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Abstract The thyroid gland's neurovascular relationship is commonly portrayed as the recurrent laryngeal nerve (RLN) coursing posteriorly to the thyroid gland. We report a rare case with the RLN running anteriorly to a thyroid tumor. A 56-year-old Japanese woman underwent a thyroidectomy for a benign thyroid tumor. Preoperatively, computed tomography confirmed that part of the tumor had extended into the mediastinum and was descending posteriorly up to the brachiocephalic artery. Intraoperatively, when the sternothyroid muscle was incised to expose the thyroid gland, a cord (nerve)-like structure was observed directly anterior to the thyroid tumor. Although the course of this cord-like structure was clearly different from the "traditional" course of the right RLN, the possibility that the structure was the RLN could not be excluded. The structure was traced back in order to preserve it; we saw that it entered the larynx at the lower margin of the cricothyroid muscle and approximately at the level of the cricothyroid junction through the back of the normal thyroid tissue. With intraoperative neuromonitoring, the structure was identified as the RLN. As a result, the course of the RLN run anterior to the tumor but then posterior to the 'normal thyroid' i.e. into it normal anatomical position. Had we assumed that the RLN was behind the thyroid tumor, we would have damaged the RLN. It would not be possible to diagnose this abnormal running course of the RLN reliably before surgery, but extra care should be taken in similar cases, that is, when a large thyroid tumor is descending posteriorly up to the brachiocephalic artery on the right side.

Abstract Background The major sites of distant metastases of papillary thyroid carcinoma (PTC) are the lung and bone; metastasis to the liver is rare. Although the postoperative serum thyroglobulin (Tg) level after total thyroidectomy is a good prognostic indicator for PTC when anti-thyroglobulin antibody (TgAb) is negative, the presence of TgAb interferes with the Tg assay, making serum Tg levels unreliable. Here we report a case of liver metastasis of PTC that presented with elevated serum levels of carbohydrate antigen 19-9 (CA19-9), which is usually a serum marker of pancreatic and gastrointestinal neoplasias. Case presentation A 69-year-old man was diagnosed with PTC and underwent total thyroidectomy 16 years ago. The patient’s serum Tg levels increased progressively during follow-up and his serum TgAb was negative. Positron emission tomography (PET) and computed tomography (CT) revealed metastases of the lung, cervical spine, mediastinum and liver. The liver lesion was a solitary tumor measuring 4.0 cm in the greatest dimension. His serum CA19-9 level was very high (326 U/mL), and intrahepatic cholangiocarcinoma was suspected from the results of various examinations including gastrointestinal endoscopic imaging and CT. Laparoscopic partial liver resection for segment 4 was performed. The histopathological diagnosis was a metastatic liver tumor from PTC. The immunohistological examination revealed that the liver tumor was positive for CA19-9 and Tg. The primary PTC, recovered from paraffin-embedded specimen, was also positive for CA19-9. After the surgery, his serum CA19-9 level as well as serum Tg level markedly decreased. Conclusions We presented the first reported case of liver metastasis of a PTC presenting with elevated serum levels of CA19-9 after total thyroidectomy. This case suggests that the serum CA19-9 levels may serve as a surrogate marker for PTC in place of the serum Tg level in patients with positive serum TgAb if the PTC and/or the metastatic lesions are positive for CA19-9 staining.

Abstract Background Our previous kinetic analyses of changes in the tumor volume (TV) of papillary thyroid microcarcinomas during active surveillance revealed that the tumors’ growth varied over time from rather rapid growth to shrinkage and that the hypothetical TV-doubling rates (DRs) before the patients’ presentation were much larger than their observed TV-DRs, indicating that rapid growth phases preceded their presentation. Whether this phenomenon also occurs in medullary thyroid carcinoma (MTC) was unknown. Methods We retrospectively analyzed the cases of 46 MTC patients (18 hereditary, 28 sporadic; 9–80 years old at surgery, median 53.5 years; 19 males and 27 females) with elevated postoperative calcitonin (Ct) measured with the electrochemiluminescence immunoassay suggesting persistent disease. We calculated each patient’s Ct-DR and his/her hypothetical TV-DR, using the tumor size and age at surgery. Results Ct-DRs (/year) after surgery were > 0.5, 0.1–0.5, − 0.1–0.1, and 1, 0.5–1.0, 0.1–0.5 and

