Comparison of Single-Incision Scrotal Orchiopexy and Traditional Two-Incision Inguinal Orchiopexy for Primary Palpable Undescended Testis in Children: A Systematic Review and Meta-Analysis

Purpose To compare the safety, efficacy, and cosmetic results of single-incision scrotal orchiopexy (SISO) and traditional two-incision inguinal orchiopexy (TTIO) for primary palpable undescended testes (PUDTs) in children. Materials and Methods A systematic literature search of all relevant studies published on PubMed, Embase, Medline, Cochrane Library, Web of Science database, and Wanfang data until July 2021 was conducted. The operative time, hospitalization duration, conversion rate, wound infection or dehiscence, scrotal hematoma or swelling, testicular atrophy, reascent, hernia or hydrocele, analgesics needs, and cosmetic results were compared between SISO and TTIO using the Mantel–Haenszel or inverse-variance method. Results A total of 17 studies involving 2,627 children (1,362 SISOs and 1,265 TTIOs) were included in the final analysis. The conversion rate of SISO was 3.6%. The SISO approach had a statistically significant shorter operative time than the TTIO approach for PUDT (weighted mean difference−11.96, 95% confidence interval −14.33 to −9.59, I2 = 79%, P < 0.00001) and a shorter hospital stay (weighted mean difference−1.05, 95% confidence interval −2.07 to −0.03, P = 0.04). SISO needed fewer analgesics and had better cosmetic results than TTIO. SISO had a similar total, short-term, or long-term complication rate with TTIO. Conclusion Compared with TTIO, SISO has the advantages of shorter operative time, shorter hospitalization duration, less postoperative pain, and better cosmetic appealing results. SISO is a safe, effective, promising, and potential minimal invasive surgical approach for PUDT. SISO is an alternative to TTIO in selected cryptorchid patients, especially for lower positioned ones. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42021268562.


INTRODUCTION
Cryptorchidism, or undescended testes (UDTs), is one of the most common congenital abnormalities in male neonates, with a prevalence of 1.0-4.6% in full-term boys and a higher incidence in preterm boys (1). Cryptorchidism is a wellknown independent risk fact for infertility, testicular cancer, testicular torsion, and other disease (2). It is vital to correct the UDT at an early age to avoid subsequent testicular degeneration. Fortunately, ∼80% of the UDT are palpable and located in the inguinal canal, external inguinal ring, or even upper scrotal (3), making the traditional two-incision inguinal orchiopexy (TTIO) the best surgical approach to correct cryptorchidism (4).
The TTIO has two incisions: one inguinal incision to open the external oblique fascia and inguinal canal to visualize the cord structure and dissect the processus vaginalis; another second scrotal incision to fix the descended testis within the scrotum (5,6). It was believed that the TTIO was convenient and helpful for sufficient mobilization of the spermatic cord, separation and high ligation of the processus vaginalis or hernia sac to avoid subsequent hernia or hydrocele, and most importantly, to achieve adequate vessel length for cryptorchid testis to be placed in the scrotum without tension (7,8).
In 1989, Bianchi and Squire proposed the single-incision scrotal orchiopexy (SISO) for palpable undescended testes (PUDTs) to reduce the potential morbidity and reach a goal for better cosmetic appearance (9). From then on, more and more authors pointed out that SISO had the advantages of shorter operative time and less pain; in the meanwhile, it also had considerable complication rates compared with TTIO (10)(11)(12)(13)(14)(15). This trans-scrotal surgical technique could also be applied to secondary cryptorchidism, hydrocele, and even indirect hernias (16).
In 2016, Feng et al. conducted the first systematic review and meta-analysis to compare the SISO with TTIO strategy regarding operative time and complications (17). Although the evidence was still largely limited by the small sample size in their study, these several newly published randomized controlled studies would provide more evidence. Therefore, we updated this study and compared the operative time, hospitalization duration, patent processus vaginalis, short-term and long-term complications, analgesic needs, scarring, and Abbreviations: CI, confidence interval; OR, odds ratio; PUDTs, palpable undescended testes; SISO, single-incision scrotal orchiopexy; TTIO, traditional two-incision inguinal orchiopexy.
conversions between SISO and TTIO for primary PUDT to provide strengthened evidence and to serve clinical decision and guideline making.

Search Strategy
This systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. The initial systematic literature retrieve was conducted on July 11, 2021, without the restriction of language and region. The searched databases were the following: PubMed, Medline, Embase, Cochrane Library, Web of Science Database, China National Knowledge Infrastructure, and WanFang Data. Using the Boolean approach, these databases were individually searched for the following key terms, mainly in titles, keywords, and abstracts: (cryptorchidism OR undescended test * OR non-descended test * OR non descended test * ) AND (orchidopexy OR scrotal OR inguinal OR single incision OR trans-scrotal approach). Both the Mesh Term search and keyword search were combined. In addition, the reference lists were manually retrieved to broaden the search.

