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Current perspectives in hypospadias research: A scoping review of articles published in 2021 (Review)

  • Authors:
    • Horea Gozar
    • Zsolt Bara
    • Emilia Dicu
    • Zoltán Derzsi

  • View Affiliations

  • Published online on: March 23, 2023     https://doi.org/10.3892/etm.2023.11910
  • Article Number: 211

  • Copyright: © Gozar et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hundreds of papers are written about hypospadias every year referring to all aspects of the pathology, being one of the most common congenital malformations. The present study conducted a scoping review of articles published in 2021 to present the main issues and summarize current perspectives and achievements in the field. It searched for the keyword ‘hypospadias’ in the three most popular databases (PubMed, Scopus and Web of Science). After the analysis of the publications, they were categorized into different domains. The present review was performed respecting the Preferred Reporting Items for Systematic reviews and Meta‑Analyses extension for Scoping Reviews (PRISMA ScR) guidelines. A total of 284 articles were included. These were published in 142 different journals. The most accessed was the Journal of Paediatric Urology with 54 articles. The main identified domains were related to surgical techniques, postoperative care, complications, anesthesia, anatomical factors, genetics, environmental factors, endocrinology, associated malformations, questionnaires and recommendations, management, biological materials, animal models, retrospective studies of centers, social media, bibliometrics, small gestational age, neoplasm, or fertility. Promising modifications of existing surgical techniques were presented with improved outcomes for both the proximal and distal types of hypospadias. Relevant anatomical and etiological, and also genetic factors were clarified. Aspects of the peri‑ and postoperative management referring to the antibiotherapy, analgesia, dressing techniques, and the future use of novel bioengineering agents to prevent, reduce or treat the occurring complications were discussed.

1. Introduction

Hypospadias is a congenital malformation, in which the meatus is opening on the ventral aspect of the penis, at different possible levels. Usually, the malformation is more complex and may be associated with penile curvature, glans deformation, narrow meatus or megameatus, and anomalies of the skin. Severe cases can present other urogenital or chromosomal anomalies. There are a number of unknown aspects of this malformation's etiology and development (1,2). Hypospadias repair may be a routine operation in distal cases and can be very challenging in proximal cases, even for a trained surgeon. There is no consensus on the treatment options for hypospadias and the development of treatment guidelines remains an unsolved file in medicine.

Furthermore, how the penis look is an important somatic and psychological facet of every boy or every family. In these conditions, it is obvious it became a subject of interest in medicine and a number of doctors from different specialties (especially pediatric surgeons or urologists) have tried to solve the problem (3-5).

In the last 10 years, according to the PubMed platform, an average of 313 (±38) studies were published each year (based on a search for the keyword ‘hypospadias’), the number of papers increasing each year. This pathology represents one of the most debated problems and not only among pediatric surgeons (6). For every pediatric surgeon, urologist, and specialist in this field, it is essential to know what is new about hypospadias and be up to date. The present study aims to present this pathology's current perspectives and the most important achievements in hypospadias research during 2021.

2. Materials and methods

The present study protocol was registered with the International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) on 23 November 2022 and was last updated on 23 November 2022 (registration number INPLASY2022110117). It was performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA ScR) guidelines.

The present study chose the three most popular platforms (PubMed, Scopus and Web of Science) and searched for the keyword ‘hypospadias’. All the publications were restricted to 2021. All the results were downloaded in CVS format (or directly as xls format in the case of the Web of Science platform) and processed using Microsoft Excel software. The articles from PubMed were used as a base of the research, PubMed being considered the most accessible and most frequently used database. The duplicate records were removed compared to the results from the other two platforms. The remaining articles were analyzed individually and manually by the three reviewers.

The present study included all the articles which were published in 2021 in the research field of hypospadias with valuable information relating to surgical techniques, postoperative care, complications, anesthesia, anatomical factors, genetics, environmental factors, endocrinology, associated malformations, questionnaires and recommendations, management, biological materials, animal models, retrospective studies of centers, social media, bibliometrics, small gestational age, neoplasm, or fertility. Articles which were written in English were accepted. Papers in other languages were accepted if they had an English abstract with valorous information. Papers which were published in a year other than 2021, were outside of the research field, or were referring to other pathologies were excluded. However, those articles which were published in print format in 2022 and online in 2021 were considered as 2021 articles. Books, commentaries, responses to other papers, errata and withdrawn articles were excluded.

Source selection (both at title/abstract screening and full-text screening) was performed by the three reviewers independently (HG, ZB and ED). Any disagreements were solved by consensus or by the decision of the fourth reviewer (ZD). The process was accompanied by a flowchart detailing the flow from the search, through source selection, duplicates, retrievals, and any additions. The workflow is shown in Fig. 1.

The present study extracted from every qualified paper the essential ideas and conclusions. Then, this information was arranged and grouped into categories, some of them even into subcategories. The main information of the papers on the same topic with similar conclusions was merged, reformulated, and included in the corresponding table. The databases were accessed for the last time on the 20 November 2022. The number of references and the number of included articles differ as in the introduction some papers were cited to describe hypospadias in general.

The conclusions from the included articles relating to hypospadias research were categorized into 18 chapters: Surgical techniques (Subgroups: proximal hypospadias repair, distal hypospadias repair, covering tissue, curvature, fistula and stenosis, reoperative techniques, others), Postoperative care, Complications, Anesthesia, Anatomical factors, Genetics (reviews, genetical research on a population or on hospitalized patients, genetic counseling, genetic syndromes and malformations, genetical and histological analyses), Environmental factors, Endocrinology, Associated malformations, Questionnaires and recommendations, Management, Biological materials, Animal models, Retrospective studies of centers, Social media, Bibliometrics, Small gestational age, Neoplasm, and fertility.

3. Results

A total of 284 articles were included. These were published in 142 different journals in 2021. The most accessed journal on this topic was the Journal of Paediatric Urology with 54 articles (37.75% of the analyzed publications), followed by the World Journal of Urology (nine articles), the African Journal of Urology (eight articles), Journal of Paediatric Surgery (eight articles), Urology (seven articles), Research and Reports in Urology (seven articles), Journal of Urology (seven articles), Frontiers in Pediatrics (seven articles), Andrologia (six articles), Cureus (five articles). All the other publications had fewer than five papers.

The studies were classified in the described manner and 71 referring to surgical techniques (Subgroups: 27, proximal hypospadias repair; 18, distal hypospadias repair; seven, covering tissue; four, curvature; nine, fistula and stenosis; three, reoperative techniques; and three, others), 18 to postoperative care, 16 to complications, 13 to anesthesia, 22 to anatomical factors, 41 to genetics (three, reviews; 21, genetical factors; six, genetical research on a population or on hospitalized patients; four, genetic counseling; five, genetic syndromes and malformations; and two, genetical and histological analyses), 19 to environmental factors, 11 to endocrinology, nine to associated malformations, 20 to questionnaires and recommendations, six to management, six to biological materials, 11 to animal models, 11 to retrospective studies of centers, three to social media, three to bibliometrics, two to small gestational age and two to neoplasm and fertility.

4. Surgical techniques in hypospadias repair

Surgical techniques represents the most important chapter. A number of them refer to proximal hypospadias repair, which is considered the most challenging among surgeons. There were no new techniques described, but modifications were mentioned by different authors in hope of an improved outcome and reducing the complication rate (7-9). The majority of studies concluded that two-stage surgery leads to improved results compared with one stage (9-12). The options described are modified Koyanagi technique (13-15), transverse preputial island flap urethroplasty (10,12,16), inlay (17-19), or buccal mucosa graft (20,21). Tunica vaginalis represents a good coverage material (22-24). Scrotal raphe may be considered as a reserved option in cases of lack of skin (25). The urethroplasty in proximal hypospadias has improved results when stops at the balanic sulcus. There is only one study that proposes a three-stage urethroplasty (26).

Referring to distal hypospadias, tubularized incised urethroplasty remains the most common and indicated operation (27-31). Dorsal inlay graft urethroplasty (17,19), onlay preputial flap (19) and hybrid Mathieu urethroplasty are mentioned techniques (32,33). A number of authors in the last years prefer the simple advancement of the meatus instead of a proper urethroplasty.

Neourethral covering tissues are effective to prevent complications: tunica vaginalis, dartos, or Buck's fascia are well-known, they can be used in one or two layers. Dorsal plication remains the most used and simple approach to ventral curvature (34).

Table I presents the summaries of the articles about surgical techniques in hypospadias repair.

Table I

Summary of the articles about surgical techniques in hypospadias repair.

Table I

Summary of the articles about surgical techniques in hypospadias repair.

Proximal hypospadias
Author, yearConclusions(Refs.)
Wang et al, 2021Proximal hypospadias operated with transverse preputial island flap urethroplasty: those who benefit from incised urethral diversion had improved outcomes compared with those with transurethral diversion.(8)
Ali MM et al, 2021Staged (two-stage) transverse preputial island flap urethroplasty has improved results compared with one-stage surgery.(10)
Zhu X et al, 2021 (12)
Lin et al, 2021 (16)
Zhu XJ et al, 2021 (35)
Ali and Anwar, 2022 (36)
Chan et al, 2021Proximal hypospadias repairs in two stages: Pedicled preputial flaps and inlay grafts are superior choices compared with Byars' flaps.(11)
Zhu et al, 2021Transected urethral plate and transverse preputial island flap are good techniques in severe hypospadias.(12)
Madec et al, 2022A two stage procedure Koyanagi urethroplasty allows good final results.(13)
Aziz Tamer et al, 2021 (37)
Vu et al, 2021Results of the one-stage proximal hypospadias repair with modified Koyanagi technique in a single Vietnam center.(14)
Acimi et al, 2021Despite the modifications added by Snow and Hayashi to Koyanagi urethroplasty in so-called Koyanagi-Snow-Hayashi urethroplasty, the rate of complications. remains high(15)
Silay et al, 2021Inlay graft is a good choice, but it is not superior to classic repair.(17)
Chen et al, 2021Urethroplasty with buccal mucosa graft, in the first stage, facilitates the second-stage neourethral coverage and is a good technique.(20)
Shandilya et al, 2021 (21)
Radhakrishnan et al, 2021The tunica-vaginalis flap is an excellent buttress in severe hypospadias repair.(24)
Akkary et al, 2021 (39)
Obaidullah et al, 2021Islanded scrotal raphe flap is an option in complicated hypospadias repair with skin. shortage(25)
Chen et al, 2021 (41)
Lu et al, 2021The positioning of the external urethral orifice in the coronary sulcus, and urethroplasty in case of severe hypospadias leads to superior results.(38)
Akkary et al, 2021 (39)
Ding et al, 2021Prefabricated urethra and pre-implanted urethral plate methods are suitable for the correction of severe hypospadias as staging surgery in children.(40)
Lyu et al, 2021Spongiosum-combined glanuloplasty reduces the rate of complications in proximal. hypospadias(42)
Karakuș et al, 2021Vertical plication in penile curvature displaces the urethral plate transection in proximal hypospadias.(43)
Ndiaye et al, 2021Tubed pedicled preputial island flap (DUCKETT procedure) is associated with a high complication rate.(44)
Rawashdeh et al, 2021Foreskin transplantation in a two-stage reconstruction between monozygotic twins.(45)
Blanc et al, 2021Double-face preputial island flap revisited is a reliable one-stage procedure for proximal hypospadias.(46)
Fahiem-Ul-Hassan et al, 2021Single-stage urethroplasty is a versatile approach for different types of hypospadias, with a fistula rate of 12.8%. Posterior hypospadias, pyuria, and longer urethral defect are associated with higher rates of fistula formation.(47)
Keshk et al, 2021The modified Koyanagi one-stage repair of proximal hypospadias uses a dartos muscle flap as a cover for the urethroplasty improves the results and minimizes. complications(48)
Tudu et al, 2021The outcome of pediatric urethroplasty was favourable with routine use of intermediate vascularised flap in proximal hypospadias repair.(49)
Long et al, 2021Masculinizing genitoplasty in children with genital atypia, even if the parents opted for early surgery, is associated with 41% complications in cases of severe hypospadias, in a multicentric study.(50)
Distal hypospadias
Omran et al, 2021Dorsal inlay graft urethroplasty (DIGU) has improved surgical outcome compared with Onlay preputial flap (LOF).(19)
Taneli et al, 2021Tubularized reconstructed plate urethroplasty (TRPU) is an alternative for distal hypospadias repair, without incision or grafting.(27)
Khirallah et al, 2021Hybrid Mathieu urethroplasty: the Mathieu technique associated with incision of the urethral plate.(32)
Fahiem Ul-Hassan et al, 2021Buck's fascia repair with wingless glanuloplasty is a good technique with low fistula rates and glanular dehiscence(47)
Askarpour et al, 2021Meatal advancement glandular with release chordi is superior to Snodgrass methods, regarding the repair of distal hypospadias.(51)
Edan, 2021The urethral mobilization technique is a good choice, especially in the case of circumcised patients, the cosmesis and functional results are good and the. complications are less(52)
Noureldin et al, 2021Predictors of successful outcome of TIP repair are: absence of the chordee, meatus at coronal/subcoronal level, plate width ≥9 mm, AGD >5 cm, patient younger than ≤2 years old, GMS score ≤7, SPL >3.5 cm and grooved glanular shape.(53)
Abdelhalim et al, 2021 (54)
Shoukry et al, 2021Patients with a GMS score >6 have a higher risk of complications. Glans width of ≥14 mm and a penoscrotal length of ≥5 cm is associated with less risk of complication.(55)
Macedo et a, 2021The GUD (glandular urethral disassembly) technique (without urethroplasty): disconnects the spongious and the distal urethra from the corpora and detaching partially the glans. The glans is opened in midline. It is followed by cranial mobilization of the urethra with caudal and medial rotation of glans wings.(56)
Özbey et al, 2021Modeling of the foreskin with the GFC (Glanular-Frenular-Collar) technique to obtain an anatomic aspect.(57)
Permana et al, 2021TIP urethroplasty leads to good cosmetic and functional outcomes for the cases with megameatus intact prepuce.(58)
Ahmed et al, 2021The grafted-TIP urethroplasty has comparable results with the classic-TIP in terms of cosmoses, success rate, and complications; grafted-TIP is associated with significantly longer operative time.(59)
Kızılöz et al, 2021MAGPI under local anesthesia without a catheter is an alternative to the TIP procedure in distal hypospadias repair.(60)
Alshammari et al, 2021Deepithelialized glans reconfiguration (DeGRe) is a good option for distal hypospadias.(61)
Zhang et al, 2021Reconstructing forked corpus spongiosum provides excellent outcomes.(62)
Mohajerzadeh et al, 2021With the exception of the long-term outcomes in cosmetic and functional evaluation, Mathieu incised plate technique is superior to TIP technique.(63)
Benson et al, 2021A review of long-term outcomes of one-stage augmentation anterior urethroplasty shows worse results than expected.(64)
Covering tissue
Tiwari et al, 2021Tunica vaginalis flap or graft is a viable method to repair urethra lesions.(22)
Favorito et al, 2021 (23)
Tessier et al, 2021The more severe the hypospadias, the more effective is the cover the new urethra with flap.(65)
Rudin et al, 2021The augmentation of the urethral plate of the glans and the distal urethra with the implantation of a wide rectangular free flap in to the meatus, represents an advantage over the implantation of diamond-shaped grafts using the GTIP or TIP graft technique.(66)
Verma et al, 2021Dartos Flap as an additional cover to TIP is associated with an acceptable complication and has good cosmesis compared with spongioplasty.(67)
Naumeri et al, 2021The covering of neo-urethra by a double dartos layer (compared with a single layer), significantly reduces complications after tubularized incised plate urethroplasty.(68)
Zhang et al, 2021Buck's fascia with the glans can be used as an integral covering technique in one-stage distal to proximal hypospadias and primary or re-operative hypospadias repair.(69)
Curvature
Akdemir et al, 2021Dorsal plication is a relatively simple method with low risk and a high success rate for the treatment of congenital ventral penile curvatures.(34)
Cetin et al, 2021There are no differences in outcomes between pre-pubertal and post-pubertal boys after correction of penile curvature using corporal plication.(70)
Kozyrev et al, 2021STAGE technique in ventral curvature penile allows to correct ventral curvature of 15-60˚ with minimal complications.(71)
Zhou et al, 2022Interposition urethroplasty for glandular hypospadias is a reliable technique. The staged technique had superior outcomes compared with the single-stage technique.(72)
Fistula and stenosis
Swatesutipun et al, 2021For urethral stenosis: dorsal transurethral incision, (±dilatation), then oral mucosa graft on the defect (±glans preservation) is a feasible technique. Long strictures and thickness skin grafts are associated with lower success(18)
Furr et al, 2021 (73)
Favre et al, 2021 (74)
Mershon et al, 2021Recurrent Anterior Urethral Stricture. Augmentation with genital skin flaps and/or grafts or with buccal mucosa is occasionally required. Urinary diversion and perineal urethrostomy has to be considered.(75)
Sing et al, 2022PATIO technique for small fistulae is more successful compared with standard repair.(76)
Bar-Yosef et al, 2022Concomitant repair of meatal stenosis and urethral fistula does not increase the risk of fistula recurrence.(77)
Chatterjee et al, 2021Epithelium of track of the fistula is ablated with a hypodermic needle.(78)
Shirazi et al, 2021Clamping time for >2 min may prevent bleeding during and after meatotomy.(79)
Shaw et al, 2021Asopa technique represents an option for augmenting urethral caliber for urethral strictures.(80)
Reoperative techniques
Jordan et al, 2022A 3-Stage Approach for the Reoperative Hypospadias. i) Excision and buccal mucosal graft harvest. ii) Dorsal tissue expander placement. iii) The creation of neourethra and skin closure.(26)
Xie et al, 2022The Mathieu combined tunnel technique for repairing glans dehiscence after failed hypospadias repair is a feasible and reliable procedure.(33)
Yadav et al, 2021The best treatment for hypospadic meatal stenosis might be a dorsal midline incision, as it does not lead to a proximal shift of the meatus, and heals by reepithelisation without significant scarring, which decreases fistula formation.(81)
Others
Samir et al, 2021Running sutures groups was associated with a higher complication rate compared to interrupted sutures.(82)
Spinoit et al, 2021Redistribution of the abundant dorsal skin and its hooded prepuce to the ventral side of the penis is an option in a number of situations.(83)
Alaraby et al, 2021Running sutures is a superior suture compare to Vicryl.(84)

5. Postoperative care

Post-operatory care was also a debated issue. In some authors' opinion, stented or un-stented repair may lead to a similar outcome, especially in the case of distal hypospadias (28,85). The type of the dressings was not considered as important, although a number of substances were enumerated by different authors to increase their efficacy. Using compound Chamomile and Lidocaine hydrochloride gel, Aloe vera, or autologous platelet gel might decrease pain and edema, reduce inflammation and fibrosis, tubular finger oxygen-enriched oil inside-coated device decrease complications (86,87). Hyperbaric oxygen therapy may help in wound healing (88,89). The number of diapers used is not important for the surgical outcome, but a good washing of genitalia before and after surgery may be effective (90). The use of opioids or perioperative antibiotics is not relevant for surgical success (91-93). Postoperative C-Reactive Protein value (24 h after surgery) is a reliable marker for a possible complication after hypospadias surgery (94).

