Targetoid hepatic observations on gadoxetic acid-enhanced MRI using LI-RADS version 2018: emphasis on hepatocellular carcinomas assigned to the LR-M category.

AIM: To determine useful imaging features for differentiating hepatocellular carcinoma (HCC) categorised as LR-M from non-HCC malignancies in using the Liver Imaging-Reporting and Data System (LI-RADS) version 2018 on gadoxetic acid-enhanced magnetic resonance imaging (MRI). MATERIALS AND METHODS: Patients at high-risk for HCC with surgically confirmed HCCs (n=131) and non-HCC malignancies (n=90) and who had undergone gadoxetic acid-enhanced MRI were included. LI-RADS categories were assigned to identify hepatic observations defined as LR-M by two radiologists. Major and ancillary imaging features of hepatic observation with targetoid appearance including intratumoural septa were compared between HCCs and non-HCC malignancies. A classification tree analysis (CTA) was applied to differentiate high-risk HCCs from non-HCC malignancies in the LR-M category. RESULTS: A total of 36 HCCs (27.5%) and 70 non-HCC malignancies (77.8%) were assigned as LR-M. An enhancing capsule (p=0.0293), blood products in the mass (p=0.0393), non-targetoid restriction (p=0.018), and a septum (p=0.0053) were significantly predictive of HCC. On CTA, the presence of a septum was an initial predictor for a high probability of HCC followed by non-targetoid restriction. The CTA model has a sensitivity of 63.9%, specificity of 90%, and accuracy of 81.1% for differentiating HCC assigned LR-M from non-HCC malignancy. CONCLUSION: A considerable proportion of HCCs could have been categorised as LR-M as they had a targetoid appearance on gadoxetic acid-enhanced MRI. An intratumoural septum and non-targetoid restriction as well as enhancing capsule and blood products in the mass may be useful for differentiating HCC assigned to LR-M from non-HCC malignancy on gadoxetic acid-enhanced MRI.

Comparison of the diagnostic performance of the 2017 and 2018 versions of LI-RADS for hepatocellular carcinoma on gadoxetic acid enhanced MRI.

AIM: To compare the diagnostic performance of the 2017 (v2017) and 2018 versions (v2018) of the Liver Imaging-Reporting and Data System (LI-RADS) for hepatocellular carcinoma (HCC) using gadoxetic acid-enhanced magnetic resonance imaging (Gd-EOB-MRI) and to evaluate the effect in v2018. MATERIALS AND METHODS: Treatment-naive patients at high-risk for HCC who underwent Gd-EOB-MRI were included. The LI-RADS categories were assigned according to v2017 and v2018. The diagnostic performances were compared between v2017 and v2018 according to the size and combination of imaging features. RESULTS: A total of 117 patients with 137 observations were identified, including 89 HCCs; 76.2% (64/84) of observations with threshold growth were re-classified as subthreshold growth when using v2018 instead of v2017. The final categories changed in nine (14%) cases. For the combination of LR-5/LR-5V, there were no significant differences in sensitivity and specificity between the two versions (sensitivity, 64% versus 58.4%; specificity, 87.5% versus 85.4%; all p>0.05). For the combination of LR-4 and LR-5/5V, the diagnostic performance of v2018 was inferior to that of v2017 when considering only major features (accuracy, 86.1% versus 80.3%, respectively; p=0.013), particularly in observations measuring 10-20 mm, but was comparable after adding the ancillary features (accuracy, 86.9% versus 86.1%, respectively; p=1.00). CONCLUSION: In LI-RADS v2018, although a considerable number of observations re-classified subthreshold growth, changes in the assigned categories were insignificant; overall diagnostic performance was comparable to that of v2017, but v2018 might emphasise the value of ancillary features in combination with major features for determining the probability of HCC.

Factors affecting willingness to get assessed and treated for osteoporosis.

