Attenuation of postmenopausal bone loss in patients with transient hypoparathyroidism after total thyroidectomy.

BACKGROUND: Increased bone mineral density (BMD) has been reported in patients with postsurgical permanent hypoparathyroidism. Hypoparathyroidism may attenuate the high-turnover bone loss in postmenopausal women. We reported previously that patients who had transient hypoparathyroidism postoperatively were at subclinical hypoparathyroid (hP) status even 5 years after surgery. We hypothesized that patients with transient hypoparathyroidism (ThP) may have altered BMD. METHODS: A total of 140 women who underwent total thyroidectomy had BMD measurements of the lumbar spine, femoral neck, and radius 3 years after surgery. At surgery, 99 patients were ≥50 years and 41 were <50 years. They were divided into three groups according to their postoperative parathyroid function: There were 80 patients in the no hP (NhP) group, 54 in the ThP group, and 6 in the permanent hP (PhP) group. RESULTS: Among the 99 patients aged ≥50 years, 36 ThP patients had median Z scores of the BMD in all three areas (lumbar spine, femoral neck, radius) that were significantly higher (by 1.083, 0.533, and 1.047, respectively) than those in the 60 NhP patients aged ≥50 years. The BMDs in the three PhP patients ≥50 years were higher than those in the NhP and ThP patients, but the difference did not reach significance except for in the femoral neck. Multivariate logistic regression analyses showed that Z scores > 0 were significantly associated only with the presence of ThP postoperatively. In the patients <50 years, the BMD values were not significantly different among the three groups except at the radius in PhP patients, which was significantly lower than those of the other patients. CONCLUSIONS: We found that ThP was associated with increased BMD in postmenopausal women. This may be due to attenuation of the high-turnover bone loss in postmenopausal women.

Prognostic significance of changes in serum thyroglobulin antibody levels of pre- and post-total thyroidectomy in thyroglobulin antibody-positive papillary thyroid carcinoma patients.

Although postoperative serum thyroglobulin (Tg) is a prognostic indicator for papillary thyroid carcinoma (PTC), it is unreliable when Tg antibody (TgAb) is positive. We evaluated the prognostic significance of changes in serum TgAb levels of pre- and post-total thyroidectomy in TgAb-positive PTC patients. We reviewed our medical charts of 225 TgAb-positive PTC patients in whom TgAb levels were measured before and 1-2 years after total thyroidectomy, performed between April 2002 and March 2007. We divided them into 3 groups based on changes in TgAb levels. Postoperative serum TgAb levels decreased by ≥ 50% in 181 patients (80.4%) (Group 1), by <50% in 22 patients (9.8%) (Group 2), and increased in 22 patients (9.8%) (Group 3). During the follow-up, 3 patients died of the disease and 14 patients had recurrences. All 3 patients who died of PTC were seen only in Groups 2 and 3. Groups 2 and 3 showed similar prognostic outcomes, thus were analyzed together as Group 2+3. Group 1 had significantly better lymph node recurrence-free survival and distant recurrence-free survival than Group 2+3 (96.9% vs. 90.5%, p <0.001, and 98.9% vs. 90.1%, p = 0.004, respectively at 5 years). Multivariate analyses on prognostic factors revealed that classification to Group 2+3 was the strongest indicator for poor prognosis. The present results suggest that changes in TgAb levels following total thyroidectomy can be an important dynamic prognostic factor of PTC patients. Prospective periodical measurements of TgAb are necessary to confirm these findings.

Distant metastasis at diagnosis and large tumor size are significant prognostic factors of widely invasive follicular thyroid carcinoma.

In contrast to minimally invasive follicular thyroid carcinoma (FTC), widely invasive FTC is aggressive and is associated with a dire prognosis. However, prognostic factors of widely invasive FTC have not been intensively investigated. In this study, we investigated this issue in a series of 79 widely invasive FTC patients. In the subset of 70 patients who did not show distant metastasis at diagnosis (M0), only a tumor size larger than 4 cm had a prognostic impact on disease-free survival (DFS) both on uni- and multivariate analyses. Regarding the cause-specific survival (CSS) of 79 patients, only distant metastasis at diagnosis (M1) had a significant prognostic value on uni- and multivariate analyses. None of the 70 M0 patients with a tumor measuring 4 cm or less died of FTC. Other clinicopathological features such as age, gender, and oxyphilic carcinoma were of no prognostic value. These findings suggest that 1) M1 is the strongest prognostic factor for CSS of widely invasive FTC patients, and 2) a tumor size larger than 4 cm significantly affects the DFS and CSS of M0 patients. Aggressive therapies with careful follow-up are recommended, especially for these patients.

