CD44v8-10 and CD44s Are Age-dependently Expressed in Primary Cultured Papillary Thyroid Carcinoma Cells and Are Associated with Cell Proliferation.

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy, arising from follicular cells, and accounts for more than 80% of all thyroid malignant tumors. Although age is the strongest prognostic factor of PTC, and various cut-off ages (40-55 years) were suggested in previous studies, the molecular mechanisms causing age-related changes of PTC cell proliferation remain unclear. CD44 is a major cell surface receptor for hyaluronate and is known as a cancer stem cell marker. However, the association between CD44 and PTC is still unknown. Therefore, we determined the proliferation of primary cultured cells obtained from patients with PTC, and the CD44 mRNA expression profile to elucidate age-related association of CD44 with PTC. The results showed that cell proliferation was significantly decreased according to age. We also found that CD44v8-10 and CD44 splice variants were expressed dominantly in patients with PTC. Moreover, the CD44v8-10/CD44s mRNA expression ratio was significantly increased according to age, and there was a significant negative correlation between this expression ratio and cell proliferation. Our findings suggest that the CD44v8-10/CD44s expression ratio in PTC cells is useful for screening for aggressive PTC and may provide clinically valuable information.

Prognostic Impact of the Turin Criteria in Poorly Differentiated Thyroid Carcinoma.

BACKGROUND: The Turin criteria including solid, trabecular, and/or insular architecture, lack of typical nuclear features of papillary carcinoma, and mitoses, necrosis, or convoluted nuclei were adopted in the recent 4th edition of the World Health Organization classification published in 2017. MATERIALS AND METHODS: Between 2006 and 2017, 11,001 cases underwent initial surgery for primary malignant thyroid tumor derived from follicular cells. A total of 75 (0.7%) cases were diagnosed with PDTC according to the 2004 WHO classification. Based on the Turin criteria, 30 (40%) cases were re-classified as PDTC-Turin (+) and 45 (60%) cases were PDTC-Turin (-). Clinicopathological features and prognosis were compared between PDTC-Turin (+) and PDTC-Turin (-). RESULTS: Seventy-five patients (48 females and 27 males) had a median age at the time of surgery of 57 years. Preoperative diagnosis was benign in 16 (21%), follicular tumor in 40 (53%), and malignant in 19 (25%). The 5-year cause-specific survival (CSS) and disease-free survival (DFS) rates were 97% and 44% for PDTC-Turin (+) and 100% and 88% for PDTC-Turin (-). On univariate analysis, CSS and DFS rates were significantly worse in the PDTC-Turin (+) than in the PDTC-Turin (-) (p = 0.0096, and p = 0.0016). Multivariate analysis showed that Turin criteria status, Ki-67 labeling index ≥ 10%, and age 55 ≥ years were the independent prognostic factors for recurrence. CONCLUSIONS: The prevalence of PDTC diagnosed with the Turin criteria was low, but it showed more aggressive behavior. The 2017 WHO classification reflects the prognosis more accurately than the 2004 WHO classification.

Usefulness of Stereotactic Radiotherapy Using the CyberKnife for Patients with Inoperable Locoregional Recurrences of Differentiated Thyroid Cancer.

BACKGROUND: Surgical resection is the preferred treatment for locoregional recurrence of differentiated thyroid cancer (DTC). However, some recurrences are unresectable because of their aggressive invasion or severe adhesions. On the other hand, stereotactic radiotherapy (SRT) enables high-dose irradiation to target lesions, and its usefulness for various cancers has been reported. The objective of the present study was to investigate the feasibility and efficacy of SRT as salvage treatment for locoregional recurrence of DTC. METHODS: Between August 2011 and December 2017, 52 locoregional recurrent lesions in 31 patients with recurrent DTC were treated by SRT using the CyberKnife system. Information on the adverse events associated with SRT was retrospectively collected from the patients' medical records. Of the 52 lesions, 33 could be evaluated for therapeutic effectiveness by follow-up CT, and response was assessed using the RECIST criteria. RESULTS: Twenty-five patients had papillary carcinoma, 5 had follicular carcinoma, and 1 had poorly differentiated cancer. SRT was delivered in one to 20 fractions, and the median dose was 30 Gy (range 15-60 Gy). Adverse events were not frequent, but 1 patient developed bilateral vocal cord palsy that required emergent tracheostomy. The median follow-up period of 33 lesions was 14 months (range 1-54 months). Complete response, partial response, stable disease, and progressive disease were seen in 10, 11, 9, and 3 patients, respectively. The 3-year local control rate was 84.6%. CONCLUSION: SRT using the CyberKnife system was found to be a feasible and effective treatment to suppress the growth of locoregional recurrence of DTC.

