Perivascular Epithelioid Cell Tumor (PEComa) of Abdominal Cavity from Falciform Ligament: A Case Report

We present a case of perivascular epithelioid cell tumors (PEComas) in the abdominal cavity at the falciform ligament. A 30-yr-old Korean man visited to hospital for the evaluation of a growing, palpable abdominal mass. He had felt the mass growing over 6 months. There was no family or personal history of tuberous sclerosis. The resected specimen showed a mass of 8.0×7.0×5.5 cm in size. Histological examination showed sheets of spindle-to-epithelioid cells with clear-to-eosinophilic cytoplasm. Immunohistochemically, tumor cells were positive for HMB-4 (gp100) and smooth muscle actin. They were also positive for the S-100, which is a marker of neurogenic and melanocytic tumors. Patient was treated with radical resection of tumor without any adjuvant therapy. He is well and on follow-up visits without tumor recurrence

Spontaneous Non-Traumatic Stress Fractures in Bilateral Femoral Shafts in a Patient Treated with Bisphosphonates

Bisphosphonates are potent inhibitors of bone resorption and widely used to treat osteoporosis. Extensive studies have shown that therapy with bisphosphonates improves bone density and decreases fracture risk. However, concerns have been raised about potential over-suppression of bone turnover during long-term use of bisphosphonates, resulting in increased susceptibility to and delayed healing of non-spinal fractures. We report a patient who sustained non-traumatic stress fractures in bilateral femoral shafts with delayed healing after long-term bisphosphonate therapy. She underwent open reduction and surgical internal fixation. Although bisphosphonates effectively prevent vertebral fractures, and their safety has been tested in randomized trials, we must emphasize the need for awareness of the possibility that long-term suppression of bone turnover with bisphosphonates may eventually lead to an accumulation of fatigue-induced damage and adverse skeletal effects such as delayed fracture healing

Higher Lesion Detection by 3.0T MRI in Patient with Transient Global Amnesia

PURPOSE: Transient global amnesia (TGA) patients were retrospectively reviewed to determine the usefulness of high-field strength MRI in detecting probable ischemic lesions in TGA. MATERIALS AND METHODS: We investigated the lesion detection rate in patients with TGA using 1.5T and 3.0T MRI. Acute probable ischemic lesions were defined as regions of high-signal intensity in diffusion weighted image with corresponding low-signal intensity in apparent diffusion coefficient map. RESULTS: 3.0T MRI showed 11 out of 32 patients with probable ischemic lesions in the hippocampus with mean lesion size of 2.8 +/- 0.6 mm, whereas 1.5T MRI detected no lesion in any of 11 patients. There were no significant differences in clinical characteristics between the groups of 1.5 and 3.0T MRI. CONCLUSION: High-field strength MRI has a higher detection rate of probable ischemic lesions than low-field strength MRI in patients with TGA.ope

The Effect of Breastfeeding Duration and Parity on the Risk of Epithelial Ovarian Cancer: A Systematic Review and Meta-analysis

