Prognostic significance of patient age in papillary thyroid carcinoma with no high-risk features.

Older age is recognized as a predictor of poor prognosis in papillary thyroid carcinoma (PTC) patients. However, young age is associated with disease progression of PTC measuring 1 cm or smaller in patients on active surveillance. In this study, we investigated the relationship between patient age and prognosis of PTC belonging to very low-, low-, and intermediate-risk groups based on the guidelines published by the Japan Association of Endocrine Surgery in 2018. We enrolled 4,870 PTC patients with no high-risk features and assigned each to one of three categories: very low risk (N = 1,161), low risk (N = 1,746), and intermediate risk (N = 1,963). In very low-risk patients, the local recurrence-free survival (RFS) rate of young patients (<55 years) was significantly worse (p = 0.0437) than that of older patients (≥55 years). In low-risk patients, although age did not affect local recurrence, older patients were more likely to show distant recurrence on univariate (p = 0.0005) and multivariate analyses (p = 0.0017). In the intermediate-risk series, the local RFS rate of older patients tended to be poor (p = 0.0538), and older age was significantly associated with distant RFS (univariate, p = 0.0356; multivariate, p = 0.0439) and carcinoma death (univariate, p < 0.0001; multivariate, not done because of no other suitable factors). The prognostic significance of patient age depends on risk classification: younger age significantly predicts local recurrence in very low-risk PTC, while older age predicts worse prognosis in low- and intermediate-risk patients. These findings indicate that young age is related to rapid growth in early-phase PTC.

Prognostic factors for follicular thyroid carcinoma: the importance of vascular invasion.

The World Health Organization (WHO) classifies follicular thyroid carcinoma (FTC) into three categories: minimally invasive (mFTC), encapsulated angioinvasive (eaFTC), and widely invasive (wFTC). This study investigated whether this classification is appropriate. We enrolled 523 patients who underwent initial surgery at Kuma Hospital between 1998 and 2015 and were diagnosed with FTC. Capsular invasion (CI) was classified as none, minimal (microscopic), or wide (macroscopic) invasion. Vascular invasion (VI) was divided according to the number of invasive foci into three degrees: VI(-), VI(1+), and VI(2+). For 507 M0 patients, age ≥55 years (p = 0.004), non-oxyphilic histology (p = 0.043), and male sex (p < 0.001) predicted poor distant recurrence-free survival (DR-FS) on univariate analysis; however, tumor size >4 cm and wide CI did not. The DR-FS rates significantly decreased from VI(-) to VI(2+) in a step-by-step fashion, including VI(-) vs. VI(1+) (p = 0.011) and VI(1+) vs. VI(2+) (p = 0.014). Multivariate analysis revealed that older age (p = 0.0004), non-oxyphilic histology (p = 0.041), male sex (p = 0.0052), VI(1+) (p = 0.017), and VI(2+) (p < 0.001) independently predicted distant recurrence. The DR-FS rates did not significantly differ among mFTC, wFTC/VI(-), and eaFTC/VI(1+). The DR-FS rate of eaFTC/VI(2+) was worse than that of eaFTC/VI(1+) (p = 0.042), but did not differ from that of wFTC/VI(1+/2+). Our findings suggest that subclassifying eaFTC according to the degree of VI and restricting wFTC to VI-positive cases would be better in the WHO classification. Revising the definition for wide CI is recommended.

Lipoadenoma of the parathyroid: characteristics of a rare cause of hyperparathyroidism.

Parathyroid Lipoadenoma (PLA) contains abundant mature adipose tissue and is a rare cause of hyperparathyroidism. This study aimed to investigate the clinical features of PLA in nine patients with primary hyperparathyroidism, including two men and seven women, with ages ranging from 45-84 years (median 60 years). PLA accounted for 0.5% of all parathyroid tumors during the study period. One patient presented with anorexia due to hypercalcemia; however, the other eight patients were asymptomatic. The median preoperative serum intact-parathyroid hormone (iPTH) and calcium levels were 143 pg/mL (range, 102-378) and 10.8 mg/dL (range, 10.3-11.3), respectively. PLA was difficult to identify using ultrasonography (US) as it appears as a moderately hyperechoic nodule and is difficult to distinguish from the surrounding adipose tissues. Only 33% of the lesions (three out of nine lesions) were accurately identified. However, they could be distinctly differentiated from the surrounding tissue using computed tomography (CT). All PLAs were also detected using the sesta-methoxyisobutylisonitrile single-photon emission-computed tomography (SPECT). All the patients were treated by a single gland extirpation. The median size and weight of the PLA were 14 mm (range, 10-22) and 567 mg (range, 200-1,533), respectively. In conclusion, the clinical manifestations of PLA are similar to those of ordinal parathyroid adenomas, except for their unique US and CT images. PLA should be considered as a potential etiologic factor in cases of hyperparathyroidism when the lesions are demonstrated as hyperechoic nodules or unidentified by US but detected by CT or SPECT imaging.

