隐睾症的主要治疗方法是通过手术将睾丸放入阴囊。 对于手术疗法的最佳时机尚存争议,但是数据显示早期实施手术可更好地保留精子发生和激素分泌的功能,并降低睾丸癌症的风险,理想时机是 12 至 18 月龄之前。[1]Ritzén EM, Bergh A, Bjerknes R, et al. Nordic consensus on treatment of undescended testes. Acta Paediatr. 2007 May;96(5):638-43.https://onlinelibrary.wiley.com/doi/full/10.1111/j.1651-2227.2006.00159.xhttp://www.ncbi.nlm.nih.gov/pubmed/17326760?tool=bestpractice.com[65]Ritzén EM. Undescended testes: a consensus on management. Eur J Endocrinol. 2008 Dec;159(suppl 1):S87-90.https://eje.bioscientifica.com/view/journals/eje/159/suppl_1/S87.xmlhttp://www.ncbi.nlm.nih.gov/pubmed/18728121?tool=bestpractice.com[66]Chan E, Wayne C, Nasr A, et al; FRCSC for Canadian Association of Pediatric Surgeon Evidence-Based Resource. Ideal timing of orchiopexy: a systematic review. Pediatr Surg Int. 2014 Jan;30(1):87-97.http://www.ncbi.nlm.nih.gov/pubmed/24232174?tool=bestpractice.com[67]Komarowska MD, Hermanowicz A, Debek W. Putting the pieces together: cryptorchidism - do we know everything? J Pediatr Endocrinol Metab. 2015 Nov 1;28(11-12):1247-56.http://www.ncbi.nlm.nih.gov/pubmed/26226123?tool=bestpractice.com 随机研究表明,对于随机在 9 个月时接受睾丸固定术的男孩,超声测定的睾丸体积和生殖细胞数目都超过在 3 岁时接受手术的儿童。[57]Kollin C, Hesser U, Ritzén EM, et al. Testicular growth from birth to two years of age, and the effect of orchidopexy at age nine months: a randomized, controlled study. Acta Paediatr. 2016 Jun;101(6):2570-7.http://www.ncbi.nlm.nih.gov/pubmed/16497643?tool=bestpractice.com[68]Kollin C, Stukenborg JB, Nurmio M, et al. Boys with undescended testes: endocrine, volumetric and morphometric studies on testicular function before and after orchidopexy at nine months or three years of age. J Clin Endocrinol Metab. 2012 Dec;97(12):4588-95.http://www.ncbi.nlm.nih.gov/pubmed/23015652?tool=bestpractice.com 治疗出现的主要问题包括手术相关并发症,最常见的是麻醉并发症、睾丸再上升、伤口感染、血肿、反应性鞘膜积液和睾丸萎缩。相对于使用安慰剂的患者,接受激素治疗患者的下降率并没有出现>10%的升高,因此不常建议将激素治疗(人绒毛膜促性腺激素 [human chorionic gonadotrophin, hCG] 或促性腺激素释放激素 [gonadotrophin-releasing hormone, GnRH])作为隐睾症的一线治疗;[69]Thorsson AV, Christiansen P, Ritzén M. Efficacy and safety of hormonal treatment of cryptorchidism: current state of the art. Acta Paediatr. 2007 May;96(5):628-30.http://www.ncbi.nlm.nih.gov/pubmed/17462056?tool=bestpractice.com[70]Penson D, Krishnaswami S, Jules A, et al. Effectiveness of hormonal and surgical therapies for cryptorchidism: a systematic review. Pediatrics. 2013 Jun;131(6):e1897-907.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4074661/http://www.ncbi.nlm.nih.gov/pubmed/23690511?tool=bestpractice.com[71]Wei Y, Wang Y, Tang X, et al. Efficacy and safety of human chorionic gonadotropin for treatment of cryptorchidism: a meta-analysis of randomised controlled trials. J Paediatr Child Health. 2018 Apr 14;54(8):900-6.http://www.ncbi.nlm.nih.gov/pubmed/29655188?tool=bestpractice.com 对于该疗法仍或多或少存在争议。[72]Li T, Gao L, Chen P, et al. A systematic review and meta-analysis of comparative studies assessing the efficacy of luteinizing hormone-releasing hormone therapy for children with cryptorchidism. Int Urol Nephrol. 2016 May;48(5):635-44.http://www.ncbi.nlm.nih.gov/pubmed/26898822?tool=bestpractice.com
