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Cystic dysplasia of the testis.

Cystic dysplasia of the testis (CDT) is a rare congenital defect that results in the formation of numerous irregular cystic spaces within the mediastinum testis. We describe a 4-year-old boy with right testicular swelling who underwent orchiectomy for CDT after a preoperative ultrasound examination revealed a multicystic, anechoic lesion. Grossly, the lesion was 2 cm in size and was composed of multiple, irregularly shaped cystic spaces lined by flattened cuboidal epithelium. Immunohistochemical studies revealed that the epithelial cells expressed keratin, vimentin, and epithelial membrane antigen. Both the histologic appearance of the cyst lining and the immunohistochemical profile resembled the epithelium of rete testis. In our review of the literature 10 cases (including this lesion) of CDT have been described. A defect in the connection between the efferent ductules, derived from the mesonephric epithelium, and the rete testis and seminiferous tubules, derived from the gonadal blastema, is currently thought to be the most likely explanation of the pathogenesis of CDT.

Child, Preschool↗

Quantification of apoptosis (programmed cell death) in mammalian testis by DNA-fragmentation ELISA.

Apoptosis (programmed cell death) could contribute to fluctuations in sperm production and involution of testis in dependence on seasonal, genetic, environmental or individual factors. Investigations of such factors require a reliable quantitative examination of apoptotic processes. Therefore, a standardized procedure was developed for quantification of apoptosis in samples of testicular parenchyma in bull. This test is based on a highly sensitive DNA-fragmentation ELISA which was used originally for somatic cells in culture. Aliquots of testicular parenchyma were minced and homogenized by freezing/thawing and subsequent sonification at 4 degrees C. In comparison, aliquots were lysed in original buffer from the cell death detection ELISA-kit. Nucleosomes from the cell cytoplasm were obtained in supernatant of homogenate or lysate after centrifugation. The absorbance was linear over the range of sample concentrations from 5 to 20 microg testis equivalent/100 microl solution. Therefore, samples were standardized to a final concentration of 10 microg testis equivalent/100 microl. The recorded values were expressed in units per mg tissue (U/mg). The method was used to study testicular apoptotic processes in the guinea pig and roe deer. The results showed that apoptosis can be detected in testicular homogenate prepared from 0.01 mg testis parenchyma within 24 h after recovery of testes without significant variations. Detectable apoptosis levels showed differences among sexually active guinea pig (7.08 +/- 1.95 U/mg), roe deer (16.32 +/- 3.45 U/mg), and cattle (29.0 +/- 7.1 U/mg). This species-specificity suggests different cross reactivity of the monoclonal antibody used in the ELISA. A significantly higher amount of testicular apoptosis was detected in a population of guinea pigs with increased inbreeding coefficients (f = 0.785 - 0.998) than in outbred animals (11.41 +/- 3.50 U/mg and 7.08 +/- 1.95 U/mg, respectively). The inverse relationship of testicular apoptosis and proliferation in these two populations was significant (r = -0.531; P < 0.05). In conclusion, the relative simplicity and high sensitivity of this nonradioactive method provides a useful approach to investigate spermatogenesis under different conditions. Results in the guinea pig showed that apoptosis plays an important role in the regulation of gonadal efficiency.

Journal Article↗

Sensitivity of testis tumour cells to chemotherapeutic drugs: role of detoxifying pathways.

In contrast to most other types of cancer, metastatic testicular germ cell tumours (TGCT) are cured in most patients using cisplatin-based combination chemotherapy. The biochemical mechanisms underlying this sensitivity have not been defined. Drug detoxification can modulate response to chemotherapy in vivo and in vitro, and therefore we measured levels of glutathione (GSH), glutathione-S-transferase (GST) and both constitutive and cisplatin- and dexamethasone-induced levels of metallothionein (MT) in five human testis tumour cell lines. The levels were compared with those in five human bladder cancer cell lines and two cell lines with cisplatin resistance acquired in vitro. GSH levels were relatively low in the testis tumour cell lines, as might be expected in drug-sensitive cells, and there was a 77-fold increase in GSH levels in the cisplatin-resistant testis tumour cell line. GST levels were similar in the two cell types, while metallothionein levels were relatively high in the testis tumour cell lines. These data indicate that GSH may contribute to the sensitivity of TGCT to chemotherapy, and that GSH expression may be involved in the acquisition of cisplatin resistance in these tumours.

