Management of Cryptorchidism: A Survey of Clinical Practice in Italy
Management of Cryptorchidism: A Survey of Clinical Practice in Italy
Management of Cryptorchidism: A Survey of Clinical Practice in Italy
RESEARCH ARTICLE
Open Access
Abstract
Background: An evidence-based Consensus on the treatment of undescended testis (UT) was recently published,
recommending to perform orchidopexy between 6 and 12 months of age, or upon diagnosis and to avoid the use
of hormones. In Italy, current practices on UT management are little known. Our aim was to describe the current
management of UT in a cohort of Italian children in comparison with the Consensus guidelines. As management
of retractile testis (RT) differs, RT cases were described separately.
Methods: Ours is a retrospective, multicenter descriptive study. An online questionnaire was filled in by 140 Italian
Family Paediatricians (FP) from Associazione Culturale Pediatri (ACP), a national professional association of FP. The
questionnaire requested information on all children with cryptorchidism born between 1/01/2004 and 1/01/2006.
Data on 169 children were obtained. Analyses were descriptive.
Results: Overall 24% of children were diagnosed with RT, 76% with UT. Among the latter, cryptorchidism resolved
spontaneously in 10% of cases at a mean age of 21.6 months. Overall 70% of UT cases underwent orchidopexy at
a mean age of 22.8 months (SD 10.8, range 1.2-56.4), 13% of whom before 1 year. The intervention was performed
by a paediatric surgeon in 90% of cases, with a success rate of 91%. Orchidopexy was the first line treatment in
82% of cases, while preceded by hormonal treatment in the remaining 18%. Hormonal treatment was used as first
line therapy in 23% of UT cases with a reported success rate of 25%. Overall, 13 children did not undergo any
intervention (mean age at last follow up 39.6 months). We analyzed the data from the 5 Italian Regions with the
largest number of children enrolled and found a statistically significant regional difference in the use of hormonal
therapy, and in the use of and age at orchidopexy.
Conclusions: Our study showed an important delay in orchidopexy. A quarter of children with cryptorchidism was
treated with hormonal therapy. In line with the Consensus guidelines, surgery was carried out by a paediatric
surgeon in the majority of cases, with a high success rate.
Background
Undescended testicle (UT) is present at birth with a frequency varying from 2% to 8% [1]: in Italy the estimated
prevalence is 3.5% in term babies [2]. UT includes both
a non-palpable testis and a palpable supra-scrotal testis
which cannot be pulled down to the scrotum or does
not remain there by six months of age. UT should be
differed from retractile testis (RT), a condition where
the testis is palpable in the supra-scrotal region but,
once pulled down to the scrotum, remains there after
* Correspondence: marchetti@burlo.trieste.it
1
Institute for Maternal and Child Health IRCCS Burlo Garofolo, Department
of Paediatrics, Trieste, Italy
Full list of author information is available at the end of the article
2012 Marchetti et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
Methods
Ours is a descriptive and multicenter study. It enrolled
FP from Associazione Culturale Pediatri (ACP), a
national professional association represented in all
Regions of Italy.
FP work independently in their offices, providing acute
and chronic care to all children from 0 to 14 years old.
They contract directly with the National Health System
for the care of patients through a capitated reimbursement system, ensuring free paediatric care at the point
of provision to all children.
ACP has been involved in previous studies and is
representative of the Italian paediatric primary care system [16,17]. FP were invited to participate at a national
ACP meeting, where the study protocol was first presented. Each FP was asked to fill out an electronic form
for each child with UT/RT diagnosis. The form was validated by a pilot study.
The study was approved by the Independent Bioethics
Committee of the Institute for Maternal and Child Health
IRCCS Burlo Garofolo (Prot. CE/V- 86, April 28, 2008).
The research was carried out in compliance with the Helsinki Declaration. Each FP asked the parents informed
consent before filling out the electronic data base.
Inclusion criteria and data collection
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At the time of our survey (early 2008), enrolled children were aged between 24 and 56 months of age. We
excluded from the analysis all subjects with spontaneous
resolution of UT in the first 6 months of life.
An electronic data collection form (Additional files 1
and 2) was filled in directly by each participating FP for
each child with a diagnosis of cryptorchidism. Data
included: age at diagnosis, clinical type according to the
definitions above (non-palpable UT, palpable suprascrotal UT, RT), presence of a clinically significant concomitant disease, use of hormonal therapy, age at
orchidopexy, and centre at which orchidopexy was
performed.
