Renoprotective Effects of Hypoxylonol C and F Isolated from Hypoxylon truncatum against Cisplatin-Induced Cytotoxicity in LLC-PK1 Cells.

Although cisplatin is the standard platinum-based anticancer drug used to treat various solid tumors, it can cause damage in normal kidney cells. Protective strategies against cisplatin-induced nephrotoxicity are, therefore, clinically important and urgently required. To address this challenge, we investigated the renoprotective effects of Hypoxylontruncatum, a ball-shaped wood-rotting fungus. Chemical investigation of the active fraction from the methanol extract of H.truncatum resulted in the isolation and identification of the renoprotective compounds, hypoxylonol C and F, which ameliorated cisplatin-induced nephrotoxicity to approximately 80% of the control value at 5 µM. The mechanism of this effect was further investigated using hypoxylonol F, which showed a protective effect at the lowest concentration. Upregulated phosphorylation of p38, extracellular signal-regulated kinases, and c-Jun N-terminal kinases following cisplatin treatment were markedly decreased after pre-treatment with hypoxylonol F. In addition, the protein expression level of cleaved caspase-3 was significantly reduced after co-treatment with hypoxylonol F. These results show that blocking the mitogen-activated protein kinase signaling cascade plays a critical role in mediating the renoprotective effect of hypoxylonol F isolated from H.truncatum fruiting bodies.

Efficacy and Safety of Radiofrequency Ablation for Benign Thyroid Nodules: A Prospective Multicenter Study.

Objective: To assess the efficacy and safety of thyroid radiofrequency (RF) ablation for benign thyroid nodules by trained radiologists according to a unified protocol in a multi-center study. Materials and Methods: From 2010 to 2011, 345 nodules from 345 patients (M:F = 43:302; mean age ± SD = 46.0 ± 12.7 years, range = 15-79) who met eligibility criteria were enrolled from five institutions. At pre-ablation, the mean volume was 14.2 ± 13.2 mL (1.1-80.8 mL). For 12 months or longer after treatment, 276 lesions, consisting of 248 solid and 28 predominantly cystic nodules, were followed. All operators performed RF ablation with a cool-tip RF system and two standard techniques (a transisthmic approach and the moving-shot technique). Volume reduction at 12 months after RF ablation (the primary outcome), therapeutic success, improvement of symptoms as well as of cosmetic problems, and complications were evaluated. Multiple linear regression analysis was applied to identify factors that were independently predictive of volume reduction. Results: The mean volume reduction at 12 months was 80.3% (n = 276) and at the 24-, 36-, 48-, and 60-month follow-ups 84.3% (n = 198), 89.2% (n = 128), 91.9% (n = 57), and 95.3% (n = 6), respectively. Our therapeutic success was 97.8%. Both mean symptom and cosmetic scores showed significant improvements (p < 0.001). The rate of major complications was 1.0% (3/276). Solidity and applied energy were independent factors that predicted volume reduction. Conclusion: Radiofrequency ablation performed by trained radiologists from multiple institutions using a unified protocol and similar devices was effective and safe for treating benign thyroid nodules.

Core Needle Biopsy of the Thyroid: 2016 Consensus Statement and Recommendations from Korean Society of Thyroid Radiology.

Core needle biopsy (CNB) has been suggested as a complementary diagnostic method to fine-needle aspiration in patients with thyroid nodules. Many recent CNB studies have suggested a more advanced role for CNB, but there are still no guidelines on its use. Therefore, the Task Force Committee of the Korean Society of Thyroid Radiology has developed the present consensus statement and recommendations for the role of CNB in the diagnosis of thyroid nodules. These recommendations are based on evidence from the current literature and expert consensus.

Variability in Observer Performance Between Faculty Members and Residents Using Breast Imaging Reporting and Data System (BI-RADS)-Ultrasound, Fifth Edition (2013).

BACKGROUND: Ultrasonography (US) is a useful tool for breast imaging, yet is highly operator-dependent. OBJECTIVES: We evaluated inter-observer variability and performance discrepancies between faculty members and radiology residents when describing breast lesions, by the fifth edition of breast imaging reporting and data system (BI-RADS)-US lexicon, and then attempted to identify whether inter-observer variability could be improved after one education session. PATIENTS AND METHODS: In total, 50 malignant lesions and 70 benign lesions were considered in our retrospective study. Two faculty members, two senior residents, and two junior residents separately assessed the US images. After the first assessment, the readers received one education session, and then reassessed the images in a random order. Inter-observer variability was measured using the kappa coefficient (κ). Performance discrepancy was evaluated by receiver operating characteristic (ROC) curves. RESULTS: For the faculty members, fair-to-good agreement was obtained in all descriptors and final assessment, while for residents, poor-to-moderate agreement was obtained. The areas under the ROC curves were 0.78 for the faculty members, 0.59 for the senior residents, and 0.52 for the junior residents, respectively. Diagnostic performance was significantly higher in the faculty members than the senior and junior residents (P = 0.0001 and < 0.0001, respectively). After one education session, the agreement in the final assessment was one level higher in the faculty members and senior residents, yet in the senior residents, the degree of agreement was still only fair. Moreover, in the junior residents, there was no improvement. CONCLUSION: Investigative assessment of breast US by residents is inadvisable. We recommend continued professional resident training to improve the degree of agreement and performance.