Individuals with poor knowledge of osteoporosis and lower socioeconomic status, including being single and having a lower level of annual income, are less likely to be assessed or treated for osteoporosis. Individuals with particular osteoporosis risk factors such as smokers and heavy drinkers are overlooked for diagnosis. Further study is needed to identify and address the existing barriers and to promote osteoporosis management for women with these risk factors. INTRODUCTION: Despite the negative health consequences of osteoporosis and the availability of effective treatment, a pervasive and persistent prevention care gap for osteoporosis remains present throughout the world. We attempted to identify the factors affecting the willingness of patients to either undergo or avoid assessment and treatment for osteoporosis. METHODS: A nationwide online survey was conducted in 926 Korean women over age 50. The survey included questions addressing three domains: (1) clinical and socio-demographic characteristics, (2) questions concerning the reasons for undergoing or avoiding osteoporosis assessment or treatment, and (3) knowledge of osteoporosis as measured using the modified Korean version of Facts on Osteoporosis Quiz. The assessed and non-assessed participants were compared in terms of their clinical and socioeconomic statuses, reasons for undergoing or avoiding osteoporosis management, and levels of knowledge of osteoporosis. RESULTS: The highest-ranked reason for undergoing osteoporosis assessment was fear of osteoporotic fracture, while the highest-ranked reason for avoiding osteoporosis assessment was not feeling a need to get tested for osteoporosis. Participants who sought assessment for osteoporosis were older and more likely to be married, and had greater knowledge of osteoporosis than those who did not seek assessment. The two groups were found to be similar in terms of tobacco use and daily alcohol use. Patients who had been diagnosed with osteoporosis but either did not initiate or discontinued osteoporosis treatment within 1 year were younger and had lower levels of annual income than those who began and continued treatment. CONCLUSION: Individuals with poor knowledge of osteoporosis and those of lower socioeconomic status, including those who were single and had a lower level of annual income, were less likely to be assessed and treated for osteoporosis. Individuals with particular osteoporosis risk factors such as smokers and heavy drinkers are overlooked for diagnosis. Further study is needed to identify and address the existing barriers and to promote osteoporosis management for women with these risk factors.

A novel indeno[1,2-b]pyridinone derivative, a DNA intercalative human topoisomerase IIα catalytic inhibitor, for caspase 3-independent anticancer activity.

A novel 2-(furan-2-yl)-4-(pyridin-2-yl)-5H-indeno[1,2-b]pyridin-5-one (TI-1-190) was synthesized using a simple microwave-assisted method and its mode of action was systematically characterized. It is a DNA intercalative human topoisomerase IIα catalytic inhibitor with much stronger activity and less DNA toxicity than etoposide, a topoisomerase II poison. TI-1-190 displays caspase 3-independent anticancer activity, unlike etoposide.

Mandibular stability using sliding or conventional four-hole plates for fixation after bilateral sagittal split ramus osteotomy for mandibular setback.

Our aim was to compare the postoperative stability of the mandible when two different fixation methods had been used after bilateral sagittal split ramus osteotomy (BSSRO) for mandibular setback. The study included 23 patients who had two-jaw BSSRO mandibular setback at the Department of Oromaxillofacial Surgery, Korea University Guro Hospital, between January 2011 and June 2014. The first group (four-hole (control) group, n=13) comprised patients whose bony segments were fixed with conventional four-hole plates, and the second (sliding plate (experimental) group, n=10) included patients whose bone segments were fixed with sliding plates. Lateral cephalograms were taken and analysed at three time points: preoperatively (T1), and one week (T2), and 1year (T3) postoperatively. The Mann-Whitney U test was used to compare the postoperative stability of the mandible in each group. There were no significant differences between the two groups in changes in the horizontal and vertical positions of point B and pogonion postoperatively, nor were there any significant differences between them in ramal inclination and inclination of the SN plane with point B at the given time points (p=>0.05 in surgical changes in the mandible immediately after surgery and 0.397, 0.616, 0.082, 0.951, 0.901, 0.476 in postoperative changes in the mandible 1 week to 1 year after surgery). Like the conventional four-hole plate, the sliding plate can also be used to achieve stability in the fixation of mandibular bone segments after BSSRO.

Clinical benefit of nomogram for predicting positive resection margins in breast conserving surgery.

