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Biomedical subjects

A Giwercman

Publications and source records attributed to A Giwercman.

At least 109 records · Page 6Linked to original sources

Testicular cancer after vasectomy: origin from carcinoma in situ of the testis.

Vasectomy is a commonly used male contraceptive procedure. Reports have indicated that vasectomy is associated with an increased risk of development of germinal testicular cancer. Carcinoma in situ of the testis (CIS) is a preinvasive lesion which precedes germinal testicular cancer. CIS is almost always found in the tissue adjacent to a germinal testicular cancer. It is believed that CIS is a malignant gonocyte formed during embryogenesis. We have studied the testicular tissue from 5 previously vasectomised patients with testicular cancer and found CIS in the tissue adjacent to their cancer as well as changes in the epididymis of the patients. We discuss the findings and conclude that testicular cancers occurring after vasectomy is not an exception from the rule that testicular cancer originates from CIS. Thus, there is no causal relationship between vasectomy and testicular cancer, but vasectomy might precipitate the development of testicular cancer from the preinvasive CIS lesion.

Carcinoma in Situ↗

Immunohistochemical markers of carcinoma in situ of the testis also expressed in normal infantile germ cells.

Carcinoma in situ of the testis is an intratubular, pre-invasive lesion preceding germ cell tumour. In adult men, carcinoma in situ cells differ in several aspects from normal germ cells. For example, placental-like alkaline phosphatase and/or the epitopes for the monoclonal antibodies M2A, 43-9F and TRA-1-60 are not seen in normal germ cells, whereas their presence is considered a specific sign of carcinoma in situ. As it is known that placental-like alkaline phosphatase and the epitope for TRA-1-60 are expressed in normal fetal germ cells it is possible that the markers could appear in normal infantile germ cells in a period after birth before they lose their expression. In children, carcinoma in situ cells may be difficult to identify morphologically and the use of the markers could be of great value. However, little information is available on the expression of the markers of adult carcinoma in situ in normal infantile germ cells. We investigated gonads from 66 boys less than 15 years old who died suddenly. Their deaths were unrelated to testicular disease. Immunohistochemical staining with anti-placental-like alkaline phosphatase antibody and monoclonal antibodies TRA-1-60 and 43-9F were performed. We found that these markers were expressed in some normal infantile germ cells until the age of 1 year. Therefore, these markers are not suitable for diagnosis of carcinoma in situ during the early postnatal period of life.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Ultrasonic testicular texture and size in 444 men from the general population: correlation to semen quality.

Scrotal ultrasonography was performed in 888 testes of 444 randomly selected men appearing before the medical board prior to military service (Mili group, 287 men, median age 18.8 years), and in employees from an industrial company (Empl group, 157 men, median age 35.6 years). The ultrasonic volume of each testis was calculated from 3 perpendicular measurements. The ultrasonic texture on sectional planes was scored using a scale from 1 to 5, 1 being very regular, 2 slightly irregular, 3 moderately irregular, 4 very irregular or with bright echogenic points, and 5 with demarcated tumor suspicious areas. Orchidometer measurements were performed in 258 men in Mili group, and semen samples were obtained from 121 men in Empl group. The ultrasonic volume of the right testis (median 14.1 ml, range 3.0-31.4 ml) was bigger than that of the left testis (median 13.0 ml, range 3.5-35.2). The volume was dependent on age for men under 20 years, but not for men aged 20 years or more. The subgroup of men with a history of cryptorchidism had a smaller average testicular volume (median 10.5 ml) compared with men with normal descent (median 14.1 ml). Ultrasonic volume was positively correlated to the total sperm count in the ejaculate, to sperm penetration in egg white, and to normal sperm morphology. The echo score distribution showed slightly higher scores in Empl for both the right and the left testis. Men in Empl group were older, and it could not be precluded that this difference was due to age.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Hormones and growth factors in germ cell neoplasia: general discussion.

