Cases Of Testicular Cancer Research Articles

Candidate regions for testicular cancer susceptibility genes

Although the aetiology of testicular cancer is unknown, a clear familial component has been identified in a number of studies. In an effort to identify susceptibility genes for testicular cancer, the International Testis Cancer Linkage Consortium has been collecting families with multiple cases of testicular cancer. These families have been genotyped for a set of markers across the genome in two separate studies. The family information has also been pooled across the two studies so that the combined evidence can be assessed. While no genomic region gives overwhelming support for a testicular cancer predisposition gene, several regions, notably on chromosomes 3, 5, 12 and 18 show suggestive evidence worthy of further examination. The Consortium is now attempting to identify further families in an attempt to confirm or deny these leads.

Is Testicular Cancer an Occupational Disease? A Case-Control Study of Royal Naval Personnel

Testicular cancer is the commonest malignancy arising in men actively serving in the Royal Navy. This study, which includes a literature review of the aetiology of the disease, is designed to determine the relative risk of developing testicular cancer in various occupational groups within the Service by means of a Case-Control study. All cases of testicular cancer occurring in serving personnel between 1976 and June 1994, inclusive, were identified. One hundred and ten cases were found. Four randomly selected controls were matched on the basis of date of birth and length of service to each case. Results reveal statistically significant increased Odds Ratios for members of the Fleet Air Arm (OR = 1.90 95% CI: 1.04-3.48). Air Engineers (OR = 2.32 95% CI: 1.20-4.48) and the Aircraft Handling sub-specialty (OR = 7.31 95% CI: 1.81-29.53). It is speculated that exposure to glycol ethers in aviation fuel may be the causative mechanism. No associations were found in relation to ionising radiation exposures or length of time served in nuclear submarines.

Tumor markers in hydrocele fluids of patients with benign and malignant scrotal diseases.

We evaluated the presence of human chorionic gonadotropin (hCG), alpha-fetoprotein (AFP) and a panel of other tumor markers in the compartment next to the tumor (that is, the malignant hydrocele fluid). We measured hCG, AFP, neuron-specific enolase, carcinoembryonic antigen and cytokeratin-19 fragments in cubital vein sera and in hydrocele fluids of patients with testicular cancer. Results were compared with those obtained from hydrocele fluids of patients with benign disease. All tumor markers remained under the respective cutoff values in benign hydroceles. In patients with pure seminomas, hCG levels were elevated in 66% of hydroceles but only once in peripheral sera, whereas AFP remained low in both compartments. Furthermore, of 11 cases of nonseminomatous germ cell tumor hydrocele fluids, 3 with negative peripheral tumor marker values had to be reclassified marker positive, of which 2 showed elevated hCG levels and 1 had increased levels of AFP. Significant changes of neuron-specific enolase and carcinoembryonic antigen concentrations could not be observed. However, a cytokeratin-19 fragment measured by Cyfra 21-1 assay was elevated in 2 of 3 seminomatous and in 4 of 8 nonseminomatous hydroceles. These data give a new insight into the in vivo secretion pattern of testicular germ cell neoplasms, which demonstrates that the term "marker negative" should be restricted to selected cases of testicular cancer. Analysis of tumor markers in hydrocele fluids may be a helpful tool in patients with scrotal swelling if clinical and sonographic results remain uncertain.

Tumor Markers in Hydrocele Fluids of Patients With Benign and Malignant Scrotal Diseases

Purpose We evaluated the presence of human chorionic gonadotropin (hCG), alpha-fetoprotein (AFP) and a panel of other tumor markers in the compartment next to the tumor (that is, the malignant hydrocele fluid). Materials and Methods We measured hCG, AFP, neuron-specific enolase, carcinoembryonic antigen and cytokeratin-19 fragments in cubital vein sera and in hydrocele fluids of patients with testicular cancer. Results were compared with those obtained from hydrocele fluids of patients with benign disease. Results All tumor markers remained under the respective cutoff values in benign hydroceles. In patients with pure seminomas, hCG levels were elevated in 66% of hydroceles but only once in peripheral sera, whereas AFP remained low in both compartments. Furthermore, of 11 cases of nonseminomatous germ cell tumor hydrocele fluids, 3 with negative peripheral tumor marker values had to be reclassified marker positive, of which 2 showed elevated hCG levels and 1 had increased levels of AFP. Significant changes of neuron-specific enolase and carcinoembryonic antigen concentrations could not be observed. However, a cytokeratin-19 fragment measured by Cyfra 21-1 assay was elevated in 2 of 3 seminomatous and in 4 of 8 nonseminomatous hydroceles. Conclusions These data give a new insight into the in vivo secretion pattern of testicular germ cell neoplasms, which demonstrates that the term “marker negative” should be restricted to selected cases of testicular cancer. Analysis of tumor markers in hydrocele fluids may be a helpful tool in patients with scrotal swelling if clinical and sonographic results remain uncertain.