PURPOSE: Previously, we reported a nomogram for the prediction of positive resection margin (RM) after breast conserving surgery (BCS). This study was conducted to evaluate the clinical usefulness of the nomogram. METHODS: Prospective patients who underwent operations using the nomogram between July 2012 and August 2013 (nomogram group; N = 260) were compared with past control patients who underwent operations between July 2010 and October 2011 and underwent frozen section biopsy (FSB) without use of the nomogram (N = 266). In the nomogram group, an intraoperative assessment of RM using FSB was only performed when the nomogram score was higher than predefined cut-off (>80). In addition, we conducted retrospective analysis of additional 181 patients who received BCS in another institute (Kyoto University Hospital). These patients did not undergo FSBs for RMs. RESULTS: Of 260 patients, 161 (61.9%) presented low nomogram scores and avoided FSB. The surgical decision to use the nomogram did not significantly increase reoperation rate due to positive RM compared with the control FSB group (4.6% vs. 3.8%, p = 0.47). The surgery time was significantly reduced by 18.1% (mean 14.7 min) in nomogram group (p < 0.001). Of 99 nomogram high-score patients, 14 presented with positive RM on FSB and 11 of them avoided reoperation. In the Kyoto cohort, the reoperation rate was significantly lower in low-score patients than in high-score patients (2.7% vs. 11.4%, p < 0.001). CONCLUSIONS: We showed that our nomogram is useful to reduce FSBs without increasing reoperation rate for surgeons who perform routine FSBs. For most surgeons, it can give useful information about the possibility of tumor-positive RMs.

Identifying the potential long-term survivors among breast cancer patients with distant metastasis.

BACKGROUND: We aimed to develop a prediction model to identify long-term survivors after developing distant metastasis from breast cancer. PATIENTS AND METHODS: From the institution's database, we collected data of 547 patients who developed distant metastasis during their follow-ups. We developed a model that predicts the post-metastasis overall survival (PMOS) based on the clinicopathologic factors of the primary tumors and the characteristics of the distant metastasis. For validation, the survival data of 254 patients from four independent institutions were used. RESULTS: The median duration of the PMOS was 31.0 months. The characteristics of the initial primary tumor, such as tumor stage, hormone receptor status, and Ki-67 expression level, and the characteristics of the distant metastasis presentation including the duration of disease-free interval, the site of metastasis, and the presence of metastasis-related symptoms were independent prognostic factors determining the PMOS. The association between tumor stage and the PMOS was only seen in tumors with early relapses. The PMOS score, which was developed based on the above six factors, successfully identified patients with superior survival after metastasis. The median PMOS for patients with a PMOS score of <2 and for patients with a PMOS score of >5 were 71.0 and 12 months, respectively. The clinical significance of the PMOS score was further validated using independent multicenter datasets. CONCLUSIONS: We have developed a novel prediction model that can classify breast cancer patients with distant metastasis according to their survival after metastasis. Our model can be a valuable tool to identify long-term survivors who can be potential candidates for more intensive multidisciplinary approaches. Furthermore, our model can provide a more reliable survival information for both physicians and patients during their informed decision-making process.

Correlation of antibiotic prophylaxis and difficulty of extraction with postoperative inflammatory complications in the lower third molar surgery.

Our aim was to investigate the correlation among antibiotic prophylaxis, difficulty of extraction, and postoperative complications in the removal of lower 3rd molars. A total of 1222 such extractions in 890 patients between January 2010 and January 2012 were analysed retrospectively. The difficulty of extraction measured by Pederson's index, antibiotic prophylaxis with cefditoren, and postoperative complications were recorded. The difficulty of extraction was significantly associated with postoperative complications (p=0.03). There were no significant associations between antibiotic prophylaxis and postoperative complications in groups of equal difficulty ("easy" group (class I) p=1.00; "moderate" group (class II) p=1.00; and "difficult" group (class III) p=0.65). There was a small but insignificant increase in the number of dry sockets and infections in class III cases. In conclusion, this study provides further evidence that antibiotic prophylaxis for the prevention of postoperative inflammatory complications is unnecessary for extraction of 3rd molars.

RETRACTED: Different bone mineral density in cervical and endometrial cancer.