Antineoplastic Agents↗

Immunohistochemical study of flotillin-1 in rat testis with ischemia/reperfusion injury.

To investigate the involvement of flotillin-1 in acute experimental testicular torsion, we examined the expression and cellular localization of flotillin-1 and cathepsin D in the rat testis with ischemia/reperfusion (I/R) injury. Western blot analysis showed that the expression of flotillin-1 increased significantly 6h after I/R and that the level remained elevated for 48 h. Immunohistochemically, flotillin-1 was constitutively localized in some Sertoli cells, peritubular myoid cells, and interstitial cells in the normal testis. After I/R injury, Sertoli cells in the damaged tubules were intensely immunostained for flotillin-1 at 24 and 48 h after I/R. Flotillin-1 was also detected in some inflammatory cells in the interstitial space around damaged tubules. Furthermore, flotillin-1 was colocalized with cathepsin D, a lysosomal marker, in normal testis (mainly in Sertoli cells), and the colocalization was greater in Sertoli cells and macrophages in I/R injured testes. Therefore, we postulate that flotillin-1 immunoreactivity is increased in some Sertoli and inflammatory cells (especially in ED1-positive activated macrophages) in testicular torsion and that flotillin-1 in the injured testis associates with lysosomes in Sertoli cells and macrophages, activating subsequent signals in inflammatory macrophages and Sertoli cells after I/R.

Animals↗

Management of stage I testis cancer.

OBJECTIVE: Over the last 5 years the management of stage I testis cancer has changed tremendously. This review focuses on the latest changes in diagnostics and treatment of clinical stage I non-seminomatous and seminomatous germ cell tumors. METHODS: A non-structured literature search (MEDLINE) was performed, including recently published papers (up to March 2006) on the subject. RESULTS: Organ-sparing surgery has become an accepted approach to treat malignant and nonmalignant tumours in a solitary testis. With certain precautions and adjuvant radiotherapy, this approach has proven to be as effective as orchidectomy. Prognostic factors strongly influence the decision for or against adjuvant treatment in seminoma and non-seminoma. With the help of a risk-adapted approach, about 50% of patients with clinical stage I testis cancer will favour close surveillance instead of immediate adjuvant treatment. Several well-conducted trials have helped to substantiate the management. Surgical staging by retroperitoneal lymph node dissection became an exception. Patients with non-seminoma with high risk for occult metastatic disease will favour adjuvant chemotherapy and in patients with seminoma radiotherapy with reduced dosage will be challenged by carboplatin monotherapy. CONCLUSION: With adequate diagnostics and treatment, 100% of patients with stage I testis cancer will survive. Future research will focus on quality control, adherence to guideline recommendations, and further reduction of treatment to diminish the risk of late sequalae for patients with adjuvant radiotherapy or chemotherapy.

Chemotherapy, Adjuvant↗

Bilateral asynchronous metastatic carcinoid tumor of the testis.

Carcinoid tumor of the testis represents only 0.23% of all testicular malignancies. We report the first case of bilateral asynchronous carcinoid tumor of the testis with a primary site in the small bowel. A 49-year-old man presented with several months of painless enlargement of the left testis. Orchiectomy revealed carcinoid tumor. The patient presented to the emergency room 2 weeks later and was found to have small bowel obstruction due to an ileal mass. The resected mass was the primary source of the carcinoid tumor. Four years later, examination revealed carcinoid tumor in his remaining testis.

Abdominal Neoplasms↗

Transcutaneous high-intensity focused ultrasonography can cure testicular cancer in solitary testis.

