Use of a topoisomerase I inhibitor (irinotecan, CPT-11) in metastatic adrenocortical carcinoma.
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BACKGROUND: Complete responses are rare after medical treatment of adrenocortical tumors. We performed a single center prospective study of the antitumor effect of irinotecan (CPT-11) in patients with metastatic adrenocortical cancer. PATIENTS AND METHODS: Since 1999, all patients with advanced progressive adrenocortical carcinoma, referred to the Institut Gustave-Roussy, have been enrolled prospectively in this study. CPT-11 (250 mg/m(2)) was administered intravenously on day 1 in a 2-h infusion, every 14 days. World Health Organization (WHO) criteria were used to evaluate tumor response and toxicity. RESULTS: During treatment, no dose or schedule modifications were made. A median of three courses were given (range 1-8), and all but two patients received at least three complete chemotherapy courses. No objective or complete responses were observed. The best response achieved was stabilization in three patients, lasting from 1.5 to 4 months. Significant toxicity occurred in two patients. CONCLUSIONS: Our results do not support a major role of CPT-11 in adrenocortical carcinoma. (+info)
Radiofrequency ablation of adrenal tumors and adrenocortical carcinoma metastases.
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BACKGROUND: The current study was performed to analyze the feasibility, safety, imaging appearance, and short-term efficacy of image-guided percutaneous radiofrequency ablation (RFA) of primary and metastatic adrenal neoplasms including adrenocortical carcinoma. METHODS: The procedure was performed using 36 treatment spheres on 15 adrenocortical carcinoma primary or metastatic tumors in eight patients over 27 months. Tumors ranged from 15 to 90 mm in greatest dimension with a mean of 43 mm. All patients had unresectable tumors or were poor candidates for surgery. Mean follow-up was 10.3 months. RESULTS: All patients were discharged or were free of procedure-related medical care 6-48 hours after the procedures without major complications. All treatments resulted in presumptive coagulation necrosis by imaging criteria, which manifested as loss of previous contrast enhancement in ablated tissue. Eight of 15 (53%) posttreatment thermal lesions lost enhancement and stopped growing on latest follow-up computed tomographic scan. Three of 15 (20%) demonstrated interval growth and four did not change in size. Of these four lesions, two showed contrast enhancement. For smaller tumors with a mean greatest dimension less than or equal to 5 cm, 8 of 12 (67%) tumors were completely ablated, as defined by decreasing size and complete loss of contrast enhancement. Three of 15 (20 %) tumors and related thermal lesions were found to have disappeared nearly completely on imaging. CONCLUSIONS: Percutaneous, image-guided RFA is a safe and well tolerated procedure for the treatment of unresectable primary or metastatic adrenocortical carcinoma. The procedure is effective for the short-term local control of small adrenal tumors, and is most effective for tumors less than 5 cm. The survival rate for patients with adrenocortical carcinoma improves when radical excision is performed in selected patients. Aggressive local disease control may potentially influence survival as well. However, further study is required to evaluate survival impact, document long-term efficacy, and to determine if RFA can obviate repeated surgical intervention in specific clinical scenarios. (+info)
Adrenocortical tumors: results of treatment and study of Weiss's score as a prognostic factor.
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PURPOSE: The differential diagnosis between benign and malignant adrenal cortical tumors circumscribed to the gland is controversial. One hundred and seven patients with adrenal cortex tumors (excluding those with primary hyperaldosteronism) were studied to assess the 5-year survival rate of adults, children, patients stratified by pathological stage, and patients stratified according to Weiss's score of <3 or >3. METHODS: The patients were evaluated both clinically and biochemically. One hundred and five patients underwent surgery and were classified pathologically as stages I, II, III, or IV. The tumors were weighed, measured, and classified according to Weiss's criteria and divided into 2 groups: <3 and >3. RESULTS: After 5 years, the survival rate was 77.5% for the whole group, 74.61% for the adults, 84.3% for the children, 100% for stage I, 83.9% for stage II, 33% for stage III, and 11.7% for stage IV groups. Additionally, after 5 years, 100% of the patients with tumors with Weiss's score <3 were alive compared to 61.65% of those with Weiss's score >3. The average weights of the tumors of score <3 and >3 were 23.38 g 41.36 g and 376.3 538.76 g, respectively, which is a statistically significant difference. The average sizes of tumors of Weiss's score <3 and >3 were 3.67 2.2 cm and 9.64 5.8 cm, respectively, which is also a statistically significant difference. CONCLUSIONS: Weiss's score may be a good prognostic factor for tumors of the adrenal cortex. Additionally, there was a statistically significant difference between the average weight and size of tumors with benign behavior (Weiss's score <3) and those with malignant behavior (Weiss's score >3). (+info)
Adrenal cortical carcinomas with myxoid differentiation in the domestic ferret (Mustela putorius furo).
