Pulmonary metastasis of cribriform-morular variant of thyroid carcinoma mimicking primary adenocarcinoma of the lung: A potential pitfall.

Cribriform-morular variant of papillary thyroid carcinoma (CMV-TC) shows a peculiar mixture of follicular, cribriform, papillary, trabecular, and solid patterns with squamoid morules. Ocassionally, lung metastasis may be interpreted incorrectly as primary lung adenocarcinoma. We illustrate a case of pulmonary meastasis of CMV-TC mimicking a primary adenocarcinoma, 7 years after diagnosis of CMV-TC. The lung metastases may be easily missed if the pathologist is unaware of the patient's prior history and a limited immunohistochemical panel (CK7 and TTF-1) is used. The histologic and immunohistochemical (ß-catenin+, ER+, PR+, TTF-1 +, and CK7+) findings were diagnostic of CMV-TC and ensured adequate treatment.

Evaluation of ultrasonographical and cytological features of thyroid nodules in patients treated with radioactive iodine for hyperthyroidism.

BACKGROUND: In this study, we aimed to evaluate ultrasonographical and cytological features of thyroid nodules in patients who were treated with radioactive iodine (RAI) for hyperthyroidism years ago. METHODS: Patients who had a history of RAI treatment for hyperthyroidism and had thyroid nodules that were evaluated with fine-needle aspiration biopsy (FNAB) were included in the study. RESULTS: There were 27 patients (22 female and 5 male) with a mean age of 59.3 ± 13.5. The indication for RAI treatment was Graves in 5 (18.6%), toxic nodular or multinodular goiter in 16 (69.2%), and unknown in 6 (22.2%) patients. A total of 48 thyroid nodules were evaluated with FNAB and cytological diagnosis were benign in 24 (50.0%), nondiagnostic in 15 (31.2%), atypia of undetermined significance in 5 (10.4%), suspicous for malignancy in 2 (4.2%), and malignant in 2 (4.2%) nodules. Thyroidectomy was performed in 10 patients, 5 were benign (50.0%), and 5 (50.0%) were malignant histopathologically. Ultrasonography features of 31 cytologically/histopathologically benign and five cytologically/histopathologically malignant nodules were compared. Prevalence of isoechoic nodules was higher in benign nodules (P = .025). Macrocalcification was observed in 4 (80.0%) of malignant and 10 (32.3%) of benign nodules (P = .042). CONCLUSION: In patients with a history of RAI treatment for hyperthyroidism, thyroid nodules with suspicious ultrasonography features, particulary hypoechoic appearence and macrocalcification, should be evaluated with FNAB irrespective of the time elapsed after RAI treatment.

Computed tomography features of the major salivary glands after radioactive iodine ablation in patients with papillary thyroid carcinoma.

OBJECTIVE: No previous study has investigated computed tomography (CT) features of the major salivary glands (MSGs) after postoperative radioactive iodine ablation (RIA). This study aimed to assess CT features of the MSGs after RIA in patients with papillary thyroid carcinoma (PTC). METHODS: The study population comprised consecutively registered PTC patients who had undergone total thyroidectomy, RIA, follow-up neck ultrasonography (US), and neck CT. The US and CT features of the parotid and submandibular glands in each patient were retrospectively evaluated by a single radiologist. Post-RIA changes were determined by comparisons between follow-up neck US results (main reference) and between preoperative and post-RIA neck CT features. RESULTS: Of the 28 patients, 13 (46.4%) showed post-RIA changes in the parotid glands (n = 8), submandibular glands (n = 0), or both (n = 5) on neck CT. Of the 56 MSGs in 28 patients, post-RIA changes were more common in the parotid glands (n = 23, 41.1%) than in the submandibular glands (n = 8, 14.3%). The common CT findings of post-RIA changes in the parotid gland included low parenchymal attenuation, decreased glandular size, a lobulated margin, decreased or increased parenchymal enhancement, and an inhomogeneous enhancement pattern, whereas common CT findings of post-RIA changes in the submandibular gland included decreased glandular size, a lobulated margin, iso-enhancement, and an inhomogeneous enhancement pattern. CONCLUSION: The common CT features of post-RIA changes in MSGs include decreased glandular size, a lobulated margin, and an inhomogeneous enhancement pattern.