Objective: Multiple endocrine neoplasia type 2A (MEN 2A) is a rare syndrome caused by RET germline mutations and has been associated with primary hyperparathyroidism (PHPT) in up to 30% of cases. Recommendations on RET screening in patients with apparently sporadic PHPT are unclear. We aimed to estimate the prevalence of cases presenting with PHPT as first manifestation among MEN 2A i ndex cases and to characterize the former cases. Design and methods: An international retrospective multicenter study of 1085 MEN 2A index cases. Experts from MEN 2 centers all over the world were invited to participate. A total of 19 centers in 17 different countries provided registr y data of index cases followed from 1974 to 2017. Results: Ten cases presented with PHPT as their first manifestation of M EN 2A, yielding a prevalence of 0.9% (95% CI: 0.4–1.6). 9/10 cases were diagnosed with medullary thyroid carcinoma (MTC) in relation to parathyroid surgery and 1/10 was diagnosed 15 years after parathyroid surgery. 7/9 cases with full TNM data were node-positive at MTC diagnosis. Conclusions: Our data suggest that the prevalence of MEN 2A index cases that present with PHPT as their first manifestation is very low. The majority of i ndex cases presenting with PHPT as first manifestation have synchronous MTC and are often n ode-positive. Thus, our observations suggest that not performing RET mutation analysis in patients with apparently sporadic PHPT would result in an extremely low false-negative rate, if no other MEN 2A component, specifically MTC, are found during work-up or resecti on of PHPT.

Introduction. Young patients with papillary thyroid carcinoma (PTC) generally have excellent prognoses despite their often-advanced disease status. The reasons for this excellent prognosis are poorly understood. Objective. To investigate the natural history of PTC in young patients, we compared the observed tumor volume-doubling rate (TV-DR) with the hypothetical tumor volume-doubling rate (hTV-DR) before presentation in young PTC patients. DR is an inverse of the doubling time and indicates the number of doublings that occur in a unit of time. A negative value indicates the number of times the volume is reduced by half per unit time. Methods. We enrolled 20 patients with the following characteristics: age ≤19 years, diagnosed with PTC according to the cytology results between 2013 and 2018 and followed-up with periodical ultrasound examinations for ≥3 months before surgery for various reasons. Seventeen patients later underwent surgery confirming the diagnosis. We calculated TV-DRs using serial measurements of tumor diameters after presentation and hTV-DRs using tumor diameters and patients’ age at presentation, assuming that a single cancer cell was present at the patient’s birth and that the tumor grew at a constant rate. These values indicate the lowest growth rates necessary for a single cancer cell to achieve the full tumor size at presentation. Results. Thirteen patients had positive TV-DRs (/year) ranging from 0.09 to 1.89, indicating tumor growth, and the remaining seven patients had negative values (−0.08 to −1.21), indicating regression. The median TV-DR was 0.29. The hTV-DRs (1.48–2.66, median 1.71) were significantly larger than the TV-DRs (p

Abstract Purpose For the differential diagnosis of medullary thyroid carcinoma (MTC) on thyroid nodules, ultrasound-guided fine-needle aspiration cytology is a useful and safe procedure, but its diagnostic accuracy is not high enough. As an ancillary method to accurately diagnose MTC, the calcitonin in fine-needle aspirate washout fluid (FNA-Ct) is used. However, no data are available about cut-off values of FNA-Ct using the currently available electrochemiluminescence immunoassay (ECLIA). Methods We investigated 180 thyroid nodules in 141 patients. After smearing, the syringe and needle used for the FNA were rinsed with normal saline (0.5 mL). The calcitonin in the washout was measured by ECLIA. Results The FNA-Ct in the non-MTC nodules of MTC patients, non-MTC nodules of non-MTC patients, and MTC nodules were 10.6–2100 pg/mL (median 24.6 pg/mL),

