, 12). Bella, et al. (24) reported that the IS acts as an inner supporting frame, resisting dorsal and ventral bending forces during tumescence. A trauma during intercourse causes pressure on the connection of IS, causing delamination of the septal fibers at the point of insertion. Devine, et al. (25) showed that a repetitive trauma during intercourse might result in delamination between the layers of the IS and microvascular injury, which causes haemorrhage into the intralaminar space. The final results are production of fibroblasts and inflammatory mediators, and accumulation of collagen at the site of the injury. After plaque evaluation, a CDU study should be done, and erectile response of the patients should be evaluated. CDU of the cavernosal arteries gives information on penile blood flows, which is useful in planning medical or surgical treatments (15). Moreover, with the power mode, one can find hyperperfusion around the plaques as a sign of inflammation in the active state of the disease (26). Lue, et al. (27) reported a strong correlation between CDU results and clinical outcomes. The presence of IS fibrosis and tunical thickening were associated with decreased ability to have intercourse. As ED occurs in 30% in patients affected by PD (8, 12), however, penile vascular disease was common in our study (48.8%) because it was supported by the presence of cardiovascular risk factors in most of our patients.

CONCLUSIONS Multiple therapies have been offered for the management of PD, their efficacy is uncertain because numerous trials have lacked to demonstrate favourite findings. Because no single treatment is appropriate for everyone, it is critical to make an exact diagnosis prior to treatment, and factors such as plaque size, location, stability and ultrastructural alterations associated with the disease, should be determined prior to instituting any form of therapy. US has been showed to be a method of choice because it is cost-effective, painless, non-invasive, has no negative side effects and can define both ultrastructural patterns and corporal hemodynamic status. This US stratification may help therapeutic decisions making.

REFERENCES 1. Nehra A, Alterowitz R, Culkin DJ, et al. Peyronie's Disease: AUA Guideline. J Urol. 2015; 194:745-753. 2. Joice GA, Burnett AL. Nonsurgical Interventions for Peyronie's Disease: Update as of 2016. World J Mens Health. 2016; 34:65-72. 3. Ralph D, Gonzalez-Cadavid N, Mirone V, et al. The management of Peyronie's disease: evidence-based 2010 guidelines. J Sex Med. 2010; 7:2359-2374. 4. LaRochelle JC, Levine LA. A Survey of primary-care physicians and urologists regarding Peyronie's disease. J Sex Med. 2007; 4:11671173. 5. Patel DV, Halls J, Patel U. Investigation of erectile dysfunction. Br J Radiol. 2012; 85:S69-78. Advances in Urological Diagnosis and Imaging - 2018; 1,2

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L. Dell’Atti, S. Scarcella, M. Tallè, M. Polito, AB. Galosi with palpation and ultrasound in the evaluation of plaque formation. Eur Urol. 2003; 43:293-299.

6. Mander A, Palleschi G, Gentile V, et al. Early echographical assessment of minimal lesions of cavernosum corpora and tunica albuginea in subjects with erectile dysfunction, suggestive of La Peyronie's disease. Int J Impot Res. 2006; 18:517-521.

18. Kadioglu A,Tefekli A, Erol B, et al. A retrospective review of 307 men with Peyronie's disease. J Urol. 2002; 168:1075-1079.

7. Smith CJ, McMahon C, Shabsigh R. Peyronie's disease: the epidemiology, aetiology and clinical evaluation of deformity. BJU Int. 2005; 95:729-732.

19. Ahmed M, Chilton CP, Munson KW, et al. The role of colour Doppler imaging in the management of Peyronie's disease. Br J Urol. 1998; 81:604-606.

8. Prando D. New sonographic aspects of peyronie disease. J Ultrasound Med. 2009; 28:217-232. 9. Bilgutay AN, Pastuszak AW. Peyronie’s disease: a review of etiology, diagnosis and management. Curr Sex Health Rep. 2015; 7:117-131.

20. Carbone M, Rossi E, Iurassich S, et al. Assessment of microvascularization around the plaques in Peyronie’s disease with Doppler color ultrasonography, power Doppler and ultrasonography contrast media. Radiol Med. 1999; 97:66-69.

10. De la Peyronie F. Sur quelques obstacles qui s’opposent à l’èjaculation naturelle de la semence. Mèm Acad Roy Chir 1743; 1:425-434.

21. Kalokairinou K, Konstantinidis C, Domazou M, et al. US Imaging in Peyronie’s Disease. J Clin Imaging Sci. 2012; 2:63.

11. Chong W, Tan RB. Injectable therapy for Peyronie's disease. Transl Androl Urol. 2016; 5:310-317.

22. Usta MF, Adams DM, Zhang JW, et al. Penile epithelioid sarcoma and the case for a histopathological diagnosis in Peyronie's disease. BJU Int. 2003; 91:519-521.

12. Mulhall JP, Schiff J, Guhring P. An analysis of the natural history of Peyronie's disease. J Urol. 2006; 175:2115-2118. 13. Bertolotto M, Pavlica P, Serafini G, et al. Painful penile induration: imaging findings and management. Radiographics. 2009; 29:477-493.

23. Bekos A, Arvaniti M, Hatzimouratidis K, et al. The natural history of Peyronie's disease: an ultrasonography-based study. Eur Urol. 2008; 53:644-650.

14. Hellstrom WJ, Feldman R, Rosen RC, et al. Bother and distress associated with Peyronie's disease: validation of the Peyronie's disease questionnaire. J Urol. 2013; 190:627-634.

24. Bella AJ, Sener A, Foell K, Brock GP. Nonpalpable scarring of the penile septum as a cause of erectile dysfunction: an atypical form of Peyronie's disease. J Sex Med. 2007; 4:226-230.

15. Pawłowska E, Bianek-Bodzak A. Imaging modalities and clinical assesment in men affected with Peyronie's disease. Pol J Radiol. 2011; 76:33-37.

25. Devine CJ Jr, Somers KD, Jordan SG, et al. Proposal: trauma as the cause of the Peyronie's lesion. J Urol. 1997; 157:285-290.

16. Vosshenrich R, Schroeder-Printzen I, Weidner W, et al. Value of magnetic resonance imaging in patients with penile induration (Peyronie's disease). J Urol. 1995; 153:1122-1125.

26. Carbone M, Rossi E, Iurassich S, Schlossberg SM. Assessment of microvascularization around the plaques in Peyronie’s disease with Doppler color ultrasonography, power Doppler and ultrasonography contrast media. Radiol Med. 1999; 97:66-69.

17. Hauck EW, Hackstein N, Vosshenrich R, et al. Diagnostic value of magnetic resonance imaging in Peyronie's disease a comparison both

27. Lue TF. Peyronie’s disease: an anatomically-based hypothesis and beyond. Int J Impot Res. 2002; 14:411-413.

CORRESPONDENCE Lucio Dell’Atti, MD, PhD Department of Urology Polytechnic University of Marche Region University Hospital “Ospedali Riuniti” 71 Conca Street - 60126 Ancona - Italy dellatti@hotmail.com Tel: +39 071 5966523 Fax: +39 071 5963367

Advances in Urological Diagnosis and Imaging - 2018; 1,2

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ORIGINAL

PAPER

Ultrasound-guided placement of hemodialysis central venous catheters: Usefulness, methods and training programs SIEUN National Annual Meeting Tutorial Session Vittorio Di Maso, Francesco Bianco, Giuliano Boscutti ASUITS Nephrology and Dialysis Unit â&#x20AC;&#x201C; Internal Medicine Department â&#x20AC;&#x201C; Trieste Hospital, Italy.

Objective: Hemodialysis central venous catheter (HD-CVC) placement is an important skill for Nephrologists. Ultrasound (US) guidance significantly increased safety, effectiveness and efficiency of HD-CVC placement and requires training and experience. This review points to assess literature indications and to describe practical skills and advantages of US-Guide HD-CVC insertion. Material and Methods: Medical literature on US-guided vascular cannulation was reviewed up to June 2018 using Pubmed and focusing on US-guided HD-CVC insertion guidelines, methods and training programs. Results: HD-CVC placement can often present some complexity (anatomical variations, venous insufficiency, edema, clinical instability) and complications rate increases with each attempt. US-guided venipuncture is associated with fewer complications and faster access. US imaging allows to visualize target vein and surrounding structures and to evaluate the adequate vein size excluding thrombosis. Full benefits of US are obtained using preprocedural ultrasound evaluation and real-time US-guided venipuncture for both short-term and long-term hemodialysis CVC. Although, US-guided CVC insertion has diffused widely throughout clinical practice, it is not always supported with a formal training. There is a general consensus that formal education and training are necessary to achieve knowledge on US vascular anatomy and pathology and to learn technical skills required for US-guided venipuncture. Conclusions: 1. Ultrasound guidance has to be considered the method of choice for any kind of vascular cannulation since it improves the success rate of CVC placement reducing complication rate. 2. Education, training and accreditation programs have a central role in standardization and diffusion of this technique. 3. The efforts of National and International Societies in developing tutorial programs allows Nephrologists to easily acquire and maintain practical skills in US-guided HD-CVC insertion.

SUMMARY

KEY WORDS: Hemodialysis, Ultrasound, Central Venous Catheters, Training, Chronic Kidney Disease. No conflict of interest declared.