Objectives Patients with cervical cancer have lower bone mass than women without cancer, whereas women with endometrial cancer have higher bone mineral density (BMD) than control subjects, possibly due to the prevalence of high body-fat mass. The aim of this study was to compare BMD in patients with cervical cancer, endometrial cancer and controls. Methods We analyzed and compared spinal and femoral BMD in 130 patients with cervical cancer, 68 with endometrial cancer, and 140 age-matched menopausal female control subjects. We also compared serum calcium, phosphorus, total alkaline phosphatase, osteocalcin, and urinary deoxypyridinoline levels. Results Compared with the control group, T-scores for some lumbar vertebrae (L4), the femoral neck, and Ward's triangle were lower in patients with cervical cancer, whereas only L4 T-scores were significantly lower in patients with endometrial cancer. Deoxypyridinoline levels were significantly lower in women with endometrial cancer (p < 0.002) than in women with cervical cancer, but no other biochemical variables differed among groups. Conclusions Cervical cancer was associated with lower BMD, especially in femoral BMD, and may be a risk factor for secondary osteoporosis. However, endometrial cancer generally seemed to have no damaging effect on bone except at L4. A further larger follow-up study in more populations is required to clarify these findings.

Identification of biomarkers for preterm delivery in mid-trimester amniotic fluid.

OBJECTIVE: We investigated whether the level of vascular endothelial growth factor (VEGF) and inflammatory markers in mid-trimester amniotic fluid have predictive value for spontaneous preterm birth in singleton pregnancy. METHOD: Our subjects were 72 pregnant women who were undertaken with amniocentesis from 16 to 19 weeks of gestation. 36 cases were women with preterm delivery, and other 36 cases were matched women with full-term delivery. Stored amniotic fluid was investigated after the delivery. The levels of matrix metalloproteinases-8 (MMP-8), interleukin-6 (IL-6), C-reactive protein (CRP), and VEGF were measured by enzyme-linked immunosorbent assay (ELISA) and Western blot. RESULTS: The levels of MMP-8 and IL-6 in preterm group were significantly higher than control group (5.76 ± 1.53 ng/ml vs 4.89 ± 1.77 ng/ml and 170.54 ± 55.69 pg/ml vs 141.92 ± 57.21 pg/ml, respectively) (p < 0.05). In terms of VEGF, the levels were elevated in preterm group (30.76 ± 4.06 pg/ml vs 22.36 ± 7.03 pg/ml) (p < 0.05). CONCLUSION: This study suggests that elevated levels of IL-6 and MMP-8 in amniotic fluid at mid-trimester are predictive of preterm delivery, and that VEGF which is representative of angiogenesis can be a new and useful predictor of preterm delivery.

Hypopigmented keratosis: is it a hyperkeratotic variant of idiopathic guttate hypomelanosis?

We have occasionally seen patients with acquired well-demarcated, scattered hypopigmented papules. In this study, we investigated the clinical and histopathological characteristics of such lesions. Biopsies were taken from the lesional and perilesional normal skin from 10 of 13 patients, which were compared with 10 idiopathic guttate hypomelanosis (IGH) samples. The lesions were scattered, well-circumscribed, flat-topped, hypopigmented papules. There was no age or gender predilection. Marked hyperkeratosis was present, with clear-cut margins distinguishable from the adjacent normal epidermis. The melanin content was decreased in the lesional epidermis, which was associated with a decrease in expression of melanogenesis-associated markers such as tyrosinase and NKI/beteb (marker of gp100) and reduction in the number of melanocytes. These histological findings were similar to those of IGH except for the additional finding of a thicker stratum corneum in this case seem to represent a 'hyperkeratotic' variant of IGH.

Differential effects of colchicine in blood mononuclear cells of patients with Behçet disease in relation to colchicine responsiveness.

