Human Endometrium Derived Induced Pluripotent Stem Cells Are Amenable to Directed Erythroid Differentiation

BACKGROUND@#A protocol for using human endometrium derived induced pluripotent stem cells (iPSCs) to derive hematopoietic and erythroid lineages will be elaborated, through a two-phase culture system. @*METHODS@#Discarded endometrial tissues were obtained from women receiving hysterectomy in their 4th to 5th decade due to benign uterine conditions. pCE-Sox2, Oct4, Klf4, L-Myc and Lin28 episomal vectors were used to electrotransfect the endometrial stromal cells. The first 8 days involves commitment to hematopoietic stem cells through embryoid body with robust expansion on murine bone marrow stromal cells. The second phase involves feeder free conditions with hydrocortisone, stem cell factor, interleukin-3, and recombinant EPO. After 22 days of feeder free culture, the expression profiles of CD235a+ , CD34+ , CD43+ and CD 71+ were analyzed by flow cytometry and Wright-Giemsa staining for differential counting. The oxygen carrying capacity of cultured RBCs was measured using a hemoxanalyser. @*RESULTS@#As a result of inducing these cells via co-culture with murine stromal fibroblasts, all endometrium derived iPSCs were differentiated into erythroblasts with a stable yield of approximately 80% for polychromatic and orthochromatic normoblasts. The protocol for complete induction of erythroid lineage cells starting from human endometrial tissue via iPS cells has been optimized. @*CONCLUSION@#Successful directed erythroid differentiation has occurred from human endometrium-derived iPS cells. A comprehensive process of actually deriving iPS cells using discarded surgical hysterectomy specimens to the erythroid fate has significance in that the scope of using human iPSC cell lines for tissue regeneration could be expanded in the future.

Next-generation sequencing analysis of hepatitis C virus resistance–associated substitutions in direct-acting antiviral failure in South Korea

Background/Aims@#We used next-generation sequencing (NGS) to analyze resistance-associated substitutions (RASs) and retreatment outcomes in patients with chronic hepatitis C virus (HCV) infection who failed direct-acting antiviral agent (DAA) treatment in South Korea. @*Methods@#Using prospectively collected data from the Korean HCV cohort study, we recruited 36 patients who failed DAA treatment in 10 centers between 2007 and 2020; 29 blood samples were available from 24 patients. RASs were analyzed using NGS. @*Results@#RASs were analyzed for 13 patients with genotype 1b, 10 with genotype 2, and one with genotype 3a. The unsuccessful DAA regimens were daclatasvir+asunaprevir (n=11), sofosbuvir+ribavirin (n=9), ledipasvir/sofosbuvir (n=3), and glecaprevir/pibrentasvir (n=1). In the patients with genotype 1b, NS3, NS5A, and NS5B RASs were detected in eight, seven, and seven of 10 patients at baseline and in four, six, and two of six patients after DAA failure, respectively. Among the 10 patients with genotype 2, the only baseline RAS was NS3 Y56F, which was detected in one patient. NS5A F28C was detected after DAA failure in a patient with genotype 2 infection who was erroneously treated with daclatasvir+asunaprevir. After retreatment, 16 patients had a 100% sustained virological response rate. @*Conclusions@#NS3 and NS5A RASs were commonly present at baseline, and there was an increasing trend of NS5A RASs after failed DAA treatment in genotype 1b. However, RASs were rarely present in patients with genotype 2 who were treated with sofosbuvir+ribavirin. Despite baseline or treatment-emergent RASs, retreatment with pan-genotypic DAA was highly successful in Korea, so we encourage active retreatment after unsuccessful DAA treatment.

