Anticancer Effects of BRD4 Inhibitor in Epithelial Ovarian Cancer.

Efforts have been made to develop bromodomain inhibitors as cancer treatments. Sub-pathways, particularly in ovarian cancer, affected by bromodomain-containing protein (BRD) remain unclear. This study verified the antitumor effects of a new drug that can overcome OPT-0139-chemoresistance to treat ovarian cancer. A mouse xenograft model of human ovarian cancer cells, SKOV3 and OVCAR3, was used in this study. Cell viability and proliferation were assessed using MTT and ATP assays. Cell cycle arrest and apoptosis were determined using flow cytometry. BRD4 and c-Myc expression and apoptosis-related molecules were detected using RT-PCR and real-time PCR and Western blot. We confirmed the OPT-0139 effect and mechanism of action in epithelial ovarian cancer. OPT-0139 significantly reduced cell viability and proliferation and induced apoptosis and cell cycle arrest. In the mouse xenograft model, significant changes in tumor growth, volume, weight, and BRD4-related gene expression were observed, suggesting the antitumor effects of BRD4 inhibitors. Combination therapy with cisplatin promoted apoptosis and suppressed tumor growth in vitro and in vivo. Our results suggest OPT-0139, a BRD4 inhibitor, as a promising anticancer drug for the treatment of ovarian cancer by inhibiting cell proliferation, decreasing cell viability, arresting cell cycle, and inducing apoptosis.

A differential diagnosis between uterine leiomyoma and leiomyosarcoma using transcriptome analysis.

BACKGROUND: The objective of this study was to estimate the accuracy of transcriptome-based classifier in differential diagnosis of uterine leiomyoma and leiomyosarcoma. We manually selected 114 normal uterine tissue and 31 leiomyosarcoma samples from publicly available transcriptome data in UCSC Xena as training/validation sets. We developed pre-processing procedure and gene selection method to sensitively find genes of larger variance in leiomyosarcoma than normal uterine tissues. Through our method, 17 genes were selected to build transcriptome-based classifier. The prediction accuracies of deep feedforward neural network (DNN), support vector machine (SVM), random forest (RF), and gradient boosting (GB) models were examined. We interpret the biological functionality of selected genes via network-based analysis using GeneMANIA. To validate the performance of trained model, we additionally collected 35 clinical samples of leiomyosarcoma and leiomyoma as a test set (18 + 17 as 1st and 2nd test sets). RESULTS: We discovered genes expressed in a highly variable way in leiomyosarcoma while these genes are expressed in a conserved way in normal uterine samples. These genes were mainly associated with DNA replication. As gene selection and model training were made in leiomyosarcoma and uterine normal tissue, proving discriminant of ability between leiomyosarcoma and leiomyoma is necessary. Thus, further validation of trained model was conducted in newly collected clinical samples of leiomyosarcoma and leiomyoma. The DNN classifier performed sensitivity 0.88, 0.77 (8/9, 7/9) while the specificity 1.0 (8/8, 8/8) in two test data set supporting that the selected genes in conjunction with DNN classifier are well discriminating the difference between leiomyosarcoma and leiomyoma in clinical sample. CONCLUSION: The transcriptome-based classifier accurately distinguished uterine leiomyosarcoma from leiomyoma. Our method can be helpful in clinical practice through the biopsy of sample in advance of surgery. Identification of leiomyosarcoma let the doctor avoid of laparoscopic surgery, thus it minimizes un-wanted tumor spread.

Reinforced technique of tension band wiring for tibial tuberosity fracture in adolescents: a case report for surgical technique.