INTRODUCTION Central Venous Catheter (CVC) placement is an important skill for Nephrologists albeit the arteriovenous fistula (AVF) is considered the gold standard vascular access for hemodialysis. AVF needs a proper maturation time before its use and a relevant number of patients starts dialysis with either temporary or tunneled cuffed catheters (1). Percutaneous insertion of HD-CVC is an invasive procedure with a specific risk of complications such as arterial puncture, hematoma, pneumothorax and hemothorax (2). Hemodialysis catheters are placed using Seldinger technique. Identification of target veins can be achieved by using either traditional anatomic landmarks (landmark method) or real-time US guidance (US-guided method). US-guided method minimizes complications of CVC insertion procedures providing real-time imaging of target vessel and monitoring of needle route. The use of landmark method in non-dialysis population is associated with not neglectable failure rates and periprocedural complications while US-guidance has been shown to reduce catheterization-related morbidity with an higher rate of first-pass cannulation success and a lower rate of carotid artery puncture (3). The UK National Institute for Clinical Excellence (NICE) (4) and the other Renal National and International Associations recommend the use of US imaging for HDCVC insertion (Table 1). However, US-guided procedures are far from being systematic. As several surveys have shown, many physicians continue to adopt landmark method especially in the case of femoral vein (FV) cannulation. The reasons why operators are reluctant to use ultrasound are mainly the absence of training in US techniques, lack of equipment and the belief that US is not necessary (5). The organization of training sessions is a key element to increase the use of US-guided technique and this is particularly true for dialysis patients who are at higher risk of complications. This review assesses the potential advantages of the use of US imaging for HD-CVC insertion, summarizes practical rules for HD-CVC placement and elucidates the role Advances in Urological Diagnosis and Imaging - 2018; 1,2

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V. Di Maso1, F. Bianco1, G. Boscutti Table 1. Guidelines recommendations on ultrasound guidance for hemodialysis catheter placement. A brief summary of guidelines recommendations is reported according to the level of evidence for each reference: 1 Kidney Disease Outcomes Quality Initiative (KDOQI) clinical practice guidelines and clinical practice recommendations for 2006 updates: vascular access. Am J Kidney Dis 2006; 48:S176-S307; 2 European Best Practice Guidelines (EBPG) on Vascular Access Nephrology Dialysis Transplantation, 2007; 22,S288-117; 3 Kidney Improving Global Outcome (KDIGO) Clinical Practice Guideline for Acute Kidney Injury. Kidney International Supplement 2 (2012); 4 Kidney Health Australia - Caring for Australians with Renal Impairment (KHA-CARI) Guideline: Vascular access – central venous catheters, arteriovenous fistulae and arteriovenous grafts. Nephrology. 2013; 18,701-705; 5 The UK Renal Association - Clinical Practice Guidelines – Vascular Access for Hemodialysis. 6th Edition, 2015.

Guideline

Recommendation

KDOQI – USA, 2006 1

Ultrasound-directed cannulation of noncuffed catheters minimizes insertion complications, as it does with tunneled cuffed catheters, and should be used when available. Because most noncuffed catheters are placed at the bedside, the need for a postinsertion chest radiograph after internal jugular or subclavian insertion is mandatory to confirm the position of the catheter tip in the superior vena cava and exclude such complications as pneumothorax and hemothorax.

EBPG – EU, 2007 2

The percutaneous route should be used for both acute and chronic catheter insertion. Insertion should be guided by ultrasound. A plain X-Ray (chest or abdomen) should be performed before use to locate catheter and detect any complication.

KDIGO – USA, 2012 3

We recommend using ultrasound guidance for dialysis catheter insertion. Ultrasound-guided venous access increases the probability of successful catheter placement and reduces the risk of complications, the need for multiple catheter placement attempts, and the time required for the procedure. The advantage appears most pronounced for the jugular vein, whereas the evidence is scarce for the subclavian and femoral vein.

KHA-CARI – Australia, 2013 4

The use of real-time ultrasound guidance is strongly recommended for the placement of haemodialysis catheters and results in improved rates of successful catheter placement, and reduced rates of both haematoma formation and inadvertent arterial puncture.

The Renal Association – UK, 2015 5

Placement of both tunnelled and non-tunnelled catheters should be performed under ultrasonographic guidance to reduce the risk of procedure related complications.

of training programs. Special attention is given in reviewing the US-guided HD-CVC insertion tutorial session of the Italian Society of Integrated Diagnostic in Urology, Andrology and Nephrology (SIEUN) annual meeting organized in Trieste (Italy) 2018.

BRIEF

HISTORY OF HEMODIALYTIC VASCULAR ACCESS EVOLUTION

Modern hemodialysis started on 1943 with Willem Kolff who constructed the first dialysis machine and treated a young patient affected by kidney failure. He used only venipuncture needles obtaining blood from the femoral artery and reinfusing blood by puncturing a vein. The Achilles heel of hemodialysis remained a reliable vascular access for a long period of time. In 1960 Quinton, Dillard and Scribner developed an arteriovenous Teflon shunt connecting an artery and a vein for dialysis purpose (6). Finally, in 1966 Brescia, Cimino, Appel and Hurwich described the technique to create the AVF for hemodialisys that is still considered the gold standard (7). Nevertheless, hemodialysis represents the therapy for both chronic kidney disease (CKD) and acute kidney injury (AKI), often hemodialytic access has to be available for immediate use requiring an urgent CVC insertion. In 1951 Pierce discovered a new flexible polyethylene catheter and allowed Seldinger to develop his technique based on the use of a flexible, round-ended, metal leader (guidewire). The vein is punctured with a finder needle, the guidewire is inserted

Advances in Urological Diagnosis and Imaging - 2018; 1,2

Evidence

through needle and the flexible catheter threaded over the guidewire which is removed immediately after. This process allows a catheter to be inserted percutaneously without surgical exposure of the vessels. It was used for the first time to obtain an hemodialysis vascular access in 1961 by Stanley Shaldon who cannulated the femoral artery and vein using the Seldinger technique (6). The additional use of ultrasound for vessel localization and CVC placement started in early ’80 improving the CVC insertion procedure (8).

ROLE

OF ULTRASOUND IN HEMODIALYSIS CVC INSERTION An increasing number of patients starts hemodialysis with either temporary or tunneled cuffed CVCs especially when urgent HD is required (1) and also when patients are waiting for maturation of an AVF, there are no suitable sites to create an AVF or in presence of contraindications (9). Internal jugular vein (IJV) and femoral vein (FV) are the preferable locations of HD-CVCs, rarely the subclavian vein (SCV). The IJV has a straight course into the superior vena cava or right atrium and allows HD-CVC high blood flow rate. Traditionally, the vein has been located by the landmark technique since the proximal tract of the IJV lies behind a triangle formed by the junction of the sternal and clavicular insertions of the sternomastoid muscle and the clavicle. However, ultrasound guidance is now recom-

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Ultrasound-guided placement of hemodialysis central venous catheters: Usefulness, methods and training programs Figure 1. Anatomical variants of femoral vein and internal jugular vein and complications of HD-CVC insertion according with cannulation site. Panel A: representation of US short-axis view of FV anatomical variants with respect to the common femoral artery. Right side, axial section. Most anatomy textbooks describe the common femoral artery as lateral to the common femoral vein. It has been demonstrated that this is the case when the two vessels are evaluated at the level of the inguinal ligament. However, proceeding from the inguinal ligament to the knee, a portion of the femoral artery becomes overlapped to the vein. * 4cm below the inguinal ligament in almost all patients there is some degree of overlap, being it complete in 50% of the cases. This variation in anatomic relationship between femoral artery and femoral vein is clinically significant, since an accidental puncture of the femoral artery while using a â&#x20AC;&#x153;blindâ&#x20AC;? technique can lead to complications such as peri-arterial hematoma, arteriovenous fistulas, or pseudoaneurysms. Cannulation of the femoral vein should be performed as close to the inguinal ligament as possible and ultrasound guidance of needle insertion should be used to reduce the risk of complications. FV: common femoral vein; FA: common femoral artery. Hughes P, et al. Anaesthesia 2000; 55:1198-202. Panel B: representation of US short-axis view of the anatomical variants of the internal jugular vein with respect to the common carotid artery. Right side, axial section. In the majority of cases the internal jugular vein is anterolateral to the common carotid artery. Notably, up to 18% of internal jugular veins are not visible or are thrombosed. Variants not shown: lateral (0-84%) and far lateral (0-4%). IJV: internal jugular vein; CA: common carotid artery. Adapted from Maecken T, et al. Crit Care Med 2007; 35 S5:S178 E. Clark, et al. Kidney International 2014 86, 888â&#x20AC;&#x201C;895. Panel C: Common complications of HD-CVC insertion according with cannulation site.

mended as the preferred method for insertion of CVCs into IJV (10). The FV represents a good option for inserting temporary HD-CVC because this procedure does not require any radiological control after insertion and is associated with a lower bleeding risk. In the landmark method CVC is inserted into the femoral vein 2 cm below the inguinal ligament medially to the beating of the femoral artery. The SCV route is considered as third choice because of the high risk of subclavian thrombosis and stenosis with complication to create a AVF in the ipsilateral arm (11). The use of landmark techniques for puncture of the central veins may result in significant immediate complications (arterial puncture, hematoma, pneumothorax, hemothorax) that are reported in around 5-10% of the procedures

and may be as high as 40% if the operator is inexperienced (2). Pneumothorax, pneumopericardium, air and guidewire embolism, and arrhythmia are the less frequent complications but can be fatal. Common complications of HD-CVC placement are summarized in Figure 1 (Panel C) according to the insertion site (12). The use of ultrasound enables the operator to detect possible anatomical variations in IJV and FV locations with respect to the artery (Figure 1, Panel A-B). It has been well demonstrated that the use of real-time US guidance reduces mechanical complications since US accurately locates the target vein providing information about venous diameter, surrounding structures and presence of intravascular thrombi (4). In these terms preprocedural US is of the utmost importance in patients needing HD as subjects with a history of prior HD-CVC Advances in Urological Diagnosis and Imaging - 2018; 1,2

