Evaluation of factors predicting postoperative recurrence and metastasis of parathyroid cancer: a single-center study.

PURPOSE: The purpose of this study was to examine the postoperative clinical course of parathyroid carcinoma to determine factors that predict postoperative recurrence and distant metastasis. METHODS: In this retrospective study, we included 38 patients with parathyroid carcinoma who received surgical intervention at Itoh Hospital between 1979 and 2020. Clinicopathologic characteristics (age, sex, intact PTH, serum Ca level, operation type, parathyroid weight, parathyroid size, histopathologic findings: vascular invasion, capsular invasion, necrosis, histological type, and Ki-67 staining) were used. The median follow-up observation period was 63.7 months. RESULTS: Postoperatively, 5 patients (13.2%) developed distant metastasis or had localized recurrence, and 3 patients died (7.9%). The results of the univariate analysis revealed three factors affecting distant metastasis and recurrence, which were Ki-67 (p = 0.0041), the presence or absence of necrosis (p = 0.0163), and tumor weight (p = 00,189). Using the cutoff values obtained by ROC analysis, which were 4.1 for Ki-67 (sensitivity of 80% and specificity of 96.9%) and 4890 mg for tumor weight (sensitivity of 100% and specificity of 60.9%), we calculated the cumulative incidence of recurrence and distant metastasis by the three factors retained. We found that the presence of the three factors was associated with a high possibility of distant metastasis or recurrence during the 5-year follow-up period. CONCLUSIONS: Three factors, Ki-67, necrosis, and tumor weight in parathyroid carcinoma, may predict outcomes of postoperative recurrence and distant metastasis.

Reconfirmation of the accuracy of the taller-than-wide sign in multicenter collaborative research in Japan.

The taller-than-wide sign indicates that the anteroposterior dimension-to-transverse dimension ratio (AP/T ratio) is higher than 1. The aim of the present study was to reconfirm the accuracy of the taller-than-wide sign for diagnosing malignant thyroid nodules by ultrasonography in multicenter collaborative research, and investigate differences according to tumor sizes, histological types, and the influence of the tilt and orientation of the probe. At 6 registered institutes, 2,032 thyroid nodules were successively operated on and diagnosed pathologically. The accuracy of the taller-than-wide sign for diagnosing malignant tumors by ultrasonography was retrospectively analyzed across all nodules as well as in analyses separately stratified by tumor size and histology. The influence of the tilt and orientation of the probe was also assessed. The taller-than-wide sign showed high specificity for diagnosing malignancy in all nodules tested. It also showed high specificity regardless of the tumor size. When tumors were analyzed by histological types, the AP/T ratio of papillary carcinoma was significantly higher than that of benign nodules, whereas no significant difference was observed between follicular carcinoma and benign nodules. The specificity of longitudinal sections was significantly higher, while the AUC of longitudinal sections was significantly larger than those of transverse sections. The AP/T ratio obtained when the probe was tilted was not significantly different from that when it was straight. The present results support the usefulness of the taller-than-wide sign for diagnosing malignant tumors regardless of size, but not follicular carcinoma. The influence of the tilt and orientation of the probe was negligible.

Radiofrequency Ablation of Benign Thyroid Nodules: Recommendations from the Asian Conference on Tumor Ablation Task Force - Secondary Publication.

Radiofrequency ablation (RFA) is a thermal ablation technique widely used for the management of benign thyroid nodules. To date, five academic societies in various countries have reported clinical practice guidelines, opinion statements, or recommendations regarding the use of thyroid RFA. However, despite some similarities, there are also differences among the guidelines, and a consensus is required regarding safe and effective treatment in Asian countries. Therefore, a task force was organized by the guideline committee of the Asian Conference on Tumor Ablation with the goal of devising recommendations for the clinical use of thyroid RFA. The recommendations in this article are based on a comprehensive analysis of the current literature and the consensus opinion of the task force members.

[Surgery of the parathyroid gland].

The introduction of various techniques for minimally invasive parathyroidectomy (MIP) has changed both the conceptual and surgical approach to parathyroid disease. The perceived advantages of minimally invasive surgery among both clinicians and patients have been a major factor in the development of new surgical techniques, as well as refinement of preoperative localization techniques such as high-sensitive ultrasound and technetium sestamibi scanning. MIP for primary hyperparathyroidism has become an accepted part of endocrine surgical practice worldwide. In recent years, medical management of hyperparathyroidism has been made possible with the use of therapeutics specifically aimed at the calcium-sensing receptor, a cell-surface protein widely viewed as the primary regulator of parathyroid hormone secretion. The calcimimetic agent cinacalcet is approved for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis and for the treatment of hypercalcemia in patients with parathyroid carcinoma. Cinacalcet is also expected to be useful in the treatment of intractable hypercalcemia in patients with primary hyperparathyroidism for whom parathyroidectomy is indicated but surgery is clinically inappropriate or contraindicated.

