Stesura Seveso Archivio Italiano di Urologia e Andrologia 2023; 95, 2 120 REVIEW midshaft penis are the most commonly affected sites by PF (1, 4). Clinically, the onset of PF is usually accompanied by a loud cracking sound, followed by penile localized swelling, bruises, pain, and immediate detumescence. Many reviews report that the diagnosis of penis fractures can depend exclusively on clinical findings, based on patient history and physical examination (2, 5). Multiple studies have reported that a wide diversity of investigations are useful in the diagnosis of PF as X-ray imaging, Doppler ultrasound, retrograde urethrocystography (RGU), flexible cystoscopy, and magnetic resonance imag- ing (MRI) (6-8). However, it is unnecessary to use radio- logical investigations in most cases where the history and the clinical examination are sufficient to confirm the diag- nosis. The X-ray imaging may still be required in some cases, especially in patients with atypical clinical presenta- tion (9). Some authors consider the Doppler ultrasound as the preferred radiological tool for investigating penile trau- ma cases given that it is a non-invasive and inexpensive procedure. On the other hand, MRI is the most accurate test in diagnosing the PF as it shows high contrast resolu- tion between tissues and identifies the pathological processes of soft tissues. Studies also reported that it can be used in the evaluation of the urethral injury, although it is not commonly used because of its low cost-effectiveness and long execution time (10, 11). RUG is the gold standard for urethra evaluation. The RUG is easy to perform on trau- ma patients at the bedside: 20 to 30 mL of diluted water- soluble contrast is injected into the urethral meatus, before x-raying. A positive RUG will show contrast outside the urethral serpentine cylinder. Retrograde urethrograms are sensitive in detecting urethral injuries but can't pinpoint their location and are operator-dependent (12). Previous reports demonstrated that urethral injuries are present in 1-38% of the PF cases. Patients with an associ- ated urethral injury can present with blood at the meatus, leading to hematuria and urinary retention (5, 13, 14). However, these findings are not specific as previous case reports indicated that some PF cases with associated ure- thral injuries had no suspected symptoms. Thus, investiga- tions, particularly urine analysis and retrograde urethrogram (RGU), are of paramount importance for identifications of associated urethral injuries (15). Accurate identification of urethral injuries is critical before PF repair to avoid the risk of postoperative complications, including urethral stricture and urethrocutaneous fistula (16). However, due to the rarity of the disease, little literature has been published so Purposes: Penile fracture (PF) with associat- ed urethral injury has been described as a rare condition yet a serious urological emergency. We conducted this systematic review to address the current literature concern- ing the etiology, presentations, intra-operative findings, site of injury, and complications of PF with associated urethral injury, Materials and Methods: The present systematic review was lim- ited to human-based studies published in English language, and reporting clinical data on PF cases with associated urethral injuries. A comprehensive search of the literature was conduct- ed on five electronic databases from their inception to May 2022: Medline via PubMed, Web of Science, Google Scholar, Scopus, and EBSCO host. Results: A total of 15 studies were included encompassing 1671 patients with PF. Out of 1665 patients with PF retrieved from the case series studies, 65 patients had associated urethral injuries giving a point prevalence of 3.9%. The vast majority of the patients had blood on the meatus and hematuria suggestive of urethral injury (57/59; 96.6%). Forty patients had partial urethral disruption and the rest of the patients had a complete rupture. All patients received primary urethroplasty as the main modality of treatment. The median hospital stay was two days and the median duration of transurethral catheterization was 21 days. Five patients (8.5%) developed urethral stricture; other complications included penile curvature (6.7%), palpable fibrosis (6.7%), and erectile dysfunction (3.4%). Conclusions: Urethral injuries are uncommon, but serious find- ings, in patients with PF. Primary urethroplasty appears to achieve satisfactory outcomes with a low incidence of short and long-term complications. KEY WORDS: Penile