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placement had a significant rate of IJV thrombosis that bosis). Non-tunneled catheters are used as temporary occlude the vessel in around 62% of cases (13). HD vascular access being designed for immediate use and In difficult cases, several needle passes are frequently short-term permanence. These CVCs are composed of required, US guidance guarantees a higher success rate on different materials (polyurethane, polyethylene, polyvinyl the first attempt and lower technical failure and complicachloride, medical-grade silicone) and have one or two tions. In 2011 Rabindranath KS, et al. published a systematic lumens connected to two ports. Red port identifies the review considering 7 randomized clinical trials (830 arterial-flow drawing blood from the patient, blue-port hemodialysis catheters including non-tunneled and tunidentifies the venous-flow returning blood to the patient. neled) and found that the use of real-time US was associNon-tunneled HD-CVCs length ranges from 9 to 30 cm ated with a significant reduction in catheter placements failand lumen diameter from 8 to 13.5 French providing ure (RR 0.12; 95% CI 0.04-0.37), improved the successful pump flow rates of 200 to 400 mL/minute. These CVCs insertion rate on the first attempt (RR 0.40; 95% CI 0.29are relatively rigid at room temperature and become soft0.56) reducing rate of arterial puncture (RR 0.22; 95% CI er at body temperature minimizing vessel trauma proba0.06-0.81), hematoma formation (RR 0.27; 95% CI 0.08bility. Selection of the appropriate catheter type depends 0.88) and time needed for successful vein (14). on both the insertion site and the patientâ&#x20AC;&#x2122;s characteristics The femoral route is considered the easiest method to obtain a quick Figure 2. Central Venous Catheters (CVC) for hemodialysis, technical features. central venous access. Althoug, seri- CVC prepared for insertion (left panels) and after insertion (right panels). Panel A: singlelumen femoral venous catheter, polyurethane, 8F x 25 cm length; flexible J-tip wire guide; ous albeit rare complications (severe introducer needle (17-gauge x 70mm) on a 20ml syringe. Panel B: double-lumen right jugular retroperitoneal hemorrhage) relat- venous catheter, polyurethane, 11F x 15cm length; flexible J-tip wire guide; dilator device; ed to femoral HD-CVC placement introducer needle (17gauge x 70mm) on a 20ml syringe. Panel C: tunneled right jugular vein have been described, US is used less catheters (two lines with their connectors), polyurethane, 10F, arterial cuff 18,2cm from tip, frequently for FV cannulation (15). venous cuff 21,2 cm from tip; metal tunnelers; dilator device; flexible J-tip wire guide; Different studies reported that US introducer needle (17gauge x 70mm) on a 20ml syringe. (Van Der Meersch H, De Bacquer D, guided HD-CVC placement is asso- Vandecasteele SJ, et al. Hemodialysis catheter design and catheter performance: a randomized ciated with a significant lower com- controlled trial. Am J Kidney Dis 2014; 64:902; Power A, Hill P, Singh SK, et al. Comparison of Tesio plications rate, procedure time, and and LifeCath twin permanent hemodialysis catheters: the VyTes randomized trial. J Vasc Access number of attempts in the setting 2014; 15:108; Gallieni M, Brenna I, Brunini F, et al. Dialysis central venous catheter types and performance. J Vasc Access 2014; 15(Suppl 7): S140- S146; Schwab SJ, Beathard G. The of acute hemodialysis with a higher hemodialysis catheter conundrum: hate living with them, but canâ&#x20AC;&#x2122;t live without them. Kidney Int success rate compared with land- 1999; 56:1; Schwab S, Besarab A, Beathard G, et al. NKF-K/DOQI clinical practice guidelines for mark technique (100% vs 89.5%, vascular access: Update 2000. Am J Kidney Dis. 2001). respectively) both in IJV and FV (16). These data has been confirmed by another more recent study that farther suggests that operator experience is of lesser significance when the veins are cannulated under real-time US (17). Ultrasound-guided venous access also decreases the likelihood of arterial puncture or pneumothorax in patients undergoing hemodialysis catheter placement (17) and the current level of evidence suggests that all operators should use realtime US guidance for insertion of HD-CVC (12) as indicated also by Renal Organizations internationally (Table 1).

HEMODIALYSIS CVC TYPES

The HD-CVC categories include non-tunneled and tunneled catheters (Figure 2). There are many types of HD-CVCs, but only few trials comparing different materials and shapes according to blood flow volume and incidence of complications (infection, throm-

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Ultrasound-guided placement of hemodialysis central venous catheters: Usefulness, methods and training programs

(Figure 2, Panel A-B). Life length of non-tunneled catheters varies according to the insertion site being mechanical malfunction and infections the main cause of CVC removal. Indeed, CVC related infection rate increases according to the period of permanence in the central vein and rises significantly two weeks after CVC insertion in both the FV (18-29%) and IJV (5-10%) (18). On the other hand, tunneled HD-CVCs are used as long-term vascular access when patients are poor candidates for AVF creation, require a long AVF maturation time, are latereferral or when dialysis is likely to become a chronic treatment. Tunneled dialysis catheters are composed of silicone and other soft flexible polymers, double-lumen catheters ore a couple of single lumen catheters (Tesio) with a polyester cuff that is positioned subcutaneously 1 to 2 cm from the skin exit site (Figure 2, Panel C). The subcutaneous tract represents a barrier against bacterial diffusion and significantly reduce the risk of infections. Thus, tunneled HD-CVCs are associated with lower infection rates compared with non-tunneled CVCs and allow higher blood flow rates (>400 mL/minute). It has been demonstrated that overall survival of tunneled HDCVC is around 77.8% (1 year) and 44% (3 years) with low rates of access-related infection and access-related sepsis (9.6 deaths/1000 patient years at risk). Tesio HD-CVCs provide good dialysis adequacy, low complication rates and a good patient and CVC survival (19).

TECHNIQUE

OF ULTRASOUNDGUIDED HEMODIALYSIS CVC PLACEMENT Hemodialysis CVCs insertion requires the use of linear probes with high-frequency transducers (5-15 MHz) allowing high-resolution imaging of superficial anatomic structures. All US probes have an index mark to orientate the US scan area on the screen (10). Ultrasound can guide vein puncture and CVC placement either with static-US or dinamic-US. Static-US technique is performed to identify target vein and surrounding anatomic structure before CVC placement as a pre-procedural imaging (US-assisted CVC placement) while in dinamic-US technique needle advancement and vessel puncture is performed under permanent US control (real time US-guided CVC placement). Both these techniques are associated with an improvement in successful insertion rate but real-time guidance is considered superior to the ultrasound-assisted CVC insertion (17). In detail, US probe can be placed to obtain either a crosssectional image of the target vessel (short-axis view) or a longitudinal image parallel to length vessel course (longaxis view). In short-axis view, target vessel appears a dark anechoic circular structure with a clear visualization of the surrounding structures. Long-axis view produces a sonographic image along the length of the vessel losing visualization of anatomic relationship between vessels. The terms out-of-plane and in-plane describe the advancement of the needle with respect to the US plane. Thus, US guidance can be performed using either shortaxis probe orientation and out-of-plane view of the nee-

dle (Figure 3, Panel A) or long-axis probe orientation and in-plane view of the needle (Figure 3, Panel B). In shortaxis/out of-plane view, needle appears on the screen as a point. Otherwise in long-axis/in-plane view alignment needle appears as an echogenic line with ring-down artifacts. In the short-axis/out-of-plane view needle tip is visualized only as an echogenic point. This approach allows better visualization of the vein in relation to the artery and other anatomic structures. In the long-axis/in-plane approach the needle can be visualized in all its length during catheterization but anatomic structures surrounding the target vessel cannot be visualized. There is insufficient evidence to define which approach has to be preferred. Finally, preventing infection related to hemodialysis catheters requires adherence to proper technique and optimal catheter management (20). HD-CVC US-guided placement goes through the following steps. After checking for coagulation status, hemoglobin and platelet level an appropriate informed consent is collected. HD-CVC are inserted percutaneously using a modified Seldinger technique with antiseptic approach. For FV cannulation patient lies in a supine position, legs are slightly abducted, physicians stand and perform the procedure on same side of the target vein. Inguinal ligament course is identified between the anterior superior iliac spine and pubic tubercle. Femoral artery is recognized by Figure 3. US-guide and needle orientation during realtime US-guided HD-CVC insertion. Panel A: Short-axis and out of plane combination; Panel B: long-axis and in-plane combination. (Press D. Comparison between the long-axis/in-plane and short-axis/out-of-plane approaches for ultrasound-guided vascular catheterization: an updated meta-analysis and trial sequential analysis. 2018; 331-340).

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its pulsation and the FV lies approximately 1 cm medially running in a parallel direction. US scan allow to identify all these structures. Vein puncture is performed under realtime US guide. J-flex guidewire is then inserted in the needle and removed after CVC is placed in FV. For IJV catheterization patient lies in Trendelenburg position, both the right or left side may be used, but right side is usually preferred due to some anatomical advantages (straight pathway to the superior vena cava) and reduced risk of complications (pneumothorax, injury of the thoracic duct). Patientâ&#x20AC;&#x2122;s head is turned away from the site of cannulation, the physician standing at the head of the bed identifies the triangle formed by the medial and lateral portions of the sternocleidomastoid muscle and the clav-

icle as IJV goes from the apex of the triangle toward the base. Pre-procedural US scan allows to visualize all these structures identifying any anatomical variation. The needle is advanced to the target vein under US control and CVC is placed following the modified Seldinger technique. For tunneled catheters, the insertion technique varies depending upon the type of catheter. Figure 4 illustrates step by step the procedure of US real-time guided tunneled hemodialysis Tesio CVC placement. Of note, before using hemodialysis CVCs for renal replacement therapy the positioning of the tip of the catheter needs to be verified using plain radiography.The tip of nontunneled jugular hemodialysis CVC should be positioned in the superior vena cava, while the tip of high-flow tunneled

Figure 4. Schematic step by step procedure summary of real-time US-guided tunneled HD-CVC (Tesio) insertion in the Right IJV. Panel A: After the identification of anatomic structures by landmark locate the target vein by US-image identifying surrounding structures and excluding vessel thrombosis; Panel B: Use an antiseptic approach to prepare Tesio CVCs and instruments then place patient in Trendelenburg position with his head turn on the left, neck and top of the chest will be cleaned with antiseptic solution and covered with sterile drape; Panel C: Locate the IJV with US, administer local anesthetic infiltrating subcutaneous tissue, proceed under real-time US-guidance to IJV puncture with the insertion needle and aspirate some blood, detach the syringe leaving the needle in place; Panel D: Introduce the J-flex guidewire trough the needle into the IJV, the guide should enter without resistance, remove the needle leaving guidewires in place; Panel E: make an incision on the skin surface from one guidewire to the other and enlarge this area with Kelly forceps making it wide enough to contain catheterâ&#x20AC;&#x2122;s cuffs; Panel F: introduce the dilatators over the guidewires to dilatate the vessel, remove the guidewire introduce the catheter, remove dilatator shell by peel away technique; Panel G: Create a subcutaneous tunnel grabbing the catheter from the cutaneous exit site on the chest, avoid CVC kinking; Panel H: place adapters and extension sets on the catheters, close CVC with heparin lock, confirm the correct position and exclude pneumothorax using Thorax X-Ray before using.