Review Objectives: We conducted a systematic review and meta-analysis to summarize current evidence regarding the association of parity and duration of breastfeeding with the risk of epithelial ovarian cancer (EOC). Methods: A systematic search of relevant studies published by December 31, 2015 was performed in PubMed and EMBASE. A random-effect model was used to obtain the summary relative risks (RRs) and 95% confidence intervals (CIs). Results: Thirty-two studies had parity categories of 1, 2, and ≥3. The summary RRs for EOC were 0.72 (95% CI, 0.65 to 0.79), 0.57 (95% CI, 0.49 to 0.65), and 0.46 (95% CI, 0.41 to 0.52), respectively. Small to moderate heterogeneity was observed for one birth (p<0.01; Q=59.46; I 2 =47.9%). Fifteen studies had breastfeeding categories of <6 months, 6-12 months, and >13 months. The summary RRs were 0.79 (95% CI, 0.72 to 0.87), 0.72 (95% CI, 0.64 to 0.81), and 0.67 (95% CI, 0.56 to 0.79), respectively. Only small heterogeneity was observed for <6 months of breastfeeding (p=0.17; Q=18.79, I 2 =25.5%). Compared to nulliparous women with no history of breastfeeding, the joint effects of two births and <6 months of breastfeeding resulted in a 0.5-fold reduced risk for EOC. Conclusions: The first birth and breastfeeding for <6 months were associated with significant reductions in EOC risk. Key words: Ovarian neoplasms, Parity, Breast feeding, Reproduction, Risk factors, Meta-analysis Received: June 29, 2016 Accepted: September 8, 2016 Corresponding author: Suekyung Park, MD, PhD 103 Daehak-ro, Jongno-gu, Seoul 03080, Korea Tel: +82-2-740-8338, Fax: +82-2-747-4830 E-mail: [email protected] This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/bync/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Worldwide, ovarian cancer is the seventh most common cancer in women. Furthermore, it is the sixth leading cause of cancer deaths in women and the second most common cause of death among those with gynecologic cancers 350 to 8%), germ cell tumors (3% to 5%), and other rare types of ovarian cancer Most ovarian cancers are life-threatening and are notorious for having a poor prognosis, as they are usually diagnosed at an advanced stage. Moreover, screening results based on pelvic imaging or tumor markers for early detection remain unsatisfactory Reproductive risk factors for epithelial ovarian cancer (EOC) have been extensively explored in epidemiologic studies. For instance, a pooled analysis of 12 US case-control studies in 1992 showed that parous women and those who had breastfed had a lower risk of EOC Since 1992, many studies from around the world have reported associations of parity and breastfeeding with ovarian cancer. However, findings concerning the protective role of increasing parity and duration of breastfeeding remain inconsistent. For parity, some studies have indicated that the first birth reduces ovarian cancer risk more than subsequent births Therefore, we conducted a systematic review and metaanalysis to summarize the current evidence regarding the association of parity and duration of breastfeeding with EOC risk. The aim of this study was to clarify the threshold for risk reduction among the studies without heterogeneity across the results. An additional aim was to perform a meta-analysis to estimate the joint risk reductions associated with parity and breastfeeding. METHODS Search Strategy We performed a literature search including studies published through December 2015 using the following search terms in the PubMed and EMBASE databases (1) (parity or "number of live births") and (ovary or ovarian) and (cancer or tumor or neoplasm or malignancy) or (2) (breastfeeding or lactation) and (ovary or ovarian) and (cancer or tumor or neoplasm or malignancy). Furthermore, to find any additional published studies, a manual search was performed by checking all references of prior meta-analyses [5,6.8,20-23] and of all the original studies. This systematic review was planned, conducted, and reported in adherence to the standards of quality for reporting meta-analyses Study Selection To be included, studies had to meet the following criteria: (1) the studies were observational (case-control or cohort studies), (2) the exposures of interest were the number of live births and the total duration of breastfeeding, (3) the outcome of interest was EOC, (4) odds ratios (ORs) or relative risk (RR) estimates with 95% confidence intervals (CIs) were reported or sufficient data were present to allow the calculation of these effect measures, and (5) articles were published in the English language. In the case of overlapping data, the study with the largest number of cases was included. As fertility treatments and BRCA mutation effects on EOC may alter the association between parity/breastfeeding and EOC [26], we excluded studies conducted on specific populations, such as BRCA-1 or BRCA-2 mutation carriers or infertile women treated with fertility drugs. The detailed steps of our literature search are shown in Data Extraction Data extraction was conducted independently by two authors. Disagreements were discussed and resolved by consensus. The following data were collected from each study: the first author's last name, publication year, study region and design, study period, participant age, sample size (cases and 351 Parity and Breastfeeding Effects on Ovarian Cancer Risk controls or cohort size), exposure variables (parity or total breastfeeding duration), study-specific adjusted RR or OR with 95% CIs for each exposure category, and factors matched or adjusted for in the design or data analysis. If no adjusted RR or OR was presented, we included crude estimates. If no RRs or ORs were presented in a given study, we calculated them and the 95% CIs according to the raw frequencies presented in the article. The quality of the study was assessed independently by two authors using the 9-star Newcastle-Ottawa Scale (range, 0 to 9 stars) Statistical Analysis The study-specific RRs or ORs with 95% CIs were used to determine the principal outcome. Because the OR closely approximates the RR for rare diseases, the RR can be estimated from a case-control study using the OR as an approximation One study did not provide the required risk estimates for analysis or separate the risk estimates for different categories of parity or breastfeeding duration. For this study, we used the method proposed by Fleiss and Gross [30]. This method allows adjusted effect estimates and CIs to be calculated for any alternative comparison of levels and can help in a dose-response meta-analysis. Briefly, we combined risk estimates obtained through a simple fixed-effects meta-analysis wherein the subjects were divided into unexposed groups (i=0) and exposed groups (i=1, …, n), and estimates (Ri) with lower and upper 95% CIs were available. To obtain the R1+, we meta-analyzed R1, R2, R3, …, Rn using a fixed-effect model. The categories of parity or breastfeeding duration varied across