Prognostic factors of minimally invasive follicular thyroid carcinoma: extensive vascular invasion significantly affects patient prognosis.

Follicular thyroid carcinoma (FTC) is divided into two categories: minimally and widely invasive FTC. Generally, the prognosis of minimally invasive FTC is excellent, but patients showing certain characteristics have a dire prognosis. In this study, we investigated the prognostic factors of minimally invasive FTC using a series of 292 patients. On multivariate analysis, extensive (4 or more) vascular invasion, age ≥ 45 years, and tumor size > 4 cm were independent prognostic factors of patient disease-free survival (DFS). Distant metastasis at diagnosis (M1) was the strongest prognostic factor of cause-specific survival (CSS). Extensive vascular invasion and tumor size > 4 cm also independently affected patient carcinoma death. Capsular invasion was not related to patient prognosis. The ten-year DFS rate of patients with extensive vascular invasion was 80%, which was poorer than that of those having tumor size > 4 cm (91%) and aged 45 years or older (90%). These findings suggest that 1) M1 most strongly affects the CSS of patients, and 2) M0 patients with extensive vascular invasion may be candidates for completion total thyroidectomy and radioactive iodine ablation.

Tumor size is the strongest predictor of microscopic lymph node metastasis and lymph node recurrence of N0 papillary thyroid carcinoma.

It is well-known that papillary thyroid carcinoma (PTC) frequently metastasizes to the regional (central and lateral) lymph nodes, even though it is diagnosed as node-negative on preoperative imaging studies. In this study, we investigated predictors of microscopic node metastasis and lymph node recurrence of PTC without node metastasis detected preoperatively (N0). Of the clinicopathological features that can be evaluated pre- and intraoperatively, tumor size (> 2 cm) was the strongest predictor of microscopic central and lateral node metastasis on multivariate logistic analysis. Also, the tumor size most markedly affected lymph node recurrence, but not distant recurrence. Lymph node recurrence may not be immediately life-threatening, but it can be a stressor both for physicians and patients. Therefore, careful lymph node dissection is recommended for PTC with a large size, even though it is prophylactic.

The ima approach for the quick identification of the right recurrent laryngeal nerve in thyroid cancer surgery.

BACKGROUND: The right recurrent laryngeal nerve (RLN) is more difficult to identify than the left RLN. The superior, lateral and inferior approaches are currently used to identify the RLN. This report presents a new technique, called the ima approach (the most inferior approach) for the quick identification of the right RLN. METHODS: The ima approach involves dissection along the right common carotid artery and division of the most lateral branch of the inferior thyroid veins. The right RLN is identified at the bottom of the RLN triangle. This technique and the conventional inferior approach were applied to 81 and 19 patients with thyroid cancer, respectively. RESULTS: The ima approach required a significantly shorter time in identifying the nerve than the inferior approach (9.6 ± 16.6 and 31.2 ± 24.4 s, respectively, p < 0.0001). CONCLUSION: The ima approach is an easy, quick and safe technique for identifying the right RLN.

Evaluation of cytologically benign solitary thyroid nodules by ultrasonography: a retrospective analysis of 1877 cases.

OBJECTIVE: The purpose of this study is to evaluate the role of ultrasonography (US) in the management of thyroid nodules when the cytology is benign tumor on fine needle aspiration biopsy (FNAB). METHODS: Between 2006 and 2011, we investigated 13,972 patients who had solitary thyroid nodule with cytological findings of benign. Surgery was performed according to our criteria for surgical indication. Of these patients, 1877 (13%) patients who underwent surgery were enrolled in this study. We compared the results of clinical findings including US classification and final histopathological diagnosis. RESULTS: One hundred seven (6%) after surgery were diagnosed as malignancy pathologically. Large nodule or high serum thyroglobulin level were not associated with an increased risk of malignancy. Ultrasonographic evaluation as malignancy was directly linked to pathological diagnosis as thyroid carcinoma (p<0.001). CONCLUSION: US may help to play a role in deciding whether surgical treatment is necessary for cytologically benign thyroid nodules.

