Testicular Cancer

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Together with infertility, increased testicular cancer risk is considered to be a major potential consequence of cryptorchidism. The origin of malignant cells is germ cells that remain in the early stages of differentiation. This may be a consequence of excessive proliferation of precursor germ cells, with associated loss of intercellular communications (177) or from a failure of maturation of these precursors. Testicular carcinoma-in-situ (CIS) precedes germ cell tumors (178), although it is not clear that all CIS instances ultimately develop into tumors. Placenta-like alkaline phosphatase antibody positive cells (a marker of both undifferentiated germ cells and unclassified germ cell neoplasia) have been identified at biopsy during orchiopexy at young ages (149). Thus far, no patient with these markers who was followed for two subsequent decades has developed testicular cancer.

Traditional reports suggested that patients with cryptorchidism had a 4- to 10-fold increased risk of tumors (179). In all men who have cryptorchidism, the lifetime risk of a testicular cancer has been reported to be 2 to 3%, which is at least four times greater than the general population (180,181). Based on the development of testicular tumors in men with a history of cryptorchidism, the risk was 4.7, compared with the general population (179). The odds ratio was 9.3 in men with bilateral cryptorchidism and 2.4 in the unilateral group. Even the contralateral descended testis is at increased cancer risk. Furthermore, a much greater cancer risk is present in men with uncorrected cryp-torchidism (RR 15.9 or 11/69) (182). However, many of the rates reported may be falsely reduced by the inclusion of patients who had retractile testes.

The rate of development of testicular cancer has typically been assessed as the proportion of testicular cancer patients with a history of cryptorchidism, rather than the percentage of men who were formerly cryptorchid (114) who develop testicular tumors. In either situation, the risk may differ depending on the inclusion of patients with unilateral or bilateral cryptorchidism, age and mode of therapy, occurrence of spontaneous descent or ascent, location of the undescended testis, and the presence of other developmental anomalies.

A case-control study of men with testicular germ cell tumors found a significant association with cryptorchidism, with an odds ratio of 3.8 (183). The odds ratio was 5.9 for bilateral and 2.7 for unilateral cryptorchidism. When the men in the unilateral group who had a tumor in the contralateral testis were assessed separately, the odds ratio for the ipsilateral testis was 4.0 and 1.4 for the contralateral testis. Positive associations with testicular cancer for the entire population, not just those who had cryp-torchidism, were also noted for early onset of puberty (voice change and shaving), infertility, and a sedentary lifestyle. A protective effect of exercise was found, but no association with vasectomy was identified.

In addition to the generalized increased risk with cryptorchidism, certain factors stand out as adding to the cancer risk. In one study, testicular neoplasia, including CIS, was seen in 7 of 1249 biopsies of undescended testes (184). This and previous reports (178) suggest an increased cancer risk in boys with intra-abdominal testes, an abnormal karyotype, or abnormal external genitalia. This reasoning has led to the proposal that testicular biopsy should be considered at the time of initial surgery. Inclusion of such patients may explain the high relative risk of testicular cancer in various study cohorts. Also, testicular biopsy itself may increase the cancer risk. In a cohort of 1124 men with cryptorchidism treated with surgery or hormones between 1951 and 1964 in which outcome data were obtained for 792 (70%) (185), the risk was reported to be increased 8.5-fold for unilateral cryptorchidism, with a risk of 14.4-fold for the undescended testis and 2.1-fold for the scrotal testis. In that cohort, there was a substantial increase in risk in testes that were biopsied at orchiopexy, although this was done in only 9% of testes (120 of 1305 undescended testes from 1075 boys). The increase in cancer risk may relate to the reason the testes were biopsied, such as a dysgenetic appearance or the surgeon's view that the risk of neoplasia was increased.

Tumors and Age at Orchiopexy

It is not known whether bringing the testis into a scrotal location reduces the risk of testicular cancer. Indeed, a relatively small study in which most surgery was done in late childhood found no effect of age of treatment on risk of cancer (182). Conversely, when age at correction was considered for patients with previous unilateral cryp-torchidism (183), no increased risk of cancer was found for those who had successful surgery before the age of 10 yr (odds ratio 0.60), whereas the risk was increased with surgery at age 10 yr or older (odds ratio 6.75). It is noteworthy that the risk associated with undescended testes was eliminated in that study by orchiopexy before the age of 10 yr. In addition, there was a significant association between age at orchiopexy (age 3 to > 14 yr) and risk of cancer.

Although the benefits of orchiopexy in reducing the risk of neoplasia may be unclear, the general view is that bringing the testis into a scrotal or near-scrotal position is indicated. A scrotal position would allow for earlier detection of physical changes that might indicate malignancy. For this reason, orchiopexy has been recommended, even for postpubertal males who are healthy except for cryptorchidism, because the risk of malignancy is considered to exceed the perioperative morbidity and mortality (186). Most also recommend biopsy of the testis at the time of orchiopexy in pubertal and postpubertal boys. In the past, some have argued for orchiectomy for the unilateral high testis, but this approach is less acceptable in the current era of assisted reproductive technology in which a single sperm may be sufficient to father a child.

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100 Pregnancy Tips

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