Efficacy and Safety of Radiofrequency Ablation Versus Observation for Nonfunctioning Benign Thyroid Nodules: A Randomized Controlled International Collaborative Trial.

BACKGROUND: Percutaneous radiofrequency thermal ablation (RFA) has been reported as an effective tool for the management of benign thyroid nodules (BTN). However, large, randomized controlled trials (RCTs) are lacking. OBJECTIVE: The aims of this study were to assess the volume reduction of BTN after a single RFA performed using the moving-shot technique and to compare the volume reduction obtained in patients treated in two centers with different experience of the moving-shot technique. METHOD: This study was an international prospective RCT. It was carried out at the Mauriziano Hospital (Turin, Italy) and the Asan Medical Center (Seoul, Korea). Eighty patients harboring solid, compressive, nonfunctioning BTN (volume 10-20 mL) were enrolled. Twenty patients in each country were treated by RFA using a 18-Gauge internally cooled electrode (group A); 20 nontreated patients in each country were followed as controls (group B). RESULTS: At six months, BTN volume significantly decreased in group A (15.1±3.1 mL vs. 4.2±2.7 mL; p<0.0001), whereas it remained unchanged in group B (14.4±3.3 mL vs. 15.2±3.5 mL). The baseline volume was larger in the Italian series (16.4±2.5 mL vs. 13.9±3.3 mL, p=0.009). However, at six months, there was no significant difference between the Korean group and the Italian group (3.7±2.9 mL vs. 5.5±2.2 mL). Both cosmetic and compressive symptoms significantly improved (3.6±0.5 vs. 1.7±0.4 and 3.6±1.9 vs. 0.4±0.7, respectively; p<0.001). No side effects occurred. CONCLUSIONS: RFA was effective in reducing the volume of BTN. The outcome was similar in centers with different experience in the moving-shot technique.

Radiofrequency ablation for autonomously functioning thyroid nodules: a multicenter study.

BACKGROUND: The purpose of this study is to validate the generalizability of the efficacy and safety of radiofrequency (RF) ablation for treating autonomously functioning thyroid nodules (AFTN) in a large population multicenter study. METHODS: This study included 44 patients from 5 institutions who refused or were not suitable for surgery or radioiodine therapy. Twenty-three patients were affected by a toxic nodule and 21 by a pretoxic nodule. RF ablation was performed using an 18-gauge, internally cooled electrode. Nodule volume, thyroid function, scintigraphy, symptom/cosmetic scores, and complications were evaluated before treatment and during each follow-up. RESULTS: The mean follow-up period was 19.9±12.6 months. The mean nodule volume was initially 18.5±30.1 mL and significantly decreased after treatment at 1 month (11.8±26.9 mL, p<0.001) and the last month (4.5±9.8 mL, p<0.001). Significant improvement of triiodothyronine, free thyroxine, and thyrotropin was observed at the last follow-up. Regarding scintigraphy, 35 hot nodules became cold or were normal when scanned and 9 decreased uptake, although they remained hot nodules. The mean symptom and cosmetic scores were significantly reduced at the last follow-up. No major complications were encountered. CONCLUSIONS: This multicenter study validated the efficacy and safety of RF ablation for treating AFTN; RF ablation can be considered an alternative to surgery or radioiodine therapy.

Detection of thyroid pyramidal lobe by ultrasound versus computed tomography: a single-center study.

