Papillary thyroid cancer in black thyroid: a case report and literature review.

Background: Black thyroid is a rare incidental finding during surgery. We report the case of a patient with papillary thyroid cancer who was incidentally found to have minocycline-induced black thyroid. Case Description: A 29-year-old woman presented with a left thyroid nodule and metastatic papillary thyroid cancer involving the left neck level IV lymph nodes. She had a medical history of anxiety disorder with depression, severe acne, and rosacea, and had been taking benzodiazepines, selective serotonin reuptake inhibitors, isotretinoin, and minocycline for a few years. The patient underwent a total thyroidectomy with left central compartment neck dissection and ipsilateral modified radical neck dissection. A black thyroid gland was identified during thyroidectomy. During level IV dissection, we noticed a similar black discoloration in the adipose tissue of the lower neck. Pathological examination revealed brown pigmentation with few macrophages on several foci of the thyroid parenchyma. Brown pigmentation was not identified in the thyroid tumor, metastatic and normal lymph nodes, or background adipose tissue. Conclusions: We report a case of papillary thyroid microcarcinoma with cervical lymph node metastases in a black thyroid. The clinical findings were consistent with those of previous reports. Based on the literature, it remains unclear if this minocycline triggered finding is associated with an increased frequency and/or aggressiveness of thyroid carcinomas. In the absence of adequate evidence, prolonged minocycline users should ideally undergo routine thyroid assessment to identify possible malignancy.

Frozen section analysis of central lymph nodes in papillary thyroid cancer: the significance in determining the extent of surgery.

Background: The indolent feature of papillary thyroid cancer (PTC) has recently led to an increase in less aggressive treatment options instead of total thyroidectomy (TT). We aimed to investigate the clinical significance of elective central compartment neck dissection (CCND) with intraoperative frozen analyses of the central lymph nodes (LNs) to determine the surgical extent of unilateral clinically node-negative PTC. Methods: We retrospectively reviewed the medical records of 290 patients with unilateral clinically node-negative PTC who underwent surgery and performed frozen analyses of the central LNs from 2020 to 2021 using our own nodal criteria with cut-off size 5 mm. The patients were divided and investigated according to the surgical extent and the National Comprehensive Cancer Network (NCCN) guidelines; diagnostic accuracy of the frozen analyses was estimated. Results: TT was performed in 16.2% of patients. The TT group had more metastatic nodes with a larger size, higher LN ratio (LNR), and more extranodal extension. The analyses based on the NCCN guidelines showed similar findings, but more completion TT was required compared with our criteria. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the frozen analyses were 94.6%, 100%, 100%, and 96.1%, respectively. Conclusions: Elective CCND with intraoperative frozen analyses is a highly reliable procedure that detects occult nodal metastasis in unilateral node-negative PTC patients. Our nodal criteria yielded significant aggressive nodal characteristics in the TT group while yielding less TTs compared with the NCCN guidelines. The concept and clinical significance of small-volume nodal metastasis in PTC should be further investigated.

Survival With Lenvatinib for the Treatment of Progressive Anaplastic Thyroid Cancer: A Single-Center, Retrospective Analysis.

Background: Survival rates for anaplastic thyroid cancer (ATC) have not improved in the past four decades; however, preliminary clinical data indicate that lenvatinib may provide efficacy benefits for patients with ATC. This real-world study aimed to define the potential role of lenvatinib in ATC by examining the impact of treatment administered alongside existing therapies. Methods: This was a retrospective, single-center analysis of Korean patients with confirmed ATC who received lenvatinib between October 2015 and February 2018. Eighteen patients were included (mean ± standard deviation age, 64.9 ± 11.1 years; 61.1% female). Six [33.3%] had resectable disease that progressed after a combination of surgery, radiotherapy, and chemotherapy, and 12 [66.7%] had unresectable disease that progressed after radiation treatment and chemotherapy. Study endpoints were overall survival (OS) and change in volume of the largest tumor assessed via imaging. Results: Median OS for the 18 lenvatinib-treated patients was 230 days (range 64-839 days). Survival rates at 6 months and 1 year were 61.1 and 22.2%, respectively. Three patients (16.7%) survived beyond 1 year; 15 patients died, of whom four (26.7%) had local disease and 11 (73.3%) had distant metastasis. Two patients (11.1%) had tumor volume increases of 9-10%. The other 16 patients (88.9%) had tumor volume reductions of 2-69%. Six patients (33.3%) had tumor volume reductions ≥50%. Conclusions: In patients with ATC who had progressed on prior therapy, addition of lenvatinib could improve survival duration and reduce tumor volume. Further studies of lenvatinib in ATC are warranted.