Targeting telomerase with radiolabeled inhibitors.

The expression of telomerase in approximately 85% of cancers and its absence in the majority of normal cells makes it an attractive target for cancer therapy. However the lag period between initiation of telomerase inhibition and growth arrest makes direct inhibition alone an insufficient method of treatment. However, telomerase inhibition has been shown to enhance cancer cell radiosensitivity. To investigate the strategy of simultaneously inhibiting telomerase while delivering targeted radionuclide therapy to cancer cells, 123I-radiolabeled inhibitors of telomerase were synthesized and their effects on cancer cell survival studied. An 123I-labeled analogue of the telomerase inhibitor MST-312 inhibited telomerase with an IC50 of 1.58 µM (MST-312 IC50: 0.23 µM). Clonogenic assays showed a dose dependant effect of 123I-MST-312 on cell survival in a telomerase positive cell line, MDA-MB-435.

Assessing protection against radiation exposure after prostate (125)I brachytherapy.

PURPOSE: To expand the radiation dose rate measurement data set by measuring radiation under various prostate (125)I brachytherapy situations. METHODS AND MATERIALS: Measurements were obtained from 63 consecutive unselected patients at Tokyo Medical Center, Japan. Differences in factors during measurements, such as body postures, distances from the skin surface, and measurement directions were considered. Furthermore, shielding effects of lead-lined underwear, consisting mainly of 0.1-mm thickness of lead, were also assessed. RESULTS: Radiation exposure varies according to the patient's body posture, with results differing as much as approximately 40.0% in measured radiation dose rates at 30cm from the anterior skin surface. Weight, body mass index, and tissue thickness showed good correlations with measured radiation dose rates. The magnitude of radiation exposure attenuation by shielding was approximately 95.8%, similar to the attenuation ratio based on tissue measurements made in the lateral direction. The respective mean times required to reach 1mSv were 1.2, 7.6, and 65.4 days in the standing position and 0.6, 4.6, and 40.4 days in the supine position at the site of contact, and at 30 and 100cm from the anterior skin surface. CONCLUSIONS: This study obtained supplemental information pertaining to radiological protection and confirmed that shielding can be an effective tool for reducing exposures.

Management of thyroid carcinoma in children and young adults.

Thyroid cancers represent the largest group of pediatric carcinomas. Unlike other cancers of childhood, they have not been prospectively studied; instead adult data has been extrapolated to childhood and adolescent treatment. In this article we review the treatment of both well differentiated thyroid cancer (WDTC), as well as medullary thyroid cancer (MTC). The approach to both cancers relies on a low threshold of suspicion, and a willingness to biopsy suspicious lesions. Surgery remains the primary method of curing these patients, although radioactive iodine (RAI) may offer some benefit in WDTC for selected patients. For patients with MTC new medications, such as Vandetanib, may offer some adjuvant benefit following surgery. Lastly, suppression of thyroid stimulating hormone (TSH) may be one of the most beneficial treatments for WDTC.

[Prognosis and long-term results of treatment of patients with differentiated thyroid carcinoma].

Results of treatment of 67 patients with differentiated thyroid carcinoma were analyzed. Pathological changes in the thyroid residue structure were found in 42.3% of patients after subtotal resection of the thyroid gland (SRTG), 38.8% of the total number of patients were given inadequate suppressive therapy. Only 63.4% of women with thyroid carcinoma were found to have pathology of organs of the reproductive system. SRTG is thought to be an unreasonable volume of operative treatment. For the determination of strategy of treatment it is expedient to use the systems of risk assessment of MACIS, TNM, Clinical Class (University of Chicago).

CT-guided interstitial brachytherapy of inoperable non-small cell lung cancer.