Fetal germ cells migrate along the dorsal mesentery to the genital ridge, and migration in the bloodstream occurs in some animals. Malignant transformation may occur before migration, and it is possible that testicular germ cell tumours have a monoclonal origin, even when bilateral. Different tumour foci have homogeneous chromosomal abnormalities. Migrating germ cells may lodge in extragonadal sites and give rise to tumours. Mouse fetuses exposed to oestrogen and testosterone in utero have an increased incidence of testicular maldescent and teratoma. Oestrogens and mullerian inhibitory substance in the fetus may influence human testicular tumour development. Testicular tumour patients may have elevated serum oestrogen levels which may be related to prognosis. Increased serum FSH may stimulate germ cell tumour growth. Ultrastructural studies indicate that malignant transformation of germ cells occurs early, but final tumour differentiation does not occur till after the malignant cells have invaded extratubular tissue.

Animals↗

Evidence for increasing incidence of abnormalities of the human testis: a review.

Recent reports have suggested that the incidence of genitourinary abnormalities in human males has increased during the past 50 years, including congenital abnormalities such as cryptorchidism and hypospadia, which seem to be occurring more commonly. Also, the incidence of testicular cancer has increased 3- to 4-fold since the 1940s. This increase seems to be worldwide including countries with a very high frequency of testicular neoplasia as well as those in which this cancer is rather uncommon. It has also been postulated that semen quality has been decreasing for the last half century. A recent study showed that the average sperm density has decreased significantly from 113 million/mL in 1940 to 66 million/mL in 1990. The mean seminal volume has also declined, indicating that the decrease in the total sperm count is even more pronounced than the fall in sperm density would indicate. The remarkable increase in frequency of testicular abnormalities over a relatively short period of time may be due to environmental rather than genetic factors. There is an epidemiological link between the occurrence of different testicular abnormalities. Therefore, common prenatally acting etiological factors with adverse effects on the fetal male gonad might be suspected. However, postnatal influences may also have a deleterious effect on male fertility. From the reproductive point of view, an increased impact on the human male gonad is of concern.

Cryptorchidism↗

Epidemiological and clinical aspects of carcinoma in situ of the testis.

Despite the high cure rate in men with testicular cancer, efforts should be made to diagnose the disease at the preinvasive stage. The disease, which affects young males, is potentially lethal. Furthermore, testicular neoplasia diagnosed at the stage of CIS can be cured without the negative impact on the life-quality of the survivors, as chemotherapy and other systemic treatment can be avoided. The treatment of choice is orchidectomy if the neoplasia is unilateral, or localized irradiation in bilateral cases. Testicular biopsy performed after puberty is at present the only reliable diagnostic method. Screening for CIS in the contralateral testis should be offered to men with unilateral testicular cancer. Patients with assumed extragonadal germ cell tumour and intersex individuals are also recommended to have a biopsy for CIS. Biopsies should also be considered in adults with maldescended testes and in selected cases of infertility. In the future the techniques of detecting of CIS cells in semen may become refined. In such circumstances, the general male population may be targeted for screening and more cases of testicular cancer could then be prevented.

Carcinoma in Situ↗

Evidence for decreasing quality of semen during past 50 years.

OBJECTIVE: To investigate whether semen quality has changed during the past 50 years. DESIGN: Review of publications on semen quality in men without a history of infertility selected by means of Cumulated Index Medicus and Current List (1930-1965) and MEDLINE Silver Platter database (1966-August 1991). SUBJECTS: 14,947 men included in a total of 61 papers published between 1938 and 1991. MAIN OUTCOME MEASURES: Mean sperm density and mean seminal volume. RESULTS: Linear regression of data weighted by number of men in each study showed a significant decrease in mean sperm count from 113 x 10(6)/ml in 1940 to 66 x 10(6)/ml in 1990 (p < 0.0001) and in seminal volume from 3.40 ml to 2.75 ml (p = 0.027), indicating an even more pronounced decrease in sperm production than expressed by the decline in sperm density. CONCLUSIONS: There has been a genuine decline in semen quality over the past 50 years. As male fertility is to some extent correlated with sperm count the results may reflect an overall reduction in male fertility. The biological significance of these changes is emphasised by a concomitant increase in the incidence of genitourinary abnormalities such as testicular cancer and possibly also cryptorchidism and hypospadias, suggesting a growing impact of factors with serious effects on male gonadal function.

