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Biomedical subjects

E E Fraley

Publications and source records attributed to E E Fraley.

At least 55 records · Page 3Linked to original sources

Return of fertility after treatment for nonseminomatous testicular cancer: changing concepts.

We studied the return of ejaculation in 31 patients who had undergone retroperitoneal lymphadenectomy for stage I or II nonseminomatous germ cell testicular cancer. Ejaculation returned spontaneously in 13 patients and was restored by sympathomimetic drugs in 5 of 8 patients treated. Both patients known to have tried to father a child succeeded. We also studied the effects of chemotherapy (vinblastine and bleomycin with or without cisplatin) in 34 patients, 24 of whom also had undergone retroperitoneal lymphadenectomy. Although chemotherapy profoundly depressed spermatogenesis during treatment 75 per cent of the patients tested 18 months or more after completion of treatment had some return of function, as evidenced by normal follicle-stimulating hormone levels and/or the presence of live sperm in the ejaculate. We concluded that it is possible to perform a therapeutically sound retroperitoneal lymphadenectomy for low stage nonseminomatous testicular cancer that permits return of ejaculation in many patients and that spermatogenesis recovers in a significant number of patients treated for this cancer with modern chemotherapy. Thus, traditional beliefs that operative and drug treatment of nonseminomatous testicular cancer invariably causes infertility must be revised.

Antineoplastic Agents↗

Stage II nonseminomatous testicular cancer: a 10-year experience.

Between 1970 and 1980, 82 patients with pathologic stage II nonseminomatous germ cell testicular carcinoma were treated at the University of Minnesota. Of the 30 patients treated with a retroperitoneal lymph node dissection, 22 (77%) relapsed. Of the 18 patients treated with retroperitoneal lymph node dissection and adjuvant radiotherapy, 12 (63%) relapsed. Sixteen patients received adjuvant chemotherapy before 1976, and 14 (87.5%) relapsed. After 1976, 18 patients received adjuvant chemotherapy (11 with cisplatin) and 2 (11%) have relapsed. No patient treated with cisplatin-based adjuvant chemotherapy has relapsed. The toxicity has been modest. Cisplatin-based chemotherapy is an effective and a safe adjuvant therapy for stage II nonseminomatous germ cell testicular carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗

Erythropoietin production by a human testicular germ cell line.

An established human testis germ cell line (1411-H) was found to produce significant amounts of erythropoietin (Ep), the primary regulator of erythropoiesis. Media conditioned by the 1411-H cells stimulated erythropoiesis both in vivo and in vitro. This activity was neutralized by anti-Ep. This continuous cell line provides a unique model for the study of the mechanisms of control of Ep biogenesis.

Cell Line↗

Tumor classification and size in germ-cell testicular cancer: influence on the occurrence of metastases.

The influence of local tumor spread (T-classification) and of tumor size on the occurrence of metastases was studied in 241 patients with testicular germ-cell neoplasms. All patients underwent thorough clinical or pathologic staging, or both, and were treated at the University of Minnesota Hospitals. Spread of tumor through the tunica vaginalis (T2) was associated with abdominal lymph node or distant metastases in eight of nine patients. Local tumor extension to the spermatic cord (T4a) was associated with metastatic spread in 29 of 31 men. Tumor size did not appear to correlate with metastatic rate. These findings are an important aid in designing adjuvant therapy trials and in establishing a "no treatment" approach after orchiectomy.

Adolescent↗

Marker half-life analysis as a prognostic tool in testicular cancer.

In a retrospective study we compared the actual half-life of the serum tumor markers alphafetoprotein and human chorionic gonadotropin to the clinical course of patients who underwent an operation or chemotherapy for germ cell cancer. Of the 7 patients with residual disease postoperatively 5 had abnormal half-life values and in 3 this knowledge would have been of clinical value. Only 1 of 10 patients with a complete response to chemotherapy had an unfavorable actual half-life compared to 17 of 19 with a less than complete response. Prolonged marker decay rates during the first month of chemotherapy reflected ineffective chemotherapy and appeared to be independent of tumor bulk. Postoperatively, actual half-lives probably are useful prognostically only if the values are abnormal. Similar calculation may be of prognostic value early in the course of induction chemotherapy.