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A total of 15 adrenocortical carcinomas with myxoid differentiation from 15 ferrets were evaluated in this retrospective study. Six of these ferrets (40%) either were euthanatized or died due to invasive and/or metastatic disease. The myxoid component was a variable part (between 5% and 95%) of the adrenal cortical neoplasm and consisted of sheets and cords of small, polygonal neoplastic cells that formed lumenlike spaces. Such spaces contained a variable amount of alcian blue (pH 2.5)-positive mucinous product (i.e., acidic mucopolysaccharides). Neoplastic cells were negative for the argentaffin reaction, but immunohistochemically they were strongly positive for vimentin and alpha-inhibin and lightly positive for synaptophysin. Proliferating cell nuclear antigen (PCNA)-labeling indices (LI) of adrenal cortical neoplastic cells within the myxoid component of the neoplasm were significantly elevated (P < 0.05) compared with those of typical neoplastic adrenal cortical cells or the adjacent nonneoplastic zona reticularis. Ultrastructurally, cells in the myxoid component exhibited a typical adrenocortical phenotype characterized by cytoplasmic lipid vacuoles, prominent rough and smooth endoplasmic reticulum, and zonula adherens. This lesion was interpreted as an adrenal cortical carcinoma with myxoid differentiation and appeared to be highly malignant based on PCNA LI, rate of invasion into adjacent tissue, and metastasis (6/15). This report is the first description of this histologic variant in the ferret, which morphologically resembled the rare myxoid variant of adrenocortical carcinoma described in humans. (+info)
Activin induces x-zone apoptosis that inhibits luteinizing hormone-dependent adrenocortical tumor formation in inhibin-deficient mice.
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Inhibin and activin are members of the transforming growth factor beta (TGF-beta) family of ligands produced and secreted primarily by the gonads and adrenals. Inhibin-null (INH(-/-)) mice develop gonadal tumors and-when gonadectomized-adrenocortical carcinoma. The mechanisms leading to adrenal tumorigenesis have been proposed to involve the lack of a gonadal factor and/or a compensatory increase in gonadotropins. In order to achieve elevation of gonadotropins without the concomitant loss of a gonadal hormone, we crossed INH(-/-) mice with a transgenic mouse strain that has chronically elevated luteinizing hormone (LH) levels (LH-CTP). Compound INH(-/-)-LH-CTP mice die within 6 weeks of age from severe cancer cachexia induced by large, activin-secreting ovarian tumors. Unexpectedly, INH(-/-)-LH-CTP mice not only fail to develop adrenal tumors but have smaller adrenals, with a regressed x zone, indicating that elevated LH levels are not sufficient to induce adrenal tumor formation. However, following gonadectomy, INH(-/-)-LH-CTP mice develop large, sex steroid-producing adrenal tumors that arise from the x zone, indicating a growth-promoting effect of high levels of LH on the adrenal cortex in the absence of ovarian tumors. In addition, in vivo and in vitro data indicate that activin induces apoptosis specifically in the adrenal x zone. The restricted expression of activin receptor subunits and Smad2 in cells of the adrenal x zone, together with the elevated activin levels in INH(-/-)-LH-CTP mice, supports the conclusion that activin inhibits adrenal tumor growth by inducing x-zone regression. (+info)
Extension of adrenocortical carcinoma into the right atrium--echocardiographic diagnosis: a case report.