Humans↗

Monoclonal antibody 43-9F: an immunohistochemical marker of embryonal carcinoma of the testis.

Discrimination between different types of germ cell tumours may be difficult in routine histological preparations. Additionally, none of the established immunohistochemical markers is completely reliable in diagnosis of embryonal carcinoma. A pilot study indicated that monoclonal antibody 43-9F--a marker of carcinoma-in-situ germ cells--may also react with embryonal carcinoma of the testis. In order to elucidate the applicability of 43-9F in diagnosis of embryonal carcinoma, 42 consecutive testicular germ cell tumours were tested immunohistochemically. Among the 42 tumours, 23 were seminomas and 19 were non-seminomas with seminomatous components in seven of them. Embryonal carcinomas were found in 15 tumours, two being of pure type and the remaining 13 a part of mixed tumours. Additionally, the material included 11 teratomas, nine yolk sac tumours and one choriocarcinoma. Immunohistochemical stainings were performed with 43-9F and additionally with antibodies against placental-like alkaline phosphatase, cytokeratins, alpha-foetoprotein and human chorionic gonadotropin. Using 43-9F a strong colour reaction was found in 13 of the embryonal carcinomas, whereas the reaction was moderate in the remaining two cases. A weak positive reaction was found in six seminomas and the remaining 24 did not react at all. 43-9F exhibited a positive reaction in four of 11 teratomas. The reactivity was generally weak with some focal areas with strong staining. In five cases the yolk sac tumour elements did not stain with this monoclonal antibody. The reaction was weak in three cases and in only one case was the staining intensity scored as moderate. Finally, no reaction was found in the choriocarcinoma element. Compared to the other antibodies tested, including the antibody against cytokeratins, in embryonal carcinoma immunohistochemical staining with 43-9F was more specific, stronger and more constantly expressed. The monoclonal antibody 43-9F may be of value in histological diagnosis of germ cell tumours. Additionally, the study confirmed the pathogenetical link between pre-invasive carcinoma in situ and embryonal carcinoma.

Antibodies, Monoclonal↗

DNA distributions in maldescended testes: hyperdiploid aneuploidy without evidence of germ cell neoplasia.

Fine-needle aspiration biopsies and surgical biopsies were obtained from maldescended testes of 149 consecutive men. The aspirates were subjected to quantitative DNA flow cytometry and the surgical biopsy to histological evaluation. From more than 80% of the gonads, sufficient material was obtained for both examinations. A significant hyperdiploid cell population with a mean DNA index of 1.23 (range 1.17-1.31) was found in six gonads. Hyperdiploid aneuploidy was found in gonads without, as well as with, complete spermatogenesis. In none of the six cases did the surgical biopsy show evidence of early testicular neoplasia by morphology or by immunohistochemical methods with antibodies against carcinoma in situ. This indicates that aneuploidies in maldescended testes do not necessarily indicate malignancy. It may be speculated that hyperdiploid aneuploidy is related to the development of preneoplastic lesions.

Adult↗

Prevalence of carcinoma in situ and other histopathological abnormalities in testes from 399 men who died suddenly and unexpectedly.