Most of the fractures had been previously treated with open reduction and internal fixation. Although there are a number of fixation methods, a consensus on the treatment options has not been reached yet. Case presentation: We demonstrated the reinforced technique of tension band wiring and its surgical outcomes in the tibial tuberosity fracture of a 14-year-old male basketball player. For the modified technique, the wire was inserted between the patellar tendon and tibial tuberosity (insertion site of patellar tendon) and passed distally through the 2-mm-sized predrill cortical hole. Tightening the figure of the eight loops draws the fractured fragments together and anatomically reduces under appropriate compression. This technique can achieve the reduction and fixation of the fracture simultaneously. We confirmed the fixation stability with a range of knee joint motions. The patient was able to return back to the pre-injury level of sports activity at postoperative 2 months. Clinical discussion: The original technique of tension band wiring utilized the Kirschner wire to make a figure-of-eight loop. However, we used the patellar tendon and its insertion site of the tibial tuberosity for making a figure-of-eight loop. Moreover, the reduction and fixation of fracture were achieved simultaneously by tightening the tension band wire. This reinforced technique was firm enough for postoperative rehabilitation. Conclusion: The most certain advantage of this technique was to be able to reduce anatomically and fixate firmly with appropriate compression simultaneously. We recommend open reduction internal fixation with the reinforced technique of tension band wiring for displaced tibial tuberosity fracture in adolescent athletes.

Longitudinal changes in shoulder arthroplasty stratified by age groups, types of surgical facilities, and geographical regions in Korea from 2010 to 2020.

BACKGROUND: Shoulder arthroplasty (SA), including hemiarthroplasty, reverse and anatomical total SA (TSA), improves quality of life by reducing shoulder pain and restoring function in patients not only with irreparable rotator cuff tears and/or cuff tear arthropathy but also with osteoarthritis posttraumatic arthritis, proximal humeral fractures, etc. Given the rapid developments in artificial joints and improvements in postoperative outcomes, the number of SA surgeries is increasing worldwide. Therefore, we investigated changes in trends over time in Korea. METHODS: We analyzed the longitudinal changes in the incidence of SA including anatomic and reverse TSA, hemiarthroplasty, and shoulder revision arthroplasty (SRA) by changes in the Korean age profile, surgical facilities, and geographical regions using the Korean Health Insurance Review and Assessment Service database from 2010 to 2020. Data were also collected from the National Health Insurance Service and the Korean Statistical Information Service. RESULTS: From 2010 to 2020, the TSA rate per 1,000,000 person-years increased from 10.571 to 101.372 (time trend = 1.252; 95% CI 1.233-1.271, P < .001). The shoulder hemiarthroplasty (SH) rate per 1,000,000 person-years decreased from 6.414 to 3.685 (time trend = 0.933; 95% CI 0.907-0.960, P < .001). The SRA rate per 1,000,000 person-years increased from 0.792 to 2.315; the increase was significant (time trend = 1.133; 95% CI 1.101-1.166, P < .001). DISCUSSION: Overall, TSA and SRA are increasing and SH is decreasing. For both total TSA and SRA, steep increases are evident in the numbers of patients in their 70s and older than 80 years. The SH trend is decreasing regardless of differences in age groups, surgical facilities, and geographical regions. SRA is preferentially performed in Seoul.

Effect of Low or High Pressure Alveolar Recruitment Maneuver on Postoperative Pain and Quality of Recovery in Patients with Obesity Undergoing Laparoscopic Sleeve Gastrectomy.

Background: This study aimed to evaluate whether a low- or high-pressure alveolar recruitment maneuver (ARM) might reduce postoperative pain and improve the quality of recovery after laparoscopic bariatric surgery. Methods: 90 patients with a body mass index > 30 kg/m2 scheduled for laparoscopic sleeve gastrectomy were randomly assigned to control (n = 30), low ARM (n = 30), or high ARM groups (n = 30). For the low and high ARM groups, ARM was repeated five times to hold the peak airway pressure at 30 cmH2O and 60 cmH2O for 5 s, respectively, before removal of the trocar. Conventional methods to reduce post-laparoscopic pain, such as intraperitoneal saline irrigation, hemovac drainage, and gentle abdominal compression were performed in all patients, regardless of the assigned group. Results: Shoulder and surgical site pain scores 24 h postoperatively and rescue meperidine requirement were similar between the groups (p = 0.141, 0.101, and 0.82, respectively). The quality of recovery 40 (QoR40) score 24 h postoperatively was similar between the groups (p = 0.755). Postoperative pulmonary complications were similar between the groups (p = 0.124). Conclusion: Application of a low- or high-pressure ARM in addition to conventional methods to remove remnant peritoneal CO2 gas did not reduce postoperative shoulder or surgical site pain or improve the quality of recovery after laparoscopic sleeve gastrectomy.

