Synergistic Anticancer Activity of N-Hydroxy-7-(2-Naphthylthio) Heptanomide, Sorafenib, and Radiation Therapy in Patient-Derived Anaplastic Thyroid Cancer Models.

Anaplastic thyroid cancer (ATC) is an undifferentiated and advanced form of thyroid cancer, accompanied with a high ratio of epigenetic adjustment, which occurs more than genetic mutations. In this study, we aimed to evaluate the synergistic anticancer effect (in vitro and in vivo) of the new combination of N-hydroxy-7-(2-naphthylthio) heptanomide (HNHA) and sorafenib with radiation therapy in pre-clinical models of ATC. The ATC cell lines, YUMC-A1 and YUMC-A2, were isolated from the current patients who were treated with HNHA and sorafenib, either as monotherapy or combination therapy. Synergistic anticancer effect of the combination therapy on the intracellular signaling pathways and cell cycle was assessed via flow cytometry and immunoblot analysis. To examine tumor shrinkage activity in vivo, an ATC cell line-derived mouse xenograft model was used. Results showed that the combination therapy of HNHA and sorafenib with radiation promoted tumor suppression via caspase cleavage and cell cycle arrest in patient-derived ATC. In addition, the combination therapy of HNHA and sorafenib with radiation was more effective against ATC than therapy with HNHA or sorafenib with radiation. Thus, the combination of HNHA and sorafenib with radiation may be used as a novel curative approach for the treatment of ATC.

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.

Patient-Derived, Drug-Resistant Colon Cancer Cells Evade Chemotherapeutic Drug Effects via the Induction of Epithelial-Mesenchymal Transition-Mediated Angiogenesis.

Cancer cells can exhibit resistance to different anticancer drugs by acquiring enhanced anti-apoptotic potential, improved DNA injury resistance, diminished enzymatic inactivation, and enhanced permeability, allowing for cell survival. However, the genetic mechanisms for these effects are unknown. Therefore, in this study, we obtained drug-sensitive HT-29 cells (commercially) and drug-resistant cancer cells (derived from biochemically and histologically confirmed colon cancer patients) and performed microarray analysis to identify genetic differences. Cellular proliferation and other properties were determined after treatment with oxaliplatin, lenvatinib, or their combination. In vivo, tumor volume and other properties were examined using a mouse xenograft model. The oxaliplatin and lenvatinib cotreatment group showed more significant cell cycle arrest than the control group and groups treated with either agent alone. Oxaliplatin and lenvatinib cotreatment induced the most significant tumor shrinkage in the xenograft model. Drug-resistant and metastatic colon cancer cells evaded the anticancer drug effects via angiogenesis. These findings present a breakthrough strategy for treating drug-resistant cancer.

The Prognosis of Papillary Thyroid Cancer with Initial Distant Metastasis is Strongly Associated with Extensive Extrathyroidal Extension: A Retrospective Cohort Study.

BACKGROUND: Extensive extrathyroidal extension (ETE) has a significant role in the prognosis of papillary thyroid cancer (PTC) without distant metastasis, but its role in PTC with initial distant metastasis has never been studied. This study aimed to evaluate the prognostic significance of extensive ETE regarding disease progression, survival, and remission in PTC patients with initial distant metastasis. METHODS: This retrospective cohort study included PTC patients with initial distant metastasis who underwent total thyroidectomy with a median follow-up period of 6.7 years. The prognostic significance of extensive ETE was assessed in terms of time to tumor progression (TTP), cancer-specific survival (CSS), and cumulative incidence of remission with all-cause death as the competing event. RESULTS: The study enrolled 64 patients. Of these patients, 21 (32.8%) had extensive ETE, which was associated with a shorter TTP (adjusted hazard ratio [HR], 4.10; p = 0.015) and a lower CSS rate (p = 0.002, log-rank), particularly for patients 55 years of age or older with stage 4b disease (10-year CSS rate: 33.3% in those with and 92.3% in those without extensive ETE; p = 0.017). Additionally, remission was observed only in patients without extensive ETE (10-year cumulative incidence of remission: 0.0% in those with and 29.3% in those without extensive ETE; p = 0.013). CONCLUSIONS: Extensive ETE of the primary lesion results in poorer prognoses for PTC patients with initial distant metastasis. The high CSS rate for patients with stage 4b PTC but no extensive ETE indicates that the prognosis of this patient population should be distinguished from that of other stage 4 cases.

