Hypospadias is a relatively common congenital anomaly in the pediatric urological system, which is autosomal dominant and has an incidence of about 3.2 per 1,000 (1/300), with geographic and racial differences. Hypospadias is formed when the urethral groove is not fully fused for any reason during the embryonic period and manifests as ectopic external urethral opening, hypospadias, and abnormal distribution of the foreskin. It is currently believed that environmental factors, endocrine factors and abnormal gene expression may be the main causes of hypospadias. It has been found that transcriptional activator factor 3 (ATF3) protein and mRNA are significantly upregulated in most patients with hypospadias [1, 2, 3, 4]. ATF3 can induce cells to enter the cell cycle from stationary phase, however, overexpression of ATF3 also induces proliferation inhibition and slows down the transition of cells from G1 to S phase. The gene encoding the ATF3 protein has estrogen susceptibility. Therefore, it is suggested that environmental estrogenic substances (EEs) may cause hypospadias through the ATF3 pathway.
Hypospadias is typed according to the location of the urethral orifice after penile straightening as follows: 1: anterior hypospadias (65%) glans type (the urethral orifice is located on the ventral side of the glans, proximal to the normal urethral orifice location) coronal sulcus type (the urethral orifice is located in the coronal sulcus, which is the location of the interglans groove of the penis) anterior penile type (the urethral orifice is located in the distal 1/3 of the penile shaft) 2: mid-penile hypospadias (15%) mid-penile type ( urethral orifice is located in the middle 1/3 of the penis) 3: posterior hypospadias (20%) posterior penile type (urethral orifice is located in the posterior 1/3 of the penile shaft), penile scrotal type (urethral orifice is located in front of the scrotum at the root of the penis) scrotal type (urethral orifice is located in the scrotum), and perineal type (urethral orifice is located behind the scrotum). 2011 Marek proposed that based on where the urethral corpus cavernosum really develops after penile straightening as location of the urethral orifice is more plausible and has more surgical guidance [5].
Hypospadias generally requires surgical treatment, and since Duplay reported the success of urethroplasty for hypospadias in 1880, more than three hundred surgical approaches have been reported to date. There are many different surgical procedures for hypospadias, each with its own advantages and disadvantages. In-depth study of a procedure, mastering the main points, improving surgical skills, and careful preoperative, intraoperative, and postoperative management are the keys to improving the success rate. The selection of surgery should take into account many factors, not only to restore the normal physiological function of the patient in the near future, but also to strive for the perfection of the morphology and the normal physiology in the long term. The literature on the treatment of hypospadias at home and abroad in recent years is summarized and reviewed as follows.
1.Surgery timing
In the 1980s, Schultz proposed that the ideal time for treatment is 6-18 months after birth, because this period is the psychological window of the child, and the surgical blow has the least impact on its psychology. Moreover, as age increases, the fascial layer becomes more fibrotic and more vascular due to the stimulation by testosterone, which can increase the difficulty of freeing. this idea was also repeated by Upadhyay et al [6] in 2002. However, a recent study by Nicol, Corbin, Bush et al. on 669 children (aged 3-144 months) with hypospadias who underwent Snodgrass found that age was not a factor that increased the complications of urethroplasty, and they concluded that surgery at any time after 3 months was feasible [7]. It is now believed nationally that the success rate of surgery is higher up to 3 years of age, which may be related to the strong healing ability, less erection and more frequent urination in infancy. In general, penile growth is minimal until the age of 4 years, and the degree of penile development should not be an important factor in the selection of the age for suburethral cleft surgery. Obviously, under the condition of good anesthesia and surgical experience, the age of surgery should be earlier [8].