Association of Down's Syndrome and Testicular Cancer

Purpose We present additional clinical evidence for the suspected association of Down's syndrome and testicular germ cell tumors. Material and Methods Four cases of Down's syndrome and testicular cancer are reported. The literature was reviewed for previous cases and analysis regarding common features. Results The 4 patients were 29 to 35 years old and had clinical stage I seminoma of the testis. Two patients received prophylactic abdominal radiotherapy, 1 is being followed and 1 received adjuvant carboplatin treatment. There was no relapse at followup of 1 to 8 years. One patient also had contralateral cryptorchidism. A total of 16 cases with the association of Down's syndrome and testicular germ cell cancer was documented previously. Conclusions Evidence for the suspected association of Down's syndrome and testicular cancer is now accumulating. Etiologically it is suspected that, along with genetically determined malformations in many other organs in trisomy 21, the gonads also undergo maldevelopment, thus creating the conditions for step 1 of germ cell tumor oncogenesis in utero. Physicians caring for patients with Down's syndrome should be aware of the possible association with testicular neoplasms.

A segregation analysis of testicular cancer based on Norwegian and Swedish families.

Clustering of testicular cancer cases in families is well known, although the aetiology is not. We present the results of a segregation analysis performed with the algorithm Pointer on familial data on 978 Scandinavian patients with testicular cancer. The segregation analysis favoured the involvement of major gene effects over models incorporating solely polygenic effects in testicular cancer aetiology. Overall, a recessive model best fits the family observations with an estimated gene frequency of 3.8% and a lifetime risk for homozygous men of developing the disease of 43%. This implies that 7.6% of men in the general population will be carriers of the mutant allele and that 0.1% would be homozygote and are, therefore, at high risk of developing the cancer. The testicular cancer incidence has changed greatly during the last generation. Also, the lethality of the disease has changed because of the introduction of new therapy. As failure to take account of such time trends might lead to inappropriate evidence for a recessive model, the analyses were repeated under different assumptions. The analyses favoured a recessive model of inheritance under all assumptions tested. However, the assumptions underlying the analyses are complex and, as this is the first segregation analysis of testicular cancer, the results must be interpreted cautiously.

Increase in testicular cancer incidence in six European countries: a birth cohort phenomenon.

For unknown reasons, the age-standardized incidence of testicular cancer has shown a rapid increase in virtually all countries (mostly Western) studied. For populations with a sufficiently long period of cancer registration, this development can be traced back to the first half of this century. By evaluating data from six countries with long periods of cancer registration (Denmark, Norway, Sweden, the former German Democratic Republic [East Germany], Finland, and Poland), we sought to determine whether the increase in testicular cancer risk follows a birth cohort pattern and, if so, to quantify and compare any birth cohort effects. A total of 30,908 incident cases of testicular cancer, diagnosed from 1945 through 1989 in men who were 20-84 years of age, were identified in population-based cancer registries in the six countries. In addition to performing simple trend analyses, we fitted several Poisson regression models (with the explanatory variables age, time period [calendar time], and birth cohort) to the data. Individual models were estimated by the maximum likelihood method. The age-standardized incidence of testicular cancer was found to vary among the six populations and, on the basis of total registration data, increased annually at rates ranging from 2.3% (in Sweden) to 5.2% (in East Germany). A comparison of several regression models indicated that birth cohort was a stronger determinant of testicular cancer risk than was calendar time for all six populations. Within each population, little variation in testicular cancer risk was observed for men born between 1880 and 1920; thereafter, the risk began to increase. Among men born in Denmark, Norway, and Sweden between 1930 and 1945 (the period encompassing the Second World War), the increasing trend in risk was interrupted (i.e., a leveling in risk occurred). After 1945, an uninterrupted increase in risk was observed for all six populations. With men born around 1905 as the reference group, the relative risk of testicular cancer for those born around 1965 varied from 3.9 (95% confidence interval [CI] = 2.7-5.6) in Sweden to 11.4 (95% CI = 8.3-15.5) in East Germany. The increasing trend in testicular cancer risk observed for these six populations follows a birth cohort pattern. This distinct risk pattern provides a framework for the identification of specific etiologic factors.

