Hypospadias English name: Hypospadias Department: Urology Common drugs: Symptoms: hermaphroditism, developmental malformations, external genitalia hermaphroditism, hypospadias, infection, masculinization, malformation, anus malformation, penile curvature, extra small penis, cryptorchid urethra ectopic opening on the ventral side of the urethra is called hypospadias. Hypospadias can occur anywhere between the perineum and the head of the penis. The distal end of the external urethral opening, the urethra and surrounding tissues are underdeveloped, forming fibrous cords that pull on the penis and bend it ventrally. Those with congenital hypospadias do not all have hypospadias, but all hypospadias have different degrees of penile hypospadias. 1. Etiology and pathogenesis Etiology Recent studies on the etiology of hypospadias include several aspects in a nutshell. Endocrine factors: androgen receptor and 5α-reductase defects in some cases. It has also been found that in human chorionic gonadotropin? (humanchorionicgonadotropin, HCG) stimulation, patients with hypospadias have a significantly lower androgenic response than normal control populations, suggesting that the hypothalamic-pituitary-gonadal axis is abnormal in patients with hypospadias. Environmental factors: Some studies have found a higher incidence of hypospadias in newborns who had progesterone for fetal preservation in early pregnancy, while some studies have shown increased levels of estradiol and estrone in patients with hypospadias. These studies suggest that estrogens have an antagonistic effect on androgens. Chromosomal abnormalities: There is a significantly higher rate of chromosomal aberrations in patients with hypospadias compared to the normal population, including autosomal and sex chromosomal aberrations. Mutations in the androgen receptor gene, sex-determining gene, 5α-reductase gene, anti-mullerian hormone gene, and CYP21B gene have been found to be present in patients with hypospadias. Pathogenesis During embryonic development, the development and fusion of the ventral urogenital groove of the penis is influenced by the pituitary gland and androgens. If androgen deficiency occurs, the fusion of the folds on both sides of the urogenital groove becomes impaired, resulting in a defect in the ventral wall of the urethra and the urethra opening behind the normal urethral orifice on the ventral side of the penis, forming hypospadias. According to the location of the urethral orifice, hypospadias can be divided into four types: penile head type, penile type, penile scrotum type, and perineum type. Among them, the penile head type and penile type are the majority. 2. Epidemiology According to statistics, one out of every 300 male babies born has hypospadias. In the United States, about 6,000 male babies with hypospadias are born each year, and 8% of the children have a father with hypospadias. The incidence is higher in Caucasians than in Blacks. In 1988, there were 6 cases among 3000 male infants in the infant unit of Beijing Maternity Hospital, and Huang Wanfen et al. investigated 6 cases of hypospadias and 3 cases of hypospadias among 2257 male infants in Qingdao (1981-1986) within 6 weeks of age. 3. Clinical manifestations Hypospadias can have the following manifestations: ectopic urethral orifice. The urethral orifice can appear anywhere from the proximal end of the normal urethra to the perineal urethra. Penile hypospadias means that the penis bends ventrally and cannot urinate and have sex normally. Causes of penile hypospadias include ventral hypoplasia of the penis and axial shortening of the tissue. Abnormal distribution of foreskin The ventral foreskin of the head of the penis has a V-shaped defect because it fails to fuse in the midline, the foreskin tether is absent, and all the foreskin is turned to the dorsal side of the head of the penis in a cap-like accumulation. The urine stream splashes during urination. Hypospadias can be divided into 4 types according to the anatomical location of the urethral orifice penile head type: the urethral orifice is located on the ventral side of the coronal groove, often in the form of a cleft, some can be complicated by urethral stricture, long dorsal foreskin, and no foreskin and tethering on the ventral side. The head of the penis is exposed, smaller and slightly flat and wide, in the shape of a ball. The penis is bent ventrally, but to a lesser extent, and does not affect sexual intercourse and urination. Penile type: the urethral orifice is located at the ventral side of any part of the junction from the coronal groove to the penile scrotum, the urethral plate at the distal end of the urethral orifice is separated and does not form a tube, the penis bends ventrally, the closer the urethral orifice is to the side the more serious the bending is, affecting intercourse and urination, and also affecting fertility. The shape of the head of the penis and the foreskin is the same as that of the hypospadias of the head of the penis. Penile scrotum type: The urethral orifice is located on the median line of the scrotum, and the scrotum is often split like the female labia majora. The distal end of the urethral orifice forms a fibrous cord. The penis is severely bent and requires squatting to urinate. The penis is short and flat, some resemble the female clitoris, and some testicles do not descend into the divided scrotum or form a penile scrotal transposition. Perineal type: The urethral orifice is located in the perineum, the scrotum is divided and underdeveloped, cryptorchidism may be combined, and the penis is small and curved, resembling the enlarged clitoris. The entire genital development resembles female vulva, so that many parents mistake it for female. It needs to squat to urinate. 