2. One-stage surgery and staged surgery
At the earliest, surgery was performed in stages, and the commonly used ones were buried skin strip urethroplasty (Denis-Browne method), penile skin tube urethroplasty (Thiersch-Duplay method) and penile skin tube urethroplasty scrotal skin covering (Cecil method). Phase I of staged surgery first corrects the downward curvature of the penis, while those without downward curvature have the lesion incised with the distal urethra, transfer the ample skin or mucosa to the ventral side of the penis, and then perform urethroplasty six months later. Staged surgery increases the psychological and treatment cost burden on the patient. With the awareness of surgical treatment for hypospadias, there is a trend toward doing one-stage surgery. One-stage surgery has the advantages of high success rate, short hospital stay and reduced financial burden on patients, which is more acceptable to patients and their families. Alexander, Springer et al [9] made a more extensive survey and analysis and found that most patients still need to be operated again after the first-stage surgery, and a small number of patients become urethral invalids, and some children are not satisfied with the appearance and function after adulthood, so they think that staged surgery is an effective method to treat severe hypospadias. Duckett believes that with the application of penile and scrotal flaps, the most severe hypospadias can be urethroplasty in one stage and there is no need to return to staged surgery again.
3.Materials for urethral reconstruction
The materials used for urethral reconstruction are mainly: (1) the use of foreskin with vascular tip, penile and scrotal skin; (2) the use of grafts such as: free skin, testicular sheath, bladder mucosa, buccal mucosa, etc.; (3) tissue engineering to produce urethral substitutes.
4.One-stage urethroplasty and surgical selection
In the middle of 1950s and 1950s, one-stage urethroplasty for congenital hypospadias has developed greatly. Although there are various surgical procedures, there is no specific procedure that can be used for all types of hypospadias until now. The surgical experience of the operator, the local deformity of the patient, the urethral covering barrier and the quality of the sutures are important to guarantee the success of the procedure.
4.1,, urethral advancement and penile head plication (MAGPI procedure): this procedure is the classic procedure for correction of penile head type and coronal hypospadias, with positive results, but it is difficult to correct penile hypospadias. 1981 Duckett first reported this procedure, and only 1 case of urethral fistula occurred in more than 200 patients. It is to move the external urethral opening forward to the glans proper through the glans median incision and the covering of the two lateral glans flaps. It is simple to operate, reasonably designed, with good surgical results, perfect postoperative appearance, basically similar to normal, and few complications. If the skin on the ventral side of the ectopic urethral orifice is thicker and more elastic, it is easy to move forward, and there are more soft tissue sutures to fix it, which can avoid the retraction of the forward urethral orifice, but if the tension is high, the forward urethral orifice may retract to the proximal side or even return to the coronal sulcus. 2010 Ahmed, T reported that the modified MAGPI procedure (double Y penile headplasty) was used to treat 97 children with glans type hypospadias, and found that it easy operation, short hospital stay and good appearance [10].
4.2,, urethral base vascular flap urethroplasty (Mathieu procedure): In 1932, Mathieu reported that urethral base vascular flap urethroplasty was widely used for anterior hypospadias without hypospadias where the coronal groove and urethral orifice were located in the anterior 1/3 of the penile body, and the postoperative penile appearance and function were good. The method is: at the proximal end of the urethra, a flap is formed with the base of the urethra as the vascular tip, lifted and flipped toward the glans, and the urethra is reconstructed with the urethral plate at the distal end of the urethra or the urethral groove at the head of the glans in a loose-leaf suture, and then the new urethra is covered with glans tissue. The key to the procedure is that the flap must have an adequate blood supply.In 2010, Behtash, Ghazi, and Nezami reported the use of the Mathieu method combined with a dorsal penile meatus flap to cover the new urethra in 54 children with anterior segment hypospadias, which not only improved the success rate of the procedure but also improved the appearance of the glans [11].In 2012, Ehab, O. ElGanainy reported that the Mathieu method of preserving the foreskin not only shortened the operative time but also did not increase the incidence of postoperative complications, while preserving the foreskin could prepare for the management of future complications [12].