Incidence and predictors of right paraesophageal lymph node metastasis of N0 papillary thyroid carcinoma located in the right lobe.

Papillary thyroid carcinoma (PTC) frequently metastasizes to the regional lymph nodes and, thus, guidelines edited by Japan Association of Endocrine Surgeons/Japanese Society of Thyroid Surgery routinely recommend central node dissection even for patients with no clinically detectable node metastasis (N0). However, in the central compartment, metastasis to the right paraesophageal node has not been intensively investigated. We investigated the incidence and predictors of right paraesophageal node metastasis based on pre- and intraoperative findings in 922 patients with N0 PTC in the right lobe. Fourteen percent of patients were microscopically positive for right paraesophageal node metastasis, and the incidence was smaller than that for pre- and right paratracheal node metastasis (46%). On multivariate analysis, a tumor size ≥ 2 cm and significant extrathyroid extension were independent predictors of metastasis. Microscopically pre- and right paratracheal node-positive PTC more often (p < 0.0001) metastasized to the right paraesophageal node. Taken together, in N0 PTC in the right lobe, right paraesophageal node dissection should be considered in tumors 2 cm or larger and/or with significant extrathyroid extension, or when pre- and right paratracheal node metastasis is suspected based on the intraoperative findings.

Papillary thyroid carcinoma with honeycomb-like multiple small cysts: characteristic features on ultrasonography.

BACKGROUND: Thyroid nodules with cystic content or mixed sponge-like aspect on ultrasonography and a concordant cytology are strongly predictive of benignity. OBJECTIVES: We present 8 patients with honeycomb-like papillary thyroid carcinoma with multiple small cysts on ultrasonography. METHODS: The patients were 6 women and 2 men aged between 30 and 57 years. The tumors of these patients showed honeycomb-like multiple small cysts that were aggregated in some area of the thyroid gland on ultrasonography. Histopathological examination indicated a well-differentiated type of papillary thyroid carcinoma with multiple small cysts and a small solid lesion. The cysts were lined with papillary carcinoma cells, and normal thyroid tissue lay between the cysts. RESULTS: There is a peculiar type of papillary thyroid carcinoma that histopathologically shows honeycomb-like multiple small cysts in the thyroid gland. Ultrasonography can be used to identify characteristic features of honeycomb-like multiple small cysts in the thyroid gland in such patients. CONCLUSIONS: One should be aware of this peculiar type of papillary thyroid carcinoma with honeycomb-like multiple small cysts on ultrasonography, although thyroid nodules with cystic lesions are generally regarded as benign in clinical management.

Improvement of lymph node recurrence rate, but not distant recurrence and carcinoma death rates, in patients with papillary thyroid carcinoma after disease-free survival for 5 years.

In this study, we investigated the difference in lymph node-recurrence free survival (LN-RFS), distant recurrence-free survival (DRFS), and cause-specific survival (CSS) between patients with papillary thyroid carcinoma (PTC) in the entire group (Group I) and those with lymph node- and distant-recurrence-free survival (DFS) for 5 years after initial surgery (Group II). The LN-RFS of patients with all risk classifications in Group II was significantly better than that of those in Group I. The LN-RFS of intermediate-risk patients in Group II did not differ from that of low-risk patients in Group I, but LN-RFS of high-risk patients in Group II was significantly poorer than intermediate- and low-risk patients in Group I. DRFS and CSS of Group II patients did not significantly differ from those of Group I patients in the same risk classification. DRFS and CSS of high-risk patients in Group II were significantly poorer than those of intermediate- and low-risk patients in Group I, and those of intermediate-risk patients in Group II were also significantly poorer than those of low-risk patients in Group I. Taken together, the lymph node recurrence rate, but not distant recurrence and carcinoma death rates, of patients in all classifications significantly improved after DFS for 5 years. However, careful follow-up for lymph node recurrence of high-risk patients and for distant recurrence of intermediate- and high-risk patients is necessary thereafter.