Table II presents the summaries of the articles about postoperative care.

Table II

Summary of the articles about surgical techniques in hypospadias repair.

Table II

Summary of the articles about surgical techniques in hypospadias repair.

Author, yearConclusions(Refs.)
Abdel-Hamid El-Hawy et al, 2021The outcome after stented and un-stented distal urethroplasty reveals similar results.(28)
Scarpa et al, 2021 (85)
Zhang et al, 2021Compound chamomile and Lidocaine hydrochloride gel relieve pain and reduce edema following hypospadias surgery.(86)
Doluoglu et al, 2022Aloe vera applied to the wound decreases inflammation and fibrosis after the tubularized incised plate urethroplasty model on rats.(87)
Anand et al, 2022Hyperbaric oxygen therapy prevents wound infection and helps in wound healing and decreases graft failure.(89)
Donelly et al, 2021Factors associated with opioid prescriptions in postoperative pediatric urology prescription were increasing age and scrotal surgery.(91)
Basin et al, 2021 (93)
Cornwell et al, 2022Children undergoing hypospadias surgery usually do not require opioid analgesics and are more likely to endorse pain.(92)
Ji F et al, 2021Postoperative C-Reactive Protein value (24 h after surgery) is a reliable marker for a possible complication after hypospadias surgery.(94)
Karakaya et al, 2021Functional and cosmetic results after TIPU are independent of dressing.(95)
Esposito et al, 2021Dressing using a tubular finger oxygen-enriched oil inside-coated device is effective, easy to manage, cheaper and decreases the rate of complications.(96,97)
Anand, 2021Tissue glue-based dressings following hypospadias repair do not represent a major change in postoperative care.(98)
Elsayem et al, 2022Autologous platelet gel improves outcomes in tubularized incised plate repair and limits surgical complications.(99)
Murakami et al, 2021Washing the genitals and groin 2 h preoperatively as well as immediately after the removal of a stent, to prevent infections after hypospadias repair.(100)
Canon et al, 2021The use of perioperative prophylactic antibiotics in hypospadias surgery does not reduce the possibility of infections.(101)

6. Complications after hypospadias repair

The most common complications after hypospadias repair remain fistula or stenosis. In some cases, they are easy to treat, but some of them require special interventions with grafts or dilatations and perineal diversion of the urine (28,102,103). For urethra suturing, interrupted sutures are an improvement on running sutures and PDS an improvement on Vicryl (82,104).

Wound dehiscence also remains a debated problem. Factors affecting glanular dehiscence are anatomical (glans width <14 mm, urethral plate width <7 mm), age (before 6 months of age and after puberty), and anesthesia (caudal block). All of these required reinterventions (42,105). Reoperation rate after distal hypospadias repair ranges from 3.3-6.7% (106,107). Other related complications are penile curvature that appears in 25% of cases (>30˚) (43,102,108-110), hairy urethra (111,112), erectile dysfunctions (113,114) and lower urinary tract symptoms (115). There were similar complications every surgeon is acquainted with.

Table III summarizes the articles on complications.

Table III

Summary of the articles about complications after hypospadias repair.

Table III

Summary of the articles about complications after hypospadias repair.

Author, yearConclusions(Refs.)
Kim et al, 2021Penile curvature appears in 25% (>30 degrees) of patients operated on hypospadias within the first 2 years.(102)
Snodgrass et al, 2021 (108)
Spinoit et al, 2021 (110)
Arslan et al, 2022Unusual case: Combined dorsal and lateral subcoronal urethrocutaneous fistula.(103)
Karabulut et al, 2022Factors affecting glanular dehiscence: anatomical (glans width <14 mm, urethral plate width <7 mm), age (before 6 months of age and after puberty), anesthesia (caudal block).(105)
Nguyen et al, 2021Reoperation rate after distal hypospadias repair: 3.3 to 6.7%. Follow-up at least 6 years is mandatory.(106)
Varea et al, 2021Hairy urethra or diverticulum found after hypospadias surgery using flap.(111)
Kumar et al, 2021 (112)
Husmann, 2021Erectile dysfunction after multiple hypospadias surgery is associated with advancing age, division of the urethral plate, prior ventral corporal grafting and repetitive internal urethrotomy for strictures.(114)
Chapman et al, 2021The consequence after urethroplasty: LUTS (lower urinary tract symptoms) related to detrusor underactivity.(115)
Favre et al, 2021The main etiological factor for urethral stricture is hypospadias.(116)
Faraj et al, 202225% of adults presenting with bulbar strictures have a history of hypospadias repair in childhood.(117)
Ali et al, 2021Failing to correct the deficient corpus spongiosum during hypospadias surgery, may become symptomatic in adolescence.(118)
Tack et al, 2021Hypospadias repair: More reinterventions if the initial repair was performed under 12 months, urinary problems and/or suboptimal sexual functional (52.9%), suboptimal voiding (22.1%).(119)
Godfrey, 2021Patients with hypospadias or complete androgen insensitivity syndrome reported better mental health than patients with other 46, XY (disorders of sexual development) diagnoses.(120)
Sembring et al, 2021Preoperative testosterone administration is accompanied by decreased risk of. glandular dehiscence(121)
Lucas-Herald et al, 2022Hypospadias is associated with vascular dysfunction including hypercontractility and impaired vasodilation. Secondary endothelial dysfunction and vascular injury early in life predispose to hypertension and cardiovascular events in adulthood.(122)

7. Anesthesia

General anesthesia remains the most widely accepted type of anesthesia in hypospadias repair (29,123-125). It is difficult to recommend regional anesthesia for pediatric penoscrotal procedures (127). The usefulness of caudal block-type anesthesia in postoperative pain control and its potential to favor complications represent a common topic. According to Routh (127) caudal block ‘is not a cause of complication-according to the data- and it is not a key to success’. A restrictive regimen is preferred over the conventional intraoperative fluid regimen during hypospadias surgery (128).

Table IV summarizes the articles on anesthesia.

Table IV

Summary of the articles about anesthesia.

Table IV

Summary of the articles about anesthesia.

Author, yearConclusions(Refs.)
Zhang et al, 2021There are similar rates of complications between groups receiving caudal block and general anesthesia vs general anesthesia in hypospadias surgery.(29)
Alizadeh et al, 2022 (123)
Koul et al, 2022 (124)
Adler et al, 2021 (125)
Osmani et al, 2021It is difficult to recommend regional anesthesia for ambulatory pediatric penoscrotal procedures. It depends on the patient, anatomy, medical history, duration of surgery.(126)
Elsonbaty et al, 2021A restrictive regimen is preferred over the conventional intraoperative fluid regimen during hypospadias surgery, in terms of respiratory function and recovery.(128)
Kandirici et al, 2021Caudal block administration does not contributes to urethral fistula formation.(129)
Sisay et al, 2021A rare case report: total spinal anesthesia following caudal block.(130)
Ponde et al, 2021No difference between the success rate of the caudal block techniques: landmark guided, stimulation-guided, and ultrasound-guided; US-guided pudendal block gives more postoperative pain control.(131)
Abdalla et al, 2021 (132)
Wang et al, 2021Administration of 1.5 µg kg-1 of dexmedetomidine in the caudal block is most adequate to reduce anesthesia, and operation associated adverse events.(133)
Hassan et al, 2021Adding nalbuphine to levobupivacaine in caudal block had a longer duration for postoperative analgesia and showed more sedation time than fentanyl and dexamethasone with more stability in hemodynamics.(134)
Karami et al, 2021Caudal block can provide longer postoperative analgesia compared to penile block using rectal acetaminophen.(135)

8. Anatomical factors

There are some anatomical factors associated with hypospadias and the severity of the malformation. Glans width, urethral plate width and shape and history of previous surgery are the most important factors in hypospadias (136). In addition, the anogenital distance and penile length are diminished in children having this malformation (137). Small glans are associated with the severity of hypospadias (138). Penile curvature accompanies almost all cases of hypospadias. To objectively measure the penile curvature different degrees were defined, but it is difficult to standardize them (139,140). A paper proposes a 3D-printed penile model from a set of five pictures obtained from a lateral view (141).

Microvascular density in the prepuce is not clear which is correlated with the severity of the malformation (142). Magnetic resonance imaging is a solution to a improved view of anatomical components of the penis, even from the intrauterine stage, but we cannot imagine this procedure performed on every child presenting hypospadias (143,144). Artificial intelligence is not advanced enough to recognize and classify hypospadias (145). As another observation, 2/3 of the patients having prostatic utricle cysts present hypospadias (146).

The appetite for quantification is present in hypospadias. The Hypospadias Objective Penile Evaluation (HOPE) score, the Plate Objective Scoring Tool (POST), or the Glans-Meatus-Shaft score are proposed for an improved evaluation of hypospadias (30,147,148). Risk factors associated with complications were severe ventral curvature (the main factor), followed by urethral stricture, dehiscence, and reoperation (107).

Table V summarizes the articles about anatomical factors.

Table V

Summary of the articles about anatomical factors.

Table V

Summary of the articles about anatomical factors.

Author, yearConclusions(Refs.)
Zhang et al, 2021Urethral plate quality is an independent factor influencing postoperative outcomes of hypospadias surgery. Urethral plate width has to be ≥6 mm in tubularized incised plate urethroplasty.(29)
Abbas, 2021 (140)
Galal et al, 2021The urethral plate width and glandular width are not correlated with the TIP outcome. HOPE score is correlated with a wide urethral plate.(30)
Ru et al, 2021Risk factors associated with numerous reoperations: severe ventral curvature (the main factor), followed by urethral stricture, dehiscence, and primary staged repair.(107)
Ben-David et al, 2021Dorsal penile curvature associated with megameatus intact prepuce hypospadias required ventral plication.(109)
Goel et al, 2021Anatomical factors affecting the outcome of hypospadias repair: glans width (most important), urethral plate width and shape, and history of previous surgery.(136)
Sennert et al, 2022A small glans is found in about a third of distal, two-thirds in proximal, and more than 90% of perineal hypospadias.(138)
Abbas, 2022Patients having hypospadias had the lower scrotal base distance, anogenital distance, and penile length compared with a group of full-term healthy boys; a number of methods measure and make a degree of curvature, with strong and weak points, but no one became a standard. It is very important to have a preoperative objective quantification of curvature.(139)
Fernandez et al, 2021Standardization of penile angle with a set of 5 pictures obtained from a lateral view (00, 150, 300, 450, 600) at a standard distance of 75 cm results in a 3-D printed penile model with a curvature angle ranging from 10 to 90˚.(141)
Zhao et al, 2021The lower preputial microvessel density is correlated with the severity of hypospadias and early postoperative complications.(142)
Li et al, 2021Magnetic resonance imaging studies in hypospadias can present more accurate anatomical structures and the vascularization of the penis. This conduces to better preparation of surgery. This method can diagnose fetal hypospadias and evaluate the severity.(143)
Chaudhary et al, 2022 (144)
Fernandez et al, 2021Artificial intelligence with digital pattern recognition used for the diagnosis and classification of hypospadias is less accurate than an experienced pediatric urologist. With an increasing number of images, the accuracy of diagnosis becomes better.(145)
Dai et al, 20212/3 of the patients having prostatic utricle cysts present hypospadias.(146)
Abbas, 2021Plate Objective Scoring Tool (POST) proposes some important anatomical landmarks on the urethral plate to have an objective and accurate evaluation of this.(147)
D'Oro et al, 2021The pre-operative Glans-Meatus-Shaft Score can be altered after penile degloving and meatal displacement, resulting in a ‘meatal mismatch’ (20% of patients). This mismatch increase (3 times) the risk of fistula.(148)
Gopal et al, 2021Patients with and short anoscrotal distance have more chance to present severe chordee.(149)
Yeşildal et al, 2021Microvascular density in the prepuce with hypospadias is increased (also inflammation), compared to the healthy prepuce. The density of androgen and estrogen receptors are. similar(150)
Seleim et al, 2021Topographic labeling of glans and corpus spongiosum can lead to better planning of the. surgery(151)
Abdullaev et al, 2021The type of hypospadias and the length of the urethral defect are the main risk factors for recurrent fistula after primary urethrocutaneous fistulectomy.(152)
Özbey et al, 2021Long-term urethral catheterization can lead to disruption in a tear in the septum glandis and produce iatrogenic hypospadias.(153)

9. Genetics

Gene mutation is a proven cause for a part of these penile malformations. Table VI presents a number of cases of patients with hypospadias who had a novel mutation or a formerly mentioned one, syndromes, or complex malformations. Some genes can be associated with hypospadias in some geographical regions (such as, Algeria and China). There are only a few reviews (three) about gene complexes or syndromes that are associated with hypospadias (154-156). Genetic counseling for patients with hypospadias is mandatory, especially when hypospadias is associated with other malformations, is the conclusion of one study (157). Future studies will appear with more information and predictability and easier and more organized systems for managing genetic issues.

Table VI

Summary of the articles about genetical factors.

Table VI

Summary of the articles about genetical factors.

Genetics-Reviews
Author, yearConclusions(Refs.)
Gao et al, 2021There is a significant association between patients carrying MAMLD1 gene variants and micropenis, hypospadias, cryptorchidism, or split scrotum.(154)
Ibba et al, 2021DSD may be very different, with clinical variants and genetic or molecular alterations.(155)
Nassau et al, 2021Classic Klinefelter syndrome (46XXY) or mosaicism can be associated with a decrease of testosterone ambiguous genitalia, cryptorchidism, and/or hypospadias.(156)
Genetical factors
Fendereski et al, 2021A prenatally diagnosed 46, XY DSD with a typical female phenotype caused by two heterozygous variants in LHCGR including a novel c.29_55 alteration.(158)
Alfei et al, 2022A child with BCL11B missense mutation. Hypospadias and neurologic disorders.(159)
Li et al, 2021A novel variant of SRD5A2 gene in a child featuring steroid 5α-reductase type 2 deficiency in a boy with hypospadias.(160)
Strong et al, 2022A novel MBTPS2 variant (c.766 G>A; (p.Val256Leu) is associated with Bresheck syndrome (with genotypic and phenotypic manifestation) and hypospadias.(161)
Arsov et al, 2021A novel variant in NR2F2 is associated with asplenia, immune deficiency, glandular hypospadias, and cryptorchidism.(162)
Thomas et al, 2021Two patients with Desbuquois dysplasia due to homozygous CANT1 mutations presented hypoplastic scrotum and hypospadias.(163)
Bouhouche et al, 2021A new mutation c.461G>A (p.Arg154Gln) in the short-chain dehydrogenase/reductase family 42E member 1 (SDR42E1) gene in a boy with hypospadias and ocular. malformation(164)
Luo et al, 2021A novel mutation in the HRAS gene (c.38G>T; p.Gly13Val) was detected in a patient with Schimmelpenning-Feuerstein-Mims syndrome and hypospadias.(165)
Akramov et al, 2021The WT1 gene (chr11: 32417947G>A), leads to translation termination site in the 369 codons (p.Arg369Ter, NM_024426.4) in a boy with bilateral Wilms' tumor and. scrotal hypospadias(166)
Elghezal et al, 2021HSD17B3 variants (c.239 G>A, p.R80Q) are rare causes of 46, XY DSD. Whole exome sequencing can increase diagnostic and identify genomic variants; Ring X syndrome, hypospadias with 923 Kb terminal deletion on the pseudoautosomal region 1 (PAR1) including SHOX gene followed by a duplication of 2.4 Mb.(167)
Ravirajendran et al, 2021A young adult with 45X0/46XY mixed gonadal dysgenesis who had Mullerian remnants that tend to enlarge in size over time.(168)
Correya et al, 2021Two patients presenting DSD, ambiguous genitalia with a 45XO/46XY mosaic chromosome pattern, hypospadias, Mullerian remnants, gonadal dysgenesis, streak gonad.(169)
Chen et al, 2021Mutations c.154_162delinsTCCTGTT and c.674T>A leads to3β-HSD deficiency with adrenal insufficiency and sex hormone synthesis dysfunction and hypospadias.(170)
Saida et al, 2021X-linked intellectual disability with OTUD5 gene variants: c.878A>T, p.Asn293Ile [NM_017602.4], c.1210 C>T, p.Arg404Trp and p.Arg404Trp.(171)
Çiftci et al, 2022A case of 46XY patient with female phenotype who had a variation in the HSD17B3 gene: c.673_1G>C homozygous class 2 (splice site) variation in intron 9.(172)
Laan et al, 2021Partial gonadal dysgenesis in 46XY patients with NR5A1 c.991-1G > C splice-site variants: OTX2 p.P134R or PROP1 c.301_302delAG.(173)
Gerber et al, 2021Robinow syndrome is a rare, genetic disorder. Boys may have genitourinary atypicality, among them hypospadias in 5/8 patients.(174)
Sheppard et al, 2021Heterozygous recurrent HNF4A variant p.Arg85Trp causes Fanconi renotubular syndrome 4, diabetes, Fanconi Bickel syndrome with colobomas and hypospadias.(175)
Tripolszki et al, 2021X-linked syndrome in 13 males of a family with a missense variant in the OTUD5 gene. Neurodevelopmental problems, congenital heart defects, and hypospadias were noted.(176)
Hage et al, 2021A novel androgen receptor gene mutation in two patients with mild insensitivity syndrome. It was found a novel missense mutation, Ala699Thr, in exon 4 within the ligand-binding domain.(177)
Basa et al, 2021Pathogenic Aristaless novel gene-variant C1010_1013dupGCTA; p.Tyr338 in a lissen cephaly boy with ambiguous genitalia.(178)
Genetic research on a population or on hospitalized patients
Li et al, 2021SRD5A2 and AR genes are two top candidate genes associated with 46, XY hypospadias in Chinese patients.(160)
Kherouatou-Chaoui et al, 2021It was found the absence of SRY and NR5A1 gene mutation in Algerian children. with DSD(179)
Chen et al, 2021An important link was found between rs12458 (3'-UTR of GATA4) and susceptibility to hypospadias.(180)
Wong et al, 2022Children affected by 45, X/46, XY mosaicism have a wide spectrum in their phenotypes.(181)
Deng et al, 2021GREM1 is associated with susceptibility to hypospadias in the European population. GREM1 risk allele rs3743104[G] increases hypospadias susceptibility among the southern Han population.(182)
Siregar et al, 2021ESR1 gene polymorphisms (PvuII, XbaI, and SNP 12) were found in hypospadias patients and there are correlate with the severity of hypospadias.(183)
Genetic counseling
Nordenskjöld et al, 2021Genetic counseling for patients with hypospadias is mandatory, especially when hypospadias is associated with other malformations. The risk of low fertility is a reality.(157)
Saraç et al, 2021Genes involved in the sonic hedgehog homolog pathway might play a role in the etiology of hypospadias.(184)
Tenenbaum-Rakover et al, 2021In DSD, 78% of our patients indicate a major role for whole-exome sequencing and its role in the diagnosis and management of the cases.(185)
Ea et al, 2021Next-generation sequencing reveals different forms of DSD (including hypospadias). It is important to have a follow-up and medical counseling in future.(186)
Genetical syndromes and malformations
Schmidt et al, 2022Variants in the transcription of the factor TP63 have been linked to several autosomal dominantly inherited malformations. Hypospadias is one of these malformations.(187)
Ding et al, 2021Noonan syndrome (frequently with hypospadias and cryptorchidism), is associated with PTPN11 variation, and SOS2 gene variation more often than previously reported.(188)
Lourenço et al, 2021An aberrant right subclavian artery may be associated with mosaicism 45, X [13]/46, X,e(X) (p22.1q22.1) and in some cases with hypospadias.(189)
Konishi et al, 20215α-reductase type 2 deficiency may lead to ambiguous phenotypes.(190)
Rjiba et al, 2021In Wolf-Hirschhorn syndrome we find a partial deletion of the short arm of chromosome 4. MSX1 gene absence might be responsible for the hypospadias phenotype in these children.(191)
Genetical and histological analyses
Yuri et al, 2021The expression of mRNA vascular endothelial growth factor in hypospadias patients does not affect the severity of hypospadias (dartos).(192)
Kong et al, 2021The expression of the Mafb gene and protein in the foreskin of children with hypospa dias is lower than that in the normal foreskin.(193)

Table VI summarizes the articles about genetical factors.

