Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extensive hormonal evaluation was performed in a girl with adrenal carcinoma during the primary tumor stage, following adrenalectomy, during the period when metastases were evident and while on treatment with o,p'-DDD. At the age of 14 months a diagnosis of congenital adrenal hyperplasia was made and treatment with dexamethasone (0.125 to 0.25 mg/day) resulted in a fall-off in growth rate, normal advancement in bone age, decrease in virilization and suppression of 17- ketosteroid excretion which continued until 4 3/12 years of age when virilization increased. At five years of age elevated serum and urinary androgen levels unsuppressible with dexamethasone were noted. Following removal of a large right adrenal carcinoma, serum and urinary hormone levels returned to normal. There months following surgery, liver metastases were documented associated with elevated levels of serum androgens. With o,p'-DDD treatment, serum dehydroepiandrosterone sulfate (DS) and urinary 17-ketosteroid (17-KS) excretion fell rapidly while there was a delay in the fall of free androgens. The persistence of free steroid secretion with decreased formation of DS suggests that the o,p'-DDD may have altered sulfatase activity before causing tumor necrosis and total decrease in steroidogenesis.
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PMID:Virilizing adrenal tumor in a child suppressed with dexamethasone for three years. Effect of o,p'-DDD on serum and urinary androgens. 13 87

o,p'-DDD, administered by mouth in doses of 1 to 7 grams daily for 5 to 42 days, was found to lower serum uric acid concentration in each of eight normouricemic patients (one with Cushing's disease and seven with metastatic cancer). The decrease ranged from 21 to 53% (average 39%) and the maximum effect was apparent in five to ten days. Urinary uric acid excretion showed no change, indicating that uric acid production was unaffected and that the hypouricemic effect resulted from an increase in the renal clearance of uric acid. The present findings introduce a new type of chemical compound to the group of known hypouricemic agents.
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PMID:The hypouricemic effect of o,p'-DDD. 51 67

A 56-year-old patient is described who presented with retroperitoneal lymph node metastases 2 years after resection of a Leydig cell tumor of the left testis. The patient did not suffer from endocrinological imbalance. Surgical removal of the metastases alleviated abdominal symptoms for 1 year. o,p'-Dichlorodiphenyl-dichloroethane (o,p'-DDD) treatment was started at the time of recurrence of the retroperitoneal mass and the appearance of a hepatic metastasis. Tumors were remarkably responsive to o,p'-DDD, since 2 complete remissions could be obtained for extended periods. The o,p'-DDD was tolerated reasonably well and serum levels of 15 to 20 mg./l. were sustained for many months. Unfortunately, the patient could not be cured with this effective treatment.
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PMID:Malignant Leydig cell tumor of the testis in complete remission on o,p'-dichlorodiphenyl-dichloroethane. 140 49

Data from ten cases with carcinoma of the adrenal cortex, diagnosed between 1981 and 1988, have been extensively reevaluated. Six patients suffered from a hormonally active tumor with proven clinical and laboratory signs of hypercortisolism and/or hyperandrogenism. Female patients dominated the cohort (eight of ten). No preference for particular age (35 to 64, mean 52) or lateralisation of the tumor was recognisable. In all cases signs for endocrinopathy and/or tumor disease lead to investigative intervention. Nonspecific symptoms like pain, reduction of weight and fatigue were registered most frequently. In three patients an abdominal tumor was palpable. Investigation of hormone levels and imaging procedures (sonography and CT scan) assured correct diagnosis in all cases. Since prior to operation metastases have been detected in five cases and in eight cases capsular invasion was proven histologically only, one patient was free of tumor after operation but developed hepatic metastases later on. Altogether nine of ten patients developed metastases later on. Seven of the patients died from the perioperative period up to 8.4 +/- 8.15 months. Mean survival of all patients was 20.5 +/- 24.5 months. Histological grading and assessment of anaplasia did not correlate with either survival or tumor stage. None of the patients presented with tumor stage I according to the TNM system by MacFarlane (55). All four patients with advanced disease in stage IV died within the first year after operation. Eight patients were treated with 1 to 6 g of the adrenolytic o,p'DDD (mitotane, Lysodren). In one of these cases, a sonographically documented remission lasting for over eight years was observed. A second patient with anaplastic carcinoma showed a reduction of the size of pulmonary metastases under continuous therapy with o,p'DDD and a cyclic polychemotherapy. After the latter was discontinued, the course was progressive.
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PMID:[Adrenal cortex carcinoma: diagnosis, therapy and course in 10 cases]. 143 4

