Clinical radioimmunodetection of cancer with radioactive antibodies to human chorionic gonadotropin.

Injection of iodine-131-labeled goat immunoglobulin G antibody to human chorionic gonadotropin (hCG) into patients with hCG-secreting trophoblastic and germinal tumors permitted tumor detection and location by external gamma-ray scintigraphy. Excision of one of the metastatic tumors located by this method indicated a tumor/nontumor ration of 39.29. The method appears to offer a new clinical tool for precisely locating hCG-producing tumors in the body, even when tumor identification by other clinical methods has failed.

Increased "pregnancy-specific" beta1-glycoprotein in certain nonseminomatous germ cell tumors.

Schwangerschafts (pregnancy) protein No. 1 (SP1), a recently identified beta1-glycoprotein that occurs during pregnancy, was assayed in the sera of 97 men with germ cell tumors of the testis. SP1 was elevated at 11-440 ng/ml in 3 of 6 men with choriocarcinomas, in 5 of 17 men with teratomas or "teratocarcinomas" (embryonal carcinomas and teratomas), and in 5 of 50 men with embryonal carcinomas; the highest value in 143 patients with nonmalignant diseases was 9.1 ng/ml. None of 24 sera from men with seminomas and none of 5 sera from men with orchitis had elevated SP1. In the 1 patient examined, testicular choriocarcinoma SP1 had immunochemical and gel chromatographic properties similar to those of highly purified SP1 of placental origin.

Failure of cryosurgical treatment of experimental intradermal tumors to eradicate microscopic lymph node metastases in guinea pigs.

Inbred Sewall Wright strain 2 male guinea pigs with established intradermal tumors and microscopic lymph node metastases were treated either by local excision, cryosurgery, or intralesional injection of BCG. Cryosurgery and local excision were effective in eliminating growth of the primary tumor but failed to prevent growth of lymph node metastases. In contrast, intralesional injection of BCG caused regression of primary tumors and prevented growth of lymph node metastases.

Testicular cancer risk among young men: role of cryptorchidism and inguinal hernia.

The role of cryptorchidism (undescended testis) and inguinal hernia in the etiology of testicular cancer among men aged 18-42 years was evaluated in a case-control study of 271 cases and 259 controls referred to three collaborating medical centers in the Washington, DC, area. The relative risk of testicular cancer for men who reported a history of an undescended testis was 3.7 (95% confidence interval = 1.6-8.6). The risk increased with increasing age at correction; the risk was highest for those men whose cryptorchid testis was never corrected. Among unilateral cryptorchids, no increased risk of testicular cancer was observed for the normally descended testis. There was only a slight excess risk for men without cryptorchidism who had a herniorrhaphy; however, those who underwent a hernia operation after age 7 had a significantly elevated risk of testicular cancer on the same side as the hernia. This case-control study is the first one to support the clinical recommendations for early surgical correction of cryptorchidism and inguinal hernia. Data from this study suggest that the excess cancer risk associated with cryptorchidism is due to internal factors that affect the undescended testis rather than to some underlying developmental abnormality.

A trial of combination chemotherapy followed by hormonal therapy for previously untreated metastatic carcinoma of the prostate.

We administered combination chemotherapy with cyclophosphamide, doxorubicin, and cisplatin to 25 previously untreated patients with metastatic prostate cancer in order to assess the efficacy of chemotherapy before any hormonal manipulation. Hormonal therapy was administered only after progression of disease to chemotherapy. All 25 patients were followed until time of death and all were able to receive hormonal therapy. We did not find substantially improved response rates when combination chemotherapy was applied before endocrine treatment since the 33% objective response rate to chemotherapy was only minimally higher than the response in our patients who had failed hormonal therapy and then received identical or similar chemotherapy. Furthermore, the introduction of intensive combination chemotherapy before hormonal therapy in our study did not result in any striking improvement in overall survival compared with patients who received initial hormonal therapy in many other studies. Responses to chemotherapy were not attributable to suppression of serum testosterone since all 12 patients with partial response (PR) or stable disease (SD) and four of seven patients with no response (NR) had normal testosterone levels at the time of response assessment. The initial use of chemotherapy did not adversely affect the expected high percentage of objective responses (68%) to subsequent hormonal manipulation. The frequency, duration, and quality of responses to hormonal therapy exceeded the responses to chemotherapy. The disappointing responses to chemotherapy reflect the very modest efficacy of even aggressively delivered cytotoxic agents.

Serum and cellular biologic tumor markers in patients with urologic cancer.

During the past several years the development of radioimmunoassay and immunocytochemical techniques to detect small amounts of marker in the sera and cancer cells of cancer patients has made a significant impact on the diagnosis and management of certain cancers. Among these markers alpha-fetoprotein, human chorionic gonadotropin, and pregnancy specific beta-1 glycoprotein have been useful in the staging, detection of recurrence, prognosis, and management of testicular cancer. In this article the recent developments and future perspectives concerning these and other newer markers are discussed.

Occupation and risk for testicular cancer: a case-control study.