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Ultrasound-guided placement of hemodialysis central venous catheters: Usefulness, methods and training programs

hemodialysis catheters should be positioned within the superior vena cava and right upper atrium. The tip of femoral HD-CVC (non-tunneled or tunneled) should be placed in the distal inferior vena cava (21).

TRAINING PROGRAMS

GUIDED HEMODIALYSIS PLACEMENT

USCVC

FOR

In 2002, the NICE recommended that physicians placing CVCs under US guidance should undergo appropriate training (4). However, Intensivists have still little formal training and there is a lack of consensus related to standards of training and certification (10). This is associated with a limited diffusion of the use of US-guidance for CVC placement, as approximately the half of physicians involved in this field continue to perform procedures using only landmark technique, particularly in the case of FV cannulation. The main reasons for this hesitation include the absence of training programs, absence of US machine, the belief that US-guide is not necessary and the consideration that landmark technique should be known by trainees (22). US does not increase safety by itself, it requires a specific training to learn applied ultrasound physics, to correctly identify anatomical structures and to guide the needle. Indeed, US guidance used by inexperienced physicians is associated with a higher risk of injury to target vessel or nontarget structure depending on a false sense of security and overestimation of achieved skills (23). The correct interpretation of US images induces changes in CVC insertion’ management. Thus, dedicated educational training programs, aside from physician’s personal experience, have a central role in preventing dangerous procedures and incorrect CVC placements. In fact, use of standardized teaching program on US-guided CVC insertion allows a rapid learning of the technique also by novices (eight procedures) and reduces the importance of previous clinical experience (24). The American Society of Diagnostic and Interventional Nephrology stated rules for interventional nephrology training standards. Simulation–based mastery learning (SBML) training for HD-CVC insertion is a competency based education module in which participants learn a procedure through the use of realistic simulators and clinical scenarios (25). Before any formal teaching, learners undergo pre-training test to evaluate their skills and knowledge. Then they start a didactic session learning the correct technique for US guided CVC placement followed by a period of practice using the simulator. The final evaluation is based on a post-training test that is compared with pretesting. Learners continue to practice and repeat posttesting until they obtain a predetermined minimum passing score. SBML based educational program teaching USguided CVC insertion improves patient outcomes according to the amelioration of residents’ skills and containment of both mechanical and infective complications (25). Retention of acquired skills is another central point in the organization of US guided CVC placement learning trainings. So far, there are limited data about skills retention after SBML programs. One study assessed skill retention among Nephrology fellows after SBML training demon-

strating that it lasts for around 6 months suggesting the need for repeated training program within one year (26). More studies are required to assess the persistence of competence after SBML training in the real world setting in relation to the number of procedures that trained physicians perform after their initial training. An additional factor supporting the use of SBML training is the quality of instruction available in the clinical setting. There is evidence to suggest that many of the attending Nephrologists responsible for supervising and teaching HD-CVC insertion may be not skilled enough in performing the procedure themselves. A recent single-center study by McQuillan, et al. showed that skills of attending Nephrologists were highly variable and did not differ significantly from those of their Nephrology fellowship trainees (27). Another open question on CVC educational training programs regards the assessment of acquired proficiency that is usually based on both minimum number of procedures performed and competence assessment by the trainer. The American Society of Diagnostic and Interventional Nephrology guidelines have established the minimum number of procedures as primary operator required to certify Nephrologists proficiency in HD-CVC placement. This number varies on the basis of CVC type being 25 procedures for temporary HD-CVC and 10 in addition to the requirement for temporary catheters for tunneled HD-CVC (28). However, the need of procedural training programs for nephrology fellows is an ongoing debate within the Nephrology community especially in the United States where some program directors argue that Nephrologists should be trained for HD-CVC insertion, while others believe that HD-CVC placement skills should not be necessarily required to Nephrologists, since often HD-CVC placement is performed by other Intensivists (29). Notably, SBML for CVC insertion reduces the complication rate in terms of number of needle passes, arterial punctures, line malposition, insertion failures and central line-associated bloodstream infections. This is true also in the case of National Meetings that could be considered an effective venue to educate a relatively large group of trainees coming from multiple centers. SBML during a National Conference is an effective method to train current and future Nephrologists and should be considered for incoming nephrology fellows prior to performing these procedures on patients (30). In Europe, both the European Society of Nephrology (ERAEDTA) and the Italian Society of Nephrology (SIN) organize Interventional Nephrology courses including also SBML based practical training sessions on HD-CVC insertion. SIN is also involved in continuing educational training programs on ultrasonography that include a final formal evaluation of the acquired skills. Finally, the Italian Society of Integrated Diagnostic in Urology, Andrology and Nephrology (SIEUN) organizes an Annual Meeting comprising a specific training session on US-guided CVC insertion and the present review summarizes the SIEUN US-guided CVC insertion training session. All these programs indicate that Nephrology Societies in Europe are directly involved in the organization of training programs for the use of ultraAdvances in Urological Diagnosis and Imaging - 2018; 1,2

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sound and US-guided procedures with dedicated courses and annual national meetings. These efforts are of the utmost importance in spreading guidelines indication pointing to standardize US-guidance application not only for young fellows but also for those more experienced. It has to be considered that teaching to a group gives a team effect that has a central role in strengthening the impact of Nephrology specialty.

CONCLUSIONS HD-CVC placement is an essential procedure in Nephrology daily practice but it may present possible complications. Historically, physicians placed HD-CVC using landmark technique. Although, in the last three decades clinical practice has seen an increasing application of US-guided procedures, there are still many practitioners that consider its use not imperative. US-guidance for HDCVC placement is associated with a significant reduction in catheter placements failure, rate of arterial puncture, hematoma formation and improves the successful insertion rate at first attempt. Guidelines of national and international societies clearly indicate that US guidance is the method of choice for any kind of vascular cannulation. Structured educational and accreditation programs for US-guided HD-CVC insertion are essential to optimize procedural skill, success rate and patient safety. Finally, these trainings are potentially the best way to over-come the still remaining barriers against US-guided method and to standardize the technique according to guidelines indications. In this contest annual meeting programs including tutorial session on US-guided HD-CVC insertion, as in the case of SIEUN annual meeting, have to be considered of the utmost importance in Nephrology procedural skills improvement.

REFERENCES 1. Ethier J, Mendelssohn DC, Elder SJ, et al. Vascular access use and outcomes: An international perspective from the dialysis outcomes and practice patterns study. Nephrol Dial Transplant. 2008. 2. McGee DC, Gould MK. Preventing Complications of Central Venous Catheterization. N Engl J Med. 2003. 3. Oom R, Casaca R, Barroca R, et al. Transitioning from anatomic landmarks to ultrasound guided central venous catheterizations: Guidelines applied to clinical practice. J Vasc Access. 2017; 18(4):328-333. 4. Guidance on the use of ultrasound locating devices for placing central venous catheters | Guidance and guidelines | NICE. https://www.nice.org.uk/guidance/ta49/documents/appraisal-consultation-document-ultrasound-locating-devices-for-placing-central-venouslines. Accessed July. 2018; 17. 5. Zieleskiewicz L, Muller L, Lakhal K, et al. Point-of-care ultrasound in intensive care units: assessment of 1073 procedures in a multicentric, prospective, observational study. Intensive Care Med. 2015.

8. Legler D, Nugent M. Doppler localization of the internal jugular vein facilitates central venous cannulation. Anesthesiology. 1984. 9. Vaux EC, Shail R, Rabindranath KS. Ultrasound use for the placement of haemodialysis catheters. Cochrane Database Syst Rev. 2009; (1). 10. Lamperti M, Bodenham AR, Pittiruti M, et al. International evidencebased recommendations on ultrasound-guided vascular access. In: Intensive Care Medicine. 2012. 11. Santoro D, Benedetto F, Mondello P, et al. Vascular access for hemodialysis: current perspectives. Int J Nephrol Renovasc Dis. 2014; 7:281-294. 12. Clark EG, Barsuk JH. Temporary hemodialysis catheters: Recent advances. Kidney Int. 2014; 86(5):888-895. 13. Wilkin TD, Kraus MA, Lane KA, Trerotola SO. Internal Jugular Vein Thrombosis Associated with Hemodialysis Catheters. Radiology. 2003. 14. Rabindranath KS, Kumar E, Shail R, Vaux E. Use of real-time ultrasound guidance for the placement of hemodialysis catheters: A systematic review and meta-analysis of randomized controlled trials. Am J Kidney Dis. 2011; 58(6):964-970. 15. Berns JS, Oâ&#x20AC;&#x2122;Neill WC, Clark EG, et al. Temporary hemodialysis catheter placement by nephrology fellows: Implications for nephrology training. Clin J Am Soc Nephrol. 2014; 1(1):346. 16. Farrell J, Gellens M. Ultrasound-guided cannulation verus the landmark-guided technique for acute haemodialysis access. Nephrol Dial Transplant. 1997. 17. Prabhu MV, Juneja D, Gopal PB, et al. Ultrasound-guided femoral dialysis access placement: A single-center randomized trial. Clin J Am Soc Nephrol. 2010; 5(2):235-239. 18. Oliver MJ, Callery SM, Thorpe KE, et al. Risk of bacteremia from temporary hemodialysis catheters by site of insertion and duration of use: A prospective study. Kidney Int. 2000. 19. Duncan NDC, Singh S, Cairns TDH, et al. Tesio-Caths provide effective and safe long-term vascular access. Nephrol Dial Transplant. 2004. 20. George A,Tokars JI, Clutterbuck EJ, et al. Reducing dialysis associated bacteraemia, and recommendations for surveillance in the United Kingdom: prospective study. Bmj. 2006. 21. Gallieni M, Martina V, Rizzo MA, et al. Central venous catheters: legal issues. J Vasc Access. 2011. 22. Maizel J, Bastide MA, Richecoeur J, et al. Practice of ultrasound-guided central venous catheter technique by the French intensivists: a survey from the BoReal study group. Ann Intensive Care. 2016; 6(1). 23. Blaivas M, Adhikari S. An unseen danger: Frequency of posterior vessel wall penetration by needles during attempts to place internal jugular vein central catheters using ultrasound guidance. Crit Care Med. 2009. 24. Nguyen BV, Prat G, Vincent JL, et al. Determination of the learning curve for ultrasound-guided jugular central venous catheter placement. Intensive Care Med. 2014; 40(1):66-73. 25. Clark E, Barsuk JH, Karpinski J, McQuillan R. Achieving procedural competence during nephrology fellowship training: Current requirements and educational research. Clin J Am Soc Nephrol. 2016. 26. Ahya SN, Barsuk JH, Cohen ER, et al. Clinical Performance and Skill Retention after Simulation-based Education for Nephrology Fellows. Semin Dial. 2012.

