Treatment and outcome of patients with Graves' disease and metastatic differentiated thyroid cancer.

BACKGROUND: The aim of the study was to report on the experience in a single tertiary cancer center about the treatment and outcome of patients with Graves' disease (GD) and metastatic thyroid cancer as compared with patients without GD in our country. PATIENTS AND METHODS: Altogether, 28 patients (8 males, 20 females; 49-85 years of age; median 74 years) were treated because of differentiated thyroid cancer and distant metastasis at the time of diagnosis during a 10-year period (from 2010 to 2019) in the Republic of Slovenia. The subject of our retrospective study were four patients (three men, one female; 64-76 years of age, median 73 years) who had Graves' disease and metastatic thyroid cancer. RESULTS: The mean age of patients without GD and with GD was 74 years and 71 years, respectively (p = 0.36). There was a trend for male predominance in patients with GD (p = 0.06). There was no statistical difference in size of primary tumors, pT stage or pN stage between the group of patients without GD and with GD. The median length of follow-up was 3.33 years (range 0.04-7.83) and 5-year disease-specific survival was 51%. One of four patients with GD and 14 of 24 patients without GD died of thyroid cancer. There was no statistical difference in disease-specific survival between patients' group of without GD and with GD (p = 0.59). CONCLUSIONS: In our country Slovenia, 14% of patients with metastatic differentiated thyroid carcinoma at the time of diagnosis had Graves' disease. There was no difference in the treatment, outcome or survival of patients with GD in comparison to those without GD.

Graves disease and metastatic hormonal-active Hürthle cell thyroid cancer: A case report.

RATIONALE: A hormone-active metastatic Hürthle cell thyroid carcinoma (HCTC) and Graves disease (GD) present a therapeutic challenge and is rarely reported. PATIENT CONCERNS: We present a 64-year-old male patient, who had dyspnea and left hip pain lasting 4 months. He had clinical signs of hyperthyroidism and a tumor measuring 9 cm in diameter of the left thyroid lobe, metastatic neck lymph node and metastases in the lungs, mediastinum, and bones. DIAGNOSIS: Laboratory findings confirmed hyperthyroidism and GD. Fine-needle aspiration biopsy and cytological investigation revealed metastases of HCTC in the skull and in the 8th right rib. A CT examination showed a thyroid tumor, metastatic neck lymph node, metastases in the lungs, mediastinum and in the 8th right rib measuring 20 × 5.6 × 4.5 cm, in the left acetabulum measuring 9 × 9 × 3 cm and parietooccipitally in the skull measuring 5 × 4 × 2 cm. Histology after total thyroidectomy and resection of the 8th right rib confirmed metastatic HCTC. INTERVENTIONS: The region of the left hip had been irradiated with concomitant doxorubicin 20 mg once weekly. When hyperthyroidism was controlled with thiamazole, a total thyroidectomy was performed. Persistent T3 hyperthyroidism, most likely caused by TSH-R-stimulated T3 production in large metastasis in the 8th right rib, was eliminated by rib resection. Thereafter, the patient was treated with 3 radioactive iodine-131 (RAI) therapies (cumulative dose of 515 mCi). Unfortunately, the tumor rapidly progressed after treatment with RAI and progressed 10 months after therapy with sorafenib. OUTCOMES: Despite treatment, the disease rapidly progressed and patient died due to distant metastases. He survived for 28 months from diagnosis. LESSONS: Simultaneous hormone-active HCTC and GD is extremely rare and prognosis is dismal. Concomitant external beam radiotherapy and doxorubicin chemotherapy, followed by RAI therapy, prevented the growth of a large metastasis in the left hip in our patient. However, a large metastasis in the 8th right rib presented an unresolved problem. Treatment with rib resection and RAI did not prevent tumor recurrence. External beam radiotherapy and sorafenib treatment failed to prevent tumor growth.

Cardiac monitoring in patients on trastuzumab: correlation of ultrasound and radionuclide ventriculography.

BACKGROUND: Guidance on cardiac surveillance during adjuvant trastuzumab therapy remains elusive. The recommended methods are two-dimensional echocardiography (2D-ECHO) and electrocardiography gated equilibrium radionuclide ventriculography (RNV). We assessed the correlation and possible specific merits of these two methods. METHODS: In a prospective cohort study in patients undergoing post-anthracycline adjuvant trastuzumab therapy, clinical assessment, 2D-ECHO and RNV were performed at baseline, 4, 8 and 12 months. The correlation between used methods was estimated with Pearson's correlation coefficient and Bland-Altman analysis. RESULTS: Ninety-two patients (mean age 53.6±9.0 years) were included. The correlation of LVEF measured by ECHO and RNV at each time point was statistically insignificant. Values obtained by ECHO were on average higher (3.7% to 4.5%). A decline in LVEF of ≥10% from baseline was noticed in 19 (24.4%) and 13 (14.9%) patients with ECHO and RNV, respectively, however in only one patient by both methods simultaneously. A decline in LVEF of ≥10% to below 50% was found in three and none patients according to RNV and ECHO measurements, respectively. CONCLUSIONS: There is a weak correlation of ECHO and RNV measurements in individual patient, the results obtained by the methods are not interchangeable. LVEF values determined by 2D-ECHO were on average higher compared to RNV determined ones. When in an asymptomatic patient a decline in LVEF requiring treatment interruption is detected by RNV ECHO re-evaluation and referral to a cardiologist is advised.