Transoral endoscopic thyroidectomy using the vestibular approach with an endoscopic retractor in thyroid cancer: experience with the first 132 patients.

BACKGROUND: Transoral endoscopic thyroidectomy using the vestibular approach (TOETVA) is a novel technique for thyroid cancer surgery. We aimed to review our initial experiences with TOETVA for the management of thyroid carcinoma, using retrospective analyses of a larger single-center case series. METHODS: From September 2016 to April 2018, 132 patients with thyroid cancer underwent TOETVA. A three-port technique through the oral vestibule was used to perform endoscopic thyroidectomy with ipsilateral central compartment dissection using conventional laparoscopic instruments, and an endoscopic retractor that we developed. RESULTS: All patients had papillary thyroid carcinoma. Less-than total or total thyroidectomy with ipsilateral central compartment node dissection was performed (124 vs. 8). The mean operation time was 87.6 min (range 56-213 min). The average number of lymph nodes resected was 2.6 (range 1-12). Six patients experienced transient hoarseness, which was resolved within 3 months. Most of the patients were discharged within 3 days after surgery. CONCLUSIONS: In this large series from a single center, we found that TOETVA with the endoscopic retractor can be performed safely and radically in selected patients with thyroid cancer.

Lateral neck metastases in the ipsilateral and contralateral compartments of papillary thyroid carcinoma located in one lobe.

BACKGROUND: Papillary thyroid carcinoma (PTC) frequently involves lymph nodes in the lateral compartment, but PTC located in one lobe rarely metastasizes to bilateral lateral nodes. This study was designed to evaluate the clinicopathological features of patients with PTC limited to one lobe but with bilateral lateral neck metastasis (LNM). METHODS: Between January 2009 and December 2013, 698 patients with unilateral PTC with LNM were analysed. Of these patients, 651 had unilateral LNM (ULNM) and 47 had bilateral LNM (BLNM). The clinicopathological characteristics of the two groups were analysed. RESULTS: There were no significant between-group differences in age, extrathyroidal extension, multifocality in one lobe, thyroiditis or psammomatous calcification. Male sex (51.1% versus 29.8%; P = 0.002), central compartment metastasis (91.5% versus 78.6%, P = 0.035), aggressive subtype of PTC (23.4% versus 8.8%; P = 0.001) and Delphian node metastasis (36.2% versus 18.1% versus 36.2%, P = 0.002) were significantly more frequent, and mean primary tumour size (1.79 ± 1.12 cm versus 1.34 ± 0.83 cm, P = 0.010) significantly larger in the BLNM than in the ULNM group. CONCLUSIONS: Although few patients with PTC located in one lobe have BLNM, the contralateral lateral compartment should be carefully evaluated for BLNM in males and in patients with a primary tumour size >2 cm, aggressive subtype of PTC, central node metastasis and Delphian node metastasis.

Safety of Tyrosine Kinase Inhibitors in Patients With Differentiated Thyroid Cancer: Real-World Use of Lenvatinib and Sorafenib in Korea.