Observational management of papillary microcarcinoma appearing in the remnant thyroid after hemithyroidectomy.

Active surveillance for papillary thyroid microcarcinomas (PTMCs) initiated in Japan is becoming adopted worldwide as a management option. However, it remains unclear how to manage newly appearing PTMCs in the remnant thyroid after hemithyroidectomy. We investigated the outcomes of similar observational management (OM) for PTMCs appearing in the remnant thyroid after hemithyroidectomy for papillary thyroid carcinoma (PTC) and benign thyroid nodules. Eighty-three patients were newly diagnosed with PTMC in the remnant thyroid between January 1998 and March 2017. Of these, 42 patients underwent OM with >3 times ultrasound examinations. Their initial diagnoses were PTC (initially malignant group) in 37 patients and benign nodule (initially benign group) in 5 patients. We calculated the tumor volume doubling rate (TV-DR) during OM for each PTMC. The TV-DR (/year) was <-0.1, -0.1-0.1, 0.1-0.5, and >0.5 in 12, 19, 5, and 6 patients, respectively. The TV-DRs in both groups did not statistically differ, but six patients (16%) in the initially malignant group showed moderate growth (TV-DR >0.5/year). They underwent conversion surgery and none of them had further recurrence. The remaining 36 patients retained OM without disease progression. The TV-DR in the initially malignant group was not significantly associated with patients' backgrounds or their initial clinicopathological features. None of the patients in this study showed distant metastases/recurrences or died of thyroid carcinoma. Although a portion of PTMCs appearing after hemithyroidectomy for thyroid malignancy are moderately progressive, OM may be acceptable as a management option for PTMCs appearing in the remnant thyroid after hemithyroidectomy.

Long-term outcomes of cytologically benign thyroid tumors: a retrospective analysis of 3,102 patients at a single institution.

Some thyroid tumors that are cytologically diagnosed as benign may be pathologically diagnosed as malignant. Here, we investigated the long-term outcomes of patients with thyroid tumors with benign cytology, and the factors for malignancy. We retrospectively reviewed the cases of 3,102 patients with thyroid tumors >1 cm cytologically diagnosed as benign at our hospital during a 1-year period from January 2007. The median follow-up duration for all patients was 68.7 (range 0.0-168.7) months. Immediate surgery and delayed surgery were performed in 393 and 148 patients, respectively. Eventually, 541 (17.4%) of the 3,102 patients underwent a thyroidectomy, and 2,561 (82.6%) were observed without surgery. Among the surgically treated patients, the tumors of 525 (97.0%) and 16 (3.0%) were pathologically diagnosed as benign and malignant, respectively. There was no significant difference in age, gender, tumor size, serum thyroglobulin level at surgery, or the tumor volume-doubling rate (TV-DR) between the benign and malignant cases. Only the ultrasonographic findings based on our hospital's classification system were directly and significantly linked to pathological diagnosis (p < 0.01). Among the tumors of the 667 patients who were followed without surgery for >10 years, 89.9% remained unchanged and 7.2% were reduced in size. Ultrasonographic evaluation provides important information for therapeutic decision-making regarding surgery versus observation for cytologically benign tumors.

Prognostic significance of vascular invasion and cell-proliferation activity in widely invasive follicular carcinoma of the thyroid.