世界范围内的各种研究表明睾丸固定术的平均年龄仍然超过 18 个月,[73]Wei Y, Wu SD, Wang YC, et al. A 22-year retrospective study: educational update and new referral pattern of age at orchidopexy. BJU Int. 2016 Dec;118(6):987-93.http://www.ncbi.nlm.nih.gov/pubmed/27430859?tool=bestpractice.com[74]Vikraman J, Donath S, Hutson Ao JM. Undescended testes: diagnosis and timely treatment in Australia (1995-2014). Aust Fam Physician. 2017 Mar;46(3):152-8.http://www.ncbi.nlm.nih.gov/pubmed/28260279?tool=bestpractice.com[75]Williams K, Baumann L, Shah A, et al. Age at orchiopexy for undescended testis in the United States. J Pediatr Surg. 2018 Jan;53(1):86-9.http://www.ncbi.nlm.nih.gov/pubmed/29102151?tool=bestpractice.com[76]Bergbrant S, Omling E, Björk J, et al. Cryptorchidism in Sweden: a nationwide study of prevalence, operative management, and complications. J Pediatr. 2018 Jan 10;194:197-203.e6.http://www.ncbi.nlm.nih.gov/pubmed/29331326?tool=bestpractice.com 尽管受到许多专业的组织推荐。[55]Kolon TF, Herndon CD, Baker LA, et al. Evaluation and treatment of cryptorchidism: AUA guideline. J Urol. 2014 Aug;192(2):337-45.https://www.auanet.org/guidelines/cryptorchidism-(2014)http://www.ncbi.nlm.nih.gov/pubmed/24857650?tool=bestpractice.com[77]European Association of Urology. Paediatric urology. 2019 [internet publication].https://uroweb.org/guideline/paediatric-urology/[78]Braga LH, Lorenzo AJ, Romao RLP. Canadian Urological Association-Pediatric Urologists of Canada (CUA-PUC) guideline for the diagnosis, management, and followup of cryptorchidism. Can Urol Assoc J. 2017 Jul;11(7):E251-60.https://www.cua.org/themes/web/assets/files/4585_cryptorchidism.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/28761584?tool=bestpractice.com 可能的病因包括低估睾丸上升的风险、缺乏专业知识或难以获得诊疗服务。[79]Savoie KB, Bachier-Rodriguez M, Schurtz E, et al. Health disparities in the appropriate management of cryptorchidism. J Pediatr. 2017 Jun;185:187-92.e1.http://www.ncbi.nlm.nih.gov/pubmed/28408128?tool=bestpractice.com[80]Boehme P, Geis B, Doerner J, et al. Shortcomings in the management of undescended testis: guideline intention vs reality and the underlying causes - insights from the biggest German cohort. BJU Int. 2018 Mar 9;122(4):644-53.http://www.ncbi.nlm.nih.gov/pubmed/29451709?tool=bestpractice.com
回缩性睾丸
需要每年进行随访检查。如果在随后的每年检查中发现隐睾症或睾丸不对称,则需要进一步的手术干预。如果患者的上升睾丸再也无法向下放回至阴囊的下垂部分和/或睾丸不对称,应当像可触及未降睾丸患者一样接受睾丸固定术。如果在需要手术的对侧未降睾丸中存在可伸缩的睾丸,由于存在异时性未降睾丸的风险,讨论“主动”进行双侧睾丸固定术可能是合理的选择。[81]Cancian M, Ellsworth P, Caldamone A. Contralateral metachronous undescended testis: is it predictable? J Pediatr Urol. 2017 Mar 28;13(5):504.e1-5.http://www.ncbi.nlm.nih.gov/pubmed/28434636?tool=bestpractice.com
