Tomoo Jikuzono

Clinical Significance of Lymph Node Metastasis of Thyroid Papillary Carcinoma Located in One Lobe

BackgroundPrevious studies have shown that lymph node metastasis can be of prognostic value. In this study, we investigated the clinical significance of node metastasis focusing on metastasis in the central compartment for patients with papillary carcinoma located in one lobe.Patients and MethodsWe investigated the frequency of lymph node metastasis in 759 patients with papillary carcinoma to determine whether and how such metastasis affects disease-free survival (DFS).ResultsCentral node metastasis was observed in 63% of patients, and the frequency was increased in relation to tumor size. The frequency of lateral node metastasis was 62.0%, which was also directly related to tumor size. On multivariate analysis of cases showing tumor larger than 1 cm, central node metastasis was recognized as an independent prognostic factor of DFS. The frequency of metastasis to the paratracheal nodes contralateral to the tumor was drastically elevated for tumors larger than 1 cm, but metastasis to this region did not independently predict worse DFS.ConclusionCentral node metastasis independently predicts a worse DFS for patients with papillary carcinoma larger than 1 cm.

Risk Factors Contributing to a Poor Prognosis of Papillary Thyroid Carcinoma: Validity of UICC/AJCC TNM Classification and Stage Grouping

BackgroundIn 2002, the UICC/AJCC TNM classification for papillary thyroid carcinoma was revised. In this study, we examined the validity of this classification system by investigating the predictors of disease-free survival (DFS) and cause-specific survival (CSS) in patients.MethodsWe examined various clinicopathological features, including the component of the TNM classification, for 1,740 patients who underwent initial and curative surgery for papillary carcinoma between 1987 and 1995.ResultsClinical and pathological T4a, clinical N1b in the TNM classification, and patient age were recognized as independent predictors of not only DFS, but also CSS of patients. Tumor size, male gender, and central node metastasis independently affected DFS only. There were 1,005 pathological N1b patients, but pathological N1b did not independently affect either DFS or CSS. Regarding the stage grouping, clinical stage IVA including clinical N1b more clearly affected DFS and CSS than pathological stage IVA including pathological N1b.ConclusionClinical stage grouping was more useful than pathological stage grouping for predicting the prognosis of papillary carcinoma patients possibly because pathological stage overestimates the biological characteristics of many pathological N1b tumors.

Extranodal tumor extension to adjacent organs predicts a worse cause-specific survival in patients with papillary thyroid carcinoma

BackgroundWe previously reported that massive extrathyroid extension has an independent prognostic value in patients with thyroid papillary carcinoma. However, tumor extension to adjacent organs can be observed not only in primary tumor but also in metastatic nodes. In this study we investigated the clinical significance of extranodal tumor extension to adjacent organs (nodal ex) in papillary thyroid carcinoma.MethodsWe classified all cases into three categories based on the degree of nodal ex: nodal ex0, no apparent extranodal tumor extension; nodal ex1, hard metastatic nodes with perinodal growth extending to adjacent organs, which require separation of the nodes from the organs; and nodal ex2, metastatic nodes with perinodal growth completely invading the adjacent organs and requiring excision of nodes together with these organs. We investigated the clinical significance of each grade in 1,692 patients who underwent initial surgery for papillary carcinoma between 1987 and 1995.ResultsThe presence of nodal ex was significantly linked to various clinicopathological features such as male gender, N1b, large number of metastatic nodes, pT4a, and distant metastasis. On univariate analysis, patients with either nodal ex1 or ex2 showed significantly worse disease-free and cause-specific survival rates, although these rates did not differ between patients with nodal ex1 and those with nodal ex2. Furthermore, multivariate analysis demonstrated that nodal ex independently predicts worse cause-specific survival of these patients.ConclusionsPresence of nodal ex significantly reflects the biologically aggressive behaviors of papillary carcinoma and has a prognostic value, especially for cause-specific survival of patients.