10. Environmental factors

Maternal exposure to different chemicals can induce malformation of the penis. The most incriminated chemicals in this process are bisphenol, inorganic solvents, alkyl phenolic compounds, phthalates, benzophenones, parabens, siloxanes, pesticides or herbicides, diethylstilbestrol, cadmium, DDT, vinclozolin (fungicide), petroleum solvents and SO2 (194-201). Some studies are more general and incriminate the air pollution, heat, or the proximity of a vineyard in the development of hypospadias (202-204).

Table VII summarizes the articles on environmental factors.

Table VII

Summary of the articles about environmental factors.

Table VII

Summary of the articles about environmental factors.

Author, yearConclusions(Refs.)
Spinder et al, 2021Maternal exposure to Bisphenol A, organic solvents/alkyl phenolic compounds and phthalates/benzophenones/parabens/siloxanes, pesticides in early pregnancy is associated with urogenital anomalies in the offspring.(194)
Rodprasert et al, 2021 (195)
Mesquita et al, 2021 (205)
Mattiske et al, 2021Genistein, Bisphenol A (BPA), Phthalates, Parabens, flame retardants, solvents, agricultural chemicals, Atrazine (herbicide), DDT, and Vinclozolin (fungicide) can interfere with androgen and estrogen levels during the development and result hypospadias.(196)
Laws et al, 2021Plasticizers (bisphenols and phthalates), personal care products (parabens), environmental contaminants (polychlorinated biphenyls), herbicides or pesticides, cadmium, conduct to male disorders: infertility, cryptorchidism, hypospadias, and testicular cancer.(197)
Stukenborg et al, 2021 (198)
Giovanni et al, 2022 (199)
 We have to focus on prenatal exposure to mild analgesics: acetaminophen (more involved) and Ibuprofen (less involved). 
Wu et al, 2022Maternal exposure to pesticides, phthalates, bisphenol A, and polychlorinated biphenyls are associated with hypospadias and micropenis in offspring. They have transgenerational effects with long-term effect.(200)
Gaspari et al, 2021 (201)
Huang et al, 2021Air pollution during pregnancy was associated with the occurrence of hypospadias, but conclusions have been inconsistent. Some ethnic groups may present a type of such malformation.(202)
Xing et al, 2021Air pollution and risk of hypospadias in offspring: there is an effect of PM2.5 exposure on hypospadias risk.(203)
Bougnères et al, 2021The residence of pregnant mothers close to vineyards was statistically linked with the risk of hypospadias in children.(204)
Soyer-Gobillard et al, 2021Prenatal exposure to Diethylstilbestrol produced multigenerational phenotypic (hypospadias endometriosis) and psychiatric disorders.(206)
Zhang ZC et al, 2021Dibutyl phthalate is an endocrine disruptor. It has anti-androgenic effects and a weak estrogenic effects. Lower doses cause more adverse effects than the highest dose.(207)
Zhang S et al, 2021Maternal exposure to SO2 during the 3 months before and the first and second months after conception may increase the risk of hypospadias in offspring.(208)
Rouget et al, 2021An association between petroleum solvents and hypospadias has been observed.(209)
Haghighi et al, 2021The appearance of hypospadias is linked to heat exposure. Effects increased with the duration and intensity of heat exposure.(210)
Gadagbui et al, 2021Procymidone as an endocrine disrupting chemical can produce hypospadias but is not very suggestive for other malformations.(211)
Lin et al, 2021There is a modest association between prenatal PM2.5 (fine particulate matter) exposure during 1 month before pregnancy or within the first trimester and the risk of hypospadias in offspring.(212)

11. Endocrinological factors

In regard to endocrinological factors, two main hypotheses were identified. One is that prenatal factors: diabetes, intake of progestins, estrogens, β-blockers, assisted reproductive technology, and diethylstilbestrol (treatment in grandmothers can lead to a greater risk for hypospadias in offspring and grandsons) (207,213-217). The other is that in some penile malformations, preoperatory testosterone treatment is conducted for improved results (218-220).

Table VIII summarizes the articles about endocrinological factors.

Table VIII

Summary of the articles about endocrinological factors.

Table VIII

Summary of the articles about endocrinological factors.

Author, yearConclusions(Refs.)
Zhan ZC, 2021Prenatal and/or gestational factors (diabetes), intake of different treatments during pregnancy (progestins, estrogens, β-blockers), assisted reproductive technology and diethylstilbestrol treatment in grandmothers can lead to a greater risk for hypospadias in offspring and grandsons.(207)
Akay et al, 2021 (213)
Chung et al, 2021 (214)
Baskin et al, 2021 (215)
Wu et al, 2021 (216)
Schraw et al, 2021 (217)
Liu et al, 2021Testosterone treatment in children with hypospadias, especially those with a 5α-reductase deficiency, can alter its degree and lead to a greater success for the operation.(218)
Khokar et al, 2021 (221)
Li et al, 2021Preoperative androgen stimulation is used in proximal hypospadias or small glans size. It appears it does not affect the operative outcome, but it is not certain.(219)
Chukwubuike et al, 2021 (222)
Concepción et al, 2021Boy with partial androgen insensitivity syndrome (having hypospadias and cryptorchidy), required testosterone therapy and genitoplasty.(220)

12. Associated malformations

The best-known associated malformation with proximal hypospadias is cryptorchidism (223). Hypospadias is frequently associated with cardiac, renal and skeletal malformations (224). There is also a correlation between anorectal malformation complexity and associated urologic abnormalities (225). In addition, a number of genetic syndromes are associated with hypospadias, some of which are described in the Genetics section (section 9). A peculiarity is cases of hypospadias with disorders of sex development. Severe genital ambiguity requires complex genetic and anatomic investigation to declare the patient as a male (226-228). Other observations note that talipes, hypospadias and septal heart defects are more frequent mild defects associated with prematurity and gonadal neoplastic lesions appearing frequently together with hypospadias (229).

Table IX summarizes the articles on associated malformations.

Table IX

Summary of the articles about associated malformations.

Table IX

Summary of the articles about associated malformations.

Author, yearConclusions(Refs.)
D'Oro et al, 2021Patients with proximal hypospadias present a higher risk of acquired. cryptorchidism(223)
Ludorf et al, 2021Hypospadias is most frequently associated with cardiac, renal, and skeletal malformations. Hypospadias in combination with eye defects did not include defects in other organ systems.(224)
Fuchs et al, 2021There is a correlation between anorectal malformation complexity and associated urologic abnormalities.(225)
De Jesus et al, 2021Cases of hypospadias in the disorder of sex development (DSD) associated with ovotestis, severe genital ambiguity, and the child was declared male after elaborate analysis or an apparent male with infertility who presented 46 XX karyotype.(226)
Nelwan et al, 2021 (227)
Ashfaq et al, 2021 (228)
Álvarez-Álvarez et al, 2021Cases of hypospadias associated with Dandy-Walker malformation (75), bifid phallus (77), dorsal penile curvature with megameatus (136), Wolf-Hirschhorn syndrome (262).(230)
Viet Nguyen et al, 2021 (231)
Çelik et al, 2021 (232)

13. Questionnaires and malformations

Some papers refer to the outcome following hypospadias surgery. Some authors call for standardization of penile appearance. The Penile Perception Score-PPS, Hypospadias Objective Score Evaluation-HOSE, International Index of Erectile Function-5-IIEF5, or Health-related quality of life (HRQoL) were conceived for that purpose (6,233). These scores are different from the point of view of patients, parents, or surgeons so there is no standard yet. Curvature and shortening are the anatomical modifications most perceived by the patients (234). Voiding, erectile problems, social interaction and psychological issues are the functional problems after surgery (233,235).

Table X summarizes the articles about questionnaires and malformations.

Table X

Summary of the articles about questionnaires and malformations.

Table X

Summary of the articles about questionnaires and malformations.

Author, yearConclusions(Refs.)
Snodgrass et al, 2021Parents of boys with hypospadias: the majority never previously heard of it, wondered if they are to blame for it and are concerned about future boys. A part of the report is that doctors did not spend enough time discussing these problems.(3)
van Engelen et al, 2021A substantial number of parents report some form of decisional regret regarding the elective surgery for hypospadias in their child.(4)
Costa et al, 2021Surgeons seem more concerned about the cosmetic part of hypospadias surgery than parents. Photography appears to be suitable for documenting corrections of hypospadias regarding penile curvature, and postoperative cosmetic results.(5)
Ceccarelli et al, 2021Three questionnaires: The Penile Perception Score-PPS, the Hypospadias Objective Score Evaluation-HOSE, and the International Index of Erectile Function-5-IIEF5 to patients, parents, and surgeons. The results are different, so there is a need for standardization.(6)
Hismatsu et al, 2021The learning curve in proximal hypospadias repair appears after 50 cases, supervised by an experienced surgeon.(7)
Ludovica et al, 2021Self-reported outcomes in adolescent patients who had TIP repair are similar to the control group. Preputial reconstruction or circumcision did not affect the outcome.(31)
Bhatia et al, 2021Health-related quality of life (HRQoL): penile appearance, voiding, social interaction, sexual health and psychological or behavioral function, have to serve as a guide for future assessments. Patients are usually focused on penile appearance.(233)
Hoare et al, 2021Penile modifications after urethroplasty is perceived by individuals, especially in curvature and shortening.(234)
Chang et al, 2021A significant percentage of adolescents or young adults operated in childhood with hypospadias, present aesthetic complaints (majority) or functional problems (fistula, spaying).(236)
Sinatti et al, 2021Psychosexual satisfaction of adults who had hypospadias surgery demonstrates equal satisfaction rates to those in control group. Interventions on the penile urethra, long panurethral urethroplasties, and reinterventions are associated with greater risks. The functional benefit of non-transecting approaches and grafting techniques on bulbar urethra remains controversial.(237)
Hermosa et al, 2021 (238)
Mallenahalli et al, 2021 (239)
Zhang et al, 2021Delayed surgery in children with hypospadias is determined by the economy of the area where the family lives, the educational level of the parents, and the location of the urethral opening.(240)
Bennecke et al, 2021From patients' perspective, early genital surgery in DSD is more accepted, but every case has its complexity, so it cannot be applied as a rule.(241)
Bangalore et al, 2021The patient's family is encouraged to make individualized treatment guided by shared decision.(242)
Cakmak et al, 2022Hypospadias and neurologic impairment may share common etiologic factors, thus every patient with hypospadias should be evaluated for neurodevelopmental status.(243)
van de Grift et al, 2022The majority of patients with DSD, who had a history of surgery were neutral to satisfied with the appearance and function after masculinizing operations.(244)
Gul et al, 2021Sexual functions and fertility outcomes after hypospadias repair may be affected in some patients.(245)
Guner et al, 2021Hypospadias was one of the early reported malformations in the history of medicine, but very little specific urogenital disease information is mentioned in ancient age sanctuary medicine. Surgical techniques used now were elaborated in the 20th century.(246)
Buyukunal et al, 2021 (247)

14. Management

For most families, a boy having hypospadias is a psychological trauma. Usually, parents do not know about this malformation and have to be informed, and this is not always, in terms of time and explanation, what they expect. The need for reintervention is perceived in the majority of cases as a trauma for patients and parents (3,38). An article claims that hypospadias and neurologic impairment may share common etiologic factors, thus every patient with hypospadias should be evaluated for neurodevelopmental status (243). Timing for complex malformations has to be considered individually in every case. Delayed surgery in children with hypospadias is also determined by the economy of the area where the family lives and the educational level of the parents (240).

In a hospital register, it is not easy to classify hypospadias properly, although there are algorithms for identification (248). Another question is: ‘What are the specialties of the surgeons who are managing these cases?’ Usually, they are pediatric surgeons or pediatric urologists (depending on the country) (249). Regardless of the specialty, the repair of hypospadias requires an experienced doctor. The learning curve seems quite long; surgeons are considered experienced in the field after treating a minimum of 50 cases, supervised by an experienced surgeon (7). When the child becomes an adult, it is better to be managed by urologists trained in genitourinary reconstructive surgery (250). It is important to inform general practitioners, and pediatricians about the management of hypospadias, as it seems that a number of them do have not adequate knowledge about the condition (251).

Table XI summarizes the articles on hypospadias management.

Table XI

Summary of the articles about hypospadias management.

Table XI

Summary of the articles about hypospadias management.

Author, yearConclusions(Refs.)
Baker et al, 2021Methods for classifying distal hypospadias and other urologic problems in registers, present a high risk for misclassification.(248)
Maier et al, 2021In Germany, hypospadias surgery has shown a relevant shift towards pediatric surgery, from pediatric urology.(249)
Scarberry et al, 2021Patients who become adults are better managed by urologists trained in genitourinary reconstruction.(250)
Mahalik et al, 2021Indian questionary among pediatricians: about half of them know what to do and recommend to a patient with hypospadias.(251)
Kharbanda et al, 2021Algorithms can identify infants with selected birth defects using automated health care data with reasonable accuracy.(252)

15. Biological materials

Biological engineering materials and products are becoming increasingly popular in hypospadias repair and the present study enumerated some of them which were used in urethroplasties. Acellular dermal matrix grafts (with Collagen-Binding VEGF), harvested from the bladder or derm were successfully used in the urethral reconstruction and authors claim that the results were comparable with tunica vaginalis (253). Tissue sealants such as fibrin glue, cyanoacrylate glue, Bio Glue, and cryocalcium glue were used to reduce fistula-related complications (254).

Table XII summarizes the articles about biological materials in hypospadias repair.

Table XII

Summary of the articles about biological materials in hypospadias repair.

Table XII

Summary of the articles about biological materials in hypospadias repair.

Author, yearConclusions(Refs.)
Wu et al, 2021Acellular dermal matrix graft is a good material for ventral lengthening of the penis, comparable with tunica vaginalis.(253)
Singh et al, 2021A review of tissue sealants: fibrin glue, cyanoacrylate glue, Bio Glue, and cryocalcium glue. They can reduce complications (fistula, cutaneous lesions), but they remain inconclusive.(254)
Wang et al, 2021Acellular dermal matrix modified with Collagen-Binding VEGF was successfully used in the urethral reconstruction of a dog without severe inflammation.(255)
Morgante et al, 2021Two acellular matrix grafts for tissue bed for surgical repair were compared: full-thickness porcine acellular bladder matrix and commercially-sourced cross-linked acellular matrix from the porcine dermis (Permacol™). The two were conducive to good results.(256)
Tawfeek et al, 2021The application of cyanoacrylate during fistula repair is feasible and safe.(257)
Shenoy et al, 2021Fibrin sealant, applied over the urethroplasty suture represents a good cover and improves the outcome in patients with hypospadias.(258)

16. Animal models

Experiments on animals are rare, poorly reported, less detailed and not reproducible (as a review found) (259). A single urethral reconstruction is reported in a rabbit model. It used a decellularized intestinal submucosa, seeded with urothelial cells (260). Specific genes were discovered and involved in hypospadias formation in rats and mice (261-264). Prenatal atrazine and vinclozolin exposure can affect penile and testicular development (265).

Table XIII summarizes the articles about animal models.

Table XIII

Summary of the articles about animal models.

Table XIII

Summary of the articles about animal models.

Author, yearConclusions(Refs.)
Abbas et al, 2021Urethral repair experiments on animals are poorly reported, less detailed and are not reproducible.(259,266)
Amesty et al, 2021Rabbit urethral defect: neourethra is created by seeding autologous urothelial cells by bladder washing on a decellularized intestinal submucosa matrix (Biodesign® Cook-Biotech®).(260)
 Cell-seeded transplants are superior to nonseeded. 
Palermo et al, 2021A putative pathway network for a male rat, sustained expression of Coup-tfII and hypospadias.(261)
Alcantara et al, 2021Wnt5a contributes to urethral tube formation in mice.(262)
Xiang et al, 2021c-Fos overexpression might contribute to hypospadias (rats and humans) and(263)
Feng et al, 2021NONRATT008453.2 may have an influence on autophagy in the fibroblasts of the genital tubercle in dibutyl phthalate-induced hypospadias in rats.(264)
Yu et al, 2021Maternal vinclozolin exposure can lead to penile and testicular damage (via miR132, miR195a) in the offspring. Prenatal atrazine exposure can induce hypospadias and cryptorchidism in mice.(265)
Tan et al, 2021 (267)
Tokat et al, 2021Intraurethral erythropoietin administration facilitates wound healing after hypospadias correction in rats.(268)
Gulburun et al, 2021Hydrogen-rich saline solution reduces inflammation on the flap tissue in the hypospadias model in rats.(269)

17. Retrospective studies of centers

Table XIV summarizes the articles about retrospective studies of centers.