Chorionic Gonadotropin↗

Percutaneous circle-tube nephroureterostomy.

A method for placement of a circle nephroureterostomy tube in patients with cutaneous ureterostomies is described. The technique requires local anesthesia only and, because the 16F tubes become incrusted less often in these patients than do ureteral stents, the tubes need to be changed only every 3 to 6 months.

Fistula↗

Surgical and urologic manpower in the United States, 1969 to 1978.

Between 1969 and 1978 the number of board-certified urologists increased by 71 per cent, while the population of the United States increased by 8.2 per cent. In 1978 the ratio of board-certified urologists to population was 1:32,416 and 326 of 370 first-year residency positions available in urology in the United States were filled. If we continue to produce urologists at the present rate the urologist to population ratio will be approximately 1:25,972 by year 2000. Thus, it appears that there are now too many urologists being trained yearly, which was indicated by 68 per cent of the academic program directors surveyed in 1979. In fact, to restore the ratio of urologist to population approximately 1:35,000 by year 2000 the number of urologists being trained yearly should be reduced to 156 or by approximately 50 per cent. The only reasonable chance of achieving a reduction in urologists being trained in the near future is by voluntary decreases in the size of training programs. There are many consequences of overproduction of urologists, including unnecessary surgery, atrophy of skills among practitioners and diminution of major training programs because of lack of patient referrals. Therefore, this issue is of equal importance to private practitioners and to academicians.

General Surgery↗

Ejaculation and fertility after extended retroperitoneal lymph node dissection for testicular cancer.

We studied ejaculation and fertility in 55 men who had undergone suprahilar extended retroperitoneal lymphadenectomy for nonseminomatous testicular cancer between 1972 and 1980. Antegrade ejaculation had returned spontaneously in 25 patients, with sperm counts of 35 to 190 million per ml., and normal morphology and motility in 20. The other 5 men either refused to provide semen for analysis or had had vasectomies but all had fathered children postoperatively. Ten men in whom antegrade ejaculation had not returned spontaneously were treated wih sympathomimetic drugs. Antegrade ejaculation was induced in 5 patients, 1 of whom fathered a child while taking the drugs. Two other patients who had only small volumes of ejaculate also responded well to sympathomimetic drugs. A therapeutically sound retroperitoneal node dissection can be performed for testicular cancer without impairing fertility permanently in a significant number of patients.

Adolescent↗

Immunohistochemical localization of murine stage-specific embryonic antigens in human testicular germ cell tumors.

Monoclonal antibodies raised against and/or recognizing stage-specific antigens on preimplantation mouse embryos and stem cells of murine teratocarcinoma were used to localize these antigens immunohistochemically on human testicular germ cell tumors. SSEA-1, the antigen found on mouse embryonal carcinoma (EC) cells and embryonic cells from the 8-cell stage embryo onward, including the fetal primordial germ cells, was detected on yolk sac carcinoma components of human tumors, but not on EC cells. SSEA-3, the antigen found on follicular ova, fertilized eggs, early cleavage stage embryonic cells, and visceral endodermal cells of the mouse embryo, but not on mouse EC cells, was detected on human EC cells. Both antigens were found on the cell surface of fetal testicular germ cells but not in the seminiferous tubules of adult human testes. These data point out differences between human and murine EC cells suggesting that human EC cells correspond developmentally to a less mature embryonic cell than the murine EC cells. The possible histogenesis of human germ cell tumors from primordial and/or fetal germ cells is briefly discussed.

Animals↗

Acute changes of alpha-fetoprotein and human chorionic gonadotropin during induction chemotherapy of germ cell tumors.

