Robotic thyroidectomy learning curve for beginning surgeons with little or no experience of endoscopic surgery.

BACKGROUND: This study assessed the results of robotic thyroidectomy by fellowship-trained surgeons in their initial independent practice, and whether standard fellowship training for robotic surgery shortens the learning curve. METHODS: This prospective cohort study evaluated outcomes in 125 patients who underwent robotic thyroidectomy using gasless transaxillary single-incision technique by 2 recently graduated fellowship-trained surgeons. Learning curves were analyzed by operation time, with proficiency defined as the point at which the slope of the time curve became less steep. RESULTS: Of the 125 patients, 113 underwent robotic less-than-total thyroidectomy, 9 underwent robotic total thyroidectomy and 3 underwent robotic total thyroidectomy with modified radical neck dissection. Mean total times for these 3 operations were 100.8 ± 20.6 minutes, 134.2 ± 38.7 minutes, and 284.7 ± 60.4 minutes, respectively. For both surgeons, the operation times gradually decreased, reaching a plateau after 20 robotic less-than-total thyroidectomies. CONCLUSION: The surgical learning curve for robotic thyroidectomy performed by recently graduated fellowship-trained surgeons with little or no experience in endoscopic surgery showed excellent results compared with those in a large series of more experienced surgeons.

Adipose tissue-derived mesenchymal stem cells cultured at high density express IFN-ß and suppress the growth of MCF-7 human breast cancer cells.

Although it has been reported that mesenchymal stem cells (MSCs) suppress tumor growth in vitro and in vivo, little is known about the underlying molecular mechanisms. We found that type I interferon is expressed in adipose tissue-derived stem cells (ASCs) cultured at high density, and ASCs and their conditioned medium (ASC-CM) suppress the growth of MCF-7 cells in vitro. Growth inhibition was amplified by glucose deprivation that resulted from high density culture of ASCs after 3days. The cytotoxic effect of the ASC-CM obtained from high density culture of ASCs was neutralized by anti-IFN-ß antibody. STAT1 was phosphorylated in MCF-7 cells treated with ASC-CM, and JAK1/JAK2 inhibitor treatment decreased STAT1 phosphorylation. The cytotoxic effect of ASC-CM was reduced especially by JAK1 inhibitors in MCF-7 cells. Our findings suggest that ASCs cultured at high density express type I interferons, which suppresses tumor growth via STAT1 activation resulting from IFN-ß secretion in MCF-7 breast cancer cells.

Bone mineral density and bone turnover markers in patients on long-term suppressive levothyroxine therapy for differentiated thyroid cancer.

PURPOSE: Current management for patients with differentiated thyroid cancer includes near total thyroidectomy and radioactive iodine therapy followed by administration of supraphysiological doses of levothyroxine (L-T4). Although hyperthyroidism is a well known risk factor for osteoporosis, the effects of L-T4 treatment on bone mineral density (BMD) in patients with thyroid cancer do not appear to be as significant as with endogenous hyperthyroidism. In this study, we evaluated the impact of long-term suppressive therapy with L-T4 on BMD and bone turn over markers in Korean female patients receiving L-T4 suppressive therapy. METHODS: We enrolled 94 female subjects (mean age, 50.84 ± 11.43 years) receiving L-T4 after total or near total thyroidectomy and radioactive iodine therapy for thyroid cancer (mean follow-up period, 12.17 ± 4.27 years). The subjects were divided into three groups by thyroid stimulating hormone (TSH) level (group 1 with TSH level ≤0.001 µIU/mL, group 2 with TSH level between 0.001 and 0.17 µIU/mL, group 3 with TSH level >0.17 µIU/mL) and four groups by quartile of free T4 level. L-T4 dosage, BMD (examined by dual-energy x-ray absorptiometry), and bone turnover markers were evaluated according to TSH and free T4 levels. RESULTS: No significant decrease was detected in BMD or bone turnover markers according to TSH level or free T4 level. Also, the prevalence of osteoporosis and osteopenia was not different among groups. CONCLUSION: Long-term L-T4 suppressive therapy after thyroid cancer management did not affect bone density or increase the prevalence of osteoporosis even though TSH levels were supraphysiologically suppressed.

Ultrasonographic guideline for thyroid nodules cytology: single institute experience.