Widely invasive follicular thyroid carcinoma (wi-FTC) is regarded as having an aggressive character and a dire prognosis, but it has not been known whether all wi-FTCs have a dire prognosis. Herein we retrospectively analyzed the cases of 133 patients with wi-FTCs to determine the prognostic significance of vascular invasion and cell-proliferation activity based on the Ki-67 labeling index (LI). Of the 119 patients without distant metastasis (M0), 11 (9.2%) showed recurrence during the postoperative follow-up. In a univariate analysis, the recurrence-free survival (RFS) rates of the M0 patients with vascular invasion and those with a Ki-67 LI ≥5% were significantly poorer (p = 0.0013 and p = 0.0268, respectively) than those of the patients without vascular invasion or with a Ki-67 LI <5%. Other clinicopathological factors such as patient age, gender, tumor size, and oxyphilic tumor were not significantly related to the patients' RFS. In a multivariate analysis, positive vascular invasion independently affected the RFS (p = 0.0133), but Ki-67 >5% did not (p = 0.1348). To date, only five patients have died of their thyroid carcinoma; four cases were M1. In conclusion, although M0 wi-FTC generally has a favorable prognosis, cases with positive vascular invasion or a high Ki-67 LI are likely to recur, and careful postoperative follow-up is necessary.

Evaluation of the diagnostic utility of the aminotransferase/lactate dehydrogenase ratio for the suspension of tissue specimens during thyroid surgery for the identification of parathyroid tissue.

Identification of the parathyroid glands during surgery is crucial for preventing postoperative hypoparathyroidism. Kikumori et al. reported that the aspartate aminotransferase (AST)/lactate dehydrogenase (LDH) ratio for the saline suspension of a suspicious tissue can differentiate parathyroid tissue from other tissues. The aim of this study was to evaluate the utility of this method and investigate the appropriate time for measurement. We obtained 465 tissue specimens during thyroidectomy of 102 patients with papillary thyroid carcinoma (PTC), and 422 specimens (129 parathyroid, 92 PTC, and 201 other tissues) with measurable AST and LDH were analyzed. Small pieces of the tissues were immersed in saline and sent for measurement of AST and LDH. The assay was performed immediately after thyroidectomy for 245 specimens (the same-day group) and during the next morning for the remaining 177 specimens (the next-day group). The accuracy of diagnosing parathyroid tissue was significantly better in the same-day group than in the next-day group. A cut-off value of 0.18 gave the best diagnostic precision, with an area under the receiver operating characteristic curve of 0.95 and 88.7% sensitivity and specificity in the same-day group. When the cut-off value was set to 0.20, the specificity for excluding carcinomatous tissues was 100%. When measured on the day of the surgery, the AST/LDH ratio for the saline suspension of the surgical specimens is useful for discriminating parathyroid tissues from other tissues. This method can be utilized at most hospitals where intraoperative frozen sections or rapid parathyroid hormone assays are not available.

Thyroid Tubercle of Zuckerkandl May Not Arise from the Ultimobranchial Body: Results from Histological Analysis.

Thyroid tubercle of Zuckerkandl (TZ) is a nodule arising from the posterolateral thyroid, considered to be a remnant of the ultimobranchial body (UB). Considering that C cells and solid cell nests also arise from the UB, we hypothesized that these would be present in the TZ. We examined the presence of C cells and solid cell nests in the TZ using the histological analyses of 21 patients with grade 2 or 3 TZs following Pelizzo's grading system. Out of 21 TZs, 19 (90.5%) were located in the right lobe of the thyroid. Microscopically, solid cell nests were found within the TZ in 1 case (4.8%), and within the main thyroid tissues in 3 cases (14.3%). Calcitonin-positive C cells were scattered within the TZ in 1 case (4.8%), and within the main thyroid tissue in 15 cases (71.4%). The distribution of C cells within the main thyroid tissue was denser than that within the TZ. The above-mentioned results indicated the lack of C cells and solid cell nests in the TZ. Although the TZ may have an embryological origin different from that of ordinary thyroid tissue, it is unlikely that the remnants of the UB are involved in the formation of the TZ.

Subclassification of Tumor Extension and Nodal Metastasis in Papillary Thyroid Cancer to Improve Prognostic Accuracy of the Eighth Edition of the Tumor-Node-Metastasis Classification.