Prognostic value of poorly differentiated carcinoma in Japanese Society of Thyroid Surgery in a series of papillary thyroid carcinoma patients: comparison with risk classification system in Kuma Hospital.

Papillary thyroid carcinoma (PTC) often has poorly differentiated components, and it is discriminated from others and classified as an independent entity in the General Rules for the Description of Thyroid Cancer by Japanese Society of Thyroid Surgery (JSTS). In this study, we compared the prognostic significance between this type of poorly differentiated carcinoma (PDC-JSTS) and our risk classification system based on pre- and intraoperative findings in a series of PTC patients. The 10-year lymph node- and distant organ recurrence-free survival (LN-DFS and DRFS) and cause-specific survival (CSS) of high-risk patients were much poorer than in PDC-JSTS patients. In multivariate analysis, PDC-JSTS independently predicted a poor prognosis, but prognostic impacts for LN-DFS, DRFS, and CSS of high-risk in our risk classification were stronger than those of PDC-JSTS. In conclusion, it is appropriate that PDC-JSTS is defined as a subtype of PTC rather than as an independent entity.

Clinical trial of weekly paclitaxel chemotherapy for papillary thyroid carcinoma with squamous cell carcinoma component.

Papillary thyroid carcinoma (PC) can occasionally include a squamous cell carcinoma (SCC) component. In this study, we evaluated the effect of weekly paclitaxel chemotherapy in 3 patients with PC including an SCC component. None of these patients had lesions of anaplastic carcinoma on pathological examination. Weekly paclitaxel chemotherapy was performed as an induction chemotherapy for 2 patients. All 3 patients underwent locally curative surgery and weekly paclitaxel chemotherapy after surgery as an adjuvant therapy. The response to the chemotherapy was evaluated based on the RECIST guideline (version 1.1). Two patients had partial responses (PRs) and the remaining 1 had stable disease (SD). The response rate was 67% and the clinical benefit rate (PR+SD) was 100%. One patient died of the growth of lung metastases that had been detected before surgery 22 months after the diagnosis. The remaining 2 are still alive, 14 and 22 months after the diagnosis, respectively. Taken together, weekly paclitaxel may be one of the effective adjuvant therapies for PC with an SCC component.

TSH-suppressive doses of levothyroxine are required to achieve preoperative native serum triiodothyronine levels in patients who have undergone total thyroidectomy.

OBJECTIVE: Thyroidal production of triiodothyronine (T(3)) is absent in patients who have undergone total thyroidectomy. Therefore, relative T(3) deficiency may occur during postoperative levothyroxine (L-T(4)) therapy. The objective of this study was to evaluate how the individual serum T(3) level changes between preoperative native thyroid function and postoperative L-T(4) therapy. METHODS: We retrospectively studied 135 consecutive patients with papillary thyroid carcinoma, who underwent total thyroidectomy. Serum free T(4) (FT(4)), free T(3) (FT(3)), and TSH levels measured preoperatively were compared with those levels measured on postoperative L-T(4) therapy. RESULTS: serum tsh levels during postoperative L-T(4) therapy were significantly decreased compared with native TSH levels (P<0.001). serum FT(4) levels were significantly increased (P<0.001). Serum FT(3) levels were significantly decreased (P=0.029). We divided the patients into four groups according to postoperative serum TSH levels: strongly suppressed (less than one-tenth of the lower limit); moderately suppressed (between one-tenth of the lower limit and the lower limit); normal limit; and more than upper limit. Patients with strongly suppressed TSH levels had serum FT(3) levels significantly higher than the native levels (P<0.001). Patients with moderately suppressed TSH levels had serum FT(3) levels equivalent to the native levels (P=0.51), and patients with normal TSH levels had significantly lower serum FT(3) levels (P<0.001). CONCLUSIONS: Serum FT(3) levels during postoperative L-T(4) therapy were equivalent to the preoperative levels in patients with moderately suppressed TSH levels. Our study indicated that a moderately TSH-suppressive dose of L-T(4) is required to achieve the preoperative native serum T(3) levels in postoperative L-T(4) therapy.

Prognosis and prognostic factors of papillary thyroid carcinoma in patients under 20 years.