Purpose The purpose of the study is to clarify the prevalence of calcifications within thyroid tumors on ultrasonography as well as the relationship between the calcification and histopathological types. Materials and Methods Calcifications were classified into 6 (or 8) types according to their shape, size, and region. The prevalence of calcifications and types were investigated in new outpatients and patients who underwent thyroid surgery. Results Among 2,902 nodules in 2,678 new outpatients, 747 nodules (26%) had calcifications. The types showed a wide distribution. Among 941 patients with papillary carcinoma (PC), 725 patients (77%) had calcifications, and the types showed a wide distribution. 18 patients with the diffuse sclerosing variant of PC only showed punctate microcalcifications in the parenchyma (100%), 32 patients with the cyst-forming type of PC mostly fragmentary and massive types (100%), and 161 metastatic lymph nodes from PC mostly punctate microcalcifications and fragmentary types (48%). Among 337 patients with follicular carcinoma, 79 patients (23%) had calcifications, and the types were mostly fragmentary, massive, and egg-shell types. Among 41 patients with undifferentiated carcinoma, 33 patients (80%) presented with calcifications, which were mostly the massive and egg-shell types. Among 137 patients with medullary carcinoma, 99 patients (72%) had calcification, and the types showed a wide distribution. None of 173 patients with primary thyroid lymphoma had calcifications (0%). Conclusion Calcifications on ultrasonography can be one of the characteristic findings and a full understanding of the prevalence of calcifications and types will markedly contribute to the ultrasonic diagnosis of thyroid tumors.

Background. Children and adolescents with papillary thyroid carcinomas (PTCs) have generally excellent prognoses despite their frequent extended disease. The tumor growth of young patients’ PTCs might show spontaneous slowing postoperatively. We compared young PTC patients’ postoperative thyroglobulin-doubling time (Tg-DT) with their preoperative hypothetical tumor volume-doubling time (hTV-DT). Methods. Fourteen PTC patients aged ≤18 years who underwent total thyroidectomy at Kuma Hospital in 1998–2016 had biochemically persistent disease postoperatively. We calculated their Tg-DTs and estimated their preoperative TV-DTs with the tumor size and the patient’s age at surgery, presuming that a single cancer cell was present at the patient’s birth. Results. Twelve patients had positive Tg-DTs ranging from 2.0 to 147 years, and the remaining two had negative Tg-DTs, indicating slow growth or even regression. The hTV-DTs were 0.3–0.6 years (median 0.5 years), which were significantly shorter than the Tg-DTs (p

Since papillary thyroid carcinoma (PTC) with tracheal invasion shows a worse prognosis, aggressive surgical treatment including airway resection has been recommended. However, little is known about local recurrence of PTC with minimal tracheal invasion after shaving or laminated resection of the tracheal cartilage. In this study, we investigated the local prognosis of patients who were intra-operatively diagnosed as having minimal tracheal invasion. Methods: Of 6,015 patients who underwent initial surgery for PTC between 1987 and 2004, 127 (2.1%) were intra-operatively suspected of having minimal invasion to the trachea and underwent shaving or laminated resection of the tracheal cartilage. These 127 patients were enrolled in this study. Results: Of 127 patients, 107 were intra-operatively regarded as having received macroscopically curative treatment (curative group), whereas minimal carcinoma remnants were suspected in the remaining 20 patients (suspicious group). To date, six patients (4.6%) (one patient in the curative group and five in the suspicious group) showed local recurrence at the tracheal edge. The local disease-free survival of patients in the curative group was better than that of those in the suspicious group (p = 0.0007), although the cause-specific survival of patients in the two groups did not differ. Cut surfaces of resected carcinoma were also pathologically examined for 119 patients and 58 (48.7%) were diagnosed as carcinoma-positive, but the cut surface status was not related to macroscopic curative treatment. Of six patients showing local recurrence, only one died of lung metastasis of carcinoma. Conclusion: The incidence of local recurrence of PTC with minimal tracheal invasion is low at 4.6%. Although this event might not be immediately life-threatening for patients, to improve local prognosis, local curative treatment should be pursued. In cases that are suspected of persistent carcinoma remnants, further shaving or laminated dissection should be performed, and if the carcinoma remnant cannot be eliminated, tracheal fenestration should be considered, although such high-risk tumours may be likely to recur regardless of surgical radicality.