Efficacy and safety of sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir for hepatitis C in Korea: a Phase 3b study

Despite the availability of direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection in Korea, need remains for pangenotypic regimens that can be used in the presence of hepatic impairment, comorbidities, or prior treatment failure. We investigated the efficacy and safety of sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir for 12 weeks in HCV-infected Korean adults. Methods: This Phase 3b, multicenter, open-label study included 2 cohorts. In Cohort 1, participants with HCV genotype 1 or 2 and who were treatment-naive or treatment-experienced with interferon-based treatments, received sofosbuvir–velpatasvir 400/100 mg/day. In Cohort 2, HCV genotype 1 infected individuals who previously received an NS5A inhibitor-containing regimen ≥ 4 weeks received sofosbuvir–velpatasvir–voxilaprevir 400/100/100 mg/day. Decompensated cirrhosis was an exclusion criterion. The primary endpoint was SVR12, defined as HCV RNA < 15 IU/mL 12 weeks following treatment. Results: Of 53 participants receiving sofosbuvir–velpatasvir, 52 (98.1%) achieved SVR12. The single participant who did not achieve SVR12 experienced an asymptomatic Grade 3 ASL/ALT elevation on day 15 and discontinued treatment. The event resolved without intervention. All 33 participants (100%) treated with sofosbuvir–velpatasvir–voxilaprevir achieved SVR 12. Overall, sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir were safe and well tolerated. Three participants (5.6%) in Cohort 1 and 1 participant (3.0%) in Cohort 2 had serious adverse events, but none were considered treatment-related. No deaths or grade 4 laboratory abnormalities were reported. Conclusions: Treatment with sofosbuvir–velpatasvir or sofosbuvir–velpatasvir–voxilaprevir was safe and resulted in high SVR12 rates in Korean HCV patients.

A Multi-Center, Double-Blind Randomized Controlled Phase III Clinical Trial to Evaluate the Antiviral Activity and Safety of DA-2802 (Tenofovir Disoproxil Orotate) and Viread (Tenofovir Disoproxil Fumarate) in Chronic Hepatitis B Patients

Background@#Tenofovir disoproxil fumarate (TDF, Viread® ) had been used as a standard treatment option of chronic hepatitis B (CHB). This clinical trial was conducted to evaluate the efficacy and safety of DA-2802 (tenofovir disoproxil orotate) compared to TDF. @*Methods@#The present study was a double blind randomized controlled trial. Patients with CHB were recruited from 25 hospitals in Korea and given DA-2802 at a dose of 319 mg once daily or Viread® at a dose of 300 mg once daily for 48 weeks from March 2017 to January 2019. Change in hepatitis B virus (HBV) DNA level at week 48 after dosing compared to baseline was the primary efficacy endpoint. Secondary efficacy endpoints were proportions of subjects with undetectable HBV DNA, those with normal alanine aminotransferase (ALT) levels, and those with loss of hepatitis B envelop antigen (HBeAg), those with loss of hepatitis B surface antigen (HBsAg). Adverse events (AEs) were also investigated. @*Results@#A total of 122 patients (DA-2802 group: n = 61, Viread® group: n = 61) were used as full analysis set for efficacy analysis. Mean age, proportion of males, laboratory results and virologic characteristics were not different between the two groups. The change in HBV DNA level at week 48 from baseline was −5.13 ± 1.40 in the DA-2802 group and −4.97 ± 1.40 log 10 copies/mL in the Viread® group. The analysis of primary endpoint using the nonparametric analysis of covariance showed statistically significant results (P < 0.001), which confirmed non-inferiority of DA-2802 to Viread® by a prespecified noninferiority margin of 1. The proportion of undetectable HBV DNA was 78.7% in the DA-2802 group and 75.4% in the Viread® group (P = 0.698). The proportion of subjects who had normal ALT levels was 75.4% in the DA-2802 group and 73.3% in the Viread® group (P = 0.795). The proportion of those with HBeAg loss was 8.1% in the DA-2802 group and 10.8% in the Viread® group (P = 1.000). No subject showed HBsAg loss. The frequency of AEs during treatment was similar between the two groups. Most AEs were mild to moderate in severity. @*Conclusion@#DA-2802 is considered an effective and safe treatment for patients with CHB.

Delayed postpartum regression of theca lutein cysts with maternal virilization: A case report / 대한생식의학회지

Theca lutein cysts are rare, benign lesions responsible for gross cystic enlargement of both ovaries during pregnancy. This condition is also termed hyperreactio luteinalis. Elevated human chorionic gonadotropin (hCG) levels or states of hCG hypersensitivity seem to promote these changes, which in up to 30% of patients produce clinical signs of hyperandrogenism. Given the self-limiting course of theca lutein cysts, which are subject to spontaneous postpartum resolution, conservative treatment is the mainstay of patient management. Described herein is a rare case of theca lutein cysts with maternal virilization that failed to regress by 9 months after childbirth. Surgical intervention was eventually undertaken, necessitated by adnexal torsion.