OBJECTIVE: The prevalence and features of the thyroid pyramidal lobe (TPL) on computed tomography (CT) have been reported, but no ultrasound (US) study has been found. The purposes of the current study were to assess the sonographic prevalence and features of TPLs and to compare the US and CT parameters of TPLs. METHODS: From November 2012 to February 2013, a total of 160 patients who were scheduled for surgical treatment of thyroid cancers and follicular neoplasms were enrolled. A single radiologist prospectively evaluated the presence and features of TPLs on preoperative thyroid US, noting the size, location, degree of continuity with the main thyroid gland, and superior extent of each TPL. On a different day, the same radiologist retrospectively evaluated CT findings in the same patients from a picture archiving and communication system. RESULTS: Ultrasound revealed TPLs in 82 cases (50.6%) and CT revealed TPLs in 96 cases (59.3%). Thyroid pyramidal lobes predominantly originated from the left thyroid lobe on both US (34/82, 41.5%) and CT (40/96, 41.7%). The mean length, anteroposterior diameter, transverse diameter, and volume of the TPLs were 20.9 mm, 2.0 mm, 5.8 mm, and 268.6 mm on US and 22.8 mm, 1.9 mm, 6.1 mm, and 344.0 mm on CT, respectively. When CT findings were used as the reference standard, the sensitivity, specificity, positive and negative predictive values, as well as accuracy of US for detecting TPLs were 82.3, 95.3, 93.3, 78.2, and 87.5%, respectively. CONCLUSIONS: Like neck CT, thyroid US may be useful in evaluating TPLs.

Collision tumor with inflammatory breast carcinoma and malignant phyllodes tumor: a case report and literature review.

There have been some reports of coincidental presentation of breast carcinoma and phyllodes tumor in the same breast. Most of the cases were carcinoma that arose from a phyllodes tumor with a histologically identified transitional area, and they behaved less aggressively than the usually encountered carcinoma. Collision tumors are rare clinical entities in which two histologically distinct tumor types show involvement at the same site. The occurrence of these tumors in the breast is extremely rare. Here, we report a case of 45-year-old woman who had both invasive ductal carcinoma as the finding of inflammatory carcinoma and a malignant phyllodes tumor in the same breast. There was no evidence of a transitional area between the phyllodes tumor and the invasive ductal carcinoma. To our knowledge, this is the first report of a collision tumor of inflammatory breast carcinoma coincident with a malignant phyllodes tumor in same breast.

Single-session treatment of benign cystic thyroid nodules with ethanol versus radiofrequency ablation: a prospective randomized study.

PURPOSE: To compare volume reduction of single-session ethanol ablation (EA) and radiofrequency (RF) ablation for cystic thyroid nodule treatment. MATERIALS AND METHODS: All patients gave written informed consent to participate in this prospective institutional review board-approved study. From May 6, 2010, to August 8, 2011, in this single-institutional, noninferiority trial, 50 patients, each with a single cystic thyroid nodule, were randomly assigned to EA (25 patients; mean age for women, 45.7 years, and for men, 37.5 years) or RF ablation (25 patients; mean age for women, 45.1 years, and for men, 43.7 years) treatment. Internal fluid was aspirated prior to EA or RF ablation. Primary end point was the volume reduction ratio (percentage) at 6-month follow-up; the noninferiority margin was chosen as -8% (EA minus RF ablation). Secondary end points included therapeutic success rate, improvement of symptoms and cosmetic problems, and number of major complications. Analysis was performed primarily in intention-to-treat manner. A one-sided 95% confidence interval (CI) for the mean difference in volume reduction ratio 6 months after treatment was calculated to test for noninferiority. Subsequent superiority comparison of EA with RF ablation on a condition of establishment of the noninferiority of EA to RF ablation was preplanned and used two-sided 95% CI of the outcome difference. RESULTS: The mean volume reduction was 96.9% in EA and 93.3% in RF ablation (n = 21 for each) (difference, 3.6%; lower bound of the one-sided 95% CI of the difference, 1.2%), thus demonstrating the noninferiority of EA to RF ablation. Two-sided 95% CI of the outcome difference was 0.7% to 6.5%, demonstrating significant superiority of EA to RF ablation. All patients demonstrated therapeutic success (P > .99). Mean symptom and cosmetic scores showed no significant difference in either group (P = .806 and P = .682, respectively). There were no major complications (P > .99). CONCLUSION: EA may be the first-line treatment modality for cystic thyroid nodules, which has comparable therapeutic efficacy to, but is less expensive than, RF ablation.

Image reporting and characterization system for ultrasound features of thyroid nodules: multicentric Korean retrospective study.

