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Laparoscopic orchiectomy for unilateral intra-abdominal testis.

PURPOSE: A brief description of laparoscopic orchiectomy for undescended testis and a representative case report. METHODS: A 22-year-old Chinese man was admitted for removal of an intra-abdominal testis. Laparoscopic orchiectomy was used to remove the testis at the time of laparoscopic orchiectomy. The patient had an uneventful postoperative course. RESULTS: A concurrent inguinal hernia was discovered during the procedure and repaired. CONCLUSIONS: The use of laparoscopic surgery has proven to be a safe and effective means of treatment for the intra-abdominal testis.

Journal Article↗

Testicular germ cell cancer despite previous local radiotherapy to the testis.

BACKGROUND: Testicular intraepithelial neoplasia (TIN, also carcinoma in situ of the testis) is the uniform precursor of testicular germ cell cancer. Local radiotherapy to the testis with dosages of 18-20 Gy has been found to safely eradicate TIN and germ cells, too. Thus, the general assumption is that the development of invasive germ cell tumours can be prevented by this radiotherapy. PATIENTS AND METHODS: Herein, we report two patients with one-sided testicular tumour and biopsy-proven contralateral TIN. Both of them developed germ cell neoplasms in the remaining testis although local radiotherapy with 20 Gy had been applied to the testis. RESULTS: One patient developed pure seminoma 7 years after completion of radiotherapy, the other developed a combined tumour consisting of embryonal carcinoma and seminoma after 5 years. Treatment consisted of orchiectomy in each of the cases. Histologically, both had TIN in the testicular tissue surrounding the new growths. CONCLUSIONS: Pathogenetically, a small fraction of radioresistent TIN cells overcoming irradiation and progressing to full-blown germ cell cancer in the later course may be the histogenetic clue to explain these unexpected events. Other explanations, though less probable, could be technical radiotherapeutic failure due to targeting problems and a pre-existing radioresistent germ cell tumour in the irradiated testicle.

Adolescent↗

The role of retroperitoneal surgery in testis cancer.

Testis cancer is today a curable malignancy. But controversy remains about the appropriate management of patients presenting different stages. There is an increasing interest in surveillance rather than in primary retroperitoneal lymph node dissection (RPLND) for stage I non-seminomatous germ cell tumors (NSGCT). Adjuvant chemotherapy has become an efficient treatment option for high risk non-seminomatous germ cell testis cancer, however, biological and histologic risk factors of the primary tumor are not yet precisely defined. To determine the appropriate management of patients with testicular cancer, postoperative morbidity after RPLND and risk of chemotherapy-induced morbidity must be balanced. Whoever reviews the literature must take into consideration that the excellent postoperative results after RPLND depend on high volume and large experience with testis cancer. As treatment morbidity and its intensity have a major impact on testis cancer patient quality of life, the choice of management must be based on the patient's social situation, his personal needs, and the doctor's experience and resources.

Antineoplastic Agents↗

The effect of medroxyprogesterone acetate on bone marrow and testis during cytotoxic chemotherapy.

The effect of medroxyprogesterone acetate (MPA) on the mitotic activity of bone marrow and testis during chemotherapy was investigated experimentally in an animal study. A total of 120 male Swiss albino mice were included in this study. Six groups were formed, each consisting of 20 mice. Low-dose MPA (LD-MPA) (15 mg/kg), high-dose MPA (HD-MPA) (100 mg/kg), LD-MPA plus cyclophosphamide (CP) (65 mg/kg), HD-MPA plus CP (65 mg/kg), and CP (65 mg/kg) were administered to the test groups and no drug was administered to the control group. Bone marrow samples and testis were examined for mitotic activity rate (MAR) on days 0, 18, 22, 26, and 30. In groups with regimens containing CP, MAR of hematopoietic cells in bone marrow was suppressed significantly (p<0.05). There was no difference in MAR of hematopoietic cells in bone marrow between the groups given MPA or not (p>0.05). Mitotic activity rate of the testis cells was significantly suppressed in groups with regimens containing MPA (p<0.05). In conclusion, MPA inhibited mitotic activity of testis, but there was no effect on the mitotic activity of bone marrow. These data do not seem to confirm the hypothesis of a myeloprotective effect of MPA.