The usefulness of non-specific chemotherapy for advanced adrenocortical carcinoma (ACC) is controversial. We report on 2 young female patients (25 and 19 yr) who presented with a clinical picture of Cushing's syndrome due to histologically confirmed ACC. The first patient underwent radical surgery, but after a disease-free interval of 6 months a local recurrence was apparent. She was reoperated and treated with 6 courses of cisplatin and etoposide chemotherapy. Mitotane (8 g daily) was begun, but 2 months later debulking surgery was again performed. A second-line chemotherapy with the etoposide, adriamycin, cisplatin (EAP) scheme attained a partial remission lasting 7 months, then metastatic spread to the brain led to death of the patient. The survival time was 30 months. The second patient underwent radical surgery and adjuvant mitotane (4 g daily), but multiple lung and mediastinal metastases were diagnosed after an interval of 29 months. Chemotherapy with the EAP regimen (6 courses) without interrupting mitotane attained a partial remission lasting 21+ months. We suggest that the EAP scheme is active in advanced ACC and that its association with mitotane is feasible.
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PMID:Favorable response of metastatic adrenocortical carcinoma to etoposide, adriamycin and cisplatin (EAP) chemotherapy. Report of two cases. 149 8

The existing hypothesis of a viral etiology of penile cancer has been further supported. Exposure to ultraviolet radiation might be another etiologic factor. Controversies still exist as to whether immediate or delayed inguinal lymphadenectomy should be performed in all patients or only in those who are at high risk for developing metastases (histologic dedifferentiation, vascular invasion). 5-Fluorouracil, cisplatin, bleomycin, and methotrexate are active cytostatic drugs in penile cancer and may have a role in the multimodality treatment of this condition. The sensitivity of abdominal computed tomography in detecting adrenal tumors is reported to be 20% to 41%, and the specificity, 85% to 99%. Immunohistopathology may facilitate the differential diagnosis between malignant and benign adrenal cortical tumors. In a retrospective analysis of 105 patients with adrenal cortical cancer, the overall 5-year survival was 22%. Seventy-nine percent of the tumors were hormone producing. Mitotane yielded biochemical and objective responses without impact on survival.
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PMID:Penile and adrenal cancer. 189 24

Ten patients, seven women and three men, ages 47 to 76 years (mean 58.6 years), treated for adrenal cortical carcinoma between 1971 and 1989, were reviewed. Three (30%) of the tumors were nonfunctioning. The remaining seven (70%) were functioning, six of them occurring in women. Common presenting features were hormonal excess, distant metastases, weight loss, and abdominal pain. The primary tumor was resected in all patients, only two of whom had disease confined to the adrenal gland. Tumor diameter ranged from 9 to 21 cm (mean 15.7 cm). Inferior vena caval or right atrial extension of tumor thrombus was present in two patients. Excluding two deaths from postoperative complications, seven patients died of their disease after a mean survival of 25 months (range 2 to 84 months). Of seven patients who received o,p'-DDD treatment for metastatic or recurrent tumor, three (43%) had an objective response. In two patients, tumor regression was complete and was associated with prolonged survival. The first patient underwent resection of recurrent tumor on two occasions in addition to receiving o,p'-DDD and survived 84 months. The second patient had complete regression of pulmonary and liver metastases confirmed at laparotomy and thoracotomy and remains free of disease at 78 months. None of the five patients treated with various combinations of cytotoxic chemotherapy had an observable response, and no measurable effect was seen in a single patient following abdominal radiotherapy. It is concluded that resection for local recurrence may prolong survival and that significant and lasting tumor regression is possible with o,p'-DDD administration. Beneficial results from cytotoxic agents, however, could not be demonstrated.
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PMID:Adrenocortical carcinoma. 192 92

