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Papers by Jasna Mihailovic

Best Practice & Research Clinical Endocrinology & Metabolism, 2008

Iodide uptake across the membranes of thyroid follicular cells and cancer cells occurs through an... more Iodide uptake across the membranes of thyroid follicular cells and cancer cells occurs through an active transport process mediated by the sodium-iodide symporter (NIS). The rat and human NIS-coding genes were cloned and identified in 1996. Evaluation of NIS gene and protein expression is critical for the management of thyroid cancer, and several approaches to increase NIS levels have been tried. Identification of the NIS gene has provided a means of expanding its role in radionuclide therapy and molecular target-specific theragnosis (therapy and diagnosis using the same molecular target). In this article, we describe the relationship between NIS expression and the thyroid carcinoma treatment using I-131 and alternative therapeutic approaches.

Archive of Oncology, 2012

Esophageal carcinoma is a relatively rare disease with approximately 13,200 new cases detected in... more Esophageal carcinoma is a relatively rare disease with approximately 13,200 new cases detected in 2001 in the United States (1). It is most common between 50 and 60 years of age with a male to female ratio of 4:1 (2). According to the SEER database, an annual age-adjusted incidence rate is 4.5 per 100,000 men and women. Esophageal cancer is a highly lethal neoplasm with the reported annual age-adjusted mortality rate of 4.3 per 100,000 men and women (3). For the period between 2001 and 2007, in less than 25% of patients who were diagnosed without nodal involvement, the 5-year relative survival was 37.3%; while in 32% of those diagnosed with regional nodal involvement or documented metastatic disease, the 5-year survival was 18.4%, and 3.1%, respectively (2). The gold standard for conventional staging in esophageal cancer includes CT and endoscopic ultrasound (EUS) with associated biopsy of the mucosa. The depth of tumor invasion is usually assessed by combination of esophagogastroduodenoscopy and endosonography. This approach evaluates extent of mucosal involvement and peritumoral nodal metastases, but is limited in patients with stenoses and strictures due to incomplete passage of the endoscope. CT may detect both local invasion of neighboring mediastinal structures and regional nodal and distal metastases (4). CT is less sensitive, however, for detection of regional and distant metastases compared to FDG PET. FDG PET or FDG PET/CT imaging has a significant role in primary staging of esophageal cancer (5-12). FDG PET provides more accurate staging and more accurate prognostic stratification than CT alone. It may alter the treatment strategy in more than 30% of patients (9, 12). Nevertheless, both FDG PET and CT

Archive of Oncology, 2012

Journal of Nuclear Medicine, 2014

The overall prognosis in pediatric differentiated thyroid carcinoma (DTC) is excellent. Recurrent... more The overall prognosis in pediatric differentiated thyroid carcinoma (DTC) is excellent. Recurrent disease is frequent, however, and requires additional treatment. We analyzed the probability of recurrence, prognostic factors, treatment, and outcome of juvenile DTC. Methods: Fifty-one DTC patients (32 girls and 19 boys; ≤20 y old; mean age, 16.5 y) were treated with 131 I (radioiodine, or radioactive iodine [RAI]); the median follow-up was 10 y. Patients underwent different initial treatments: 46 patients received total thyroidectomy and RAI, 3 patients received total thyroidectomy, and 3 patients received subtotal thyroidectomy. The probability of recurrence and prognostic factors were tested with the Kaplan-Meier method. Results: Initially, 36 of 51 patients achieved complete remission, 14 of 51 achieved partial remission, and 1 of 51 had progressive disease. By the follow-up, 11 of 51 patients (21.6%) had developed recurrent disease; the median appearance time was 4 y (range, 1-15 y). The probabilities of recurrence were 16.7% at 5 y, 22.3% at 10 y, and 33.3% at 15 and 23 y after the initial treatments. Factors that were strongly predictive of recurrence were age (P 5 0.001), initial treatment (P 5 0.0001), and tumor multifocality (P 5 0.011). Sex, nodal metastases at presentation, distal metastases at presentation, histologic type of the tumor, T stage, and clinical stage had no influence on relapse (P 5 0.180, P 5 0.786, P 5 0.796, P 5 0.944, P 5 0.352, and P 5 0.729, respectively). Patients with recurrent disease, partial remission, and progressive disease were retreated, with either surgery or surgery and RAI, receiving cumulative activities of up to 40 GBq. The overall outcome in our patients was excellent: 90.2% complete remission, 3.92% partial remission, 1.96% stable disease, 1.96% disease-related death, and 1.96% another cause of death. Conclusion: Younger age at diagnosis, less radical primary surgery without subsequent RAI, and tumor multifocality are factors that are strongly prognostic for recurrence. For reducing the rate of relapse and improving surveillance for recurrent disease, total thyroidectomy followed by RAI appears to be the most beneficial initial treatment for patients with juvenile DTC. The use of RAI seems to be safe, with no adverse effects on subsequent fertility and pregnancy or secondary malignancy.