Animals↗

Clinical profile and problems of management of 108 cases of germ cell tumours of testis at Institute Rotary Cancer Hospital, All India Institute of Medical Sciences New Delhi 1985-1990.

A retrospective analysis of 108 cases of primary germ cell tumours of testis seen over a 6 year period at Institute Rotary Cancer Hospital of All India Institute of Medical Sciences, New Delhi is presented. There were 45 (42%) cases of seminoma and 63 (48%) of non-seminomatous germ cell tumours (NSGCT). The median age at presentation was 35 and 30 years respectively. Almost half (56) patients presented in advanced stage (stages IIc-IV). Tumours in undescended testis formed an important subgroup (14%). The standard approach of treatment was radiotherapy in stages I & II seminomas and chemotherapy in bulky seminomas and metastatic NSGCT. Chemotherapy protocols used were VAB-6 and PVB. Although a policy of surveillance has been practised for stage I NSGCT, it is debatable whether it is universally suitable for our patients. The results of treatment in low volume disease are comparable to that in the west but the management of bulky disease requires a more aggressive approach. Unfortunately only 74 out of 108 (68.5%) patients were able to complete the treatment prescribed. Most of the defaulters were from the chemotherapy group because of inability to afford the drugs. The probability of survival of those who completed treatment was 0.77 at 4 years. Since testicular tumours are largely curable, a more vigorous policy of detection, follow up and treatment needs to be pursued. Better screening of children with undescended testis will reduce cancer in this group. Failure to provide chemotherapy to all patients is particularly unfortunate for a curable disease like testis cancer.

Adult↗

Clinical aspects of male germ cell apoptosis during testis development and spermatogenesis.

Apoptosis appears to have an essential role in the control of germ cell number in testes. During spermatogenesis germ cell deletion has been estimated to result in the loss of up to 75% of the potential number of mature sperm cells. At least three factors seem to determine the onset of apoptosis in male germ cells: (1) lack of hormones, especially gonadotropins and androgens; (2) the specific stage in the spermatogenic cycle; (3) and the developmental stage of the animal. Although male germ cell apoptosis has been well characterized in various animal models, few studies are presently available regarding germ cell apoptosis in the human testis. The first part of this review is focused on germ cell apoptosis in testes of prepubertal boys, with special emphasis on apoptosis in normal and cryptorchid testes. A higher percentage of apoptotic spermatogonia was seen in the cryptorchid testes than in the scrotal testes. The hCG-treatment increased the number of apoptotic spermatogonia. The hCG-treatment-induced apoptosis in spermatogonia had severe long-term consequences in reproductive functions in adulthood. Increased apoptosis after hCG-treatment was associated with subnormal testis volumes, subnormal sperm density and pathologically elevated serum FSH. This finding indicates that increased apoptosis in spermatogonia in prepuberty leads to disruption of testis development. To evaluate the role of apoptosis in human adult testes, apoptosis was induced in seminiferous tubules that were incubated under serum-free conditions in the absence or presence of testosterone. Most frequently apoptosis was identified in spermatocytes. Occasionally some spermatids also showed signs of apoptosis. In short term incubations apoptosis was suppressed by testosterone. Our findings lead to the conclusion that apoptosis is a normal, hormonally controlled phenomenon in the human testis. The role of apoptosis in disorders of spermatogenesis remains to be established.

Journal Article↗

Testis conservation studies in germ cell cancer justified by improved primary chemotherapy response and reduced delay, 1978-1994.