Trends of Total Knee Arthroplasty According to Age Structural Changes in Korea from 2011 to 2018.

Total Knee Arthroplasty (TKA) is one of the most commonly performed surgeries worldwide since it can improve pain, quality of life, and functional outcome. Due to the expansion of hospitals specialized in joint surgery, the topography of TKA implementation in Korea is changing. This study analyzed longitudinal trends of TKA based on changes in age distribution, sex, hospital, and region based on the Health Insurance Review and Assessment Service (HIRA) of Korea database. Data were collected from the National Health Insurance Service (NHIS), the Korean Statistical Information Service (KOSIS), and the Health Insurance Review and Assessment Service (HIRA) in Korea for the period 2011-2018. Results show the total number of surgeries increased and the number of patients by age decreased in those under the age of 70, while the number of patients over 70 years of age increased. A remarkable increase in women was found, and there was no significant difference between regions. TKA is spreading in a more universal and easily accessible form in Korea and has increased more in other relatively small medical institutions compared to tertiary referral medical centers. Due to the increase of orthopedics' specialized hospitals and clinics, TKA is becoming more prominent in those hospitals.

Effect of risk-reducing salpingo-oophorectomy on the quality of life in Korean BRCA mutation carriers.

BACKGROUND: This study aimed to compare the quality of life (QOL), psychosocial status, sexual function, and menopausal symptoms between the risk-reducing salpingo-oophorectomy (RRSO) and non-RRSO groups comprising BRCA mutation carriers and to evaluate the effect of timing of RRSO on those aspects. METHODS: This cross-sectional study recruited BRCA mutation carriers aged ≥35 years between September 2015 and September 2016. Demographic data of carriers were collected. Outcomes were measured using the questionnaires addressing QOL, anxiety, depression, optimism, sexual function, and menopausal symptoms. RESULTS: Of 52 participants, 30 (57.7%) underwent RRSO, whereas 22 (42.3%) did not. In the RRSO group, 16 (53.3%) and 14 (46.7%) women underwent RRSO before and after menopause, respectively. The mean age in the RRSO group was higher than that in the non-RRSO group (49.8 vs. 42.1 years, respectively, p = 0.002). The scores for QOL, anxiety, depression, optimism, sexual function, and menopausal symptoms were similar between both groups. In the multivariate analysis, RRSO uptake was associated with worse physical QOL (coefficient, -5.350; 95% confidence interval, -10.593 to -0.108). With respect to the timing of RRSO, only the mental QOL was significantly lower in the postmenopausal RRSO group than in the premenopausal RRSO group (39.2 vs. 43.7, respectively, p = 0.043). CONCLUSION: We could not find any difference in mental QOL, psychosocial status, sexual function, and menopausal symptoms between the RRSO and non-RRSO groups. RRSO uptake only affected worse physical QOL. These results will help physicians counsel BRCA mutation carriers about the effect of RRSO on QOL.

Diagnosis and treatment of bullous pemphigoid that developed twice after total knee replacement arthroplasty: a case report.

BACKGROUND: Total knee replacement arthroplasty (TKA) is frequently performed in South Korea. Simple swelling-associated blistering around the periphery of the operative wound is a well-known adverse effect. However, in rare cases, the blisters are bullous pemphigoid (BP). CASE PRESENTATION: A 75-year-old male presented with knee pain that had not improved despite 5 years of medication. We performed TKA of the left knee, placing a Stryker posteriorly stabilized prosthesis. Three days later, blisters developed near the buttocks and thighs and, on day 10 after surgery, around the operative site. A skin biopsy revealed BP. Commencing on day 14 after surgery, prednisolone 10 mg was administered twice daily. The symptoms improved by 3 weeks after surgery and were healed at 4 months. After 1 year, we performed TKA of the right knee. On day 2 after surgery, as formerly, blisters developed on the buttocks and an immediate biopsy revealed BP. Commencing on day 3 after surgery, prednisolone 10 mg was administered twice daily. On day 10 after surgery, the blisters on the buttocks had improved and no blisters were observed at the surgical site. All symptoms had resolved by 2.5 months after surgery. CONCLUSIONS: After TKA surgery, generalized BP may develop, diagnosed via skin biopsy. A quick diagnosis is important because early treatment can prevent symptom progression and shorten treatment.