Table XIV

Summary of the articles about retrospective studies of centers.

Table XIV

Summary of the articles about retrospective studies of centers.

Author, yearConclusions(Refs.)
Kaefer et al, 2021A great lesson and the experience of a top surgeon regarding hypospadias.(2)
Fruntelată et al, 2021Overview of center regarding hypospadias from Romania, Afghanistan, Kenya, Pakistan or Saudi Arabia in time of COVID.(270)
Raheem et al, 2021 (271)
Jurat et al, 2021, 2021 (272)
Irene et al, 2021 (273)
Khan et al, 2021 (274)
Ashwin et al, 2021A lifelong view and review of staged and multiple urological surgeries or the treatment of strictures(275)
Wiener et al, 2021 (276)
Ács et al, 2021A database of the Hungarian congenital abnormalities. Hypospadias is number four.(277)
Benavides et al, 2022Birth defects prevalence in Texas, where hypospadias is less prevalent in rural counties compared with urban counties.(278)
Arulanandam et al, 2021In Quebec, the compliance rates, regarding hypospadias are inadequate and need improvement.(279)

18. Social media

On social media (Facebook, Twitter and others), the problem of hypospadias is debated, but much of the shared content does not have supporting evidence and is not affiliated with medical journals, hospitals, or academic institutions. For parents with insufficient medical knowledge, it could be difficult to identify whether the articles shared on social media are a reliable resource for health. YouTube videos present different surgical treatments for this malformation, but the majority of the content is non-medical and may lead to health misinformation (280-282).

Table XV summarizes the articles about social media.

Table XV

Summary of the articles about social media.

Table XV

Summary of the articles about social media.

Author, yearConclusions(Refs.)
Karabay et al, 2021There is a scarcity of high-quality videos on YouTube describing distal hypospadias repair techniques and, further, their quality regarding educational content seems to be unsatisfactory.(280)
Jones et al, 2022 (281)
Cheng et al, 2022Most interesting pediatric urologic issues (including hypospadias), debated on social media (Facebook, Twitter) are debated strongly, but not very relevant.(282)

19. Others

Table XVI summarizes the articles about bibliometrics, small gestational age, neoplasm and fertility.

Table XVI

Others.

Table XVI

Others.

Bibliometrics
Author, yearConclusions(Refs.)
Ghidini et al, 2022The top-cited articles were dispersed among 27 journals of different areas with a median impact factor of 2.676. Current scientific literature deals with congenital anomalies, more specifically with obstructive uropathies and hypospadias. In the last decade, one of the most relevant innovations in pediatric urology was the introduction of robotic surgery.(283)
Matta et al, 2021The list of top 100 most cited articles in pediatric urology is an important resource for clinicians and trainees to understand the body of knowledge and trajectory of this field, charting the evolution of the field and highlighting areas of a potential investigation.(284)
Dogan et al, 2021Between 1980 and 2018, there were 1940 articles about hypospadias, the USA was the top country that contributed to the literature and the top active 3 journals were the Journal of Urology, Journal of Pediatric Urology, and Urology.(285)
Small gestational age
Rittler et al, 2021Talipes, hypospadias, and septal heart defects are more frequent mild defects significantly associated with prematurity.(229)
Braga et al, 2022Children born small for gestational age present a high frequency of hypospadias. Cases were studied genetically, but it was not identified the cause. They conclude that multifactorial causes or unidentified epigenetic defects produce the malformation.(286)
Neoplasm, fertility
Huilin et al, 2021A series of cases with gonadal neoplastic lesions associated with hypospadias Men with hypospadias do not present impaired semen quality using dizygotic twinning as an epidemiological indicator.(287)
Philips et al, 2021 (288)

20. Discussion

As can be seen, hundreds of papers are written every year about hypospadias, referring to all aspects of the pathology. 2021 was mostly a year of accumulation, with a number of papers comparing and hoping for new surgical techniques with improved outcomes, clarifying the relevant anatomical, etiological and genetic factors, assuming the complications, and describing solutions to prevent or treat them. As a limitation of the present study, quality assessment of the included articles was not performed.

According to the findings of the present study, it is possible to highlight the following ideas considering that these might have direct clinical significance: Promising modifications in proximal hypospadias repair were presented and transverse preputial island flap urethroplasty with incised urethral diversion appeared a superior option compared with transurethral diversion (8). Two-stage urethroplasty had improved results compared with one-stage surgery (10,12,16,35,36). Tubed pedicled preputial island flap, Duckett's procedure, was associated with a high complication rate (44). Predictors of a successful outcome of tubularized incised plate (TIP) repair in cases of distal hypospadias were described by different authors (53,86). Dorsal inlay graft urethroplasty was considered a superior technique compared with onlay preputial flap (LOF) (19). With the exception of the long-term outcomes in cosmetic and functional evaluation, Mathieu incised plate technique had improved outcomes compared with the TIP technique (63). For the treatment of congenital ventral penile curvatures, dorsal plication was defined as a relatively simple and successful method with low risks (34). There were no differences in outcomes between pre-pubertal and post-pubertal boys after the correction of penile curvature using corporal plication (70). In order to decrease the rate of complications new dressing techniques, and topical agents were mentioned along the hyperbaric oxygen therapy (88,89,96,97,99). Perioperative prophylactic antibiotics appeared not to reduce the possibility of infections (101). A total of 25% of adults presenting with bulbar strictures had a hypospadias surgery in childhood (117). Penile curvature could appear in 25% of patients within the first 2 years (102,108,110). According to postoperative care, surgeons appear more concerned about the cosmesis than do the parents. Photo documentation of cosmesis (and to evaluate penile curvature) is appropriate at present (5). Self-reported outcomes in adolescent patients with TIP repair were similar to those in a control group (31). Delayed surgery could be determined by the region's economy, the parent's educational level and the urethral opening site (29). There were noteworthy pediatric urologic issues, including hypospadias, on social media and they are debated, but most of them are not very relevant. There is a scarcity of high-quality videos on YouTube describing hypospadias repair techniques, and their quality regarding educational content appears unsatisfactory (280-282).

The novelty of the present study consisted of the lack of similar analyses. To the best of the authors' knowledge, no similarly conceptualized studies have been previously performed in this research field. As a scoping review, the present study represented a well-structured and reproducible mapping of the literature. It aimed to define and clarify key concepts, theories, the most important results and achievements, and to present them in a transparent way, highlighting areas where researchers could identify gaps in the current literature that may require further inquiry. The present study presented sources of evidence that inform practice in the field, eases further investigations and saves time and resources. Hypospadias research in 2021 represents a very complex field. A comprehensive scoping review such as the present constitutes essential information for every pediatric surgeon, urologist, and specialist in this field.

21. Conclusion

According to the papers published in 2021, promising modifications of existing surgical techniques were presented with improved outcomes for the proximal and distal types of hypospadias forms. The present study highlighted and clarified the presented relevant anatomical, etiological and genetic factors. For an improved understanding of the aspects of peri- and postoperative management of hypospadias the antibiotherapy, analgesia, dressing techniques and the future use of novel bioengineering agents to prevent, reduce or treat the occurring complications, were also discussed.

Acknowledgements

Not applicable.

Funding

Funding: No funding was received.

Availability of data and materials

Data sharing is not applicable to this article, as no data sets were generated or analyzed during the current study.

Authors' contributions

HG and ZB were responsible for conceptualization and methodology. ZB was responsible for software. HG, ZB, ED and ZD were responsible for validation. ZB was responsible for formal analysis. HG was responsible for investigation. ED and ZD were responsible for data curation. HG wrote the original draft. HG, ZB, ED and ZD wrote, reviewed and edited the manuscript. ZB was responsible for visualization and supervision. HG was responsible for project administration. All authors read and approved the final manuscript. Data authentication is not applicable.

Ethics approval and consent to participate

Not applicable.

Patient consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

References

1 

van der Horst HJR and de Wall LL: Hypospadias, all there is to know. Eur J Pediatr. 176:435–441. 2017.PubMed/NCBI View Article : Google Scholar

2 

Kaefer M: Hypospadias. Semin Pediatr Surg. 30(151080)2021.PubMed/NCBI View Article : Google Scholar

3 

Snodgrass P, Snodgrass W and Bush N: Parental concerns of boys with hypospadias. Res Rep Urol. 13:73–77. 2021.PubMed/NCBI View Article : Google Scholar

4 

van Engelen H, Custers JAE, Kortmann BM, Oerlemans AJM, van Rooij IALM and Verhaak CM: Parental decisional regret after surgical treatment in young boys born with hypospadias. J Pediatr Urol. 17:691.e1–691.e7. 2021.PubMed/NCBI View Article : Google Scholar

5 

Costa E, Fraga JC, Salle JP and Rosito N: Does parental opinion differ from the health care team regarding cosmesis after hypospadias repair? Rev Assoc Med Bras (1992). 67:33–38. 2021.PubMed/NCBI View Article : Google Scholar

6 

Ceccarelli PL, Lucaccioni L, Poluzzi F, Bianchini A, Biondini D, Iughetti L and Predieri B: Hypospadias: Clinical approach, surgical technique and long-term outcome. BMC Pediatr. 21(523)2021.PubMed/NCBI View Article : Google Scholar

7 

Hisamatsu E, Sugita Y, Haruna A, Shibata R and Yoshino K: The learning curve in proximal hypospadias repair. J Pediatr Urol. 17:330.e1–330.e6. 2021.PubMed/NCBI View Article : Google Scholar

8 

Wang C, Ma N, Wang W, Endo Y, Chen W and Li S: Incised urethral diversion reduces the rate of fistula after one-stage hypospadias repair: A single-center retrospective controlled study. World J Urol. 39:4235–4240. 2021.PubMed/NCBI View Article : Google Scholar

9 

Babu R and Chandrasekharam VVS: Meta-analysis comparing the outcomes of single stage (foreskin pedicled tube) versus two stage (foreskin free graft & foreskin pedicled flap) repair for proximal hypospadias in the last decade. J Pediatr Urol. 17:681–689. 2021.PubMed/NCBI View Article : Google Scholar

10 

Ali MM, El-Hawy MM, Galal EM, Tawfiek ER and Anwar AZ: Results of two-stage transverse preputial island flap urethroplasty for proximal hypospadias with chordee that mandate division of the urethral plate. Cent European J Urol. 74:89–94. 2021.PubMed/NCBI View Article : Google Scholar

11 

Chan YY, D'Oro A, Yerkes EB, Rosoklija I, Balmert LC, Lindgren BW, Gong EM, Liu DB, Johnson EK, Chu DI and Cheng EY: Challenging proximal hypospadias repairs: An evolution of technique for two stage repairs. J Pediatr Urol. 17:225.e1–225.e8. 2021.PubMed/NCBI View Article : Google Scholar

12 

Zhu X, Huang L, Wang J, Zhu H, Chen C, Wang L, Deng Y, Ma G, Guo Y and Ge Z: Comparative study of one-stage and the novel two-stage urethroplasty using the transected urethral plate and transverse preputial island flap (TPIF) for severe hypospadias: A single-center experience. Transl Pediatr. 10:843–850. 2021.PubMed/NCBI View Article : Google Scholar

13 

Madec FX, Desplanches M, Chabaud M, Irtan S, Suply E and Audry G: Koyanagi urethroplasty for proximal hypospadias: A stage procedure? Prog Urol. 32:312–318. 2022.PubMed/NCBI View Article : Google Scholar

14 

Vu TH, Viet Nguyen H, Quy Hong Q, Quang Pham H, Thanh Pham T, Hai Do Đ and Đo Truong T: Results of the one-stage proximal hypospadias repair with modified Koyanagi technique: A prospective cohort study in a single Vietnam centre. Ann Med Surg (Lond). 71(103012)2021.PubMed/NCBI View Article : Google Scholar

15 

Acimi S, Abderrahmane N, Debbous L, Acimi MA and Mansouri J: Koyanagi-snow-hayashi urethroplasty in severe hypospadias repair: Between hope and reality. Urology. 152:129–135. 2021.PubMed/NCBI View Article : Google Scholar

16 

Lin H, Wang YY, Li SB, Chen ZT and Su LJ: Staged transverse preputial island flap urethroplasty for some proximal hypospadias with moderate-to-severe chordee. BMC Urol. 21(182)2021.PubMed/NCBI View Article : Google Scholar

17 

Silay MS, 't Hoen L, Bhatt N, Quaedackers J, Bogaert G, Dogan HS, Nijman RJM, Rawashdeh Y, Stein R, Tekgul S and Radmayr C: Are there any benefits of using an inlay graft in the treatment of primary hypospadias in children? A systematic review and metanalysis. J Pediatr Urol. 17:303–315. 2021.PubMed/NCBI View Article : Google Scholar

18 

Swatesutipun V, Yoosuksomboon N and Zaontz MR: A novel transurethral approach to inlay oral mucosal graft urethroplasty technique for meatal and fossa navicularis stricture resulting from distal hypospadias repair. J Pediatr Urol. 17:585–586. 2021.PubMed/NCBI View Article : Google Scholar

19 

Omran M, Sakr A, Elgalaly H, Fawzy A and Abdalla M: Narrow urethral plate augmentation in anterior and middle hypospadias repair: Onlay flap vs Inlay graft. A prospective randomized comparative study. J Pediatr Urol. 17:216.e1–216.e8. 2021.PubMed/NCBI View Article : Google Scholar

20 

Chen S, Li Y, Ma N, Wang W, Xu L and Yang Z: Staged buccal mucosa graft urethroplasty for proximal hypospadias in children: A short- to mid-term follow-up retrospective study. Eur J Pediatr Surg. 31:420–426. 2021.PubMed/NCBI View Article : Google Scholar

21 

Shandilya G, Kureel SN, Gupta A, Singh GP, Pandey A, Rawat JD and Wakhlu A: Bracka urethroplasty with buccal mucosa graft: Ergonomic management of penile skin dartos in the first stage to facilitate second-stage neourethral coverage. J Indian Assoc Pediatr Surg. 26:11–15. 2021.PubMed/NCBI View Article : Google Scholar

22 

Tiwari C and Borkar N: Evaluation of tunica vaginalis free graft as a better alternative to tunica vaginalis pedicled flap for providing waterproof cover in stage II hypospadias repair. Afr J Paediatr Surg. 18:90–93. 2021.PubMed/NCBI View Article : Google Scholar

23 

Favorito LA, da Silva Filho FS and de Resende Junior JA: A new option to prevent fistulas in anterior urethroplasty in patients with kippered urethra: The tunica vaginalis flap. Int Braz J Urol. 47:1032–1036. 2021.PubMed/NCBI View Article : Google Scholar

24 

Radhakrishnan CN and Radhakrishna V: The tunica-vaginalis flap to prevent postoperative fistula following severe hypospadias repair: Has the search for Holy Grail ended? Actas Urol Esp (Engl Ed). 45:552–556. 2021.PubMed/NCBI View Article : Google Scholar

25 

Obaidullah Shami HB, Obaid O, Alvi HF, Mahboob M and Akbar F: Outcomes of islanded scrotal raphe flap employment for skin shortage in complicated hypospadias repair. J Plast Reconstr Aesthet Surg. 74:3386–3393. 2021.PubMed/NCBI View Article : Google Scholar

26 

Jordan A, Sumfest J and Desantis J: A new 3-stage approach for reoperative hypospadias. Ann Plast Surg. 88:544–548. 2022.PubMed/NCBI View Article : Google Scholar

27 

Taneli C, Tanriverdi HI, Genc A, Sencan A, Gunsar C and Yilmaz O: Tubularized reconstructed plate urethroplasty: An alternative technique for distal hypospadias repair. Urology. 148:243–249. 2021.PubMed/NCBI View Article : Google Scholar

28 

Abdel-Hamid El-Hawy M, Ali MM, Abdelhamid AM, Fawzy AM, Hussein A and Elsharkawy MSM: Long-term outcome of non-stented tubularized incised plate urethroplasty for distal hypospadias repair: A complication analysis. Cent European J Urol. 74:595–600. 2021.PubMed/NCBI View Article : Google Scholar

29 

Zhang J, Zhu S, Zhang L, Fu W, Hu J, Zhang Z and Jia W: The association between caudal block and urethroplasty complications of distal tubularized incised plate repair: Experience from a South China National Children's Medical Center. Transl Androl Urol. 10:2084–2090. 2021.PubMed/NCBI View Article : Google Scholar

30 

Galal M, Taha DE, Elabden KZ, Nabeeh H and Abdelbaky T: The effect of pre-incision urethral plate width and glanular width on the outcome of tubularized incised urethral plate repair surgery in distal penile hypospadias, a prospective study. Urol J. 19:50–55. 2021.PubMed/NCBI View Article : Google Scholar

31 

Ludovica D, Bianco M, Pelizzari A, Mandato F, Esposito C and Castagnetti M: Self-reported outcomes after the onset of puberty in patients undergoing primary distal hypospadias repair by the tubularized incised plate technique combined with preputial reconstruction vs circumcision: A norm related study. J Pediatr Surg. 56:1411–1416. 2021.PubMed/NCBI View Article : Google Scholar

32 

Khirallah M and El-Dossuky N: Hybrid mathieu urethroplasty: A simple modification outcomes. Res Rep Urol. 13:473–478. 2021.PubMed/NCBI View Article : Google Scholar

33 

Xie QG, Xia K, Li XP, Luo P, Li ZQ, Su C and Deng CH: Application of the Mathieu combined tunnel technique for repairing glans dehiscence after failed hypospadias repair. Asian J Androl. 24:311–316. 2022.PubMed/NCBI View Article : Google Scholar

34 

Akdemir F, Kayıgil Ö and Okulu E: DORSAL plication technique for the treatment of congenital ventral penile curvature: Long-term outcomes of 72 cases. J Sex Med. 18:1715–1720. 2021.PubMed/NCBI View Article : Google Scholar

35 

Zhu XJ, Dong J, Ge Z and Guo YF: Staged urethroplasty by tubularization of reconstructed urethral plate using the preputial island flap for severe hypospadias. Zhonghua Nan Ke Xue. 27:134–139. 2021.PubMed/NCBI(In Chinese).