Thirty-seven consecutive patients with germ cell cancers (34 testicular, three extragonadal) and elevated serum levels of alpha-fetoprotein (AFP) and/or human chorionic gonadotropin (HCG) were treated with vinblastine, bleomycin, and cis-diamminedichloroplatinum induction chemotherapy. The AFP and/or HCG normalized in 36 patients. The AFP half-life was 7.9 days between Days 1 and 21 postchemotherapy but 6.0 days between Days 21 and 42 (p less than 0.05). The prolonged AFP half-life between Days 1 and 21 was related to a median increase of 57.5% (range, 22 to 219%) in the AFP level. This increase in the marker value occurred between Days 2 and 9 of therapy (median, Day 5). There was also a median increase of 181% (range, 27 to 600%) in the HCG level at a median of 5 days after the start of therapy. The increase in the AFP and HCG levels occurred in 63 and 70% of evaluable patients, respectively, and correlated with the presence of a large volume of metastatic disease (chi 2 = 8.87). Patients with relapsed or refractory disease had prolongation of the AFP half-life between Days 21 and 42 as compared to nonrelapsed patients. AFP and HCG half-life calculations should be used in the management of patients with germ cell cancers.

Adolescent↗

Tumor markers in advanced nonseminomatous testicular cancer.

The serum levels of human chorionic gonadotropin (HCG), alphafetoprotein (AFP), lactic dehydrogenase (LDH), and carcinoembryonic antigen (CEA) were measured in 62 men with advanced nonseminomatous germ-cell testicular tumors. The HCG level was elevated in 64%, the AFP level in 67%, and the LDH level in 62%, including three of the six men with normal levels of the other two markers. At least one of these three markers was elevated in 91% of patients. Sustained or rising levels of HCG or AFP always were accompanied by persistent or recurrent tumor. Carcinoembryonic antigen was found not to be a useful marker in testicular cancer. Patients whose tumors contained yolk-sac elements always had elevated AFP levels, and patients with choriocarcinoma always had elevated levels of HCG. However, absence of these histologic types did not preclude elevations of the respective markers. Tumor markers are indispensable in the management of patients with testicular cancer, and several markers must be measured repeatedly if the greatest percentage of patients is to benefit.

Adolescent↗

Human chorionic gonadotropin and alphafetoprotein in the staging of nonseminomatous testicular cancer.

Thirty patients with nonseminomatous testicular cancer and no evidence of metastases outside the retroperitoneum were evaluated for discrepancy between the clinical and pathologic stages and also for frequency of elevations of the serum levels of human chorionic gonadotropin (hCG) and alphafetoprotein (AFP). When marker-level data were not considered in the staging, the clinical and pathologic stages differed in 47% of the patients; the inclusion of marker data reduced the staging error to 37%. Seven of ten patients with clinical Stage I, pathologic Stage II disease had normal marker levels (false-negative results). However, there were no false-positive results: abnormal marker levels before retroperitoneal lymphadenectomy always signalled persistent tumor unless the level could be accounted for by the metabolic decay rate of marker produced by the primary tumor. Comparison of marker-level data from these patients with data from 48 patients with Stage III disease demonstrated increasing frequency of elevated marker levels with increasing stage (P less than 0.001). Serial determinations of HCG and AFP are helpful in clinical staging and are necessary in clinical management.

Chorionic Gonadotropin↗

Cytogenetic evidence for premeiotic transformation of human testicular cancers.

To determine the point at which transformation of the germ cell occurs during meiosis in nonseminomatous testicular cancer, the sex chromosome compositions of 15 cell lines derived from primary tumors or metastases of 12 patients with testicular cancer were analyzed by trypsin G-banding analysis and Y-body staining. The simultaneous existence of both X- and Y-chromosomes in a single cell has been confirmed in 14 cell lines. This suggests that transformation of the cell occurs before the first meiotic division because it is known that segregation of X- and Y-chromosomes occurs during the first meiotic division. An incidental finding was the presence of Barr bodies in some cell lines containing more than one X-chromosome, which is consistent with the known primitive nature of testicular cancer and its ability to differentiate independently from the male host.

Cell Differentiation↗