Change of surgical strategy for Graves' disease from subtotal thyroidectomy to total thyroidectomy: a single institutional experience.

The extent of thyroidectomy in Graves' disease remains controversial. In our institution, long-term euthyroidism without thyroxin replacement therapy has been the aim, and it has long been the standard surgical procedure used to treat Graves' disease in many institutions, including our hospital. Based our several clinical studies, it was concluded that subtotal thyroidectomy is not suitable as a standard surgical procedure for the treatment of Graves' disease. In 2009, the surgical strategy for Graves' disease was changed from subtotal thyroidectomy to total thyroidectomy in our hospital. In this study, how surgical complications have changed after this modification was examined. The subjects were 1,476 patients with Graves' disease treated by thyroidectomy between 2006 and 2014. There were 1,119 females and 357 males with a median age of 39 years. A total of 660 patients underwent bilateral subtotal thyroidectomy (ST group), and 816 patients underwent total thyroidectomy (TT group). Both transient hypocalcemia and prolonged hypocalcemia were observed significantly more frequently in the TT group than in the ST group (p < 0.001). Total thyroidectomy was identified as risk factors for prolonged hypocalcemia on multivariate analysis. In conclusion, total thyroidectomy is a reliable and effective therapy for controlling hyperthyroidism in terms of controlling of hyperthyroidism. However, it should be noted that total thyroidectomy resulted in increased rate of prolonged hypocalcemia. Surgeons should try to reduce the surgical complication rate as much as possible.

Calcifications in Thyroid Tumors on Ultrasonography: Calcification Types and Relationship with Histopathological Type.

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.

Cribriform-Morular Variant of Papillary Thyroid Carcinoma: Clinical and Pathological Features of 30 Cases.

BACKGROUND: Cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) is rare; it may occur in cases of familial adenomatous polyposis (FAP) or be sporadic. To clarify the clinicopathological features of CMV-PTC, the medical records of these patients were investigated retrospectively. MATERIALS AND METHODS: Between 1979 and 2016, a total of 17,062 cases with PTC underwent initial surgery at Ito Hospital. Of these, 30 (0.2%) cases histologically diagnosed with CMV-PTC were reviewed. RESULT: The patients were all women, with a mean age at the time of surgery of 24 years. Seven (23%) cases were thought to have FAP because they had colonic polyposis or a family history of FAP or APC gene mutation. The remaining 23 (77%) were thought to be sporadic. Multiple tumors were detected in 6 cases, with a solitary tumor in 24. One patient had lung metastasis at diagnosis. Eleven patients underwent total thyroidectomy or subtotal thyroidectomy, and 19 underwent lobectomy. Twenty-six (87%) patients underwent neck lymph node dissection. Three patients had tumor metastasis in central lymph nodes, but these were incidentally detected metastatic classical PTC (cPTC) based on histological examination. In this series, there were no cases of LN metastases of CMV-PTC. During a mean follow-up of 15 years, one patient had new cPTC in the remnant thyroid after initial surgery, and the other patients showed no signs of recurrence. CONCLUSION: CMV-PTC occurred in young women, their long-term prognosis was excellent. Total thyroidectomy is recommended for FAP-associated CMV-PTC, but modified neck lymph node dissection is not necessary.

"Nodule in Nodule" on Thyroid Ultrasonography: Possibility of Follicular Carcinoma Transformed from Benign Thyroid Tumor.

BACKGROUND: It is generally considered impossible to differentiate follicular carcinomas from follicular adenomas by means of ultrasonography or cytology before surgery. Therefore, follicular carcinoma is histopathologically diagnosed by verifying capsular and/or vascular invasion after surgery. However, ultrasonography may play an important role in diagnosing follicular carcinoma preoperatively in a small number of cases. CASE DESCRIPTION: Four cases of follicular carcinoma or follicular neoplasm that transformed from a benign thyroid tumor and demonstrated a "nodule in nodule" appearance on ultrasonography are presented in this report. Characteristic ultrasound features of such patients are: (1) a "nodule in nodule" appearance, (2) a well-defined boundary line between the nodules, and (3) separate distribution of blood signals within each nodule. CONCLUSION: A small number of patients with follicular carcinomas or follicular neoplasms may present with a "nodule in nodule" appearance on ultrasonography. It was suggested a long time ago that follicular carcinomas may develop from benign thyroid tumors. The fact that follicular carcinomas appear within benign tumors may be evidence of thyroid tumorigenesis.