4.3,, Urethral lengthening: This method extends the urethra by freeing the anterior urethra and pushing it to the top of the glans, with the trauma covered by the glans and penile skin. Theoretically, the longer the urethra is freed, the greater the risk of blood flow disorders at its distal end. This method is suitable for coronal and corporal urethral hypospadias; the extension length is appropriate for the urethral corpus cavernosum without ischemia, and the extension length should not exceed 3 cm in children and 5 cm in adults. it was found that the blood flow of the anterior urethra is wrapped in the white membrane and connected with the blood flow of the posterior urethra, and the white membrane of the urethral corpus cavernosum is not damaged when the urethra is freed, which ensures the blood flow of the urethra, and no necrosis occurs after the urethra is moved forward, and it is convenient to take the material. The use of the original urethra makes the operation simple, and no urethral fistula or urethral stricture occurs after the operation. Several scholars have applied this method to treat hypospadias with success.
4.4, Transverse (Duckett) or longitudinal (Hodgson) foreskin island flap urethroplasty: This method is suitable for those whose urethra is located at the middle or proximal end of the penile shaft and whose dorsal foreskin is abundant. The method is to make a circumferential incision distal to the urethra and 1 cm proximal to the coronal sulcus, cut the urethral plate, decapitate the penile skin over the dorsal neurovascular bundle to the root of the penis, excise the fibrous cords around the ventral and urethral orifices of the penis, fully correct the downward curve, trim the end of the urethra to the developed part of the corpus cavernosum, make the external orifice beveled, cut the inner foreskin plate transversely or longitudinally, separate the vascular tissues supplying the blood flow of the flap, and form The flap with the tip is separated and sewn around the stent to form a new tubular urethra, and a hole is separated at the root of the tip, through which the penis passes or the tube with the tip is passed around the side of the penis and transferred to the ventral urethra, with one end anastomosing obliquely with the original urethral orifice and the other end anastomosing with the head of the penis from the tunnel under the head of the penis to form an orthodontic urethral orifice, and the dorsal flap is transferred to the ventral side to repair the wound. In the case of perineal hypospadias, a “U” shaped incision can be made around the urethral orifice, and a section of scrotal skin can be freed to make an anastomosis with a tipped foreskin duct, i.e. Duckett or Hodgson plus Duplay urethroplasty. The incidence of urethral fistula in this procedure is about 15-30%,.
4.5,, Covered island flap method (OIF): based on Duckett transverse foreskin island flap urethroplasty. For cases with well-developed urethral plate, urethral orifice located in the middle and posterior 1/3 of the penile body or at the root of the penis, without penile curvature or with mild penile curvature, and with better glans development, this method is available. In 2011, Waifro, Rigamonti, and [13] reported that this procedure was used to treat 14 children with severe hypospadias, with penile recurvature Over 30 degrees, the urethral plate was separated in the middle, and the two ends were anastomosed to the urethral plate when an island flap was added, which was sutured around the stent tube in the middle to the penile tunica albuginea. Waifro and Rigamonti concluded that this procedure is also more effective for proximal hypospadias.
4.6, scrotal longitudinal flap urethroplasty: The earliest reported in China by Ying Li, which preserves the vascular plexus of the scrotal longitudinal septum and forms an axial flap with a vascular tip in the central part of the scrotum, which is sutured into a tube to repair the urethra and complete the repair of hypospadias in one phase. The success rate is high due to the preservation of good blood supply to the skin tube, and the scrotal skin and endothelium are stretchable, so that the skin tube is made to be attached to the white membrane of the penis backwards without tension, which does not affect blood flow and ensures the patency of the new urethra and normal erection of the penis. The suture surface of the skin tube is attached to the corpus cavernosum, and the incidence of postoperative urinary fistula is low. The disadvantage is that the scrotal skin is hairy, and the single-tipped scrotal flap is caused by the penile skin when the urethra is buried by the penis skin is too tense to make the edema formed by poor blood return, which hinders the healing of the incision and increases the chance of infection and complications.