BACKGROUND: The eighth edition of the tumor-node-metastasis classification system (TNM-8th) reflects the prognosis of papillary thyroid cancer (PTC) better than the seventh edition. This study investigated methods to further improve the prognostic accuracy of the TNM-8th. METHODS: We enrolled 5683 patients who underwent surgery for PTC at the Kuma Hospital. We subdivided tumor extension (T4a) into T4a1 and T4a2 based on intraoperative gross findings and N1 according to size ( < 3 cm and ≥ 3 cm) based on preoperative imaging findings. RESULTS: The corresponding 20-year cancer-specific survival (CSS) rates of 4846, 403, 406, and 28 patients with TNM-8th stages I, II, III, and IVB, respectively, were 99.3%, 93.4%, 82.6%, and 11.3%. Owing to a CSS similar to that of stage II patients, N2 or T4a2 patients <55 years were upstaged to revised stage (re-stage) II. The CSS of stage III patients with T4a1 was significantly better (p < 0.0001) than that of those with T4a2, and the CSS of T4a1 patients was similar to that of stage II patients. Therefore, T4a1 patients ≥ 55 years were downstaged to re-stage II. Owing to a CSS similar to that of T4a2 stage III patients, N2 stage II patients were upstaged to re-stage III. The 20-year CSS was poorer in re-stage III (69.5%) than in stage III patients and similar in re-stage II patients (91.8%) and stage II patients. CONCLUSION: Subdivision of clinical tumor extension and node metastasis further improves the TNM-8th for PTC and identifies poor risk patients more accurately.

Prognostic Value of Extranodal Tumor Extension in Papillary Thyroid Carcinoma: Proposal for Upstaging of Cases with Extranodal Tumor Extension.

BACKGROUND: Recently, we have created a revised version of the eighth edition of the tumor-node-metastasis classification for papillary thyroid carcinomas (PTCs) by subdividing the T4a (T4a1 [moderate] and T4a2 [significant]) and N (N1 [N ≤ 3 cm] and N2 [N > 3 cm]) classifications. This re-staging better stratified patient outcomes. In this study, we investigated the prognostic significance of extranodal tumor extension (LNEx) in PTC. METHODS: Five thousand six hundred and eighty-three patients with PTC surgically treated in Kuma Hospital were enrolled. We evaluated LNEx based on intraoperative findings. RESULTS: One hundred and twenty-seven patients (2%) displayed LNEx. In contrast to what we observed for extrathyroid extension, the prognostic value of LNEx did not change based on the organ that had been invaded, and we therefore analyzed LNEx patients as a single group. In patients aged 55 or older, LNEx independently affected patients' prognoses, as did T4a2 and N2. The cancer-specific survival (CSS) of patients in Stage I but having LNEx demonstrated the similar prognosis to patients in Stage II. Further, in the subset analysis for Stage II patients aged 55 or older, LNEx had a significant prognostic value for CSS in both the univariate and multivariate analyses, as did N2. The CSS of Stage II patients aged 55 or older with LNEx did not differ from that of Stage III patients. CONCLUSIONS: It is appropriate that, similar to T4a2 or N2 patients, LNEx-positive patients younger than 55 years in Stage I and those aged 55 or older in Stage II are re-staged to II and III, respectively.

Older Age Significantly Affects Mortality of Patients with Papillary Thyroid Carcinoma Only When They Have High-Risk Features.

BACKGROUND: Old age is a known prognostic factor for mortality in patients with papillary thyroid carcinoma (PTC). This study aimed to investigate the relationship between cause-specific survival (CSS) following PTC and the extent of old age. METHODS: We enrolled 4692 patients aged ≥ 55 years with PTC who underwent surgery between 1989 and 2009 at Kuma Hospital (median follow-up period 140 months). The presence of at least one of the following was used to classify the patients as high risk: (1) tumor sizes > 4 cm, (2) node metastasis ≥ 3 cm, (3) significant extrathyroid extension corresponding to T4a, (4) extranodal tumor extension, and (5) distant metastasis. T1N0M0 PTC was classified as low risk, and all other patients were classified as intermediate risk. We divided all patients into three categories based on age: 55-64, 65-74, and ≥ 75 years. RESULTS: One low-risk patient (0.04%), 18 intermediate-risk patients (1.5%), and 105 high-risk patients (9.4%) died of PTC, and CSS of high-risk patients was poorer than that of others (p < 0.0001). The CSS of low and intermediate-risk patients did not differ with age. However, CSS of high-risk patients became significantly poorer with advancing age (p = 0.0017 for 55-64 years vs. 65-74 years, and p = 0.0109 for 65-74 years vs. ≥ 75 years). CONCLUSIONS: Advanced age has a significant prognostic impact on CSS only for high-risk patients with PTC.

Subset analysis of the Japanese risk classification guidelines for papillary thyroid carcinoma.