Treatment and outcome of 32 patients with distant metastases of Hürthle cell thyroid carcinoma: a single-institution experience.

BACKGROUND: It is generally believed that patients with Hürthle cell thyroid carcinoma (HCTC) have a poor prognosis. Furthermore, distant metastases represent the most frequent cause of thyroid cancer-related death of patients with HCTC. The aim of this study was to report the treatment and outcomes of patients with distant metastases. METHODS: Altogether 108 patients were treated for HCTC from 1972 to 2011 in our tertiary center and 32 patients (19 females, 13 males; median age 64.5 years) had either initially proven metastatic disease (N = 12) or distant progression of HCTC after initial treatment (N = 20). Patients with metastases were followed for 1-226 (median 77) months. Data were collected on the patients' gender and age, extent of their disease, morphologic characteristics, therapy, outcome, and survival rate. Statistical correlation between possible prognostic factors and cause-specific survival from time of detection of metastases was analyzed by univariate analysis and log-rank test. RESULTS: The most common were lung metastases, followed by bone, mediastinum, kidney, and liver in 24, 8, 2, 1, and 1 case, respectively. Total thyroidectomy, lobectomy, subtotal thyroidectomy and neck dissection were performed in 19, 10, 3, and 7 patients, respectively. Radioiodine (RAI) ablation of thyroid remnant was performed in 30 patients, while 20 of them had RAI therapy (median 4 times). RAI uptake in metastases was present in 16 patients and ranged from 0.05 % to 12 %. Chemotherapy was used in 13 patients and external beam radiotherapy in 19 patients. Locoregional control of disease was achieved in 19/21 (90 %) cases who succumbed due to HCTC. Estimated 10-year disease-specific survival for all patients was 60 %. 10-year disease-specific survival for patients with pulmonary metastases and other sites metastases was 60 % and 62 %, respectively. 10-year disease-specific survival for patients with single organ and multiple organ metastases was 52 %, and 100 %, respectively. Estimated median disease-specific survival after the diagnosis of metastatic disease for all patients was 77 months. The median disease-specific survival after the diagnosis of metastatic disease for patients with pulmonary metastases and other sites metastases was 72 and 138 months, respectively. CONCLUSIONS: Ten-year disease-specific survival for all patients with metastatic Hürthle cell thyroid carcinoma, patients with pulmonary metastases and bone metastases was 60 %, 60 % and 68 %, respectively.

Neoadjuvant chemotherapy in 16 patients with locally advanced papillary thyroid carcinoma.

BACKGROUND: It is believed that chemotherapy (ChT) is ineffective in papillary thyroid carcinoma (PTC). The aim of our retrospective chart review was to find out if neoadjuvant ChT before thyroid surgery had any effect on the size of primary tumors in patients with PTC. METHODS: The study included 16 patients (13 women, 3 men; median age 63.5 years) with PTC, who were treated with neoadjuvant ChT from 1988 to 2005. Poorly differentiated PTC, classical PTC, a follicular variant of PTC, and a Hürthle cell variant of PTC were diagnosed in 5, 5, 3, and 3 cases, respectively. The mean tumor diameter was 9.67 cm. Seven patients had a pT4 tumor. Regional and distant metastases were detected in 10 and 7 patients, respectively. ChT consisted of vinblastine in 11 cases, vinblastine with adriamycin in 2 cases, and other schedules in 3 cases. Four patients were also treated with preoperative external irradiation. RESULTS: Altogether, 40 cycles of ChT were given. After ChT, the tumor size decreased in all 16 patients: by >50% in 7 (44%) patients and by <50% in 9 patients. R0, R1, and R2 resection was performed in 2, 10, and 4 cases, respectively. The median survival time of our patients was 88 months. Six patients are still alive; two died of causes not related to carcinoma, while eight patients died of PTC. CONCLUSIONS: Neoadjuvant ChT before thyroid surgery may be effective in patients with locally advanced PTC. After neoadjuvant ChT, in 44% of patients, the tumor size decreased by >50%.

Recombinant human thyrotropin-aided radioiodine therapy in patients with metastatic differentiated thyroid carcinoma.

Our aim was to test the efficacy of 131-I therapy (RIT) using recombinant human TSH (rhTSH) in patients with differentiated thyroid carcinoma (DTC) in whom endogenous TSH stimulation was not an option due to the poor patient's physical condition or due to the disease progression during L-thyroxin withdrawal. The study comprised 18 patients, who already have undergone total or near-total thyroidectomy and radioiodine ablation and 0-12 (median 5) RITs after L-thyroxin withdrawal. Our patients received altogether 44 RITs using rhTSH while on L-thyroxin. Six to 12 months after the first rhTSH-aided RIT, PR and SD was achieved in 3/18 (17%) and 4/18 patients (22%), respectively. In most patients (n = 12; 61%) disease progressed despite rhTSH-aided RITs. As a conclusion, rhTSH-aided RIT proved to add some therapeutic benefit in 39% our patients with metastatic DTC, who otherwise could not be efficiently treated with RIT.