Diagnostic Strategies for Thyroid Nodules Based on Ultrasonographic Findings in Japan.

In recent years, the incidence of thyroid cancer has been increasing worldwide, which is believed to be mainly due to the widespread use of imaging examinations, such as ultrasonography. In this context, ultrasonography has become increasingly important because it can evaluate not only the presence or absence of nodules, but also the detailed characteristics of the nodule, making it possible to diagnose benign or malignant nodules before cytology is performed. In Japan, the third edition of the sonographic diagnostic criteria for thyroid nodules is currently widely used, and its content is similar to that of recent meta-analyses and guidelines from medical societies in other countries. In addition, since overdiagnosis of very-low-risk thyroid cancer has recently become an issue, criteria for the implementation of fine needle aspiration cytology (FNAC) have been published by various countries. The Japan Society of Breast and Thyroid Sonology provides guidelines for FNAC implementation for solid and cystic nodules. In the United States, the ATA, NCCA, and ACR have published guidelines, whereas in Europe, the ESMO and ETA have done the same. All of these guidelines used to classify risk are based on nodule size and sonographic findings. This article outlines the diagnostic criteria and management guidelines in Japan in comparison with those published in other countries. Case studies using actual images were also performed to examine the differences in the FNAC guidelines.

Radiofrequency ablation of benign thyroid nodules: recommendations from the Asian Conference on Tumor Ablation Task Force.

Radiofrequency ablation (RFA) is a thermal ablation technique widely used for the management of benign thyroid nodules. To date, five academic societies in various countries have reported clinical practice guidelines, opinion statements, or recommendations regarding the use of thyroid RFA. However, despite some similarities, there are also differences among the guidelines, and a consensus is required regarding safe and effective treatment in Asian countries. Therefore, a task force was organized by the guideline committee of the Asian Conference on Tumor Ablation with the goal of devising recommendations for the clinical use of thyroid RFA. The recommendations in this article are based on a comprehensive analysis of the current literature and the consensus opinion of the task force members.

[Ultrasonography of thyroid cancer].

The diagnosis and management of follicular carcinoma of the thyroid gland remains a controversial topic. Color-Doppler (CD) imaging has been expected for the differential diagnosis between follicular adenoma and follicular carcinoma. CD imaging examination of follicular tumors has revealed that high-velocity pulsative blood flow penetrating the tumor is a characteristic finding of follicular carcinoma. Real-time tissue elastography (RTE), which enable to demonstrate the tissue elasticity, has begun to be applied for the thyroid disease. In follicular cancer, the difference of elasticity from core of the tumor and periphery is supposed to be depend on the difference of hypercellurality. RTE can provide new useful information for the differential diagnosis of thyroid follicular lesions.

Distinct diagnostic criteria for ultrasonographic examination of papillary thyroid carcinoma: a multicenter study.

Recent advances permitting high-resolution ultrasonography have made ultrasonographic examination of nodular thyroid diseases an accessible examination for routine practice. However, diagnostic criteria for ultrasonographic examination of thyroid nodules are not surely established. To identify the optimal strategy for well standardized differential diagnosis of papillary thyroid carcinoma and benign nodules, we evaluated the significance of individual ultrasonographic characteristics of thyroid nodules in a multicenter study. Ten characteristics in ultrasonograms from 53 patients scored by 17 investigators from 15 centers were analyzed by t tests and logistic regression analyses. Between benign and papillary thyroid cancer groups, all characteristics but not size or multiplicity of strong echoes, which suggest calcifications, were significant parameters. Logistic regression analyses showed that border character, shape, and internal echo level are highly significant parameters (p < 0.0005). A multiple logistic regression showed to be the most important predictors of pathologic diagnosis. The diagnostic criterion with border character and internal echo level yielded 93% sensitivity and 92% specificity. In conclusion, univariate and multivariate analyses identified border character, shape, internal echo level, but not strong echoes (calcifications), as important characteristics in differentiating papillary thyroid carcinoma from benign nodules. These results will contribute to standardization of accurate ultrasonographic diagnosis of papillary thyroid carcinoma.