Enhanced Efficacy of Combined Therapy with Checkpoint Kinase 1 Inhibitor and Rucaparib via Regulation of Rad51 Expression in BRCA Wild-Type Epithelial Ovarian Cancer Cells.

PURPOSE: This study aimed to evaluate anticancer effects of combination treatment with poly(ADP-ribose) polymerase (PARP) and checkpoint kinase 1 (Chk1) inhibitors in BRCA wild-type ovarian cancer. PARP inhibitors can function as DNA-damaging agents in BRCA wild-type cancer, even if clinical activity is limited. Most epithelial ovarian cancers are characterized by a TP53 mutation causing dysfunction at the G1/S checkpoint, which makes tumor cells highly dependent on Chk1-mediated G/M phase cell-cycle arrest for DNA repair. MATERIALS AND METHODS: We investigated the anticancer effects of combination treatment with prexasertib (LY2606368), a selective ATP competitive small molecule inhibitor of Chk1 and Chk2, and rucaparib, a PARP inhibitor, in BRCA wild-type ovarian cancer cell lines (OVCAR3 and SKOV3). RESULTS: We found that combined treatment significantly decreased cell viability in all cell lines and induced greater DNA damage and apoptosis than in the control and/or using monotherapies. Moreover, we found that prexasertib significantly inhibited homologous recombination-mediated DNA repair and thus showed a marked anticancer effect in combination treatment with rucaparib. The anticancer mechanism of prexasertib and rucaparib was considered to be caused by an impaired G2/M checkpoint due to prexasertib treatment, which forced mitotic catastrophe in the presence of rucaparib. CONCLUSION: Our results suggest a novel effective therapeutic strategy for BRCA wild-type epithelial ovarian cancer using a combination of Chk1 and PARP inhibitors.

Comparison of functional outcomes between single-radius and multi-radius femoral components in primary total knee arthroplasty: a meta-analysis of randomized controlled trials.

PURPOSE: Our purpose in the current meta-analysis was to compare the functional outcomes in patients who have received single-radius (SR) or multi-radius (MR) femoral components in randomized controlled trials (RCTs) for primary total knee arthroplasty (TKA). The hypothesis was that there would be no statistically significant difference between two groups in terms of functional outcomes. MATERIALS AND METHODS: We searched the international electronic databases PubMed, Embase, and the Cochrane Central Register of Controlled Trials up to February 2020 for RCTs that compared functional outcomes of SR and MR femoral component designs after primary TKA. We performed a meta-analysis of nine RCTs using the Knee Society Score for the knee (KSS-knee), KSS-function, Knee Injury and Osteoarthritis Outcome Score (KOOS), Oxford Knee Score (OKS), degree of knee flexion, extension, and complications, including postoperative infection and revision surgery. RESULTS: The meta-analysis revealed no statistically significant differences in all the analyzed variables, including KSS-knee, KSS-function, KOOS, OKS, knee flexion, and knee extension. For postoperative complications, no statistically significant differences were detected for femoral component designs in postoperative infection or incidence of revision surgery between the two groups. CONCLUSIONS: The current meta-analysis of RCTs did not show any statistically significant differences between SR and MR femoral component designs in terms of postoperative functional outcomes. Evaluated outcomes included functional outcome scores, degree of knee flexion, extension, and complications. However, because of the limited clinical evidence of this study owing to the heterogeneity between the included RCTs, a careful approach should be made in order not to arrive at definite conclusions.

