Interleukin‐13 receptor alpha2 is a novel therapeutic target for human adrenocortical carcinoma

BACKGROUND.

Adrenocortical carcinoma (ACC) is a relatively rare but aggressive malignancy with limited therapeutic options. Previous genome‐wide expression studies have demonstrated the overexpression of interleukin‐13 receptor alpha2 (IL13Rα2) in some human malignancies.

METHODS.

The authors evaluated IL13Rα2 mRNA and protein expression in 21 normal samples, 78 benign samples, 10 primary malignant samples, and 25 metastatic/recurrent samples and performed functional analyses with IL13 ligand and IL13 Rα2 knockdown in vitro. The sensitivity of 2 ACC cell lines (NCI‐H295R [high IL13Rα2 expression] and SW13 [low IL13Rα2 expression]) to a highly specific IL‐13 conjugated with Pseudomonas exotoxin (IL‐13‐PE) also was evaluated in both in vitro and in vivo models.

RESULTS.

IL13Rα2 was overexpressed in malignant tumors compared with benign and normal samples (15‐fold higher; P < .05). Immunohistochemistry also confirmed higher protein expression in malignant and benign tumors than in normal adrenocortical tissues (P < .05). The half‐maximal inhibitory concentration for IL‐13‐PE was 1.3 ng/mL in the NCI‐H295R cell line and 1000 ng/mL in the SW13 cell line. Mice that received intratumoral or intraperitoneal IL‐13‐PE injection had a significant reduction in tumor size and increased tumor necrosis compared with control groups (P < .05) and also had prolonged survival (P < .05). IL13Rα2 protein expression increased in cells that were treated with IL‐13 ligand along with cell invasion (P < .05). Direct IL13Rα2 knockdown decreased cellular proliferation and invasion (P < .05).

CONCLUSIONS.

The current results indicated that IL13Rα2 is overexpressed in ACC and regulates cell invasion and proliferation. IL13Rα2 is a novel therapeutic target for the treatment of human ACC. Cancer 2012. © 2012 American Cancer Society.     

The aldosteronoma resolution score: predicting complete resolution of hypertension after adrenalectomy for aldosteronoma

OBJECTIVE: To develop a prediction model using information readily available, at clinical presentation, which could determine whether patients with aldosterone-producing adenomas would have complete resolution of hypertension after adrenalectomy. BACKGROUND: Primary aldosteronism is the most common curable cause of secondary hypertension. However, a large number of patients continue to require antihypertensive medications to control their blood pressure. Differentiating patients that will have complete resolution of hypertension without the need for antihypertensive medications from patients that will require continued use of antihypertensive medications is difficult before adrenalectomy. METHODS: The predictive logistic regression model was derived using data on 100 patients who underwent adrenalectomy for primary aldosteronism at one tertiary medical center and was externally validated using an independent series of 67 patients from another center. RESULTS: Clinical features were similar for patients in the derivation and validation groups. Four readily available predictors (2 or fewer antihypertensive medications, body mass index < or =25 kg/m, duration of hypertension < or =6 years, and female sex) yielded the best predictive model for complete resolution of hypertension after adrenalectomy. Based on the resulting 4-item aldosteronoma resolution score (ARS), 3 likelihood levels for complete resolution were identified: low (0-1), medium (2-3), and high (4-5) with a predictive accuracy of 27%, 46%, and 75%, respectively. CONCLUSION: The ARS accurately identifies individuals at low (ARS < or =1) or high (ARS > or =4) likelihood of complete resolution of hypertension without further need of lifelong antihypertensive medications after adrenalectomy for aldosteronoma. This scoring system can help clinicians objectively inform patients of likely clinical outcomes before surgical intervention.     

Anaplastic thyroid carcinoma. Treatment outcome and prognostic factors

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is rare but is one of the most aggressive human malignancies. Several prognostic factors have been observed in patients with ATC, and some experts advocate aggressive multimodal therapy in selected patients. However, it is unclear whether such an approach significantly improves survival. The authors analyzed prognostic factors and treatment outcomes in patients with ATC reported in the National Cancer Institute's Surveillance, Epidemiology, and End Results data base. METHODS: The cohort consisted of 516 patients with ATC reported to 12 population-based cancer registries between 1973 and 2000. Demographic, pathologic, and treatment data were used for univariate and multivariate survival analyses. RESULTS: The mean patient age at diagnosis was 71.3 years, and there were 171 men and 345 women. Eight percent of patients had intrathyroidal tumors, 38% had extrathyroidal tumors and/or lymph node invasion, and 43% of patients had distant metastasis. The average tumor size was 6.4 cm (range, 1-15 cm). Sixty-four percent of patients underwent surgical resection of their primary tumor, and 63% received external beam radiotherapy. The overall cause-specific mortality rate was 68.4% at 6 months and 80.7% at 12 months. Univariate analysis showed that age < 60 years, female gender, intrathyroidal tumor, external beam radiotherapy, surgical resection, and combined surgical resection of tumor and radiotherapy were associated with a lower cause-specific mortality. On multivariate analysis, only age < 60 years, an intrathyroidal tumor, and the combined use of surgical and external beam radiation therapy were identified as independent predictors of lower cause-specific mortality. CONCLUSIONS: Although most patients with ATC had an extremely poor prognosis, patients < 60 years old with intrathyroidal tumors survived longer. Surgical resection with external beam radiotherapy for ATC was associated with lower cause-specific mortality.     