studies; accordingly, the number of studies included in each metaanalysis and the summary RRs in each meta-analysis were different depending upon the number of categories. Statistical heterogeneity among studies was evaluated with the Cochran Q and I-squared statistics 352 with ≤7 stars considered low-quality as per the 9-star Newcastle-Ottawa Scale; and (3) year of publication (<2000, ≥ 2000), respectively. Publication bias was evaluated using the Begg rank correlation and the Egger linear regression test, in which p-vlaue <0.05 were considered representative of statistically significant publication bias From the meta-analyzed result, to calculate the RR for the joint effect of parity and breastfeeding, we applied the log-linear dose-response model proposed by Berlin et al. We configured the following formula for the multivariate linear logit regression of two factors: Logit P=α + β1χ1 + β2χ2; where P is the probability of a particular outcome (EOC risk), α is the intercept from the linear regression equation, β is the regression coefficient multiplied by some value of the predictor, and χ is the risk factor (parity and breastfeeding). Using this equation yields the value of the RR for the joint effects of parity and breastfeeding duration. For example, in the case of a subject who has no risk factors, logit(P) is α. In this case, the probability of EOC is exp(α)=1.0. In the case of a subject with only χ1, logit(P) is α+β1. In the case of a subject with both χ1 and χ2, logit(P) is α+β1+β2. Accordingly, the probability of EOC is exp(β1+β2)=OR1×OR2. Since the category of parity and breastfeeding duration varied across studies, to calculate the RR for the joint effect of parity and breastfeeding, we used the summary RR for parity and breastfeeding duration that contained the largest number of studies. All statistical analyses were performed with Stata version 12.0 (StataCorp., College Station, TX, USA). RESULTS Study Characteristics The characteristics of the 32 studies included with data regarding parity and the 15 studies included with data regarding breastfeeding are shown in Supplemental 353 Parity and Breastfeeding Effects on Ovarian Cancer Risk Africa. For breastfeeding, two cohort studies and 13 case-control studies were included. The included studies were conducted between 1978 and 2008. Of the 15 studies, seven were performed in North America, six in Europe, one in Asia, and one in Australia. Parity and Epithelial Ovarian Cancer Risk Thirty-two studies had parity categories of 1, 2, and ≥3. The summary RRs for the first, second, and third births were 0.72 (95% CI, 0.65 to 0.79), 0.57 (95% CI, 0.49 to 0.65), and 0.46 (95% CI, 0.41 to 0.52), respectively Duration of Breastfeeding and Epithelial Ovarian Cancer Risk Fifteen studies had breastfeeding categories of <6 months, 6-12 months, and ≥13 months. The summary RRs for these categories were 0.79 (95% CI, 0.72 to 0.87), 0.72 (95% CI, 0.64 to 0.81) and 0.67 (95% CI, 0.56 to 0.79), respectively Subgroup Analysis According to Study Design, Study Quality, and Publication Year The results from the subgroup analysis according to study design, study quality, and publication year are shown in Relative Risk for the Joint Effect of Parity and Breastfeeding The RR for the joint effect of parity and breastfeeding, obtained using the summary RR from the analysis of 32 studies with parity categories of 1, 2, and ≥3 and 15 studies with breastfeeding categories of <6 months, 6-12 months, and ≥ 13 months, is shown in DISCUSSION The findings of this meta-analysis indicate that parity and breastfeeding experiences in women can help prevent EOC, which is typically life-threatening and has a poor prognosis. In particular, the first birth and the first six months of breastfeeding had a greater protective effect than did subsequent births and/or additional breastfeeding, although multiparity and additional breastfeeding did provide some additional protection. The risk reduction effect of the first birth on EOC risk was almost 30%, and the combined effect of the first birth and <6 months of breastfeeding was 40%; thus, breastfeeding provided a nearly 10% greater risk reduction. In regards to parity, the EOC risk reduction was highest for the first birth, with some additional protection from the second birth. However, slightly less risk reduction was observed for the third birth Pregnancy and breastfeeding are thought to reduce EOC risk Ho Kyung Sung, et al. 354 by decreasing pituitary gonadotropin levels and inducing anovulation [7,35]. Pregnancy and breastfeeding are expected to decrease the likelihood of spontaneous genetic mutation under the incessant ovulation hypothesis and of the hyperproliferation of inclusion cysts under the gonadotropin hypothesis. However, the observation that multiparity and additional breastfeeding did not provide an equal amount of protection does not provide evidence for either of these hypotheses. Nev- The summary RRs (95% CIs) in each meta-analysis were estimated using a random effect model. 3 Studies with ≥8 stars were considered high-quality as per the 9-star Newcastle-Ottawa Scale. 4 Studies with ≤7 stars were considered low-quality as per the 9-star Newcastle-Ottawa Scale. 355 Parity and Breastfeeding Effects on Ovarian Cancer Risk ertheless, the results of two experimental studies provide biological evidence for the relatively weaker protective effect of additional parity and breastfeeding [36,37]. For instance, high progesterone levels during pregnancy can increase apoptosis, which may clear transformed cells from the ovarian epithelium, meaning that all the accumulated transformed cells are washed fully out by the first pregnancy. Therefore, the first pregnancy provides a stronger protective effect than subsequent pregnancies [36]. In regards to breastfeeding, breastfeeding in the first few months completely inhibits the pulsatile secretion of gonadotropin-releasing hormone and luteinizing hormone, leading to suppression of ovulation [37]. After a couple of months, ovulatory activity may return, even though breastfeeding continues [37]; thus, a longer duration of breastfeeding does not provide an additional protective effect. Our finding of decreased EOC risk with longer breastfeeding is similar to that reported by prior meta-analyses in 2013 and 2014 [22,23], but differs from that of a meta-analysis of nine case-control studies conducted in developed countries in 2001, in which breastfeeding for ≥12 months was associated with a significant 0.72-fold reduced risk of EOC compared to never having breastfed, while breastfeeding <12 months did not show such an association (OR, 0.95; 95% CI, 0.80 to 1.12) The strength of this meta-analysis is that it included all available studies, and the large number of EOC cases allowed for the investigation of the risk associated with different categories of parity and breastfeeding duration. However, the current study also has several limitations. First, our meta-analysis wa