Effectiveness and safety of elbasvir/grazoprevir in Korean patients with hepatitis C virus infection: a nationwide real-world study

Background@#/Aim: This study aimed to establish the real-world effectiveness and safety of grazoprevir/elbasvir (EBR/GZR) therapy in South Korea. @*Methods@#A total of 242 patients with chronic hepatitis C virus (HCV) genotype 1 or 4 infection who started EBR/GZR were consecutively enrolled from seven tertiary hospitals. Retrospective analysis of the fractions of patients that achieved sustained virological response (SVR) was performed, and the incidence of adverse events was noted. @*Results@#The mean age of enrolled patients was 59.0 ± 12.6 years and 47.5% were males. Patients with HCV genotype 1b accounted for 93.8% (n = 227), and patients with HCV of unspecified genotype 1 accounted for 5.8% (n = 14). Hypertension was the most common comorbid disease (29.8%) followed by diabetes (22.7%) and chronic kidney disease (CKD, 12.4%). SVR rates of treatment-naïve and treatment-experienced patients were 85.5% (182/213) and 93.1% (27/29), respectively, in the intention-to-treat analyses, whereas in the per-protocol analyses, those were 97.8% (179/183) and 100% (28/28), respectively. Fewer patients with HCV genotype 1 of unspecified subtype achieved SVR (81.8%, n = 11) compared to the patients with SVR infected with genotype 1b (99%, n = 198, p < 0.001). All patients with CKD showed SVR. Itching (12%) and dyspepsia (4.1%) were common adverse events. Of the four patients who discontinued the antiviral therapy, one experienced mild fatigue but neither treatment withdrawal was because of an adverse event. @*Conclusions@#EBR/GZR showed high real-world effectiveness and safety in Korean patients with chronic HCV infection regardless of the previous antiviral treatment, liver cirrhosis, or CKD status.

Association between new-onset liver cirrhosis and suicide risk in South Korea: A nationwide cohort study

Background/Aims@#Current evidence suggests that liver cirrhosis (LC) causes severe psychological stress and depression, which are risk factors for suicide. Although previous studies reported the association between LC and suicidal thoughts, little is known of its effect on suicidal deaths. Therefore, this study was undertaken to investigate the effect of new-onset LC on suicide. @*Methods@#From the National Health Insurance Service-National Sample Cohort of South Korea, 5,809 incident LC patients and 11,618 risk-set controls matched by propensity score were selected for follow-up. The incidence rate of suicide was estimated using a generalized estimating equation with a Poisson distribution. Effect size was presented as a hazard ratio (HR) using Cox’s proportional hazards model. @*Results@#The incidence rate of suicide was 143.3 cases per 100,000 person years (95% confidence interval [CI], 100.2–205.1) among the LC cohort. The LC patients were 2.37 times more likely to commit suicide compared with matched controls (HR, 2.37; 95% CI, 1.44–3.88). Increased suicide risk was evident within the first 2 years of the follow-up period (HR, 2.59; 95% CI, 1.20–5.60) and among the 18–49-year-old age group (HR, 3.72; 95% CI, 1.45–9.56). @*Conclusions@#Our study found increased risk of suicide in patients with new onset LC, especially during the early period following diagnosis and in younger patients. To decrease this suicide risk, a regular and continuous social support system is required.

Continuing besifovir dipivoxil maleate versus switching from tenofovir disoproxil fumarate for treatment of chronic hepatitis B: Results of 192-week phase 3 trial

Background/Aims@#Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. @*Methods@#Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). @*Results@#Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. @*Conclusions@#BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).