OBJECTIVE: To investigate the need for the continued encouragement of early diagnosis of germ cell cancer of the testis, in view of the prevailing cure rate of 95%. PATIENTS AND METHODS: The study comprised a retrospective review of 453 unselected and previously untreated patients referred to one centre between 1978 and 1984, comparing the delay from first symptoms with the histological diagnosis. RESULTS: With a delay of < 30 days, 20% of patients had overt metastases at presentation and if the delay was > 4 months. 55% had metastases (chi-squared trend = 15.9, P < 0.001); 18% of Stage-1 patients under surveillance with a delay of < 30 days relapsed, compared with 38% of those with a delay of > 4 months. During the period 1978-1983, 16% of patients were seen after a delay of < 60 days, during the period 1984-1988 the proportion was 22% and during 1989-1994, 31% (chi-squared trend = 8.2, P < 0.004). There was a non-significant trend for a more prolonged delay in those aged < 21 years and > 40 years. Thirty-two patients had chemotherapy with the primary tumour in situ; at orchidectomy, 13 of 18 had no viable malignancy and four of five with viable malignancy also had drug-resistant metastases. Fourteen did not undergo orchidectomy; within a median follow-up of 9 years, one developed a second (histologically different) tumour after 12 years. The outcome of preliminary attempts to use neoadjuvant chemotherapy with or without partial orchidectomy for patients with tumours in a solitary testis is discussed. CONCLUSION: These findings clearly justify the continued encouragement of early diagnosis, possibly best performed as part of an extended educational programme of genital health at puberty. The long-term potential for testis conservation should be explored initially in tumours in a solitary testis.

Adult↗

Impact of diagnostic laparoscopy in the management of the unilateral impalpable testis.

OBJECTIVE: To evaluate the impact of laparoscopy on the management of children with a unilateral impalpable testis. PATIENTS AND METHODS: The study population consisted of 27 children who underwent a primary inguinal exploration for a unilateral impalpable testis. RESULTS: Twelve of 27 (44%) children had inguinal or 'peeping' testes and 10 of 27 (37%) had blind-ending vasa and vessels in the inguinal canal; four of these 10 had atrophic tubular tissue in the excised remant. Four of 27 (15%) had blind-ending vasa and vessels proximal to the internal ring. Only one child had a testis proximal to the internal ring. Only the four children (15%) with blind-ending vasa and vessels proximal to the internal ring would have benefited from a laparoscopy by avoiding an inguinal exploration. CONCLUSIONS: Because of the time, expense and limited usefulness of laparoscopy in altering the management of children with a unilateral unpalpable testis, we reserve laparoscopy for cases where inguinal exploration has failed.

Child↗

Angiogenesis and lymphangiogenesis in stage 1 germ cell tumours of the testis.

OBJECTIVE: To determine whether angiogenesis can be used as an additional prognostic indicator in patients with stage 1 germ cell tumours of the testis. PATIENTS AND METHODS: Paraffin sections were assessed immunohistochemically from 51 patients with clinical stage 1 germ cell tumours of the testis (28 seminoma, 23 teratoma) treated by orchidectomy and surveillance only. Sections were analysed for microvascular density (MVD), and expression of the angiogenic factors vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP). In addition, in the seminoma cases the presence of mRNA for the lymphangiogenic factor VEGF-C was examined by in situ hybridization, and its corresponding receptor VEGFR-3 by immunohistochemistry. RESULTS: Teratoma specimens had a significantly higher mean (range) MVD (85, 26-163; P < 0.01) than both seminoma (37, 16-91) and four normal specimens (26, 18-30). Teratoma specimens also had significantly higher VEGF expression than both seminoma and normal specimens (P < 0.01). Despite these differences between groups, and indeed individual tumours, there was no significant correlation between MVD and VEGF, or between either MVD or VEGF and relapse-free survival. TP expression was significantly greater in tumours than in normal specimens (P < 0.02) but with very little inter-tumour variation. VEGF-C mRNA and VEGFR-3 protein were detected in a third to a half of cases, with expression mostly around endothelial vessels. CONCLUSIONS: The marked differences between normal testis and tumours implicate angiogenesis in the biology of germ cell tumours of the testis. In addition, the detection of factors involved in lymphangiogenesis in some seminomas, tumours which initially metastasize primarily to lymph nodes, indicate that although not prognostic in this study, further studies are warranted in both these areas in the search for further prognostic indicators and therapeutic targets.