OBJECTIVE: The objective of this retrospective study was to develop and validate a simple diagnostic prediction model by using ultrasound (US) features of thyroid nodules obtained from multicenter retrospective data. MATERIALS AND METHODS: Patient data were collected from 20 different institutions and the data included 2000 thyroid nodules from 1796 patients. For developing a diagnostic prediction model to estimate the malignant risk of thyroid nodules using suspicious malignant US features, we developed a training model in a subset of 1402 nodules from 1260 patients. Several suspicious malignant US features were evaluated to create the prediction model using a scoring tool. The scores for such US features were estimated by calculating odds ratios, and the risk score of malignancy for each thyroid nodule was defined as the sum of these individual scores. Later, we verified the usefulness of developed scoring system by applying into the remaining 598 nodules from 536 patients. RESULTS: Among 2000 tumors, 1268 were benign and 732 were malignant. In our multiple regression analysis models, the following US features were statistically significant for malignant nodules when using the training data set: hypoechogenicity, marked hypoechogenicity, non-parallel orientation, microlobulated or spiculated margin, ill-defined margins, and microcalcifications. The malignancy rate was 7.3% in thyroid nodules that did not have suspicious-malignant features on US. Area under the receiver operating characteristic (ROC) curve was 0.867, which shows that the US risk score help predict thyroid malignancy well. In the test data set, the malignancy rates were 6.2% in thyroid nodules without malignant features on US. Area under the ROC curve of the test set was 0.872 when using the prediction model. CONCLUSION: The predictor model using suspicious malignant US features may be helpful in risk stratification of thyroid nodules.

Symptomatic nonfunctioning parathyroid cysts: role of simple aspiration and ethanol ablation.

OBJECTIVES: To evaluate the outcomes of simple aspiration and ethanol ablation in the management of symptomatic nonfunctioning parathyroid cyst (PC). METHODS: We performed simple aspirations for 12 PCs in 12 patients from March 1997 to June 2010. PC was diagnosed if the aspirated fluid was clear colorless and showed an elevated parathyroid hormone (PTH) level. Ethanol ablation (EA) was performed for recurrent PCs. Simple aspirations were performed using 23-gauge needles and EAs using 18-gauge needles with 99% ethanol under ultrasound (US) guidance. We evaluated cyst volume, cosmetic score, symptom score, and complications. RESULTS: Mean follow-up period of all patients was 19.2 ± 12.9 months (median, 15.0 months; range, 7-40 months). Simple aspiration was successful in four patients, and the mean volume reduction after simple aspiration was 98.2 ± 3.5% (range, 92.9-100%). In eight recurrent cases, EA resulted in a significant decrease in volume (P=0.012), as well as in cosmetic (P=0.011) and symptom (P=0.01) scores at last follow-up; however two cases of primary failure of EA was treated by repeat EA. No major complications occurred in any patient. CONCLUSIONS: For symptomatic nonfunctioning PCs, simple aspiration could be a first line procedure for diagnosis and treatment, while EA can be a subsequent treatment modality for recurrent cases.

Radiofrequency ablation of benign thyroid nodules and recurrent thyroid cancers: consensus statement and recommendations.

Thermal ablation using radiofrequency is a new, minimally invasive modality employed as an alternative to surgery in patients with benign thyroid nodules and recurrent thyroid cancers. The Task Force Committee of the Korean Society of Thyroid Radiology has developed recommendations for the optimal use of radiofrequency ablation for thyroid nodules. These recommendations are based on a comprehensive analysis of the current literature, the results of multicenter studies, and expert consensus.

Diagnostic accuracy of fine-needle aspiration versus core-needle biopsy for the diagnosis of thyroid malignancy in a clinical cohort.

OBJECTIVES: To retrospectively compare the accuracy of fine-needle aspiration (FNA) and core-needle biopsy (CNB) for the diagnosis of thyroid malignancy METHODS: We evaluated the results of FNA and CNB in 555 consecutive thyroid nodules with final diagnoses (malignancy 318, benign 237). All patients underwent FNA and CNB simultaneously for each nodule. We assessed the sensitivity, specificity and accuracy of FNA, CNB and FNA/CNB for the diagnosis of thyroid malignancy. RESULTS: The sensitivity of FNA, CNB and FNA/CNB for thyroid malignancy was 68.6%, 86.8% and 90.6%, specificity 100%, 99.2% and 99.2%, and accuracy 82.0%, 92.1% and 94.2%, respectively. The sensitivity and accuracy of CNB or FNA/CNB for thyroid malignancy were significantly higher than those of FNA (P < 0.001). Compared with CNB alone, FNA/CNB was more accurate for thyroid malignancy only in small nodules less than 1 cm (P < 0.001). CONCLUSIONS: Our clinical cohort data demonstrated that CNB was more accurate for the diagnosis of thyroid malignancy than FNA, and FNA/CNB was more accurate than CNB alone in small thyroid nodules. CNB will play a complementary role in optimal surgical decision-making and the management of thyroid nodules. KEY POINTS: • CNB was more accurate for the diagnosis of malignancy than FNA. • Combined FNA/CNB was more accurate than CNB alone in small thyroid nodules. • CNB should play at least a complementary role in managing thyroid nodules.