Study Selection and Data Extraction
The inclusion criteria for our systematic review and metaanalysis were (1) clinical trials comparing the SISO and TTIO surgical strategy regardless of prospective or retrospective designed studies and (2) children who were diagnosed with primary PUDTs and (3) have a follow-up time of more than 3 months and adequate initial data available. Exclusion criteria were (1) no TTIO as a control group, (2) secondary cryptorchidism or has a history of former orchiopexy or inguinal operation, and (3) studies that did not provide sufficient data or repeated or duplicate publications. Only the latest study was included if there were more than one report paper from one clinical center or duplicate publications detected.
All included initial trials were thoroughly understood and analyzed; the baseline characteristics summarized were authors, publication years, countries, study periods and designs, age of participants, single-incision scrotal techniques (high transverse stria scrotal orchiopexy or low trans-scrotal mid raphe orchiopexy), laterality, and location of testes. Operative time, hospitalization duration, patent processus vaginalis, shortterm complications (wound infection or dehiscence, scrotal hematoma or severe swelling), and long-term complications (testicular atrophy, testicular reascent, hernia, or hydrocele) were extracted to compare these two surgical approaches for PUDT. We also made possible comparisons between each single-incision technique and conventional two-incision orchiopexy. Moreover, conversion rates, postoperative analgesics needs, and cosmetic results were also concerned. Cometic results were only evaluated upon exerted operation scars. Two reviewers (CJY and YH) independently conducted the literature search, screening, and data extraction. All discrepancies were resolved by discussion or, still unresolved, by a mediating reviewer (SDW).

Quality Assessment
There was no best suitable tool to assess the quality of included studies in this study. For compromising reasons, the methodological quality of retrospective case-control studies was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS), and the prospective randomized controlled trials were assessed using the Jadad Scale. This NOS used a star system (measured 0-9) to assess the quality of a study in three domains: the selection of the study groups, the comparability of the groups, and the ascertainment of exposure of interest for case-control studies. Also, the Jadad Scale evaluated the quality of a randomized study by randomization, blinding, and withdrawals, which marked 0-5; 1-2 indicated low quality and 3-5 high quality.

Statistical Analysis
All statistical data analyses were completed by Review Manager version 5.3 (Cochrane Collaboration, Oxford, United Kingdom). The odds ratios (ORs) and 95% confidence intervals (CI) were calculated for dichotomous variables using the Mantel-Haenszel method. In addition, for continuous variables, mean difference (MD) and 95% CI were applied using the inverse-variance method. The pooled heterogeneity of included studies was tested using both the chi-square test (p ≥ 0.1, indicating low heterogeneity) and I 2 index statistics (0%, indicating no interstudy heterogeneity) (18). The fixed-effect model was applied if I 2 < 50%; otherwise, the random effect model was used (19). Sensitivity analysis was conducted by removing a study per circle to detect the heterogeneity contribution of each study. Funnel plots visually detected publication basis. A P < 0.05 was considered statistically significant in this study.

Quality Assessment
The quantitative star NOS scores for retrospective case-control studies ranged from 4 to 6, indicating low to moderate quality (Supplementary Table 1). The Jadad score scale for seven randomized controlled studies ranged from 2 to 5, whereas only two of seven was assessed as high quality (with a score of 3 or 5). Among these seven studies, withdrawals were well-adopted, and the randomization and double-blind method were still a FIGURE 2 | Forest plot of (A) operative time, (B) hospitalization duration, and (C) patent processus vaginalis between single-incision scrotal orchiopexy and traditional two-incision inguinal orchiopexy for primary palpable undescended testes. big challenge. For some way, the double-blind method would be greatly restricted by the informed consent of participants and surgical strategy-designed trials.
There was no evidence for high heterogeneity for complications was observed, be it short-term, long-term, or total, so the fixed effect model was applied.

Postoperative Pain Evaluation, Cosmetic Results, and Conversions
All papers reported the conversion status of SISO to TTIO. Added in total, 49 cases (3.6%) needed an extra inguinal incision to assist dissection of the spermatic cord or high ligation of processus vaginalis, and the majority of these testes were intracanalicular. What is more, nine studies (52.9%) did not report the need for any conversion in their surgical practice ( Table 2).
Three studies evaluated postoperative pain, whereas only one study quantitatively calculated analgesics intake and pain scale assessment (15). It could be concluded that both SISO and TTIO did not need many analgesics after an operation, and relatively speaking, SISO consumed less. There were five studies that evaluated scar and cosmetic appealing satisfactory of patients. All these studies had the same conclusion that SISO provided more cosmetically appealing results than TTIO ( Table 3).