Background: Thyroid cancer has become the most common cancer in Korea. Generally, thyroid cancer patients have a good prognosis; however, 15-20% of patients experience recurrence or distant metastasis or are refractory to standard treatment. We assessed the safety of sorafenib and lenvatinib in patients with advanced or metastatic radioactive iodine-refractory differentiated thyroid cancers (DTC) consecutively treated at a tertiary center in South Korea. Methods: We retrospectively reviewed the charts of all consecutive patients with DTC treated during ≥6 months with lenvatinib (February 2016-April 2018) and sorafenib (January 2014-April 2018) at Gangnam Severance Hospital. Patients were treated according to the prescribing information of each drug and were followed up for 2 months. We evaluated the adverse events (AEs) reported with each drug. Results: A total of 71 medical records (lenvatinib, n = 23; sorafenib, n = 48) were reviewed. The most common histological types were papillary thyroid cancer (69.0%) and follicular thyroid cancer (22.5%). All patients (n = 23) started lenvatinib at a dose of 20 mg; 41.7% of sorafenib-treated patients received an initial dose of 800 mg daily. Four (17.4%) lenvatinib-treated patients and 26 (54.2%) sorafenib-treated patients required treatment discontinuation. The most common AEs of any grade in the lenvatinib group were diarrhea (82.6%), hypertension (78.3%), hand-foot skin reaction (56.5%), weight loss (52.2%), proteinuria (47.8%), and anorexia (43.5%). In the sorafenib group, these were hand-foot skin reaction (87.5%), diarrhea (62.5%), anorexia (60.4%), alopecia (56.3%), mucositis (52.1%), weight loss and generalized weakness (each, 50%), and hypertension (43.8%). The incidence of hand-foot skin reaction, alopecia, and rash of any grade was significantly lower (P = 0.003, P = 0.017, and P = 0.017) in patients treated with lenvatinib compared with those treated with sorafenib. The incidence of hypertension, QT prolongation, and proteinuria of any grade was significantly higher (P = 0.006, P = 0.038, and P < 0.001) in patients treated with lenvatinib compared with those treated with sorafenib. Seven deaths occurred, which were attributed to disease progression. Conclusions: No new safety concerns were identified for either drug. Most AEs were managed with dose modification and medical therapy. AEs such as hypertension and proteinuria warrant close monitoring.

Cost for treatment and follow-up of thyroid cancer increases according to the severity of disease.

BACKGROUND: The aim of this study was to provide an analysis of thyroid cancer-related health care costs over a 5-year period, according to the extent of thyroid surgery. METHODS: The study included 33 patients from our institutional database who underwent thyroid cancer surgery in 2010. Patients were divided into four groups based on surgical extent: (1) hemithyroidectomy, (2) total thyroidectomy, (3) total thyroidectomy with ipsilateral radical neck dissection, and (4) total thyroidectomy with bilateral radical neck dissection and mediastinal dissection. Costs for admission and outpatient follow-up for 5 years were analyzed. RESULTS: Costs for outpatient follow-up and admission, and overall cost increased with increasing stage of disease and increasing extent of thyroid surgery. Patients who underwent only hemithyroidectomy had the lowest costs for outpatient follow-up and admission, as well as the lowest overall cost. CONCLUSION: Over the 5-year follow-up period, surgery performed at an early disease stage was the most cost-effective.

SoLAT (Sorafenib Lenvatinib alternating treatment): a new treatment protocol with alternating Sorafenib and Lenvatinib for refractory thyroid Cancer.