6. Konner K. History of vascular access for haemodialysis. Nephrol Dial Transplant. 2005; 20(12):2629-2635.

27. McQuillan RF, Clark EG, Zahirieh A, et al. Performance of temporary hemodialysis catheter insertion by nephrology fellows and attending nephrologists. Can J Kidney Heal Dis. 2014; 1(1):1767-1772.

7. Brescia MJ, Cimino JE, Appel K, Hurwich BJ. Chronic Hemodialysis Using Venipuncture and a Surgically Created Arteriovenous Fistula. N Engl J Med. 1966.

28. Beathard GA, Work J, Jackson J, et al. Guidelines for Training, Certification, and Accreditation for Hemodialysis Vascular Access and Endovascular Procedures. Semin Dial. 2003.

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Ultrasound-guided placement of hemodialysis central venous catheters: Usefulness, methods and training programs 29. Norby SM. Requirements for Procedural Skills in Nephrology Training Programs: Framing the Conversation. Clin J Am Soc Nephrol. 2018; 13(6):CJN.02210218.

30. Clark EG, Paparello JJ, Wayne DB, et al. Use of a national continuing medical education meeting to provide simulation-based training in temporary hemodialysis catheter insertion skills: A pre-test post-test study. Can J Kidney Heal Dis. 2014; 1(1):1-8.

CORRESPONDENCE Vittorio Di Maso, MD, PhD Nephrology and Dialysis Unit Internal Medicine Department ASUITS - Trieste hospital, Italy Strada di Fiume, 447 - 34149 Trieste (TS) vittorio.dimaso@asuits.sanita.fvg.it 0039 040 3994660

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ORIGINAL

PAPER

Our experience with MRI/US fusion prostate biopsy after the first 400 consecutive procedures Vito Lacetera1, Matteo Cevenini2, Emanuele Cappa1, Bernardino Cervelli1, Giuliana Gabrielloni1, Michele Montesi1, Roberto Morcellini1, Gianni Parri1, Emilio Recanatini1, Valerio Beatrici1 1 2

Division of Urology, Hospital “Ospedali Riuniti Marche Nord”, Pesaro (Italy); Department of Urology, University Hospital “Ospedali Riuniti”, Polytechnic University of Marche Region Ancona, (Italy).

Aim: To present our experience with multiparametric resonance imaging/ultrasound (MRI/US) fusion biopsy after 400 consecutive patients with suspected Prostate Cancer (PCA). Materials and Methods: We analyzed retrospectively 400 consecutive patients who underwent Transrectal ultrasound prostate (TRUS) multiparametric magnetic resonance imaging (mp-MRI) fusion biopsies by Koelis™ system. All biopsies were performed with a transrectal approach, by 3 experienced urologists dedicated to fusion biopsy. The patients were divided into 4 groups: biopsy-naïve patients (Group A); patients with at least one previous negative mapping (Group B); on active surveillance (Group C); with a previous mapping positive for ASAP (Group D). The overall (o) and clinically significant (cs) cancer detection rate (CDR) of Koelis™ system was performed. Secondary, we evaluated the diagnostic role of additional random biopsies. Results: oCDR ranged from 63% (Group C) to 33.7% (Group B); csCDR ranged from 55% (Group C) to 29.3% (Group B); additional CDR of random cores ranged from 51% (Group A) to 25% (Groups B and C), additional csCDR of random cores ranged from 59% (Group C) to 23% (Group D). Conclusions: Our experience confirms that among biopsynaïve patients with a suspicion of PCA or men with a persistent suspicion of PCA after one or more negative biopsy or men on active surveillance or a previous diagnosis of ASAP, MRI/US fusion biopsy can improve oCDR and csCDR risk stratification and can reduce undergrading and the need to repeat biopsies. Our experience confirms that the combination of target and random biopsies represents the standard for PCA detection.

SUMMARY

KEY WORDS: Multiparametric magnetic resonance imaging; Prostate biopsy; Prostate cancer, Ultrasound.

INTRODUCTION Transrectal ultrasonography (TRUS)-guided systematic biopsies (SBs) are still the gold standard for the diagnosis Conflict of interest:Vito Lacetera has worked as consultant/tutor for Koelis™

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of prostate cancer (PCA) (1).This approach is a blind sample of the prostate without focusing on any suspected lesion and it presents 3 main limitations: failure to detect clinically significant PCA (undersampling/missing relevant cancer), imprecise tumor risk stratification (undergrading/understaging) and overdetection of small, low risk clinically insignificant prostate cancers (overdiagnosis). These diagnostic limitations have led to repeat biopsies (with related side effects and costs), delayed detection of significant cancer or overtreatment of indolent PCA (2, 3). 3-D stereotactic mapping of the prostate has been proposed in order to have a three-dimensional histological mapping of the gland: this technique can be made by a templated-guided transperineal biopsy that requires anaesthesia (spinal or sedation) and hospitalization or by a software based transrectal biopsy recording all tracks of the needle on a 3-D map with only a local anaesthesia. This technique should allow not overlapping needle’s tracks with a better 3-D volumetric distribution of the biopsies into the prostatic gland with determination of the extent and location of cancer (4-6) (Figure 1). Figure 1. Three-dimensional mapping of the prostate without mp-MRI.

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Our experience with MRI/US fusion prostate biopsy after the first 400 consecutive procedures

Advances in imaging have led to the application of multiparametric magnetic resonance imaging (mp-MRI) for the detection of PCA with subsequent development of software-based co-registration allowing the integration of MRI with real-time TRUS during prostate biopsy (7-12). mpMRI has been reported to have a high accuracy for the detection of prostate cancer (13), and has already been recommended for patients with a persistent clinical suspicion of prostate cancer after prior negative biopsies in the European Association of Urology guidelines on Prostate Cancer 2017 (14). Different magnetic resonance imaging (MRI) and ultrasonography (MRI/US)-fusion platforms are now commercially available with promising results already reported in literature (15-18). We present our experience with one of these platforms after the first consecutive 400 procedures.

MATERIALS

AND METHODS

400 consecutive patients who underwent TRUS-mpMRI fusion biopsy with Koelis™ system between May 2016 and September 2018 were retrospectively analyzed. All patients had at least one suspicious lesion at mpMRI. MpMRIs were performed in different centers as it often happens in the daily practice without a central re The suspicious lesions were scored according to the PI-RADS classification version 2 (19). Fusion biopsies were performed with Koelis™ system (Koelis, Meylan, France), using Koelis Trinity™. A variable number of targeted biopsies (usually 2-4) and random biopsies (usually 10-14) was performed, depending on the clinical case and urologist preference. Only MRI-target biopsies were rarely performed if the patient had at least one or more negative recent mapping of the prostate with an adeguate sampling and histological quality of the cores or in patients with a very high risk of complications (infection, bleeding). Table 1. Characteristics of the patients Group A: biopsy-naïve patients Group B: patients with previous negative biopsies Group C: patients on active surveillance Group D: patients with a previous ASAP

Group A

Group B

Group C

144

154

Age (years), mean (CI)

66.4 ± 7.5

66.9±7.4

67.4±8.8

PSA (ng/ml), mean (CI)

7.8 ±5.6

9.4±6.3

6.7±3.3

Patients

DRE positive Prostate Volume (ml), mean (CI) PIRADS of targets (maximum score in case of multiple targets) PIRADS 3 PIRADS 4 PIRADS 5 Missing Target cores taken Random cores taken Total cores

10/144

7/154

4/36

53.4±25.3

65.3±34.9

49.2±21

48 73 20 3

65 73 16 4

3 24 6 1

147 1340 1927

647 1373 2020

142 368 510

Koelis™ system creates a precise and highly detailed 3D map of the prostate integrating 3D ultrasound, elastic fusion and Organ-Based Tracking®. All biopsies in the study were performed with a transrectal approach, by 3 experienced urologists dedicated to fusion biopsy with Koelis™. PCA was considered clinically significant in case of findings of Gleason score >6, or more than 2 cores of Gleason score 6 (or more than 1 core outside the target) as suggested by histologic criteria of PRIAS (20). The patients were divided into 4 groups: biopsy-naïve patients underwent a first stereotactic 3-D fusion biopsy of the prostate (Group A); patients with at least one previous negative mapping underwent a MRI/US fusion re-biopsy (Group B); patients on active surveillance underwent a MRI/US fusion re-biopsy (Group C); patients with a previous mapping positive for ASAP underwent a MRI/US fusion re-biopsy (Group D).The overall (o) and clinically significant (cs) cancer detection rate (CDR) of Koelis™ system was obtained. Secondary the diagnostic role of additional random biopsies was evaluated.