BACKGROUND: Colchicine, a first-line drug for the treatment of Behçet disease (BD), inhibits caspase-1 activation and inflammatory cytokine production. However, therapeutic and preventive effects are not observed in some patients with BD. OBJECTIVE: To explore whether the effects of colchicine on proinflammatory cytokine expression and cell death in peripheral blood mononuclear cells (PBMCs) from patients with BD are associated with responsiveness to colchicine. METHODS: Activation of caspase-1, transcription and secretion of interleukin (IL)-1ß, tumour necrosis factor (TNF)-α and IL-6, and release of lactate dehydrogenase (LDH) in PBMCs isolated from healthy controls and patients with BD were analysed in the presence or absence of colchicine and upon stimulation with lipopolysaccharide (LPS) plus a caspase-1 activator. RESULTS: Colchicine significantly modulated monosodium urate-induced IL-1ß release, LPS-stimulated LDH release, and basal transcript levels of TNF-α and IL-6 in healthy controls and BD colchicine responders, but not in BD colchicine nonresponders. Notably, colchicine showed contrasting effects on LPS-stimulated IL-1ß transcription, i.e. it increased in responders but decreased in nonresponders. Also, higher levels of TNF-α and IL-6 transcripts were observed in LPS-stimulated PBMCs from nonresponders compared with responders. CONCLUSIONS: This study shows different effects of colchicine on PBMCs from patients with BD according to their responsiveness to colchicine. Predicting responsiveness to colchicine in patients with BD may, therefore, be possible by examining alterations in IL-1ß transcript levels in LPS-stimulated PBMCs after colchicine treatment.

Acquired bilateral melanosis of the neck in perimenopausal women.

BACKGROUND: Acquired bilateral patchy or mottled pigmentation of the neck has occasionally been observed. OBJECTIVE: To investigate the clinical and histopathological characteristics of this pigmentation. METHODS: Fourteen patients were included in the study. Patch and photopatch tests, and laboratory tests including serum hormonal evaluation were performed. Skin biopsies were performed on lesional skin and perilesional normal skin. RESULTS: All the patients were women and all were perimenopausal. The lesions were characterized by bilateral, symmetrical, brown-to-grey patchy or mottled pigmentation on the lateral neck. There were positive photopatch results in some cases, but their relevance was doubtful. All laboratory findings were within the normal ranges. The histological findings showed marked accumulation of pigment in the dermis with perivascular lymphocytic infiltration. A significantly higher expression of melanogenesis-associated proteins and an increased number of melanocytes were observed in the epidermis of the lesional skin. The melanin-bearing cells in the dermis were stained with factor XIIIa or CD68, but the majority of these cells were identified as factor XIIIa+ dermal dendrocytes. Some brown pigments were mixed with light brown or golden brown pigment that was positive in iron staining. CONCLUSIONS: These cases seem to represent a continuum of Riehl melanosis. However, the principal distribution of the pigmentation is a distinguishing feature. Any consistent predisposing factors were not established, but there may be a role for subclinical injury or inflammation as possible causative factors for development of the pigmentation.

AKR1B10 is associated with smoking and smoking-related non-small-cell lung cancer.

This prospective study explored the relationship between expression of AKR1B10 mRNA and various clinical parameters in non-small-cell lung cancer (NSCLC) in terms of its validation as a marker for NSCLC. Tumour tissue samples were collected from 229 patients with NSCLC. Tissue samples from adjacent non-malignant lung tissue (> 5 cm from the tumour) of 89 of these patients and samples from 20 patients with benign lung disease were used as controls. Quantitative reverse transcription- polymerase chain reaction showed significantly higher levels of AKR1B10 mRNA expression in NSCLC tumour tissue than in adjacent non-malignant lung tissue and benign lung tissue. Statistically significant factors for AKR1B10 mRNA over-expression were found to be male gender, smoking, squamous cell carcinoma and moderate or poor cell differentiation. It is concluded that AKR1B10 seems to have potential as a prognostic marker for NSCLC and warrants further investigation.

Immunohistochemical expression of matrix metalloproteinases in the granulomatous rosacea compared with the non-granulomatous rosacea.