4.7,, urethral plate longitudinal coil urethroplasty (TIP): also known as the Snodgrass method, was first reported in 1994. It is currently the treatment of choice for distal and mid-type hypospadias. By cutting the flat urethral plate dorsally and medially longitudinally, it allows for freeing and extension to the sides and ventral side, and allows tension-free wrapping around the catheter to form a urethra. Compared to the Mathieu and Onlay urethroplasty method, this procedure not only takes less time, but also creates a more aesthetically pleasing penile head and urethral opening. For those who fail after hypospadias urethroplasty and have very little skin left, urethral plate longitudinal coil urethroplasty is particularly suitable [14]. snodgrass, the midline incision of the urethral plate in the procedure is dependent on the migration of epithelial cells on both sides of the cut edge to cover the wound during healing, thus avoiding the stenosis caused by scar formation after suturing. In addition, the new urethra has an intact and continuous epithelial tissue structure in the dorsal half and the ventral half of the incisional margin is closed longitudinally without creating a circular scar stenosis during healing, so the chance of urethral stricture is low with this procedure. 2010 Snodgrass reported that only 19 of 551 children with distal hypospadias who underwent Snodgrass had complications, including urethral fistula, glans dehiscence, and Urethral stricture [15]. The Snodgrass procedure has now been extended to the proximal penile body and penoscrotal junction type hypospadias with good results [16]. The choice of surgical approach for the treatment of hypospadias with urethrotomy tubularization is not based on the location of the external urethral opening, but on the degree of penile hypospadias and the availability of the urethral plate for use as a urethra.TIP can treat most cases of hypospadias. And a number of authors have modified the Snodgrass method. Antonio, Savanelli, [17] reported 65 cases of distal hypospadias using the Snodgrass technique and covering the new urethra with a ventral sarcoid flap, with only 3.8% postoperative complications. sarhan [18] et al. in 500 children repaired by TIP applied sarcoid In 2010, Murat, [19] reported 6 cases (26%) of urethral fistula in 23 children with unilateral sarcoid flap coverage and 1 case (0.7%) of urethral fistula in 131 children with double pterygoid sarcoid flap cross-coverage. Salim [20] reported 6 cases (8%) of urethral fistula in 75 children with double pterygoid flaps, while 85 cases had no urethral fistula with double pterygoid flaps crossed over the new urethra using urethral cavernous suture.
4.8, bladder mucosa substitution urethroplasty: Since Memmal, -, laar founded bladder mucosa transplantation for hypospadias in 1947, the value of this procedure in clinical practice has been controversial. The focus is that the free bladder mucosa itself has no blood supply and is prone to contracture and postoperative urethral stricture. in 1975, Memmal first reported the free bladder mucosa sheet in lieu of urethra in China. After years of efforts, the surgical methods and techniques of bladder mucosa transplantation have been significantly improved, mainly in the following aspects: (1) submerged free excision of the mucosa in a semi-filled bladder state with unbroken mucosa; (2) use of splitting of the penile head or tunneling to establish a new external urethral opening; (3) alignment of the anastomotic margin of the mucosal tube with the intercavernous groove of the penile corpus cavernosum. Usually, for cases where a tipped flap cannot be applied or where local retrieval is difficult after multiple surgeries, mucosal urethroplasty of the bladder is considered.
4.9 Repair of hypospadias using tissue engineering materials: Tissue engineering is performed by obtaining normal tissue cells or replacement cells, regulating the growth and proliferation of the cells in vitro, and using synthetic scaffolds or biological scaffolds as carriers to implant the cells in vivo so that they continue to grow and eventually mold into the desired normal tissues and structures. Experimental studies using tissue engineering materials have developed considerably in the last five years, but clinical studies are still rare. Bhargava [21] et al. reported the successful construction of tissue-engineered oral mucosa (, TEBM,) by separating oral keratinized cells from the epithelium and fibroblasts from the dermis and then expanding them in vitro, and compounding them with dermal tissue that had been decellularized and sterilized, and in In 2008, we applied it to 5 cases of urethral reconstruction.