RESULTS The characteristics of the patients are summarized in Table 1. 356/400 patients with complete bioptical and histological data were analyzed: Group A: 144 patients (mean age = 66.4 years, CI ± 7.5); mean PSA = 7.8 ± 5.6 ng/ml; mean Prostate Volume = 53.4 ± 25.3 ml; digital rectal examination (DRE) positive in 10/144; lesions dectected by MRI (48 pts in PIRADS 3; 73 pts in PIRADS 4; 20 pts in PIRADS 5; missing 3 pts among all); mean cores from each MRI target lesion = 2.3 ± 1.7; mean total cores = 14.1 ± 2.4. Group B: 154 patients (mean age = 66.9 years, CI ± 7.4); mean PSA = 9.4 ± 6.3 ng/ml; mean Prostate Volume = 65.3 ± 34.9ml, DRE positive in 7/154; lesions dectected by MRI (65 pts in PIRADS 3; 73 pts in PIRADS 4; 16 pts in PIRADS 5; missing 4 pts among all); mean cores from each MRI target lesion = 2.5 ±1.5; mean total cores = 15 ± 3.4. Group C: 36 patients (mean age = 67.4 years, CI ± 8,8); mean PSA = 6.7 ± 3,3 ng/ml; mean Prostate Volume = 49.2 ± 21 ml; DRE positive in Group D 4/36; lesions dectected by MRI (3 pts in PIRADS 3 = 24 pts; in PIRADS 4 =; 6 pts in PIRADS 5; miss22 ing =1 pt); mean cores from each MRI target 65.8±6.9 lesion = 2.1 ± 1.1; mean total cores = 13 ± 2.4. 7.96±4.1 Group D: 22 patients (mean age = 65,8 years,CI ± 6.9); mean PSA = 7.96 ± 4.1 ng/ml; mean Prostate 0/22 Volume = 48 ± 15.5 ml; DRE positive in 0/22; 48±15.5 lesions dectected by MRI (4 pts in PIRADS 3 =; 14 pts in PIRADS 4=; 2 pts in PIRADS 5 =, missing = 2 pts among all); mean cores from each MRI target lesion = 3,1 ± 2.1; mean total cores = 14 ± 2.1. 4 14 2 2 94 197 291

MRI/US fusion biopsy technique using Koelis Trinity is standardized in 5 steps: First step: MRI T2 and/or DWI images were loaded into the Trinity, we manually bordered the prostate signing the apex, the base, the midgland and additional landmarks of the prostate obtaining Advances in Urological Diagnosis and Imaging - 2018; 1,2

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V. Lacetera, M. Cevenini, E. Cappa, B. Cervelli, G. Gabrielloni, M. Montesi, R. Morcellini, G. Parri, E. Recanatini, V. Beatrici Figure 2. MRI T2 and/or DWI images are loaded into the machine, than we border the prostate signing the apex, the base the midgland and additional landmarks of the prostate obtaining a 3-D MRI volume; than we target the suspected areas described in the MRI report in a semiautomatic process. This step is usually done the day before procedure.

Figure 3. 3D TRUS volume is obtained by a real-time TRUS examination in 3 planes (transversal, 60 degree longitudinal turning the probe on the right and on left).

a 3-D MRI volume; then we targeted the suspected areas described in the MRI report in a semiautomatic process. This step is usually performed the day before the procedure (Figure 2).

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Second step: A 3D TRUS volume was obtained by a realtime TRUS examination in 3 planes (transversal, 60 degree longitudinal, turning the probe on the right and on left) by an endfire probe with a rotating 360Â° degree head. We

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Our experience with MRI/US fusion prostate biopsy after the first 400 consecutive procedures

bordered the prostate volume in a way similar to MRI process (Figure 3). Third step: Automatic elastic fusion of the MRI and ultrasound volumes were done by the machine’s software pressing a button. We checked the correct fusion of the volumes (Figure 4). Fourth step: Virtual simulation of bioptical tracking with a visual feedback on the fused target volume were done. Fifth step: If the virtual simulation of the track was inside the target lesion, we pushed the button of the needle and a real biopsy was performed followed by 3D-TRUS acquisition of the track with the needle still in the gland. A mean Figure 4. Automatic elastic fusion of the MRI and ultrasound volumes is done by the machine’s software.

of 2 cores were obtained from each MRI-target area. Then at least 10-14 cores random biopsy were performed in all patients (Figures 5-7). The results are summarized below (see also Table 2): Group A (biopsy-naïve): Overall PCA detection rate = 49%; Significant PCA detection rate = 43%; PCA in target core = 42%; PCA in random core = 51%; Significant PCA based on PIRADS lesion = 17% in PIRADS 3; 41% in PIRADS 4; 60% in PIRADS 5; Significant PCA in random core = 26%. Group B (re-biopsy): Overall PCA detection rate = 33.7%; Significant PCA detection rate = 29.4%; PCA in target core = 26%; PCA in random core = 24.6%; Significant PCA based on PIRDAS lesion = 6.5% in PIRADS 3; 19% in PIRADS 4; 75% in PIRADS 5; Significant PCA in random core = 15%. Group C (Active Surveillance): Overall PCA detection rate = 63%; Significant PCA detection rate = 55%; PCA in target core = 50%; PCA in random core = 25%; Significant PCA based on PIRADS lesion = 45% in PIRADS 4; 62% in PIRADS 5; Significant PCA in random core = 59%. Group D (ASAP): Overall PCA detection rate was 50%; Significant PCA detection rate 40%, PCA in target core 36.3%; PCA in random core 40%; Significant PCA based on PIRDAS lesion = 25% in PIRADS 3; 35% in PIRADS 4; 60% in PIRADS 5; Significant PCA in random core 23%.

DISCUSSION Many commercial platforms of co-registered MRI/US fusion biopsy devices commercially available have been considered. These devices vary by method of co-registration (mechanical, electromagnetic or real-time) and use a different hardware platform to align the biopsy with the co-registered image. We choose Koelis Trinity because it is supported by a quite robust evidence, showing a CDR Figure 5. Target fusion biopsies.

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V. Lacetera, M. Cevenini, E. Cappa, B. Cervelli, G. Gabrielloni, M. Montesi, R. Morcellini, G. Parri, E. Recanatini, V. Beatrici Figure 6-7. Target and random three-dimensional mapping of the prostate.

Table 2. Overall PCA detection rate, Significant PCA detection rate, PCA in target lesion, PCA in random biopsy core, Significant PCA detected in target lesion based on PIRADS score, Significant PCA in random biopsy core in the 4 groups considered.

Group A

Group B

Group C

Group D

Overall PCA detection rate

49% (n 71)

33,7% (n 52)

63% (n 23)

50% (n 11)

Significant PCA detection rate

43% (n 63)

29.4% (n 45)

55% (n 20)

40% (n 9)

PCA in target lesion

42% (n 61)

26% (n 39)

50% (n 18)

36,3% (n 8)

PCA in random biopsy core

51% (n 72)

24.6 (n 38)

25% (n 9)

40% (n 9)

17% (n 8) 41% (n 30) 60% (n 12)

6,5% (n 4) 19% (n 14) 75% (n 12)

0 45% (n 10) 62% (n 5)

25% (n 1) 35% (n 5) 0

26% (n 38)

15% (n 23)

59% (n 20)

23% (n 5)

Significant PCA detected in target lesion based on P IRADS score PIRADS 3 PIRADS 4 PIRADS 5 Significant PCA in random biopsy core

ranging from 48% to 80% (20-27); we considered this platform to be the best compromise between accuracy, reproducibility and feasibility in our daily practice. Several systematic reviews (28-31) show that MRI-TRUS image fusion targeted biopsies, detect more clinically significant cancers compared with standard biopsy techniques: the median detection rate of any cancer was 43.4% and 50.5% in the standard biopsy strategy vs MRI-TRUS image fusion biopsy; the median detection of clinically significant disease was 23.6% (range: 4.8–52%) for standard biopsy and 33.3% (range: 13.2–50%) for MRI-TRUS image fusion targeted biopsy. However, patient population differ among the studies either about the amount of patients with a previous negative biopsy or about patients biopsy naïve or about patients on active surveillance or with a previous diagnosis of ASAP. In our study we decided to divide these different populations into 4 groups: our overall detection rate (oCDR) ranged from 63% (AS) to 33,7% (re-biopsy); our cs-CDR ranged from 55% in C group to 29% (re-biopsy); our additional random biopsy CDR ranged from 51% (biopsy naïve) to 25% (AS); our additional random biopsy clinical significant CDR ranged from 59% (AS) to 15% (rebiopsy). The present data confirm that the combination of target and random biopsies represent the standard for PCA detection and it furtherly shows that additional, random cores improve the CDR for all PCA and clinically significant PCA, mainly in biopsy naïve patients or men on active surveillance.

CONCLUSIONS MRI/US fusion biopsy represents a useful tool to address many of the limitations of contemporary systematic biopsy: it reduces false-negatives, improves risk classification,

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Our experience with MRI/US fusion prostate biopsy after the first 400 consecutive procedures Figure 8. MRI-US fusion re-biopsy in patient with ASAP (left base). Zonal saturation, target and random three-dimensional mapping of the prostate.

8. Schoots IG, et al. Magnetic resonance imaging-targeted biopsy may enhance the diagnostic accuracy of significant prostate cancer detection compared to standard transrectal ultrasound-guided biopsy: a systematic review and meta-analysis. Eur Urol. 2015; 68:438. 9. Panebianco V, et al. Multiparametric magnetic resonance imaging vs. standard care in men being evaluated for prostate cancer: a randomized study. Urol Oncol. 2015; 33:17e1. 10. Barentsz JO, et al. Synopsis of the PI-RADS v2 Guidelines for Multiparametric Prostate Magnetic Resonance Imaging and Recommendations for Use. Eur Urol. 2015. 11. Vache T, et al. Characterization of prostate lesions as benign or malignant at multiparametric MR imaging: comparison of three scoring systems in patients treated with radical prostatectomy. Radiology. 2014; 272:446. 12. Barentsz JO, et al. ESUR prostate MR guidelines 2012. Eur Radiol. 2012; 22:746.

contributes to the reduction of repeating biopsies and overdetection. Without mp-MRI we believe that a stereotactic first bioptical mapping (recording all bioptical tracks in a 3-D map) can increase the best distribution of the core and, if a re-biopsy is necessary, a MRI-US fusion biopsy can be done by the previous recorded 3-D map, avoiding the same tracks of first mapping to improve the results of this technique(Figure 8). Based on our experience, it is possible to concludethat among men with a persistent suspicion of PCA after one or more negative biopsy or men on active surveillance or a previous diagnosis of ASAP, MRI/US fusion re-biopsy can improve overall cancer detection rate, clinical significant cancer detection rate, risk stratification and can reduce understaging, undergrading and the need for repeated biopsies. The optimal method for MR targeted biopsy has not yet been established and further comparative studies with standard of practice and evaluation of cost-effectiveness are needed.

REFERENCES 1. Bjurlin MA, Carter HB, Schellhammer P, et al. Optimization of initial prostate biopsy in clinical practice: sampling, labeling and specimen processing. J Urol. 2013; 189:2039. 2. Serefoglu EC, Altinova S, Ugras NS, et al. How reliable is 12-core prostate biopsy procedure in the detection of prostate cancer? Can Urol Assoc J. 2012; 1. 3. Mufarrij P, Sankin A, Godoy G, et al. Pathologic outcomes of candidates for active surveillance undergoing radical prostatectomy. Urology. 2010; 76:689. 4. Walz J, et al. High incidence of prostate cancer detected by saturation biopsy after previous negative biopsy series. Eur Urol. 2006; 50:498. 5. Eichler K, et al. Diagnostic value of systematic biopsy methods in the investigation of prostate cancer: a systematic review. J Urol. 2006; 175:1605. 6. Moran BJ, et al. Re-biopsy of the prostate using a stereotactic transperineal technique. J Urol. 2006; 176:1376. 7. Futterer JJ, et al. Can Clinically Significant Prostate Cancer Be Detected with Multiparametric Magnetic Resonance Imaging? A Systematic Review of the Literature. Eur Urol. 2015; 68:1045.

