Endocrine function in patients treated for carcinoma in situ in the testis with irradiation

Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Apmis (Impact Factor: 2.04). 02/2003; 111(1):93-8; discussion 98-9. DOI: 10.1034/j.1600-0463.2003.11101131.x
Source: PubMed


CIS is found in the contralateral testis in 5% of the patients with testicular germ cell cancer. The management of CIS in the contralateral testis is important because the majority - if not all - cases of CIS will progress to invasive disease without treatment. It is well documented that testicular irradiation with a total dose of 14-20 Gy (2 Gy x 7-10) is an effective and safe treatment for CIS in the contralateral testis in patients with unilateral testicular germ cell cancer. However few relapses of testicular cancer have been observed in testis treated with these regimens and the data on 14 Gy are sparse. One study has indicated that more radiotherapy with lower doses per fraction could be useful, but more data are needed to confirm this. Endocrine testicular function has been shown to be impaired already before treatment in patients with CIS and is further impaired after testicular irradiation with 14-20 Gy (2 Gy x 7-10) and only minor dose dependency is seen in the impairment of Leydig cell function. The optimal treatment of CIS in the contralateral testicle in patients orchidectomised for testicular cancer seems to be local radiotherapy of the testis with CIS in order to preserve at least a part of the Leydig cell function. However, the optimal dose level has to be defined.

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    • "The proliferation might arise due to a decreased testosterone production by the Leydig cells pi, which will induce increased LH production that may stimulate proliferation of pre-Leydig cells and their differentiation to Leydig cells. This is also the clinical observation upon irradiation of human testis harbouring carcinoma in situ[41] and in rats with Sertoli cell-only testes [42]. However, it is not clear if a dose of 1 Gy leads to reduced testosterone production and increased LH level, although higher irradiation doses lead to changes in testosterone and LH levels [43]. "
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    ABSTRACT: Background Radiotherapy is used routinely to treat testicular cancer. Testicular cells vary in radio-sensitivity and the aim of this study was to investigate cellular and molecular changes caused by low dose irradiation of mice testis and to identify transcripts from different cell types in the adult testis. Methods Transcriptome profiling was performed on total RNA from testes sampled at various time points (n = 17) after 1 Gy of irradiation. Transcripts displaying large overall expression changes during the time series, but small expression changes between neighbouring time points were selected for further analysis. These transcripts were separated into clusters and their cellular origin was determined. Immunohistochemistry and in silico quantification was further used to study cellular changes post-irradiation (pi). Results We identified a subset of transcripts (n = 988) where changes in expression pi can be explained by changes in cellularity. We separated the transcripts into five unique clusters that we associated with spermatogonia, spermatocytes, early spermatids, late spermatids and somatic cells, respectively. Transcripts in the somatic cell cluster showed large changes in expression pi, mainly caused by changes in cellularity. Further investigations revealed that the low dose irradiation seemed to cause Leydig cell hyperplasia, which contributed to the detected expression changes in the somatic cell cluster. Conclusions The five clusters represent gene expression in distinct cell types of the adult testis. We observed large expression changes in the somatic cell profile, which mainly could be attributed to changes in cellularity, but hyperplasia of Leydig cells may also play a role. We speculate that the possible hyperplasia may be caused by lower testosterone production and inadequate inhibin signalling due to missing germ cells.
    Reproductive Biology and Endocrinology 05/2013; 11(1):50. DOI:10.1186/1477-7827-11-50 · 2.23 Impact Factor
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    • "Fractional radiotherapy to testes for treatment of carcinoma-insitu of the testis usually involves high doses of radiotherapy which lead to permanent azoospermia [21–23]. Interestingly, the Leydig cells of the testis seem far more resistant to radiation effect and therefore testosterone production is usually less impaired in patients receiving even relatively high dosages of radiotherapy relative to its effects on sperm production [24]. In addition, libido and erection will usually remain normal in the male and its sterility that is the main concern. "
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    ABSTRACT: Infertility can arise as a consequence of treatment of oncological conditions. The parallel and continued improvement in both the management of oncology and fertility cases in recent times has brought to the fore-front the potential for fertility preservation in patients being treated for cancer. Oncologists must be aware of situations where their treatment will affect fertility in patients who are being treated for cancer and they must also be aware of the pathways available for procedures such as cryopreservation of gametes and/or embryos. Improved cancer care associated with increased cure rates and long term survival, coupled with advances in fertility treatment means that it is now imperative that fertility preservation is considered as part of the care offered to these patients. This can only be approached within a multidisciplinary setting. There are obvious challenges that still remain to be resolved, especially in the area of fertility preservation in prepubertal patients. These include ethical issues, such as valid consent and research in the area of tissue retrieval, cryopreservation, and transplantation.
    Obstetrics and Gynecology International 03/2010; 2010:160386. DOI:10.1155/2010/160386

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