Peripubertal orchidectomy transitorily affects age-associated thymic involution in rats

The role of gonadal hormones in induction and, particularly, maintenance/progression of rat thymic involution, which normally starts around puberty, was reassessed by examining the effects of peripubertal orchidectomy on thymic weight and morphometric parameters at different times up to the age of 10 months. Up to 6 months post-castration both thymic weight and cellularity in orchidectomized (Cx) rats were greater than in age-matched control rats, sham Cx (Sx). The increase in thymic cellularity reflected an increase in thymocyte proliferation rate (the proportion of proliferating cells was 18.6 ± 0.7% in 2-month-old Cx (N = 5) vs 13.4 ± 0.3% (N = 5) in age-matched Sx rats) followed by reduced sensitivity to apoptotic signals (apoptotic thymocytes were 9.8 ± 0.9% in 2-month-old Cx (N = 5) vs 15.5 ± 0.3% (N = 5) age-matched Sx rats). However, 9 months post-orchidectomy, neither thymic weight and cellularity nor any of the morphometric parameters analyzed differed between Cx and control rats. The reduction of thymic cellularity in Cx rats to control values may be related to increased sensitivity of their thymocytes to apoptotic signals in culture (72.6 ± 1.2% in 10-month-old vs 9.8 ± 0.9% in 2-month-old Cx rats) followed by reduced responsiveness to proliferative stimuli (14.1 ± 0.2% in 10-month-old vs 18.6 ± 0.7% in 2-month-old Cx rats). Thus, the study indicates that the effects of peripubertal orchidectomy on thymic weight and cellularity, as well as on the main morphometric indices, are long-lasting but not permanent, i.e., that removal of the testes can only postpone but not prevent age-related organ atrophy and consequently functional deterioration of the immune system.

Orchidectomy enhances the effects of phenylephrine in rat isolated portal vein

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Enhanced Proinflammatory Cytokine Response to Bacterial Lipopolysaccharide in the Adult Male Rat after either Neonatal or Prepubertal Ablation of Biological Testosterone Activity.

A sex steroid-dependent modulation of the immune function in mammals is accepted, and evidence suggests that while estrogens enhance, androgens inhibit the immune response. The aim of this study was to explore in the adult male rat the effect of either neonatal flutamide (FTM) treatment or prepubertal orchidectomy (ODX) on endocrine markers in the basal condition and peripheral tumor necrosis factor alpha (TNFα) levels during inflammatory stress. For these purposes, (1) 5-day-old male rats were subcutaneously injected with either sterile vehicle alone or containing 1.75 mg FTM, and (2) 25-day-old male rats were sham operated or had ODX. Rats were sacrificed (at 100 days of age) in the basal condition for determination of peripheral metabolite levels. Additional rats were intravenously injected with bacterial lipopolysaccharide (LPS; 25 μg/kg body weight, i.v.) and bled for up to 4 h. Data indicate that (1) ODX increased peripheral glucocorticoid levels and reduced those of testosterone, whereas FTM-treated rats displayed low circulating leptin concentrations, and (2) LPS-induced TNFα secretion in plasma was significantly enhanced in the FTM and ODX groups. Our study supports that neonatal FTM treatment affected adiposity function, and adds data maintaining that androgens have a suppressive role in proinflammatory cytokine release in plasma during inflammation.

Well-differentiated papillary mesothelioma of the tunica vaginalis testis: imaging on Tc-99m heat-denatured red blood cell scintigraphy.

An 18-year-old man presented with a growing painless left scrotal mass. Sonography showed a hydrocele and a homogeneous, well-encapsulated left extratesticular mass with similar echogenicity as the normal testis, suggestive of a splenogonadal fusion. To substantiate the diagnosis, the patient underwent Tc-99m heat-denatured red blood cell scintigraphy showing normal physiological hyperactivity in the spleen but activity similar to the blood pool projecting on the upper part of the left testis. This made testicular splenic tissue less likely. The patient underwent resection and histopathology revealed a well-differentiated papillary mesothelioma. Inguinal orchidectomy was subsequently performed and the patient was free of recurrence at 18 months.

Primary testicular lymphoma: review

Primary testicular lymphoma is a rare form of non-Hodgkin's lymphoma. It occurs more frequently in older patients, and it is a potentially lethal disease. For early stages (I and II), the management consists of orchidectomy followed by chemotherapy combined with monoclonal antibodies directed against the CD20 antigen and scrotal radiotherapy (sanctuary site) with/or without iliac and/or paraaortic lymph node radiotherapy. For advanced stages (III and IV), chemo-immunotherapy is the treatment of choice while scrotal radiotherapy can be discussed. Both in early or advanced disease, intrathecal chemotherapy is necessary to prevent central nervous system relapse. New molecular approaches and/or more aggressive treatments are to be explored in this rare disease. To cite this journal: Oncologie 13 (2011).

Outcome and patterns of failure in testicular lymphoma: a multicenter Rare Cancer Network study.