fracture; Urethra; Urethral injury; Systematic review. Submitted 12 December 2022; Accepted 7 April 2023 INTRODUCTION Penile fracture (PF) with associated urethral injury has been described as a rare condition yet a serious urological emer- gency (1). PF is characterized by signification injury of cor- pus cavernosum anatomy due to profound trauma or manipulation of an erect penis; while traumas to the flac- cid penis or the suspensor ligament are not usually con- sidered as PF (2, 3). Commonly, PF is caused by severe bending of the erect penis during sexual intercourse, mas- turbation, rolling over during sleep, and powerful meth- ods of sexual arousal. To a lesser extent, PF can result from direct trauma or fall onto the erect penis. The basal and The presentation and outcomes of penile fracture with associated urethral injury: A systematic literature review Salah E. Shebl Urology Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt. DOI: 10.4081/aiua.2023.11082 Summary Archivio Italiano di Urologia e Andrologia 2023; 95, 2 S.E. Shebl 121 far concerning the presentation and outcomes of PF with associated PF. Therefore, we conducted this systematic review to address the current literature concerning the eti- ology, presentations, intra-operative findings, site of injury, and complications of PF with associated urethral injury. MATERIALS AND METHODS The present systematic review receives PROSPERO ID 342298 and adhered to the recommendations of the recent version of the Cochrane Collaboration Handbook and the MOOSE statement (17, 18). Eligibility criteria and literature search The present systematic review was limited to human-based studies, published in the English language, and reporting clinical data on PF cases with associated urethral injuries. There were no limitations regarding the date of publication or study design. Studies were excluded if they were review articles, duplicate datasets, or they had no separate data on patients with associated urethral injuries. Besides, we excluded conference abstracts with no available full texts. A comprehensive literature search was conducted on five electronic databases from their inception to May 2022. These bibliographic databases were: Medline via PubMed, Web of Science, Google Scholar, Scopus, and EBSCO host. Various combinations of the following queries were uti- lized: penile, penis, fracture, injury, urethra. Following the literature search, retrieved citations were imported to EndNote X7 for duplicates removal. Unique records were then screened through two stages: the first stage was a screening by titles and abstracts, while the second stage was an full-text evaluation of potentially eligible abstracts for final inclusion in the present systematic review. Quality assessment The quality assessment of the included case reports and case series was conducted using Murad's tool (19), which is specifically designed to evaluate the methodological quali- ty of case reports and case series. This tool consists of eight criteria that cover four primary domains: selection, ascertainment, causality, and reporting. Two independent reviewers conducted the quality assess- ment of the included studies, in case of any discrepancies Figure 1. PRISMA flow diagram. Archivio Italiano di Urologia e Andrologia 2023; 95, 2 122 The presentation and outcomes of penile fracture with associated urethral injury between the reviewers, a consensus was reached through discussion or, if necessary, by involving a third reviewer. Data extraction Standardized data extraction was done using Excel soft- ware for data retrieval and processing. The following data were extracted from each eligible study: year of publica- tion, country, study design, number of patients with PF, number of cases with confirmed urethral injuries, cause of PF, presentation of urethral injury, location of the injury, intraoperative findings, need for supra-pubic cystostomy tube, treatment, complications, hospital stay, and duration of follow-up. RESULTS A total of 7242 records were retrieved from online search and 12 records were identified by manual searching. Of them, 4201 records were screened after duplicates removal. After the initial screening, 55 full texts were retained for a full evaluation. Out of them, 40 studies were excluded as they were narrative or systematic review (n = 8), animal models (n = 3), irrelevant (n = 16), simulation-based stud- ies (n = 6), or they had no data on urethral injuries (n = 7). Finally, 15 studies were included in the present systematic review (See PRISMA flow diagram; Figure 1). General