36 

Ali MM and Anwar AZ: Experience with modified two stage inner preputial flap for repair of proximal hypospadias with chordee: A single institution study with intermediate follow up. J Pediatr Surg. 57:1404–1408. 2022.PubMed/NCBI View Article : Google Scholar

37 

Aziz Tamer FA, El Zalabany Ahmed M and Lolah Magdy M: The modified Koyanagi technique versus two-staged urethroplasty using buccal mucosal graft in managing proximal hypospadias: A randomized clinical trial. Egypt J Surg. 40:633–639. 2021.

38 

Lu J, Cen J, Wang W, Zhao H, Li P, Mo J, Chen Z, Tang Y, Wei J, Luo J, et al: Localization of external urethral orifice in coronary sulcus during urethroplasty in case of severe hypospadias accompanied by prostatic utricle cyst. BMC Urol. 21(149)2021.PubMed/NCBI View Article : Google Scholar

39 

Akkary R, Ripepi M, Akokpe O, Louati H, Klipfel C and Geiss S: Two simple modifications can potentially change the future of proximal hypospadias surgery. Our series and a review of the literature. Int J Pediatr Adolesc Med. 8:172–176. 2021.PubMed/NCBI View Article : Google Scholar

40 

Ding Y, Gu S, Xia X and Yu Z: Comparison of penile appearance and outcomes between prefabricated urethra and pre-implanted urethral plate for treatment of children with severe hypospadias: A retrospective study. Front Pediatr. 9(719551)2021.PubMed/NCBI View Article : Google Scholar

41 

Chen S, Yang Z, Ma N, Wang WX, Xu LS, Liu QY and Li YQ: Scrotal septal flap and two-stage operation for complex hypospadias: A retrospective study. World J Clin Cases. 9:2983–2993. 2021.PubMed/NCBI View Article : Google Scholar

42 

Lyu YQ, Yu L, Xie H, Huang YC, Li XX, Sun L, Liang Y and Chen F: Spongiosum-combined glanuloplasty reduces glans complications after proximal hypospadias repair. Asian J Androl. 23:532–536. 2021.PubMed/NCBI View Article : Google Scholar

43 

Karakuş SC and Süzen A: Vertical plication: A penile curvature correction technique that reduces the need for urethral plate transection in penoscrotal hypospadias. J Pediatr Urol. 17:516.e1–516.e5. 2021.PubMed/NCBI View Article : Google Scholar

44 

Ndiaye M, Sow Y, Sarr A, Thiam A, Faye ST, Ndour NS, Sine B, Zé-Ondo C, Sow O, Ndiath A, et al: Hypospadias treatment by tubulated pedicled preputial island flap according to the DUCKETT technique: Single-center experience in sub-Saharan Africa. Afr J Urol. 27(156)2021.

45 

Rawashdeh YF, Hvistendal GM and Olsen LH: Foreskin transplantation between monozygotic twins discordant for hypospadias. Ugeskr Laeger. 183(V10200788)2021.PubMed/NCBI(In Danish).

46 

Blanc T, Peycelon M, Siddiqui M, Muller C, Paye-Jaouen A and El-Ghoneimi A: Double-face preputial island flap revisited: Is it a reliable one-stage repair for severe hypospadias? World J Urol. 39:1613–1624. 2021.PubMed/NCBI View Article : Google Scholar

47 

Fahiem-Ul-Hassan M, Jadhav V, Munianjanappa N, Saroja M and Santhanakrishnan R: Outcome of Buck's fascia repair with wingless glanuloplasty in distal penile hypospadias. Afr J Urol. 27(73)2021.

48 

Keshk TAEH, El Sheikh YMO, El Rahman MA, Rezq HSA and Dawod HAA: New modification of Koyanagi technique using dartos muscle flap in management of proximal hypospadias. Egypt J Hosp Med. 84:1832–1838. 2021.

49 

Tudu HC, Mishra A, Mohanty SK, Prashanthi N, Roy I, Bhardwaj P and Pujari PS: Outcome of proximal hypospadias repair in children using standard surgical technique with intermediate vascularised flap-a retrospective cohort study. J Clin Diagn Res. 15:9–12. 2021.

50 

Long CJ, van Batavia J, Wisniewski AB, Aston CE, Baskin L, Cheng EY, Lakshmanan Y, Meyer T, Kropp B, Palmer B, et al: Post-operative complications following masculinizing genitoplasty in moderate to severe genital atypia: Results from a multicenter, observational prospective cohort study. J Pediatr Urol. 17:379–386. 2021.PubMed/NCBI View Article : Google Scholar

51 

Askarpour S, Peyvasteh M, Mohamadi A and Khoshkhabar M: Comparative study of modifying meatal advancement glandular with release chordi versus snodgrass surgical methods regarding the repair of distal hypospadias. World J Plast Surg. 10:73–77. 2021.PubMed/NCBI View Article : Google Scholar

52 

Edan OAA: Urethral mobilization and advancement technique in distal types of hypospadias: Short-term local experience. Ann Pediatr Surgery. 17(60)2021.

53 

Noureldin YA, Gharib TM, El Attar KA, El Karamany TM and Al Adl AM: Extended TIP vs standard TIP for primary distal hypospadias repair: Randomized study for comparing functional and cosmetic outcomes. Scand J Urol. 55:466–473. 2021.PubMed/NCBI View Article : Google Scholar

54 

Abdelhalim KM, Abdelwahab HA, Abdelgawad E, Kadry AM and Sherief MH: Predictors of successful outcome of tubularized incised plate for primary distal hypospadias repair. Afr J Urol. 27(164)2021.PubMed/NCBI View Article : Google Scholar

55 

Shoukry A, Abbas A, Abdelwahab M, Ghoneima W, Shouman A, El Ghoneimy M, Morsi H, Badawy H, Eissa M and Aboulela W: Glans-urethral meatus-shaft score and penile parameters as preoperative assessment tools for hypospadias surgery outcome. Afr J Urol. 27(102)2021.

56 

Macedo A Jr, Ottoni SL, Di Migueli RDD, de Mattos RM, Garrone G and Leal da Cruz M: A different approach to distal hypospadias repair: The GUD (glandular urethral disassembly) technique. J Pediatr Urol. 17:690.e1–690.e6. 2021.PubMed/NCBI View Article : Google Scholar

57 

Özbey H, Ayryan E, Staroverov O and Morozov DA: Anatomical modeling of the foreskin for the reconstruction of glanular hypospadias. J Pediatr Urol. 17:335–337. 2021.PubMed/NCBI View Article : Google Scholar

58 

Permana W, Djojodimedjo T and Renaldo J: Tubularized incised plate urethroplasty for megameatus intact prepuce hypospadias variant: First reported case in Indonesia. Int J Surg Case Rep. 80(105698)2021.PubMed/NCBI View Article : Google Scholar

59 

Ahmed S, Noureldin YA, Sherif H, Zahran A and Omar R: Cosmetic outcomes of grafted tubularized incised plate urethroplasty in primary distal penile hypospadias: Prospective comparative study with the classic snodgrass repair. Afr J Urol. 27(152)2021.

60 

Kızılöz H, Okçelik S and Temel MC: MAGPI under local anaesthesia without catheter as an alternative to standard TIP procedure in distal hypospadias repair. Andrologia. 53(e13949)2021.PubMed/NCBI View Article : Google Scholar

61 

Alshammari D and Harper L: Deepithelialized glans reconfiguration (DeGRe) for distal hypospadias repair. J Pediatr Urol. 17:59.e1–59.e8. 2021.PubMed/NCBI View Article : Google Scholar

62 

Zhang B, Bi YL and Ruan SS: Application and efficacy of reconstructing forked corpus spongiosum in distal/midshaft hypospadias repair. Asian J Androl. 23:47–51. 2021.PubMed/NCBI View Article : Google Scholar

63 

Mohajerzadeh L, Moghadam AD, Tabari AK, Rouzrokh M and Moghimi N: Comparing mathieu and tubularized incised-plate urethroplasties for repairing distal penile hypospadias: A single-center experience with long-term outcome. Iran J Pediatr. 31(e111184)2021.

64 

Benson CR, Li G and Brandes SB: Long term outcomes of one-stage augmentation anterior urethroplasty: A systematic review and meta-analysis. Int Braz J Urol. 47:237–250. 2021.PubMed/NCBI View Article : Google Scholar

65 

Tessier B, Sfar S, Garnier S, Coffy A, Borrego P, Gaspari L, Paris F and Kalfa N: A cover flap reduces the rate of fistula after urethroplasty whatever the severity of hypospadias. World J Urol. 39:2691–2695. 2021.PubMed/NCBI View Article : Google Scholar

66 

Rudin YE, Maruhnenko DV, Rudin AY, Aliev DK, Lagutin GV and Vardak AB: Augmentation of the urethral plate in the glans penis area and the distal urethra-effective method of fistula correction in children with hypospadias. Androl Gen Surg. 22:62–70. 2021.

67 

Verma A, Murtaza S, Kundal VK, Sen A and Gali D: Comparison of dartos flap and spongioplasty in snodgrass urethroplasty in distal penile hypospadias. World J Pediatr Surg. 4(e000294)2021.PubMed/NCBI View Article : Google Scholar

68 

Naumeri F, Munir MA, Ahmad HM, Sharif M, Awan NU and Butt G: Comparison of urethrocutaneous fistula rate after single dartos and double dartos tubularized incised plate urethroplasty in pediatric hypospadias. Cureus. 13(e13378)2021.PubMed/NCBI View Article : Google Scholar

69 

Zhang Y, Chao M, Zhang WP, Tang YM, Chen HC, Zhang KP, Lu RG, Zhang XS and Lou DH: Using Buck's fascia as an integral covering in urethroplasty to restore the anatomical structure of the penis in one-stage hypospadias repair: A multicenter chinese study comprising 1,386 surgeries. Front Pediatr. 9(695912)2021.PubMed/NCBI View Article : Google Scholar

70 

Cetin S, Budak FC, Tan MO, Biri H, Sen I, Kupeli AB, Bozkirli I and Gurocak OS: Comparison of corporal plication for the correction of congenital penile curvature in pre-pubertal and post-pubertal patients: Does age matter? Andrologia. 53(e13965)2021.PubMed/NCBI View Article : Google Scholar

71 

Kozyrev GV, Manasherova DT and Abdulkarimov GA: Ventral penis curvature correction in children with hypospadias. Urologiia. 74–77. 2021.PubMed/NCBI(In Russian).

72 

Zhou G, Xu W, Yin J, Sun J, Yang Z and Li S: Single-stage versus staged interposition urethroplasty for glandular hypospadias with severe penile curvature: 15-Year experience. World J Urol. 40:155–160. 2022.PubMed/NCBI View Article : Google Scholar

73 

Furr JR, Wisenbaugh ES and Gelman J: Long-term outcomes for 2-stage urethroplasty: An analysis of risk factors for urethral stricture recurrence. World J Urol. 39:3903–3911. 2021.PubMed/NCBI View Article : Google Scholar

74 

Favre GA, Villa SG, Scherñuk J, Tobia IP and Giudice CR: Glans preservation in surgical treatment of distal urethral strictures with dorsal buccal mucosa graft onlay by subcoronal approach. Urology. 152:148–152. 2021.PubMed/NCBI View Article : Google Scholar

75 

Mershon JP and Baradaran N: Recurrent anterior urethral stricture: challenges and solutions. Res Rep Urol. 13:237–249. 2021.PubMed/NCBI View Article : Google Scholar

76 

Singh J: Urethrocutaneous fistula repair following hypospadias surgery using the PATIO technique for small fistulae: A single centre experience. J Pediatr Urol. 18:60.e1–60.e7. 2022.PubMed/NCBI View Article : Google Scholar

77 

Bar-Yosef Y, Ben-Chaim J, Ekstein M, Ben-David R, Savin Z, Yossepowitch O, Mano R and Dekalo S: Concomitant repair of meatal stenosis and urethral fistula does not increase the risk of fistula recurrence post hypospadias surgery. Urology. 160:187–190. 2022.PubMed/NCBI View Article : Google Scholar

78 

Chatterjee US, Basu AK and Bhaumik K: Needling for suture track fistula. J Indian Assoc Pediatr Surg. 26:203–205. 2021.PubMed/NCBI View Article : Google Scholar

79 

Shirazi M, Chowdhury U, Ahmed F, Rajabalian MB, Nikbakht HA, Al-Naggar K and Al-Shami E: Optimal clamping time in meatotomy procedure for children with meatal stenosis: Experience with 120 cases. Arch Ital Urol Androl. 93:244–247. 2021.PubMed/NCBI View Article : Google Scholar

80 

Shaw NM, Mallahan C, Joshi P, Venkatesan K and Kulkarni S: Novel use of Asopa technique for penile urethrocutaneous fistula repair. Int Urol Nephrol. 53:1127–1133. 2021.PubMed/NCBI View Article : Google Scholar

81 

Yadav S, Bamaniya M, Agarwal V, Tomar V, Gupta A and Kumawat G: Dorsal midline incision: A versatile technique for correction of meatal stenosis during hypospadias repair. J Clin Urol. 14:43–46. 2021.

82 

Samir M, Mahmoud MA, Azazy S and Tawfick A: Does the suturing technique (continuous versus interrupted) have an impact on the outcome of tubularized incised plate in hypospadias repair with adequate urethral plate? A prospective randomized study. J Pediatr Urol. 17:519.e1–519.e7. 2021.PubMed/NCBI View Article : Google Scholar

83 

Spinoit AF, Sinatti C, Lambert E, Pauwaert K, Verla W, van Laecke E and Hoebeke P: How I do it: Buttonholing the preputial hood in hypospadias repair-related ventral skin shortage. J Pediatr Urol. 17:332–334. 2021.PubMed/NCBI View Article : Google Scholar

84 

Mohamed Ali Alaraby SO, Abdeljaleel IA, Hamza AA and Elawad Elhassan AE: A comparative study of polydioxanone (PDS) and polyglactin (Vicryl) in hypospadias repair. Afr J Paediatr Surg. 18:53–57. 2021.PubMed/NCBI View Article : Google Scholar

85 

Scarpa MG, Codrich D, Iaquinto M, Guida E, Cerrina A and Schleef J: Medium-term outcome after stented and un-stented distal urethroplasty: A retrospective analysis on redo-urethroplasty need and cosmetic results. Actas Actas Urol Esp (Engl Ed). 45:642–647. 2021.PubMed/NCBI View Article : Google Scholar

86 

Zhang SY, Han C, Zhou HX, Li P, Ma LF, Tao T, Zhou XG, Tao YD, Zhu WW, Zhao Y, et al: Clinical evaluation of compound chamomile and lidocaine hydrochloride gel for postoperative hypospadias in children. Zhonghua Nan Ke Xue. 27:815–818. 2021.PubMed/NCBI(In Chinese).

87 

Doluoglu OG, Yıldız Y, Tokat E, Ozgur BC, Kılınc MF, Inan MA, Gonul II and Hoscan MB: The histopathological effect of aloe vera on the wound healing process in a surgically created tubularized incised plate urethroplasty model on rats. J Invest Surg. 35:1062–1066. 2022.PubMed/NCBI View Article : Google Scholar

88 

Oley MH, Oley MC, Iskandar AAA, Toreh C, Tulong MT and Faruk M: Hyperbaric oxygen therapy for reconstructive urology wounds: A case series. Res Rep Urol. 13:841–852. 2021.PubMed/NCBI View Article : Google Scholar

89 

Anand S, Krishnan N and Bajpai M: Utility and safety of hyperbaric oxygen therapy as a rescue treatment in complicated cases of hypospadias: A systematic review and meta-analysis. J Pediatr Urol. 18:39–46. 2022.PubMed/NCBI View Article : Google Scholar

90 

Anand S: Single-diaper, double-diaper, or no diaper: Does it make any difference following the repair of hypospadias? J Pediatr Urol. 17(885)2021.PubMed/NCBI View Article : Google Scholar

91 

Donnelly L, Feustel PJ, Cangero T and Kogan B: Postoperative pediatric urology opioid prescriptions at a tertiary academic medical center. J Pediatr Urol. 17:633.e1–633.e6. 2021.PubMed/NCBI View Article : Google Scholar

92 

Cornwell LB, Campbell PC, Ewing E and Swords KA: Children undergoing outpatient complex penile surgery and hypospadias repair may not require opioid analgesics. J Pediatr Surg. 57:678–682. 2022.PubMed/NCBI View Article : Google Scholar

93 

Basin MF, Baker ZG, Trabold M, Zhu T, Kelley-Quon LI, Bhaskar N, Vazirani R, Chen J and Kokorowski PJ: The impact of patient age and procedure type on postoperative opioid use following ambulatory pediatric urologic procedures. Pediatr Surg Int. 37:1127–1133. 2021.PubMed/NCBI View Article : Google Scholar

94 

Ji F, Tang H, Wu C, Chen L, Wang H and Yan B: Predictive value of C-reactive protein for early postoperative complications in children after hypospadias surgery. Front Pediatr. 9(690863)2021.PubMed/NCBI View Article : Google Scholar

95 

Karakaya AE, Güler AG and Doǧan AB: Dressing or not after tubularized incised plate urethroplasty. Urol Int. 105:1029–1033. 2021.PubMed/NCBI View Article : Google Scholar

96 

Esposito C, Coppola V, Del Conte F, Cerulo M, Esposito G, Crocetto F, Castagnetti M, Calignano A and Escolino M: Evaluation of a new tubular finger oxygen-enriched oil inside-coated dressing device in pediatric patients undergoing distal hypospadias repair: A prospective randomized clinical trial part II. Front Pediatr. 9(638406)2021.PubMed/NCBI View Article : Google Scholar

97 

Esposito C, Del Conte F, Cerulo M, Coppola V, Esposito G, Ricciardi E, Crocetto F, Castagnetti M, Calignano A and Escolino M: Evaluation of efficacy of oxygen-enriched oil-based gel dressing in patients who underwent surgical repair of distal hypospadias: A prospective randomised clinical trial. World J Urol. 39:2205–2215. 2021.PubMed/NCBI View Article : Google Scholar

98 

Anand S: Tissue glue-based dressings following hypospadias repair: A game-changer or a useless gimmick! J Pediatr Urol. 17:679–680. 2021.PubMed/NCBI View Article : Google Scholar

99 

Elsayem K, Darwish AS, AbouZeid AA, Kamel N, Dahab MM and El-Naggar O: Autologous platelet gel improves outcomes in tubularized incised plate repair of hypospadias. J Pediatr Surg. 57:488–491. 2022.PubMed/NCBI View Article : Google Scholar

100 

Murakami H, Seo S, Ochi T, Yazaki Y, Takeda M and Yamataka A: A useful tip for preventing surgical site infections after hypospadias repair. A single surgeon's experience of 376 cases. Afr J Paediatr Surg. 18:5–8. 2021.PubMed/NCBI View Article : Google Scholar

101 

Canon SJ, Smith JC, Sullivan E, Patel A and Zamilpa I: Comparative analysis of perioperative prophylactic antibiotics in prevention of surgical site infections in stented, distal hypospadias repair. J Pediatr Urol. 17:256.e1–256.e5. 2021.PubMed/NCBI View Article : Google Scholar

102 

Kim JK, Shiff M, Chua ME, Zu'bi F, Ming JM, Pokarowski M and Farhat WA: Time to event analysis for post-hypospadias repair complications: A single-surgeon experience. World J Urol. 39:3913–3919. 2021.PubMed/NCBI View Article : Google Scholar

103 

Arslan Alıcı Ç, Karkın EB and Tokar B: An atypical complication after hypospadias repair: A combined dorsal and lateral subcoronal urethrocutaneous fistulas. Andrologia. 54(e14276)2022.PubMed/NCBI View Article : Google Scholar

104 

Shirazi M, Haghpanah A, Dehghani A, Haghpanah S, Ghahartars M and Rahmanian M: Comparison of post-urethroplasty complication rates in pediatric cases with hypospadias using Vicryl or polydioxanone sutures. Asian J Urol. 9:165–169. 2022.PubMed/NCBI View Article : Google Scholar

105 

Karabulut R, Turkyilmaz Z, Atan A, Kaya C and Sonmez K: What are the factors affecting glanular dehiscence after hypospadias surgery? Actas Urol Esp (Engl Ed). 46:4–15. 2022.PubMed/NCBI View Article : Google Scholar : (In English, Spanish).

