Can "no-touch" radiofrequency ablation for hepatocellular carcinoma improve local tumor control? Systematic review and meta-analysis.

OBJECTIVES: Percutaneous radiofrequency ablation (RFA) is one of the curative treatments for hepatocellular carcinoma (HCC), but local tumor progression (LTP) has been a main limitation of RFA. This study aims to evaluate the LTP of percutaneous no-touch RFA (NtRFA) for HCC ≤ 5 cm and compare with conventional RFA (intratumoral puncture) through a systematic review and meta-analysis. METHODS: MEDLINE, EMBASE, and Cochrane Library were searched for studies on percutaneous NtRFA for HCC ≤ 5 cm. The pooled proportions of the overall and cumulative incidence rates at 1, 2, and 3 years for LTP after NtRFA were assessed using a random-effects model. For studies comparing NtRFA with conventional RFA, relative risks (RR) and hazard ratios (HR) were meta-analytically pooled with LTP as the outcome. RESULTS: Twelve studies with 900 patients were included. The pooled overall rate of LTP after NtRFA was 6% (95% CI, 4-8%). The pooled 1-, 2-, and 3-year cumulative incidence rates of LTP were 3% (95% CI, 2-5%), 5% (95% CI, 3- 9%), and 8% (95% CI, 6-11%), respectively. Compared to conventional RFA, the pooled RR and HR of LTP were 0.26 (95% CI, 0.16-0.41) and 0.28 (95% CI, 0.11-0.70), respectively (both p < 0.01). Subgroup analysis including only randomized controlled studies also showed better local tumor control of NtRFA with HR of 0.13 (95% CI, 0.14-0.42). CONCLUSIONS: Percutaneous NtRFA is an effective treatment for HCC ≤ 5 cm with an overall LTP rate of 6% and provides lower LTP compared with conventional RFA. KEY POINTS: • The pooled 1-, 2-, and 3-year cumulative incidence rates of local tumor progression after no-touch radiofrequency ablation for HCC ≤ 5 cm were 3% (95% CI, 2-5%), 5% (95% CI, 3-9%), and 8% (95% CI, 6-11%). • No-touch radiofrequency ablation had significantly lower rates of local tumor progression compared to conventional radiofrequency ablation (hazard ratio, 0.28; 95% CI, 0.11-0.70; relative risk, 0.26; 95% CI, 0.16-0.41; p < 0.01, respectively).

Distribution Pattern of Atherosclerosis in the Abdomen and Lower Extremities and Its Association with Clinical and Hematological Factors.

PURPOSE: Abdominal arteries differ from the arteries located at the extremities in histological composition and clinical features. This study investigated the distributional pattern of atherosclerosis in arteries of the abdomen and lower extremities and its association with clinical and hematologic factors. PATIENTS AND METHODS: This retrospective study included 227 patients with atherosclerosis who underwent computed tomography angiography (CTA) of the abdomen and lower extremities. The distributional pattern of atherosclerosis was categorized into type 1 (suprainguinal elastic), type 2 (infrainguinal muscular), and type 3 (both arterial involvement). Chi-square tests, Mann-Whitney U-tests, and logistic regression analysis were used to investigate the data. RESULTS: Of the 227 patients, 132 (58%) had type 1 and 95 (42%) had type 3 atherosclerosis. None had type 2. Older age, heavier smoking, and higher levels of HbA1c and homocysteine were the significant risk factors for type 3 atherosclerosis (odds ratio: 1.076, 1.023, 1.426, and 1.130, respectively). Patients with type 3 showed significantly lower right and left ankle and toe brachial indices compared to type 1 (P: 0.029, 0.023, 0.003, and <0.001, respectively). CONCLUSION: In arteries of the abdomen and lower extremities, atherosclerosis may occur initially at suprainguinal elastic arteries. In addition, the significant risk factors for type 3 atherosclerosis may contribute to the development of atherosclerosis at infrainguinal muscular arteries and deteriorate the peripheral arterial circulation. Therefore, if atherosclerotic lesions are found at the suprainguinal elastic arteries on CTA, to prevent atherosclerosis at infrainguinal muscular arteries and subsequent peripheral arterial ischemic disease, cessation of smoking and control of blood glucose and homocysteine may be recommended, especially in elderly patients.