Adult↗

Mature teratoma arising in intraabdominal undescended testis in an infant with previous inguinal exploration: case report and review of intraabdominal testicular tumors in children.

The authors report the youngest case of postoperative intraabdominal mature testicular teratoma in a 5-year-old boy after previous exploration for impalpable testis. A total of 26 cases of intraabdominal testicular tumor in children including our case were reviewed and discussed from both the English- and the Japanese-language literature. The average age was 2.5 years, and, in the 13 children younger than 1 year there were no malignant teratomas, although there was one immature teratoma. Four of these had undergone previous inguinal exploration in which 3 patients except our patient were more than 10 years old. This case report confirms the importance of finding an intraabdominal testis at operation for impalpable testis. Early detection of the testicular location near the internal inguinal ring in these patients supports the hypothesis that the intraabdominal testicular teratoma itself may have been the primary cause of the undescended testis. Furthermore, it is suspected that many of the intraabdominal testicular malignant teratomas in adults may have arisen from these mature testicular teratomas in infants.

Child, Preschool↗

[Endocrine and morphological investigation in undescended testis (author's transl)].

Determination of the basal and LH-RH-stimulated luteinizing hormone (LH) levels as well as testicular morphology in patients with surgically treated (n equals 112) and non-treated (n equal 96) undescended testes gave the following results: Unilateral of bilateral undescended testes are probably a form of primary, secondary or tertiary hypogonadism. In a high percentage abnormal basal and stimulated serum-LH values can be demonstrated. The testosterone values are within normal limits. The gonadal tissue damage in the abnormally situated testes of prepubertal boys seem to be congenital. With increasing duration of the malposition, particularly after the onset of puberty, a secondary tissue degeneration in the dystopic testis occurs. The damaging influence on the testicular tissue caused by the abnormal position seems to take place mostly at the end of prepuberty. A decrease in the number of spermatogonia in the tubuli of dystopic testes during the first 2 years of life is physiological. A surgical repositioning of the dystopic testis into the scrotum within the first 2 years of life is not indicated. Damage of gonadal tissue in the scrotal testis caused by the dystopic testis in unilateral maldescent could not be demonstrated. The optimal space for orchidopexy is between the third and fifth year of life.

Adolescent↗

PKCtheta II, a new isoform of protein kinase C specifically expressed in the seminiferous tubules of mouse testis.

Protein kinase C (PKC) theta, a Ca(2+)-independent isoform of PKC, has been known to be expressed in skeletal muscle and T cells. In the present study, we isolated and characterized a smaller transcript expressed in the mouse testis, the cDNA of which is referred hereafter as PKCthetaII and the original PKCtheta as PKCthetaI. The cDNA clone of PKCthetaII has 2184 base pairs and 464 amino acids in the possible open reading frame, consisting of the 5' unique sequence of 20 amino acids and the PKCthetaI sequence of 444 amino acids. Genomic DNA analysis revealed that transcription of PKCthetaII is initiated from the PKCthetaII-specific exon, which is located between exons 7 and 8 of the PKCtheta gene, indicating that alternative splicing is the mechanism by which PKCthetaII is generated. PKCthetaII is expressed exclusively in the testis in an age-dependent manner with sexual maturation. In situ hybridization and reverse transcription-polymerase chain reaction of microdissected tissues clearly demonstrated that PKCthetaII is expressed in the seminiferous tubules of the mouse testis. Consistent with its molecular structure lacking the C1 regulatory domain, PKCthetaII is constitutively active as determined by an in vitro kinase assay, being independent of PKC activators, e.g. phosphatidylserine and phorbol ester. PKCthetaII may play a crucial role in spermatogenesis or some related function of the testis.

Alternative Splicing↗

The steroidogenic capacity of the aging rat testis.

Factors bearing on the steroidogenic capacity of the aging testis have been examined in Sprague-Dawley rats between 3 and 24 months of age. Neither the number nor the binding affinity of testicular receptors for 125I-hCG changed with age. The ability of the aging testis to synthesize cholesterol from octanoate was similarly undiminished. Testicular conversion of cholesterol to pregnenolone, the gonadotropin-responsive, rate-limiting portion of the androgenic pathway, remained near young adult levels with advancing age. The rate at which the testis converted pregnenolone to testosterone actually increased by almost 25% in the oldest rats. Hence, the steroidogenic capacity of the Sprague-Dawley rat testis does not decline with advancing age.