Efficacy of the chemosensitivity test using collagen gel matrix-supported culture system for urogenital tumors

We evaluated the usefulness of in vitro tumor culture system using a specialized collagen gel matrix (CGM assay) as a chemosensitivity test. Chemosensitivity results of CGM assay were compared with other in vivo and in vitro assays on an implantable murine bladder tumor cell line (MBT-2). In addition we investigated the possibility of the clinical use of CGM assay using clinical specimens obtained from urogenital malignant tumor patients by comparing the result with that of the other chemosensitivity test, SDI testing using single cells (conventional SDI test). Methods of CGM assay were as follows. Tumor tissues on the collagen gel matrices were incubated under the existence of anticancer drugs following 4 days preculture. Drug sensitivities were evaluated by counting the number of viable cells adjusted to the tumor weight. Inhibition rates in MBT-2 were high in the order of mitomycin C, cisdiamminedichloroplatinum (II), (2"R)-4'-0-tetrahydropyranyl adriamycin. Four of 6 anticancer drugs were decided as chemosensitive drugs. These results corresponded to the results of the antitumor effects on subcutaneously transplanted MBT-2 in vivo, moreover was correlated well with those of the conventional SDI test. Twenty of 22 cases, including 11 of 13 bladder cancer cases, 1 of 3 renal cancer cases, 2 of 3 testicular cancer cases and 1 of 1 adrenal cortical cancer cases, were evaluable in the clinical study of the CGM assay. Corresponding rates between the results of the CGM assay and those of the conventional SDI test performed simultaneously in 12 cases were excellent for each anticancer drug. This CGM assay can serve as an effective tool for chemosensitivity testing because of its convenience and high evaluable rate.

Familial testicular cancer in a population-based cancer registry.

The population-based Connecticut Tumor Registry was used to identify 18 testicular cancer cases (diagnosed 1973-1991) with a family history of testicular cancer (including 4 father-son pairs and 8 sibling pairs) and to describe the age at diagnosis, histology and other characteristics of these familial cases. Collaboration among cancer registries is needed to identify cases for genetic studies.

Trends in incidence of testicular cancer in Norway 1955-1992.

The aim of this study was to explore the incidence of testicular cancer (TC) in Norway, and thereby to increase the understanding of aetiological factors. From 1995 to 1992, a total number of 3927 TC cases were recorded in Norway, of which 51% were seminomas, 45% non-seminomas and 4% other and unspecified types. The age-standardised incidence rate increased from 2.7 to 8.5 per 100,000. The age-specific incidence rate increased in all age groups, but was most marked in the younger population. The significance of birth cohort as a risk factor for development of TC was confirmed. The incidence by birth cohorts from 1916 to 1970 showed an increase by later birth cohorts during the whole period, with the exception of a marked fall for the cohort born during the Second World War. The largest increase occurred after the war. We conclude that environmental factors acting very early in life are of significance in the development of TC.

High frequency of metalworkers among patients with seminomatous tumors of the testis: a case-control study.

Occupational analyses were conducted between 1971 and 1978 comparing 165 cases of testicular cancer in the Hannover region of Germany with 187 controls without neoplastic diseases admitted to the Hannover University Medical School during the same period. The results showed a significantly higher risk of metal workers developing seminomas and mixed seminomatous tumors compared to the controls (odds ratio 2.05; 1.17-3.58). There was a lack of risk for the nonseminomatous tumors as a whole group, and cases with a history of metal work may have a decreased risk for embryonal carcinomas. No definite single noxious substance responsible for the development of testicular tumors could be detected. In view of the results in animal experiments, cadmium and zinc are especially considered in the discussion.

Candidate regions for a testicular cancer susceptibility gene.

Epidemiological data suggest the presence of a susceptibility gene for testicular cancer in some families. Families with multiple cases of testicular cancer are rare and almost all those reported have only two affected members. We have performed a sib-pair analysis on 35 families in which there are either two or three affected brothers. These families have been typed for 220 autosomal microsatellite markers spaced 10-20 cM throughout the genome. Six regions which gave a LOD score of more than 1.0 on formal linkage analysis or a P value of 0.05 or less using a non-parametric approach are considered as candidate regions for a susceptibility gene. Of particular interest is one region on chromosome 4. Two neighbouring probes in this region both scored positively with LOD score of 2.60 on multipoint analysis. An International Testis Cancer Linkage Consortium has been formed to pool resources and will investigate these findings further with the world-wide collection of families.