Age is an important prognostic factor of papillary thyroid carcinoma (PTC). In this study, we investigated the prognosis and prognostic factors of PTC in patients younger than 20 years. We enrolled 110 patients who underwent initial surgery at Kuma Hospital between 1987 and 2008. Tumor size > 4 cm, metastatic node ≥ 3 cm, and significant extrathyroid extension were more frequently detected in 8 patients with distant metastasis at diagnosis than in 102 patients without distant metastasis. Ten- and 20-year lymph node recurrence-free survival (LN-RFS) and distant recurrence-free survival (DRFS) rates were 84 and 80%, and 95 and 89%, respectively. Metastatic node ≥ 3 cm, age ≤ 16 years, tumor size > 4 cm, and male gender affected LN-RFS, and the former two had an independent prognostic value in multivariate analysis. Metastastic node ≥ 3 cm, significant extrathyroid extension, age ≤ 16 years, tumor size > 4 cm, and a male gender predicted a poor DRFS, and the former two were independent prognostic factors. To date, only 2 patients have died of PTC. These findings suggest that, in the subset of PTC patients younger than 20 years, metastatic node ≥ 3 cm, significant extension, and age ≤ 16 were important signs of aggressiveness of carcinoma, and careful treatment is necessary for patients with these characteristics, although the cause-specific survival was excellent.

Investigation of the prognosis of patients with papillary thyroid carcinoma by tumor size.

In papillary thyroid carcinoma (PTC), extrathyroid extension (Ex) and clinical lymph node metastasis (N) significantly affect the prognosis. We investigated the prognosis of patients with PTC 1 cm or less (1,220 patients), 1.1-2 cm (2,101 patients), 2.1-3 cm (1,249 patients), 3.1-4 cm (645 patients), and larger than 4 cm (563 patients). We classified N factor into three categories: N0, no clinical node metastasis: N1, clinical node metastasis smaller than 3 cm and without extranodal tumor extension requiring at least partial excision of adjacent organs for node dissection: and N2, clinical node metastasis 3 cm or larger or showing extranodal tumor extension. N2 markedly affected lymph node and distant recurrence-free survivals and cause-specific survival, regardless of the tumor size. N1 also adversely affected lymph node and distant recurrence-free survival but not cause-specific survival. Ex did not affect patients' prognosis with PTC 1 cm or less. It became a prognostic factor with PTC larger than 1 cm, and worsened lymph node and distant recurrence-free survival not only for N0 but also for N1 PTC larger than 3 cm and larger than 2 cm, respectively. However, its influence is limited for N2 PTC patients. Furthermore, Ex worsened the CSS with PTC larger than 2 cm in combination with N2. We have to note that the prognostic significance for lymph node and distant recurrence-free and cause-specific survival of Ex and N varies according to the tumor size in order to accurately predict the clinical outcomes and establish therapeutic strategies for PTC patients.

Relationship between prognosis of papillary thyroid carcinoma patient and age: a retrospective single-institution study.

Age is an important prognostic factor in papillary thyroid carcinoma (PTC). In this study, we investigated the difference in prognosis of 7 subsets of PTC patients without distant metastasis at presentation or a history of radiation exposure (20 years or younger, 21-30 years, 31-40 years, 41-50 years, 51-60 years, 61-70 years, and older than 70 years). The lymph node recurrence rate was high in patients 20 years or younger and those older than 60 years. Distant recurrence and carcinoma death rates significantly elevated in patients older than 60 years. The incidence of significant extrathyroid extension markedly increased with age, although that of large node metastasis or extranodal tumor extension did not differ much among the 7 subsets. With the Kaplan-Meier method, lymph node recurrence rate was poor in patients 20 years or younger and in those older than 60 years. Poor distant recurrence-free and cause specific survivals of patients older than 60 years were identified in the series of PTC patients with and without these aggressive features. It is therefore suggested that 1) Lymph node recurrence rate was high in patients 20 years or younger and those older than 60 years and 2) prognosis, including distant recurrence-free survival and cause-specific survival, of patients older than 60 years was poor regardless of clinicopathological features of PTC at initial surgery.

Validity of 6(th) edition of UICC TNM classification system for medullary thyroid carcinoma: a proposal for intraoperative evaluation of T category.