Non-strangulated adhesive small bowel obstruction: CT findings predicting outcome of conservative treatment.

OBJECTIVES: To clarify CT findings that predict outcome of conservative treatment in patients with non-strangulated adhesive small bowel obstruction (SBO). METHODS: Unenhanced and contrast-enhanced abdominopelvic CT studies in 189 patients with adhesive SBO who had initial conservative treatment were reviewed. The CT findings included transition zone, beak signs, maximum bowel diameter, bowel diameter ratio, decreased bowel wall enhancement, increased unenhanced bowel wall attenuation, anterior parietal adhesion, bowel wall thickening, closed-loop obstruction, small bowel feces sign, whirl sign, mesenteric haziness, mesenteric, peritoneal fluid, and submucosal edema. These findings were statistically compared according to the success or failure of treatment. RESULTS: Conservative treatment succeeded in 144 patients (76.2%) and failed in 45 patients (23.8%). At multivariate analysis, the lack of small bowel feces sign, focal, diffuse mesenteric haziness, and moderate amount of mesenteric fluid were independent findings predicting failure of conservative treatment, with odds ratios of 5.23, 5.5, 13.55, and 4.89, respectively. The presence of all significant findings showed a high specificity of 97.2% with positive likelihood ratio of 8.8. If CT scans showed none of the three significant findings, the negative predictive value was 97.6% and negative likelihood ratio was 0.08. CONCLUSIONS: The lack of small bowel feces sign, focal, diffuse mesenteric haziness, and moderate amount of mesenteric fluid are independent CT findings predicting the failure of conservative treatment in patients with non-strangulated adhesive SBO. The combination of all CT findings suggests the need for surgery; absence of two or all CT findings should suggest an attempt for conservative treatment. KEY POINTS: • To minimize delayed operation, it is important to identify non-strangulated adhesive small bowel obstruction patients in whom initial conservative treatment is likely to fail. • The lack of small bowel feces sign, the presence of mesenteric haziness, and a moderate amount of mesenteric fluid are independent factors predicting the failure of conservative treatment in patients with non-strangulated adhesive small bowel obstruction. • The combination of all three CT findings suggests the need for surgery; absence of two or all three CT findings should suggest an attempt for conservative treatment.

Intraobserver and interobserver reliability in sonographic size measurements of gallbladder polyps.

OBJECTIVES: To evaluate the intraobserver and interobserver reliability of gallbladder polyp measurements using transabdominal US and the factors that affect reliability. METHODS: From November 2017 to February 2018, two radiologists measured the maximum diameter of 91 gallbladder polyps using transabdominal US. Intraobserver and interobserver agreement were determined using 95% Bland-Altman limits of agreement and intraclass correlation coefficients (ICCs). The effects of image settings, polyp location, and polyp size were evaluated by comparing ICCs using z tests. RESULTS: The intraobserver agreement rates were 0.960 (95% confidence interval [CI], 0.939-0.973) for observer 1 and 0.962 (95% CI, 0.943-0.975) for observer 2. The ICCs between the two observers were 0.963 (95% CI, 0.926-0.979) for the first measurement and 0.973 (95% CI, 0.950-0.984) for the second measurement. The 95% limits of agreement on repeated measurements were 22.3-25.2% of the mean, and those between the two observers were 25.5-34.2% of the mean. ICCs for large polyps (≥ 5 mm) were significantly higher than those for small polyps (< 5 mm). There were no significant differences in the ICCs between image settings and polyp location. CONCLUSIONS: Polyp size measurements using transabdominal US are highly repeatable and reproducible. Polyp size significantly affects the reliability of measurement. Diameter changes of approximately less than 25% may fall within the measurement error; this should be considered while interpreting the change in size during follow-up US, especially for small polyps. KEY POINTS: • Gallbladder polyp size measurement using transabdominal US is highly repeatable and reproducible. • Diameter changes of approximately less than 25% should be interpreted carefully, especially in small polyps.

Canine pyoderma gangrenosum with recurring skin lesions of unknown origin and splenic involvement.