Physical activity and the risk of prostate and testicular cancer: a cohort study of 53,000 Norwegian men

The associations between recreational and occupational physical activity and the subsequent risk of prostate and testicular cancer were examined in a population-based cohort study of 53,242 men in Norway. Age at study entry was 19 to 50 years. Information on physical activity was based on questionnaire responses and a brief clinical examination. A total of 220 prostate and 47 testicular cancer cases were recorded in the Cancer Registry of Norway during a mean follow-up time of 16.3 years. We found a nonsignificant, reduced, adjusted relative risk (RR) of prostate cancer with increased level of physical activity at work and among those men with the greatest recreational physical activity. When occupational and recreational physical activity were combined, a reduced adjusted risk of prostate cancer was observed among men who walked during occupational hours and performed either moderate recreational activity (RR = 0.61, 95 percent confidence interval [CI] = 0.36 to 1.01) or regular recreational training (RR = 0.45, CI = 0.20 to 1.01) relative to sedentary men (test for trend, P = 0.03). Physically active men who were older than 60 years of age at diagnosis showed a reduced adjusted RR of borderline significance, while no association was observed for younger men. No evidence was found for any association between physical activity and testicular cancer regardless of physical activity at work and recreation.

Testicular cancer in blacks. A multicenter experience.

The rarity of testis tumor in black patients has made the study of a large series difficult. Much of the epidemiologic and clinical information regarding this neoplasm in this population is in dispute, including data on incidence, prognosis, histologic distribution, age and stage at presentation, and side distribution. A retrospective review of 66 blacks with testicular tumors from seven military medical centers was performed. Similar results were found for blacks with testis tumor to those of the general testis cancer population regarding prognosis, side distribution, and age of onset for nonseminoma and interstitial tumors. There is a slight increase in the expected number of interstitial tumors in blacks, but the distribution between seminoma and nonseminoma is similar to the general population. The mean age of presentation for seminoma in blacks was younger than that of the general testis cancer population. For testis tumor treated at the same institution, there was an increased delay of diagnosis in blacks compared with whites. The number of new cases of testicular cancer between 1979 and 1991 at one major center was increased for whites but not for blacks. The availability of cisplatin-based combination chemotherapy has resulted in an improved prognosis for blacks, as has already been demonstrated for white populations. Testis tumor in blacks behaves similarly to testis tumor in the general population except that in blacks there are more interstitial tumors and the mean age of presentation for seminoma is younger. Further, there is an increased delay in diagnosis for blacks compared with whites, but the incidence of this tumor in this population does not appear to be increasing. Cisplatin-based chemotherapy has significantly improved survival in this population.

泌尿器科病棟における菌血症の臨床統計的観察

Thirty cases of bacteremia out of 1512 patients who had been admitted to our Department between February 1988 and June 1991 were reviewed. They consisted of 22 males and 8 females and their age ranged from 32 to 88 years (mean 62.7). 25 of the patients (83.3%) had malignant diseases of which bladder cancer (15 cases) was predominant and 5 had benign diseases. Gram positive bacteria were isolated in 18 cases (56.2%) and fungi in 4 cases (12.5%) from blood culture. Of these MRSA was most prevalent: 6 cases (18.8%), followed by S. epidermidis: 4 cases (12.5%), P. aeruginosa: 3 cases: E. faecalis: 3 cases and Corynebacterium: 3 cases (9.4%). Analysing the onset of bacteremia for each case, in three cases urinary tract infections, in one case a surgical wound infection and in one case a skin infection were prominent before the diagnosis of bacteremia. From their background, 23 cases (76.7%) were so-called compromised hosts. A total of 7 cases had died, 6 cases of bladder cancer and one case of testicular cancer, five of them were on systemic anti-cancer chemotherapy. Of those cases who expired, P. aeruginosa was isolated in two cases, Candida in two cases, MRSA in one case and E. faecium in one case, Corynebacterium in one case. It was noteworthy that in two cases where blood cultures were positive for P. aeruginosa and one case where the blood culture proved positive for Candida, drastic decrease of the peripheral leukocyte number during anti-cancer chemotherapy was seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Cluster of testicular cancer in police officers exposed to hand-held radar.