106 

Nguyen S, Durbin-Johnson B and Kurzrock EA: Reoperation after hypospadias repair: Long-term analysis. J Urol. 205:1778–1784. 2021.PubMed/NCBI View Article : Google Scholar

107 

Ru W, Tang D, Wu D, Tao C, Chen G, Wei J, Tian H and Shu Q: Identification of risk factors associated with numerous reoperations following primary hypospadias repair. J Pediatr Urol. 17:61.e1–61.e5. 2021.PubMed/NCBI View Article : Google Scholar

108 

Snodgrass W and Bush N: Recurrent ventral curvature after proximal TIP hypospadias repair. J Pediatr Urol. 17:222.e1–222.e5. 2021.PubMed/NCBI View Article : Google Scholar

109 

Ben-David R, Kupershmidt A, Dekalo S, Herzberg H, Mano R, Dubi-Sobol A, Ben-Chaim J and Bar-Yosef Y: Dorsal penile curvature and megameatus intact prepuce hypospadias: A common association in a rare variant of hypospadias. J Pediatr Urol. 17:517.e1–517.e4. 2021.PubMed/NCBI View Article : Google Scholar

110 

Spinoit AF, Waterschoot M, Sinatti C, Abbas T, Callens N, Cools M, Hamid R, Hanna MK, Joshi P, Misseri R, et al: Fertility and sexuality issues in congenital lifelong urology patients: male aspects. World J Urol. 39:1013–1019. 2021.PubMed/NCBI View Article : Google Scholar

111 

Varea-Malo R, Martínez Revuelta D, Campos-Juanatey F, Calleja Hermosa P and Correas Gómez MA: Long-term undesirable consequences of penile skin island flap to correct penoescrotal transposition: A case report and review of literature. Case Rep Urol. 2021(6656540)2021.PubMed/NCBI View Article : Google Scholar

112 

Kumar S, Mittal A, Panwar VK and Mandal AK: Laser epilation of luminal hair following skin graft urethroplasty for hypospadias: The hair snare. BMJ Case Rep. 14(e244123)2021.PubMed/NCBI View Article : Google Scholar

113 

Özbey H and Morozov D: Hypospadias surgery, erectile dysfunction and the distal ligament. J Pediatr Urol. 17:592–593. 2021.PubMed/NCBI View Article : Google Scholar

114 

Husmann DA: Erectile dysfunction in patients undergoing multiple attempts at hypospadias repair: Etiologies and concerns. J Pediatr Urol. 17:166.e1–166.e7. 2021.PubMed/NCBI View Article : Google Scholar

115 

Chapman DW, Bekkema J and Rourke K: Urinary symptom nonresponse (‘LUTS failure’) after urethroplasty: Incidence and Associations. J Urol. 206:986–993. 2021.PubMed/NCBI View Article : Google Scholar

116 

Favre G, Gil S, Carminatti T, Tobia I and Giudice C and Giudice C: Predictors of complex urethral surgery in anterior urethral stricture disease. Arch Esp Urol. 74:547–553. 2021.PubMed/NCBI

117 

Faraj S, Loubersac T, Bouchot O, Heloury Y and Leclair MD: Adults with previous hypospadias surgery during childhood: Beware of bulbar strictures. J Pediatr Urol. 18:4.e1–4.e8. 2022.PubMed/NCBI View Article : Google Scholar

118 

Ali D and Hanna MK: Symptomatic corpus spongiosum defect in adolescents and young adults who underwent distal hypospadias repair during childhood. J Pediatr Urol. 17:814.e1–814.e5. 2021.PubMed/NCBI View Article : Google Scholar

119 

Tack LJW, Springer A, Riedl S, Tonnhofer U, Hiess M, Weninger J, Mahmoud A, Van Laecke E, Hoebeke P, Cools M and Spinoit AF: Adolescent and young adult urogenital outcome following childhood hypospadias repair: Perfection revisited. J Urol. 206:734–744. 2021.PubMed/NCBI View Article : Google Scholar

120 

Godfrey LM: Mental health outcomes among individuals with 46,XY disorders of sex development: A systematic review. J Health Psychol. 26:40–59. 2021.PubMed/NCBI View Article : Google Scholar

121 

Sembiring G and Sigumonrong Y: Efficacy of preoperative testosterone therapy in hypospadias: A systematic review and meta-analysis. Ann Pediatr Surg. 17(56)2021.

122 

Lucas-Herald AK, Montezano AC, Alves-Lopes R, Haddow L, Alimussina M, O'Toole S, Flett M, Lee B, Amjad SB, Steven M, et al: Vascular dysfunction and increased cardiovascular risk in hypospadias. Eur Heart J. 43:1832–1845. 2022.PubMed/NCBI View Article : Google Scholar

123 

Alizadeh F, Amraei M, Haghdani S and Honarmand A: The effect of caudal epidural block on the surgical complications of hypospadias repair in children aged 6 to 35 months: A randomized controlled trial. J Pediatr Urol. 18:59.e1–59.e6. 2022.PubMed/NCBI View Article : Google Scholar

124 

Koul A, Shukla D, Aggrawal SK and Sethi N: Incidence of urethrocutaneous fistula following distal hypospadias repair with and without caudal epidural block: A randomized pilot study. J Pediatr Urol. 18:58.e1–58.e7. 2022.PubMed/NCBI View Article : Google Scholar

125 

Adler AC, Chandrakantan A, Lee AD, Koh CJ, Janzen NK and Austin PF: Effect of caudal vs penile block on the incidence of hypospadias complications following primary repairs: A retrospective cohort study. J Urol. 205:1454–1459. 2021.PubMed/NCBI View Article : Google Scholar

126 

Osmani F, Ferrer F and Barnett NR: Regional anesthesia for ambulatory pediatric penoscrotal procedures. J Pediatr Urol. 17:836–844. 2021.PubMed/NCBI View Article : Google Scholar

127 

Routh JC: Caudal blocks and hypospadias repair complications-much ado about nothing or the real deal? J Urol. 205:1252–1253. 2021.PubMed/NCBI View Article : Google Scholar

128 

Elsonbaty M, Abdullah S and Elsonbaty A: Lung ultrasound assisted comparison of volume effects of fluid replacement regimens in pediatric patients undergoing penile hypospadias repair: A randomized controlled trial. Anesth Pain Med. 11(e115152)2021.PubMed/NCBI View Article : Google Scholar

129 

Kandirici A, Mutlu M and Yiğit D: Does block anesthesia used in hypospadias surgery increase complication rates? İzmir Dr Behçet Uz Çocuk Hast Dergis. 11:328–332. 2021.

130 

Sisay A, Girma B, Negusie T, Abdi S, Horsa B and Ayele K: Inadvertent life-threatening total spinal anesthesia following caudal block in a preschool child underwent urologic surgery: A rare case report. Int J Surg Case Rep. 88(106541)2021.PubMed/NCBI View Article : Google Scholar

131 

Ponde V, Singh N, Nair A, Ongaigui CJ and Nagdev T: Comparison of landmark-guided, nerve stimulation-guided, and ultrasound-guided techniques for pediatric caudal epidural anesthesia: A prospective randomized controlled trial. Clin J Pain. 38:114–118. 2021.PubMed/NCBI View Article : Google Scholar

132 

Ahmed WAI, Shokier MHEHAEW, Kasem AAA, El Aziz MHA and Saed SGA: Comparative study between ultrasound-guided pudendal nerve block and caudal epidural block anesthesia in children undergoing hypospadias surgery. Ain-Shams J Anesthesiol. 13(50)2021.PubMed/NCBI View Article : Google Scholar

133 

Wang Y, Jia YP, Zhao LY, He QJ, Qi JL, Zhou R, Yang T, Zhao ZX and Wei HQ: Effects of three different doses of dexmedetomidine and ropivacaine on analgesia and the stress response in hypospadias surgery: A randomized trial. Front Pharmacol. 12(612216)2021.PubMed/NCBI View Article : Google Scholar

134 

Hassan AH, Amer IA and Abdelkareem AM: Comparative study between different additives to levobupivacaine in caudal block for postoperative pain management in pediatrics undergoing hypospadias repair: Randomized controlled study. Egypt J Hosp Med. 83:1120–1128. 2021.

135 

Karami T, Hoshyar H and Tavana AM: Comparing caudal block and penile block using rectal acetaminophen in postoperative analgesia of hypospadias repair: A randomized clinical trial study. Int J Surg Open. 29:9–13. 2021.

136 

Goel HK, Tirthraj CM, Kabra S, Gahlawat S, Sharma U and Sood R: Factors affecting outcome of adult hypospadias single stage repair: A prospective observational study. Turk J Urol. 47:420–426. 2021.PubMed/NCBI View Article : Google Scholar

137 

Abbas TO and Ali M: Scrotal base distance: A new key genital measurement in males with hypospadias and cryptorchidism. Curr Urol. 15:214–218. 2021.PubMed/NCBI View Article : Google Scholar

138 

Sennert M, Wirmer J and Hadidi AT: Preoperative glans & penile dimensions in different hypospadias grades. J Pediatr Urol. 18:47–53. 2022.PubMed/NCBI View Article : Google Scholar

139 

Abbas TO: Evaluation of penile curvature in patients with hypospadias; gaps in the current practice and future perspectives. J Pediatr Urol. 18:151–159. 2022.PubMed/NCBI View Article : Google Scholar

140 

Abbas TO: The rising need for preoperative objective quantification of curvature in patients with hypospadias. J Pediatr Urol. 17:599–600. 2021.PubMed/NCBI View Article : Google Scholar

141 

Fernandez N, Flórez-Valencia L, Prada JG, Chua M and Villanueva C: Standardization of penile angle estimation with a semi-automated algorithm. J Pediatr Urol. 17:226.e1–226.e6. 2021.PubMed/NCBI View Article : Google Scholar

142 

Zhao Z, Liu GC, Zhang LY, Fu W, Jia W and Hu JH: Mean microvessel density of the prepuce and its relationship with the severity of hypospadias and early postoperative complications. Zhonghua Nan Ke Xue. 27:725–728. 2021.PubMed/NCBI(In Chinese).

143 

Li K, Zhang X, Yan G, Zheng W and Zou Y: Prenatal diagnosis and classification of fetal hypospadias: The role and value of magnetic resonance imaging. J Magn Reson Imaging. 53:1862–1870. 2021.PubMed/NCBI View Article : Google Scholar

144 

Chaudhary G, Yhoshu E, Chauhan U, Ahmed I, Gupta MK, Piplani R and Balija SS: Anatomical study of hypospadias penis using magnetic resonance imaging in children. J Pediatr Urol. 18:57.e1–57.e7. 2022.PubMed/NCBI View Article : Google Scholar

145 

Fernandez N, Lorenzo AJ, Rickard M, Chua M, Pippi-Salle JL, Perez J, Braga LH and Matava C: Digital pattern recognition for the identification and classification of hypospadias using artificial intelligence vs experienced pediatric urologist. Urology. 147:264–269. 2021.PubMed/NCBI View Article : Google Scholar

146 

Dai LN, He R, Wu SF, Zhao HT and Sun J: Surgical treatment for prostatic utricle cyst in children: A single-center report of 15 patients. Int J Urol. 28:689–694. 2021.PubMed/NCBI View Article : Google Scholar

147 

Abbas TO: The plate objective scoring tool (POST): Further reflections and extended applications. Res Rep Urol. 13:783–791. 2021.PubMed/NCBI View Article : Google Scholar

148 

D'Oro A, Chan YY, Rosoklija I, Meyer T, Shannon R, Johnson EK, Liu DB, Gong EM, Maizels M, Matoka DJ, et al: Association between intra-operative meatal mismatch and urethrocutaneous fistula development in hypospadias repair. J Pediatr Urol. 17:223.e1–223.e8. 2021.PubMed/NCBI View Article : Google Scholar

149 

Gopal M: Ano-scrotal distance (ASD): Is it a marker for the severity of chordee? J Pediatr Urol. 17:672–673. 2021.PubMed/NCBI View Article : Google Scholar

150 

Yeşildal C, Yilmaz Ö, Akan S, Küçükodaci Z, Yenigürbüz S and Ediz C: Is primary adult hypospadiatic prepuce different from healthy prepuce in terms of microvascular density and androgen-estrogen-progesterone receptors? Andrologia. 53(e13857)2021.PubMed/NCBI View Article : Google Scholar

151 

Seleim HM: Topographic labeling of glans penis and corpus spongiosum when planning surgery for distal hypospadias. Res Rep Urol. 13:167–173. 2021.PubMed/NCBI View Article : Google Scholar

152 

Abdullaev Z, Agzamkhodjaev S, Chung JM and Lee SD: Risk factors for fistula recurrence after urethrocutaneous fistulectomy in children with hypospadias. Turk J Urol. 47:237–241. 2021.PubMed/NCBI View Article : Google Scholar

153 

Özbey H, Devecioğlu D and Staroverov O: A closer look at iatrogenic hypospadias. Andrologia. 53(e13803)2021.PubMed/NCBI View Article : Google Scholar

154 

Gao F, Gong C and Li L: Advance in research on the role of MAMLD1 gene in disorders of sex development. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 38:912–916. 2021.PubMed/NCBI View Article : Google Scholar : (In Chinese).

155 

Ibba A, Del Pistoia M, Balsamo A, Baronio F, Capalbo D, Russo G, DE Sanctis L and Bizzarri C: Differences of sex development in the newborn: From clinical scenario to molecular diagnosis. Minerva Pediatr (Torino). 73:606–620. 2021.PubMed/NCBI View Article : Google Scholar

156 

Nassau DE, Best JC, Cohen J, Gonzalez DC, Alam A and Ramasamy R: Androgenization in Klinefelter syndrome: Clinical spectrum from infancy through young adulthood. J Pediatr Urol. 17:346–352. 2021.PubMed/NCBI View Article : Google Scholar

157 

Nordenskjöld A and Holmdahl G: Role of genetic counseling for patients with hypospadias and their families. Eur J Pediatr Surg. 31:492–496. 2021.PubMed/NCBI View Article : Google Scholar

158 

Fendereski K, Carey J, Timme K, Hayes K, Robnett J and Schaeffer A: 46 XY undervirulized male DSD: Reporting a patient with prenatally diagnosed disorder/difference of sex development (DSD) with heterozygous LHCGR mutations. Urol Case Rep. 41(101971)2021.PubMed/NCBI View Article : Google Scholar

159 

Alfei E, Cattaneo E, Spaccini L, Iascone M, Veggiotti P and Doneda C: Progressive clinical and neuroradiological findings in a child with BCL11B missense mutation: Expanding the phenotypic spectrum of related disorder. Neuropediatrics. 53:283–286. 2022.PubMed/NCBI View Article : Google Scholar

160 

Li M, Che F, Qiu S and Wang Z: Identification of a novel variant of SRD5A2 gene in a child featuring steroid 5α-reductase type 2 deficiency. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 38:1233–1236. 2021.PubMed/NCBI View Article : Google Scholar : (In Chinese).