BACKGROUND: In the last decade, several tyrosine kinase inhibitors (TKIs), which disrupt pathways involved in the proliferation and tumorigenesis of thyroid cancer, have been extensively studied. Two different TKIs, lenvatinib and sorafenib, were recently approved by both the US FDA and European Medicine Agency. Until date, the duration of the TKI response is not sufficient and resistance eventually occurs. The goal of this study was to investigate a new treatment protocol, SoLAT, using sorafenib and lenvatinib alternatively on refractory thyroid cancer. METHODS: Patient-derived aggressive papillary thyroid cancer (PTC) cell lines from patients with biochemical and histologically proven aggressive RAI-refractory papillary thyroid cancer were exposed to sorafenib and lenvatinib alternatively. Human thyroid cancer cell xenografts were obtained by injecting patient-derived aggressive PTC cell lines into the flank of female BALB/c nude mice. Tumor-bearing mice were treated with sorafenib and lenvatinib alternatively. Cell viability assay, immunofluorescence analysis, confocal imaging, immunoblot analysis, flow cytometry analysis of cell cycle and a tube formation assay were performed. RESULTS: SoLAT was more effective for advanced PTC cell lines than individual treatment. Immunoblot analysis showed that SoLAT markedly increased levels of cell cycle inhibitors (p53 and p21), and pro-apoptotic factors (Apaf-1 and cleaved caspase 3) and decreased levels of positive cell cycle regulators (cyclin D1, CDK4, CDK6) and anti-apoptotic factors (p-NFκB, Bcl-2). Increased sub-G0/G1 population was observed in the SoLAT group, leading to apoptosis, cell cycle arrest, and strong inhibition of advanced PTC cell viability. SoLAT reduced the level of EMT markers such as vimentin, E-cadherin, Snail and Zeb1 by FGFR inhibition. In the xenograft model, individual treatment with sorafenib or lenvatinib did not markedly suppress patient-derived aggressive PTC cell xenograft tumors, whereas SoLAT significantly suppressed the proliferation of these tumors. CONCLUSIONS: SoLAT was more effective than individual treatment with sorafenib or lenvatinib in inhibiting PTC progression by inducing cell cycle arrest. Studies using both in vitro cell culture and an in vivo xenograft model provided evidence of tumor shrinkage with SoLAT. We suggest that these effects may be due to reduced EMT-mediated drug resistance in the aggressive PTC model.

Genotypic characteristics and their association with phenotypic characteristics of hereditary medullary thyroid carcinoma in Korea.

BACKGROUND: Hereditary medullary thyroid carcinoma can present as a part of multiple endocrine neoplasia syndrome by rearranged during transfection gene mutation. We evaluated the prevalence of rearranged during transfection gene mutation in patients who have medullary thyroid carcinoma and the correlations of genotype with medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism according to the revised American Thyroid Association risk level. METHODS: A total of 331 patients were diagnosed with medullary thyroid carcinoma, 172 of whom were tested for the rearranged during transfection germline mutation by sequencing of exon 8, 10, 11, and 13-16. These patients were diagnosed during the years 1982-2012 at 2 Korean tertiary hospitals. Patients were analyzed according to the route of diagnosis (screened versus index cases) or the mutational site of rearranged during transfection gene (the American Thyroid Association risk group). RESULTS: Rearranged during transfection mutation was found in 23.8% of patients tested, showing a decreasing trend with time. The most commonly mutated codon was codon 634 (37.1%), followed by codon 918 (14.3%). rearranged during transfection-positive patients were younger than rearranged during transfection-negative patients, although no other clinicopathologic characteristics differed. Screened cases were younger and had smaller tumors than index cases. Among rearranged during transfection-positive patients, pheochromocytoma manifested in 35.1% and hyperparathyroidism in 7.0%. Notably, pheochromocytoma and hyperparathyroidism emerged at any time after the diagnosis of medullary thyroid carcinoma. The American Thyroid Association risk-group analysis demonstrated that medullary thyroid carcinoma patients in the highest risk group were younger, had larger tumors, and higher disease-specific mortality. Similar results for pheochromocytoma were found, according to the American Thyroid Association risk group, although the results were not significant. CONCLUSIONS: Korean patients who have medullary thyroid carcinoma showed a similar distribution of rearranged during transfection gene mutation with those in Western countries. The American Thyroid Association risk classification was shown to be useful for pheochromocytoma, as well as for medullary thyroid carcinoma. Familial screening for rearranged during transfection mutation and lifelong monitoring for associated pheochromocytoma should be emphasized in hereditary medullary thyroid carcinoma.

Ultrasonographic features and clinicopathologic characteristics of macrofollicular variant papillary thyroid carcinoma.