4.Complications Cryptorchidism and inguinal hernia: The most common complication of hypospadias is cryptorchidism and inguinal hernia, the incidence of which is 7% to 13%, and the closer the urethral opening is to the scrotum, the higher the incidence. Urethral malformations: The incidence of posterior hypospadias is about 1% to 5%, and the incidence of combined malformations of other systems is high, with the incidence of combined malformations of one system 7%, two systems 13%, and three systems 37%. Prostatic bursa: Prostatic bursa is a manifestation of incomplete inhibition of the mullerian ducts or incomplete masculinization of the urogenital sinus during embryonic development, with an incidence of 10% to 15% in patients with posterior hypospadias. Prostatic bursa can cause urinary obstruction, intracapsular stone formation and infection. Hermaphroditism: In severe hypospadias with combined manifestations of ambiguous gender characteristics of external genitalia such as incomplete testicular descent, micropenis, penile scrotal transposition, scrotal splitting, etc., attention should be paid to hermaphroditism and chromosomal examination and related endocrine function tests should be performed. The rare concomitant anomalies are anal atresia, spinal bulge, etc. 5.Examination Hypospadias is an external genital malformation, which is easily diagnosed according to the typical clinical manifestations and physical examination. In severe cases of hypospadias, further urological examination, such as cystourethrography, should be performed to exclude other urological anomalies. When hypospadias is combined with bilateral cryptorchidism, attention should be paid to the presence of gender abnormalities. Physical examination: observe the patient’s body shape, physical development, secondary sexual characteristics, external genital examination with or without vagina, and touch the surface texture and volume of both testicles. Ultrasound of the abdomen. Chromosome examination. Urinary 17 ketosteroid determination. Laparoscopy and gonadal biopsy. 6.Diagnosis The diagnosis of penile head type and penile hypospadias is relatively easy and can be diagnosed by the appearance characteristics. 7.Differential diagnosis The penile scrotal and perineal hypospadias should be distinguished from female pseudohermaphroditism and true hermaphroditism, especially in combination with cryptorchidism. Regardless of the type of hypospadias, the sex chromatin should be negative, the sex chromosome should be XY, the urinary 17-ketosteroids should be normal, and the gonads should be testicular. Female pseudohermaphroditism: The cause is due to congenital defects in some enzymes of the adrenal cortex, resulting in abnormal synthesis and metabolism of hormones in the adrenal cortex, resulting in an increase in intermediate metabolites of androgenic nature and masculinization of the external genitalia of female fetuses. After birth, the vulva continues to develop in the male direction, with an enlarged clitoris that resembles a penis, an urethral orifice located at the root of the enlarged clitoris that strongly resembles hypospadias, and a small vagina. The main points of differentiation are as follows. Careful examination of the vulva: in addition to the urethral opening, there is also a vaginal opening; there are no testes inside the hypertrophied labia majora. Urinary 17-ketosteroid examination: elevated values. Sex chromatin examination: with oral mucosal epithelium or vaginal mucosal epithelium, skin or white blood cells, the positive rate of sex chromatin is checked by special staining. The rate of positivity should be higher than 10% in this disease for females. Sex chromosome examination: should be XX. adrenal gland imaging can be done if necessary to exclude adrenal cortical tumors. True hermaphroditism: In true hermaphroditism, the gonads have both testes and ovaries, or oviducts. Therefore, the external genitalia may show the appearance of both sexes, and may also have the typical appearance of hypospadias. The sex chromatin can be positive or negative; 2/3 of the sex chromosomes are XX and 1/3 are XY. If the sex chromatin is positive and the sex chromosomes are XX, hypospadias can be excluded. If the sex cannot be determined or the final diagnosis is true hermaphroditism, the gonadal biopsy is used as the basis. 8.Treatment The principle of treatment is the 1st important part of the treatment of hypospadias. The surgical method is determined according to the degree of penile recurvature and the presence or absence of hypospadias. This is the 2nd important part of the treatment of hypospadias. The failure rate of urethroplasty is high and is summarized in 2 categories. There are 4 common reasons for failure of hypospadias surgery as follows Incomplete correction of hypospadias: It is an important cause of surgical failure, mostly due to incomplete surgical removal of the urethral fibrous cords, inelastic skin not ever removed, failure to separate the external urethral opening, and the occurrence of hematoma and infection. In order to determine whether the penile recurvature has been completely corrected during surgery, the penis can be tied with a rubber band at the root, sterile saline is injected into the penile corpus cavernosum, and an artificial erection is made to observe whether the penis is still recurved. Do not remove the white membrane during surgery, otherwise the penis can be recurved, and this penile recurvature is difficult to correct. Formation of urethral fistula: It is another important cause of surgical failure, with some reports