Results of laparoscopic adrenalectomy for suspected and unsuspected malignant adrenal neoplasms

BACKGROUND: Laparoscopic resection for malignant adrenal tumors is controversial, because they are rare and limited data exist in the literature. HYPOTHESIS: Laparoscopic adrenalectomy for malignant adrenal tumors is safe and effective. PATIENTS AND METHODS: Twenty-three patients who had a laparoscopic approach for suspected and unsuspected malignant adrenal tumors were studied retrospectively. The adrenal mass was suspected to be metastatic if the patient had a history of previous extra-adrenal primary malignancy and/or positive fine-needle aspiration cytologic findings. A primary adrenal cancer was suspected if there were positive fine-needle aspiration cytologic findings and/or a malignant adrenal imaging phenotype. MAIN OUTCOME MEASURES: (1) Margins of tumor resection, (2) tumor recurrence (locoregional, port site, and distant), and (3) disease-free survival. RESULTS: Twenty-three patients (15 men and 8 women) had 24 laparoscopic procedures (20 adrenalectomies, 3 biopsies, and 1 diagnostic laparoscopy). Permanent histologic specimens in the 23 patients showed 5 adrenocortical cancers, 1 undifferentiated adrenal cancer, 13 adrenal metastases, 2 lymphomas, and 2 cases with no evidence of tumor. Clinically suspected adrenal metastases were true positive in 19 patients (83%). The sensitivity of fine-needle aspiration cytology was 57% (n = 7). Only 1 of 6 patients with primary adrenal cancer was suspected to have a malignant tumor preoperatively. The tumor resection margin was negative in all adrenalectomies. There were 3 locoregional recurrences (2 local and 1 lymph node metastasis) in the 6 patients with primary adrenal cancer, no port site recurrences, and 4 distant recurrences in 13 patients with metastatic adrenal tumors. The disease-free survival was 65% at a mean follow-up time of 3.3 years (range, 1-7 years). CONCLUSIONS: A laparoscopic approach in patients with suspected adrenal metastasis can be both diagnostic and therapeutic, and achieves complete tumor resection. In contrast, laparoscopic adrenalectomy for clinically unsuspected adrenocortical cancer is associated with a high recurrence rate. Furthermore, preoperative fine-needle aspiration cytology for the evaluation of suspected malignant adrenal tumors is unreliable.     

Long-term results of reoperation and localizing studies in patients with persistent or recurrent medullary thyroid cancer

HYPOTHESIS: Reoperation benefits patients with locoregional, persistent, or recurrent medullary thyroid cancer (MTC). Currently available localizing studies have limited utility for detecting all foci of residual MTC. DESIGN: A retrospective study with a mean follow-up time of 7.5 years (median, 13 years; range, 2.2-29 years). SETTING: A tertiary referral medical center. PATIENTS: Thirty-three patients who underwent 46 reoperations for locoregional residual MTC. RESULTS: Sixty-four percent of residual MTC was located in the lateral cervical nodes, 22% in the central cervical nodes or thyroid bed, and 14% in the anterior mediastinum (197 of 1128 nodes resected were positive for MTC). After reoperation, basal calcitonin levels were undetectable in 2 patients, reduced by greater than 50% in 10 patients, and either increased or were not reduced by greater than 50% in the remaining patients. On reoperation, one patient had a thoracic duct injury that required reexploration and ligation. Patients who had a greater than 50% decrease in calcitonin levels after reoperation were less likely to develop distant metastases compared with patients who did not have a greater than 50% decrease (P<.05). The sensitivities of magnetic resonance imaging (n = 31), computed tomographic scan (n = 16), ultrasound (n = 9), and dimercaptosuccinic acid scan (n = 3) were 91%, 86%, 88%, and 100%, respectively. CONCLUSIONS: Although reoperation in patients with residual MTC rarely results in biochemical cure, cervical reexploration is safe and in selected patients may limit MTC progression. Lateral cervical node dissection could be beneficial at the time of initial surgical treatment because of the high frequency of residual MTC in the lateral cervical nodes. Noninvasive imaging studies were helpful but far from perfect for guiding the reexploration for locoregional residual MTC.     

Epidemiology of Infectious Keratoconjunctivitis in Cattle in South‐east Ethiopia

The aim of the study was to determine the prevalence of infectious keratoconjunctivitis on cross‐breed dairy farms and to evaluate factors that influence its distribution. A total of 11 dairy farms and one cattle cross‐breeding farm in different parts of Arsi region, south‐east Ethiopia were clinically and bacteriologically investigated from February 1989 to December 1990. Out of 5221 local zebu and cross‐breed dairy animals, 110 were found to have different degrees of infectious bovine keratoconjunctivitis. Of these, 94 (85.5 %) were unilateral and 16 (14.5 %) were bilateral. The prevalence of the disease was significantly (P < 0.001) influenced by age and breed; high exotic blood level and younger age groups were mainly affected. However, severity of the disease was not significantly associated with age (P > 0.750). Moraxella bovis was isolated from 88 (80 %) of the 110 bacteriologically positive cases. Of these isolates, 61 (69 %) were haemolytic and 27 (31 %) were non‐haemolytic strains. Infection with M. bovis was unilateral. Concurrent infections with M. bovis included Actinomyces pyogenes 23 (21 %), Staphylococcus aureus 17 (15 %), Pasteurella haemolytica nine (8 %), Escherichia coli eight (7 %) and Proteus spp. four (3.6 %).