Outcome variables
Primary outcome variables were: mean age at orchidopexy, prevalence of hormonal therapy and of referral to
a paediatric surgery centre. Secondary outcome variables
were: prevalence of reported success and failure of hormonal therapy and of surgery complications.
We analyzed the data from the 5 Italian Regions with
the largest number of children enrolled in order to
check for any regional difference for primary outcomes.
Data Analysis
Results
One-hundred and sixty-two FP were enrolled in the
study; 140 (86%) responded to the questionnaire. Mean
age of enrolled FP was 51,7 years (SD 4,7), with a mean
of 26.3 years of clinical experience (SD 5.1) after medical degree. A mean of 895 (SD 148) patients were followed by each FP. Participating FP were representative
of the whole country as they came from 18 out of the
20 Italian administrative regions.
Eighty-three out of 140 FP (59%) followed at least 1
patient with UT or RT in the defined period, adding up
to a total of 177 children. After the exclusion of 3 cases
who did not meet the inclusion criteria and 5 cases with
spontaneous resolution of cryptorchidism in the first 6
months of age, 169 children were considered in the final
analysis: 127 with UT and 41 with RT (1 with unknown
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non-palpable. In 18% of cases (n = 23) there was an associated disease or syndrome. The mean age at last follow-up
was 35.1 months (SD 13.1, range 4.8-58.8; 5 missing data).
Mean birthweight was 3262 grams (SD 615) and gestational age 39 weeks (SD 2.1), with the majority of cases
(88%) born between 37 and 41 weeks.
Sixteen percent of children had bilateral cryptorchidism,
while 45% had right and 33% left cryptorchidism. Seventytwo (57%) were in inguinal position, while 55 (43%) were
Hormonal therapy
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Table 1 Main outcome measures for children with cryptorchidism as a whole, and divided in UT and RT subgroups.
UT #
RT #
Spontaneous resolution
13/127 (10%)
14/41 (34%)
4 (31%)
2 (14%)
3 (23%)
5 (36%)
24 months or more
6 (46%)
7 (50%)
29/127 (23%)
4/41 (10%)
16/29 (55%)
13/29 (45%)
2/4 (50%)
2/4 (50%)
30 (7.2; 20.4-36)
24 (13.2; 6-50.4)
30 (3.6; 43.2-33.6)
7/28 (25%)*
1/4 (25%)
Surgical treatment
88/126 (70%)
10/40 (25%)**
3 (3%)
9 (10%)
1 (10%)
44 (51%)
4 (40%)
24 months or more
31 (36%)
5 (50%)
79/88 (90%)
8/10 (80%)
12/12 (100%)
1/1 (100%)
74/85 (87%)
8/9 (89%)
- Scheduled orchidopexy
Surgery outcome
7/126 (6%)
4/40 (10%)
- Descended testis
80/88 (91%)
10/10 (100%)
2/88 (2%)
1/88 (1%)
5/88 (6%)
11/126 (9%)
10/11 (91%)
- LHRH
1/11 (9%)
Categorical variables are presented as percentages, continuous variables as mean (SD; range).
* 1 child lost at follow up from FP after beginning of treatment
** 1 child lost at follow up after sending to surgeon
17 children after hormonal treatment; 82 underwent surgery as first line treatment
# 1 child without indication of physical examination and clinical type
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Table 2 Regional differences in the use of hormonal therapy, use of surgery and mean age at surgery
Hormonal therapy*
Surgery**
Friuli-Venezia Giulia
18.2% (2/11)
90% (9/10)
21,5 ( 8,0)
Veneto
9.4% (3/32)
71.9% (23/32)
23,9 ( 10,85)
Lombardy
30% (6/20)
75% (15/20)
21,2 ( 10,6)
Umbria
41.7% (5/12)
58.3% (7/12)
23,6 ( 18,7)
Sicily
53.3% (8/15)
46.7% (7/15)
25,0 ( 6,6)
* c per trend, p = 0,001; ** c per trend, p = 0,026; p = 0.7, 1 children lost at follow up after starting hormonal therapy
2
In 90% of cases, orchidopexy was carried out by a paediatric surgeon, in 100% of cases in children younger
than 12 months. The 2 cases who needed a second surgery came both from a paediatric surgery centre. In 87%
of cases, children underwent orchidopexy in the same
region from where they came.