5.Postoperative management
Postoperative management of hypospadias is extremely important to ensure the success of the surgery, but not much has been reported in the literature. The main issues are management of postoperative pain, management of drains, postoperative penile erection and management of trauma. For postoperative pain and penile erection, an analgesic pump is advocated to be left in place for the first 3 d postoperatively for pain relief and prevention of penile erection. As for the management of the trauma, there is no definite opinion on whether to keep the trauma dry or to provide a wet healing environment for the trauma. Some scholars reported that early removal of the bandage, exposure of the trauma, and infrared physical therapy resulted in rapid absorption of foreskin edema, dry trauma, and normal color of the formed urethral skin flap. And some scholars believe that providing a wet healing environment for the wound surface can promote wound healing and reduce the pain of dressing changes.
6.Surgical complications and treatment
The main postoperative complications of hypospadias include urinary fistula, stricture, urethral diverticulum, flap necrosis, infection, etc. The main causes of serious postoperative complications are wrong design of surgical method, improper intraoperative operation, tissue ischemia and necrosis, tension in suture, local infection, and poor postoperative urinary drainage. Among them, urethral fistula and urethral stricture are among the most common complications after hypospadias repair. The prevention of serious postoperative complications of hypospadias lies in: ① Design a reasonable surgical method according to the degree of hypospadias deformity and penile development, and try to use tissues with good blood supply for the urethra. We should not force the operation to be completed in one phase for perineal hypospadias, but sometimes a more satisfactory result can be obtained by staging the operation; ② Strictly follow the principles of plastic surgery, with light movements, careful dissection, tissue care, careful hemostasis, full correction of penile hypospadias, ensuring good blood supply to the formed urethra and ventral skin of the penis, and accurate tissue alignment; ③ Strengthen postoperative care, ensure smooth drainage, remove the new urethra at any time If the urinary line becomes thin or even dripping, urethral dilatation should be performed by the surgeon in time. If the child does not cooperate, it should be performed carefully under intravenous anesthesia to avoid causing urethral injury and aggravating the difficulty of urination. If the dilatation is not smooth and there is blood flow from the external urethra, a suprapubic cystostomy should be made if necessary to temporarily divert the urine. It has been proven that minor surgery on severely diseased tissues, whether to repair the fistula or to release the urethral stricture, is hardly effective and can cause new injuries. Therefore, if serious complications occur after the treatment of hypospadias, the entire diseased urethra and its surrounding scar tissue should be completely excised and the hypospadias should be fully corrected at the same time or the urethroplasty should be performed at the second stage. Using the radical surgical method, the urethra was reconstructed after complete removal of the diseased tissue and full straightening of the penis to obtain more satisfactory results. As for the ventral scar tissue of the penis will all be removed, penile hypospadias correction is the same time or second stage urethroplasty depends on the specific circumstances, if the surrounding tissue is no obvious inflammatory lesions, skin elasticity is good, can be made at the same time bladder mucosa for urethra or transfer scrotal septum flap and its nearby tipped flap reconstruction urethra, otherwise rather in penile hypospadias correction after the first urethral posterior stoma, the first solution to urination difficulties and penile curvature Hayrettin and Ozturk used a penile meatus flap to cover the new urethra or urethral fistula repair, which significantly improved the success rate of the operation [22].
7 Outlook
Throughout the history of the treatment of hypospadias, with the advent of the Snodgrass method, there has been a relatively large change in the surgical treatment of hypospadias, and urethroplasty with preservation of the urethral plate may become the main procedure for repairing hypospadias. In the future, tissue-engineered urethra will be a major research direction in urethral repair and reconstructive surgery. And with the development and combination of medicine, engineering and material science, it will definitely promote the productization of tissue-engineered urethra and make it a clinically available repair material, and there will be an essential change in the surgical treatment of hypospadias. In addition, the development of genetic technology will also make it possible to diagnose and treat hypospadias at the genetic level.