OBJECTIVES: To report the long-term results in 7 patients (including the 5-year results in 3 patients) after high-intensity focused ultrasonography (HIFU) combined with irradiation to treat testicular tumors in a solitary testis. METHODS: Transcutaneous HIFU ablation of testicular tumors is based on a technique using a piezoceramic transducer operating at 4.0 MHz with a site intensity of 1600 to 2000 W/cm2. In a Phase II trial, 7 patients with the typical sonographic pattern of a tumor in a solitary testis were treated with transcutaneous HIFU, as a minimally invasive organ-preserving approach, followed 6 weeks later by prophylactic testicular irradiation (range 18 to 20 Gy). The aim was to ablate the entire cancer in a single therapeutic HIFU session. In all 7 patients, the contralateral testis had previously been removed because of testicular cancer. RESULTS: One patient received two cycles of chemotherapy for a single suspicious retroperitoneal lymph node diagnosed 6 months after HIFU. The other 6 protocol-treated patients remained tumor free at a mean follow-up of 42 months (range 3 to 93). One patient, who had refused postoperative irradiation, developed a recurrent tumor within 6 months. No patient showed any signs of clinical hypogonadism, and the International Index of Erectile Function score was normal for all patients. No androgen substitution was necessary. The only adverse effect noted was a small thermal lesion of the scrotum in 1 patient. CONCLUSIONS: Despite the lack of tumor histologic examination, transcutaneous HIFU followed by irradiation permits a minimally invasive, organ-preserving, curative treatment for tumors in a solitary testis.

Adult↗

Microsurgical "testis-sparing" surgery for nonpalpable hypoechoic testicular lesions.

OBJECTIVES: With the increased use of trans-scrotal ultrasonography, the unexpected detection of nonpalpable hypoechoic testicular lesions has become more frequent. The different approaches vary from radical orchiectomy to simple ultrasound follow-up, but definitive guidelines do not yet exist about the management of these lesions. We report our series of patients with hypoechoic testicular lesions who underwent surgical exploration with the aid of an operating microscope. METHODS: A total of 7 patients were considered for microsurgical exploration of a nonpalpable hypoechoic testicular lesion from April 2003 to June 2005. The hospital records and ultrasound and operative reports were reviewed retrospectively. RESULTS: The side of the lesion was the left testis in 4 patients and the right testis in 3. The mean size of the hypoechoic area was 5.7 +/- 4.6 mm (range 2.5 to 16). The microsurgical technique allowed us to identify and successfully excise the lesion in all patients. Intraoperative frozen section examination revealed a benign lesion in 6 cases and testicular intraepithelial neoplasia in 1. The patient with testicular intraepithelial neoplasia underwent radical orchiectomy. The definitive histologic analysis always confirmed the frozen section examination report. The patients were evaluated clinically and by ultrasonography for a mean follow-up of 15 months. No complications occurred. CONCLUSIONS: Microsurgical exploration of the testis combined with frozen section examination represents a safe, effective, and reliable technique for evaluation of nonpalpable hypoechoic testicular lesions. This approach has significant advantages and should be considered in particular for patients with a solitary testis or presenting with bilateral lesions and wishing to father a child.

Adult↗

Lymphomas of the testis-results of treatment 1960-77.

Fifty-one patients with malignant lymphoma presenting in the testis are reported. The tumours were all diffuse non-Hodgkin's lymphoma. Eight patients had bilateral involvement. Fifty-three per cent of patients had evidence of spread beyond the testis at presentation and 75% at some time. The actuarial survival for all patients was 20% and for patients with disease apparently confined to the testis 40%. There was a survival advantage for patients with right sided tumours and lymphocytic histology. Chemotherapy using the VAP regime followed by radiotherapy to sites of bulky disease is recommended for patients with evidence of spread at presentation. For patients with disease apparently confined to the testis it is suggested that consideration should be given to adjuvant chemotherapy following radiotherapy to the abdominal nodes and scrotum.

Adult↗

Inguinal hernia revisited through comparative evaluation of peritoneum, processus vaginalis, and sacs obtained from children with hernia, hydrocele, and undescended testis.