Posterior Retroperitoneoscopic Resection of Extra-adrenal Paraganglioma Located in the Aorto-caval Space.

BACKGROUND: The posterior retroperitoneoscopic adrenalec tomy has several advantages compared with the transperitoneal approach such as a shorter and more direct route to the target organ, no breach of the intraperitoneal space, and no required retraction of the adjacent organs. It also is a safe procedure with a short learning curve.1-5 This report presents a challenging case of an extra-adrenal paraganglioma located in the aorto-caval space and managed using the retroperitoneal approach. METHODS: A 39-year-old man was placed in the prone jackknife position, and three incisions were made in the right posterior abdominal wall for placement of the laparoscopic ports. The retroperitoneal space was entered with diathermy and blunt finger dissection, and retropneumoperitoneum was achieved with carbon dioxide insufflation pressure up to 18 mmHg. After identification of the right kidney and vessels, the tumor was meticulously dissected and excised with an energy device. The specimen was removed using a laparoscopic specimen retrieval bag, and the port sites were closed in layers. RESULTS: The operative time was 130 min, and the total blood loss was 30 ml. The tumor was diagnosed as a moderately differentiated extra-adrenal paraganglioma. The Von Hippel-Lindau gene mutation was detected using next-generation sequencing. CONCLUSIONS: The posterior retroperitoneoscopic approach is a safe, feasible, and effective method for excising an extra-adrenal paraganglioma even in the aorto-caval space. The authors suggest that this procedure is a useful surgical option for treatment of an aorto-caval paraganglioma for selected patients and by experienced surgeons.

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.

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.

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.

Changing trends in the management of well-differentiated thyroid carcinoma in Korea.

A questionnaire administered in 2009 found that members of the Korean Association of Thyroid-Endocrine Surgeons (KATES) favored more aggressive treatment of well-differentiated thyroid carcinoma (WDTC) than physicians from other countries. This study assessed the changes in practical management of WDTC in Korea from the previous survey. Questionnaires were sent by e-mail to KATES members. A total of 101 members completed the questionnaire. Their responses were compared with response for the 2009 survey. Of the respondents, 53.5% and 80.2% indicated that they would perform fine-needle aspiration cytology on nodules that were <0.5 cm and 0.5-1.0 cm in diameter, respectively. If the cytology was positive, a large number of respondents favored surgical treatment, regardless of tumor size. Compared with the 2009 survey, a slightly higher percentage favored observation for patients with tumors that were <0.5 cm in diameter, and a larger percentage recommended less-than-total thyroidectomy for patients with T1 cancers. Respondents in 2014 favored aggressive lymph node dissection less, irrespective of tumor size, preferring short-term treatment with thyroid stimulating hormone suppressors. The percentage preferring postoperative high-dose radioactive iodine therapy slightly increased, whereas the percentage favoring external irradiation decreased, in 2014 compared with 2009. The management of Korean patients with WDTC changed from 2009 to 2014. In 2009, Korean respondents favored more aggressive treatment of WDTC compared with respondents from other countries. In 2014, however, Korean respondents favored a more conservative approach, especially in patients with microcarcinomas.

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.

Prognostic significance of tumor multifocality in papillary thyroid carcinoma and its relationship with primary tumor size: a retrospective study of 2,309 consecutive patients.

BACKGROUND: Tumor multifocality is frequently observed in papillary thyroid carcinoma (PTC), but its prognostic value is controversial. We investigated the prognostic significance of multifocality in PTCs larger than 1 cm and papillary thyroid microcarcinomas (PTMC). METHODS: Medical records and pathologic results of 2,309 patients who received thyroidectomy and lymph node dissection for PTC were retrospectively reviewed. We identified 648 patients who had PTC with a primary tumor exceeding 1 cm, and 1,661 patients with PTMC. In each group, we compared patients with unifocal and multifocal disease. Cox regression analyses of disease persistence and recurrence were performed to identify the prognostic significance of multifocality. RESULTS: The mean follow-up period was 5.6 years. In the analyses of PTCs larger than 1 cm, the multifocal group included more extensive thyroid surgeries (p = 0.039), radioactive iodine therapies with higher doses (p < 0.001), and significantly higher rates of disease persistence and recurrence (p = 0.001) compared with the unifocal group. In analogous analyses of patients with PTMC, disease persistence and recurrence did not differ significantly between the unifocal and multifocal groups. Cox regression analyses indicated that multifocality was an independent risk factor for disease persistence and recurrence in patients who had PTC with a tumor exceeding 1 cm, but not in patients with PTMC. CONCLUSION: Tumor multifocality appears to be an important prognostic factor for PTCs larger than 1 cm, but may have little or no prognostic significance for PTMC.