Macrofollicular variant papillary thyroid carcinoma (MFV-PTC) is defined as papillary thyroid carcinoma with macrofollicles of >200 µm in more than 50% of the cross-sectional area of the specimen. The aim of this study was to evaluate the clinicopathologic characteristics of the MFV-PTC treated in the Yonsei University College of Medicine.Between September 2007 and July 2012, 18,697 patients with PTC were treated in our institution. Of these, 10 patients (0.05%) were diagnosed as the MFV-PTC in final pathologic report.Mean age of 10 patients were 42.5 years old, ranging from 26 to 69 years. Twelve lesions were found in 10 patients. On preoperative ultrasonographic examination, most of tumors looked like benign nodules. The tumor nodules varied in size from 0.3 to 3.5 cm in greatest dimension. Microscopically, the macrofollicles were surrounded by cuboidal cells with hyperchromatic nuclei and occupied entire nodule.MFV-PTC showed the benign appearance in ultrasonography. To avoid misdiagnosis of MFV-PTC, clinicians should be aware of the characteristics of MFV-PTC and perform ultrasonography with fine needle aspiration biopsy appropriately.

Anti-cancer Effects of HNHA and Lenvatinib by the Suppression of EMT-Mediated Drug Resistance in Cancer Stem Cells.

Anaplastic thyroid cancer (ATC) constitutes less than 2% of total thyroid cancers but accounts for 20-40% of thyroid cancer-related deaths. Cancer stem cell drug resistance represents a primary factor hindering treatment. This study aimed to develop targeted agents against thyroid malignancy, focusing on individual and synergistic effects of HNHA (histone deacetylase), lenvatinib (FGFR), and sorafenib (tyrosine kinase) inhibitors. Patients with biochemically and histologically proven papillary thyroid cancer (PTC) and ATC were included. Cell samples were obtained from patients at the Thyroid Cancer Center, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. PTC and ATC cells were treated with lenvatinib or sorafenib, alone or in combination with HNHA. Tumor-bearing mice (10/group) were administered 10 mg/kg lenvatinib (p.o.) or 40 mg/kg sorafenib (p.o.), alone or in combination with 25 mg/kg HNHA (i.p.) once every three days. Gene expression in patient-derived PTC and ATC cells was compared using a microarray approach. Cellular apoptosis and proliferation were examined by immunohistochemistry and MTT assays. Tumor volume and cell properties were examined in the mouse xenograft model. HNHA-lenvatinib combined treatment induced markers of cell cycle arrest and apoptosis and suppressed anti-apoptosis markers, epithelial-mesenchymal transition (EMT), and the FGFR signaling pathway. Combined treatment induced significant tumor shrinkage in the xenograft model. HNHA-lenvatinib combination treatment thus blocked the FGFR signaling pathway, which is important for EMT. Treatment with HNHA-lenvatinib combination was more effective than either agent alone or sorafenib-HNHA combination. These findings have implications for ATC treatment by preventing drug resistance in cancer stem cells.

Macrometastasis in Papillary Thyroid Cancer Patients is Associated with Higher Recurrence in Lateral Neck Nodes.

BACKGROUND: The use of routine central compartment neck dissection surgery for papillary thyroid carcinoma (PTC) is controversial. Although macroscopic central neck lymph node metastasis (CNLN) in PTC is a poor prognostic factor correlated with increased loco-regional recurrence, the significance of microscopic metastasis to the central lymph nodes is not established. Herein, we aimed to assess the influence of the size of CNLN on disease recurrence among PTC patients. METHODS: Data from 233 patients who underwent less than total thyroidectomy with CNLN dissection in 1989-1999 were retrospectively reviewed. The patients were assigned to three groups according to the central node metastasis: no metastasis (Group I), micrometastasis (<2 mm, Group II), and macrometastasis (≥2 mm, Group III). Clinicopathological features, recurrence rate, site of recurrence, and disease-free survival (DFS) were assessed. RESULTS: Of the 233 patients enrolled (mean follow-up period, 16.1 years), 134 (57.5%) had no central neck metastasis, 37 (15.9%) had micrometastasis, and 62 (26.6%) had macrometastasis. Demographics and tumour variables were similar among the three groups. Recurrence rates were 12.7, 16.2, and 43.5% in Groups I, II, and III, respectively (p < 0.001). Group III had a 3.2-fold increased relative risk of recurrence and a significantly decreased DFS compared to Group I. Group III showed significantly higher rates of lateral neck nodes metastasis than Groups I and II. CONCLUSIONS: In conclusion, macrometastasis significantly affects disease recurrence in PTC patients, whereas microscopic metastasis has only marginal effects. Macroscopic CNLN metastasis showed a significantly higher recurrence in the lateral neck node compared to micrometastasis.