Medullary thyroid carcinoma (MTC) accounts for 1.4% of all thyroid malignancies in Japan. Here, we studied the validity of a staging system evaluated preoperatively (Stage), intraoperatively (intra-Stage), and pathologically (pStage) based on the 6(th) and 7(th) UICC TNM classifications. One hundred and nineteen MTC patients who did not show distant metastasis at diagnosis and underwent locally curative surgery were enrolled in this study (average follow-up period: 173.4 months). Twenty-year clinical (not biochemical) disease-free survival (DFS) rates of Stage I, II, III, and IVA patients based on the 6(th) edition were 100, 88.2, 66.8, and 38.9%, respectively. DFS of Stage IVA patients was significantly poorer than that of Stage III patients (p = 0.03137). However, using the 7(th) edition, only 1 patient was classified with Stage III. Intra-Stage III patients based on the 6th edition showed a significantly poorer DFS (20-year DFS 50.0%) than intra-Stage II patients (92.9%) (p = 0.02668), and DFS of intra-Stage IVA patients (38.9%) tended to be poorer than that of intra-Stage III patients (p = 0.05439). Only one patient was classified with intra-Stage III using the 7(th) edition. In pStage, as many as 56 patients (47.1%) were classified with pStage IVA employing both editions. Taken together, Stage and intra-Stage were more useful to accurately discriminate high-risk patients than pStage, and their 6(th) editions were better than 7(th) editions. Although the number of patients was small, our data showed the possibility that intra-Stage in the 6(th) edition was the best staging system for MTC patients.

Laryngeal approach to the recurrent laryngeal nerve involved by thyroid cancer at the ligament of Berry.

BACKGROUND: Thyroid cancer often involves the RLN at the ligament of Berry, which makes preservation of the nerve difficult. If the portion of RLN is resected, finding the peripheral RLN for reconstruction is difficult. Here we describe a laryngeal approach performed before dissecting the RLN to overcome these problems. METHODS: Between January 2007 and April 2011, 13 patients with papillary thyroid carcinoma had unilateral RLN involvement by the cancer at the ligament of Berry. Preoperatively, 8 had functioning vocal cords and 5 had unilateral paralysis. The laryngeal approach involves dividing the inferior pharyngeal constrictor muscle along the lateral edge of the thyroid cartilage and identifying the nerve under the muscle or behind the thyroid cartilage. This procedure was performed before resecting the tumor in 10 patients (Group 1) and after resection in the remaining 3 (Group 2). RESULTS: In Group 1, the RLN could be preserved with sharp dissection in 3 with functioning vocal cords preoperatively. Postoperatively they restored vocal cord function. The remaining 7 needed resection of the portion of RLN. RLN reconstruction was easily, since the peripheral RLN had already been identified. All patients in Group 2 needed resection of the portion of RLN. The peripheral RLN was identified in 2, and ansa-RLN anastomosis was performed. However, this was not possible in 1 patient. CONCLUSION: In patients with thyroid cancer involving the RLN at the ligament of Berry, performing the laryngeal approach before dissecting the nerve facilitates preservation or reconstruction of the nerve.

Biological behavior of papillary carcinoma of the thyroid including squamous cell carcinoma components and prognosis of patients who underwent locally curative surgery.

Thyroid carcinoma showing squamous differentiation throughout the entire lesion is diagnosed as squamous cell carcinoma of the thyroid (SCCT) in the WHO classification. This entity is a rare disease and shows a dire prognosis; however, squamous differentiation is more frequently detected in only a portion of papillary thyroid carcinoma. In this paper, we present our experience of 10 patients (8 primary lesions and 2 with recurrence in the lymph nodes) with papillary thyroid carcinoma having an SCC component (PTC-SCC). Only 3 of 8 primary lesions (38%) and none of the 2 recurrent nodes were preoperatively diagnosed as or suspected of having SCC components. All 10 patients underwent locally curative surgery. To date, 3 patients have died of carcinoma, and 2 had distant metastasis at diagnosis or had an undifferentiated carcinoma component. The other 7 are currently alive 5 to 43 months after diagnosis. Systemic adjuvant therapy after the detection of recurrence was effective for 2 patients. It is possible that some PTC-SCC patients without distant metastasis who undergo locally curative surgery can survive for a prolonged period and adjuvant therapies can be effective for local and distant recurrences.