BACKGROUND: There is a granulomatous variant which is recognized in the rosacea spectrum. However, the pathogenesis of granuloma formation in rosacea has not been clearly demonstrated. Matrix metalloproteinases (MMPs) are required for recruitment of inflammatory cells and for tissue remodelling, making way for the development of well-organized granuloma. OBJECTIVE: The aim of this study was to investigate the expression of transforming growth factor (TGF)-ß, TGF-ß type II receptor (TßRII), Tumour necrosis factor (TNF)-α, MMP-1, 2 and 9 in the granulomatous rosacea (GR) compared with the non-granulomatous rosacea (NGR) and test the hypothesis that the changes of these profiles in GR would be related with chronic ultraviolet radiation (UVR)-exposure. METHODS: Facial skin samples were obtained from 20 patients with GR and NGR (control group). The sections were stained using haematoxylin and eosin, Verhoeff's elastic stain, and antibodies to TGF-ß, TßRII, TNF-α, MMP-1, -2 and -9. RESULTS: The amount of elastotic material was significantly increased in the dermis of GR lesions. Expression of TGF-ß was significantly decreased in the epidermis of GR lesions compared with NGR lesions. In addition, the expression of MMP-9 was significantly increased in the dermis of GR lesions compared with NGR lesions, especially at the centre of the granuloma on a semi-quantitative analysis. MMP-2 expression was also increased in GR lesions, although the difference between the two groups was not statistically significant. CONCLUSIONS: The results of this study suggest that the increased expression of MMPs in the dermis may participate in granuloma formation of GR in association with UVR.

Acquired bilateral naevus of Ota-like macules: an immunohistological analysis of dermal melanogenic paracrine cytokine networks.

BACKGROUND: Acquired bilateral naevus of Ota-like macules (ABNOM) is similar to melasma with regard to their clinical features, including female predominance, acquired onset, and predominant involvement of the malar area. The similar clinical features suggest the possibility of a shared pathogenesis. Dermal factors including vascularity and melanogenic paracrine networks such as the stem cell factor (SCF)/c-kit pathway have recently been suggested to play an important role in the pathogenesis of melasma. However, the role of dermal factors in ABNOM remains unknown. OBJECTIVES: To provide a novel view on the pathogenesis of ABNOM, we studied the expression of melanogenic paracrine cytokines such as SCF/c-kit, and assessed dermal vascularity. METHODS: Thirty-seven patients with ABNOM and 20 patients with melasma were enrolled in this study. Skin samples were obtained from lesional and perilesional normal skin. Immunohistochemistry was performed. RESULTS: Solar elastosis was slightly more intense in the lesional skin of ABNOM. In contrast to dermal pigmentation and melanocytes, the amounts of epidermal pigmentation and melanocytes were not increased in the lesional skin of patients with ABNOM. The expression of dermal SCF and c-kit was increased; however, the expression of epidermal SCF and c-kit and dermal factor VIII-related antigen was not increased in the lesional skin of ABNOM. CONCLUSIONS: These results suggest that the increased expression of the SCF/c-kit pathway between dermal fibroblasts and dermal melanocytes may play an important role in the pathogenesis of ABNOM.

Oestrogen and progesterone receptor expression in melasma: an immunohistochemical analysis.

BACKGROUND: Melasma is a commonly acquired symmetrical hypermelanosis on sun-exposed areas of the skin. The development of melasma appears to be associated with increased levels of oestrogen, exposure to sunlight and a genetic predisposition. Several in vitro studies have partially clarified the effects of oestrogen and progesterone on melasma. However, oestrogen receptor (ER) and progesterone receptor (PR) expression in melasma-affected skin has not been investigated to date, except for one case report on ER expression. OBJECTIVE: The purpose of this study was to compare ER and PR expression between hyperpigmented areas and unaffected areas of facial skin in patients with melasma. METHODS: Biopsies were performed on skin lesions and adjacent-unaffected facial skin in 33 Korean women with melasma. The sections were stained using haematoxylin and eosin, Fontana-Masson, and antibodies to NKI/beteb, ERα, ß and PR. RESULTS: The immunohistochemical expression of ERß showed an increasing tendency in epidermal lesions without statistical significance. Expression of PR was significantly increased in the epidermal lesions compared with unaffected skin on the computer-assisted image analysis. Interestingly, there was increased ERß expression in the dermal lesions especially around small blood vessels and fibroblast-like cells compared with unaffected dermis on the semi-quantitative analysis. However, there was no significant difference in the expression of PR between the dermal lesions and unaffected dermis. CONCLUSION: The results of this study may provide useful information for further investigation into the pathogenesis and therapeutic approaches for treating melasma in relation to hormonal factors. The role of ER in the dermis in association with dermal environment such as blood vessels and fibroblasts remains to be further clarified.