13. de Rooij M, Hamoen EH, Futterer JJ, et al. Accuracy of multiparametric MRI for prostate cancer detection: a meta-analysis. AJR Am J Roentgenol. 2014; 202:343-51. 14. Mottet N, Bastian PJ, Bellmunt J, et al. Guidelines on Prostate Cancer, 2014. European Association of Urology. Available at: http://uroweb.org/wp-content/uploads/1607-Prostate-Cancer_LRV3. pdf. Accessed August 2015 15. Verma S, Choyke PL, Eberhardt SC, et al. The current state of MR imaging-targeted biopsy techniques for detection of prostate cancer. Radiology. 2017; 285:343-56. 16. Ukimura O, Desai MM, Palmer S, et al. 3-Dimensional elastic registration system of prostate biopsy location by real-time 3-dimensional transrectal ultrasound guidance with magnetic resonance/transrectal ultrasound image fusion. J. Urol. 2012; 187:1080-6. 17. Mozer P, RouprĂŞt M, Le Cossec C, et al. First round of targeted biopsies using magnetic resonance imaging/ultrasonography fusion compared with conventional transrectal ultrasonography-guided biopsies for the diagnosis of localised prostate cancer. BJU Int. 2015; 115:50-7. 18. Baco E, Rud E, Eri LM, et al. A randomized controlled trial to assess and compare the outcomes of two-core prostate biopsy guided by fused magnetic resonance and transrectal ultrasound images and traditional 12-core systematic biopsy. Eur. Urol. 2016; 69:149-56. 19. Barentz JO, Weinreh JC, Verma S, et al. Synopsis of the PI-RADS v2 guide-lines for multiparametric prostate magnetic resonance imaging and recommendations for use. Eur. Urol. 2016; 69:41-9. 20. van den Bergh RC, Roemeling S, Roobol MJ, et al. Prospective validation of active surveillance in prostate cancer: the PRIAS study. Eur. Urol. 2007; 52:1560-3. 21. Mozer P, RouprĂŞt M, Le Cossec C et al. First round of targeted biopsies using magnetic resonance imaging/ultrasonography fusion compared with conventional transrectal ultrasonography-guided biopsies for the diagnosis of localised prostate cancer. BJU Int. 2015; 115:50-7. 22. Peltier A, Aoun F, Lemort M, et al. MRI-targeted biopsies versus systematic transrectal ultrasound guided biopsies for the diagnosis of localized prostate cancer in Biopsy Naive Men. Biomed. Res. Int. 2015; 201:1-6. 23. Ukimura O, Gross ME, de Castro Abreu AL, et al. A novel technique using three-dimensionally documented biopsy mapping allows precise revisiting of prostate cancer foci with serial surveillance of cell cycle progression gene panel. Prostate. 2015; 75:863-71. 24. Delongchamps NB, Peyromaure M, Schull A, et al. Prebiopsy magnetic resonance imaging and prostate cancer detection: comparison of random and targeted biopsies. J. Urol. 2013; 189:493-9. 25. Fiard G, Hohn N, Descotes JL, et al. Targeted MRI-guided prostate Advances in Urological Diagnosis and Imaging - 2018; 1,2

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V. Lacetera, M. Cevenini, E. Cappa, B. Cervelli, G. Gabrielloni, M. Montesi, R. Morcellini, G. Parri, E. Recanatini, V. Beatrici biopsies for the detection of prostate cancer: initial clinical experience with real-time 3-dimensional transrectal ultrasound guidance and magnetic resonance/transrectal ultrasound image fusion. Urology. 2013; 81:1372-8. 26. Portalez D, Mozer P, Cornud F, et al. Validation of the European Society of Urogenital Radiology scoring system for prostate cancer diagnosis on multiparametric magnetic resonance imaging in a cohort of repeat biopsy patients. Eur. Urol. 2012; 62:986-96. 27. Baco E, Rud E, Eri LM, et al. A randomized controlled trial to assess and compare the outcomes of two-core prostate biopsy guided by fused magnetic resonance and transrectal ultrasound images and traditional 12-core systematic biopsy. Eur. Urol. 2016; 69:149-56. 28. 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(1):8-19. 29. Moore CM, Robertson NL, Arsanious N, et al. Image-guided prostate biopsy using magnetic resonance imaging-derived targets: a systematic review. Eur Urol. 2013; 63:125. 30. Van Hove A, et al. Comparison of image-guided targeted biopsies versus systematic randomized biopsies in the detection of prostate cancer: A systematic literature review of well-designed studies. World J Urol. 2014; 32:847. 31. Siddiqui MM, et al. Comparison of MR/ultrasound fusion-guided biopsy with ultrasound-guided biopsy for the diagnosis of prostate cancer. JAMA. 2015; 313:390.

CORRESPONDENCE Vito Lacetera, MD Division of Urology. Hospital “Ospedali Riuniti Marche Nord” Piazzale Cinelli, 4 - 61121 Pesaro (PU) vlacetera@gmail.com +39.0721.365039

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C ASE

SERIES

Uretero-iliac artery fistula: A challenge diagnosis for a life-threatening condition. Monocentric experience and review of the literature Luca Leone1, Lucio Dell’Atti1, Marco Tiroli1, Francesca Sternardi2, Andrea Benedetto Galosi1 1 2

Department of Urology, University Hospital “Ospedali Riuniti”, Ancona (Italy); Department of Radiology, University Hospital “Ospedali Riuniti”, Ancona (Italy).

Introduction: Uretero-iliac artery fistulae (UIAF) are the consequence of chronic inflammatory events that create a fibrous and poorly vascularized uretero-vascular adhesion. They often occur in patients with a history of surgery, pelvic radiotherapy, and chronic ureteral stenting. The presentation is usually massive gross hematuria with acute anemia unto to hemorrhagic shock, representing a life-threating condition. High mortality rate is reported (7-23%) in literature. Methods: We present 4 cases in 3 patients treated in our Institution in the last 5 years and review the published literature. UIAF was defined as the ratified presence of an abnormal gap between the ureter and any artery. In all patients, the UIAF was initially evaluated by contrast-enhanced CT angiography. The management strategy was defined individually based on the specific risk profile of each patient. Results: In our Institution, an endovascular treatment proved good outcomes in terms of early complications and associated mortality. In all cases ureteral-iliac artery fistula occurred in female previous surgery or radiation and with presence of indwelling ureteral stent. In every case the hematuria was massive and life-threating. The diagnostic pathway adopted in every case lead to overtreatment and deferred diagnosis. Placement of an endoprosthesis resulted an effective solution. Conclusion: A multidisciplinary approach is highly preferable for treating UIAF. Endovascular treatment with stent grafts is recommended in selected patients whenever possible. Open surgical treatment is still required, especially in patients with first failed an endovascular treatment or enteric contamination, abscess, and local sepsis. However, a nephrostomy tube was placed in all patients after resolution of fistula.

SUMMARY

KEY WORDS: Ureteroiliac fistula, Ureteral stricture, Hematuria, Iliac endoprosthesis, Pelvic surgery.

INTRODUCTION Uretero-iliac artery fistula (UIAF) is a recognized but uncommon condition due to multiple factors. Few cases No conflict of interest declared.

are described in literature (less than 150) (1), but incidence of case reported is increased; at the beginning of 90’s only 20 cases were described (2). Diagnosis and management are still a challenge for urologist (2). Uretero-arterial fistulas can develop with aorta, common iliac artery, external iliac artery and hypogastric artery. Aortic fistulas are usually associated with aneurysms; hypogastric fistulas are very uncommon. Fistulas between ureter and common or external iliac artery are usually combined with a history of pelvic surgery, pelvic irradiation, chronic ureteral stenting and vascular disease (3). The presentation is usually massive gross hematuria with acute anemia unto to hemorrhagic shock, representing a life-threating condition. High mortality rate is reported (723%) in literature (4). However, endovascular techniques have improved morbidity and mortality (3, 4). Gold standard for diagnosis are angiography and computed tomography (CT)-scan but these methodic have a low sensibility when fistula is too small and it can be difficult to achieve diagnosis; in these cases patients often undergo explorative laparotomy (5). In this study, the authors aim to describe three patients with UIAF treated by classical and endovascular approach.

MATERIALS

AND

METHODS

This single-center, retrospective observational study was based on data obtained from patient’ medical records in the last 5 years in our institution. We collected 4 consecutive cases in 3 patients who were diagnosed with UIAF. UIAF was defined as the ratified presence of an abnormal gap between the ureter and any artery. In all patients, the UIAF was initially evaluated by contrast-enhanced CT angiography. The management strategy was defined individually based on the specific risk profile of each patient. Clinical characteristics, diagnosis, management and followup of patients affected by UIAF were recorded prospectively in an Excel database and were analyzed retrospectively. Advances in Urological Diagnosis and Imaging - 2018; 1,2

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RESULTS

Figure 2. Left ureter-iliac artery fistula detected during angiographt.

All patients (100%) were female. Mean age was 66 (57-83). All patients underwent radical hysterectomy and radiation therapy for cervical carcinoma 13 (11-15) years before. Two patients (66,6%) underwent radical cystectomy with Bricker diversion for actinic cystitis. All patients (100%) had bilateral ureteral stent for stenosis of ureter (1 patient) or ureter-iliac anastomosis stenosis (2 patients). Presentation was the same for all 3 patients: massive gross hematuria during periodic change of ureteral stent. Immediate management was the stabilization of vital parameters with infusion of colloidal solutions and adrenergic drugs. Blood transfusions were necessaries in all cases. Hematuria was temporary auto-resolved in all cases. Two patients were submitted to a CT scan, finding clots in renal pelvis and underwent urgent radical nephrectomy (Figure 1). Figure 1. Intra-ureteral contrast medium in areterial phase of CT-Scan.