PURPOSE: To assess the outcome and patterns of failure in patients with testicular lymphoma treated by chemotherapy (CT) and/or radiation therapy (RT). METHODS AND MATERIALS: Data from a series of 36 adult patients with Ann Arbor Stage I (n = 21), II (n = 9), III (n = 3), or IV (n = 3) primary testicular lymphoma, consecutively treated between 1980 and 1999, were collected in a retrospective multicenter study by the Rare Cancer Network. Median age was 64 years (range: 21-91 years). Full staging workup (chest X-ray, testicular ultrasound, abdominal ultrasound, and/or thoracoabdominal computer tomography, bone marrow assessment, full blood count, lactate dehydrogenase, and cerebrospinal fluid evaluation) was completed in 18 (50%) patients. All but one patient underwent orchidectomy, and spermatic cord infiltration was found in 9 patients. Most patients (n = 29) had CT, consisting in most cases of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) with (n = 17) or without intrathecal CT. External RT was delivered to scrotum alone (n = 12) or testicular, iliac, and para-aortic regions (n = 8). The median RT dose was 31 Gy (range: 20-44 Gy) in a median of 17 fractions (10-24), using a median of 1.8 Gy (range: 1.5-2.5 Gy) per fraction. The median follow-up period was 42 months (range: 6-138 months). RESULTS: After a median period of 11 months (range: 1-76 months), 14 patients presented lymphoma progression, mostly in the central nervous system (CNS) (n = 8). Among the 17 patients who received intrathecal CT, 4 had a CNS relapse (p = NS). No testicular, iliac, or para-aortic relapse was observed in patients receiving RT to these regions. The 5-year overall, lymphoma-specific, and disease-free survival was 47%, 66%, and 43%, respectively. In univariate analyses, statistically significant factors favorably influencing the outcome were early-stage and combined modality treatment. Neither RT technique nor total dose influenced the outcome. Multivariate analysis revealed that the most favorable independent factors predicting the outcome were younger age, early-stage disease, and combined modality treatment. CONCLUSIONS: In this multicenter retrospective study, CNS was found to be the principal site of relapse, and no extra-CNS lymphoma progression was observed in the irradiated volumes. More effective CNS prophylaxis, including combined modalities, should be prospectively explored in this uncommon site of extranodal lymphoma.

Efeito da orquidectomia e da reposição com testosterona sobre as respostas vasomotoras de veias isoladas de rato a agonistas simpatomiméticos

Pós-graduação em Ciências Biológicas (Farmacologia) - IBB

Análise comparativa por meio da densidade óptica radiográfica entre o grau de osteopenia induzida pela fenitoína e ausência hormonal em ratos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Efeito da orquidectomia, seguida ou não de reposição com testosterona, sobre as respostas vasomotoras de veias de rato à estimulação de receptores adrenérgicos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

[Follow-up in a boy with Leydig cell tumor after selective surgery]

A 8(6/12) year-old-boy presented with precocious puberty and a slightly enlarged left testis. After a detailed examination a Leydig cell tumour was diagnosed. Surgical exploration revealed an encapsulated tumour, 2.7 cm in length, which was selectively removed without orchidectomy. Within one year the clinical signs of pubertal precocity disappeared, the bone age did not further advance and height velocity declined from 8.2 cm / year (+3.9 SDS) to 4.1 cm/year (-1.0 SDS). Physiologically, he entered puberty at the chronological age of twelve years, presenting at that age, in comparison to his peer group, a slightly decreased pubertal growth spurt. However, bearing in mind that being precocious in puberty he started in fact his pubertal growth spurt at a far earlier age, therefore, this acceleration of height before operation has to be added to the centimetres gained during pubertal development thereafter resuiting consequently in an absolute normal pubertal growth spurt. This underlines the fact that the individual growth spurt and, therefore, the total amount of centimetres gained is very much robust. Ten years later, the patient ended up well within his familial target height and remained free of disease. We report on a long-term follow-up of a prepubertal boy after testis-sparing surgery for Leydig-cell-tumour.

Outcomes of Second Look Exploration in Testicular Torsion of Children

Background: Testicular torsion (TT), or twisting of the testicle resulting in a strangulation of the blood supply, occurs in men whose tissue surrounding the testicle is not well attached to the scrotum. It is important to emphasize that testicular torsion is a medical emergency. Objectives: The aim of this study is to evaluate the second look exploration and outcomes in TT. Patients and Methods: Seventy boys out of 124 patients underwent early exploration and 48 hours later second look exploration due to TT. All patients were checked with preoperative color-doppler ultrasonography (CDU) and intraoperative bleeding test. Data included age at admission, side of pathology, relation of TT with season of year, duration of preoperative history, degree of testicular torsion, CDU findings, and degree of bleeding; results of second look exploration, follow-up, and outcomes were analyzed. Results: Totally 70 patients were included in this study within five years, of which mean age was 28.6 ± 32.9 months (range 1 to 144), 48% of our patients had nausea and vomiting. Preoperative CDU showed absent/weak flow in 50 (71%) cases. Winter showed most frequently (44%) referred cases of testicular torsion. Orchidopexy was performed in 44 (63%) and orchidectomy in 26 (37%) cases after second look exploration. Mean follow-up duration was 3.1 ± 1.4 years. 4 (9%) cases in orchidopexy group developed testicular atrophy during follow-up, all four cases had a history of longer than 12 hours and grade II testicular bleeding test intra-operatively. Other orchidopexy patients salvaged. 26 patients, who were in grade III, underwent orchidectomy in second look exploration. Conclusions: TT requires emergency attention. The ischemia time of the testis is traditionally after 6 hours, and imaging or other diagnostic modality should not be a cause of delay. Early surgical exploration is modality of choice, and second look exploration after 48 hours can be more effective and salvageable in these patients.