BACKGROUND: Reports of canine pyoderma gangrenosum (PG) are uncommon in the veterinary literature. Rarer still are cases describing dogs with both skin lesions and internal organ involvement. OBJECTIVE: To describe a case of canine PG with skin and internal organ involvement. ANIMALS: A client-owned dog. METHODS AND MATERIALS: Complete blood count, serum chemistry, C-reactive protein and SNAP cPL tests, and abdominal ultrasonography and fine-needle aspiration of the spleen were performed. RESULTS: The dog was treated with oral prednisolone and ciclosporin. After three months of therapy, ultrasonography revealed normalization of the spleen and resolution of skin lesions. CONCLUSION AND CLINICAL IMPORTANCE: Dogs with skin lesions compatible with PG should be screened carefully for internal organ involvement. Ciclosporin may be a useful treatment for the immediate and long-term management of canine PG.

Preclinical study of safety of Dendropanax morbifera Leveille leaf extract: General and genetic toxicology.

ETHNOPHARMACOLOGY RELEVANCE: Dendropanax morbifera Leveille (DM) has been used in traditional medicines for infectious and skin diseases, and dysmenorrhea. It exhibits a diverse therapeutic potential including anti-cancer, anti-thrombotic, anti-diabetic, anti-oxidant, and anti-inflammatory activities. AIM OF THE STUDY: Despite promising health benefits of DM, knowledge of its potential adverse effects is very limited. The current study focused on the investigation of subchronic toxicity and genotoxicity of extract obtained from DM according to the test guidelines published by the Organization for Economic Cooperation and Development. MATERIALS AND METHODS: We conducted a toxicological evaluation of DM extracts using 14-day repeated-dose toxicity study and 13-week repeated-dose toxicity study in Sprague-Dawley rats administered orally at doses of 500, 1000, or 2000 mg/kg/day. The clastogenicity of DM extract was also evaluated by in vitro chromosome aberration assay and in vivo micronucleus assay. RESULTS: Assessment of subchronic toxicity of DM extract by oral administration in rats revealed unremarkable treatment-related findings with respect to food/water consumption, body weight, mortality, urinalysis, hematology, serum biochemistry, necropsy, organ weight and histopathology at doses of 500, 1000, and 2000 mg/kg. Accordingly, the level of no-observed-adverse-effect for DM extract in 13-week subchronic toxicity study was considered to be 2000 mg/kg/day in rats. The data observed from in vitro chromosome aberration assay and in vivo micronucleus assay exclude any clastogenicity of DM extract. CONCLUSION: The results suggest that the oral consumption of DM extract has no adverse effects in humans and represents a safe traditional medicine.

In vitro and in vivo safety studies of cinnamon extract (Cinnamomum cassia) on general and genetic toxicology.

Cinnamomum cassia has been widely used as a natural product to treat diseases in Asia due to its diverse pharmacological functions including anti-inflammatory, anti-oxidant, anti-microbial, anti-diabetic, and anti-tumor effects. Despite its ethnomedicinal benefits, little information regarding its toxicity is currently available. The aim of this study was to evaluate its potential long-term toxicity and genotoxicity in compliance with test guidelines of the Organization for Economic Cooperation and Development. A 13-week repeat-dose oral toxicity study revealed that body weights of rats were normal after receiving cinnamon extract at up to 2000 mg/kg. High-dose intake of cinnamon extract (2000 mg/kg) showed potential nephrotoxicity and hepatotoxicity to both males and females as evidenced by obvious increases of kidney/liver weight along with a small but statistically elevation of total cholesterol level. Overall findings from genetic toxicity testing battery including Ames test, in vitro mammalian cell micronucleus assay, and in vivo bone marrow micronucleus assay indicated that cinnamon extract was not mutagenic or clastogenic. In conclusion, cinnamon extract may possess potential nephrotoxicity and hepatotoxicity at dose higher than its recommended daily safe dose. Further study is needed to clarify the mechanism involved in its induction of liver and kidney injury.

Enzymatic extract from Ecklonia cava: Acute and subchronic oral toxicity and genotoxicity studies.