as high as 55%. Urethral fistula occurs in relation to the surgical method, with a high incidence of phase I surgery, which occurs due to newly formed urethra or urethral orifice with strictures, incomplete hemostasis leading to hematoma formation, excessive hemostatic ligature threads and incisional infection. For this reason, the flap forming the urethra should be wider the more distal it is to prevent urethral stricture, and hemostasis with an electrocoagulator can prevent foreign body retention. Hemostasis must be complete to prevent hematoma formation. Skin necrosis and fissures: Those with complete necrosis of the formed urethra are mostly seen in bladder mucosa transplantation and free skin tube transplantation. Urethral necrosis can also occur with foreskin for urethroplasty if there is poor blood flow. Other procedures are mostly seen with partial skin splitting. Common causes include infection, overly tight skin sutures, and ischemic necrosis of the edges. Postoperative dressings that are too tightly wrapped can also affect blood flow and allow skin necrosis. In the DenisBrowne procedure, insufficient length of the dorsal penile reduction incision is also a significant cause of wound dehiscence. External urethral stricture: Once detected, immediate plastic surgery should be performed to dilate the external opening. One-stage surgery: correction of penile deformity with urethroplasty is done at once, mostly for penile-type hypospadias. Most of the urethra is selected for circumcision. The advantages of the foreskin are thin, elastic, hairless, close, good blood flow, so that the urethra formed does not cause necrosis and has a high success rate. There are also those who choose to form the urethra with strips of mucous membrane of the bladder, the advantage is that it is in accordance with the physiology of the urethra, the disadvantage is that if it fails, the necrosis of the entire formed urethra cannot be compensated. Regardless of what tissue is used to form the urethra, the common advantage of stage I surgery is that it is completed in one operation, with less pain and a shorter treatment period. Staged surgery: Staged surgery is a phased correction of penile deformity with urethroplasty. There are many surgical methods, many of which evolved from the Thietsch, DenisBrowne and Cecil 3 surgical methods, which are still the basic methods of urethroplasty. Causes of surgical failure and prevention of penile recurvature without hypospadias: It is generally advocated that the urethra should not be cut off, the fibrous tissue around the urethra should be carefully removed, and the foreskin on the back of the head of the penis should be turned to the ventral side to cover the top of the urethra. If the penis cannot be straightened with this method, the urethra is cut off, the penis is straightened, and the urethra is defective in the middle and urethroplasty is performed. Hypospadias combined with hypospadias: Hypospadias combined with hypospadias of the penis, the extent of the defective tissue around the urethra is mostly grade I. Therefore, it is generally required to cut the penile fascia to the outside of the white membrane, do not hurt the white membrane, and completely remove the fibrous tissue around the cords outside the white membrane, while freeing the urethra and removing the fibrous tissue around the urethra that adheres to the penis, so that the urethra can be moved back, so that the penis can be straightened. Some scholars believe that the skin around the fibrous cords is often inelastic and its pull on the penis also affects penile straightening, emphasizing that these skins should be removed and the defective skin can be covered by transferring the foreskin to the ventral side. Urethroplasty When the gender is determined to be male, a comprehensive treatment plan should be developed based on the type of hypospadias, combined with the presence or absence of female genital tract and testicular development. This is done in stages, and continuity of the treatment plan should be maintained at each stage. If a pediatric patient has poor penile development, he may be treated with 1 to 2 courses of chorionic gonadotropin before surgery and then operated on after the penis has developed. The purpose of surgery is to correct the downward curvature of the penis so that the urethral opening is restored or close to the position of the normal penile head, enabling the pediatric patient to urinate standing up and have the ability to reproduce as an adult. For those who have urinary tract infection, the infection must be strictly controlled before surgery. Urethroplasty should be performed temporarily with a urinary diversion and, depending on the type of hypospadias, either suprapubic cystostomy or perineal urethrostomy should be chosen. Early treatment is favored. In fact, the size of penis development in 1-year-old children is similar to that of 5-6-year-old children, and the reaction of young children after surgery is light, so early surgery can relieve the mental stress of the family and the child. Correction of penile deformity 9. prognosis In conclusion, there are still many complications and a high failure rate for hypospadias surgery. Careful surgical techniques, thorough hemostasis, and prevention of infection can improve the success rate of the surgery. 10.Prevention For hypospadias, there is no clear method or medicine for prevention. Pregnant women should have scientific perinatal health care and regular prenatal checkups during the perinatal period to help the early detection of this disease. Choosing the right time and surgical method for the surgery will help the patient’s smooth recovery.