Guidelines published by the Japan Association of Endocrine Surgeons (JAES)/Japanese Society of Thyroid Surgery (JSTS) for patients with papillary thyroid carcinoma describe four risk classes (very low-, low-, intermediate- and high-risk) for deciding on therapeutic strategies. Here, we investigate cause-specific survival (CSS) of high- and intermediate-risk patients, taking their age into consideration. CSS of intermediate-risk patients ≥55 years was poorer than that of those <55 years (p < 0.0001) (20-year CSS rates, 96.9% vs. 98.7%). CSS of intermediate-risk patients <55 years was excellent but still poorer (p = 0.0152) than that of low- or very low-risk patients (20-year CSS rates, 100%). CSS of high-risk patients <55 years (20-year CSS rates, 96.0%) was similar (p = 0.7412) to that of intermediate-risk patients ≥55 years, while high-risk patients ≥55 years (20-year CSS rates, 80.6%) showed much poorer prognosis (p < 0.0001) than the others. In high-risk patients <55 years, distant metastasis (M1), extrathyroid extension (Ex), node metastasis ≥3 cm, and extranodal tumor extension, and in those ≥55 years, M1, Ex, and tumor size >4 cm were regarded as prognostic factors on multivariate analysis. We therefore conclude that 1) prognosis of high-risk patients ≥55 years should be carefully treated because of significantly poor prognosis, 2) prognostic factors of high-risk patients vary according to patient age, and 3) overtreatment of intermediate-risk patients and young high-risk patients should be avoided; however, appropriate treatment strategies need to be established, considering that their prognoses are excellent, but still poorer than low- or very low-risk patients.

Appropriateness of the revised Japanese guidelines' risk classification for the prognosis of papillary thyroid carcinoma: a retrospective analysis of 5,845 papillary thyroid carcinoma patients.

The revised Japan Association of Endocrine Surgeons (JAES)/Japanese Society of Thyroid Surgery (JSTS) guidelines for patients with papillary thyroid carcinoma (PTC) describe four risk classes: very-low-risk, low-risk, intermediate-risk, and high-risk. Here we conducted a retrospective analysis to evaluate the appropriateness of these guidelines' risk classification of PTCs. Lymph node recurrence-free, distant recurrence-free and cause-specific survivals at 15-year of high-risk group were significantly poorer than those at 15-year of intermediate-group and these survivals of intermediate-group were poorer than of low- or very-low-risk patients. In the subset analyses based on patient age (≥55 years and <55 years), we obtained the same results in both subsets. Age significantly worsen the whole prognosis of high-risk patients and cause-specific survival of intermediate-risk patients, but not the prognosis of low- or very-low-risk patients. Therefore, the risk classification of the revised JAES/JSTS guidelines is appropriate, and therapeutic strategies should be decided based on the risk class together with the patients' age.

Excellent Prognosis of Central Lymph Node Recurrence-Free Survival for cN0M0 Papillary Thyroid Carcinoma Patients Who Underwent Routine Prophylactic Central Node Dissection.

INTRODUCTION: In Japan, prophylactic central node dissection (p-CND) for papillary thyroid carcinoma (PTC) has been routinely performed in many institutions, including ours (Kuma Hospital, Japan). We evaluated the recurrence to a central lymph node in patients with cN0M0 PTC who underwent routine p-CND. MATERIALS AND METHODS: We enrolled 4301 patients with cN0M0 PTC who underwent an initial surgery between 1987 and 2005 (median age 51 years). The postoperative follow-up periods ranged from 4 to 362 months (median 164 months). Only 15 patients underwent radioactive iodine (RAI) ablation (≥30 mCi) after total or near total thyroidectomy. RESULTS: Of the 4301 patients with N0M0 PTC who underwent p-CND, 2548 (59%) were diagnosed as pN1a on postoperative pathological examination. To date, only 52 cases (1.2%) showed recurrence to a central lymph node. The 10-year and 20-year central node recurrence-free survival rates were excellent at 99.1 and 98.2%, respectively. On multivariate analysis, age ≥55 years, significant extrathyroid extension, tumor size >2 cm, and ≥5 pathologically confirmed central node metastases (but not the presence of central node metastasis) independently affected central node recurrence. CONCLUSIONS: Under the situation of routine p-CND, the central node recurrence-free survival of cN0M0 PTC is excellent. However, future studies, including double-arm studies from Japan, should examine whether the omission of p-CND cN0M0 PTC is appropriate without RAI ablation in consideration of various factors, including the pros and cons of p-CND.

Prognostic value of the 8th tumor-node-metastasis classification for follicular carcinoma and poorly differentiated carcinoma of the thyroid in Japan.