After radical nephrectomy, both 2 patients had a massive hemorrhage from the drain in the first post-operative day and angiography finally reported the fistula between distal tract of right ureter, left in place during nephrectomy, and right common iliac artery. One of these patients 3 years after developed a contralateral fistula in the left side, diagnosed with massive hematuria during change of the left ureteral stent, but angiography and CT scan did not show the fistula. The other patient had diagnosis through angiography (Figure 2) during second episode of massive hematuria because in the first presentation angiography and CT scan resulted negative. In all 4 cases (100%), after the detection of the UIAF, a vascular procedure was performed and an endo-prosthesis was put in common iliac artery to solve the fistula; endovascular procedures resulted safe, without complications; observation of patients was continued in hospital for 18 (5-21) days. Uretheral stent was removed in all cases and a nephrostomy tube was placed to drain the kidney. After placement of endoprosthesis, 1 patient underwent massive deep vein thrombosis

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despite low molecular weight heparin prophylaxis; an inferior caval vein filter was placed and removed after 3 months of anticoagulant therapy. Follow-up is of 49 (25-66) months, and resulted uneventful in all patients (Table 1).

DISCUSSION In our experience, in all cases UIAF occurred in female patients with previous medical history of hysterectomy and radiation therapy for cervical carcinoma. In literature, 57% of UIAF occur in women at a mean age of 58 years (6). Two patients underwent also a Bricker derivation for actinic cystitis. All patients had an indwelling stent for stenosis of ureter or ureteral-iliac anastomosis. We know that radiation is a risk factor for stenosis of uretero-iliac anastomosis in Bricker derivation and the ureteral stent is the most adopted treatment. The presence of an indwelling stent and periodical change is a risk factor for inflammation, traumatic lesions, infections and hematuria; the risk is increased in radiated patients (7). The ureter

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Uretero-iliac artery fistula: A challenge diagnosis for a life-threatening condition. Monocentric experience and review of the literature Table 1. Clinical characteristics, diagnostic modalities, management strategies, and clinical outcomes in the three cases study patients affected by UIAF.

also the constancy and the hardness of stent may had contributed to Patient 1, 1st case Patient 1, 2nd case Patient 2 Patient 3 increase the damage. Gross hematuria was 66 68 57 73 Age episodic. One possible Yes Yes Yes explanation is the Hx of pelvic radiation therapy Yes increase of blood presYes Yes Yes Yes Hx of pelvic surgery sure in some moments, for example due to anxiIleal conduit Ileal conduit No Ileal conduit Urinary diversion ety for the change of Anastomosis Anastomosis Pelvic urether Anastomosis Level of stenosis stent, made as outpatient procedure without anesSingle-J Double-J Single-J Indwelling uretheral catheter Single-J thesia, a possible valve Right Left Right Left Side mechanism of fistula can explain passage of blood Negative Negative Negative Negative CT scan with arterial pressure Positive Negative Negative Negative Angiography from artery to ureter overcoming the flap of Endoprosthesis Endoprosthesis Endoprosthesis Endoprosthesis Therapy of fistula valve. Another possible Nephrostomy tube Nephrostomy tube Nephrostomy tube Nephrostomy tube Diversion subsequent explanation is the pres48 24 45 7 Follow-up (months) ence of stent compressing the fistula and preControlateral No No No Recurrence venting the continuous passage of blood. Those reasons can explain the Table 2. Revision of the literature and comparison with our experience. difficulty to detect fistula with angiography in cases Araki et al. (7) Krambeck et al. (8) Okada et al. (13) Fox et al. (14) Our experience when hematuria is temporary solved; the false 2 7 11 20 4 Cases negative result during Risk factors diagnosis is due to the closing of the flap of valve 100% 91% 84% 100% Chronic indwelling 100% in that definite moment. stents In our experience blood 100% 100% 73% 100% 100% Pelvic surgery refluxed in renal pelvis provided a false positive 0% 100% 45% 74% 100% Pelivc radiation for kidney hemorrhage Diagnosis and lad to radical nephrectomy in two Negative Negative Positive in 55% Negative in 100% CT scan cases; also, chronic Positive in 100 % Positive in 63% Positive in 45% Positive in 50% Angiography pyelonephritis (probably due to a chronic presTreatmen ence of a stent) increased 100% 100% 70% 100% Endovascular graft 100% the false imaging of a stent blooding kidney. During nephrectomy, ureter was 0% 0% 0% 30% 0% Open repair cut proximal to the cross Follow-up with iliac artery because absence of suspicious of 18 15 49 Follow-up (months) 12 the fistula and without an 0% 36% 0% Recurrence history of urothelial cancer. For this reason, after 0% 0% 0% 10% 0% Mortality the passage in the ureter, blood went in the renal loggia and drained, leading to repeat CT scan and finally crossing iliac vessels makes a turn and is narrower than diagnosing the fistula.The patient with late contralateral fisothers tracts: it may suffer more traumatism during stent tula and the other patient whit negative first angiography, change. Furthermore, radiated tissues are less resistant underwent immediate placement of preventive endoprosand softer and are predisposed to more damage. In our thesis at the moment of clinical suspicious. Laparotomy cases those factors can have contributed to lesion the was unnecessary for diagnosis and treatment in our expeureter forming fistula with the common iliac artery. Maybe rience, but in many cases reported in literature it can be Advances in Urological Diagnosis and Imaging - 2018; 1,2

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an effective method to solve the condition (8). A multidisciplinary discussion with radiologist, interventional radiologist, vascular surgery is mandatory to settle and solve the problem (9, 10). Endoprostheis seems to be very effective: with a mean follow-up of 31 months we didn’t observed any complication. Also in literature is resulted to be the preferred option (11, 12). Okada T, et al. reported 36% of recurrence of hematuria in a series of 11 patients underwent placement of endoprosthesis for UIAF, with need for a surgical approach in 2 patients (13). The bigger series reported in literature, by Fox JA, et al., comparing retrospectively endovascular versus surgical approach, didn’t show a difference between the two methods, reporting the same rate of recurrence of hematuria, complications and mortality with a follow-up of 15 months (14, 15) (Table 2). One important topic is the management of urological condition. After a placement of endoprosthesis, is advisable to remove indwelling ureteral stent to avoid further complications. Nephrostomy catheter is the preferred option (16, 17). However, several limitations of our study should be observed. Our data were retrospective in its design and had a low level of evidence. This is, however, inevitable in studies of highly rare status, resulting in a small sample size. Therefore, future studies on larger cohorts of patients are assured.

CONCLUSIONS In our experience in all cases ureteral-iliac artery fistula occurred in female previous surgery or radiation and with presence of indwelling ureteral stent. In every case the hematuria was massive and life-threating. The diagnostic pathway adopted in every case lead to overtreatment and deferred diagnosis. Placement of an endoprosthesis resulted an effective solution in selected patients whenever possible. Open surgical treatment is still required, especially in patients with first failed an endovascular treatment or enteric contamination, abscess, and local sepsis. However, a nephrostomy tube was placed in all patients after resolution of fistula.

REFERENCES 1. Pillai Ak, Anderson ME, Reddick MA, et al. Ureteroarterial fistula: diagnosis and management. AJR Am J Roentgenol. 2015; 204(5):592-8. 2. Puppo P, Perachino M, Ricciotti G, et al. Uretreroarterial fistula: a case report. J Urol. 1992; 148(3):863-4. 3. Escobar PF, Howard JL, Kelly J. Ureteroarterial fistulas after radical pelvic surgery: pathogenesis, diagnosis and therapeutic modalities. Int J Gyn Cancer. 2008; 18:862-867. 4. Rafiei A, Weber TA, Kongnyuy M, Ordorica R. Bilateral ureteral-iliac artery fistula in a patient with chronic indwelling ureteral stents: a case report and review. Case Rep Urol. 2015; 826760. 5. Melegari S, Paprella S, Follini ML, et al. Bilateral ureteroarterial fistula: a case report and review of literature. Urologia. 2016; 83(3):168-172. 6. McCollough MC, Oh E, Lucci JA, Alvarez EA. Ureteroarterial fistula. J Obstet Gynaecol. 2012; 32(7):617-20. 7. Araki T, Nagata M, Takihana Y, Takeda M. Endovascular treatment of ureteroarterial fistulas with stent-grafts. Radiation Medicine. 2008; 26(6):372-375. 8. Krambeck AE, Di Marco DS, Gettman MT, Segura JW. Ureteroiliac artery fistula: diagnosis and treatment algorithm. Urology. 2005; 66(5):990-4. 9. Dangle PP, Bahnson R, Patel A. Ureteral stent-related aortoureteric fistula: case report an literature review. Can Urol Assoc J. 2009; 3(6):84-6. 10. Rittemberg L, Nordsiek M, Cahn D, et al. Diagnosis and management of a challenging patient: ureteroarterial fistula. Urology. 2016; 97:e9-10. 11. Das A, Lewandoski P, Laganosky D, et al. Ureteroarterial fistula: a review of the literature. Vascular. 2016; 24(3): 203-7. 12. Feur DS, Ciocca RG, Nackman R, et al. Endovascular management of ureteroarterial fistula. J Vasc Surg. 1999; 30(6):1146-1149. 13. Okada T, Yamagouchi M, Muradi Am, et al. Long-term results of endovascular stent graft placement of ureteroarterial fistula. Cardiovasc Intervent Radiol. 2013; 36(4):950-6. 14. Fox JA, Krambeck A, McPhail EF, Lightener D. Ureteroarterial fistula treatment with open surgery versus endovascular management: longterm outcomes. J Urol. 2011; 185(3):945-50. 15. Popuri R, Zuckerman DA. Semin Intervent Radiol. 2011; 28(4):392-5. 16. Hong SY, Noh M, Ko GY, et al. Ann Vasc Surg. 2016; 36:22-7. 17. Copelan A, Chehab M, Cash C, et al. Endovascular management of ureteroarterial fistula: a rare potentially life threatening cause of hematuria. J Radiol Case Rep. 2014; 8(7):37-45.

CORRESPONDENCE Luca Leone, MD Department of Urology, University Hospital “Ospedali Riuniti” Ancona (AN) luca.leone.1985@gmail.com +39 339 3750522

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