Intestinal Perforation as a Paradoxical Reaction to Antitubercular Therapy: A Case Report

Paradoxical reactions to tuberculosis (TB) treatment are characterized by an initial improvement of the clinical symptoms followed by clinical or radiological deterioration of existing tuberculous lesions, or by development of new lesions. Intestinal perforation in gastrointestinal TB can occur as a paradoxical reaction to antitubercular therapy. A 55-year-old man visited the outpatient department with lower abdominal pain and weight loss. He was diagnosed with intestinal TB and started antitubercular therapy. After 3 months of antitubercular therapy, a colonoscopy revealed improvement of the disease. Three days after the colonoscopy, the patient visited the emergency room complaining of abdominal pain. Abdominal computed tomography revealed extraluminal air-filled spaces in the pelvic cavity. We diagnosed a small bowel perforation and performed an emergency laparotomy and a right hemicolectomy with small bowel resection. This report describes the case of intestinal perforation presenting as a paradoxical reaction to antitubercular and provides a brief literature review.

Association between new-onset liver cirrhosis and suicide risk in South Korea: A nationwide cohort study

Background/Aims@#Current evidence suggests that liver cirrhosis (LC) causes severe psychological stress and depression, which are risk factors for suicide. Although previous studies reported the association between LC and suicidal thoughts, little is known of its effect on suicidal deaths. Therefore, this study was undertaken to investigate the effect of new-onset LC on suicide. @*Methods@#From the National Health Insurance Service-National Sample Cohort of South Korea, 5,809 incident LC patients and 11,618 risk-set controls matched by propensity score were selected for follow-up. The incidence rate of suicide was estimated using a generalized estimating equation with a Poisson distribution. Effect size was presented as a hazard ratio (HR) using Cox’s proportional hazards model. @*Results@#The incidence rate of suicide was 143.3 cases per 100,000 person years (95% confidence interval [CI], 100.2–205.1) among the LC cohort. The LC patients were 2.37 times more likely to commit suicide compared with matched controls (HR, 2.37; 95% CI, 1.44–3.88). Increased suicide risk was evident within the first 2 years of the follow-up period (HR, 2.59; 95% CI, 1.20–5.60) and among the 18–49-year-old age group (HR, 3.72; 95% CI, 1.45–9.56). @*Conclusions@#Our study found increased risk of suicide in patients with new onset LC, especially during the early period following diagnosis and in younger patients. To decrease this suicide risk, a regular and continuous social support system is required.

Continuing besifovir dipivoxil maleate versus switching from tenofovir disoproxil fumarate for treatment of chronic hepatitis B: Results of 192-week phase 3 trial

Background/Aims@#Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. @*Methods@#Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). @*Results@#Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. @*Conclusions@#BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).

Intestinal Perforation as a Paradoxical Reaction to Antitubercular Therapy: A Case Report

Paradoxical reactions to tuberculosis (TB) treatment are characterized by an initial improvement of the clinical symptoms followed by clinical or radiological deterioration of existing tuberculous lesions, or by development of new lesions. Intestinal perforation in gastrointestinal TB can occur as a paradoxical reaction to antitubercular therapy. A 55-year-old man visited the outpatient department with lower abdominal pain and weight loss. He was diagnosed with intestinal TB and started antitubercular therapy. After 3 months of antitubercular therapy, a colonoscopy revealed improvement of the disease. Three days after the colonoscopy, the patient visited the emergency room complaining of abdominal pain. Abdominal computed tomography revealed extraluminal air-filled spaces in the pelvic cavity. We diagnosed a small bowel perforation and performed an emergency laparotomy and a right hemicolectomy with small bowel resection. This report describes the case of intestinal perforation presenting as a paradoxical reaction to antitubercular and provides a brief literature review.

Refractory Hepatic Hydrothorax in Chronic Hepatitis C Controlled by Direct-acting Antivirals / 대한소화기학회지

Hepatic hydrothorax is a transudative pleural effusion that complicates advanced liver cirrhosis. Patients refractory to medical treatment plus salt restriction and diuretics are considered to have refractory hepatic hydrothorax and may require transjugular intrahepatic portosystemic shunt (TIPS) or liver transplant. Successful antiviral therapy reduces the incidence of some complications of cirrhosis secondary to HCV infection. We report a case of hepatic hydrothorax in a 55-year-old female patient with HCV cirrhosis, which exhibited a spontaneous decrease in pleural effusion after direct antiviral agent (DAA) therapy. In cases of HCV cirrhosis, DAAs are worth administering before treatment by TIPS or liver transplantation.