青春期前隐睾:单侧或双侧睾丸可触及
许多专业组织推荐将睾丸固定术作为 6 月龄时可触及睾丸未降至阴囊下垂部分的首选治疗。[55]Kolon TF, Herndon CD, Baker LA, et al. Evaluation and treatment of cryptorchidism: AUA guideline. J Urol. 2014 Aug;192(2):337-45.https://www.auanet.org/guidelines/cryptorchidism-(2014)http://www.ncbi.nlm.nih.gov/pubmed/24857650?tool=bestpractice.com[77]European Association of Urology. Paediatric urology. 2019 [internet publication].https://uroweb.org/guideline/paediatric-urology/[78]Braga LH, Lorenzo AJ, Romao RLP. Canadian Urological Association-Pediatric Urologists of Canada (CUA-PUC) guideline for the diagnosis, management, and followup of cryptorchidism. Can Urol Assoc J. 2017 Jul;11(7):E251-60.https://www.cua.org/themes/web/assets/files/4585_cryptorchidism.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/28761584?tool=bestpractice.com 手术方法由外科医生偏好决定,一般是通过腹股沟或阴囊切口,治疗效果差异极小。[82]Dayanc M, Kibar Y, Irkilata H, et al. Long-term outcome of scrotal incision orchiopexy for undescended testis. Urology. 2007 Oct;70(4):786-8.http://www.ncbi.nlm.nih.gov/pubmed/17991558?tool=bestpractice.com[83]Feng S, Yang H, Li X, et al. Single scrotal incision orchiopexy versus the inguinal approach in children with palpable undescended testis: a systematic review and meta-analysis. Pediatr Surg Int. 2016 Oct;32(10):989-95.http://www.ncbi.nlm.nih.gov/pubmed/27510940?tool=bestpractice.com 同时进行腹股沟疝修补术以关闭伴随的开放性鞘状突。 随机对照研究表明,随机分配至阴囊单切口手术或传统(2 个切口)腹股沟手术方法患者的成功率或术后并发症没有差异。[84]Na SW, Kim SO, Hwang EC, et al. Single scrotal incision orchiopexy for children with palpable low-lying undescended testis: early outcome of a prospective randomized controlled study. Korean J Urol. 2011 Sep;52(9):637-41.https://synapse.koreamed.org/DOIx.php?id=10.4111/kju.2011.52.9.637http://www.ncbi.nlm.nih.gov/pubmed/22025961?tool=bestpractice.com[85]Ramzan M, Sheikh AH, Qureshi MS, et al. Single incision trans scrotal versus standard inguino-scrotal orchidopexy in children with palpable undescended testis: our experience from April 2007 to April 2010. Pak J Med Sci. 2012 Oct-Dec;28(5):827-9.http://pjms.com.pk/index.php/pjms/article/view/2424/931 使用阴囊单切口方法,手术时间和住院时间似乎较短。这也是进行睾丸再固定术的合理考虑。[86]Lopes RI, Naoum NK, Chua ME, et al. Outcome analysis of redo orchiopexy: scrotal vs inguinal. J Urol. 2016 Sep;196(3):869-74.http://www.ncbi.nlm.nih.gov/pubmed/27157374?tool=bestpractice.com
成功治疗(到达阴囊位置并且无萎缩)取决于睾丸位置、患者年龄和手术方式,但已有报道称睾丸位于腹股沟外环之外时,成功率是 92% 至 95%。[87]Docimo SG. The results of surgical therapy for cryptorchidism: a literature review and analysis. J Urol. 1995 Sep;154(3):1148-52.http://www.ncbi.nlm.nih.gov/pubmed/7637073?tool=bestpractice.com[88]Taran I, Elder JS. Results of orchiopexy for the undescended testis. World J Urol. 2006 Aug;24(3):231-9.http://www.ncbi.nlm.nih.gov/pubmed/16676187?tool=bestpractice.com