Adrenocortical carcinoma is a rare tumor, and only limited information is available about its natural history and the effects of therapy. We studied 105 patients (75 female and 30 male; mean age, 46 years) with adrenocortical carcinoma who were referred to us between 1963 and 1987. The average duration of symptoms before diagnosis was 8.7 months. At the time of diagnosis, 68 percent of the patients had endocrine symptoms, and 30 percent had distant metastases. Hormonal studies showed that 79 percent of the tumors were functional. Eighty patients underwent surgery, and 59 also received the adrenal cytotoxic agent mitotane. The median disease-free interval after surgery was 12.1 months (range, 1 to 175). Tumor dissemination occurred in 82 percent of the patients, most commonly to the lung, liver, and adjacent organs. The median survival time was 14.5 months (range, less than 1 to 175), and the five-year survival was 22 percent. Age over 40 years and the presence of metastases at the time of diagnosis were the only factors recognized as indicating a poor prognosis. Mitotane controlled hormonal secretion in 75 percent of the patients. Eight mitotane-treated patients had partial tumor regression, but the drug did not have a significant effect on survival. We conclude that adrenocortical carcinoma carries a poor prognosis. Mitotane therapy may offer transient benefits, particularly in controlling endocrine symptoms.
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PMID:Clinical features of adrenocortical carcinoma, prognostic factors, and the effect of mitotane therapy. 238 76

A right adrenocortical carcinoma (weighing 978 g) was removed from a 45-year-old man in April 1986, the tumour bed then being irradiated with 40 Gy. Subsequently discovered multiple lung metastases were treated with cisplatin, etoposide and bleomycin, without improvement. Treatment with mitotane (Lysodren) was also without effect and had to be discontinued because of severe side effects. Treatment with suramin (Germanin) was begun in August 1987. After a loading dose of 10.7 g for six weeks the lung metastases regressed almost completely. But lung metastases were again demonstrated in January 1988 during a low-dose maintenance regimen of suramin. Increased dosage arrested further growth, but achieved no regression of the metastases. The patient died unexpectedly in April 1988 of acute circulatory failure. Suramin administration had been discontinued six weeks earlier because of bronchopneumonia and general deterioration. Thrombocytopenia, coagulation disorders and moderate proteinuria were the side effects of suramin treatment.
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PMID:[Treatment of metastatic adrenal carcinoma with suramin]. 292 93

In the present study, the effects of o,p'-DDD on plasma levels of pregnenolone, 17 alpha-hydroxypregnenolone, progesterone, 17 alpha-hydroxyprogesterone, 11-deoxycorticosterone, deoxycortisol, corticosterone, cortisol, androstenedione and testosterone were studied in 6 patients with adrenal carcinoma (3 with Cushing's syndrome, 2 with adrenogenital syndrome, one without clinical manifestation) and 6 with Cushing's disease. Plasma levels of these steroids were decreased in all of the patients with adrenal carcinoma. The decrement of progesterone and 17 alpha-hydroxyprogesterone was greater than that of pregnenolone and 17 alpha-hydroxypregnenolone. These results indicate that o,p'-DDD inhibits both cholesterol cleavage enzyme and 3 beta-hydroxysteroid dehydrogenase coupled with delta 5 to 4 isomerase system. Plasma levels of pregnenolone and 17 alpha-hydroxypregnenolone showed a twofold increase on the 7th day after consecutive administrations of o,p'-DDD in patients with Cushing's disease. Plasma levels of cortisol were decreased to normal one month after continuous o,p'-DDD treatment. Urinary 17-OHCS and 17-KS have been decreased out of proportion to the decrease in plasma cortisol in the first week of o,p'-DDD treatment. Such a disparity suggests that o,p'-DDD might affect the extra-adrenal metabolism of cortisol. However, no evidence was found for the inhibition of hepatic C17-20lyase and glucuronyl transferase. Regression of pulmonary metastases was observed in one case with Cushing's syndrome due to adrenal carcinoma, suggesting that o,p'-DDD causes necrosis of the metastatic adrenal carcinoma. A remission of the disease was obtained in one patient with Cushing's disease after 6 months of continuous o,p'-DDD treatment. The usefulness of o,p'-DDD for the treatment of adrenal carcinoma with metastases and Cushing's disease was confirmed.
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PMID:[The effects of o,p'-DDD on human adrenal steroid synthesis]. 609 74


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