PURPOSE: The main issue with the current ultrasonography (US) guidelines is the overestimation of malignant and indeterminate nodules as they do not aid in making decisions to treat patients. To overcome this, new US guidelines for thyroid nodules that have been shown to be better correlated with cytologic results have been proposed. We also suggested specific indications for US-guided fine needle aspiration (FNA) using the new US guidelines. METHODS: Clinical and pathologic data from 925 patients and 1,419 thyroid nodules were retrospectively collected. All subjects underwent US- and US-guided FNA at Department of Surgery, Wonju Christian Hospital, between March 2010 and July 2011. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were calculated for both the current guidelines and the new guidelines. RESULTS: The accuracy, sensitivity, specificity, PPV, and NPV for the current guidelines in predicting malignancy were 24.1%, 99.3%, 62.2%, 25.0%, and 99.8%, respectively. The accuracy, sensitivity, specificity, PPV, and NPV for the new guidelines in predicting malignancy were 66.0%, 96.0%, 86.7%, 47.7%, and 99.4%, respectively. CONCLUSION: The use of the new US guidelines allow for a more accurate and specific diagnosis and a better treatment plan than the current guidelines. Additionally, the use of the new FNA guidelines may help prevent unnecessary FNAs and promote cost-effective follow-up for patients.

Clinical prognostic index for recurrence of papillary thyroid carcinoma including intraoperative findings.

This study created a new staging system using a risk model that employed clinical factors that were associated with recurrence, verified by preoperative clinical information and intraoperative finding and was compared with other staging systems. A review was conducted of patients who have undergone thyroidectomy and followed-up between January 1, 1983 and September 31, 2007 at Yonsei University Wonju Christian Hospital. The final prognostic staging system was defined as University of Yonsei clinical staging system (Prognostic score = 0.03 × Age + 0.8 × (if male gender) + 0.5 × (if extrathyroidal tumor extension present) + 0.7 × (if clinically apparent lymph node metastasis present), Stage I, less than 1.50; Stage II, 1.50 to 2.29; Stage III, 2.30 to 3.29; Stage IV 4, 3.3 or more). Compared with the other staging systems, the proportion of variation explained (PVE %) was calculated for each. The University of Yonsei clinical staging system appeared to be first as an accurate prognosis predictor with 11.9%. New staging system can predict recurrence and has advantage can use preoperative clinical information and intraoperative finding. Those who are diagnosed as high risk patients using the new staging system should be treated with aggressive surgical treatment and close follow-up.

Analysis of prognostic factors in patients with multiple recurrences of papillary thyroid carcinoma.

PURPOSE: Numerous studies in the past have mentioned various factors that influence the recurrence of papillary thyroid carcinoma, including age, tumor size, advanced stage, extrathyroidal extension, and distant metastasis, and attempts have been made to classify the disease into low-risk and high-risk group based on these clinicopathological factors. However, there has been relatively scarce study on patients with multiple recurrent papillary thyroid carcinoma. This study analyzed the risk factors associated with such cases. MATERIALS AND METHODS: This study investigated various clinicopathological factors of 416 patients who were diagnosed with papillary thyroid carcinoma and received primary surgery at Yonsei University Wonju College of Medicine, Department of Surgery, from January 1983 to December 2006 and were followed up until October 2010. An investigation of factors associated with patients showing multiple recurrences was made. RESULTS: Patients were divided into 3 groups: group 1 (no recurrence, n=380), group 2 (1 recurrence only, n=21), and group 3 (multiple recurrences, n=15). The univariate analysis on risk factors revealed tumor size greater than 2 cm, multifocality, clinical apparent lymph node metastasis to be risk factors associated with multiple recurrences of papillary thyroid carcinoma. A multivariate analysis performed on variables selected from univariate analysis demonstrated no significant risk factor. The 10-year disease-specific survival for 3 different patient groups (group 1, 2, and 3) was 100%, 100%, and 83.1%, respectively, and patients in more clinically advanced group demonstrated poorer prognosis (p<0.001). The 10-year overall survival rate for the 3 patient groups was 93.9%, 100%, and 92%, respectively, and clinically advanced groups tended to show poorer overall survival rate as well (p=0.046). DISCUSSION: A more aggressive and extensive surgery, as well as closer follow up, is to be required when operating on patients with tumor size greater than 2 cm, multifocality, clinical apparent lymph node metastasis. The use of imaging modalities, such as ultrasonography and PET-CT scan, may be desirable when monitoring such patients.