The role of preoperative ultrasonography in reducing the number of sentinel lymph node procedures in melanoma.

Sentinel lymph node (SLN) biopsy is the most effective method to nodally stage patients with melanoma. However, SLN metastases are an indication for a complete regional lymphadenectomy. The aim of this study was to evaluate the ability of ultrasound (US) and US-guided fine needle aspiration biopsy (US-FNAB) to reduce the number of patients requiring a second surgical procedure. Fifty-seven patients with melanoma underwent preoperative US of the regional lymph nodes before SLN biopsy. In patients with US malignant lymph nodes, US-FNAB was performed. Only patients with cytologically proven lymph node metastases proceeded directly to a complete regional lymphadenectomy, whereas, in all others, SLN biopsy was performed. Fourteen patients (25%) had metastases in the regional lymph nodes. There were 40 benign and 17 malignant US results. US-FNAB was performed in 14 patients. It was positive in three, negative in nine and inadequate sampling was obtained in two. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of US were 71%, 84%, 59% and 90%, respectively. US of the regional lymph nodes with US-FNAB enables the safe selection of patients who should proceed directly to a complete regional lymphadenectomy. However, the sensitivity and PPV of the method are low.

Low sensitivity of the touch imprint cytology of the sentinel lymph node in breast cancer patients--results of a large series.

BACKGROUND AND OBJECTIVES: Touch imprint cytology (TIC) was reported to be a sensitive method of intraoperative sentinel lymph node (SLN) assessment. The objective of our study was to assess the value of the TIC as an intraoperative SLN evaluation method and to determine a subgroup of patients in whom TIC should not be indicated. METHODS: In 250 breast cancer patients with SLN biopsy, TIC of SLNs was performed intraoperatively. The results of TIC were compared to the final histopathological analysis of SLNs. A subgroup analysis of the TIC value was performed with regard to the tumor size. RESULTS: SLN metastases were found in 102/250 patients (41%). Two cases were false positive. The sensitivity of TIC was 34%, specificity 98.6%, accuracy 72%, negative predictive value 69%, and positive predictive value 95%. TIC was significantly more sensitive to detect macrometastases (32/43) compared to micrometastases or ITC (3/59) (P < 0.001). TIC was positive in only 5% (4/77) in T < 10 mm tumors compared to 18% (31/168) in T > 10 mm (P = 0.01). CONCLUSIONS: TIC is a simple, quick, and sensitive method of intraoperative SLNs evaluation for the presence of the macrometastases. TIC has a very limited value in detecting micrometastases and no value in detecting ITC. TIC may not be indicated in T1a + b tumors.

The role of radioactive iodine in the treatment of Hürthle cell carcinoma of the thyroid.

It is generally believed that Hürthle cell thyroid carcinoma (HCTC) does not accumulate radioactive iodine (RAI). The aim of our retrospective study was to find out if, after thyroid surgery and RAI ablation of the thyroid remnant, the metastatic or recurrent HCTC accumulates RAI. We reviewed the charts of 48 patients with histopathologically verified HCTC, who were treated at the Institute of Oncology in Ljubljana, Slovenia, from 1972 to 2000. In 16 patients (11 women, five men; 47-77 years old), who had distant metastases at presentation (eight patients) or recurrence (eight patients), whole-body RAI scanning was performed after the withdrawal of thyroid hormone replacement. Whenever RAI uptake was confirmed, the therapy with 5.6 GBq of RAI was performed. In 11 of 16 patients, the uptake (range 0.1-12%) of RAI was confirmed. Altogether, 46 therapeutic applications of RAI were given. We conclude that whole-body scanning with RAI should be performed in HCTC. RAI may be effective in the treatment of HCTC.

Columnar cell thyroid carcinoma - diagnostic dilemmas and pitfalls.

BACKGROUND: Columnar cell carcinoma is a rare variant of papillary thyroid carcinoma associated with aggressive clinical behaviour. A CASE REPORT: of a 34-year-old male patient, who presented with the rapidly growing mass in the neck, extending to the anterior and middle mediastinum, tightly closing the upper thoracic apperture and causing tracheal and oesophageal deviation, with minimal compression and stenosis. A diagnosis of columnar cell carcinoma, arising from the ectopic thyroid tissue just adjacent to the left thyroid lobe was based on histological and intraoperative findings. Near total thyroidectomy and lymph-node dissection were followed by external beam radiotherapy of the neck and mediastinum, chemotherapy and radioiodine ablation of the remaining functional thyroid tissue. Pre-and post-operative radionuclide imaging (99mTc(V)-DMSA, 99mTc-MIBI, 123-I-mIBG and Octreoscan findings are discussed, with a special emphasis given to the dilemmas in histological characterisation of the tumor, the problems in therapeutic approach and the dilemmas and pitfalls in the interpretation of radionuclide findings in this patient, especially the ones performed post radiotherapy of the neck and mediastinum.