Follicular thyroid carcinoma (FTC), a form of differentiated thyroid carcinoma, is the second most common malignancy arising from thyroid follicular cells. Recently, the tumor-node-metastasis (TNM) classification for differentiated thyroid carcinoma was revised from the 7th to the 8th edition. The diagnostic criteria for poorly differentiated carcinoma (PDC) were also updated in the latest World Health Organization (WHO) classification. In this study, we investigated whether these changes are appropriate for accurately predicting prognosis. Three hundred and twenty-nine patients diagnosed with postoperative pathologically confirmed FTC, who underwent initial surgery at our hospital between 1984 and 2004, were enrolled. For this study, patients were re-evaluated and diagnosed with FTC (N = 285) or PDC (N = 44) without typical nuclear findings of papillary thyroid carcinoma. For FTC, the 8th TNM classification was a more accurate predictor of prognosis than the 7th TNM classification. In the 8th TNM classification, cause-specific survival became significantly poorer from Stage I to IVB. The cause-specific survival of PDC based on the latest WHO classification was worse than, but did not significantly differ from, that of PDC based only on the former WHO classification. For PDC, neither of the TNM classifications could accurately predict prognosis. Taken together, we conclude that (1) the 8th TNM classification more accurately reflects the prognosis of FTC than the 7th TNM classification; (2) PDC based on the former WHO classification should be retained, at least in Japan; and (3) the TNM classification may not be suitable for predicting the prognosis of PDC.

Prognostic value of the 8th edition of the tumor-node-metastasis classification for patients with papillary thyroid carcinoma: a single-institution study at a high-volume center in Japan.

The tumor-node-metastasis (TNM) staging system is most commonly adopted to evaluate the prognosis of patients with thyroid carcinoma. The 8th edition of the TNM staging system, an extensively revised version of the 7th edition, was recently released. We aimed to investigate whether and how well the 8th edition reflects the cause-specific survival (CSS) of patients with papillary thyroid carcinoma by analyzing the cases in 5,892 patients who underwent initial surgery at Kuma Hospital between 1987 and 2005. The median postoperative follow-up duration was 178 months (range: 6-357 months). One patient with T4b disease was excluded from the analysis. Overall, 116 (2.0%) patients died of thyroid carcinoma. The proportion of variance explained (PVE) for CSS in the 7th and 8th editions was 10.69 and 10.97, respectively. Using the 7th edition, CSS of patients with stage IVA and stage III disease was similar (p = 0.32). In contrast, using the 8th edition, CSS was poorer in stage II than in stage I (p < 0.001), in stage III than in stage II (p < 0.001), and in stage IVB than in stage III (p < 0.001). Similar results were observed for disease-free survival. Although we could not establish any objective evidence that the 8th edition is superior to the 7th edition, the 8th edition is simpler and more convenient, as it includes fewer stages and addresses the issue of the 7th edition where stage IVA and III patients had similar prognoses.

Comparison of the costs of active surveillance and immediate surgery in the management of low-risk papillary microcarcinoma of the thyroid.

The incidence of thyroid cancer is increasing rapidly in many countries, resulting in rising societal costs of the care of thyroid cancer. We reported that the active surveillance of low-risk papillary microcarcinoma had less unfavorable events than immediate surgery, while the oncological outcomes of these managements were similarly excellent. Here we calculated the medical costs of these two managements. We created a model of the flow of these managements, based on our previous study. The flow and costs include the step of diagnosis, surgery, prescription of medicine, recurrence, salvage surgery for recurrence, and care for 10 years after the diagnosis. The costs were calculated according to the typical clinical practices at Kuma Hospital performed under the Japanese Health Care Insurance System. If conversion surgeries were not considered, the 'simple cost' of active surveillance for 10 years was 167,780 yen/patient. If there were no recurrences, the 'simple cost' of immediate surgery was calculated as 794,770 yen/patient to 1,086,070 yen/patient, depending on the type of surgery and postoperative medication. The 'simple cost' of surgery was 4.7 to 6.5 times the 'simple cost' of surveillance. When conversion surgeries and recurrence were considered, the 'total cost' of active surveillance for 10 years became 225,695 yen/patient. When recurrence were considered, the 'total cost' of immediate surgery was 928,094 yen/patient, which was 4.1 times the 'total cost' of the active surveillance. At Kuma Hospital in Japan, the 10-year total cost of immediate surgery was 4.1 times expensive than active surveillance.