Long-term outcomes of ethanol injection therapy for locally recurrent papillary thyroid cancer.

The standard treatment regimen for locally recurrent lesions is total thyroidectomy, or complete removal of the recurrent thyroid lesion within the thyroid bed. However, reoperation increases the risk of complications and patients have to undergo general anesthesia. Percutaneous ethanol injection therapy represents a far less invasive procedure without general anesthesia and with lower risk of complications. Thirty-four patients who received PEIT at Yonsei University Medical Center between October 2002 and August 2009 for recurrent cervical nodal metastases of differentiated papillary thyroid cancer were included in this retrospective study. During a minimum follow-up of 60 months, treatment outcomes were determined by measuring the lesion size prior to the first injection and 3 months after the last injection. A total of 46 recurrent lesions were detected in 34 patients. Five patients underwent surgery and PEIT was administered to the remaining 19 and 22 lesions in the central compartment and lateral neck lymph nodes, respectively. Size increases were observed in seven (17.1%) lesions, whereas no changes in size and decreases were detected in 10 (24.4%) and 24 (58.5%) lesions. Patients with increased lymph nodes were significantly older (65.3 ± 14.4 vs. 48.2 ± 16.3 years; p = 0.02) and had smaller sizes (9.3 ± 1.0 vs. 12.3 ± 6.4 mm; p = 0.012). Although reoperation remains the first-line treatment for recurrent thyroid cancer, PEIT may be considered as a treatment option in selected patients with lesions larger than 1 cm who are ineligible for surgery or have refused reoperation.

Parathyroid score can predict the duration of required calcium supplementation after total thyroidectomy.

BACKGROUND: Postoperative hypoparathyroidism is the most common complication after total thyroidectomy, owing to unintentional injury or decreased blood flow to the parathyroid glands. Prediction of postoperative hypoparathyroidism would be helpful for surgeons to manage postoperative hypocalcemia. In this study, we scored the discoloration of the parathyroid glands using a new parathyroid scoring system and evaluated the correlation between the parathyroid score and duration of required calcium supplementation after total thyroidectomy. METHODS: A total of 316 patients undergoing total thyroidectomy between November 2009 and April 2010 were enrolled in this retrospective study. Parathyroid scoring was performed by one experienced surgeon. The status of each of the 4 parathyroid glands was classified as normal color (3 points), slightly discolored (2 points), dark discoloration (1 point), or loss of the gland (0 points), resulting in possible total scores of 0-12. Serum parathyroid hormone (PTH), serum calcium, and ionized calcium concentrations were measured at 2 hours, 2 weeks, 3 months, 6 months, and 1 year after surgery. Patients were also divided into three groups based on the duration of required calcium supplementation: no required supplementation (n = 260, 82.3%), required supplementation for <6 months (n = 38, 12%), and required supplementation for ≥6 months (n = 18, 5.75%). RESULTS: Parathyroid scores were positively correlated with ionized PTH concentrations at 2 hours (r = 0.053, p < 0.001), 2 weeks (r = 0.056, p < 0.001), 3 months (r = 0.032, p<0.001), 6 months (r = 0.072, p < 0.001), and 1 year (r = 0.071, p < 0.001) after thyroidectomy. Parathyroid scores were significantly and inversely associated with the duration of required calcium supplementation (p = 0.001). CONCLUSIONS: Parathyroid scores at the end of surgery might be helpful for predicting the degree of postoperative hypocalcemia after total thyroidetomy.