副作用包括手术相关并发症,最常见的是麻醉并发症、睾丸再上升、伤口感染、血肿、反应性鞘膜积液和罕见的睾丸萎缩。
青春期前隐睾:单侧或双侧睾丸不可触及
这些患者适用麻醉下检查以定位不可触及的睾丸。 该检查的结果可确定进一步治疗方法。
如果睾丸在麻醉下检查可触及,则医生应继续进行睾丸固定术。
如果睾丸在麻醉下检查不可触及,根据医生的偏好,可通过开腹或腹腔镜检查方式探查睾丸或睾丸残余物。[89]SAGES Guidelines Committee. Guidelines for diagnostic laparoscopy. 2007 [internet publication].http://www.sages.org/publications/guidelines/guidelines-for-diagnostic-laparoscopy/ 大约 50% 的不可触及睾丸可在腹部或腹股沟区发现,50% 缺如或只有少量残余物,称为睾丸残端。[90]Elder JS. Laparoscopy for impalpable testes: significance of the patent processus vaginalis. J Urol. 1994 Aug;152(2 Pt 2):776-8.http://www.ncbi.nlm.nih.gov/pubmed/7912744?tool=bestpractice.com 为了确保没有残余睾丸组织遗留在原处,使得患者患有睾丸恶性肿瘤的风险增加,必须找到性腺血管和输精管并全程跟踪。 有些外科医生倾向于通过阴囊或腹股沟切口,并且在找不到腹股沟睾丸或残端时进行腹膜后切开,而其他医生则倾向于使用腹腔镜,对于腹内睾丸,睾丸固定术成功率比开放手术高。[91]Baker LA, Docimo SG, Surer I, et al. A multi-institutional analysis of laparoscopic orchidopexy. BJU Int. 2001 Apr;87(6):484-9.http://www.ncbi.nlm.nih.gov/pubmed/11298039?tool=bestpractice.com 如果根据存在性腺血管盲端确定睾丸缺如,则终止手术。由于盲端血管与缺如的睾丸相关,除非外科医生的目标是切除所有残端,否则没有必要进行进一步的探查。[92]Sturm R, Kurzrock E, Amend G, et al. Blind ending vessels on diagnostic laparoscopy for nonpalpable testis: is a nubbin present? J Pediatr Urol. 2017 Aug;13(4):392.e1-6.http://www.ncbi.nlm.nih.gov/pubmed/28666917?tool=bestpractice.com 如果在探查过程中发现睾丸残端,外科医生经常会将其摘除用于病理学评估。在这种情况下,通常不进行对侧睾丸固定术,因为病理生理学最符合围生期鞘外扭转事件,存活的睾丸没有任何增加的风险。[93]Kehoe JE, Christman MS. To 'pex or not to 'pex: what to do for the contralateral testis when a nubbin is discovered. Curr Urol Rep. 2017 Feb;18(2):9.http://www.ncbi.nlm.nih.gov/pubmed/28213853?tool=bestpractice.com 如果确定是有活力的睾丸,则睾丸的具体位置、放回阴囊内的难易程度以及外科医生的偏好决定了是否可以进行 1 期或 2 期睾丸固定术。[94]Elyas R, Guerra LA, Pike J, et al. Is staging beneficial for Fowler-Stephens orchiopexy? A systematic review. J Urol. 2010 May;183(5):2012-8.http://www.ncbi.nlm.nih.gov/pubmed/20303527?tool=bestpractice.com 对比腹腔镜检查与开放手术治疗不可触及睾丸,实施了一项荟萃分析,包括 2 项随机对照试验和 5 项观察性研究,发现在手术成功、睾丸活力或睾丸萎缩方面没有显著差异。[95]Guo J, Liang Z, Zhang H, et al. Laparoscopic versus open orchiopexy for non-palpable undescended testes in children: a systemic review and meta-analysis. Pediatr Surg Int. 2011 Sep;27(9):943-52.http://www.ncbi.nlm.nih.gov/pubmed/21476074?tool=bestpractice.com 使用腹腔镜手术,患者的住院时间较短。
青春期前隐睾:双侧睾丸不可触及
对于双侧睾丸不可触及的足月新生男婴,应当立即转诊接受内分泌和/或遗传学评估,包括染色体核型分析和生化检查,以确定是否存在性发育异常 (disorder of sex development, DSD)。若检测不到抑制素和苗勒抑制物质 (MIS) 水平并伴随卵泡刺激素 (FSH) 水平升高,则提示双侧睾丸不可触及、具有 46 XY 表型的男性患有无睾症,这使得此亚组没有必要进行 hCG 刺激试验或手术探查。如果内分泌试验显示 Sertoli 和 Leydig 细胞功能,则睾丸组织存在,且需要手术治疗。[53]Teo AQ, Khan AR, Williams MP, et al. Is surgical exploration necessary in bilateral anorchia? J Pediatr Urol. 2013 Feb;9(1):e78-81.https://www.jpurol.com/article/S1477-5131(12)00229-X/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/23079081?tool=bestpractice.com[54]Brauner R, Neve M, Allali S, et al. Clinical, biological and genetic analysis of anorchia in 26 boys. PLoS One. 2011;6(8):e23292.https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0023292http://www.ncbi.nlm.nih.gov/pubmed/21853106?tool=bestpractice.com
