Results of examination of patients
All 40 patients in HBOT group finished the entire HBOT as planned with no severe side effect; and each patient in either group was followed up for at least 12 months postoperatively (19.8 ± 15.2 and 19.2 ± 14.3 months, respectively, P =0.830). The features of the participants in the two groups are listed in Table 1, such as the mean age at the time of TIPU (22.1 years vs. 21.9 years), the percentage of patients with proximal penile hypospadias (65% vs. 72.5%) and patients who underwent dorsal plication (77.5% vs. 72.5%); no significant differences were found between these two groups (P =0.723, 0.469 and 0.606, respectively). In the last article we wrote about the effectiveness of Cialis, but there were a number of questions about where to get Cialis online: a) online pharmacy b) ebay
Based on the opinion of each patient himself and another urologist, the satisfaction of cosmetic result was achieved in both groups. Overall UPC, as recommended by Snodgrass et al. , developed in 7 patients (17.5%) in HBOT group and 15 patients (37.5%) in Control group, with statistically significant difference across the two groups (P =0.045) (Table 2). There was one patient in HBOT group with meatal stenosis and UCF simultaneously. The most common UPC after TIPU was UCF in both groups, which occurred in 4 patients (10%) in HBOT group and 12 patients (30%) in the Control group respectively; the incidence rate was significantly lower in HBOT group (P =0.025). Meanwhile, there were no patients with urethral diverticulum or obviously recurrent curvature (>30°) in either group. As shown in Table 2, no significant differences were noted between the two groups in the incidence rates of glans dehiscence (2.5% vs. 2.5%), meatal stenosis (5.0% vs. 2.5%) and urethral stricture (2.5% vs. 2.5%) (all P values >0.05).
TIPU, which was introduced and promoted by Snodgrass et al. [1, 7], has now been accepted worldwide by urologists to correct both distal and proximal hypospadias in children and adults. Compared with other surgical techniques of urethroplasty, TIPU can provide relatively simple procedures and satisfactory cosmetic outcomes of slit-like meatus at the top of glans. Unfortunately, TIPU and other surgical techniques cannot repair both distal and proximal hypospadias without UPC [2-4, 7-13]. Furthermore, repair of proximal hypospadias in both children and adults is still a great challenge for urologists, even though great improvements, such as surgical techniques, suture materials and postoperative care, have been achieved during the past several decades. The research of Snodgrass et al.  revealed that hypospadias patients with mid-shaft meatus and proximal meatus who underwent surgical reconstruction increase UPC rate significantly when compared to those with distal meatus. The recent reports showed that overall complication rate after TIPU ranged from 4% in cases of distal hypospadias to 60% in the proximal cases [11, 12]. The incidence rates of UPC in both groups in our study were 17.5% (HBOT group) and 37.5% (Control group), which were consistent with those reported results.
As one of the most common UPC following hypospadias reconstruction, UCF needed surgical repair except for a few small ones which could heal spontaneously; its reported incidence rates ranged from 2% to 42% [11-13]. The risk factors of UPC are still controversial and inconclusive: firstly, the local vascular supply and infection is considered as one factor associated with UPC [14, 15]. Ratan et al.  pointed out that postoperative local infection had a significant association with the occurrence of UCF after hypospadias repair. Secondly, age may be another important risk factor [3, 16]. Yildiz et al.  found that the incidence rate of UCF was significantly higher in those patients aged 10 years and over.
According to the recommendation of the American Academy of Pediatrics, the primary hypospadias repair should be performed at age 6 to 12 months; age is considered to be a crucial factor influencing the final surgical outcomes . However, some patients themselves and their parents initially, especially in developing countries, ignored this condition not only because of the painless and non-lethality disease but also their illiteracy and embarrassment of seeking medical advice . Bhat et al. [3, 10] further indicated that adults with hypospadias always sought remedy for this malformation when they planned to get married. In our present study, the ages of patients undergoing their primary TIPU in both groups (22.1 ± 2.0 years and 21.9 ± 2.1 years) were consistent with those conclusions.
Although Snodgrass et al.  pointed out that there was no difference between adults and children in the incidence rate of UPC, adult hypospadias repair was traditionally and still related with higher postoperative complication rates [3, 4, 9]. Bhat et al.  prospectively compared the postoperative complication rates between adult and pediatric patients and found that the UPC rates following TIPU were significantly higher in adults (16.7%) than in children (6.7%). They further hypothesized several potential explanations such as increased susceptibility to infection, relatively reduced vascularity leading to poor wound healing and more frequent erections .
In our present study, we found that HBOT following proximal hypospadias TIPU in adult patients might be a good therapeutic strategy for reducing UPC rate, especially UCF. HBOT, providing pure oxygen at a pressure greater than atmospheric pressure at environmental temperature, can enhance the cellular oxygen supply by improving oxygen tension in arterial blood and increasing capillary-tissuecellular diffusion gradient. Although some potential risks of HBOT were reported, such as middle ear barotrauma, reversible myopia, etc. ; currently, HBOT is still recommended as one of the safest medical treatment for numerous conditions including some urological and andrological diseases [18, 19]. To our knowledge, this is the first study on applying HBOT in postoperative recovery after adult hypospadias repair. HBOT in our study was safe, and no serious side effects were noted. Moreover, significantly lower incidence rates of overall UPC and UCF were observed in HBOT group compared to Control group (P =0.045 and 0.025, respectively). We speculate two possible mechanisms to explain our results which are as follows.
Firstly, HBOT may promote the postoperative angiogenesis of neourethra and its reinforcing coverage. In order to cover the long neourethra in adult proximal hypospadias, the dartos pedicle flap should be dissected from dorsal shaft skin and preputial hood to the root of penis; and such thorough dissection and transposing to ventrum of the penis might affect vascularity of the dorsal dartos layer . Radojicic et al.  also found that vascularization of the prepuce was crucial for hypospadias repair and prepuces with unfavorable vascularity used for urethroplasty had a higher percentage of UPC. El-Sherbiny et al.  further pointed out that the low incidence of fistula after TIPU depended on the neourethral reinforcement of vascularized tissues. There were many studies that have confirmed HBOT could enhance new vessel maturation and stimulate angiogenesis [19, 23].
Secondly, HBOT helps prevent local infection and reduce inflammatory reaction after TIPU. The study of Inanmaz et al.  documented that HBOT could be a safe and effective treatment strategy to reduce postoperative infection in complex spine deformity in high risk neuromuscular patients. Furthermore, Menon et al.  found that lymphocytic infiltrates and inflammatory reaction after urethroplasty may lead to higher healing complication rates. In animal model studies, it was reported that HBOT could reduce the release of inflammatory mediators, such as the interleukin and tumor necrosis factor, to ameliorate post-inflammatory injuries .
Nevertheless, there are still several limitations to this study. Firstly, our results may be potentially limited by the relatively short duration of follow-up because of the high rate of patient non compliance after 12 months postoperatively. Secondly, the insufficient cases might influence the final results. So, further research, with larger cohorts, longer follow-up period, is required.
Our preliminary results indicate that HBOT could effectively and safely decrease the incidence rate of UPC, especially UCF, after proximal hypospadias TIPU in adults.
Compliance with ethical standards:
Funding was provided by the Natural Science Foundation of Hunan Province 2018JJ3808 (to Dr. Yuan).
Conflict of interest:
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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