characteristics of the included studies and prevalence of urethral injuries Six retrospective studies (20-25), two prospective study (26, 27), and seven case reports were included in the pres- ent systematic review (21, 28-34). Two from India, two from Egypt, two from the United States, and one from Serbia, Italy, Slovenia, Canada, China, Peru, Tunisia, Brazil and UK each. The median time from injury to presentation was six hours (range 1-48.5 hours) and the median time of follow-up was 21 months (1-107 months). A total of 1671 patients with PF were retrieved from the included studies. Out of them, 65 patients had associated urethral injuries giving a point prevalence of 3.9% (Table 1). Quality assessment of included studies The quality assessment of the included studies was con- ducted using Murad's tool. In terms of selection, eight studies did not report that this was their whole experience on penile fracture or provide a clear selection process. Regarding ascertainment, the majority of the studies (14 out of 15) adequately ascertained exposure and outcomes, while one study failed to do so. Alternative causes that could explain the observation were clearly ruled out in 12 of the included studies. Most studies (10 out of 15) ade- quately followed their patients, while five studies lacked sufficient follow-up period. Reporting: The majority of the studies (11 out of 15) provided sufficient details to allow other investigators to replicate the research or practitioners to make inferences related to their own practice. However, four studies did not provide enough details in their reports. Overall, the quality assessment revealed that most studies had ade- quately ascertained exposure and outcome, and provid- ed sufficient reporting details. However, some studies did not meet all the causality criteria (Supplementary Table 1). Presentation of the included cases Among the 65 patients with associated urethral injuries, the most common cause of fracture was sexual inter- course (41/65; 69%), followed by masturbation (8/65; 13.5%) and rolling over (6/65; 10.1%). With regard to the classic presentation of PF, the most common presen- tations were hematoma (34/65; 57%) and penile swelling (33/65; 55.9%), followed by Aubergine sign/egg-plant deformity (30/65; 50.8%) and crackling sound (29/65; 49.1%). The vast majority of the patients had blood on the meatus and hematuria suggestive of urethral injury (57/65; 87.6%). The most commonly affected location of the included patients was proximal shaft (21/65; 35.5%) followed by midshaft (19/65; 32.2%). The vast majority of the patients had unilateral corporal involvement (54.2%), mainly on the right side (30.5%). Forty patients had partial urethral disruption and the rest of the patients Table 1. General characteristics of the included studies. Authors, Year Country Study design Median time from the time Mean Hospital Total cases Confirmed of injury to the time of follow-up stay of penile urethral presentation to the Hospital (months) (days) fracture injury Amit et al, 2013 (20) India Retrospective case series NA 34.3 2 34 8 Kasaraneni et al, 2019 (27) India Prospective observational 6 24 2 75 12 Derouiche et al, 2007 (22) Tunisia Retrospective case series 10 18 14 312 10 Raheem et al, 2014 (6) Egypt Retrospective case series 5.5 72.6 2.1 246 12 Ibrahiem et al, 2010 (23) Egypt Retrospective case series 48.5 107 2.3 155 14 Barros et al, 2018 (26) Brazil Prospective observational NA NA NA 175 27 Mercado-Olivares et al, 2018 (34) Peru Case Report 19 NA NA 281 1 Ouanes et al, 2021 (24) Tunisia Retrospective case series 1 to 5 12 NA 138 15 Hughes et al, 2021 (33) UK Case Report NA NA NA 1 1 Boncher et al, 2010 (39) USA Case Report 8 48 NA 1 1 Tang et al, 2018 (25) USA Retrospective case series 1.2 ± 1.03 21 (1-73) NA 62 13 Ge et al, 2021 (31) China Case Report NA 12 NA 1 1 Garofalo et al, 2015 (30) Italy Case Report 1 12 2 1 1 Jagodic̆ et al, 2007 (29) Slovenia Case Report 6 12 13 1 1 Hoag et al, 2011 (28) Canada Case Report 1 1 2 1 1 Archivio Italiano di Urologia e Andrologia 2023; 95, 2 S.E. Shebl 123 had a complete rupture. Two studies reported the utiliza- tion of RGU for the evaluation of PF and associated ure- thral injuries (Tables 2 and 3). Treatment and outcomes of the included cases All patients received primary urethroplasty as the main modality of treatment. Besides, 15 patients needed a supra-pubic cystostomy tube. Fifty-one patients received medications to prevent erection in the form of estradiol, diazepam, sildenafil, and amyl nitrite. The median hospital stay was two