Ecklonia cava (EC) is known to have antioxidant, anti-inflammatory, antidiabetic, and anticancer properties. Despite its wide use and beneficial properties, comprehensive toxicological information regarding EC extract is currently limited. Therefore, the purpose of this study was to investigate acute toxicity, subchronic toxicity, and genotoxicity of enzymatic EC extract according to test guidelines published by Organization for Economic Cooperation and Development. The acute oral LD50 values of this EC extract administered to rats and dogs were estimated to be more than 3000 mg/kg BW. In an oral 13-week toxicity study, changes in body weights of rats exposed to the EC extract up to 3000 mg/kg BW were found to be normal. In addition, repeated doses of EC extract failed to influence any systematic parameters of treatment-related toxic symptoms such as food/water consumption, mortality, urinalysis, hematology, serum biochemistry, organ weight, or histopathology. These results indicated that the no-observed-adverse-effect level for the EC extract was 3000 mg/kg/day for male and female rats. Data obtained from Ames test, chromosome aberration assay, and micronucleus assay indicated that EC extract was not mutagenic or clastogenic. Taken together, these results support the safety of enzymatic EC extract as a potential therapeutic for human consumption against various diseases.

Absence of subchronic oral toxicity and genotoxicity of rice koji with Aspergillus terreus.

Koji products have been considered as an effective fermented food consumed in East Asia with many health benefits. Particularly, rice koji with Aspergillus terreus (RAT) has been reported to be able to prevent hyperlipidemia and hepatic steatosis through regulating cholesterol synthesis. Despite its biological activities, there is a lack of comprehensive information to give an assurance of its safety. Therefore, the objective of this study was to perform a series of toxicological studies (repeated dose oral toxicity and genotoxicity) according to test guidelines published by the Organization for Economic Cooperation and Development. Along with acute toxicity study using rats and beagle dogs, a 13-week toxicity study revealed no clear RAT-related toxic changes, including body weight, mortality, hematology, serum biochemistry, organ weight, and histopathology after oral administration at doses of 500, 1000, and 2000 mg/kg BW. The no-observed-adverse-effect level of RAT was considered to be more than 2000 mg/kg BW/day in rats of both genders. In addition, potential genotoxicity was evaluated using a standard battery of tests (Ames test, chromosome aberration assay, and micronucleus assay) which revealed that RAT showed no genotoxicity. Accordingly, these results suggest that RAT is a safe and non-toxic functional food for human consumption at proper dose.

A comprehensive study on in vitro and in vivo toxicological evaluation of Artemisia capillaris.

Artemisia capillaris (AC) has been used as an alternative therapy in obesity, atopic dermatitis, and liver diseases through several biological activity including anti-steatotic, antioxidant, and anti-inflammatory activities. Despite its ethnomedicinal benefits, no sufficient background information is available about the long-term safety and genotoxicity of the AC extract. Therefore, the present study was carried out to investigate the 13-week subchronic toxicity and genotoxicity of the AC extract according to the test guidelines published by the Organization for Economic Cooperation and Development. In the 13-week toxicity study using doses of 25, 74, 222, 667, and 2000 mg/kg body weight, oral administration of the AC extract in male and female rats did not result in any significant adverse effects in food/water consumption, body weight, mortality, hematology, serum biochemistry, organ weight and histopathology. Accordingly, the no-observed-adverse-effect level in rats of both genders was established for the AC extract at 2000 mg/kg/day, the highest dose level tested. In addition, the AC extract was not genotoxic in a battery of tests including Ames test, in vitro chromosome aberration assay and in vivo micronucleus assay. In conclusion, we demonstrated that the AC extract is considered as a safe traditional medicine for human consumption.

Comparison of T2-weighted imaging, diffusion-weighted imaging and contrast-enhanced T1-weighted MR imaging for evaluating perianal fistulas.