Shear wave elastography in evaluation of cervical lymph node metastasis of papillary thyroid carcinoma: elasticity index as a prognostic implication.

PURPOSE: The aim of this study was to evaluate the usefulness of shear wave elastography (SWE) for predicting cervical lymph node (LN) metastasis and the prognostic implication of SWE as histopathologic factors of papillary thyroid carcinoma (PTC). METHODS: Eighty-four LNs of 66 patients with PTC underwent B-mode ultrasonography (BUS) and SWE before ultrasound-guided fine-needle aspiration biopsy or preoperative evaluation. SWE elasticity indices (EI) of mean (Emean), minimum (Emin), maximum (Emax) and the ratio of Emean in LNs and surrounding muscle (Emean-m) were measured at the stiffest portion of LNs (kPa). SWE EI were correlated with the pathologic diagnosis and the histopathologic findings, including number and size of metastatic LNs, the ratio of the number of metastatic LN/dissected LN, and the presence of extranodal extension. Diagnostic performances of SWE EI and BUS for predicting LN metastasis were assessed using receiver operating curve analysis. RESULTS: All SWE EI were significantly higher in metastatic LNs than in benign LNs (p < 0.005). Combined Emean [area under the curve (AUC) 0.811] or Emin (AUC 0.812) with BUS showed significantly higher AUC than BUS (0.738) for predicting metastatic LNs (p = 0.041 and 0.033, respectively). The number of positive LNs/dissected LNs and the largest LN size were significantly correlated with SWE EI (p < 0.05 and p < 0.005, respectively). Metastatic LNs with extranodal extension showed significantly higher SWE EI (p < 0.005) than those without extranodal extension. CONCLUSIONS: Combined use of SWE and BUS was adjunctive to the diagnostic performance of BUS for the prediction of LN metastasis of PTC, and quantitative SWE could predict pathologic prognostic factors of LN metastasis of PTC.

Potential anti-cancer effect of N-hydroxy-7-(2-naphthylthio) heptanomide (HNHA), a novel histone deacetylase inhibitor, for the treatment of thyroid cancer.

BACKGROUND: Thyroid cancer has been indicated to have a higher global proportion of DNA methylation and a decreased level of histone acetylation. Previous studies showed that histone gene reviser and epigenetic changes role significant parts in papillary and anaplastic thyroid cancer tumorigenesis. The goal of this research was to study the endoplasmic reticulum (ER) stress-mediated actions of the dominant histone deacetylase (HDAC) inhibitor, N-hydroxy-7-(2-naphthylthio) hepatonomide (HNHA), in thyroid cancer and to explore its effects on apoptotic cell death pathways. METHODS: Experiments were achieved to conclude the effects of HNHA in papillary thyroid cancer (PTC) and anaplastic thyroid cancer (ATC) cell lines and xenografts, as compared with two other established HDAC inhibitors (SAHA; suberoylanilide hydroxamic acid and TSA; trichostatin A). RESULTS: Apoptosis, which was induced by all HDAC inhibitors, was particularly significant in HNHA-treated cells, where noticeable B-cell lymphoma-2 (Bcl-2) suppression and caspase activation were observed both in vitro and in vivo. HNHA increased Ca(2+) release from the ER to the cytoplasm. ER stress-dependent apoptosis was induced by HNHA, suggesting that it induced caspase-dependent apoptotic cell death in PTC and ATC. PTC and ATC xenograft studies demonstrated that the antitumor and pro-apoptotic effects of HNHA were greater than those of the established HDAC inhibitors. These HNHA activities reflected its induction of caspase-dependent and ER stress-dependent apoptosis on thyroid cancer cells. CONCLUSIONS: The present study indicated that HNHA possibly provide a new clinical approach to thyroid cancers, including ATC.

Preventive Effect of Human Acellular Dermal Matrix on Post-thyroidectomy Scars and Adhesions: A Randomized, Double-Blinded, Controlled Trial.