BACKGROUND/PURPOSE: Histological structures of peritoneum, processus vaginalis, and sacs obtained from girls with inguinal hernia and boys with inguinal hernia, hydrocele, and undescended testis have been compared through immunohistochemical features to evaluate if any clue descriptive for the etiology of inguinal hernia exists. METHODS: Parietal peritoneums (n = 6), processus vaginalises (n = 4), female hernia sacs (n = 5), male hernia sacs (n 12), and sacs from hydrocele (n = 5) and undescended testis (n = 9) were stained with indirect immunoperoxidase method. Anti-CD9, CD26, CD29, CD31, CD36, CD44, CD49a, CD49b, CD49c, CD49d, CD49e, CD49f, CD54, CD55, CD56, CD62E & P, CD71, CD98, CD102, CD106, CD146, CD151 monoclonals and NFL-NPH, S-100 antiserums were used. The histological structures of each group of samples were identified and compared. RESULTS: Smooth muscle layers have been encountered within the walls of hernia sacs of both boys and girls. Although the hydrocele sacs have shown smooth muscle bundles distributed as patchy areas, smooth muscle bundles have been observed infrequently among sacs from patients with undescended testis. Peritoneum and processus vaginalis samples have been free of smooth muscle. CONCLUSIONS: Inguinal hernia during childhood seems to be related to the presence of smooth muscle within the wall of the sac. The smooth muscle bundles may have played a role both in prevention of obliteration and clinical outcome. Because the sacs associated with undescended testis are without smooth muscles, and herniation is not a frequent association, they may not share the same etiologic basis with inguinal hernia.

Child↗

Clinical stage I testis cancer: long-term outcome of patients on surveillance.

PURPOSE: The long-term outcome results of a prospective surveillance trial for clinical stage I nonseminomatous germ cell tumors of the testis (NSGCT) are reported in an effort to define the natural history of clinical stage I testis cancer treated with orchiectomy alone, and to determine if a subset of patients exists that may be suitable for surveillance. MATERIALS AND METHODS: Between September 1979 and December 1987, 105 patients were entered into the study. Patients with persistent elevation of serum tumor markers (AFP, BHCG, and LDH) following orchiectomy, stage T2-T4 primary tumors, any evidence of metastases and pure choriocarcinoma or pure seminoma on histology were excluded from study. Enrolled patients underwent periodic physical examination, serological testing and radiological imaging according to an established protocol. RESULTS: Median followup was 11.3 years. Of the patients 78 (74.3%) have remained disease-free and 27 (25.7%) have experienced relapse. Of the patients with relapse 24 are currently disease-free after treatment for relapse for a median duration of 10.8 years and 3 (2.8%) died of disease. All relapses occurred within 24 months of orchiectomy (median 5 months). Significant predictors of relapse during surveillance were a predominant embryonal carcinoma histology (p = 0.016) and vascular invasion (p = 0.0005). In patients with neither embryonal carcinoma nor vascular invasion the relapse rate was 12%, and no patients died of disease. CONCLUSIONS: With extended followup 74% of men with clinical stage I (T1) nonseminomatous germ cell tumor of the testis were cured by orchiectomy alone, and cure rates approached 90% when patients with predominant embryonal carcinoma histology or vascular invasion were excluded from surveillance. These findings support management by surveillance alone in a highly select cohort of men who have clinical stage I (T1) nonseminomatous germ cell tumor of the testis, normal serum markers following orchiectomy and neither predominant embryonal carcinoma or vascular invasion on histology.

Adolescent↗

Is preoperative laparoscopy useful for impalpable testis?

PURPOSE: Laparoscopic assessment of pelvic anatomy has gained wide popularity over the years. Today surgical treatment of impalpable testis is nearly always preceded by diagnostic laparoscopy. The actual role of such a procedure remains undefined. We performed a prospective randomized clinical trial in patients with impalpable testis to evaluate the clinical usefulness of laparoscopy before surgical exploration. MATERIALS AND METHODS: We studied pediatric, age matched patients with impalpable testis who were randomized to group 1-30 who underwent open surgery only and group 2-31 who underwent laparoscopy and open surgery. Anatomical findings, operative procedures, operative time and cost, number of recurrences and testicular volume at followup were then compared in the 2 groups. RESULTS: There were no statistically significant differences in the 2 groups for any of the considered parameters except operative cost and time, which were significantly higher in the laparoscopy group. CONCLUSIONS: Preoperative laparoscopy does not provide any significant advantage over open surgery for treating impalpable testis.