A case-control study of 271 testicular cancer cases aged 18-42, including 60 seminomas and 206 other germinal cell tumours, and 259 controls was carried out to study the association between occupation and testicular cancer risk. Study subjects were identified at three medical centres, two of which treat military personnel. Controls were men diagnosed with a cancer other than of the genital tract. Associations were identified between professional employment (administrators, teachers and other professionals) and risk for testicular seminoma, OR = 2.8 (95% Cl: 1.4-5.4) and between employment in production work and risk for other germinal cell tumours, OR = 1.8 (95% Cl: 1.1-2.7). No specific occupations within these broad groups were responsible for observed increases. Self-reported exposure to microwave and other radio waves was associated with an excess risk for both seminomas and other germinal cell tumours. However, an assessment of radio wave exposure based on job title did not support this finding. Although testicular cancer has been increasing in recent decades among young males, occupational factors did not appear to account for a substantial proportion of testicular cancer occurrence in the population studied.

ABO(H) cell surface antigens in parathyroid adenoma and hyperplasia.

Forty-three cases of primary hyperparathyroidism were studied with the specific red cell adherence test (SRCA) to determine the presence or absence of ABO(H) cell surface antigens on abnormal parathyroid tissue. Of the 27 patients with the clinicopathologic diagnosis (CPD) of adenoma, 24 (89%) had lost the ABO(H) cell surface antigen of the abnormal gland. Among the 15 patients with the CPD of hyperplasia, the parathyroid tissue from three (20%) had lost its red cell antigen. In one patient, a metastasis from a parathyroid carcinoma had lost the ABO surface antigen. Several patients in whom conflicting SRCA and CPD were obtained had factors that raised doubts as to the validity of their CPD. The SRCA is a simple test that may aid in the difficult differentiation between parathyroid adenoma and hyperplasia.

Immunobiology of induced testis tumor.

Teratocarcinoma of the testis has been induced in the syngeneic mouse system by transplantation of embryonic genital ridges into the testes of adult mice. The regional lymph nodes of tumor-bearing animals were found to be enlarged and hyperplastic but free of tumor cells four weeks after tumor induction. The lymphocytes obtained from these lymph nodes are capable of inducing immunity against the induction of tumor when injected into a group of adult syngeneic mice. The tumor-associated antigen and in vitro cytotoxicity are being studied in our laboratory.

Pharmacology and clinical applications of cis-platinum.

Cis-platinum is one of the most efficacious platinum group metals. This agent is widely used in combination with cancer chemotherapy including urologic, gynecologic, esophageal, and head and neck cancers. The initial experience indicated dose-limiting renal nephrotoxicity. However, recent knowledge through animal and clinical experiments have led to finding ways to prevent the undesirable toxicities of this agent even in high doses. The clinical utilization of cisplatinum in various cancers, including testicular, ovarian, bladder, prostate, esophageal, have been encouraging. The use of high-dose cis-platinum (200 mg/m2) has had important therapeutic impact on patients with poor prognostic testicular cancer when compared with the conventional dosage (100 mg/m2). The current use and future potential of this anticancer metal and its potential analogs are reviewed.

Biologic tumor markers in management of testicular and bladder cancer.

The role of biologic markers in the management of testicular and bladder cancer has been described. alpha--fetoprotein (AFP) and human chorionic gonadotropin when used together have been extremely helpful in detecting recurrence, staging, and monitoring of testicular cancer. The cellular localization of these markers by immunoperoxidase has also been an aid in understanding the natural history of these tumors. The cell surface antigens in bladder cancer have been useful predictors as to whether or not Stage A bladder cancer will develop into more invasive cancer when compared with the conventional histopathologic examination of the bladder tumor. In the last six years we have prospectively utilized these markers in the management of testicular and bladder cancer. The clinical and laboratory findings of these prospective studies are reviewed.

Histopathologic changes of transitional cell carcinoma of bladder after M-VAC chemotherapy.

Over the past several years, we have utilized methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) as definitive, neoadjuvant, and adjuvant therapy for various stages of transitional cell carcinoma with reduced toxicities. Currently, there is little information concerning the histopathologic changes after M-VAC therapy. We report on the histopathologic changes of bladder transitional cell carcinoma following M-VAC chemotherapy in our protocol for treatment of bladder cancer. The main histopathologic findings after M-VAC therapy are squamous metaplasia, necrosis, fibrosis, and persistent transitional cell carcinoma. In 2 cases, there were persistent adenocarcinoma and squamous cell carcinoma. The importance of these observations in terms of diagnostic and therapeutic implications is reviewed.

En bloc resection of inferior vena cava in cytoreductive surgery for bulky retroperitoneal metastatic testicular cancer.

En bloc resection of the inferior vena cava (IVC) has been demonstrated to be of benefit in removing bulky retroperitoneal testicular tumor metastases. The major indications for its use have been to increase the amount of tumor resected, to allow access to large amounts of tumor located posterior to the aorta which would otherwise be inaccesible, to diminish the possibility of massive pulmonary embolism from clot or tumor located in the IVC, and to decrease the risk of major hemorrhage from injury to the IVC, aorta, or one of their branches. To date the surgical morbidity has been acceptable, and no direct mortality has been associated with it.