PURPOSE: The aim of this study was to assess the technical feasibility, efficacy, and complications of CT-guided interstitial brachytherapy for treating inoperable non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Twenty one patients were included in this prospective study. The median age was 72.6 years (57-85). Tumors were treated with brachytherapy that was positioned under CT-fluoroscopy. The treatment planning system (TPS) was used preoperatively to reconstruct three dimensional images of the tumor and to calculate the estimated seed number and distribution. The median matched peripheral dose (MPD) was 130 Gy (range, 100-160 Gy). All procedures were performed under local anesthesia. A follow-up CT was performed 6 weeks later and every 3 months post implantation. RESULTS: Follow-up period was 2-30 months. The mean diameter of the 21 lung tumors was 4.6 cm (range, 2.8-6.5 cm). The response rate of pain relief was 83.3% (10/12). The pain-free duration was 0-12 months (median: 6 months; 95% CI: 3-9 months). Overall responding rate (CR+PR) for this group of patients was 71.4%. Local tumor control rate was 85.7%. Six (28.6%) patients died as a result of primary tumor progression; thirteen (61.9%) patients died of multi-organ failure or other metastases. Two (9.5%) patients survived to follow-up. At the time of analysis, the median survival time for all patients was 10 months (95% CI: 6.6-13.4 months), with 1 year and 2 year survival rates were 42.4% and 6.5%, respectively. Median survival time for stage II, stage III, and stage IV was 20 months, 9 months, and 8 months, respectively. No major complications were observed. Minor complications (19%) included mild pneumothorax (n=1), hemosputum (n=1), pleural effusion (n=1), and localized skin erythema (n=1). None of these complications required further treatment, although hospital discharge was delayed. No (125)I seeds migrated to other tissues or organs. CONCLUSION: Minimally invasive CT-guided interstitial brachytherapy is safe, useful, less complicated and considered as a palliative treatment option for inoperable non-small cell lung cancer.

Development of a patient-reported questionnaire for collecting toxicity data following prostate brachytherapy.

PURPOSE: To improve a questionnaire used to collect patient-reported outcomes from patients with early stage prostate cancer treated with brachytherapy. A secondary aim was to adapt the Late Effects of Normal Tissue (LENT) subjective toxicity questionnaire for use to collect Common Terminology Criteria for Adverse Events (CTCAE) data, the current preferred platform for assessing radiation toxicity. MATERIALS AND METHODS: Three hundred and seventy-seven patients were treated with permanent iodine-125 seed implant brachytherapy for early prostate cancer. Toxicity data were collected before and at nine time points post-treatment (0-36 months). Compliance rates for patients completing individual items and item-subsection correlation coefficients were calculated. A factor analysis was carried out to analyse responses to the questionnaire and identify less informative questions, which could be removed. Cronbach's α coefficient was used to measure reliability. RESULTS: Two thousand one hundred and eighty-eight questionnaires were analysed. There was poor compliance for questions specifically relating to operations and bowel medication. We found that the division of the questionnaire into subsections based on anatomical site was reasonable and that certain items could be safely removed. The high mean value for Cronbach's α across all questionnaires (0.752; 95% CI: 0.726-0.779) indicated that the questionnaire was reliable. Fifteen of the 44 questions were removed from the original questionnaires. Questions on urinary incontinence severity, management of urinary and bowel incontinence, effects of reduced flow of urine and the effects of symptoms on activity of daily living and change in sexual function were required to adapt the LENT subjective questionnaire for use to collect CTCAE data. CONCLUSIONS: A questionnaire, validated over 6 years to collect LENT subjective data were adapted and is a reliable approach for collecting CTCAE data after prostate brachytherapy.

Targeted radiotherapy for prostate cancer with an oncolytic adenovirus coding for human sodium iodide symporter.