PURPOSE: To compare the lesion conspicuity and diagnostic performance of three imaging data sets (T2WI, combined T2WI and DWI [combined DWI], contrast-enhanced (CE)-T1WI) in assessing perianal fistulas. METHODS: Two radiologists with 7 and 15years of experience assessed 28 fistulas from 24 patients in each image set. RESULTS: The lesion conspicuity was improved for only one reader after reading the combined DWI (P=0.0039) and CE-T1WI (P=0.0215). The accuracy was stationary for fistula type (reader 1, all 93%; reader 2, all 89%) or for direction of internal opening (96% for all sets; 92% for CE-T1WI). CONCLUSION: Although combined DWI and CE-T1WI might improve fistula conspicuity, they showed comparable diagnostic performance to T2WI.

Who are happy survivors? Physical, psychosocial, and spiritual factors associated with happiness of breast cancer survivors during the transition from cancer patient to survivor.

OBJECTIVE: This study aims to evaluate physical, psychosocial, and spiritual factors associated with happiness in breast cancer survivors during the reentry period. METHODS: It is a cross-sectional study with 283 nonmetastatic breast cancer survivors who completed treatment within 1 year. We included survivors who completed questionnaires on happiness and health-related quality of life (QoL) 2 years after cancer diagnosis. Happiness and QoL was measured using the Subjective Happiness Scale and EORTC QLQ-C30, respectively. Multivariable logistic regression was used to find factors associated with happiness. RESULTS: The mean age of the study participants was 48.5 ± 7.8 years. Among the 283 survivors, 14.5%, 43.8%, 32.5%, and 2.1% reported being "very happy," "happy," "neutral," and "not happy at all," respectively. Happy survivors reported a better general health status and QoL (67.6 vs 49.6; P < .01), and fewer symptoms compared to unhappy survivors. Happy survivors were more likely to feel certain about the future (27.2% vs 11.9%, P < .01), have a strong purpose in life (22.4% vs 9.3%, P < .01), and feel hopeful (36.4% vs 8.5%, P < .01) compared to unhappy survivors. In a multivariate model, having purpose (OR = 2.50, 95% CI 1.42-4.40) and hope (OR = 4.07, 95% CI 2.23-7.45) in life were found to be associated with happiness. CONCLUSIONS: During the reentry period, breast cancer survivors who are hopeful and have a clear purpose in life are more likely to be happy than those who are not. Setting proper life goals might be beneficial to help breast cancer survivors who experience persistent QoL issues.

Comparison of Model-Based Iterative Reconstruction, Adaptive Statistical Iterative Reconstruction, and Filtered Back Projection for Detecting Hepatic Metastases on Submillisievert Low-Dose Computed Tomography.

OBJECTIVE: The aim of the study was to compare the diagnostic performance of model-based iterative reconstruction (MBIR), adaptive statistical iterative reconstruction (ASIR), and filtered back projection (FBP) on submillisievert low-dose computed tomography (LDCT) for detecting hepatic metastases. METHODS: Thirty-eight patients having hepatic metastases underwent abdomen CT. Computed tomography protocol consisted of routine standard-dose portal venous phase scan (120 kVp) and 90-second delayed low-dose scan (80 kVp). The LDCT images were reconstructed with FBP, ASIR, and MBIR, respectively. Two readers recorded the number of hepatic metastases on each image set. RESULTS: A total of 105 metastatic lesions were analyzed. For reader 1, sensitivity for detecting metastases was stationary between FBP (49%) and ASIR (52%, P = 0.0697); however, sensitivity increased in MBIR (66%, P = 0.0035). For reader 2, it was stationary for all the following sets: FBP (65%), ASIR (68%), and MBIR (67%, P > 0.05). CONCLUSIONS: The MBIR and ASIR showed a limited sensitivity for detecting hepatic metastases in submillisievert LDCT.

Exploration and comparison of in vitro eye irritation tests with the ISO standard in vivo rabbit test for the evaluation of the ocular irritancy of contact lenses.