Characteristics of children with RT
Discussion
Cryptorchidism is a relevant condition, with an estimated incidence in Italy of 3,5% yearly [2]. For unknown
reasons, UT prevalence appears to have increased in
some countries [18,19]. This increase is of concern
given the long term adverse health effects of UT, such
as altered semen quality [4,20], endocrine insufficiency
[8,21,22] and increased risk of testicular cancer
[11,23-27]. In fact cryptorchidism has been proposed to
be part of a testicular dysgenesis syndrome which
includes hypospadias, reduced semen quality and testicular cancer. These conditions are thought to have a
common origin in prenatal testicular maldevelopment,
which affects both Leydig and Sertoli cells and germ cell
differentiation [28]. The aim of an early orchidopexy is
to prevent the possible adulthood consequences on
spermatogenesis [3,29,30], while its effect on the risk of
testicular cancer remains to be established.
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Conclusions
The correct and timely management of children with
cryptorchidism is important to promote gonadal development and to avoid the adulthood consequences of
spermatogenesis defects. The results of our study
allowed for the first time to describe how was the management of cryptorchidism in Italy before the publication of the Consensus. Hormone therapy was used in
about one quarter of the cases. The average age at surgery was much higher than recommended in the Consensus, and only 13% of children underwent surgery
before 12 months of age.
Our results suggest that the spread of the Consensus
guidelines on the management of cryptorchidism among
all paediatricians is warranted in order to reduce age at
orchidopexy and to have a more homogenous approach
in the whole of Italy.
Additional material
Additional file 1: Italian data collection form. Data collection form in
Italian language as in the original electronic form.
Additional file 2: English data collection form. Data collection form
translated in English.
Abbreviations
UT: undescended testis; RT: retractile testis; FP: family paediatrician; hCG:
human chorionic gonadotropin; LHRH: luteinizing hormone-releasing
hormone.
Acknowledgements
This study was funded by the Italian Ministry of Health (research grant: 0208,
L 4). The sponsor had no role in design, data collection, analysis and
interpretation, or reporting of the study.
We thank the Italian Study Group on Undescended Testes (ISGUT): the
Scientific Committee (Francesco Chiarelli, Michele Gangemi, Jrgen Schleef,
Giorgio Tamburini, Alessandro Ventura) and all the Family Paediatricians who
participated to the data collection (Abadessa A, Accordini G, Aimini E, Alberti
A, Aloisio A, Amadio C, Amoroso B, Andreotti MF, Angelini P, Auriti L, Basilico
E, Belvedere L, Berardi C, Besoli G, Bianchi S, Binni O, Biolchini A, Bollettini S,
Bologna B, Bonin P, Bontempo F, Borghesani M, Brusadin L, Brutti P, Budassi
R, Cafaro C, Cajani M, Callegari M, Cambria R, Cammarota MS, Canfora G,
Capomolla D, Cappellani E, Casalboni R, Casiraghi EM, Cavallo R, Cazzuffi MA,
Cera M, Ciambra R, Clerici Schoeller M, Coltura E, Concas L, Conforti G, Conti
Nibali S, Corbetta D, Crupi I, De Angelis R, De Santi M, Degli Angeli M, Del
Bono GP, DellAntonia F, DellEdera L, Di Francesco C, Di Pietro ME, Donati D,
Faberi P, Faedi CM, Falasconi AM, Finco M, Fortunato V, Francano B, Frison E,
Page 7 of 8
13. Agarwal PK, Diaz M, Elder JS: Retractile testis-Is it really a normal variant?
J Urol 2006, 175:1496-1499.
14. Hack WWM, Sijstermans K, van Dijk J, van der Voort-Doedens LM, de
Kok ME, Hobbelt-Stoker MJ: Prevalence of acquired undescended testis in
6-year, 9-year and 13-year-old Dutch schoolboys. Arch Dis Child 2007,
92:17-20.
15. Hack WW, Meijer RW, Van Der Voort-Doedens LM, Bos SD, De Kok ME:
Previous testicular position in boys referred for an undescended testis:
further explanation of the late orchidopexy enigma? BJU Int 2003,
92:293-296.
16. Del Torso S, Bussi R, DeWitt TG: Primary care pediatrics in Italy: eighteen
years of clinical care, research, and teaching under a national health
service system. Pediatrics 1997, 99:E8.
17. Marchetti F, Ronfani L, Nibali SC, Tamburlini G, Italian Study Group on Acute
Otitis Media: Delayed prescription may reduce the use of antibiotics for
acute otitis media: a prospective observational study in primary care.