Outcome Differences of Remnant- Preserving versus Non-Preserving Methods in Arthroscopic Anterior Cruciate Ligament Reconstruction: A Meta-analysis with Subgroup analysis.

PURPOSE: To analyze differences in clinical outcomes of arthroscopic anterior cruciate ligament reconstruction between remnant-preserving and non-preserving methods. METHODS: International electronical databases PubMed, Embase, and the Cochrane central database from January 1966 to December 2017 were searched for randomized controlled trials (RCTs) and observational studies that compared differences of clinical outcomes of ACL reconstruction with and without remnant preservation. A meta-analysis of these studies was performed to compare clinical outcomes. Subgroup analyses were conducted to evaluate the role of methodological quality in primary meta-analysis estimates. RESULTS: Five RCTs and six observational studies were included in this meta-analysis and subgroup analysis. The remnant-preserving method in arthroscopic ACL reconstruction showed a statistically significant difference compared to the non-preserving method regarding arthrometric evaluation (side-to-side difference). Lachman test, Lysholm scores, and IKDC subjective scores showed statistically minor difference in meta-analysis, but showed no significant difference in subgroup analysis. Remained parameters including pivot shift test, IKDC grades, incidence of cyclops lesion showed no statistically differences in meta-analysis or subgroup analysis. CONCLUSIONS: This meta-analysis with subgroup analysis showed that arthroscopic remnant-preserving ACL reconstruction provided statistically significant but limited clinical relevance in terms of arthrometric evaluation. Results of Lachman test, Lysholm scores, and IKDC subjective scores demonstrated statistically minor differences.

A potential risk factor of total knee arthroplasty: an infected Baker's cyst - a case report.

BACKGROUND: In adults, Baker's cyst development is attributable principally to secondary alterations after degenerative changes. The latter changes often accompany osteoarthritis, and we frequently encounter patients with Baker's cysts seeking total knee arthroplasty (TKA). Baker's cysts are not usually subject to extensive preoperative evaluation because the cysts often disappear naturally after surgery, unaccompanied by any adverse symptoms. CASE PRESENTATION: A 63-year-old woman presented with moderate pain in the left knee joint that had developed 1 year ago. Posterior knee pain was aggravated on maximum knee flexion. Three months previously, a popliteal mass had become palpable and the patient had undergone needle mass aspiration twice in a local orthopedic hospital, but the mass had recurred. We initially considered TKA for her severe degenerative osteoarthritis. However, we decided to perform only arthroscopic debridement and cyst excision because the patient was experienced severe pain only on maximal knee flexion, and did not want TKA. Pus gushed from the torn cyst during the operation. We diagnosed an infected Baker's cyst. The patient was treated with a first-generation cephalosporin postoperatively. CONCLUSIONS: A Baker's cyst that was aspirated and still causes symptoms with altered blood tests needs to be evaluated accurately before TKA.

Development and Validation of Ovarian Symptom Index-18 and Neurotoxicity-4 for Korean Patients with Ovarian, Fallopian Tube, or Primary Peritoneal Cancer.

PURPOSE: The purpose of this study was to develop Korean versions of the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy (NCCN-FACT) Ovarian Symptom Index-18 (NFOSI-18) and FACT/Gynecologic Oncology Group (FACT-GOG) Neurotoxicity 4-item (NTX-4), evaluating their reliability and reproducibility. MATERIALS AND METHODS: In converting NFOSI-18 and NTX-4, the following steps were performed: forward translation, backward translation, expert review, pretest of preliminary format, and finalization of Korean versions (K-NFOSI-18 and K-NTX-4). Patients were enrolled from six institutions where each had completed chemotherapy for ovarian, tubal, or peritoneal cancer at least 1 month earlier. In addition to demographics obtained by questionnaire, all subjects were assessed via K-NFOSI-18, K-NTX-4, and a Korean version of the EuroQoL-5 Dimension. Internal structural validity and reliability were evaluated using item internal consistency, item discriminant validity, and Cronbach's α. To evaluate test-retest reliability, K-NFOSI-18 and K-NTX-4 were readministered after 7-21 days, and intraclass correlation coefficients (ICCs) were calculated. RESULTS: Of the 250 women enrolled during the 3-month recruitment period, 13 withdrew or did not respond, leaving 237 (94.8%) for the analyses. Mean patient age was 54.3±10.8 years. Re-testing was performed in 190 patients (80.2%). The total K-NFOSI-18 and K-NTX-4 scores were 49 (range, 20 to 72) and 9 (range, 0 to 16), respectively, with high reliability (Cronbach's α=0.84 and 0.89, respectively) and reproducibility (ICC=0.77 and 0.84, respectively) achieved in retesting. CONCLUSION: Both NFOSI-18 and NTX-4 were successfully developed in Korean with minimal modification. Each Korean version showed high internal consistency and reproducibility.