Synergistic Activity of N-hydroxy-7-(2-naphthylthio) Heptanomide and Sorafenib Against Cancer Stem Cells, Anaplastic Thyroid Cancer.

Anaplastic thyroid carcinoma (ATC) although rare is the most deadly form of thyroid cancer. The fatality rate for ATC is high-pitched, the survival rate at 1 year after diagnosis is <20%. Control of ATC is severely hard and widespread with unpredictability. We Previous proved that histone gene reviser and epigenetic changes role significant parts in papillary and anaplastic thyroid cancer tumorigenesis. Herein, the goal of this study was to investigate the anti-tumor activities of a HDAC inhibitor, HNHA alone and in combination with sorafenib in ATC cells in vitro and in vivo and to explore its effects on apoptotic cell death pathways. Three ATC cell lines were exposed to sorafenib in the presence or absence of HNHA, and cell viability was determined by MTT assay. Effects of combined treatment on cell cycle and intracellular signaling pathways were assessed by flow cytometry and western blot analysis. The ATC cell lines xenograft model was used to examine the anti-tumor activity in vivo. Our data showed that HNHA and sorafenib synergistically decreased cell viability in ATC cells, and also significantly increased apoptotic cell death in these cells, as proved by the cleavage of caspase-3 and DNA fragmentation. HNHA and sorafenib combination was reduced anti-apoptotic factor in ATC. Thus, combination therapy with HNHA and sorafenib significantly decreased vessel density, and most significantly reduced tumor volume and increased survival in ATC xenografts. These results propose that HNHA in combination with sorafenib has significant anti-cancer activity in preclinical models, potentially suggesting a new clinical approach for patients of advanced thyroid cancer type.

Clinical Experience With n-Butyl-2-Cyanoacrylate in Performing Lateral Neck Dissection for Metastatic Thyroid Cancer.

Background Chyle leakage following lateral neck dissection (LND) is rare, but can induce metabolic disturbances, delay wound healing, and prolong hospitalization. n-Butyl-2-cyanoacrylate (NBCA) has been used to achieve hemostasis and seal tissues in several surgical settings. We here assessed whether application of NBCA to the thoracic duct area is effective in sealing chyle leakage. Methods The medical records of 163 patients who underwent total thyroidectomy with unilateral LND between March 2011 and September 2012 were reviewed. NBCA was applied to 84 patients and not applied to 79. Drainage volume, duration of hospital stay, and incidence of complications were compared between the 2 groups. Results The 2 groups were not different with regard to age, body weight, gender, primary tumor histology, and number of lateral neck nodes harvested. Mean hospital stay was significantly shorter (4.3 ± 1.8 vs 5.7 ± 3.0 days, P < .001), median total drainage volume was significantly smaller (270 mL; range: 97-931 mL vs 328 mL; range: 113-2636 mL; P < .001), and rate of chyle leakage was significantly lower (0% vs 6.3%, P = .025) in the NBCA than in the non-NBCA group. Conclusion NBCA application to the dissected area of the thoracic duct posterior to its angle of junction with the internal jugular and subclavian veins could be safe and effective in reducing surgical complications related to chyle leakage after LND.

Thyroidectomy without lateral neck dissection for papillary thyroid carcinoma with lateral neck lymph node metastases and negative intraoperative frozen section.