Aging↗

Cryptorchidism, hernia, and cancer of the testis.

Risk of cancer of the testis was related to nondescent and hernia in a comparison of 596 testicular cancer patients and 602 unaffected men who had been in active service in the U.S. Army between 1950 and 1970. Medical histories were obtained from routine service records. Undescended testis was associated with a testicular cancer risk 8.8 times that of normal. Among cancer patients with a history of undescended testis, seminomas were nearly twice as frequent as in the remaining patients. Of 14 patients with unilateral undescended testis, 12 had the tumor on the side of the defect. Testicular cancer risk was estimated to be 2.9 times higher in men who had reported having had an inguinal hernia than in those who had not. Side of hernia and side of tumor were not associated; histologic type was not related to history of hernia.

Cryptorchidism↗

Expression of fractalkine in the rat testis: molecular cloning of a novel alternative transcript of its gene that is differentially regulated by pro-inflammatory cytokines.

The testis is a very complex organ in which cellular communications and interactions are central to spermatogenesis and where inflammatory processes can lead to sterility. Fractalkine (CX3CL1) is a chemokine involved in cell-cell interactions and in leukocyte chemoattraction. It has been reported to be expressed in testis, but its cellular expression and function in this organ has not been described. In this study we report constitutive expression of fractalkine in the testis. Expression is higher in Leydig cells than Sertoli cells, spermatogonia, pachytene spermatocytes and elongated spermatids. In both, Sertoli cells stimulated by interleukin-1beta and tumour necrosis factor alpha, and in Leydig cells, two forms of fractalkine mRNA were observed: the previously described transcript of 3.7 kb and a novel transcript of 4.2 kb. The 4.2 kb transcript has a 5' elongation and is differentially regulated. To investigate fractalkine function in testis, we abolished Leydig cell expression of fractalkine by specific destruction of this cell type using ethylene dimethane sulphonate. The absence of fractalkine expression in Leydig cells did not seem to affect the fractalkine expression by other testicular cells. In addition, the destruction of testicular macrophages by Cl2MDP (chlodronate) did not seem to affect Leydig cell expression of fractalkine. We conclude that Leydig cell expression of fractalkine could be preferentially involved in inflammation in interstitial space whereas fractalkine expressed by germ cells may participate in the cellular interactions between germ cells and other seminiferous tubule cell types.

Alternative Splicing↗

Studies on the onset of Leydig precursor cell differentiation in the prepubertal rat testis.

Leydig cells of the adult rat testis differentiate postnatally from spindle-shaped cells in the testis interstitium during the neonatal-prepubertal period. Which spindle-shaped cell types are the precursor for Leydig cells and the stimulus for initiation of their differentiation are, however, two unresolved issues. In the present study, our objectives were to identify unequivocally which spindle-shaped cells are the precursors to Leydig cells and to test whether the initiation of their differentiation into Leydig cells depends on LH. Testes from fifteen groups of Sprague-Dawley rats (n = 4 per group) from 7-21 days of age were fixed in Bouin solution and embedded in paraffin. Immunoexpression of 3beta-hydroxysteroid dehydrogenase (3betaHSD), cytochrome P450 side-chain cleavage (P450(scc)), 17alpha-hydroxylase cytochrome P450 (P450(c17)), and LH receptors (LHR) in interstitial cells (other than fetal Leydig cells) was observed using the avidin biotin method. Of all spindle-shaped cell types in the testis interstitium, only the peritubular mesenchymal cells showed positive immunolabeling for all three steroidogenic enzymes, beginning from the 11th postnatal day. All three enzymes were expressed simultaneously in these cells, and their numbers increased significantly thereafter. Immunoexpression of LHR in a few of these cells was just evident for the first time on postnatal Day 12 (i.e., after acquiring the steroidogenic enzyme activity). Their numbers gradually increased with time. The number of immunolabeled cells per 1000 interstitial cells (excluding fetal Leydig cells and capillary endothelial cells) was not significantly different for the three steroidogenic enzymes tested at all ages; however, a lower value was observed for LHR at each time-point. Based on these observations, we suggest that 1) the precursor cell type for the adult generation of Leydig cells in the postnatal rat testis is the peritubular mesenchymal cells, 2) precursor cells acquire 3beta-HSD, P450(scc), and P450(c17) enzyme activity simultaneously during Leydig cell differentiation, and 3) onset of precursor cell differentiation during Leydig cell development does not depend on LH.