The important role of operations in the management of anaplastic thyroid carcinoma.

BACKGROUND: Anaplastic thyroid carcinoma is a rare and highly lethal neoplasm. We investigated whether operations have an impact on the survival of patients who have anaplastic carcinoma without distant metastasis. METHODS: Between 1989 and 1999, 40 consecutive patients with anaplastic carcinoma, without distant metastasis at the time of presentation or during local treatment, were reviewed. The cumulative survival rates and 1-year survival rates were compared. RESULTS: Eleven patients had a small focus of anaplastic carcinoma in a differentiated carcinoma, and 29 patients had ordinary anaplastic thyroid carcinoma. Surgical debulking was performed in 26 patients. Radiotherapy was used for 31 patients and chemotherapy for 19 patients. The 1-year survival rates of the patients with incidental anaplastic carcinoma, ordinary anaplastic carcinoma who underwent operations, and ordinary anaplastic carcinoma who did not undergo operations were 73%, 60%, and 21%, respectively. A significantly higher cumulative survival rate was observed in patients with incidental anaplastic carcinoma than in those with ordinary anaplastic carcinoma. A significantly better outcome was obtained by surgical debulking of ordinary anaplastic carcinoma. CONCLUSIONS: Patients with incidental anaplastic carcinoma tended to have a good outcome, but some had a poor prognosis. Surgical debulking improved the outcome of patients with ordinary anaplastic carcinoma.

Surgical treatment of Graves' disease in children.

Thyroidectomy may be indicated in children with Graves' disease who have adverse reactions to antithyroid drugs or who relapse after antithyroid drug therapy. We investigated the characteristics of childhood Graves' disease from the standpoint of surgical outcome. Between 1989 and 1998, 1897 patients with Graves' disease underwent thyroidectomy and their thyroid function could be evaluated 2 to 3 years after thyroidectomy. The patients were divided into three groups according to age at thyroidectomy: 74 patients were 15 years old or less (children), 345 patients 16 to 20 years of age (adolescents), and 1478 patients 21 years of age or more (adults). The children included higher proportions of patients who had a large goiter (> 100 g), high thyrotropin-binding inhibitory immunoglobulin (TBII) level (> 50%), and small remnant thyroid (< 4 g). At 2 to 3 years after thyroidectomy, the overt recurrence rate of the children, adolescents, and adults was 9.5%, 4.9%, and 5%, respectively. The cumulative recurrence-free rate of the children, adolescents, and adults at 5 years after thyroidectomy was 82%, 90%, and 92%, respectively. Surgical complications were more frequently observed in children. Considering the aggressiveness of childhood Graves' disease, subtotal thyroidectomy with thyroid remnant less than 3 g is the procedure of choice for preventing recurrent hyperthyroidism.

Thyroid ultrasonography B-mode and color-Doppler.

Recently, ultrasonography of the thyroid gland has proved to be a useful clinical diagnostic method. The newly developed high-resolution ultrasonography with color-Doppler flow mapping function can reveal fine details of the thyroid gland and the hemodynamic features of thyroid neoplasmas. Ultrasonography can deliver a diagnostic accuracy of over 90% in thyroid carcinoma, especially papillary carcinoma. However, in the case of follicular carcinoma, neither conventional B-mode ultrasound imaging nor aspiration biopsy cytology can deliver satisfactory results. Color-Doppler imaging examination of 212 follicular tumors has been carried out, resulting in the characteristic finding that a high-velocity pulsative blood flow penetrates the tumor in the case of follicular carcinoma, which led to new diagnostic criteria with color-Doppler examination. The differential diagnostic grading score using color-Doppler examination and FFT analysis can show a dramatic diagnostic accuracy of 81.0%, a sensitivity of 88.9% and a specificity of 74.2%. Ultrasound with the color-Doppler function can play a more important role in the differential diagnosis of thyroid tumors.

PEI therapy for thyroid lesions.

PEI therapy has been applied clinically as a new treatment strategy for cystic lesions and autonomous functioning nodules of the thyroid. Some additional indications currently under consideration include cold benign tumors and inoperable advanced cancer of the thyroid, and postoperative recurrence of Graves' disease. At our institution, we have treated 2323 patients with thyroid disease by PEI therapy from 1999 to 2001. PEI is usually administered under ultrasound guidance in cases of cystic lesions, and under color-Doppler guidance in cases of solid lesions of the thyroid, with the goal of attenuating tumor blood flow. In consequence, of the total 2323 cases who received PEI therapy at our hospital, 1989 (85.6%) were classified as showing an effective response (ER) or partial response (PR). There were no major complications, such as recurrent laryngeal nerve palsy, uncontrollable pain, bleeding, or thyrotoxicosis. Our results also emphasize the importance of the use of color-Doppler guidance for control of the injection volume of ethanol to the minimum required for completely attenuating the tumor vascularity.