TERT promoter mutations and Ki-67 labeling index as a prognostic marker of papillary thyroid carcinomas: combination of two independent factors.

Although most papillary thyroid carcinomas (PTCs) have a good prognosis, a small but certain fraction shows aggressive behavior. Therefore, a novel and well-performing molecular marker is needed. In the present study, we assessed the impact of the combination of the TERT promoter/BRAF mutations and Ki-67 labeling index (LI) as a prognostic marker in PTC patients. Of 400 PTC samples, 354 were successfully genotyped for both TERT promoter/BRAF and analyzed for Ki-67 LI. Based on the combination of the mutational status and Ki-67 LI, the cases were categorized into three groups: high-, middle-, and low-risk. The recurrence rates of low-, middle-, and high-risk group were 1.9% (6 of 323), 18.2% (4 of 22), and 44.4% (4 of 9), respectively. The Kaplan-Meier curve and log-rank analyses demonstrated that there were statistical differences between any two groups. The hazard ratios for recurrence remained significant after adjustment for age, sex, tumor size, and extrathyroidal extension (low vs. middle: 8.80, 95% CI: 2.35-32.92, p = 0.001; middle vs. high: 6.255, 95% CI: 1.13-34.51, p = 0.035). In conclusion, the combination of the TERT promoter/BRAFV600E mutations and Ki-67 LI performed excellent in predicting PTC recurrence and may be clinically useful.

Frequent BRAF V600E and Absence of TERT Promoter Mutations Characterize Sporadic Pediatric Papillary Thyroid Carcinomas in Japan.

Pediatric papillary thyroid carcinoma (PTC) has unique features but requires further genetic investigation. Moreover, there has been increasing concern about the risk for pediatric PTC in Japan after the Fukushima accident. This study aims to evaluate the frequencies of BRAF and TERT promoter mutations and to examine their significance in non-radiation-associated pediatric PTCs in Japan. We enrolled 81 pediatric PTC patients aged ≤20 years. The control group included 91 adult PTCs from patients >20 years old. BRAF and TERT mutations were analyzed by allele-specific-PCR and/or Sanger sequencing. Compared with adult PTCs, pediatric PTCs exhibited larger tumor size, more frequent lymph node metastasis, and less classical histology. The prevalence of BRAF V600E in pediatric PTCs was 54% and significantly lower than that in adults of 85%. In the pediatric PTCs, BRAF V600E was positively associated with older age, classical histology, and the lymph node metastasis but independent from other clinicopathological factors. TERT mutations were identified in 13% of adults and in none of the pediatric PTCs. In conclusion, pediatric PTCs are characterized by more advanced clinicopathological features, lower BRAF V600E frequency, and absence of TERT mutation. The BRAF V600E frequency in this study is similar to the reported BRAF V600E frequency in the ultrasonographically screened pediatric PTCs in Fukushima.

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.

A Novel Germline Mutation of KEAP1 (R483H) Associated with a Non-Toxic Multinodular Goiter.

BACKGROUND: A germline mutation of KEAP1 gene was reported as a novel genetic abnormality associated with familial multinodular goiter. That report was limited, and the pathogenic features were not well established. PATIENT FINDINGS: We report a 47-year-old Japanese woman who presented with hyperthyroidism and a large multinodular goiter. The family history was notable for a paternal history of goiter. Graves' disease was diagnosed based on positive TRAb, but scintiscan imaging showed that the patient's radioiodine uptake was restricted in the non-nodular areas, indicating largely cold nodules. A total thyroidectomy was performed. The resected thyroid tissue weighed 209 g, and subsequent pathological findings were benign. The patient had a germline heterozygous KEAP1 mutation, c. 1448 G > A, resulting in an amino acid substitution (p.R483H). A next-generation sequencing analysis covering all known genes associated with multinodular goiter showed no additional germline mutation. The nuclear accumulation of NRF2, a protein associated with KEAP1, was shown at much higher rates in the patient's nodules compared with nodules obtained from four unrelated patients with multinodular goiters. CONCLUSION: A novel germline mutation (R483H) of KEAP1 gene was associated with the development of a non-toxic multinodular goiter.