Within a cohort of 340 police officers, six incident cases of testicular cancer occurred between 1979 and 1991 (O/E 6.9; p < 0.001, Poisson distribution). Occupational use of hand-held radar was the only shared risk factor among all six officers, and all routinely held the radar gun directly in close proximity to their testicles. Health effects of occupational radar use have not been widely studied, and further research into a possible association with testicular cancer is warranted.

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.

Birth order and risk of testicular cancer

To explore the etiology of testicular cancer, cases of testicular cancer were identified among members of a cohort of Danish boys born between 1941 and 1957 (inclusive), who had attended schools in Copenhagen and Gentofte and whose school health records were contained in an archive under the supervision of the Danish Cancer Registry. One hundred and eighty-three cases of testicular cancer diagnosed before 31 December 1984 were identified; 366 controls, matched to cases by sex and age, were selected from the same cohort. Information on potential risk factors and confounders was obtained from two sources: school health records and midwife protocols, both of which were recorded prior to the diagnosis of testicular cancer in cases. Relative risks (RR) approximated by the odds ratios were calculated and, in logistic regression analyses, adjustments were done for known or suspected confounders. A decreasing risk of testicular cancer with increasing birth order was observed (P = 0.020). Compared with being firstborn, being number four or more in birth order was associated with a significantly decreased RR for all testicular cancers (RR = 0.3, 95 percent confidence interval [CI] = 0.3-0.8) and testicular seminoma (RR = 0.1, CI = 0.02-0.9). No association was observed between high social class and the risk of testicular cancer (RR = 1.4, CI = 0.8-2.3); neither was age at which the study subjects had mumps or measles related to risk of testicular cancer. No cases of mumps orchitis were observed before or during school years. A slightly increased RR for testicular cancer among boys from small families could be explained by the association between family size and birth order.(ABSTRACT TRUNCATED AT 250 WORDS)

Familial testicular cancer: a report of the UK family register, estimation of risk and an HLA class 1 sib-pair analysis

Forty-two families with two or more cases of testicular cancer have been reported to the UK Register for Familial Testicular Cancer, comprising two pairs of identical twins, 27 sets of other brothers (25 pairs, two triples), nine father-son pairs, two pairs of first cousins and two uncle-nephew pairs. In total 91 testicular tumours are described in 86 individuals (42 (46%) pure seminoma, 49 (54%) other germ cell tumours). The median age at diagnosis in these patients was significantly younger than that in a comparable series of non-familial patients (29 c.f. 32.5 years, P less than 0.01). In a case-control comparison of 794 testicular cancer patients, eight patients (1.0%) had a brother and four patients (0.5%) had a father with a previous diagnosis of testicular cancer at the time of their own diagnosis (and these families are all included in this report). Two out of 794 controls (0.3%) had a first degree relative with testicular cancer. The cumulative risk to a brother of a patient for developing testicular cancer by the age of 50 years was estimated to be 2.2% (95% C.I. 0.6-3.8%) which results in a relative risk of 9.8 (95% C.I. 2.8-16.7) in comparison with the general population. HLA Class I typing of 21 affected sib-pairs demonstrated four (19%) sharing two haplotypes, 13 pairs (62%) sharing one and four pairs (19%) sharing none. This did not differ significantly from the expected proportions of 25%/50%/25%. It is unlikely, therefore, that there is a major gene associated with testicular cancer predisposition within or closely linked to the major histocompatibility gene complex on chromosome 6.

Occurrence of Testicular Cancer in Patients Operated on for Cryptorchidism and Inguinal Hernia

We studied the incidence of testicular cancer in 2 population-based cohorts comprising 2,918 men who underwent an operation for a cryptorchid testis and 30,199 who underwent surgery for an inguinal hernia. Complete followup during the 19-year period was achieved by record linkage to the National Swedish Cancer Registry. In the cryptorchidism cohort 4 cases of testicular cancer occurred versus 0.54 expected, yielding a relative risk of 7.4 (95% confidence interval 2.0 to 19.0). Of these patients 3 had undergone a bilateral operation due to intra-abdominal testes. There was no evidence of an association between inguinal hernia and risk of testicular cancer (relative risk = 1.1, 95% confidence interval 0.4 to 2.2). The validity of our data was further supported by relative risk estimates close to unity in a comparison group of appendectomy patients. We conclude that patients with a cryptorchid testis experience a substantially increased relative risk of testicular cancer. However, the low absolute risk, 4 cases during 25,360 person-years of observation, does not appear to justify special surveillance after an operation for an undescended testis.