Strong association between herpes simplex virus-1 and chemotherapy-induced oral mucositis in patients with hematologic malignancies

Background/Aims: A link between oral cavity infections and chemotherapy-induced oral mucositis (CIOM) in patients with hematological malignancies (HMs) undergoing intensive chemotherapy (IC) or hematopoietic stem cell transplantation (HSCT) has been suggested. However, conclusive data are lacking, and there are no current guidelines for the prophylactic use of antimicrobials to prevent CIOM in these populations. Methods: The relationships between herpes simplex virus (HSV) reactivation and Candida colonization in the oral cavity and CIOM in patients with HMs undergoing IC or HSCT were evaluated. Patients aged >= 19 years with HMs undergoing IC or HSCT were enrolled. Each patient was evaluated for HSV and Candida in the oral cavity along with CIOM at baseline and during the and, 3rd, and 4th weeks. Results: Seventy presentations among 56 patients were analyzed. CIOM was observed in 23 presentations (32.9%), with a higher incidence associated with HSCT (17 of 35 presentations, 48.6%) than with IC (six of 35 presentations, 8.6%). The reactivation of HSV-1 was significantly associated with an increased incidence of CIOM after adjusting for age, sex, type of disease, and treatment stage. A higher HSV-1 viral load was associated with an increased incidence of CIOM. The presence of Candida was not associated with CIOM. Conclusions: HSV-1 reactivation in the oral cavity was highly associated with CIOM in patients with HMs undergoing high-dose chemotherapy.Y

Efficacy and safety of entecavir plus carnitine complex (GODEX®) compared to entecavir monotherapy in patient with ALT elevated chronic hepatitis B: randomized, multicenter open-label trials. The GOAL study