days and the median duration of transurethral catheterization was 21 days. Five patients (8.5%) developed urethral stricture; other complications included penile curvature (6.7%), palpable fibrosis (6.7%), and erectile dysfunction (3.4%) (Table 4). DISCUSSION Urethral injuries can concurrently occur in patients with PF and a considerable proportion of these injuries are missed at initial diagnosis, despite being widely considered as a serious complication. If not discovered and managed early, associated urethral injuries can dramatically lead to short and long-term complications in patients with PF (2). However, due to the rarity of the disease, little literature has been published so far concerning the presentation and outcomes of PF with associated urethral injury. Table 3. The distribution of intraoperative findings and location of injury among the included patients. Authors, year Intra operative findings Location of injury Partial Complete Proximal Midshaft Distal Bilateral Unilateral Right Left urethral urethral shaft shaft corporal corporal corporal corporal disruption disruption of penis of penis involvement involvement involvement involvement Amit et al, 2013 (20) 7 1 6 NA NA 1 7 5 2 Kasaraneni et al, 2019 (27) 11 1 6 2 4 1 11 4 6 Derouiche et al, 2007 (22) 10 0 5 4 1 0 10 6 4 Raheem et al, 2014 (6) 1 11 0 12 0 12 0 0 0 Ibrahiem et al, 2010 (23) 11 3 NA NA NA NA NA NA NA Barros et al, 2018 (26) NA NA NA NA NA NA NA NA NA Mercado-Olivares et al, 2018 (34) NA NA 0 0 1 0 1 1 0 Ouanes et al, 2021 (24) NA NA 118 0 20 0 138 NA NA Hughes et al, 2021 (33) NA NA 0 0 1 0 1 0 1 Boncher et al, 2010 (39) NA NA 0 0 1 0 1 1 0 Tang et al, 2018 (25) NA NA 23 18 21 NA NA NA NA Ge et al, 2021 (31) 0 1 1 0 0 NA NA NA NA Garofalo et al, 2015 (30) 0 1 1 0 0 0 1 1 0 Jagodic̆ et al, 2007 (29) 0 1 1 0 0 NA NA NA NA Hoag et al, 2011 (28) 0 1 1 0 0 1 0 0 0 Table 2. The distribution of causes and presentations among the included patients. Authors, year Causes of penile fractures Presentation of penile fracture Sexual Rolling Blunt Forced Masturbation Urethral Hematoma Crackling Penile Bladder Aubergine Retention intercourse over injury penile bleed or sound swelling palpable sign/egg-plant of urine pending eccymosis deformity Amit et al, 2013 (20) 6 0 0 0 2 6 0 6 0 NA 6 NA Kasaraneni et al, 2019 (27) 9 2 1 0 0 11 0 7 0 3 12 3 Derouiche et al, 2007 (22) 0 4 0 0 6 10 0 10 0 2 10 2 Raheem et al, 2014 (6) 11 0 0 1 0 12 12 0 12 0 0 3 Ibrahiem et al, 2010 (23) 7 NA NA 0 NA 13 14 NA 14 0 0 NA Barros et al, 2018 (26) 69 0 0 5 16 NA NA NA NA NA NA NA Mercado-Olivares et al, 2018 (34) 1 0 0 0 0 0 1 0 0 0 0 0 Ouanes et al, 2021 (24) 47 NA NA 62 NA NA NA NA NA NA NA NA Hughes et al, 2021 (33) 1 0 0 0 0 1 1 1 0 0 0 0 Boncher et al, 2010 (39) 1 0 0 0 0 0 1 1 1 0 1 0 Tang et al, 2018 (25) 41 0 0 19 2 12 44 34 62 0 0 0 Ge et al, 2021 (31) 1 0 0 0 0 1 1 1 1 0 0 0 Garofalo et al, 2015 (30) 1 0 1 0 0 1 1 1 1 0 0 0 Jagodic̆ et al, 2007 (29) 1 0 0 0 0 1 1 1 1 1 0 1 Hoag et al, 2011 (28) 1 0 1 0 0 1 1 0 1 0 0 0 Archivio Italiano di Urologia e Andrologia 2023; 95, 2 124 The presentation and outcomes of penile fracture with associated urethral injury Therefore, we conducted this systematic review to address the current literature concerning the PF with associated urethral injury. Our results highlighted that there are cur- rently 65 published cases of PF with associated urethral injuries giving a point prevalence of 3.9%. Such findings are in line with a large case-series of 312 PF cases from the Middle East, in which ten cases had associated urethral injuries (22). Other reports from the Middle East reported similar findings (35). On the contrary, reports from Europe and the United States demonstrated a much higher preva- lence of associated urethral injuries, affecting up to one- third of PF cases (36-38). It is not clear why patients from the Middle East had a lower prevalence of associated ure- thral injuries; however, it was reported that a large number of PF in the Middle East is attributed to the widespread practice of “taghaandan”, which is a low-energy trauma with a low possibility of urethral injuries (35, 32). We also pos- tulated that the low prevalence of associated urethral injuries can be attributed to a large number of pooled cases with PF from the Middle East and the dependence on clin- ical examination, without further investigations, which might have led to under-detection of associated urethral injuries. As previously mentioned, the proximal and midshaft penis are the most commonly affected sites by PF; while sexual intercourse and