The miR-221/222 cluster, miR-10b and miR-92a are highly upregulated in metastatic minimally invasive follicular thyroid carcinoma

Minimally invasive follicular thyroid carcinoma (MI-FTC) is characterized by limited capsular and/or vascular invasion with good long-term outcomes. However, some cases of MI-FTC show a poor prognosis because of severe distant metastasis (i.e., metastatic MI-FTC). Nonetheless, no method has been established for predicting the prognosis of MI-FTC. This study was conducted to identify novel prognostic factors for metastatic MI-FTC by the use of microRNA (miRNA). Thirty-four patients with MI-FTC were categorized into two groups: the metastatic group, M(+) (n=12) and the non-metastatic group, M(−) (n=22). In the M(+) group, distant metastasis was recognized after the initial operation established the diagnosis of MI-FTC. In the M(−) group, no distant metastasis was recognized postoperatively for ≥10 years. Using laser micro-dissection followed by quantitative real-time PCR and PCR arrays, we performed a comprehensive expression profiling of 667 miRNAs in formalin-fixed, paraffin-embedded samples from the initial MI-FTC operation. Furthermore, we assessed the potential use of miRNAs as novel biomarkers for the metastatic potential of MI-FTC by logistic regression analysis. Comprehensive quantitative analysis of miRNA expression in MI-FTC samples revealed that the miR-221/222 cluster (i.e., miR-221, miR-222 and miR-222*), miR-10b and miR-92a were significantly upregulated in the M(+) group compared with the M(−) group. Interestingly, the expression levels of these miRNAs were also shown to be upregulated in widely invasive FTC (WI-FTC; n=13) that has distant metastasis and worse prognosis, indicating a close similarity in the miRNA expression between metastatic MI-FTC and WI-FTC. Logistic regression analysis revealed that miR-10b made a significant contribution to prognosis (OR 19.759, 95% CI 1.433–272.355, p= 0.026). Our findings suggest that miR-10b is a potential prognostic factor for evaluating the metastatic potential of MI-FTC at an initial operation stage.

Delta Np73 expression in thyroid neoplasms originating from follicular cells

Aims: p73, a homologue of p53, is known as a negative regulator of tumour progression. However, delta Np73, an isoform of p73 lacking the NH2‐terminal transactivation domain plays an oncogenic role by interfering with the activity of p53 and TA (full‐length transactivating isoforms) p73. In this study, we investigated the expression of delta Np73 in human thyroid neoplasms originating from follicular cells. Methods: We immunohistochemically investigated delta Np73 expression in 223 thyroid neoplasms. Delta Np73 expression level was evaluated as the sum of positivity score and intensity score. Results: Normal follicular cells did not express delta Np73, but 27.3% of follicular adenoma, 85.4% of follicular carcinoma, 99.2% of papillary carcinoma, and 95.7% of anaplastic carcinoma were positive for the transcript. Delta Np73 expression level did not differ between widely invasive and minimally invasive follicular carcinomas. In papillary carcinoma, the level was inversely linked to tumour size, extrathyroid extension, and clinically apparent metastasis. Furthermore, in anaplastic carcinoma, delta Np73 expression level was significantly lower than that in papillary carcinoma. Conclusions: Our findings indicate that delta Np73 plays a role predominantly in the early phase of papillary carcinoma progression.

Hyalinizing trabecular tumor of the thyroid gland: characteristic features on ultrasonography.

We report a case of hyalinizing trabecular tumor of the thyroid gland and describe the characteristic ultrasonographic features of this tumor. This was a rare tumor of follicular cell origin with a trabecular pattern of growth and marked intratrabecular hyalinization. The tumor had an irregular shape, a delicately jagged border, and hypoechoic and heterogeneous internal echoes on B-mode ultrasonography. Very rich intratumoral blood flow, the so-called “tumor inferno” was evident on power Doppler ultrasonography. In the clinical management of thyroid nodules, clinicians should be aware of this peculiar type of thyroid tumor and its characteristic ultrasonographic findings.

Introduction and use of video-assisted endoscopic thyroidectomy for patients in Belarus affected by the Chernobyl nuclear disaster.