BACKGROUND: Acellular dermal matrix (ADM) has been used for antiadhesion formation along with wound healing in various surgical fields. OBJECTIVE: The aim is to assess the efficacy of ADM implantation in the prevention of postoperative scars and adhesions after conventional, open, total thyroidectomy. MATERIALS AND METHODS: Forty-four patients with papillary thyroid carcinoma undergoing thyroidectomy were randomly assigned to the study (ADM implantation) or control group (without ADM). Global photographic assessment, Vancouver scar scale (VSS), objective scar assessment, and swallowing impairment index were assessed at baseline, immediately after surgery, and at 1 and 2 months after surgery. RESULTS: Nineteen control and 20 study group participants completed the study. The mean VSS score of the study group was significantly lower than the controls at both 1 month (3.06 ± 1.25 vs 4.41 ± 1.54, respectively) and 2 months (2.76 ± 1.56 vs 4.35 ± 1.58, respectively) after surgery. Scar quality measures (mean melanin and erythema indexes) were significantly lower in the study group compared with controls. Study group participants had significantly lower swallowing impairment scores than controls. The mean postoperative hospitalization of both groups was not significantly different. CONCLUSION: Acellular dermal matrix-assisted implants appear to improve post-thyroidectomy scar and swallowing impairments without delays in operation time.

Reducing neck incision length during thyroid surgery does not improve satisfaction in patients.

Postoperative neck cosmesis is a major concern of patients undergoing thyroid surgery. Patients will likely be more satisfied with the long-term cosmetic appearance of smaller than larger thyroidectomy scars. We, therefore, investigated the relationship between scar length following conventional thyroid surgery and patient satisfaction. An anonymous scar-assessment questionnaire was administered to patients who underwent conventional thyroid surgery. The 2,041 patients were asked to rate their satisfaction with their scars on a ten-point Likert scale, with one being very unsatisfied and ten being very satisfied. The mean satisfaction score was significantly lower in the benign condition than in malignancy (6.9 ± 2.5 vs. 7.4 ± 2.5; p = 0.021), whereas there were no differences in satisfaction score among subgroups of patients with benign condition (p = 0.837). In patients with thyroid cancer, the mean satisfaction scores were similar among subgroups according to operation type and scar length (p = 0.820). Incision length was not associated with patient satisfaction in thyroid surgery patients and therefore may not be critical in decision making for thyroid cancer surgery.

Surgical complications after robotic thyroidectomy for thyroid carcinoma: a single center experience with 3,000 patients.

BACKGROUND: Robotic thyroidectomy (RT), a new gasless, transaxillary approach developed by the Yonsei University group in Seoul, Korea, eliminates the need for a cervical incision. Since RT is technically complex and has a steep learning curve, the surgical complication rate may initially be higher than with conventional surgery. This study evaluated the complication rates of transaxillary RT and assessed ways to prevent surgical complications. METHODS: Between October 2007 and March 2013, 3,000 patients underwent RT for thyroid cancer in the Department of Surgery, Yonsei University College of Medicine at Severance Hospital, Seoul. The medical records of these patients were reviewed retrospectively, and surgical complications were assessed on the basis of clinical findings. RESULTS: The most common surgical complication was symptomatic hypocalcemia, of which 37.43 % cases were transient and 1.10 % permanent. Other surgical complications included recurrent laryngeal nerve injury (1.23 % transient, 0.27 % permanent), seroma (1.73 %), hematoma (0.37 %), chyle leakage (0.37 %), trachea injury (0.2 %), Horner's syndrome (0.03 %), carotid artery injury (0.03 %), and brachiocephalic vein injury (0.03 %). The technique-related complications, which were never seen in conventional open thyroidectomy, were axillary skin flap perforation (0.1 %), and traction injury of the arm on the side the lesion was located (0.13 %). CONCLUSIONS: Surgeons who have mastered standardized robotic surgical procedures and who understand potential complications and how to prevent them can perform RT safely.

Surgical completeness of robotic thyroidectomy: a prospective comparison with conventional open thyroidectomy in papillary thyroid carcinoma patients.