161 

Strong A, March ME, Cardinale CJ, Kim SE, Merves J, Whitworth H, Raffini L, Larosa C, Copelovitch L, Hou C, et al: A novel MBTPS2 variant associated with BRESHECK syndrome impairs sterol-regulated transcription and the endoplasmic reticulum stress response. Am J Med Genet A. 188:463–472. 2022.PubMed/NCBI View Article : Google Scholar

162 

Arsov T, Kelecic J, Frkovic SH, Sestan M, Kifer N, Andrews D, Adamski M, Jelusic M and Cook MC: Expanding the clinical spectrum of pathogenic variation in NR2F2: Asplenia. Eur J Med Genet. 64(104347)2021.PubMed/NCBI View Article : Google Scholar

163 

Thomas MM, Ashaat EA, Otaify GA, Ismail S, Essawi ML, Abdel-Hamid MS, Hassan HA, Alsaiedi SA, Aglan M, El Ruby MO and Temtamy S: First report of two egyptian patients with desbuquois dysplasia due to homozygous CANT1 mutations. Mol Syndromol. 12:279–288. 2021.PubMed/NCBI View Article : Google Scholar

164 

Bouhouche A, Albaroudi N, El Alaoui MA, Askander O, Habbadi Z, El Hassani A, Iraqi H, El Fahime E and Belmekki M: Identification of the novel SDR42E1 gene that affects steroid biosynthesis associated with the oculocutaneous genital syndrome. Exp Eye Res. 209(108671)2021.PubMed/NCBI View Article : Google Scholar

165 

Luo Q, Zhang Q, Shen J, Guan W, Li M, Zhang J and Tan Z: Expanding mutational spectrum of HRAS by a patient with schimmelpenning-feuerstein-mims syndrome. J Dermatol. 48:1273–1276. 2021.PubMed/NCBI View Article : Google Scholar

166 

Akramov NR, Shavaliev RF and Osipova IV: .: New mutation in WT1 gene in a boy with an incomplete form of Denys-Drash syndrome: A CARE-compliant case report. Medicine (Baltimore). 100(e25864)2021.PubMed/NCBI View Article : Google Scholar

167 

Elghezal H, Alfayez K, Ben Abdallah I, Alfares A, Almazyad A, Al Jasser A, Almobadel N, Alsuhaibani O and Alhashem A: Hypospadias in ring X syndrome. Eur J Med Genet. 64(104225)2021.PubMed/NCBI View Article : Google Scholar

168 

Ravirajendran S, Palaniyandi V, Arora A, Ramanan V and Kumaresan N: Mullerian remnants presenting as a pelvic cyst in a young adult with 45X0/46XY mixed gonadal dysgenesis. Urol Ann. 13:76–79. 2021.PubMed/NCBI View Article : Google Scholar

169 

Correya M, Babu R, Archana B and Ravirajendiran S: Disorders of sexual differentiation: Report of two rare cases. Indian J Pathol Microbiol. 64:390–393. 2021.PubMed/NCBI View Article : Google Scholar

170 

Chen L, Huang H, Zhang H, Zhu G and Zhu M: Three cases of 3β-hydroxysteroid dehydrogenase deficiency: Clinical analysis. Adv Clin Exp Med. 30:289–299. 2021.PubMed/NCBI View Article : Google Scholar

171 

Saida K, Fukuda T, Scott DA, Sengoku T, Ogata K, Nicosia A, Hernandez-Garcia A, Lalani SR, Azamian MS, Streff H, et al: OTUD5 variants associated with X-linked intellectual disability and congenital malformation. Front Cell Dev Biol. 9(631428)2021.PubMed/NCBI View Article : Google Scholar

172 

Çiftci N, Kayaş L, Çamtosun E and Akıncı A: 46,XY sex development defect due to a novel homozygous (splice site) c.673_1G>C variation in the HSD17B3 gene: Case report. J Clin Res Pediatr Endocrinol. 14:233–238. 2022.PubMed/NCBI View Article : Google Scholar

173 

Laan M, Kasak L, Timinskas K, Grigorova M, Venclovas Č, Renaux A, Lenaerts T and Punab M: NR5A1 c.991-1G>C splice-site variant causes familial 46,XY partial gonadal dysgenesis with incomplete penetrance. Clin Endocrinol (Oxf). 94:656–666. 2021.PubMed/NCBI View Article : Google Scholar

174 

Gerber JA, Sheth KR and Austin PF: Robinow syndrome: Genital analysis, genetic heterogeneity, and associated psychological impact. Am J Med Genet A. 185:3601–3605. 2021.PubMed/NCBI View Article : Google Scholar

175 

Sheppard SE, Barrett B, Muraresku C, McKnight H, De Leon DD, Lord K and Ganetzky R: Heterozygous recurrent HNF4A variant p.Arg85Trp causes Fanconi renotubular syndrome 4 with maturity onset diabetes of the young, an autosomal dominant phenocopy of Fanconi Bickel syndrome with colobomas. Am J Med Genet A. 185:566–570. 2021.PubMed/NCBI View Article : Google Scholar

176 

Tripolszki K, Sasaki E, Hotakainen R, Kassim AH, Pereira C, Rolfs A, Bauer P, Reardon W and Bertoli-Avella AM: An X-linked syndrome with severe neurodevelopmental delay, hydrocephalus, and early lethality caused by a missense variation in the OTUD5 gene. Clin Genet. 99:303–308. 2021.PubMed/NCBI View Article : Google Scholar

177 

Hage M, Drui D, Francou B, Mercier S, Guiochon-Mantel A, Belaisch-Allart J, Péréon Y, Cazabat L, De Mazancourt P and Raffin-Sanson ML: Structural analysis of the impact of a novel androgen receptor gene mutation in two adult patients with mild androgen insensitivity syndrome. Andrologia. 53(e13865)2021.PubMed/NCBI View Article : Google Scholar

178 

Basa M, Vukovic R, Sarajlija A, Milenkovic T, Djordjevic M, Vucetic B and Martic J: Ambiguous genitalia and lissencephaly in A 46,XY neonate with a novel variant of aristaless gene. Acta Endocrinol (Buchar). 17:402–405. 2021.PubMed/NCBI View Article : Google Scholar

179 

Kherouatou-Chaoui N, Chellat-Rezgoune D, Rezgoune ML, Mc Elreavey K, Touabti LS, Abadi N and Satta D: SRY and NR5A1 gene mutation in Algerian children and adolescents with DSD and testicular dysgenesis. Afr Health Sci. 21:1491–1497. 2021.PubMed/NCBI View Article : Google Scholar

180 

Chen J, Cui X, Li A, Li G and Sun F: Association of a GATA binding protein 4 polymorphism with the risk of hypospadias in the Chinese children. Urol Int. 105:1018–1023. 2021.PubMed/NCBI View Article : Google Scholar

181 

Wong YS, Pang KKY and Tam YH: Surgery in Chinese children affected by 45,X/46,XY disorders of sex development: A 20-year experience in a single center. J Pediatr Surg. 57:1398–1403. 2022.PubMed/NCBI View Article : Google Scholar

182 

Deng F, Zhao J, Jia W, Fu K, Zuo X, Huang L, Wang N, Xia H, Zhang Y, Fu W and Liu G: Increased hypospadias risk by GREM1 rs3743104[G] in the southern Han Chinese population. Aging (Albany NY). 13:13898–13908. 2021.PubMed/NCBI View Article : Google Scholar

183 

Siregar S, Sibarani J, Noegroho BS, Firmansyah I and Maskoen AM: Polymorphism of PvuII, Xba1, and SNP 12 estrogen receptor 1 (ESR1) in hipospadias patients at tertiary hospital center. Res Rep Urol. 13:105–110. 2021.PubMed/NCBI View Article : Google Scholar

184 

Saraç M, Canpolat Ş, Önalan Etem E, Tektemur A, Tartar T, Bakal U and Kazez A: The role of sonic hedgehog homologue signal pathway in hypospadias aetiology. J Pediatr Urol. 17:630.e1–630.e7. 2021.PubMed/NCBI View Article : Google Scholar

185 

Tenenbaum-Rakover Y, Admoni O, Elias-Assad G, London S, Noufi-Barhoum M, Ludar H, Almagor T, Zehavi Y, Sultan C, Bertalan R, et al: The evolving role of whole-exome sequencing in the management of disorders of sex development. Endocr Connect. 10:620–629. 2021.PubMed/NCBI View Article : Google Scholar

186 

Ea V, Bergougnoux A, Philibert P, Servant-Fauconnet N, Faure A, Breaud J, Gaspari L, Sultan C, Paris F and Kalfa N: How far should we explore hypospadias? Next-generation sequencing applied to a large cohort of hypospadiac patients. Eur Urol. 79:507–515. 2021.PubMed/NCBI View Article : Google Scholar

187 

Schmidt J, Schreiber G, Altmüller J, Thiele H, Nürnberg P, Li Y, Kaulfuß S, Funke R, Wilken B, Yigit G and Wollnik B: Familial cleft tongue caused by a unique translation initiation codon variant in TP63. Eur J Hum Genet. 30:211–218. 2022.PubMed/NCBI View Article : Google Scholar

188 

Ding Y, Cao BY, Su C, Liu M, Chen JJ, Fan LJ and Gong CX: Clinical and genetic analysis of Noonan syndrome in 20 children. Zhonghua Er Ke Za Zhi. 59:588–593. 2021.PubMed/NCBI View Article : Google Scholar : (In Chinese).

189 

Lourenço CSFP, Carriço AL and Valente FMDS: Prenatal diagnosis of aberrant right subclavian artery: Association with genetic abnormalities. Rev Bras Ginecol Obstet. 43:452–456. 2021.PubMed/NCBI View Article : Google Scholar

190 

Konishi A, Ida S, Matsui F, Etani Y and Kawai M: Male assignment in 5α-reductase type 2 deficiency with female external genitalia. Pediatr Int. 63:592–594. 2021.PubMed/NCBI View Article : Google Scholar

191 

Rjiba K, Ayech H, Kraiem O, Slimani W, Jelloul A, Ben Hadj Hmida I, Mahdhaoui N, Saad A and Mougou-Zerelli S: Disorders of sex development in Wolf-Hirschhorn syndrome: A genotype-phenotype correlation and MSX1 as candidate gene. Mol Cytogenet. 14(12)2021.PubMed/NCBI View Article : Google Scholar

192 

Yuri P, Gunadi Lestari RP, Fardilla FP and Dachlan I: Expression of mRNA vascular endothelial growth factor in hypospadias patients. BMC Urol. 21(163)2021.PubMed/NCBI View Article : Google Scholar

193 

Kong X, Luo J, Xiang H, Wang S, Shen L, Long C, Liu F, Lin T, He D, Liu X and Wei GH: Expression of Mafb is down-regulated in the foreskin of children with hypospadias. J Pediatr Urol. 17:70.e1–70.e6. 2021.PubMed/NCBI View Article : Google Scholar

194 

Spinder N, Bergman JEH, van Tongeren M, Boezen HM, Kromhout H and de Walle HEK: Maternal occupational exposure to endocrine-disrupting chemicals and urogenital anomalies in the offspring. Hum Reprod. 37:142–151. 2021.PubMed/NCBI View Article : Google Scholar

195 

Rodprasert W, Toppari J and Virtanen HE: Endocrine disrupting chemicals and reproductive health in boys and men. Front Endocrinol (Lausanne). 12(706532)2021.PubMed/NCBI View Article : Google Scholar

196 

Mattiske DM and Pask AJ: Endocrine disrupting chemicals in the pathogenesis of hypospadias; developmental and toxicological perspectives. Curr Res Toxicol. 2:179–191. 2021.PubMed/NCBI View Article : Google Scholar

197 

Laws MJ, Neff AM, Brehm E, Warner GR and Flaws JA: Endocrine disrupting chemicals and reproductive disorders in women, men, and animal models. Adv Pharmacol. 92:151–190. 2021.PubMed/NCBI View Article : Google Scholar

198 

Stukenborg JB, Mitchell RT and Söder O: Endocrine disruptors and the male reproductive system. Best Pract Res Clin Endocrinol Metab. 35(101567)2021.PubMed/NCBI View Article : Google Scholar

199 

Schiesaro MG, Amato AML, Maneschi C, Sciabica V, Pigatto E and Sanna M: The male reproductive system and endocrine disruptors. Endocr Metab Immune Disord Drug Targets. 22:686–703. 2022.PubMed/NCBI View Article : Google Scholar

200 

Wu Y, Wang J, Wei Y, Chen J, Kang L, Long C, Wu S, Shen L and Wei G: Contribution of prenatal endocrine-disrupting chemical exposure to genital anomalies in males: The pooled results from current evidence. Chemosphere. 286(131844)2022.PubMed/NCBI View Article : Google Scholar

201 

Gaspari L, Tessier B, Paris F, Bergougnoux A, Hamamah S, Sultan C and Kalfa N: endocrine-disrupting chemicals and disorders of penile development in humans. Sex Dev. 15:213–228. 2021.PubMed/NCBI View Article : Google Scholar

202 

Huang X, Chen J, Zeng D, Lin Z, Herbert C, Cottrell L, Liu L, Ash A and Wang B: The association between ambient air pollution and birth defects in five major ethnic groups in Liuzhou, China. BMC Pediatr. 21(232)2021.PubMed/NCBI View Article : Google Scholar

203 

Xing Z, Zhang S, Jiang YT, Wang XX and Cui H: Association between prenatal air pollution exposure and risk of hypospadias in offspring: A systematic review and meta-analysis of observational studies. Aging (Albany NY). 13:8865–8879. 2021.PubMed/NCBI View Article : Google Scholar

204 

Bougnères P, Porcher R, Esterle L, Baker D, de la Vaissière A, Meurisse S, Valtat S, Castell AL, Mouriquand P and Valleron AJ: Exploring the risk of hypospadias in children born from mothers living close to a vineyard. PLoS One. 16(e0249800)2021.PubMed/NCBI View Article : Google Scholar

205 

Mesquita I, Lorigo M and Cairrao E: Update about the disrupting-effects of phthalates on the human reproductive system. Mol Reprod Dev. 88:650–672. 2021.PubMed/NCBI View Article : Google Scholar

206 

Soyer-Gobillard MO, Gaspari L, Paris F, Kalfa N, Hamamah S, Courtet P and Sultan C: Prenatal exposure to diethylstilbestrol and multigenerational psychiatric disorders: An informative family. Int J Environ Res Public Health. 18(9965)2021.PubMed/NCBI View Article : Google Scholar

207 

Zhang ZC, Liu X, Wei C, Luo J, Shi Y, Lin T, He D and Wei G: Assisted reproductive technologies and the risk of congenital urogenital tract malformations: A systematic review and meta-analysis. J Pediatr Urol. 17:9–20. 2021.PubMed/NCBI View Article : Google Scholar

208 

Zhang S, Yue DM, Zhang JY, Huang YH, Li J, Liu S, Chen YL, Li LL, Jiang CZ, Chen ZJ, et al: Maternal exposure to sulfur dioxide before and after conception and the risk of hypospadias in offspring. Ann N Y Acad Sci. 1502:99–109. 2021.PubMed/NCBI View Article : Google Scholar

209 

Rouget F, Bihannic A, Cordier S, Multigner L, Meyer-Monath M, Mercier F, Pladys P and Garlantezec R: Petroleum and chlorinated solvents in meconium and the risk of hypospadias: A pilot study. Front Pediatr. 9(640064)2021.PubMed/NCBI View Article : Google Scholar

210 

Haghighi MM, Wright CY, Ayer J, Urban MF, Pham MD, Boeckmann M, Areal A, Wernecke B, Swift CP, Robinson M, et al: Impacts of high environmental temperatures on congenital anomalies: A systematic review. Int J Environ Res Public Health. 18(4910)2021.PubMed/NCBI View Article : Google Scholar

211 

Gadagbui BK, York RG, Dourson ML, McGinnis PM and Cope RB: Analysis for data-derived extrapolation factors for procymidone. Regul Toxicol Pharmacol. 124(104972)2021.PubMed/NCBI View Article : Google Scholar

212 

Lin HC, Guo JM, Ge P and Ou P: Association between prenatal exposure to ambient particulate matter and risk of hypospadias in offspring: A systematic review and meta-analysis. Environ Res. 192(110190)2021.PubMed/NCBI View Article : Google Scholar

213 

Akay MA and Yıldız GE: Impact of gestational and parental factors and maternal intake of progesterone on the development of hypospadias: A retrospective case-control study. Taiwan J Obstet Gynecol. 60:894–898. 2021.PubMed/NCBI View Article : Google Scholar

214 

Chung EH, Harris BS, Muasher SJ and Kuller JA: The risk of congenital anomalies by fertility treatment modality. Obstet Gynecol Surv. 76:37–47. 2021.PubMed/NCBI View Article : Google Scholar

215 

Baskin L, Sinclair A, Derpinghaus A, Cao M, Li Y, Overland M, Aksel S and Cunha GR: Estrogens and development of the mouse and human external genitalia. Differentiation. 118:82–106. 2021.PubMed/NCBI View Article : Google Scholar

216 

Wu Y, Yao J wei, Xu L jie, Chen M and Wan L: Risk of congenital malformations in offspring of women using β-blockers during early pregnancy: An updated meta-analysis of observational studies. Br J Clin Pharmacol. 87:806–815. 2021.PubMed/NCBI View Article : Google Scholar

217 

Schraw JM, Langlois PH and Lupo PJ: Comprehensive assessment of the associations between maternal diabetes and structural birth defects in offspring: A phenome-wide association study. Ann Epidemiol. 53:14–20.e8. 2021.PubMed/NCBI View Article : Google Scholar

218 

Liu Y, Fan L, Wang X and Gong C: Exploring the efficacy of testosterone undecanoate in male children with 5α-reductase deficiency. Pediatr Investig. 5:249–254. 2021.PubMed/NCBI View Article : Google Scholar

219 

Li B, Kong I, McGrath M, Farrokhyar F and Braga LH: Evaluating the literature on preoperative androgen stimulation for hypospadias repair using the fragility index-can we trust observational studies? J Pediatr Urol. 17:661–669. 2021.PubMed/NCBI View Article : Google Scholar

220 

Concepción-Zavaleta MJ, García-Villasante EJ, Zavaleta-Gutiérrez FE, Barrantes Ticlla JL and Massucco Revoredo FG: Late diagnosis of partial androgen insensitivity syndrome in a peruvian child. Cureus. 13(e16565)2021.PubMed/NCBI View Article : Google Scholar

221 

Khokar DS and Patel RV: Can testosterone alter the degree of hypospadias? A comprehensive study. J Indian Assoc Pediatr Surg. 26:38–43. 2021.PubMed/NCBI View Article : Google Scholar

222 

Chukwubuike KE: Single dose of testosterone in children with hypospadias: Any effect on the diameter of the glans penis? Afr J Urol. 27(34)2021.

223 

D'Oro A, Rosoklija I, Yerkes EB, Lindgren BW, Rychlik K and Cheng EY: Proximal hypospadias and acquired cryptorchidism: Incidence, morphology and potential clinical implications. J Urol. 206:1291–1299. 2021.PubMed/NCBI View Article : Google Scholar

224 

Ludorf KL, Benjamin RH, Navarro Sanchez ML, McLean SD, Northrup H, Mitchell LE, Langlois PH, Canfield MA, Scheuerle AE, Scott DA, et al: Patterns of co-occurring birth defects among infants with hypospadias. J Pediatr Urol. 17:64.e1–64.e8. 2021.PubMed/NCBI View Article : Google Scholar

225 

Fuchs ME, Halleran DR, Bourgeois T, Sebastião Y, Weaver L, Farrell N, Vilanova-Sánchez A, Gasior A, Halaweish I, Jayanthi VR, et al: Correlation of anorectal malformation complexity and associated urologic abnormalities. J Pediatr Surg. 56:1988–1992. 2021.PubMed/NCBI View Article : Google Scholar

226 

de Jesus Escano MR, Mejia Sang ME, Reyes-Mugica M, Colaco M and Fox J: Ovotesticular disorder of sex development: Approach and management of an index case in the dominican republic. Cureus. 13(e18512)2021.PubMed/NCBI View Article : Google Scholar

227 

Nelwan D, Mount C, Morganstern B and Chan JT: Infant with severe penoscrotal hypospadias: A complex case of genital ambiguity and mistaken identity. Cureus. 13(e15191)2021.PubMed/NCBI View Article : Google Scholar

228 

Ashfaq S, Siddiqui A, Shafiq W and Azmat U: A rare presentation of disorder of sex development. Cureus. 13(e12782)2021.PubMed/NCBI View Article : Google Scholar

229 

Rittler M, Campaña H, Heisecke S, Ratowiecki J, Elias D, Gimenez L, Poletta FA, Gili J, Pawluk M, Santos MR, et al: Lethality of birth defects in live born infants categorized by gestational age and birth weight. Am J Perinatol: Oct 11, 2021 (Epub ahead of print).