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.

Right-sided aortic arch and aberrant left subclavian artery with or without a left nonrecurrent inferior laryngeal nerve.

BACKGROUND: In thyroid surgery, preserving the recurrent laryngeal nerve (RLN) is crucial for preventing postoperative phonatory dysfunction. Right nonrecurrent laryngeal nerves (NRLNs) are not particularly rare, and they are vulnerable to injury during surgery. This anomaly is associated with a right aberrant subclavian artery. Thus, a right-sided aortic arch with an aberrant left subclavian artery (LSA) suggests a possible left NRLN. METHODS: We report the cases of 4 patients with right-sided aortic arch and aberrant LSA. Preoperative imaging studies revealed those anomalies, but no signs of situs inversus. During the surgeries, only 1 of the 4 cases had a left NRLN. We retrospectively evaluated the patients' imaging studies. RESULTS: An aortic diverticulum was found at the point at which the aberrant LSA originated in the 3 patients with left-RLNs, but not in the patient with the left-NRLN. CONCLUSION: In right-sided aortic arch + aberrant LSA cases, the absence of an aortic diverticulum suggests a left NRLN. © 2016 Wiley Periodicals, Inc. Head Neck 38: First-E2511, 2016.

Tumor protrusion with intensive blood signals on ultrasonography is a strongly suggestive finding of follicular thyroid carcinoma.

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.

Germline RET mutation carriers in Japanese patients with apparently sporadic medullary thyroid carcinoma: A single institution experience.

OBJECTIVE: Genetic testing for RET germline mutation can be useful to distinguish whether a patient with medullary thyroid carcinoma (MTC) is genuinely sporadic or hereditary. Conducting a routine preoperative germline RET genetic screening for all patients with MTC has the clinical benefit, i.e., avoidance of unnecessary total thyroidectomy in the selected patients. We sought to clarify the incidence of germline RET mutation carriers in Japanese patients with apparently sporadic MTC and to address the differences in clinicopathological characteristics between true sporadic MTC and hereditary MTC in these patients, all of whom were treated at Kuma Hospital. METHODS: A total of 134 patients with apparently sporadic MTC who underwent surgery between 1996 and 2014 were enrolled. All patients underwent a germline RET gene mutation analysis preoperatively. RESULTS: Germline mutations in RET proto-oncogene were identified in 20 of the 134 (14.9%) apparently sporadic MTC patients. No significant difference in clinicopathological characteristics was observed between the patients with sporadic MTC (n=114) and those with hereditary MTC (n=20) except for the RET gene carriers' younger age at diagnosis and presence of multifocal and bilateral lesions. CONCLUSION: Germline RET mutations were identified in 14.9% of Japanese patients with apparently sporadic MTC. No clearly decisive clinicopathological characteristics was observed to distinguish whether an apparently sporadic MTC case was genuinely sporadic or unconsciously hereditary. For the treatment strategy decision, it is advantageous to conduct a routine preoperative germline RET genetic screening for all patients with MTC, even if their MTC is apparently sporadic.

Incidences of Unfavorable Events in the Management of Low-Risk Papillary Microcarcinoma of the Thyroid by Active Surveillance Versus Immediate Surgery.