BACKGROUND: Using the da Vinci(®) robotic system, surgeons can complete secure thyroidectomy without noticeable neck scarring. This study compared the surgical completeness of transaxillary robotic thyroidectomy (RT) with conventional open procedures (OT) in treating papillary thyroid carcinoma (PTC) patients. MATERIALS AND METHODS: From April 2009 through February 2011, 94 PTC patients underwent total thyroidectomy with central compartment neck dissection (CCND) at Yonsei University College of Medicine. All patients received 1.1 GBq radioactive iodine (RAI) ablation, post-therapy whole-body scans (TxWBS), and diagnostic WBS (DxWBS) 1 year later. We prospectively compared patient clinicopathologic characteristics and surgical completeness between the two groups. RESULTS: Fifty-one patients underwent OT and 43 underwent RT. Mean age was significantly younger in the RT group. Tumor size, capsular-invasion frequency, multifocality, bilaterality, and central nodal metastasis were not different between the two groups. The number of retrieved nodes during CCND did not significantly differ between the groups. There was no significant difference between the OT and RT groups in stimulated thyroglobulin levels acquired during TxWBS and DxWBS. The RAI uptake ratios at TxWBS were significantly higher in the RT group compared with the OT group; however, follow-up DxWBS showed no difference in RAI uptake ratios. Also, the ablation success rate was similar between the two groups. There were no abnormal findings in follow-up neck ultrasonography in either group. CONCLUSION: Remnant thyroid tissue ablation after transaxillary RT was successfully managed by 1.1 GBq RAI. RT showed similar surgical completeness versus conventional OT, and provides a safe and feasible surgical option for PTC patients.

Factors contributing to surgical outcomes of transaxillary robotic thyroidectomy for papillary thyroid carcinoma.

INTRODUCTION: Transaxillary robotic thyroidectomy is considered a technically feasible and safe treatment option for patients with low-risk papillary thyroid carcinoma (PTC). The aim of the present study was to determine the factors that contribute to the perioperative surgical outcomes of robotic thyroidectomy and to suggest guidelines for patient selection to be used by surgeons inexperienced in the technique. METHOD: We reviewed the records of 275 patients with PTC who underwent robotic total thyroidectomy using a gasless, transaxillary single-incision approach at Yonsei University Health System, South Korea, between January 2011 and May 2012. The association between surgical outcomes and clinicopathologic factors was assessed using linear and logistic regression analysis. RESULTS: The contributing factors for surgical outcomes of robotic thyroidectomy were categorized as patient factors, including gender and body mass index (BMI), and thyroid-specific factors, including thyroid gland size, coexistent thyroiditis, tumor size, and serum anti-thyroglobulin antibody and anti-microsomal antibody titers. Of these, male gender, a large thyroid gland, and thyroiditis significantly increased the total operation time. Male gender, thyroiditis, and overweight BMI increased the working space time, and a large thyroid gland and overweight BMI affected the console time. A large thyroid gland and histological thyroiditis were associated with increased intraoperative blood loss. There was no association between postoperative complications and clinicopathologic parameters. CONCLUSION: Male gender, overweight BMI, a large thyroid gland, and coexistent thyroiditis adversely affected the surgical outcome of robotic thyroidectomy. Surgeons inexperienced in the technique should avoid or carefully approach individuals with these factors.

Scattered psammomatous calcifications around papillary thyroid carcinoma.

BACKGROUND: Although psammomatous calcification is a characteristic pathologic feature of papillary thyroid carcinoma (PTC), the clinical meaning of histologically determined scattered psammomatous calcifications around PTC is unknown. OBJECTIVE: The aim of this study was to evaluate the clinical significance of scattered psammomatous calcifications around PTC. MATERIALS AND METHODS: Between January 2009 and July 2009, a total of 546 patients who underwent total thyroidectomy for PTC were enrolled. They were classified into two groups: patients with scattered psammomatous calcifications and patients without psammomatous calcifications. The clinical findings, preoperative diagnostic findings, and histopathologic features were compared between the two groups. RESULTS: Scattered psammomatous calcifications around PTC were found in 209 patients (38 %), and mostly in younger patients (p = 0.007), those with infiltrative tumor margin (p = 0.022), those with capsule invasion (p = 0.013), and those with lymph node metastasis (p < 0.001). No statistical significance was found in gender, tumor size, multiplicity, and coexisting lymphocytic thyroiditis. CONCLUSIONS: Although further studies with large-scale, long-term follow-up will be necessary to validate the relationship between scattered psammomatous calcifications and prognosis, scattered psammomatous calcification around PTC may have correlations with the aggressiveness of the PTC.