Anaplastic thyroid carcinoma arises from differentiated carcinoma and has a very aggressive character. In this study, we investigated the prognosis of patients with anaplastic carcinoma based on UICC stage. Patients and Methods: We investigated the prognosis of 75 patients who were diagnosed as having anaplastic carcinoma at Kuma Hospital between 1983 and 2006. Of these patients, 14, 49 and 12 were classified into Stages IVA, IVB, and IVC respectively. Results: Stage IVA patients showed a significantly better prognosis than Stage IVB or IVC patients (p = 0.0017). All patients with Stage IVC died of carcinoma within 1 year regardless of whether locally complete resection was performed. Prognosis of Stage IVB patients who underwent curative surgery did not differ from that of Stage IVA patients, but the prognosis of those who did not undergo surgery or only received palliative surgery was as poor as that of Stage IVC patients. Conclusions: Extensive surgical treatment is recommended for Stage IVA patients and palliative care is appropriate for Stage IVC patients. For Stage IVB patients, surgical treatment as a primary therapy is appropriate only when curative resection of the tumour is expected.

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.

Background/Aim: To date, thyroglobulin-doubling rate (Tg-DR) and tumor volume-doubling rate (TVDR) of metastatic lesions have been identified as dynamic prognostic factors for differentiated thyroid carcinoma (DTC). In this study, we investigated the prognostic impact for another dynamic factor, the neutrophil-to-lymphocyte ratio (NLR), for DTC with distant metastasis. Patients and Methods: We enrolled 321 patients in total, and NLR at the first detection of distant metastasis (initial NLR) was collected for 312. Results: Patients with initial NLR >3 had a significantly poorer cause-specific survival than those with initial NLR ≤3. On multivariate analysis, initial NLR >3 was recognized as an independent prognostic factor together with Tg-DR >1/year, TV-DR >1/year, radioactive iodine-refractory distant metastasis, and distant metastasis to organs other than the lung. Conclusion: Careful observation and active therapies, including multitarget kinase inhibitors, are recommended for patients with NLR >3 at the first detection of distant metastasis or during follow-up. [ABSTRACT FROM AUTHOR]

Background/Aim: Radioactive iodine-refractory differentiated thyroid carcinoma (RR-DTC) has been treated with multi-kinase inhibitors (MKIs), e.g., sorafenib (SOR) and lenvatinib (LEN). We analyzed the outcomes of RR-DTC patients who underwent SOR or LEN treatment at Kuma Hospital. Patients and Methods: We enrolled 21 and 18 patients treated with SOR and LEN, respectively. Results: The incidence of partial response in the LEN group was significantly higher than that in the SOR group. Serum thyroglobulin significantly decreased from the beginning of treatment to 1 month later in the LEN group (not in the SOR group). The neutrophil-lymphocyte ratio (NLR) was significantly decreased at 1 month later in both groups. An NLR ≥3 at the start of MKI treatment had a prognostic impact. Conclusion: For RR-DTC, LEN could be more effective than SOR, at least in the short term. The first-line drug should be selected based on other factors (e.g., adverse events, patient background). [ABSTRACT FROM AUTHOR]

Objective: We and others recently reported that in total thyroidectomy (TT), serum triiodothyronine (T3) levels during levothyroxine (L-T4) therapy were low compared to the preoperative levels, suggesting that the presence of the thyroid tissue affects the balances of serum thyroid hormone levels. However, the effects of remnant thyroid tissue on these balances in thyroidectomized patients have not been established. Methods: We retrospectively studied 253 euthyroid patients with papillary thyroid carcinoma who underwent a TT or hemithyroidectomy (HT). We divided the cases into the TT + supplemental L-T4 (+ L-T4) group (n = 103); the HT + L-T4 group (n = 56); and the HT-alone group (n = 94). We compared the postoperative serum levels of free T4 (FT4) and free T3 (FT3) and the FT3/FT4 ratio in individual patients with those of controls matched by serum TSH levels. Results: The TT+L-T4 group had significantly higher FT4 (P<0.001), lower FT3 (P<0.01) and lower FT3/FT4 (P<0.001) levels compared to the controls. The HT+L-T4 group had FT4, FT3 and FT3/FT4 levels equivalent to those of the controls. The HT-alone group had significantly lower FT4(P<0.01), equivalent FT3 (P=0.083), and significantly higher FT3/FT4 (P<0.001) ratios than the controls. Conclusions: The presence of the remnant thyroid tissue was associated with different thyroid hormone balances in thyroidectomized patients, suggesting that T3 production by remnant thyroid tissue has a substantial effect on the maintenance of postoperative serum T3 levels. [ABSTRACT FROM AUTHOR]