血清激素评估确定睾丸缺如:患者转诊接受内分泌和/或遗传学评估和管理,可能包括睾酮补充和未来生育力咨询。 如果需要的话,家属也会得到关于未来放置睾丸假体的建议。
血清激素评估提示睾丸存在:进行手术。 如果在麻醉下检查过程中触及到一侧或两侧不可触及的睾丸,则患者将接受用于可触及睾丸的睾丸固定术。 如果发现一个睾丸在腹股沟区,另外一个则在腹内,外科医生可能需要选择分期手术法,先在腹股沟侧进行睾丸固定术,然后再对腹内的睾丸进行睾丸固定术,或可能同时进行双侧睾丸固定术。 如果在麻醉下检查过程中仍触及不到睾丸,外科医生可能选择在一侧或两侧开腹或腹腔镜下手术以进行确定并附带睾丸固定术(或对睾丸残端执行睾丸切除术),具体取决于睾丸的确切位置和将睾丸放回阴囊内的难易程度。 对于位置较高的双侧腹内睾丸,一些外科医生倾向于采用分期手术法,一次进行单侧睾丸固定术,等待愈合并确保没有出现睾丸萎缩,然后再对另外一侧睾丸进行分期睾丸固定术。
青春期前隐睾:单侧或双侧隐睾伴尿道下裂
患有尿道下裂和睾丸可触及或不可触及的新生儿,应立即转诊接受内分泌和/或遗传学评估,包括染色体核型分析和生化检查,以确定是否存在 DSD。 患有尿道下裂以及单侧或双侧隐睾的患者,应选择性地考虑接受包括染色体核型分析在内的内分泌学和/或遗传评估。 有时候,患有先天性肾上腺增生症的严重雄性化女性可能出现阴茎结构和推测的双侧隐睾,并可能出现危及生命的代谢紊乱。 还应转诊至泌尿科对尿道下裂和隐睾症做进一步评估和治疗。 已经证明这些患者存在 DSD 的风险为 27% 至 55%。[3]Brucker-Davis F, Pointis G, Chevallier D, et al. Update on cryptorchidism: endocrine, environmental and therapeutic aspects. J Endocrinol Invest. 2003 Jun;26(6):575-87.http://www.ncbi.nlm.nih.gov/pubmed/12952375?tool=bestpractice.com
青春期后患者的延误诊断
在罕见情况下,可在青春期后患者中诊断出隐睾症。 进一步治疗取决于检查发现和患者的年龄:
对于青春期后接受隐睾治疗的患者,恶性肿瘤风险显著增加。[64]Pettersson A, Richiardi L, Nordenskjold A, et al. Age at surgery for undescended testis and risk of testicular cancer. N Engl J Med. 2007 May 3;356(18):1835-41.https://www.nejm.org/doi/full/10.1056/NEJMoa067588http://www.ncbi.nlm.nih.gov/pubmed/17476009?tool=bestpractice.com[96]Wood HM, Elder JS. Cryptorchidism and testicular cancer: separating fact from fiction. J Urol. 2009 Feb;181(2):452-61.http://www.ncbi.nlm.nih.gov/pubmed/19084853?tool=bestpractice.com 基于这一原因,有人提倡对成人隐睾直接进行睾丸切除。[97]Koh KB. Beware the undescended testis and abdominal mass. Aust N Z J Surg. 1996 Dec;66(12):851-3.http://www.ncbi.nlm.nih.gov/pubmed/8996073?tool=bestpractice.com[98]Ryang SH, Jung JH, Eom M, et al. The incidence and histological characteristics of intratubular germ cell neoplasia in postpubertal cryptorchid testis. Korean J Urol. 2015 Jul;56(7):515-8.https://www.icurology.org/DOIx.php?id=10.4111/kju.2015.56.7.515http://www.ncbi.nlm.nih.gov/pubmed/26175870?tool=bestpractice.com
其他人则证明少数在青春期后被摘除的隐睾中存在精子发生,尤其是那些位于耻骨前区的隐睾,因此提倡睾丸活组织检查、睾丸固定术和定期随访。[99]Kang KJ, Kim HS, Oh TH. The clinical experience on orchiectomy in the postpubertal unilateral cryptorchidism. Korean J Urol. 1999 Oct;40(10):1371-6.http://urology.inforang.com/journal/viewJournal.html?year=1999&vol=40&page=1371
大于 50 岁和/或那些有显著合并症的患者死于麻醉并发症的风险可能大于生殖细胞瘤。 因此,对于这些患者建议连续观察。[100]Oh J, Landman J, Evers A, et al. Management of the postpubertal patient with cryptorchidism: an updated analysis. J Urol. 2002 Mar;167(3):1329-33.http://www.ncbi.nlm.nih.gov/pubmed/11832725?tool=bestpractice.com