Diagnosis and surgical indications of oxyphilic follicular tumors in Japan: Surgical specimens and cytology.

Oxyphilic cell carcinoma is a relatively rare type of differentiated thyroid carcinoma. We investigated the diagnosis of oxyphilic cell carcinoma based on surgical specimens and cytology to elucidate the indications for surgery for oxyphilic tumors. Among 330 patients pathologically diagnosed as having an oxyphilic cell carcinoma or adenoma, the incidence of carcinoma was 21%. The pathological diagnosis of oxyphilic cell carcinoma was related to tumor size (>4 cm). On cytology, 79% of the tumors were classified as category IV or greater by the Bethesda System for Reporting Thyroid Cytopathology (BSRTC), but no significant difference was established between category IV or greater and categories I-III regarding the incidence of carcinoma. Of 998 patients cytologically diagnosed as having oxyphilic cell tumors (BSRTC category IV), 426 underwent surgery and 66 (15%) were diagnosed as malignancies. In a univariate analysis, serum thyroglobulin (Tg) levels (>500 ng/dL) for anti-Tg antibody-negative patients, tumor size (>4 cm) and US class (≥3) significantly predicted malignant histology. A multivariate logistic analysis revealed that US finding was an independent predictor of malignant histology, and tumor size (>4 cm) also predicted malignancy when the Tg level was excluded from the variables. These findings suggest that, for thyroid tumors diagnosed as oxyphilic follicular neoplasms on cytology, surgical indications are tumors with US class ≥3, tumor size >4 cm, and Tg >500 ng/dL (with negative Tg-antibody). It is not appropriate to perform surgery for all cases for a precise histological classification, unlike the BSRTC recommendation.

Prognostic impact of Ki-67 labeling index in minimally invasive follicular thyroid carcinoma.

We investigated the prognostic impact of the Ki-67 labeling index (LI) in minimally invasive follicular thyroid carcinoma (FTC). We enrolled 192 patients (including four with distant metastasis at diagnosis) who were pathologically diagnosed as having minimally invasive FTC between 1998 and 2007 at Kuma Hospital. When the Ki-67 LI was higher than 5% in the hot area, we regarded it as a high Ki-67 LI. In a univariate analysis, patient age (≥45 years), high-frequent vascular invasion (≥4 in H&E specimens), and high Ki-67 LI significantly predicted the disease-free survival (DFS) of the patients. Since none of the patients <45 years old showed a recurrence, we performed a multivariate analysis of variables other than patient age. In the multivariate analysis including the presence of vascular invasion, high Ki-67 LI was an independent predictor of carcinoma recurrence. However, in the multivariate analysis including high-frequent vascular invasion, only high-frequent vascular invasion independently affected the DFS. These findings suggest that the Ki-67 LI has a rather strong prognostic value for the DFS of patients, although its impact was less than those of patient age and high-frequent vascular invasion.

Changes in serum thyroglobulin antibody levels as a dynamic prognostic factor for early-phase recurrence of thyroglobulin antibody-positive papillary thyroid carcinoma after total thyroidectomy.

We demonstrated previously that dynamic prognostic markers such as the thyroglobulin (Tg)-doubling time in thyroglobulin antibody (TgAb)-negative papillary thyroid carcinoma (PTC) and changes in pre- and postoperative TgAb levels in TgAb-positive PTC patients more keenly reflect patients' prognosis than conventional static prognostic factors. Here we investigated periodic changes in TgAb levels in 513 TgAb-positive PTC patients who underwent total thyroidectomy. The TgAb levels at 1 year after surgery decreased to <50% of the preoperative values in 407 (79%) patients, and the remaining 106 (21%) patients showed no decrease in TgAb. In 426 patients, TgAb was also measured more than 1 year after surgery. Compared with their TgAb levels 1 year after surgery, 59 patients (14%) showed an increase in TgAb levels of >20% during the follow-up. The postoperative Tg levels at 1 year after surgery remained positive in 44 (9%) patients despite their TgAb positivity. To date (median follow-up period 35 months), 12 of the 426 patients (3%) showed PTC recurrence, and 11 of these patients showed either or both a TgAb elevation later than 1 year after surgery and postoperative Tg positivity. Although further studies with longer follow-ups are necessary, we can conclude that changes in postoperative TgAb levels may be usable as a surrogate tumor marker for TgAb-positive PTC patients after total thyroidectomy.