Circulating tumor cells in the differential diagnosis of adnexal masses.

The aim of this study was to evaluate circulating tumor cell (CTC) detection in the differential diagnosis of adnexal masses. A total of 87 preoperative women with an indeterminate adnexal mass were prospectively enrolled. Preoperative diagnostic modalities including CTC detection, risk of ovarian malignancy algorithm, risk of malignancy index, and computed tomography or magnetic resonance imaging were compared. Forty-three (49.4%) benign tumors, 13 (14.9%) borderline malignant masses, and 31 (35.7%) cancers were pathologically confirmed. Forty-nine (56.3%) cases were positive for CTCs: 19/43 (44.2%) benign, 10/10 (100%) early-stage, and 14/21 (66.7%) advanced-stage cancer. CTC detection had sensitivities of 77.4%, 100%, and 100% for benign vs. all stage cancer (n = 74), benign vs. stage I-II cancer (n = 53), and benign vs. stage I cancer (n = 49), respectively. CTC detection had a specificity of 55.8% across all comparisons. The sensitivities of the other modalities assayed were decreased in stage I-II cancer and stage I cancer vs. benign masses. Receiver operating characteristic curves showed that CTCs, of which the area under the curve was modest in all stage cancer (0.655), had the widest area under the curve among the evaluated modalities in stage I-II cancer and stage I cancer (0.768 for both). In conclusion, our study findings suggest that preoperative CTCs could have a substantial role in differentiating early stage cancer from benign tumors for adnexal masses.

Identifying risk factors for occult lower extremity lymphedema using computed tomography in patients undergoing lymphadenectomy for gynecologic cancers.

OBJECTIVE: To identify risk factors for lower extremity lymphedema (LEL) using computed tomographic (CT) scan in patients undergoing lymphadenectomy for gynecologic cancers. METHODS: We retrospectively reviewed 511 consecutive gynecologic cancer patients undergoing lymphadenectomy. Mean difference (3.77±3.14mm) of subcutaneous layer thicknesses between preoperative and postoperative 1-year CT scans of 106 patients with clinical LEL was used as an objective criterion for regrouping all the patients into those with mean difference >3.77mm and ≤3.77mm. Risk factors for clinical LEL and significant increase of subcutaneous layer thickness on CT were evaluated using a logistic regression model. RESULTS: A total of 106 (20.7%) patients were clinically diagnosed with LEL by a physician. Total number of lymph nodes (LNs) retrieved >30 (Odds ratio [OR] 3.2; 95% Confidence interval [CI] 1.94-5.32; p<0.001) and adjuvant pelvic radiotherapy (OR 3.1; 95% CI 1.75-5.52; p<0.001) were risk factors for clinical LEL. One hundred-nineteen (23.3%) had subcutaneous layer thickness increase of >3.77mm. In addition to number of LNs retrieved >30 (OR 2.3; 95% CI 1.40-3.74; p=0.001) and adjuvant pelvic radiotherapy (OR 1.7; 95% CI 1.01-2.74; p=0.046), open surgery (OR 1.8; 95% CI 1.01-3.11; p=0.045), long operation time (OR 1.7; 95% CI 1.05-2.83; p=0.032), and no use of intermittent pneumatic compression (IPC) (OR 2.1; 95% CI 1.06-4.16; p=0.034) were risk factors for thick subcutaneous layer on postoperative CT. CONCLUSIONS: In addition to high LN retrieval and adjuvant pelvic radiotherapy, open surgery, long operation time, and no IPC use could be risk factors for occult LEL after lymphadenectomy in gynecologic cancers.