Composite metastatic carcinoma in lymph nodes of patients with concurrent medullary and papillary thyroid carcinoma: a report of two cases.

Synchronous occurrence of medullary and papillary carcinoma of the thyroid gland is very rare. We describe two cases of synchronous medullary and papillary carcinoma of the thyroid. In both cases, medullary carcinoma and papillary carcinoma were separate in the thyroid but mixed in some of the lymph node metastases. A review of the literature and our own cases revealed that composite medullary and papillary carcinoma metastases in the lymph nodes is a common feature of patients with synchronous medullary and papillary carcinoma of the thyroid gland.

Elastographic presentation of medullary thyroid carcinoma.

Aim of the study was to evaluate the elastographic appearance of medullary thyroid carcinoma (MTC) by a retrospective evaluation of 18 nodules histologically proven as MTC. Free-hand qualitative elastography was performed using Hitachi Logos EUB 7500. The elasticity score (ES), was assessed based on a colour elastogram, the blue colour being correlated with hard tissue, red colour with soft tissue, and green with intermediate hardness. Nodules were classified into four classes. A alleged diagnosis of malignancy was assigned to nodules with ES3 or 4 and a presumptive diagnosis of benignity was assigned to nodules with an ES1 or 2. More than half (55.6 %) of MTCs have a low-intermediate grade of elasticity. The hardest lesions (ES4) were those with ultrasonographic features highly suspicious for malignancy. In conclusion, most of MTCs present an elastographic pattern of benignity. Therefore, qualitative elastography does not add useful information in pointing out MTC on the basis of its hardness. Our data suggest a marginal role for this technique in MTC evaluation.

Clinical evaluation of color Doppler imaging for the differential diagnosis of thyroid follicular lesions.

Ultrasonography (US) of the thyroid gland has recently proved to be a useful clinical diagnostic method, and the newly developed high-resolution US with a color Doppler flow mapping function can reveal fine details of the thyroid gland and the hemodynamic features of a thyroid neoplasm. US can yield a diagnostic accuracy of more than 90% for thyroid carcinoma, especially papillary carcinoma. However, neither conventional B-mode US imaging nor aspiration biopsy cytology has delivered satisfactory results for follicular carcinoma. The aim of this study was to evaluate the clinical usefulness of color Doppler imaging for the differential diagnosis of thyroid follicular lesions. A color Doppler scan was performed in 310 patients with a solitary cold nodule, and a combination of B-mode US and color Doppler findings, including tumor vascularity and results of a fast Fourier transform (FFT) analysis were used to create the following diagnostic grading system for differential diagnosis of follicular lesions: grade 1, benign follicular lesion [no color flow mapping (CFM) inside the nodule]; grade 2, benign peripheral type [CFM only in peripheral area, pulsatility index (PI) < 1.0]; grade 3, suspected follicular carcinoma (penetrating CFM, vascularity moderate); grade 4, follicular carcinoma (high-velocity penetrating CFM, PI = 1.0). All patients were subjected to surgical resection, and histologic examination was used to confirm the diagnosis. The grades of the 177 adenomatous nodules were as follows: grade 1, 46.9%; grade 2, 48.0%; grade 3, 5.1%; grade 4, 0%. The corresponding percentages for the 89 follicular adenomas were 16.9%, 49.4%, 30.3%, and 3.4%; and for the 44 follicular carcinomas they were 0%, 13.6%, 45.5%, and 40.9%. On the assumption that grade 1 and 2 lesions are benign and grade 3 and 4 lesions are malignant, 38 of the 44 follicular carcinomas and 227 of the 266 benign tumors had been accurately diagnosed, yielding a sensitivity of 88.9%, a specificity of 74.2%, and an accuracy of 81.0% for the grading system. Color Doppler imaging of 310 follicular tumors has revealed that high-velocity pulsatile blood flow penetrating the tumor is a characteristic finding of follicular carcinoma and is a new diagnostic criterion for performing color Doppler imaging. The differential diagnostic grading scores for color Doppler examinations and the results of FFT analysis demonstrate that US with the color Doppler function can play an important role in the differential diagnosis of thyroid tumors.