Background/AimsCarnitine and vitamin complex (Godex®) is widely used in patients with chronic liver disease who show elevated liver enzyme in South Korea. The purpose of this study is to identify the efficacy and safety of carnitine from entecavir combination therapy in Alanine aminotransferase (ALT) elevated Chronic Hepatitis B (CHB) patients.Methods130 treatment-naïve patients with CHB were enrolled from 13 sites. The patients were randomly selected to the entecavir and the complex of entecavir and carnitine. The primary endpoint of the study is ALT normalization level after 12 months.ResultsAmong the 130 patients, 119 patients completed the study treatment. The ALT normalization at 3 months was 58.9% for the monotherapy and 95.2% for the combination therapy (P<0.0001). ALT normalization rate at 12 months was 85.7% for the monotherapy and 100% for the combination group (P=0.0019). The rate of less than HBV DNA 300 copies/mL at 12 months was not statistically significant (P=0.5318) 75.9% for the monotherapy, 70.7% for the combination and it was. Quantification of HBsAg level was not different from the monotherapy to combination at 12 months. Changes of ELISPOT value to evaluate the INF-γ secretion by HBsAg showed the increasing trend of combination therapy compare to mono-treatment.ConclusionsALT normalization rate was higher in carnitine complex combination group than entecavir group in CHB. Combination group was faster than entecavir mono-treatment group on ALT normalization rate. HBV DNA normalization rate and the serum HBV-DNA level were not changed by carnitine complex treatment

Genome-Wide Association Study in East Asians Identifies Novel Susceptibility Loci for Breast Cancer

Genetic factors play an important role in the etiology of both sporadic and familial breast cancer. We aimed to discover novel genetic susceptibility loci for breast cancer. We conducted a four-stage genome-wide association study (GWAS) in 19,091 cases and 20,606 controls of East-Asian descent including Chinese, Korean, and Japanese women. After analyzing 690,947 SNPs in 2,918 cases and 2,324 controls, we evaluated 5,365 SNPs for replication in 3,972 cases and 3,852 controls. Ninety-four SNPs were further evaluated in 5,203 cases and 5,138 controls, and finally the top 22 SNPs were investigated in up to 17,423 additional subjects (7,489 cases and 9,934 controls). SNP rs9485372, near the TGF-β activated kinase (TAB2) gene in chromosome 6q25.1, showed a consistent association with breast cancer risk across all four stages, with a P-value of 3.8×10−12 in the combined analysis of all samples. Adjusted odds ratios (95% confidence intervals) were 0.89 (0.85–0.94) and 0.80 (0.75–0.86) for the A/G and A/A genotypes, respectively, compared with the genotype G/G. SNP rs9383951 (P = 1.9×10−6 from the combined analysis of all samples), located in intron 5 of the ESR1 gene, and SNP rs7107217 (P = 4.6×10−7), located at 11q24.3, also showed a consistent association in each of the four stages. This study provides strong evidence for a novel breast cancer susceptibility locus represented by rs9485372, near the TAB2 gene (6q25.1), and identifies two possible susceptibility loci located in the ESR1 gene and 11q24.3, respectively

Gene-Environment Interactions Relevant to Estrogen and Risk of Breast Cancer: Can Gene-Environment Interactions Be Detected Only among Candidate SNPs from Genome-Wide Association Studies?

In this study we aim to examine gene–environment interactions (GxEs) between genes involved with estrogen metabolism and environmental factors related to estrogen exposure. GxE analyses were conducted with 1970 Korean breast cancer cases and 2052 controls in the case-control study, the Seoul Breast Cancer Study (SEBCS). A total of 11,555 SNPs from the 137 candidate genes were included in the GxE analyses with eight established environmental factors. A replication test was conducted by using an independent population from the Breast Cancer Association Consortium (BCAC), with 62,485 Europeans and 9047 Asians. The GxE tests were performed by using two-step methods in GxEScan software. Two interactions were found in the SEBCS. The first interaction was shown between rs13035764 of NCOA1 and age at menarche in the GE|2df model (p-2df = 1.2 × 10−3). The age at menarche before 14 years old was associated with the high risk of breast cancer, and the risk was higher when subjects had homozygous minor allele G. The second GxE was shown between rs851998 near ESR1 and height in the GE|2df model (p-2df = 1.1 × 10−4). Height taller than 160 cm was associated with a high risk of breast cancer, and the risk increased when the minor allele was added. The findings were not replicated in the BCAC. These results would suggest specificity in Koreans for breast cancer risk