Expression Patterns of Nrf2 and Keap1 in Ovarian Cancer Cells and their Prognostic Role in Disease Recurrence and Patient Survival.

OBJECTIVE: This study evaluated the expression patterns of nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) and assessed their clinical value as prognostic indicators in ovarian cancer. METHODS: The expression patterns of Nrf2 and Keap1 were determined in 100 epithelial ovarian cancers by immunohistochemistry analyses. The associations of Nrf2 and Keap1 expression with clinicopathological characteristics of patients were evaluated. All patients received platinum-based chemotherapy. Chemoresistance was defined as recurrence within 6 months of first-line chemotherapy. RESULTS: Cytoplasmic expression of Nrf2 and Keap1 was observed in 95% and 72%, respectively, of all 100 epithelial ovarian cancers examined. Low Keap1 expression (intensity < 1) was strongly associated with disease recurrence (P = 0.046) and death (P = 0.002). Chemoresistance was associated with high Nrf2 expression (intensity = 3) (P = 0.833; hazard ratio [HR], 1.202; 95% confidence interval [CI], 0.217-6.667) and low Keap1 expression (P = 0.862; HR, 0.899; 95% CI, 0.270-2.994). However, these associations were not statistically significant. Survival analysis indicated that high Keap1 expression (intensity ≥ 1) was strongly predictive of better overall survival (P = 0.049) and disease-free survival (P = 0.004). Cox regression analysis indicated that Keap1 expression was an independent prognostic factor for overall survival (P = 0.012; HR, 0.349; 95% CI, 0.153-0.797). Although patients with high Nrf2 expression displayed better overall survival and disease-free survival, the association was not statistically significant. CONCLUSIONS: High cytoplasmic Keap1 expression, which might prevent nuclear translocation of Nrf2 in ovarian cancer cells, was associated with lower disease recurrence and death rate. Survival analysis suggested a probable role of Keap1 expression in predicting the prognosis of ovarian cancer.

Clinical features and treatment outcomes of septic arthritis due to Mycobacterium massiliense associated with intra-articular injection: a case report.

BACKGROUND: There are increasing reports on nosocomial Mycobacterium massiliense infection, but septic arthritis and osteomyelitis because of that microorganism is rare. This report focuses on the clinical aspects of M. massiliense arthritis outbreak concurrent with soft tissue infection. CASE PRESENTATION: An outbreak of septic arthritis among patients who had been injected at a single clinic occurred in South Korea between April and September 2012. This may be associated with repeated injection of triamcinolone contaminated with M. massiliense. Nine of the Korean patients visited our hospital complaining of painful swelling of the knees. During treatment course, patients are suffered from soft tissue abscess around the injection site. Acid-fast bacilli culture for infected tissue was positive in five patients, and polymerase chain reaction for non-tuberculous mycobacteria was positive in four patients. They were treated with antibiotics, repeated arthroscopic surgeries, incision and drainage for a long time. All patients were eventually cured but three patients have suffered from a decreased range of motion. CONCLUSION: Early clinical suspicion and microbiological diagnosis are key factors in reducing morbidity since septic arthritis with M. massiliense manifests late after the injection and treatment of it is a laborious process.

Detection of high-risk human papillomavirus using menstrual blood in women with high-grade squamous intraepithelial lesions or high-risk human papillomavirus infections: A pilot study.