DISCUSSION
Our updated systematic review and meta-analysis combined the most evidence comparing SISO and TTIO for primary PUDT. We analyzed the differences in aspects of operative time, hospitalization duration, conversion rates, wound infection or dehiscence, scrotal hematoma or severe scrotal, testicular atrophy, reascent, hernia or hydrocele, postoperative analgesics needs, and cosmetic results between these two surgical approaches for PUDT. According to our meta-analysis, SISO had the advantages of shorter operative time and hospital stay, fewer analgesics needs, and better cosmetic appealing results, most importantly, in the meanwhile, did not increase the short-term and long-term complications rates. The total conversion rate of SISO was 3.6%, and the majority of which were intracanalicular. Taking all these evidence and practice into consideration, we recommend that SISO should be the first choice for primary PUDT, especially low palpable cryptorchidism.
Currently, SISO mainly contains a single high transverse stria scrotal incision and low trans-scrotal mid raphe orchiopexy (11,30). There was also low transverse stria scrotal incision orchiopexy introduced (14). Both high transverse stria scrotal incision and low trans-scrotal mid raphe had shorter operation time than TTIO, and mid raphe incision showed shorter time than stria scrotal incision (P < 0.00001, Supplementary Figure 1). Transverse stria scrotal incision showed more total complications than TTIO (P = 0.03, Supplementary Figure 2); however, differences between mid raphe orchiopexy and TTIO did not reach significance. Intuitively, both surgical technologies have less incision to close, and the incisions are invisible, and this makes SISO have shorter operative time and better cosmetic results than TTIO, although this only concerns the exerted operation scars. In addition, SISO does not open the external oblique fascia and has less dissection and anatomical disruption of the inguinal region, which would undoubtedly account for less postoperative pain and shorter hospitalization duration (10).
The main worrisome trouble of SISO for undescended testes is the difficulty for dissection of the spermatic cord and high ligation of processus vaginalis or hernia sac. This is also why TTIO lasts so long while still classic in the history of orchiopexy for cryptorchidism and could be served as the rescue method for SISO. In contrast, in a recent study, Hyuga et al. concluded that ligation of the processus vaginalis is unnecessary when it is not widely patent (31). In our opinion, this conclusion still needs to be interpreted with great caution, and studies on this topic still have a long way to go.
SISO for treatment of primary, secondary, or even trapped testes can be well-tolerated (4). Furthermore, it was reported that a single-incision scrotal surgical procedure had been successfully applied to treat communicating hydroceles and indirect hernia, or even impalpable cryptorchidism (10,32). This procedure has its own advantages superiority, and we do believe it would serve the urologists better in more aspects in the future. However, urologists and every surgeon must take their own learning experiences and familiarity with surgical strategy into the deep heart.
There are several surgical techniques to correct cryptorchidism. Cuda et al. reported their clinical experience that the rate of laparoscopic and scrotal orchiopexy increased, whereas the inguinal orchiopexy decreased (25). The laparoscopic technique gradually tends to have fewer incisions and even a single port, and the single practice trend is becoming more and more warrant in minimal invasive surgery (33). SISO meets the concept of being minimally invasive and the demands of patients; it is a safe, effective, promising, and potential surgical approach alternative to TTIO.
Our study still has some limitations that must be taken into consideration. Most importantly, high heterogeneity between studies should not be ignored. Secondly, the small sample size, low quality of the initial study, and different study designs would make the analysis somehow weaker. Third, it was impossible to match all participated children groups with age, body mass index, the accurate location of the testis, and anatomic variations. Fourth, publication bias was still a big limitation, although the funnel plot was evaluated to be acceptable. In addition, selection bias for choosing the techniques cannot really be addressed in these studies, i.e., inguinal orchiopexy for higher located testicles and single incision for the lower ones. For example, 52.9% (9/17) studies reported there was no need for conversion, whereas a randomized controlled study reported that the conversion rate of SISO was as high as 23.8% (15). Alyami et al. also pointed out that only 52.8% of surgeons used SISO for undescended testes, and there was a discrepancy in the reported advantages and success rate according to their investigation (34). Last but not least, testicle positions were not well-evaluated, and only in the low-inguinal undescended testis can the cremaster dissection be adequate for excellent results. On the contrary, the correction of the high-inguinal undescended testis may need high ligation of the processus vaginalis or hernia sac and more extended dissection of the spermatic cord until the level of the internal inguinal ring, and it can provoke more tissue damage compared with the opening of the external oblique fascia. Furthermore, we cannot randomly ignore the high incidence of ipsilateral and contralateral patent processus vaginalis or hernia, especially in lower positioned cryptorchid patients (35). Added in total, SISO should only be applied in highly selected cases. More welldesigned, high-quality, large-scale, multicenter prospective trials are still needed to explain this.

CONCLUSION
SISO is a safe, effective, promising, and potential minimal invasive surgical approach for PUDT. Compared with TTIO, SISO has the advantages of shorter operative time, shorter hospitalization duration, less postoperative pain, better cosmetic appealing results, and not increasing shortterm and long-term complications. SISO is an alternative to TTIO in selected cryptorchid patients, especially lower positioned ones.

DATA AVAILABILITY STATEMENT
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.

AUTHOR CONTRIBUTIONS
CY and SW conceived and designed the meta-analysis. CY and LK independently searched the electronic databases and independently extracted the data. CY led analysis and interpretation of data, drafted the manuscript, and revised content based on feedback. LK acted as the second reviewer. YH and LW assisted with the retrieval of database and acquisition of data. JZ and JL assisted with the interpretation of data and provided critical revision of drafts. TL, DH, and GW assisted with conception and design and provided critical revision of drafts. SW acted the role of the corresponding author, provided funding support, provided critical revision of drafts, and acted as the third (mediating) reviewer. All authors contributed to the article and approved the submitted version.