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BACKGROUND: Adrenocortical carcinoma is a rare, highly malignant tumor. Cardiac involvement of the tumor is very rare. Echocardiography facilitates the evaluation of the cardiac involvement of the tumor. CASE PRESENTATION: We describe a patient with an adrenal tumor. Transthoracic echo showed its extension into the right atrium. Accordingly, a combined abdominal and cardiac operation was performed, monitored by transesophageal echocardiography. CONCLUSION: This case highlights the importance of echocardiography in revealing the cardiac involvement by this tumor and in planning the operative procedure. (+info)
Adrenocortical adenoma and carcinoma: histopathological and molecular comparative analysis.
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We compared histomorphological features and molecular expression profiles of adrenocortical adenomas (ACAd) and carcinomas (ACCa). A critical histopathological review (mean, 11 slides per patient) was conducted of 37 ACAd and 67 ACCa. Paraffin-embedded tissue cores of ACAd (n = 33) and ACCa (n = 38) were arrayed in triplicate on tissue microarrays. Expression profiles of p53, mdm-2, p21, Bcl-2, cyclin D1, p27, and Ki-67 were investigated by immunohistochemistry and correlated with histopathology and patient outcome using standard statistical methodology. Median follow-up period was 5 years. Tumor necrosis, atypical mitoses, and >1 mitosis per 50 high-power fields were factors that were highly specific for ACCa (P <.001). Number (0 to 4) of unfavorable markers [Ki-67 (+), p21 (+), p27 (+), mdm-2(-)] expressed was significantly associated with mitotic activity and morphologic index (i.e., number of adverse morphologic features) and highly predictive of malignancy (P <.001). Ki-67 overexpression occurred in 0 ACAd and 36% ACCa (P <.001) and was significantly associated with mitotic rate and unfavorable morphologic index (P <.001). Tumor necrosis, atypical mitoses, >5 mitoses per 50 high-power fields, sinusoidal invasion, histologic index of >5, and presence of more than two unfavorable molecular markers were associated significantly with metastasis in ACCa. Well-established histopathologic criteria and Ki-67 can specifically distinguish ACCAd from ACCa. Tumor cell proliferation (Ki-67) correlates with mitotic activity and morphologic index. Tumor morphology is a better predictor of metastatic risk in ACCa than current immunohistochemistry-detected cell cycle regulatory and proliferation-associated proteins. (+info)
Carboxy derivatives of isoflavones as affinity carriers for cytotoxic drug targeting in adrenocortical H295R carcinoma cells.
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Carboxy derivatives of isoflavones that exhibit oestrogenic/anti-oestrogenic properties were used as carriers for affinity drug targeting to H295R adrenocortical carcinoma cells that express transcripts of oestrogen receptor (ER) alpha and beta. These derivatives were prepared by introducing a carboxymethyl group at the 6-position of genistein and of biochanin A, yielding 6CG and 6CB respectively. In transactivation assays, 6CG displayed mixed agonist/antagonist activity for ERalpha, whereas 6CB displayed only weak antagonist activity. Low concentrations of oestrogen, 6CG and 6CB were capable of inducing proliferation in H295R cells and of stimulating creatine kinase (CK) specific activity, suggesting that these cells were sensitive to oestrogenic compounds. In in vivo experiments, both 6CG and 6CB were capable of inhibiting oestrogen-induced CK specific activity in rat tIssues. For affinity drug targeting, the cytotoxic drug daunomycin was coupled to 6CB and 6CG, yielding 6CB-Dau and 6CG-Dau respectively. These conjugates were tested for their antiproliferative ability to inhibit DNA synthesis as assessed by incorporation of [(3)H]thymidine in H295R cells. A dose-dependent cytoxicity was observed with both conjugates. At 0.3-3 nM, both conjugates were 10 to 30 times more potent than daunomycin. At 30 nM these conjugates were two to three times more potent than daunomycin. At concentrations ranging between 300 and 3000 nM, no difference in cytotoxicity was observed between the conjugates and daunomycin. When the cells were treated over a wide range of concentrations with a combination of 6CG plus daunomycin, the observed cytotoxicity was less than with daunomycin alone. When non-transformed rat enterocytes, which do not express ER, were treated with 6CG-Dau or daunomycin, the antiproliferative effect of 6CG-Dau was the same as that of daunomycin over the concentration range tested. These pilot studies suggest that the ready availability of oestrogenic binding sites in H295R cells can be exploited for site-directed chemotherapy. (+info)