BACKGROUND: The purpose of this study was to investigate the outcomes of patients with papillary thyroid cancer (PTC) with lateral neck metastasis according to their permanent pathology report but negative frozen section findings who did not undergo lateral neck dissection. METHODS: Between September 2009 and December 2011, 575 patients at Gangnam Severance Hospital (Seoul, Korea) underwent frozen section analysis for a suspicious lateral neck lymph node. In 16 patients, the intraoperative findings were negative, but lateral neck metastasis was diagnosed on the basis of permanent pathology findings. The outcomes of these patients who underwent thyroidectomy but not lateral neck dissection were retrospectively investigated. RESULTS: One patient underwent a subsequent lateral neck dissection. After a mean (SD) follow-up period of 42.1 (8.5) months, none of the patients had distant metastasis. CONCLUSION: Total thyroidectomy with subsequent lateral neck dissection is not necessary in patients with PTC who are diagnosed with lateral neck metastasis according to their permanent pathology report but have negative intraoperative frozen section findings.

Postoperative biochemical remission of serum calcitonin is the best predictive factor for recurrence-free survival of medullary thyroid cancer: a large-scale retrospective analysis over 30 years.

CONTEXT: The increase in thyroid screening in the general population may lead to earlier detection of medullary thyroid carcinoma (MTC). OBJECTIVE: We aimed to evaluate secular trends in clinicopathological characteristics and long-term prognosis of MTC and its prognostic factors. DESIGN: This was a retrospective analysis from 1982 to 2012. PATIENTS: Three hundred and thirty-one patients with MTC were included and grouped based on the year of diagnosis (1982-2000, 2001-2005, 2006-2010 and 2011-2012). MEASUREMENTS: These included recurrence and mortality as well as biochemical remission (BCR) of serum calcitonin. RESULTS: Mean tumour size (from 2·5 cm to 1·7 cm, P < 0·001) and percentage of extrathyroidal extension (from 52·0% to 26·0%, P = 0·026) decreased. The percentage of patients achieving BCR within six postoperative months (po-BCR) increased with time (from 39·6% to 76·1%, P < 0·001). The 5-year overall recurrence rate significantly decreased in 2006-2012 compared to 1982-2005 (10% vs 18%, respectively, P = 0·031), although the 5-year survival rate did not improve (92% vs 92%, P = 0·929). Failure to achieve po-BCR was the strongest predictive factor associated with recurrence (hazard ratio [HR] = 58·04, 95% CI 7·14-472·11; P < 0·001). Male gender (HR = 3·18, 95% CI 1·18-8·56; P = 0·022), tumour size >2 cm (HR = 18·33, 95% CI 2·35-143·06; P = 0·006) and distant metastasis (HR = 4·00, 95% CI 1·31-12·21; P = 0·015) were significant prognostic factors for mortality. CONCLUSIONS: Clinicopathological characteristics and recurrence of MTC improved with time. Po-BCR was the best predictive factor for recurrence-free survival.

Tuberculosis cervical lymphadenopathy mimics lateral neck metastasis from papillary thyroid carcinoma.

BACKGROUND: Tuberculosis (TB) lymphadenitis is a frequent cause of lymphadenopathy in areas in which TB is endemic. Cervical lymphadenopathy in TB can mimic lateral neck metastasis (LNM) from papillary thyroid carcinoma (PTC). This study evaluated the clinicopathological features of patients with PTC and TB lateral neck lymphadenopathy. METHODS: Of the 9098 thyroid cancer patients who underwent thyroid cancer surgery at the Thyroid Cancer Center of Gangnam Severance Hospital between January 2009 and April 2013, 28 had PTC and showed TB lymphadenopathy of the lateral neck node. The clinicopathological features of these 28 patients were evaluated. RESULTS: Preoperatively, all 28 patients were diagnosed with PTC and showed cervical lymphadenopathy. All had radiological characteristics suspicious of metastasis in lateral neck nodes. Based upon the results from intraoperative frozen sections, lymph node dissection (LND) was not performed on 19 patients. Seven of eight patients who underwent LND had metastasis combined with tuberculous lymphadenopathy, with the remaining patient negative for LNM. CONCLUSIONS: Intraoperative sampling and frozen sectioning of lymph nodes suspicious of metastasis can help avoid unnecessary LND for tuberculous lymphadenopathy.