In an effort to explore the use of alternative methods to animal testing for the evaluation of the ocular irritancy of medical devices, we evaluated representative contact lenses with the bovine corneal opacity and permeability test (BCOP) and an in vitro eye irritation test using the three-dimensionally-reconstructed human corneal epithelium (RhCE) models, EpiOcular™ and MCTT HCE™. In addition, we compared the obtained results with the ISO standard in vivo rabbit eye irritation test (ISO10993-10). Along with the positive controls (benzalkonium chloride, BAK, 0.02, 0.2, and 1%), the extracts of 4 representative contact lenses (soft, disposable, hard, and colored lenses) and 2 reference lenses (dye-eluting and BAK-coated lenses) were tested. All the lenses, except for the BAK-coated lens, were determined non-irritants in all test methods, while the positive controls yielded relevant results. More importantly, BCOP, EpiOcular™, and MCTT HCE™ yielded a consistent decision for all the tested samples, with the exception of 0.2% BAK in BCOP, for which no prediction could be made. Overall, all the in vitro tests correlated well with the in vivo rabbit eye irritation test, and furthermore, the combination of in vitro tests as a tiered testing strategy was able to produce results similar to those seen in vivo. These observations suggest that such methods can be used as alternative assays to replace the conventional in vivo test method in the evaluation of the ocular irritancy of ophthalmic medical devices, although further study is necessary.

(NHC)Cu-Catalyzed Mild C-H Amidation of (Hetero)arenes with Deprotectable Carbamates: Scope and Mechanistic Studies.

Primary arylamines are an important unit broadly found in synthetic, biological, and materials science. Herein we describe the development of a (NHC)Cu system that mediates a direct C-H amidation of (hetero)arenes by using N-chlorocarbamates or their sodio derivatives as the practical amino sources. A facile stoichiometric reaction of reactive copper-aryl intermediates with the amidating reagent led us to isolate key copper arylcarbamate species with the formation of a C-N bond. The use of (t)BuONa base made this transformation catalytic under mild conditions. The present (NHC)Cu-catalyzed C-H amidation works efficiently and selectively on a large scale over a range of arenes including polyfluorobenzenes, azoles, and quinoline N-oxides. Deprotection of the newly installed carbamate groups such as Boc and Cbz was readily performed to afford the corresponding primary arylamines.

Role of Real-Time Elastography in the Evaluation of Cervical Lymph Nodes in Patients with Kikuchi Disease.

The purpose of this study was to compare the use of conventional ultrasound (US) and real-time elastography (RTE) in Kikuchi disease (KD, n = 48) and malignant cervical lymphadenopathy (n = 100) and to evaluate the role of RTE in patients suspected of having KD. In univariate analysis, conventional US revealed each benign feature more frequently in KD than in malignant lymphadenopathy (p < 0.05). However, a considerable number of cases (29, 60.4%) of KD were assessed as malignant with US. KD was assessed as benign by RTE more frequently than malignant lymphadenopathy (37 [77.1%] vs. 37 [37.0%], p < 0.001). In multivariate analysis, perinodal hyper-echogenicity was predictive of KD (odds ratio: 67.25, confidence interval: 10.95-413.04, p < 0.001). There was a tendency for KD to be assessed as malignant with conventional US, but benign with RTE. RTE can help to avoid unnecessary biopsy in patients suspected of having KD on the basis of conventional US.

Diffusion-weighted imaging for evaluating lymph node eradication after neoadjuvant chemoradiation therapy in locally advanced rectal cancer.

BACKGROUND: As lymph node (LN) eradication is the prerequisite for clinical surveillance or local excision for patients who have achieved a complete response after preoperative chemoradiation therapy (CRT), the radiological evaluation of LN eradication is important. PURPOSE: To evaluate the added value of diffusion-weighted imaging (DWI) in the evaluation of LN eradication after CRT in patients with locally advanced rectal cancer (LARC). MATERIAL AND METHODS: Ninety-five consecutive patients (64 men, 31 women; mean age, 59 years; range, 32-82 years) who underwent pre- and post-CRT 1.5-T MRI with DWI (b = 0, 1000 s/mm(2)) were enrolled. To evaluate the added value of DWI in the evaluation of LN eradication after CRT, two radiologists first independently read the pre- and post-CRT T2-weighted (T2W) images and then read the combined T2W imaging set and the pre- and post-CRT DWIs with a 4-week interval. The radiologists recorded their confidence scores for LN eradication using a 5-point scale on a per-patient basis. The diagnostic performances were compared between the two reading sessions for each reader with pair-wise comparisons of receiver-operating characteristic curves. Histopathological reports served as the reference standards for LN eradication. RESULTS: The study population consisted of an LN-eradicated group (n = 66) and a non-eradicated group (n = 29). The diagnostic performances did not significantly differ between the two reading sessions for the two readers (AUCs for reader 1, 0.770 and 0.774, P = 0.8155; for reader 2, 0.794 and 0.798, P = 0.8588). CONCLUSION: Adding DWI to T2W imaging provided no additional diagnostic benefit for the evaluation of LN eradication following CRT in patients with LARC.