Background: Patients with metastases to the thyroid from renal cell carcinoma (RCC) that need surgical management are not many and unfamiliar to clinicians and thyroid endocrinologists. Therefore, little information is available on ultrasonographic features of metastatic carcinoma in the thyroid. The strategic value of ultrasound in preoperative surgical planning for patients with thyroid nodules has become increasingly appreciated. The purposes of this article are to clarify the ultrasound characteristics of metastatic carcinoma to the thyroid from RCC by evaluating many patients in one institute, and to investigate the role of ultrasonography in preoperative diagnosis. Methods: Ten patients with these carcinomas who had undergone surgical management were investigated clinically and ultrasonographically. Ultrasonographic features to be evaluated were the form of involvement in the thyroid, size, shape, pattern, calcifications, vascularity, and tumor thrombus. Clinical features were previous history of RCC, serum thyroglobulin levels, cytology, preoperative diagnosis, and surgery. Results: Ultrasonographic features of these carcinomas were more likely to involve a solitary, irregular, and solid without calcifications, and prominent intra-tumoral vascularity and tumor thrombus in the vein. These patients tended to be older, and to have relatively late recurrence in the thyroid, RCC in the right kidney as the primary site, and relatively low serum thyroglobulin levels. Conclusions: Metastatic carcinomas to the thyroid from RCC presented highly characteristic features on ultrasonography. These ultrasonographic features combined with cytological findings and previous medical history of RCC can provide the optimal process for the preoperative diagnosis of such patients. [ABSTRACT FROM AUTHOR]

Purpose. Anaplastic thyroid carcinoma (ATC) is a relatively rare but very aggressive malignancy, which usually results in death a few months after diagnosis. However, some patients survive for a long time, and the purpose of this study was to identify the prognostic factors of ATC. Methods. We retrospectively analyzed the records of 19 patients diagnosed with ATC in our institution between 1984 and 2002. Results. The median survival was 9.4 months, with a range of 0.6–76.3 months, and the 1-, 2-, and 5-year survival rates were 21%, 11%, and 5%, respectively. The mean tumor size was 5.7?cm, with a range of 3.6–10.5?cm, and complete resection was achieved in 4 patients. The prognostic factors according to univariate analysis were complete resection and small tumor size of less than 5?cm ( P = 0.005 and 0.047). However, according to multivariate analysis, complete resection was the only prognostic factor for ATC ( P = 0.015). No association was found between survival and acute symptoms, chemotherapy, radiation therapy, extrathyroidal invasion, distant metastasis, age, or leukocytosis. Conclusion. At present, while there is no successful treatment regimen for ATC, only patients who undergo complete resection at a very early stage have any chance of long-term survival. [ABSTRACT FROM AUTHOR]

Aim: It is difficult to differentiate follicular carcinomas (FC) from follicular adenomas (FA) because ultrasonography and cytology provide very similar findings. FC is histopathologically diagnosed to have capsular and/or vascular invasion. In a few patients, tumor protrusions are observed by preoperative ultrasonography as large forms of capsular invasion of follicular carcinomas. The aim of the study was to clarify the predictive value of tumor protrusions on preoperative ultrasonography for follicular carcinomas. Material and Methods: A total of 531 patients (FC: 184 patients, FA: 347 patients) undergoing thyroid surgery were included in this study. A tumor protrusion on ultrasonography was defined as follows: 1) a solid tumor extending beyond a marginal line of capsular zone of the main tumor on B-mode ultrasonography; 2) intensive blood signals observed within the protrusion area on Doppler ultrasonography. The large form of capsular invasion was defined if the protrusion lesion was histopathologically diagnosed to be a capsular invasion of follicular carcinoma. Results: The sensitivity of tumor protrusion was 0.071, specificity 0.994, positive predictive value 0.867, and negative predictive value 0.669 for FC diagnosis. For the large form of capsular invasion in FC the sensitivity of tumor protrusion was 0.813, specificity 0.982, positive predictive value 0.684, and negative predictive value 0.982. Conclusions: A tumor protrusion with intensive blood signals extending from the main tumor on ultrasonography strongly suggests a large form of capsular invasion of follicular carcinoma. [ABSTRACT FROM AUTHOR]