To determine the prevalence of carcinoma in situ of the testis and other testicular histopathological abnormalities in the general male population, we examined gonads from 399 men 18 to 50 years old who died suddenly and unexpectedly. No sign of malignancy was found in any of these gonads. However, 3 of the 399 men had been previously treated for testicular tumor or carcinoma in situ. Thus, the over-all prevalence of testicular neoplasia in the population studied was 0.8% (95% confidence limits 0.2 to 2.2%). This frequency is of the same magnitude as the lifetime risk of testicular cancer in the Danish male population. The median weights of the left and right testes were 19.3 and 19.7 gm., respectively. This difference was statistically significant (p = 0.00003). Thus, our study confirmed that on average the left testis is smaller than the right testis. The median weight of the gonads collected in our study was 0.9 gm. lower than the weight of testes examined 40 years earlier at the same department of forensic medicine. However, this difference was not statistically significant (p = 0.17). Microscopic examination of the gonadal specimens revealed that 83% of the men exhibited complete spermatogenesis, including late spermatids in all tubules. In the age group studied we found no age-related changes in testicular weight or in the proportion of tubules with degenerative changes, such as spermatogenic arrest, the Sertoli-cell-only syndrome or hyalinization.

Adolescent↗

Placental-like alkaline phosphatase as a marker of carcinoma-in-situ of the testis. Comparison with monoclonal antibodies M2A and 43-9F.

In an immunohistochemical study of 59 routinely processed tissue specimens from 48 adult testes with isolated carcinoma-in-situ (CIS) changes and of 66 specimens from adult testes without neoplasia, placental-like alkaline phosphatase (PlAP) was shown to be a reliable marker of CIS cells preceding the development of a testicular tumour. Thus, a positive reaction was encountered in all 36 biopsies treated with formaldehyde, or Bouin's or Stieve's fluid. However, only 11 of 23 specimens fixed with Cleland's fluid were immunoreactive for PlAP. None of the non-malignant components of seminiferous tubules, including the large abnormal spermatogonia, reacted with the antibody against PlAP. Besides the antibody against PlAP, monoclonal antibodies M2A and 43-9F were tested on CIS specimens fixed with the above-mentioned fixatives. In the 17 specimens fixed with Stieve's or Bouin's fluid, a positive reaction was obtained in all sections with all three antibodies tested. However, for each antibody at least two specimens gave a weak staining reaction. When all three immunostainings were performed, in each case at least one of them gave a moderate or strong reaction, thus making CIS cells easily detectable. In the samples fixed with Cleland's fluid, a negative reaction was found in one to three specimens, depending on the antibody used. However, at least one of the three antibodies gave a positive reaction if all three immunostainings were applied. In only one of the formaldehyde-fixed paraffin specimens did CIS cells react with the monoclonal antibody 43-9F, whereas M2A gave no positive reaction at all if this method of fixation was used. Thus, the sensitivity of the immunohistochemical staining procedure in the detection of CIS is dependent on the fixative used and increases when immunostainings with all three markers are performed simultaneously.

Adult↗

Localized irradiation of testes with carcinoma in situ: effects on Leydig cell function and eradication of malignant germ cells in 20 patients.

Twenty men (median age, 31 yr) previously treated for unilateral testicular cancer received localized irradiation in a dose of 20 Gray in 10 fractions for carcinoma in situ of the remaining testis. Follow-up testicular biopsies performed 3 (n = 19) and 24 (n = 14) months after the treatment showed in all cases a Sertoli cell-only pattern. Hormonal evaluation was performed before as well as 3, 12, 24, and 36 months after radiation treatment. Endocrine parameters were followed for a median of 30 months (3-36 months). Baseline serum testosterone values decreased during the follow-up period from 13.3 +/- 6.0 to 10.8 +/- 6.4 nmol/L (mean +/- SD), although the decrease was not statistically significant (P = 0.06). Serum LH values increased during the first 3 months of follow-up from 10.4 +/- 5.4 to 15.6 +/- 7.3 IU/L (P less than 0.0001) and then remained unchanged. Significant decreases in GnRH- and hCG-stimulated testosterone levels also indicated an impairment of Leydig cell function. FSH levels increased (P less than 0.0001) during the first 3 months of follow-up from 21.8 +/- 11.1 to 33.2 +/- 13.2 IU/L. We conclude that localized irradiation of 20 Gray eradicated carcinoma in situ germ cells. Development of a second testicular cancer has until now been prevented. Leydig cell function was partially impaired by the radiation dose given.

Adult↗