:: International Braz J Urol ::

Age at orchiopexy and testis palpability predict germ and Leydig cell loss: clinical predictors of adverse histological features of cryptorchidism
Tasian GE, Hittelman AB, Kim GE, DiSandro MJ, Baskin LS
Department of Urology, University of California-San Francisco, San Francisco, California, USA
J Urol. 2009; 182: 704-9

Purpose: We determined the relationship between clinical variables and testicular histopathological changes associated with decreased fertility potential in children with cryptorchidism.
Materials and Methods: Testis biopsies of 274 children who underwent orchiopexy and concurrent testicular biopsy between 1991 and 2001 were analyzed for germ and Leydig cell loss, and testicular fibrosis. Multivariable logistic regression was used to determine if age at orchiopexy (analyzed as continuous and ordinal variables), preoperative testis palpability, unilateral vs bilateral disease and/or side of undescended testis was predictive of these pathological outcomes.
Results: Age at orchiopexy was associated with germ and Leydig cell depletion. Each month of testis undescent was associated with development of moderate/severe germ cell depletion (OR 1.02 for each month of age, p <0.005) and Leydig cell loss (OR 1.01 for each month of age, p <0.02). Nonpalpable testes were associated with severe germ cell depletion. Children with palpable testes had lower odds of germ cell depletion than those with nonpalpable testes (OR 0.46, p <0.005). This finding corresponds to a significant 2% risk per month of severe germ cell loss and 1% risk per month of Leydig cell depletion for each month a testis remains undescended, and a 50% greater risk of germ cell depletion in nonpalpable relative to palpable cryptorchid testes.
Conclusions: Testes that remain undescended are associated with progressive loss of germ and Leydig cells, and nonpalpable testes predict severe germ cell loss.

Editorial Comment
This is an 11-year study. Patients under 18 underwent orchiopexy with a concurrent testicular biopsy. The pathologic specimens were graded on the degree of tubular fibrosis, average number of germ cells per tubule and presence or absence of Leydig cells. Patients were grouped into 4 groups by age, 0-12 months, 13-24 months, 25-96 months, and greater than 96 months. They also had an ordinal statistical analysis.
Of the 274 patients included in the study, 68% had unilateral cryptorchidism and 32% had bilateral. The mean age was 43.6 months with a range of 1-209 months. 172 of the patients had palpable testes and 102 were non-palpable. Forty-five were intra-abdominal testes. After adjusting for variables, each month of undescended state of the testis was associated with germ cell depletion with an odds risk of 1.02 for each month. The p-value was less than 0.005 and Leydig cell loss had an odds risk ratio of 1.01 for each month with a p-value of 0.02. There was no association found between testis palpability and the absence of Leydig cells. Fibrosis was not associated with testis location or patient age. There was no pathologic correlation associated with laterality or with unilateral bilateral disease.
The results suggest a significant 2% risk per month for germ cell depletion and 1% risk per month for Leydig cell loss after the first year of life, this confirms current practice patterns of suggesting early orchiopexy for the best long-term results. Of note, the patient age in the study was older than usual practice with a mean of 43.6 months. I also wish that the authors and journal had included more data. Since 40% of their patients were younger than 18 months, this means that there was just over 1 patient per month in all of the months studied. It would be helpful to understand the statistics better and the data distribution to be certain that the statistical outcomes are correct.
The greatest concern for papers predicting outcome of undescended testes is that they are just that, predictions. It takes an extremely long study to actually document fertility and paternity and the threshold of Leydig cell depletion which affects adult hormone function is not clear.