PURPOSE: Oncolytic adenoviruses are promising tools for cancer therapy. Although several clinical reports have indicated both safety and promising antitumor capabilities for these viruses, there are only a few examples of complete tumor eradication. Thus, the antitumor efficacy of oncolytic adenoviruses needs to be improved. One potentially useful approach is combination with radiotherapy. EXPERIMENTAL DESIGN: To target systemically administered radioiodide to tumors, we created Ad5/3-Delta24-human sodium iodide symporter (hNIS), a Rb-p16 pathway selective infectivity enhanced oncolytic adenovirus encoding hNIS. RESULTS: Ad5/3-Delta24-hNIS replication effectively killed prostate cancer cells in vitro and in vivo. Also, the virus-mediated radioiodide uptake into prostate cancer cells in vitro and into tumors in vivo. Furthermore, Ad5/3-Delta24-hNIS with radioiodide was significantly more effective than virus alone in mice with prostate cancer xenografts. CONCLUSIONS: These results suggest that oncolytic adenovirus-mediated targeted radiotherapy might be a potentially useful option for enhancing the efficacy or adenoviral virotherapy.

Histologically bland "extremely well differentiated" thyroid carcinomas arising in struma ovarii can recur and metastasize.

Struma ovarii (SO) infrequently harbor carcinomas that are histologically similar to those arising in the eutopic thyroid. We identified 10 such cases in our files. Eight patients presented with pelvic-related symptoms whereas 2 were incidentally discovered during pregnancy, all with disease confined to the ovary. There were 8 papillary thyroid carcinomas (PTCs) (2 classic and 6 follicular variant) and 2 poorly differentiated thyroid carcinomas. Two of the 10 thyroid carcinomas relapsed after an initial diagnosis of "benign" struma. Both occurred in young women with ovarian cysts discovered during pregnancy. The cystectomy from 1 patient showed thyroid follicles with nuclear features of the follicular variant of PTC whereas the cyst from the second patient showed thyroid follicles with subtle nuclear features, suggestive but not diagnostic of PTC. Both patients presented with disseminated PTC 3 and 4 years after the initial diagnosis, involving the pelvis in both cases and also the liver parenchyma in 1 case. The 2 patients received radioactive iodine therapy after thyroidectomy and are both alive with disease 6 years after diagnosis. The criteria separating hyperplastic nodules from well-differentiated follicular variant of PTC in the thyroid gland seem to be applicable to thyroid-type carcinomas arising in SO. The propensity for adverse clinical behavior does not seem to be related to the grade or histologic type of carcinoma in this small series. The hormonal milieu during pregnancy may lead to progression of malignant SO and such patients should be closely followed, particularly if their treatment consists of cystectomy alone.

Juvenile hyperthyroidism: an experience.

OBJECTIVE: To analyze the clinical profile of juvenile hyperthyroidism at presentation, their treatment outcome; predictors of remission and relapse. METHODS: Retrospective analysis of medical records of 56 patients with juvenile hyperthyroidism seen over a period of 16 years. A cohort of 38 females and 18 males with mean (+/-SD) age of 14.9 +/- 3.4 years (range 3 to 18 years) was analyzed. RESULTS: Majority of patients was in the age group of 12-16 years. Common symptoms observed at presentation were weight loss (82.1%), excessive sweating (78.6%), heat intolerance (76.8%), increased appetite (73.2%) and diarrhea in 48.2%. In addition, accelerated linear growth was observed in 7.1% of patients. Goiter was present in 98.2% of children; 94.5% of which was diffuse and 4.8% was multinodular. The mean ((+/-SD) T3 was 4.8 +/- 3.4 ng/mL (N, 0.6-1.6), T4 was 218 +/- 98 ng/mL (N, 60-155) and TSH was 0.44 +/- 0.36 (N, 0.5-5.5 microIU/mL). TMA positivity seen in 36.9% of patients. All patients were treated with carbimazole; subsequently 4 patients required thyroidectomy and one required radioactive iodine ablation. Mean (+/-SD) duration of follow-up in our patients was 4.9 +/- 3 years, ranging between 1.6 to 16 years and mean (+/-SD) duration of treatment was 34.4 +/- 22.6 months (range 12 to 120 months). Mean (+/-SD) duration to achieve euthyroidism was 5.2 +/- 4.7 months, ranging between 1-33 months. On intention to treat analysis, remission with carbimazole was achieved in 47.6%, remaining patients failed to achieve remission with drug treatment. CONCLUSION: Graves disease is the commonest cause of juvenile hyperthyroidism. Carbimazole is safe, effective, cheap, and easily available form of therapy. It is occasionally associated with serious side effects but requires prolonged follow up.