Arch Pediatr Adolesc Med 2005, 159:679-684.
18. Acerini CL, Miles HL, Dunger DB, Ong KK, Hughes IA: The descriptive
epidemiology of congenital and acquired cryptorchidism in a UK infant
cohort. Arch Dis Child 2009, 94:868-872.
19. Boisen KA, Kaleva M, Main KM, Virtanen HE, Haavisto AM, Schmidt IM,
Chellakooty M, Damgaard IN, Mau C, Reunanen M, Skakkebaek NE,
Toppari J: Difference in prevalence of congenital cryptorchidism in
infants between two Nordic countries. Lancet 2004, 363:1264-1269.
20. Taskinen S, Hovatta O, Wikstrm S: Early treatment of cryptorchidism,
semen quality and testicular endocrinology. J Urol 1996, 156:82-84.
21. Andersson AM, Petersen JH, Jrgensen N, Jensen TK, Skakkebaek NE: Serum
inhibin B and follicle-stimulating hormone levels as tools in the
evaluation of infertile men: significance of adequate reference values
from proven fertile men. J Clin Endocrinol Metab 2004, 89:2873-2879.
22. Coughlin MT, Bellinger MF, Lee PA: Age at unilateral orchidopexy: effect on
hormone levels and sperm count in adulthood. J Urol 1999, 162:986-988.
23. Ritzen EM: Undescended testes: a consensus on management. Eur J of
Endocrinol 2008, 159:S87-S90.
24. Pettersson A, Richiardi L, Nordenskjold A, Kaijser M, Akre O: Age at surgery
for undescended testis and risk of testicular cancer. New Eng J Med 2007,
356:1835-1841.
25. Giwercman A, Grindsted J, Hansen B, Jensen OM, Skakkebaek NE: Testicular
cancer risk in boys with maldescended testis: a cohort study. J Urol 1987,
138:1214-1216.
26. Herrinton LJ, Zhao W, Husson G: Management of cryptorchidism and risk
of testicular cancer. Am J Epidemiol 2003, 157:602-605.
27. Pottern LM, Brown LM, Hoover RN, Javadpour N, OConnell KJ, Stutzman RE,
Blattner WA: Testicular cancer risk among young men: role of
cryptorchidism and inguinal hernia. J Natl Cancer Inst 1985, 74:377-381.
28. Skakkebaek NE, Rajpert-De Meyts E, Main KM: Testicular dysgenesis
syndrome: an increasingly common developmental disorder with
environmental aspects. Human Reprod 2001, 16:972-978.
29. Kollin C, Karpe B, Hesser U, Granholm T, Ritzen EM: Surgical treatment of
unilaterally undescended testes: testicular growth after randomization to
orchidopexy at age 9 months or 3 years. J Urol 2007, 178:1589-1593.
30. Canavese F, Mussa A, Manenti M, Cortese MG, Ferrero L, Tuli G,
Macchieraldo R, Lala R: Sperm count of young men surgically treated for
cryptorchidism in the first and second year of life: fertility is better in
children treated at a younger age. Eur J Pediatr Surg 2009, 19:388-391.
31. Henna MR, Del Nero RG, Sampaio CZ, Atallah AN, Schettini ST, Castro AA,
Soares B: Hormonal cryptorchidism therapy: systematic review with
metanalysis of randomized clinical trials. Pediatr Surg Int 2004, 20:357-359.
32. Heiskanen P, Billig H, Toppari J, Kaleva M, Arsalo A, Rapola J, Dunkel L:
Apoptotic cell death in the normal and cryptorchid human testis: the
effect of human chorionic gonadotropin on testicular cell survival.
Pediatr Res 1996, 40:351-356.
33. Kaleva M, Toppari J: Cryptorchidism: an indicator of testicular dysgenesis?
Cell Tissue Res 2005, 322:167-172.
34. Dunkel L, Taskinen S, Hovatta O, Tilly JL, Wikstrom S: Germ cell apoptosis
after treatment of cryptorchidism with human chorionic gonadotropin is
associated with impaired reproductive function in the adult. J Clin Invest
1997, 100:2341-2346.
35. Cortes D, Thorup J, Visfeldt J: Hormonal treatment may harm the germ
cells in 1 to 3-year-old boys with cryptorchidism. J Urol 2000,
163:1290-1292.
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