Child↗

Examination for intratubular germ cell neoplasia at operation for undescended testis in boys.

A total of 843 consecutive boys (median age 12.7 years) who had undergone testicular biopsy at operation for undescended testis was followed into adulthood (median age 25.2 years) to examine for testicular germ cell neoplasia. Five cases of testicular germ cell neoplasia were identified, including 1 nonseminoma of the contralateral testis, which had been treated before surgery for an undescended testis, 1 nonseminoma found at followup, 1 seminoma and 2 intratubular germ cell neoplasms. Of the later 3 patients 1 had a 45,X/46,XY karyotype and 2 had abnormal external genitalia. Previous testicular biopsy from the patient in whom nonseminoma was noted at followup showed Sertoli cells only. We recommend that testicular biopsy be performed at operation for undescended testis in boys with abnormal sex chromosomes, particularly 45,X/46,XY karyotype, and in those with abnormal external genitalia. The pattern of Sertoli cells only in biopsies from boys does not preclude the occurrence of testicular cancer in adulthood.

Biopsy↗

Laparoscopy in the management of the nonpalpable testis.

Laparoscopy was performed at operation in 32 patients between 7 and 63 months old (average age 31 months), who had 33 nonpalpable testes. Of the testes 7 (21.2 per cent) were in the inguinal region or just proximal to the internal ring, 5 (15.2 per cent) were in a high intra-abdominal position and 21 (63.6 per cent) were absent. In every instance of a nonpalpable gonad in which a testis was found to be absent at operation the vas and gonadal vessels were observed laparoscopically to exit the inguinal ring or to end blindly just proximal to the internal inguinal ring. A hernia or patent processus vaginalis was not observed in these 21 cases. In every case of an absent testis the contralateral testis was located normally in the scrotum. Furthermore, when a hernia was observed laparoscopically a testis was found on the ipsilateral side at the level of the internal ring or more distally.

Abdomen↗

The absence of premalignant changes in the cryptorchid testis before adulthood.

Previous investigators have reported that premalignant changes in the form of abnormal germ cells can be detected in the cryptorchid and infertile adult testis. These cells are characterized by a thin rim of pale-staining cytoplasm, a large hyperchromatic nucleus and prominent nucleoli. We studied 113 biopsies from 102 patients to determine if these abnormal germ cells occur in the nonadult cryptorchid testis. The patients ranged in age from 3 months to 16 years. Evaluation of testicular tissue by light microscopy disclosed histological alterations in the undescended testis, which were those commonly ascribed to the undescended testis. However, none of the changes could be interpreted as premalignant. The abnormal germ cells described by other investigators were not found in any of these specimens.

Adolescent↗

Two rare cases of ectopic testis.

A case of pubopenile testis and a case of perineal ectopic testis are presented. The mechanism of descensus is largely positive, possibly facilitated by raised intra-abdominal pressure. The testis is usually guided by the gubernaculum and ectopia results from gubernacular failure. The ectopic testis is relatively rare but is easily recognized and treated by orchiopexy.

Child, Preschool↗

Müllerian-type epithelial tumor arising within a torsed appendix testis.

Because it is a remnant of the müllerian duct system, the appendix testis contains müllerian epithelium that theoretically may produce epithelial tumors similar to those that occur in the female genital tract. Few reports of tumors of müllerian origin arising in the testis exist, and rarely are neoplasms arising from the appendix testis identified. We present a case of a serous cystic neoplasm of low malignant potential derived from müllerian-type epithelium that was located in the torsed appendix testis of a young, otherwise healthy, boy.

Adolescent↗

Fertility issues and their management in men with testis cancer.

Although a curable malignancy, testis cancer and its treatment have unique associated morbidities that largely affect reproductive dysfunction. In this focused review, the factors that contribute to infertility in men with testis cancer are outlined. The treatment-specific risks to fertility that accompany cancer management are also discussed. Contemporary methods of overcoming infertility in testis cancer patients are addressed, and several exciting and promising experimental approaches to the preservation or restoration of fertility for men with testis cancer are presented.

Humans↗