BACKGROUND: The incidence of papillary microcarcinoma (PMC) of the thyroid is rapidly increasing globally, making the management of PMC an important clinical issue. Excellent oncological outcomes of active surveillance for low-risk PMC have been reported previously. Here, unfavorable events following active surveillance and surgical treatment for PMC were studied. METHODS: From February 2005 to August 2013, 2153 patients were diagnosed with low-risk PMC. Of these, 1179 patients chose active surveillance and 974 patients chose immediate surgery. The oncological outcomes and the incidences of unfavorable events of these groups were analyzed. RESULTS: In the active surveillance group, 94 patients underwent surgery for various reasons; tumor enlargement and the appearance of novel lymph node metastases were the reasons in 27 (2.3%) and six patients (0.5%), respectively. One of the patients with conversion to surgery had nodal recurrence, and five patients in the immediate surgery group had a recurrence in a cervical node or unresected thyroid lobe. All of these recurrences were successfully treated. None of the patients had distant metastases, and none died of the disease. The immediate surgery group had significantly higher incidences of transient vocal cord paralysis (VCP), transient hypoparathyroidism, and permanent hypoparathyroidism than the active-surveillance group did (4.1% vs. 0.6%, p < 0.0001; 16.7% vs. 2.8%, p < 0.0001; and 1.6% vs. 0.08%, p < 0.0001, respectively). Permanent VCP occurred only in two patients (0.2%) in the immediate surgery group. The proportion of patients on L-thyroxine for supplemental or thyrotropin (TSH)-suppressive purposes was significantly larger in the immediate surgery group than in the active surveillance group (66.1% vs. 20.7%, p < 0.0001). The immediate surgery group had significantly higher incidences of postsurgical hematoma and surgical scar in the neck compared with the active surveillance group (0.5% vs. 0%, p < 0.05; and 8.0% vs. 100%, p < 0.0001, respectively). CONCLUSIONS: The oncological outcomes of the immediate surgery and active surveillance groups were similarly excellent, but the incidences of unfavorable events were definitely higher in the immediate surgery group. Thus, active surveillance is now recommended as the best choice for patients with low-risk PMC.

Effects of Pregnancy on Papillary Microcarcinomas of the Thyroid Re-Evaluated in the Entire Patient Series at Kuma Hospital.

BACKGROUND: An active-surveillance clinical trial of low-risk papillary microcarcinoma (PMC) patients has been performed at the authors' institution, Kuma Hospital, since 1993. Favorable oncological results have been reported. During the trial, a few patients were encountered with PMC that showed enlargement during pregnancy, and these cases have been reported. During pregnancy, a large amount of human chorionic gonadotropin (hCG) having weak thyrotropin (TSH) activity is produced, possibly affecting the progression of PMC. This study investigated how pregnancy and delivery influenced the progression of PMC in the entire active surveillance PMC patient series. METHODS: From 1993 to 2013, 1841 patients with low-risk PMC chose the active surveillance program. Fifty of the 1549 female PMC patients experienced 51 pregnancies/deliveries. To minimize observer variation, a single specialist sonographer re-evaluated the changes in the size of these 50 patients' PMCs before and after the pregnancies/deliveries. RESULTS: Four patients (8%) showed enlargement of PMC by ≥3 mm; one patient (2%) showed a decrease by ≥3 mm, and the remaining 44 patients (45 events, 90%) showed stable disease. None of the patients had a novel appearance of lymph node metastases during pregnancy. Of the four patients with enlargement, two underwent surgery after delivery, and the other two continued the active surveillance, since their tumors did not grow after the delivery. After delivery, the PMC of one of these four patients remained stable, and another showed a decrease in PMC size. To date, six more PMC patients underwent surgery after delivery for reasons other than disease progression due to pregnancy and delivery: two opted out of active surveillance, two were identified with a nodal metastasis during active surveillance after delivery, one had Graves' disease, and one showed enlargement of nodules of the contralateral lobe. CONCLUSIONS: Pregnancy and delivery was associated with an increase in size of PMCs in only 8% of the 51 pregnancies/delivery cases. None of the patients developed nodal metastasis during pregnancy. Thus, a possible future pregnancy does not prevent such patients from undergoing active surveillance, although watchful observation during pregnancy is recommended.

Innervation of the cricothyroid muscle by the recurrent laryngeal nerve.

BACKGROUND: The recurrent laryngeal nerve (RLN) and the external branch of the superior laryngeal nerve (SLN) are generally thought to innervate the endolaryngeal muscles and the cricothyroid muscle (CTM), respectively. Meticulous anatomic studies found communication between these nerves (ie, the human communicating nerve). In this study, we report the innervation of the CTM by the RLN. METHODS: We performed electromyographic studies of 50 patients during thyroidectomy (20 total and 30 hemithyroidectomies). During surgery, the external branch of the SLN, RLN, and vagus nerve were stimulated. Responses were evaluated by visual observation of the CTM and by electromyographies through needle electrodes inserted into the CTM. RESULTS: Seventy CTMs were evaluated. The RLN stimulation yielded both visible contractions and clear electromyographic responses (>300 µV) in 27 (39%), either response in 24 (34%), and neither response in 19 (27%) of the CTMs. The vagus stimulation gave similar results. CONCLUSION: The RLN innervated the CTM at least in 39% cases. © 2015 Wiley Periodicals, Inc. Head Neck 38: E441-E445, 2016.