[Choroidal metastases of malignancies. Review of treatment methods with special regard to application of radiotherapy]. / Przerzuty nowotworowe do naczyniówki galki ocznej. Przeglad metod leczenia ze szczególnym uwzglednieniem radioterapii.

Choroidal metastases are developed in 4 - 12% of patients with solid malignancies. Typical symptoms are loss of visual acuity or visual field, photophobia and floaters. In therapy of choroidal metastases are used following methods: surgery, laser photocoagulation, radiotherapy, and systemic treatment (anti-neoplastic chemotherapy or hormonotherapy). At choice of method of treatment it is taking not only features associate with choroidal metastases (as size, shape, number of changes and localization) but also: performance status of patient and the presence of metastases in any sites. The purpose of this paper is the review of treatment methods of choroidal metastases with special regard to application of radiotherapy. Radiotherapy is a conservative method of treatment, and it is used as brachytherapy or external beam irradiation (teleradiotherapy). Brachytherapy is recommended in case of single change, with base diameter below 18 mm. The positive results are observed in 90% cases. Teleradiotherapy is used in metastatic tumours which size exceed possibility successfully using of brachytherapy, and in case of multiple foci of choroidal changes, and metastases bilaterally localized. 70 - 89% patients developed regression of choroidal metastases after external beam irradiation. The preservation of bulbus oculi is observed in 98% patients. Presented paper showed application of methods of brachytherapy used in Ophthalmological Department of Jagiellonian University, and technique of teleradiotherapy used in Radiotherapy Department of Oncology Centre in Krakow, which are used in treatment of choroidal metastases.

Papillary thyroid carcinoma in children: risk factors and complications of disease recurrence.

INTRODUCTION: Optimal treatment of recurrent papillary thyroid carcinoma (PTC) in children remains controversial. We reviewed our experience with recurrent PTC to better identify children diagnosed with it. AIMS: The objective of this study was to determine the risk factors, optimal treatment, complications, and prognosis of recurrent PTC in children. METHODS: This is a retrospective review of all thyroid resections for children aged 18 years or younger who have PTC at a single institution from 1987 to 1999. RESULTS: Thirty-six children, 7 boys (19%) and 29 girls (81%), underwent initial cervical exploration for PTC. Lymph node involvement was noted in 25 patients (69%); however, there was no distal disease. An equal number of children underwent subtotal thyroidectomy (n = 18) and total (n = 18) thyroidectomy as their initial operation. Papillary thyroid carcinoma recurrences developed in 17 patients (47%) a median of 7 months (range, 1-43 months) after their initial operation. Recurrence was more common for patients with lymph node involvement (P < .01) and multiple nodules (P < .05) at presentation. Recurrence developed in 5 patients after subtotal thyroidectomy and in 12 patients after total thyroidectomy. Sixteen children with recurrent PTC had a second operation and 6 required a third operation. Total operative complications included 2 patients with permanent hypocalcemia and 1 patient with permanent recurrent laryngeal nerve injury, all of whom had a total thyroidectomy. No patient died; however, 3 continue to harbor disease. Mean follow-up for patients with PTC was 65 months (range, 15 to 144 months). CONCLUSIONS: Thyroid resection combined with selective use of radioactive iodine ablation is a safe and effective treatment for recurrent PTC in children. The best predictors of this recurrent disease are lymph node involvement and multiple thyroid nodules at presentation.

Experimental and theoretical determination of dosimetric characteristics of IsoAid ADVANTAGE 125I brachytherapy source.