AIM: Few studies have reported that human papillomavirus (HPV) tests using menstrual blood (MB) may be a convenient and effective screening modality for cervical cancer. Therefore, we aimed to investigate the efficacy of detecting high-risk (HR)-HPV from MB in women with high-grade squamous intraepithelial lesions or HR-HPV infections dependent on menstrual days. MATERIALS AND METHODS: In this prospective exploratory pilot study, a clinical trial was conducted in 19 women. On enrollment into the study, gynecologists collected cervical cells. On the first and second day of menstruation, MB was self-collected by patients using a sanitary pad with a filter. The distribution of HPVs from MB and the accuracy of menstrual HR-HPV tests were evaluated using HPV genotyping. The agreement rate of detecting HR-HPVs using cervical and MB samples was also investigated. RESULTS: The sensitivity, specificity, positive and negative predictive values of the MB HR-HPV test for detecting cervical intraepithelial neoplasia (CIN) 3 or worse were 87.5%, 45.5%, 53.8%, and 83.3%, respectively, during both menstrual cycle day (MCD) 1 and 2 and MCD 1 only; and 62.5%, 27.3%, 38.5%, and 50.0%, respectively, during MCD 2 only. For CIN 3 or worse, the agreement rate between positive cervical and MB HR-HPV test results was 87.5% during MCD 1 and 62.5% during MCD 2. CONCLUSIONS: We demonstrated the possibility of using the MB HPV test as a screening modality for cervical cancer.

Differential diagnosis between uterine sarcoma and leiomyoma using preoperative clinical characteristics.

AIM: The aim of this study was to identify the preoperative diagnostic findings suggestive of uterine sarcoma. METHODS: We retrospectively reviewed the medical records of 31 patients with pathologically confirmed uterine sarcoma including leiomyosarcoma, endometrial stromal sarcoma, and undifferentiated sarcoma, between 2003 and 2011. The cases were matched by age, year of procedure (plus or minus 1 year), and surgeon, to controls (1:3 ratio) selected from all the patients who underwent hysterectomy for uterine myoma during the same period. RESULTS: Uterine sarcomas had larger tumor size compared with leiomyoma on sonography (P = 0.006). There was no significant difference in the total number of masses found on ultrasonography (P = 0.066). On multivariate analysis increased neutrophil-to-lymphocyte ratio (NLR > 2.1), large tumor size (> 8.0 cm), and lower body mass index (BMI ≤ 20) were independent risk factors for uterine sarcoma (P = 0.014, 0.048, and 0.048, respectively). Sarcoma index was calculated by summing the number of risk factors. Higher sarcoma index was associated with increased risk of uterine sarcoma (0, 13.6%; 1, 21.7%; 2, 62.5%; 3, 100%). CONCLUSION: Preoperative NLR, tumor size, and BMI could be useful for the discrimination of sarcoma from leiomyoma of uterus.

Ataxia-Telangiectasia and RAD3-Related and Ataxia-Telangiectasia-Mutated Proteins in Epithelial Ovarian Carcinoma: Their Expression and Clinical Significance.

BACKGROUND/AIM: The expression patterns of the key DNA damage response-related proteins, ataxia-telangiectasia and tfiih/ner complex atp-dependent 5'-3' dna helicase subunit rad3 (RAD3)-related (ATR) and ataxia-telangiectasia-mutated (ATM) proteins in ovarian cancer are not well-known. This study aimed to evaluate the expressions of ATR and ATM proteins, and to investigate their clinical significance in epithelial ovarian carcinoma (EOC). MATERIALS AND METHODS: The expressions of nuclear/cytoplasmic Ser428-phosphorylated ATR (p-ATR) and Ser1981-phosphorylated ATM (p-ATM) were evaluated by immunohistochemistry in 100 patients with EOC. The clinical significances of p-ATR and p-ATM protein expression were evaluated in terms of tumor progression and survival. RESULTS: Low expression of cytoplasmic p-ATR was significantly associated with advanced stage, serous histology, large residual mass, and high preoperative serum CA125 level. Univariate survival analysis revealed that low expression of cytoplasmic p-ATR protein was significantly associated with poor disease-free survival and poor overall survival. CONCLUSION: Our study demonstrates that cytoplasmic ATR protein might serve as a prognostic biomarker for patients with EOC.