230 

Álvarez-Álvarez A, Costa-Romero M, Suárez Saavedra S, Rial JC, Lois Bermejo AM, García González N and Fernández-Rodríguez H: Dandy-Walker malformation associated with extracranial abnormalities in a newborn. Arch Argent Pediatr. 119:e526–e530. 2021.PubMed/NCBI View Article : Google Scholar : (In Spanish).

231 

Viet Nguyen H, Hong Vu T, Quy Hong Q, Quang Pham H and Bich Nguyen N: Hypospadias associated with partial bifid phallus: A case report. Urol Case Rep. 39(101840)2021.PubMed/NCBI View Article : Google Scholar

232 

Çelik G, Batu Oto B, Kızılay O, Kılıçarslan O and Toptan HH: An unusual ophthalmic presentation of Wolf-Hirschhorn syndrome. Ophthalmic Genet. 42:326–328. 2021.PubMed/NCBI View Article : Google Scholar

233 

Bhatia VP, Mittal AG, Austin PF and Hilliard ME: The hypospadias-specific health-related quality of life conceptual framework: A scoping review of the literature. Qual Life Res. 30:1537–1546. 2021.PubMed/NCBI View Article : Google Scholar

234 

Hoare DT, Bekkema J and Rourke KF: Prospective assessment of patient-perceived short-term changes in penile appearance after urethroplasty. Urology. 158:222–227. 2021.PubMed/NCBI View Article : Google Scholar

235 

Bhatia VP, Hilliard ME, Austin PF and Mittal AG: Evaluating quality of patient-reported outcome measures in patients with hypospadias. J Pediatr Urol. 17:50–58. 2021.PubMed/NCBI View Article : Google Scholar

236 

Chang C, Reifsnyder JE, Fahmy AG and Hanna MK: The adolescent glans penis: Functional and aesthetic issues following childhood hypospadias repair. J Pediatr Urol. 17:609.e1–609.e8. 2021.PubMed/NCBI View Article : Google Scholar

237 

Sinatti C, Schechter MY, Spinoit AF and Hoebeke P: Long-term outcome of urethral and genital reconstruction in hypospadias and exstrophy-epispadias complex. Curr Opin Urol. 31:480–485. 2021.PubMed/NCBI View Article : Google Scholar

238 

Calleja Hermosa P, Campos-Juanatey F, Varea Malo R, Correas Gómez MÁ and Gutiérrez Baños JL: Trauma and Reconstructive Urology Working Party of the European Association of Urology Young Academic Urologists. Sexual function after anterior urethroplasty: A systematic review. Transl Androl Urol. 10:2554–2573. 2021.PubMed/NCBI View Article : Google Scholar

239 

Mallenahalli S, Fang AH, Tong CMC and Dangle PP: A review of literature on long-term outcomes of proximal hypospadias-urinary, sexual, and psychosocial. Curr Sex Health Rep. 13:38–44. 2021.

240 

Zhang ZC, Liu X, Chen HS, Shi Y, Lin T, He DW, Wei GH and Luo YT: Analysis of the social and clinical factors affecting the age of children when receiving surgery for hypospadias: A retrospective study of 1611 cases in a single center. Asian J Androl. 23:527–531. 2021.PubMed/NCBI View Article : Google Scholar

241 

Bennecke E, Bernstein S, Lee P, van de Grift TC, Nordenskjöld A, Rapp M, Simmonds M, Streuli JC, Thyen U and Wiesemann C: dsd-LIFE Group. Early genital surgery in disorders/differences of sex development: Patients' perspectives. Arch Sex Behav. 50:913–923. 2021.PubMed/NCBI View Article : Google Scholar

242 

Bangalore Krishna K, Kogan BA, Mazur T, Hoebeke P, Bogaert G and Lee PA: Individualized care for patients with intersex (differences of sex development): Part 4/5.considering the ifs, whens, and whats regarding sexual-reproductive system surgery. J Pediatr Urol. 17:338–345. 2021.PubMed/NCBI View Article : Google Scholar

243 

Cakmak M, Gollu G, Ates U, Ergun E, Khanmammadov F, Sozduyar S, Telli O, Kose K, Dilsiz H, Cakmak A, et al: Hypospadias and the use of the ages and stages questionnaire to evaluate neurodevelopmental status of boys with hypospadias. Eur J Pediatr Surg. 32:274–279. 2022.PubMed/NCBI View Article : Google Scholar

244 

van de Grift TC, Rapp M, Holmdahl G, Duranteau L and Nordenskjold A: dsd-LIFE group. Masculinizing surgery in disorders/differences of sex development: Clinician- and participant-evaluated appearance and function. BJU Int. 129:394–405. 2022.PubMed/NCBI View Article : Google Scholar

245 

Gul M, Hildorf S and Silay MS: Sexual functions and fertility outcomes after hypospadias repair. Int J Impot Res. 33:149–163. 2021.PubMed/NCBI View Article : Google Scholar

246 

Guner E and Kadioglu A: Specific urogenital disease information-revealing male genital votive offerings dedicated to gods in ancient age sanctuary medicine. Arch Esp Urol. 74:239–246. 2021.PubMed/NCBI(In English, Spanish).

247 

Buyukunal C, Zeller KA, Emre S and Nakayama DK: The history of surgery in disorders of sexual development. J Pediatr Surg. 56:429–433. 2021.PubMed/NCBI View Article : Google Scholar

248 

Baker Z, Bhaskar N, Herbst KW, Hagadorn JI and Kokorowski P: Sample size, power, and risk of misclassification in pediatric urology hospital rankings. J Urol. 206:436–446. 2021.PubMed/NCBI View Article : Google Scholar

249 

Maier M, Ebert AK, Baunacke M, Groeben C, Eisenmenger N, Thomas C and Huber J: Health care reality of selected pediatric urologic surgeries in Germany from 2006 to 2019. Urologe A. 60:1291–1303. 2021.PubMed/NCBI View Article : Google Scholar : (In German).

250 

Scarberry KA, Gor RA and Kovell RC: Management of the transitional urology patient: The role of the adult reconstructive urologist. Curr Urol Rep. 22(15)2021.PubMed/NCBI View Article : Google Scholar

251 

Mahalik S, Pati A and Das K: Awareness of common pediatric surgical entities among practicing indian pediatricians. J Indian Assoc Pediatr Surg. 26:89–93. 2021.PubMed/NCBI View Article : Google Scholar

252 

Kharbanda EO, Vazquez-Benitez G, DeSilva MB, Spaulding AB, Daley MF, Naleway AL, Irving SA, Klein NP, Tseng HF, Jackson LA, et al: Developing algorithms for identifying major structural birth defects using automated electronic health data. Pharmacoepidemiol Drug Saf. 30:266–274. 2021.PubMed/NCBI View Article : Google Scholar

253 

Wu S, He R, Sun J and Zhao H: Acellular dermal matrix graft for ventral corporal lengthening orthoplasty in 2-stage proximal hypospadias repair. Transl Pediatr. 10:3151–3158. 2021.PubMed/NCBI View Article : Google Scholar

254 

Singh A, Anand S, Goel P, Yadav DK and Bajpai M: Can sealing promote healing?: A systematic review and meta-analysis highlighting the adjunctive role of tissue sealant application during urethroplasty for hypospadias. J Pediatr Urol. 17:805–812. 2021.PubMed/NCBI View Article : Google Scholar

255 

Wang Y, Wang G, Hou X, Zhao Y, Chen B, Dai J and Sun N: Urethral tissue reconstruction using the acellular dermal matrix patch modified with collagen-binding VEGF in beagle urethral injury models. Biomed Res Int. 2021(5502740)2021.PubMed/NCBI View Article : Google Scholar

256 

Morgante D, Radford A, Abbas SK, Ingham E, Subramaniam R and Southgate J: Augmentation of the insufficient tissue bed for surgical repair of hypospadias using acellular matrix grafts: A proof of concept study. J Tissue Eng. 12(2041731421998840)2021.PubMed/NCBI View Article : Google Scholar

257 

Tawfeek AM, Mohareb AM, Higazy A, Farouk A, Elsaeed KO, Tawfick A and Radwan A: Isoamyl 2-cyanoacrylate interposition in the urethro-cutaneous fistula repair: A randomized controlled trial. Afr J Urol. 27(94)2021.

258 

Shenoy NS, Tiwari C, Gandhi S, Kumbhar V, Joseph V, Basu S, Makan A and Shah H: Efficacy of fibrin sealant as waterproof cover in improving outcome in hypospadias surgery. Afr J Paediatr Surg. 18:215–218. 2021.PubMed/NCBI View Article : Google Scholar

259 

Abbas TO, Elawad A, Kareem A, Pullattayil S AK, Ali M and Alnaimi A: Preclinical experiments for hypospadias surgery: Systematic review and quality assessment. Front Pediatr. 9(718647)2021.PubMed/NCBI View Article : Google Scholar

260 

Amesty MV, Chamorro CI, López-Pereira P, Martínez-Urrutia MJ, Sanz B, Rivas S, Lobato R and Fossum M: Creation of tissue-engineered urethras for large urethral defect repair in a rabbit experimental model. Front Pediatr. 9(691131)2021.PubMed/NCBI View Article : Google Scholar

261 

Palermo CM, Foreman JE, Wikoff DS and Lea I: Development of a putative adverse outcome pathway network for male rat reproductive tract abnormalities with specific considerations for the androgen sensitive window of development. Curr Res Toxicol. 2:254–271. 2021.PubMed/NCBI View Article : Google Scholar

262 

Alcantara MC, Suzuki K, Acebedo AR, Sakamoto Y, Nishita M, Minami Y, Kikuchi A and Yamada G: Stage-dependent function of Wnt5a during male external genitalia development. Congenit Anom (Kyoto). 61:212–219. 2021.PubMed/NCBI View Article : Google Scholar

263 

Xiang H, Wang S, Kong X, Yu Y, Shen L, Long C, Liu X and Wei GH: c-Fos is upregulated in the genital tubercle of DEHP-induced hypospadiac rats and the prepuce of patients with hypospadias. Syst Biol Reprod Med. 67:193–200. 2021.PubMed/NCBI View Article : Google Scholar

264 

Feng X, Huang E, Gao Y, Zhang Y and Zhou Y: The effects of NONRATT008453.2 on autophagy in genital tubercle fibroblasts of rats with hypospadias induced by dibutyl phthalate. Birth Defects Res. 113:399–408. 2021.PubMed/NCBI View Article : Google Scholar

265 

Yu H, Yang J, Zhang Y, Fu H, Yan Z and Zhu Y: Vinclozolin-induced mouse penile malformation and ‘small testis’ via miR132, miR195a together with the Hippo signaling pathway. Toxicology. 460(152842)2021.PubMed/NCBI View Article : Google Scholar

266 

Abbas TO, Elawad A, Pullattayil S AK and Pennisi CP: Quality of reporting in preclinical urethral tissue engineering studies: A systematic review to assess adherence to the ARRIVE guidelines. Animals (Basel). 11(2456)2021.PubMed/NCBI View Article : Google Scholar

267 

Tan H, Wu G, Wang S, Lawless J, Sinn A, Chen D and Zheng Z: Prenatal exposure to atrazine induces cryptorchidism and hypospadias in F1 male mouse offspring. Birth Defects Res. 113:469–484. 2021.PubMed/NCBI View Article : Google Scholar

268 

Tokat E, Yildiz Y, Eser PE, Kilinc MF and Doluoglu OG: Does intraurethral erythropoietin administration effect wound healing after hypospadias correction? An experimental rat study. Int Urol Nephrol. 53:2057–2062. 2021.PubMed/NCBI View Article : Google Scholar

269 

Gulburun MA, Karabulut R, Turkyilmaz Z, Eryilmaz S, Kaya C, Arslan B, Gulbahar O, Poyraz A and Sonmez K: Protective effects of hydrogen rich saline solution on ventral penile mathieu type flap with penile tourniquet application in rats. J Pediatr Urol. 17:292.e1–292.e7. 2021.PubMed/NCBI View Article : Google Scholar

270 

Fruntelată R, Stoica GA, Ciobanu MO, Ciurea ME, Nica O and Stoica M: Retrospective study over the hypospadias surgery in a single tertiary center. Curr Health Sci J. 47:177–183. 2021.PubMed/NCBI View Article : Google Scholar

271 

Raheem AA, Banihani O, Abasher A, Alotay A, Alyami FA, Alsaad TA, Alqarni N, Alsowayan O, Jamalalali YA, Alhuwaiti M, et al: Pediatric urology surgical practice in the time of COVID-19: Results from tertiary Saudi Arabia hospitals. Urol Ann. 13:397–404. 2021.PubMed/NCBI View Article : Google Scholar

272 

Jurat R, Rahimi MT and Barolia R: Surgical outcomes and socio-demographic pattern of hypospadias patients treated in a tertiary care center in Kabul, Afghanistan. J Pediatr Urol. 17:674.e1–674.e7. 2021.PubMed/NCBI View Article : Google Scholar

273 

Irene M, Osawa F, Kuria K and Lessan J: Magnitude of post-urethroplasty urinary tract infections in children with hypospadias at a tertiary hospital in Kenya. J Pediatr Urol. 17:518.e1–518.e5. 2021.PubMed/NCBI View Article : Google Scholar

274 

Khan S, Tafweez R, Haider A and Yaqoob M: Spectrum of external genital anomalies in disorders of sex development at children hospital & institute of child health, Lahore, Pakistan. Pak J Med Sci. 37(244)2021.PubMed/NCBI View Article : Google Scholar

275 

Ashwin Shekar P, Ansari MS, Yadav P and Srivastava A: Presentation, treatment and outcomes of pediatric anterior urethral strictures: 28 Years' experience from a referral center. J Pediatr Urol. 17:398.e1–398.e9. 2021.PubMed/NCBI View Article : Google Scholar

276 

Wiener JS, Huck N, Blais AS, Rickard M, Lorenzo A, Di Carlo HNM, Mueller MG and Stein R: Challenges in pediatric urologic practice: A lifelong view. World J Urol. 39:981–991. 2021.PubMed/NCBI View Article : Google Scholar

277 

Ács N, Mátrai Á and Kaposi A: First data from the new, unified database of the Hungarian case-control surveillance of congenital abnormalities. J Matern Fetal Neonatal Med. 34:2887–2892. 2021.PubMed/NCBI View Article : Google Scholar

278 

Benavides E, Lupo PJ, Sosa M, Whitworth KW, Canfield MA, Langlois PH and Schraw JM: Urban-rural residence and birth defects prevalence in Texas: A phenome-wide association study. Pediatr Res. 91:1587–1594. 2022.PubMed/NCBI View Article : Google Scholar

279 

Arulanandam B, Dorais M, Li P and Poenaru D: The burden of waiting: Wait times for pediatric surgical procedures in Quebec and compliance with national benchmarks. Can J Surg. 64:E14–E22. 2021.PubMed/NCBI View Article : Google Scholar

280 

Karabay E, Karsiyakali N, Kayar K and Koseoglu H: Hypospadias surgery on YouTube: Is it valid? Minerva Pediatr (Torino). 73:236–242. 2021.PubMed/NCBI View Article : Google Scholar

281 

Jones P, Rajasegaran A, Brassale S, Chen Y, Haslam R, Austin C and Seideman CA: Assessment of the educational value of distal hypospadias repair videos on YouTube. Urology. 159:28–32. 2022.PubMed/NCBI View Article : Google Scholar

282 

Cheng JW, Fernandez N, Shnorhavorian M, Merguerian PA and Kieran K: Engagement of common pediatric urologic conditions on social media. J Pediatr Urol. 18:236.e1–236.e7. 2022.PubMed/NCBI View Article : Google Scholar

283 

Ghidini F and Castagnetti M: Pediatric urology research in 2020: A bibliometric analysis of the top 100 most cited articles. Urologia. 89:474–480. 2022.PubMed/NCBI View Article : Google Scholar

284 

Matta R and Schaeffer AJ: The top 100 cited articles in pediatric urology: A bibliometric analysis. J Pediatr Urol. 17:709.e1–709.e12. 2021.PubMed/NCBI View Article : Google Scholar

285 

Doğan G and İpek H: The evolution of hypospadias publications: A bibliometric approach. Rev Int Androl. 19:224–233. 2021.PubMed/NCBI View Article : Google Scholar

286 

Leitao Braga B, Lisboa Gomes N, Nishi MY, Freire BL, Batista RL, D Faria Junior JA, Funari MFA, Figueredo Benedetti AF, de Moraes Narcizo A, Cavalca Cardoso L, et al: Variants in 46,XY DSD-related genes in syndromic and non-syndromic small for gestational age children with hypospadias. Sex Dev. 16:27–33. 2022.PubMed/NCBI View Article : Google Scholar

287 

Niu HL, Yi P, Gao Q, Wang FH, Chen ZR, Li LP, Xia JQ, Cao Y and Zeng RX: Gonadal neoplastic related lesions in children with disorders of sexual development: A clinicopathological study of twelve cases. Zhonghua Bing Li Xue Za Zhi. 50:1145–1150. 2021.PubMed/NCBI View Article : Google Scholar : (In Chinese).

288 

Phillips L, Lundholm C, Örtqvist L, Almqvist C, Nordenskjöld A and Skarin Nordenvall A: Fertility in men with hypospadias: A nationwide register-based study using dizygotic twinning rates as an indicator of semen quality. Andrology. 9:810–816. 2021.PubMed/NCBI View Article : Google Scholar

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Spandidos Publications style
Gozar H, Bara Z, Dicu E and Derzsi Z: Current perspectives in hypospadias research: A scoping review of articles published in 2021 (Review). Exp Ther Med 25: 211, 2023
APA
Gozar, H., Bara, Z., Dicu, E., & Derzsi, Z. (2023). Current perspectives in hypospadias research: A scoping review of articles published in 2021 (Review). Experimental and Therapeutic Medicine, 25, 211. https://doi.org/10.3892/etm.2023.11910
MLA
Gozar, H., Bara, Z., Dicu, E., Derzsi, Z."Current perspectives in hypospadias research: A scoping review of articles published in 2021 (Review)". Experimental and Therapeutic Medicine 25.5 (2023): 211.
Chicago
Gozar, H., Bara, Z., Dicu, E., Derzsi, Z."Current perspectives in hypospadias research: A scoping review of articles published in 2021 (Review)". Experimental and Therapeutic Medicine 25, no. 5 (2023): 211. https://doi.org/10.3892/etm.2023.11910