125I brachytherapy sources are being used for interstitial implants in tumor sites such as the prostate. Recently, the ADVANTAGE 125I, Model IAI-125, source became commercially available for interstitial brachytherapy treatment. Dosimetric characteristics (dose rate constant, radial dose function, and anisotropy function) of this source were experimentally and theoretically determined, following the AAPM Task Group 43 recommendations. Derivation of the dose rate constant was based on recent NIST WAFAC calibration performed in accordance with their 1999 standard. Measurements were performed in Solid Water phantom using LiF thermoluminescent dosimeters. The theoretical calculations were performed in both Solid Water and water using the PTRAN Monte Carlo code. The results indicated that a dose rate constant of the new source in water was 0.98 +/- 0.03 cGy h(-1) U(-1). The radial dose function of the new source was measured in Solid Water and calculated both in water and Solid Water at distances up to 10.0 cm. The anisotropy function, F(r, theta), of the new source was measured and calculated in Solid Water at distances of 2 cm, 3 cm, 5 cm, and 7 cm and also was calculated in water at distances ranging from 1 cm to 7 cm from the source. From the anisotropy function, the anisotropy factors and anisotropy constant were derived. The anisotropy constant of the ADVANTAGE 125I source in water was found to be 0.97 +/- 0.03. The dosimetric characteristics of this new source compared favorably with those from the Amersham Health Model 6711 source. Complete dosimetric parameters of the new source are presented in this paper.

[Surgery and referral for subsequent 131I therapy for patients with differentiated thyroid carcinoma in the south-east of the Netherlands, 1983-1996, compared to the consensus guidelines from 1987]. / Chirurgie en 131I-nabehandeling bij patiënten met gedifferentieerde schildklierkanker in Zuidoost-Nederland, 1983-1996, vergeleken met de consensusrichtlijnen uit 1987.

OBJECTIVE: To evaluate the treatment of patients with differentiated (papillary or follicular) thyroid cancer in general hospitals in the south-east of the Netherlands during the period 1983-1996, in relation to the 1987 national consensus recommendations. DESIGN: Population-based, retrospective, descriptive. METHOD: For the period 1 January 1983-31 December 1996, data on the histology, TNM-stage and treatment (hospital, specialist, type of operation, referral for 131I therapy) of all 236 patients with differentiated thyroid cancer were obtained from the cancer registry of the Comprehensive Cancer Centre South, Eindhoven, the Netherlands. The treatment was compared with the recommendations from the consensus meeting in 1987. RESULTS: Data on 219 patients (137 papillary, 82 follicular thyroid carcinoma) treated in the general hospitals in the region were studied; the 17 remaining patients had been referred from outside the region. Patients were treated at all hospitals in the region; the number of specialists per hospital able to treat thyroid carcinoma (internist and/or surgeon) was limited. In total 79% of the patients underwent a (near-)total thyroidectomy, half of them in two phases, and in 12% of the cases combined with regional lymph node dissection. In the majority of cases, surgical treatment was in accordance with the consensus recommendations: 65-100% of the cases per hospital. The proportion of patients referred for 131I therapy varied from 17% to 90%; referral was more frequent in the case of larger tumours and/or metastases. Of the 24 patients with a small papillary carcinoma without metastases, 79% were not referred for 131I therapy. CONCLUSIONS: The recommendations laid down in the consensus meeting in 1987 were known and appeared to be followed for surgical treatment but for subsequent 131I therapy they appeared to be interpreted differently. A review of the consensus guidelines seems to be worthwhile.

Successful management of Graves' disease in a patient undergoing regular dialysis therapy.

Classic Graves' disease associated with thyroid-stimulating hormone receptor antibodies developed in a woman undergoing regular hemodialysis for uremia from chronic pyelonephritis. Her condition responded well to treatment initially with carbimazole and then an ablative dose of sodium iodide I 131 therapy. To our knowledge this is only the second documented case of hyperthyroidism in a patient with chronic renal failure, and it demonstrates that conventional forms of therapy are efficacious and safe.