Best Practice & Research Clinical Endocrinology & Metabolism, 2008

Iodide uptake across the membranes of thyroid follicular cells and cancer cells occurs through an... more Iodide uptake across the membranes of thyroid follicular cells and cancer cells occurs through an active transport process mediated by the sodium-iodide symporter (NIS). The rat and human NIS-coding genes were cloned and identified in 1996. Evaluation of NIS gene and protein expression is critical for the management of thyroid cancer, and several approaches to increase NIS levels have been tried. Identification of the NIS gene has provided a means of expanding its role in radionuclide therapy and molecular target-specific theragnosis (therapy and diagnosis using the same molecular target). In this article, we describe the relationship between NIS expression and the thyroid carcinoma treatment using I-131 and alternative therapeutic approaches.

Archive of Oncology, 2012

Esophageal carcinoma is a relatively rare disease with approximately 13,200 new cases detected in... more Esophageal carcinoma is a relatively rare disease with approximately 13,200 new cases detected in 2001 in the United States (1). It is most common between 50 and 60 years of age with a male to female ratio of 4:1 (2). According to the SEER database, an annual age-adjusted incidence rate is 4.5 per 100,000 men and women. Esophageal cancer is a highly lethal neoplasm with the reported annual age-adjusted mortality rate of 4.3 per 100,000 men and women (3). For the period between 2001 and 2007, in less than 25% of patients who were diagnosed without nodal involvement, the 5-year relative survival was 37.3%; while in 32% of those diagnosed with regional nodal involvement or documented metastatic disease, the 5-year survival was 18.4%, and 3.1%, respectively (2). The gold standard for conventional staging in esophageal cancer includes CT and endoscopic ultrasound (EUS) with associated biopsy of the mucosa. The depth of tumor invasion is usually assessed by combination of esophagogastroduodenoscopy and endosonography. This approach evaluates extent of mucosal involvement and peritumoral nodal metastases, but is limited in patients with stenoses and strictures due to incomplete passage of the endoscope. CT may detect both local invasion of neighboring mediastinal structures and regional nodal and distal metastases (4). CT is less sensitive, however, for detection of regional and distant metastases compared to FDG PET. FDG PET or FDG PET/CT imaging has a significant role in primary staging of esophageal cancer (5-12). FDG PET provides more accurate staging and more accurate prognostic stratification than CT alone. It may alter the treatment strategy in more than 30% of patients (9, 12). Nevertheless, both FDG PET and CT

Archive of Oncology, 2012

Journal of Nuclear Medicine, 2014

The overall prognosis in pediatric differentiated thyroid carcinoma (DTC) is excellent. Recurrent... more The overall prognosis in pediatric differentiated thyroid carcinoma (DTC) is excellent. Recurrent disease is frequent, however, and requires additional treatment. We analyzed the probability of recurrence, prognostic factors, treatment, and outcome of juvenile DTC. Methods: Fifty-one DTC patients (32 girls and 19 boys; ≤20 y old; mean age, 16.5 y) were treated with 131 I (radioiodine, or radioactive iodine [RAI]); the median follow-up was 10 y. Patients underwent different initial treatments: 46 patients received total thyroidectomy and RAI, 3 patients received total thyroidectomy, and 3 patients received subtotal thyroidectomy. The probability of recurrence and prognostic factors were tested with the Kaplan-Meier method. Results: Initially, 36 of 51 patients achieved complete remission, 14 of 51 achieved partial remission, and 1 of 51 had progressive disease. By the follow-up, 11 of 51 patients (21.6%) had developed recurrent disease; the median appearance time was 4 y (range, 1-15 y). The probabilities of recurrence were 16.7% at 5 y, 22.3% at 10 y, and 33.3% at 15 and 23 y after the initial treatments. Factors that were strongly predictive of recurrence were age (P 5 0.001), initial treatment (P 5 0.0001), and tumor multifocality (P 5 0.011). Sex, nodal metastases at presentation, distal metastases at presentation, histologic type of the tumor, T stage, and clinical stage had no influence on relapse (P 5 0.180, P 5 0.786, P 5 0.796, P 5 0.944, P 5 0.352, and P 5 0.729, respectively). Patients with recurrent disease, partial remission, and progressive disease were retreated, with either surgery or surgery and RAI, receiving cumulative activities of up to 40 GBq. The overall outcome in our patients was excellent: 90.2% complete remission, 3.92% partial remission, 1.96% stable disease, 1.96% disease-related death, and 1.96% another cause of death. Conclusion: Younger age at diagnosis, less radical primary surgery without subsequent RAI, and tumor multifocality are factors that are strongly prognostic for recurrence. For reducing the rate of relapse and improving surveillance for recurrent disease, total thyroidectomy followed by RAI appears to be the most beneficial initial treatment for patients with juvenile DTC. The use of RAI seems to be safe, with no adverse effects on subsequent fertility and pregnancy or secondary malignancy.