Added value of morphologic characteristics on diffusion-weighted images for characterizing lymph nodes in primary rectal cancer.

To evaluate the added value of the morphologic features of lymph nodes (LNs) on diffusion-weighted images (DWI), an interval reading was performed for the T2-weighted images (T2WI) and the combined image set (T2WI and DWI) using extracted imaging characteristics from 54 metastatic and 172 benign LNs in 44 patients with primary rectal cancer. The specificity and accuracy increased after adding DWI to T2WI for both readers (specificity: from 59% to 73% and from 41% to 68% for readers 1 and 2, respectively; accuracy: from 58% to 68% and from 44% to 64% for readers 1 and 2, respectively, P<.0001).

Gray-scale and color Doppler sonographic features of complex fibroadenomas of the breast.

PURPOSE: To investigate gray-scale and color Doppler sonographic (US) features of complex fibroadenoma (FA), according to the Breast Imaging-Reporting and Data System (BI-RADS) lexicon. METHODS: From 2010 through 2013, 586 women with FAs were seen; 101 (17%) of those lesions were diagnosed as complex FAs on percutaneous needle biopsy or surgery. Among the patients with complex FAs, 67 who had US examination results available were included in this study. In addition, the results from 98 women who had simple FAs were included as controls. US features were retrospectively analyzed by two breast radiologists in consensus for shape, margin, echogenicity, posterior acoustic pattern, boundary, orientation, and associated findings. They also reassessed the BI-RADS category for FAs. Color Doppler US examination results were classified according to the amount of vascularity as absent, moderate, or marked. RESULTS: Complex FA were larger than simple FAs were (14.5 cm versus 12.1 cm, p > 0.05). On univariate analysis, a round to irregular shape, an uncircumscribed margin, the presence of associated findings, and BI-RADS categorization as 4a and 4b were more frequently revealed in complex than in simple FAs (p < 0.05). Multivariate analysis revealed that the tumor margin was a predictive factor for complex FA (odds ratio: 6.08; 95% confidence interval: 1.14-32.49, p < 0.05). On color Doppler US, the complex FAs had higher degrees of vascularity than simple FA (p < 0.05). CONCLUSIONS: Complex FAs, in comparison with simple FAs, tend to have more aggressive features and to be in higher BI-RADS categories on US examination.

Pre-clinical in vitro and in vivo safety evaluation of Cimicifuga heracleifolia.

The rhizomes of Cimicifuga species, including Cimicifuga heracleifolia (CH), have been widely used as antipyretic, analgesic, and anti-inflammatory agents in oriental countries. However, information regarding its toxicity, especially long-term toxicity and genotoxicity, is limited. Therefore, we performed the subchronic toxicity and genotoxicity assays of the CH extract in accordance with the test guidelines published by the Organization for Economic Cooperation and Development. In a 13-week repeat-dose oral toxicity study, the CH extract did not influence body weight, food/water consumption, mortality, clinical signs, and urinalysis throughout the study. Noteworthy, the CH extract groups exhibited increased liver weights along with serum alanine transaminase activity rise at doses of 667 and 2000 mg/kg in females. No-observed-adverse-effect-level of the CH extract administered orally was concluded to be 2000 mg/kg body weight/day for male rats and 222 mg/kg body weight/day for female rats. The CH extract did not exert a mutagenic or clastogenic effect in Ames test, in vitro chromosome aberration assay and in vivo micronucleus assay. Overall findings of the subchronic toxicity study indicate for the first time that the CH extract may possess hepatotoxic potential in female rats, suggesting that further mechanistic studies should be performed to have more conclusive results on hepatotoxic potential of the CH extract.