Surgically preventable site of local recurrence of testicular carcinoma.

We report on a patient with a mixed germ cell testicular carcinoma in whom recurrence developed at the site of retained spermatic cord elements subsequent to retroperitoneal lymph node dissection. This site for recurrence can be prevented by total removal of the spermatic cord. Recurrence at this site often involves the peritoneum thus significantly reducing the survival rate. It is our policy to attach a long length of nonabsorbable suture marker material to the most proximal aspect of the spermatic cord when performing a radical inguinal orchiectomy. Such a marker facilitates the removal of the entire remaining cord if a retroperitoneal node dissection is performed.

Predictors of residual mass requiring surgical resection after chemotherapy of stage III testicular cancer. A prospective study.

In a prospective study, 63 patients with histopathologically proved Stage III nonseminomatous testicular cancer (NSTC) were analyzed to predict the need for surgical resection of residual masses after cis-platinum-based chemotherapy. Of these 63 patients, 23 (37%) had residual masses after cis-platinum-based chemotherapy requiring surgical resection. Of the 23 patients undergoing surgical resections for their residual masses, 18 patients (78%) had matured teratoma, 3 (13%) had fibrosis with necrosis, and 2 (9%) had residual tumors. Twenty of the 23 (91%) patients with residual disease had either teratomatous elements in primary tumor or bulky metastatic disease at the time of initial chemotherapy. Two patients had incomplete resection of the metastatic disease containing teratoma and required additional resection of recurrent growing matured teratomas. We conclude that teratomatous elements in primary tumor having also bulky metastatic disease are strong predictors of residual disease after initial chemotherapy requiring surgery (21 of 23 or 91%).

Total unilateral renal destruction caused by irradiation for Hodgkin's disease.

Total unilateral renal destruction has been observed in a patient who previously received irradiation for Hodgkin's disease. The clinical features, after a six-year asymptomatic interval, included recurrent calculi and infection in what was subsequently demonstrated radiographically to be a nonfunctioning kidney. The gross and microscopic characteristics of the nephrectomy specimen have been described and correlated with the magnitude of irradiation and the clinical course.

Role of lactate dehydrogenase isoenzymes in testicular cancer.

Changes in the serum levels of lactate dehydrogenase have been noted to reflect growth and/or regression in many patients with testicular tumors, but they were nonspecific. However, elevation of the first of the LDH isoenzymes (LD-1) has been found specific to testicular cancer among all neoplasms. In this prospective preliminary report of 19 testicular cancer patients serum LD-1 was found to be normal in 4 patients with no tumor present. Therefore, there were no false positive findings. Of 6 patients with microscopic disease, LD-1 level was normal. Of 9 patients with gross disease, 5 had elevated serum LD-1 and 4 had normal LD-1. Of 4 patients with seminoma, 3 had elevated LD-1 while all 4 patients had no other elevated markers. It appears that elevation of serum LD-1 provides a marker for seminoma and a marker with some specificity for testicular cancer.

Complication with mechanical stapling device in creation of ileoconduit.

Of 296 patients with pelvic malignancy and ileal urinary conduits, urinary tract calculi developed in 14. Calculi which ordinarily require surgical intervention because of their size may pass spontaneously in patients with ileoconduits because of the presence of a chronically dilated colllecting system and the surgical elimination of three of the four sites of stone impaction (pelvic brim, ureterovesical junction, and ureteral orifice). In 1 patient multiple calculi developed around the surgical staples used to create the proximal end of the ileal conduit. We recommend that autosuture with stapling devices not be used to create the proximal end of an ileal urinary conduit.

Thoracoabdominal-median sternotomy for resection of primary adrenal carcinoma extending into inferior vena cava and hepatic vein.

A technique utilizing a combined thoracoabdominal-median sternotomy approach is described for stimulatenous resection of a large adrenal cancer occluding the inferior vena cava and extending into the left hepatic vein. This technique is useful in removint an extensive extension of a renal or adrenal cancer into the inferior vena cava.

Serum beta 2 microglobulin levels in patients with testicular cancer.

To determine whether serum beta 2 microglobulin could be useful as a tumor marker in patients with testicular cancers, sera stored in our serum bank from 23 patients were assayed by radioimmunoassay for beta 2 microglobulin levels. Sera were selected from 12 preorchiectomy patients, 8 patients who had undergone orchiectomy, and 3 patients who had undergone orchiectomy and retroperitoneal lymphadenectomy. Patients with other genitourinary tract disorders and normal age and sex-matched controls were assayed for comparison. The laboratory range for normal serum beta 2 microglobulin values was 1.1 to 2.4 mg/L. Patients without documented testicular tumors had values ranging from 1.4 to 9.7 mg/L. Values for normal controls ranged from 1.7 to 2.4 mg/L. Only 3 patients (12.5 per cent) had elevated serum beta 2 microglobulin values. Serum beta 2 microglobulin seems to have no value as a tumor marker in patients with testicular tumors.