masturbation account for the vast majority of PF (1, 4). These findings appear to apply also to patients with associated urethral injuries; in this review, we found that the most common cause of fracture was sex- ual intercourse, followed by masturbation and rolling over; while the majority of the cases had proximal and midshaft fractures. Clinically, the presence of urethral injuries is suspected when there is blood at the meatus, with or without hematuria, on examination; besides, urine analysis and RGU can be useful for identifications of asso- ciated urethral injuries (15). However, as demonstrated by this systematic review, some PF cases may not exhibit spe- cific symptoms for urethral injuries (see Table 3). Besides, urine analysis and RGU exhibited false-negative results in some case-series (15, 39). Thus, a careful intraoperative inspection of the urethra is recommended in all cases with PF to avoid missed injuries. To our knowledge, there is no published systematic review that has attempted to explore the presentation and out- comes of PF cases with associated urethral injuries; nonetheless, we acknowledge the existence of several limi- tations in our review. All included studies suffered from substantial methodological flaws that can affect the quality and generalizability of our findings. The outcome measure- ments are subjective and postoperative erectile and voiding functions have not been assessed using validated tools. In conclusion, urethral injuries are uncommon, but seri- ous findings, in patients with PF. The clinical presenta- tion of patients with urethral injuries usually involves urethral bleeding and hematuria. The diagnosis of associ- ated urethral injuries can be established by clinical exam- ination with the limited role of imaging studies. Thus, a careful intraoperative inspection of the urethra is recom- mended in all cases with PF in order to avoid missed injuries. Primary urethroplasty appears to achieve satis- factory outcomes with a low incidence of short and long- term complications. Nonetheless, the current published literature is still limited by the low number of published cases and low quality of published reports; thus, further studies are needed to characterize the presentation and outcomes of PF with association urethral injuries. ACKNOWLEDGMENT The authors thank the study participants, trial staff, and investigators for their participation. REFERENCES 1. Mahapatra RS, Kundu AK, Pal DK. Penile Fracture: Our Experience in a Tertiary Care Hospital. World J Mens Health. 2015; 33:95. Table 4. The treatment and outcomes of injury among the included patients. Authors, year Treatment Supra-pubic Medication Median duration Hospital Complications cystostomy to prevent of transurethral stay Penile Palpable Erectile Stricture UTI tube erection catheterization (days) (days) curvature fibrosis dysfunction urethra Amit et al, 2013 (20) Primary urethroplasty Not used Estradiol 21 2 0 0 1 0 0 Kasaraneni et al, 2019 (27) Primary urethroplasty Not used Estradiol 21 2 1 0 0 1 2 Derouiche et al, 2007 (22) Primary urethroplasty Used Diazepam 13 14 0 0 0 0 0 Raheem et al, 2014 (6) Primary urethroplasty Used in 5 patients Sildenafil® 22.5 2.1 2 3 1 1 0 Ibrahiem et al, 2010 (23) Primary urethroplasty Not used PGE1 NA 2.3 NA 1 NA 1 0 Barros et al, 2018 (26) NA NA NA NA NA NA NA NA NA NA Mercado-Olivares et al, 2018 (34) Primary urethroplasty NA NA NA NA 0 0 0 0 0 Ouanes et al, 2021 (24) Primary urethroplasty NA NA NA NA NA NA NA NA NA Hughes et al, 2021 (33) Primary urethroplasty NA NA NA NA NA NA NA NA NA Boncher et al, 2010 (39) Primary urethroplasty NA Diazepam 28 NA 0 0 0 0 0 Tang et al, 2018 (25) Primary urethroplasty Used amyl nitate NA NA 0 0 0 0 0 Ge et al, 2021 (31) Primary urethroplasty NA NA 12 NA NA NA NA NA NA Garofalo et al, 2015 (30) Primary urethroplasty Used NA NA 2 1 0 0 1 0 Jagodic̆ et al, 2007 (29) Primary urethroplasty Used Diazepam 12 13 0 0 0 1 0 Hoag et al, 2011 (28) Primary urethroplasty Used NA 28 2 NA NA NA NA NA Archivio Italiano di Urologia e Andrologia 2023; 95, 2 S.E. 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Urethrography and caver- nosography imaging in a small series of penile fractures: A compari- son with surgical findings. Urology. 1998; 51:616-9. Correspondence Salah E. Shebl, MD (Corresponding Author) salahshebl@yahoo.com salahshebl@azhar.edu.eg Urology Department, Faculty of medicine for girls Al-Azhar University Urology Department, Alzahraa University Hospital, Cairo, Egypt Conflict of interest: The authors declare no potential conflict of interest.