We developed video‐assisted neck surgery (VANS) – a feasible, simple, and safe endoscopic thyroid procedure with cosmetic benefits – in 1998. To date, we have performed this procedure 633 times. We have also introduced the VANS method in Belarus, a country that was left contaminated by the Chernobyl nuclear disaster.

Selective axillary node dissection differed from the arm lymph flow oriented by 3D-CT lymphography.

CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts Abstract #1012 Background: In early breast cancer, the presence of metastasis in axillary lymph nodes is an important factor in prognosis and further treatment. However, axillary node dissection causes many complications such as contracture of the shoulder joint, lymph edema, and paralysis of the upper extremities. Sentinel node (SN) biopsy provides us an information about no need to dissect axillary nodes for node-negative patients. But on node-positive patients, the conventional axillary node dissection has been performed. 3D-CT lymphography (LG) can show the precise individual lymphatic flow not only from the tumor to SN but also from SN to venous angle, which means breast lymphatic channel. We applied 3D-CT LG to distinguish them from the arm channel to avoid any arm complications. Materials and Methods: 3D-CT LG was performed on the day before the surgery to mark SN on the skin. Above the tumor and near the areola, 2 ml of Iopamidol was injected subcutaneously. A 16-channel multidetector-row helical CT images were taken at 1 min after injection for SN detection, and at 3 and 5 min for observing advancement of lymph flow into venous angle. They were reconstructed to produce a 3D image of lymph ducts and lymph nodes by shaded volume rendering method. SN biopsy and axillary node sampling were performed by dye-stain method using endoscopy. Results: We performed SN biopsy with 3D-CT LG in 146 patients. 3D-CT LG showed periareolar circular lymph ducts and complicated radial breast subcutaneous lymph ducts flow. They were connected to make a network. It clearly showed the precise lymphatic flow from the tumor to SN. 3D-CT lymphography can show sentinel lymph node at only one minute after injection. But following up to 3 minutes and 5 minutes after injection, we can follow the lymph ducts beyond SN into the second and the third nodes toward the venous angle with complex plexus. It shows five beads-like grouped nodes beyond SN. Detection rate was 100% for SN; 80.1% for the third group; and 30.1% for the fifth group. The position of SN and the other groups of axillary nodes were identified by their surrounding anatomical architecture of pectoral muscles and vascular systems, such as axillary vein, lateral thoracic artery, and thoracodorsal artery. Under the endoscopic technique, we can observe the dye-stained nodes in 63.3% of the second group and in 47.9% of the third group detected by 3D-CT LG. SN metastasis was positive in 40 patients, and only SN metastasis was found in 21 patients (52.5%) among them. Any skip metastasis beyond second and third nodes was not observed. Under the direct view, we can distinguish and the axillary node drained from the breast, guided by 3D-CT LG and dye-stain, in 40 patients with SN metastasis, and sample them selectively. Conclusions: By 3D-CT LG, we can recognize the accurate and more precise lymph flow, and their positional relations to surrounding anatomical architecture. It helps us easily to pursuit lymph flow and to remove SN and the axillary nodes from the breast selectively. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1012.

Characteristic ultrasonographic features of the encapsulated variant of papillary carcinoma of the thyroid

PurposeThe purpose of this study was to evaluate the ultrasonographic and clinical features of the encapsulated variant of papillary carcinoma of the thyroid. MethodsOf a total of 2020 patients whose papillary carcinoma of the thyroid was treated surgically between 1998 and 2002, 56 patients had the encapsulated variant. Ultrasonographic features of the encapsulated variant of papillary thyroid carcinoma were classified into the following two types based on the shape and character of the border: papillary carcinoma (PC) and follicular tumor (FT). Ultrasonographic features of the PC type are a jagged border and an irregular tumor shape. Those of the FT type are a smooth border and a regular shape (spherical to oval). ResultsThe PC type was seen in 36 patients and the FT type was found in 20 patients. Both types of encapsulated variant of papillary carcinoma showed cervical lymph node metastases.ConclusionUltrasonographic findings of the FT type have characteristic features that are similar to those of benign follicular tumors of the thyroid. We should remember that some patients do not show typical and classical features of papillary carcinoma on ultrasonography.