Hungry bone syndrome after parathyroidectomy of a minimally invasive parathyroid carcinoma.

The prognosis of parathyroid carcinoma varies significantly between numerous studies. Therefore, many attempts have been made to grade the degree of parathyroid carcinoma, and recently, classifying parathyroid carcinomas into either minimally invasive or widely invasive carcinoma- similar to follicular carcinoma of the thyroid- has led to a more reliable prediction of the prognosis. Hungry bone syndrome can occur if parathyroidectomy is performed due to primary hyperparathyroidism regardless of the cause of the disease. Hungry bone syndrome is characterized by postoperative a hypocalcemic state due to remineralization of various minerals, including calcium, of the bone; this syndrome requires a long-term supplementation of calcium. The authors aim to report, along with a review of related literatures, 1 case of a 29-year-old female patient diagnosed with minimally invasive parathyroid carcinoma who fell into hungry bone syndrome after parathyroidectomy.

Neuron-like differentiation of bone marrow-derived mesenchymal stem cells.

PURPOSE: Mesenchymal stem cells (MSCs) are multipotent and give rise to distinctly differentiated cells from all three germ layers. Neuronal differentiation of MSC has great potential for cellular therapy. We examined whether the cluster of mechanically made, not neurosphere, could be differentiated into neuron-like cells by growth factors, such as epidermal growth factor (EGF), hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF). MATERIALS AND METHODS: BMSCs grown confluent were mechanically separated with cell scrapers and masses of separated cells were cultured to form cluster BMSCs. As described here cluster of BMSCs were differentiated into neuron-like cells by EGF, HGF, and VEGF. Differentiated cells were analyzed by means of phase-contrast inverted microscopy, reverse transcriptase-polymerase chain reaction (RT-PCR), immunofluorescence, and immunocytochemistry to identify the expression of neural specific markers. RESULTS: For the group with growth factors, the shapes of neuron-like cells was observable a week later, and two weeks later, most cells were similar in shape to neuron-like cells. Particularly, in the group with chemical addition, various shapes of filament structures were seen among the cells. These culture conditions induced MSCs to exhibit a neural cell phenotype, expressing several neuro-glial specific markers. CONCLUSION: bone marrow-derived mesenchymal stem cells (BMSCs) could be easily induced to form clusters using mechanical scraping, not neurospheres, which in turn could differentiate further into neuron-like cells and might open an attractive possibility for clinical cell therapy for neurodegenerative diseases. In the future, we consider that neuron-like cells differentiated from clusters of BMSCs are needed to be compared and analyzed on a physiological and molecular biological level with preexisting neuronal cells, and studies on the possibility of their transplantation and differentiation capability in animal models are further required.

First report of ovarian dysgerminoma in Cowden syndrome with germline PTEN mutation and PTEN-related 10q loss of tumor heterozygosity.

We present the first report of ovarian dysgerminoma in Cowden syndrome, presenting in a 7-year-old girl. In her second decade, a hamartomatous soft tissue extremity mass and diffuse gastrointestinal hamartomatous polyposis with pathologic features suggestive of either juvenile, Peutz-Jeghers, or Cowden polyps were identified, along with diffuse esophageal glycogenic acanthosis and skin manifestations. During regular thyroid cancer surveillance under the provisional diagnosis of Cowden syndrome, papillary thyroid carcinoma and benign follicular nodules were diagnosed at age 23. PTEN mutational analysis revealed a novel germline nonsense point mutation of Q219X. Loss of PTEN heterozygosity was also present in the ovarian dysgerminoma. Parental mutation testing and phenotype screening were negative. The correct classification of Cowden syndrome is difficult because of its protean manifestations and overlapping phenotypes with other genetic and noninherited pathologies, particularly regarding various gastrointestinal polyposis syndromes. Despite the challenges, correct classification is critical to patient care because of the associated cancer predispositions and necessary surveillance programs. This is the first report of Cowden syndrome presenting with ovarian dysgerminoma, which implicates PTEN in the molecular pathogenesis of dysgerminoma and adds it to the phenotypic manifestations of Cowden syndrome.