3-Hydroxysteroid Dehydrogenases↗

Sclerosing Sertoli cell tumor of the testis. A report of 10 cases.

Sex cord-stromal tumors of the testis are uncommon and have been less well characterized than similar tumors of the ovary, with a much greater proportion of them falling into the "unclassified" category. We report the clinical and pathological features of 10 Sertoli cell tumors of the testis with prominent sclerosis, representing a distinctive, heretofore undescribed subtype of Sertoli cell tumor in the human. The patients were mostly in their 3rd and 4th decades (median age, 30 years; range, 18-80 years). One tumor occurred in a cryptorchid testis, and one patient had had an orchidopexy several years prior to his presentation. There was no evidence of estrogen production by the tumor in any case. The tumors occurred equally often in each testis and were small (0.4-1.5 cm) in diameter, except for two tumors, which were 4.0 cm in diameter. All of them were centered in the testicular parenchyma and were well-demarcated, hard, yellow-white to tan nodules. They were characterized histologically by solid and hollow, simple and anastamosing tubules, large irregular aggregates, and thin cords of Sertoli cells in a prominent collagenous background. The tumor cells were of medium size and had pale cytoplasm, which sometimes contained large lipid vacuoles; the round nuclei varied from small and dark to large and vesicular. Follow-up information on five patients--including the only one whose tumor had malignant features histologically--showed no evidence of recurrence or metastasis 3-10 years (mean, 5.8 years) after orchidectomy alone.

Adult↗

Primary mucinous tumors of the testis and paratestis: a report of nine cases.

Ovarian-type surface epithelial tumors are rare in the testis and paratestis, with most reported examples being serous. There is little information on mucinous tumors, nine of which are described in this report, applying criteria and terminology used in the ovary. The patients were 44-69 years of age (median 64 years) and presented with masses in the testis (four) or paratestis (five). Eight tumors were cystic (median size, 3.5 cm) and contained gelatinous material; one (a paratesticular carcinoma) appeared as thickening of the tunica vaginalis. Two were classified as mucinous cystadenomas (both paratesticular), six as purely or predominantly borderline tumors (four, testis; two, paratestis; one had intraepithelial carcinoma and one microinvasive carcinoma) and one (paratestis) as mucinous carcinoma. The cystadenomas were composed of endocervical-like cells, but intestinal-like cells typified the borderline tumors and carcinomas. Cyst rupture with mucin dissection into the stroma, inflammation, and dystrophic calcification with ossification were common. No tumor was associated with intratubular germ cell neoplasia, unclassified type or with teratomatous elements. One patient with carcinoma died shortly after presentation with peritoneal spread; autopsy disclosed no other potential primary site. The follow-up (1.8-12 years) in all other cases was uneventful. Mucinous tumors of the testis and paratestis resemble their ovarian counterparts, exhibiting the same morphologic spectrum, from benign to borderline to malignant, and having both endocervical-like and intestinal features. These tumors may derive from mesothelium by the process of mullerian neometaplasia, from mullerian remnants or from the mucinous epithelium of a teratoma. The older age of the patients, lack of nonmucinous elements, and absence of intratubular germ cell neoplasia, unclassified type suggest that, if of teratomatous origin, the teratoma is different from the usual type. Clinical features are important to exclude metastasis, particularly in cases of carcinoma and, to a lesser extent, in tumors of borderline type.

Adenocarcinoma, Mucinous↗