Real-Life Effectiveness and Safety of Sofosbuvir-Based Therapy in Genotype 2 Chronic Hepatitis C Patients in South Korea, with Emphasis on the Ribavirin Dose

Background/Aims@#Sofosbuvir (SOF)-based therapy has been used in Korean patients with chronic hepatitis C virus (HCV) infection since January 2016. This study aimed to in-vestigate the real-life effectiveness and safety of SOF-based therapy in genotype 2 HCV infection. @*Methods@#From January to December 2016, 458 genotype 2 HCV-infected patients who received ≥1 dose of SOF-based therapy were consecu-tively enrolled in seven tertiary hospitals. Sustained virologic response (SVR) rates and safety were determined by inten-tion-to-treat (ITT) and per-protocol (PP) analyses. @*Results@#The mean age of the patients was 61.0 years; 183 (40%) were male, and 13.1% showed a high viral load (>6,000,000 IU/ mL). Among the 378 treatment-naïve patients, the SVR rates were 94.2% (ITT) and 96.7% (PP). Among the 80 treatmentexperienced patients, the SVR rates were 96.3% (ITT) and 98.7% (PP). Patients with a relatively high fibrosis-4 index score (>3.25) had similar SVR rates to those with a relatively low score (p=0.756). A total of 314 patients (68.6%) were treated with a reduced ribavirin dose at the prescriber’s dis-cretion, but they showed similar SVR rates to those treated with the weight-based dose (ITT: 95.5% and 92.3%, PP: 97.4% and 96.3%, respectively). Adverse events were ob-served in 191 patients (41.7%), including 86 (18.8%) with anemia, but only one (0.2%) discontinued antiviral therapy due to nausea. @*Conclusions@#SOF-based therapy showed high real-life efficacy and tolerability in Korean patients with genotype 2 chronic HCV infection, regardless of previous antiviral treatment experience and fibrosis score. A reduced ribavirin dose can be considered in this patient cohort.

Operative hysteroscopy-assisted pregnancy termination after failed surgical abortion in missed abortion of woman with complete septate uterus

Updated guideline for clinical evaluation and management of endometriosis

Endometriosis is a common disease in reproductive aged women, and it detrimentally affects patients' quality of life and fertility. Moreover, because of the complexity of the disease itself, proper effective management is difficult. Within this context, this review proposes the guidelines of the Korean Society of Endometriosis and other world leading societies for endometriosis with an emphasis on: diagnosis of endometriosis, treatment for endometriosis associated pain and infertility, management of asymptomatic women, endometriosis associated malignancy, and endometriosis in postmenopausal women. In recent years, the importance of medical treatment as opposed to surgical removal in the management of endometriosis is gaining popularity. Many guidelines recommend empirical treatment without diagnostic laparoscopy and long term use of medication. This is also closely connected to the social trend of late marriage age and childbirth age. Nevertheless, timely surgical interventions and assisted reproductive procedures are still crucial in the management of endometriosis. Because treatment goals differ in each patient's individual situation, possible treatment options may vary and individualized management is also important. Ultimately, a multimodal approach that is tailored to each individual's therapeutic purpose is of paramount importance in the treatment of endometriosis.

Efficacy and Safety of Daclatasvir and Asunaprevir in Patients with Hepatitis C Virus Genotype 1b Infection on Hemodialysis

BACKGROUND/AIMS: We evaluated the efficacy and safety of daclatasvir (DCV) and asunaprevir (ASV) in patients with chronic hepatitis C virus (HCV) infection on hemodialysis. METHODS: We performed a single-arm, multicenter prospective study. Twenty-one chronic hemodialysis patients with HCV infection were prospectively enrolled from February 2016 to April 2017. We evaluated the virological responses at weeks 4, 12, and 24 (end of treatment [EOT]) and the sustained virological response at 12 weeks after the EOT (SVR12). The tolerability and safety of the drugs were also assessed. RESULTS: None of the 20 patients had the NS5A resistance-associated variant (NS5A RAV), and one patient was indeterminate for the NS5A RAV. Seventeen patients (80%) completed the 24 weeks of treatment with DCV and ASV. Four patients discontinued the study prior to week 12. In an intention-to-treat analysis, the SVR12 was 76.1%. In a per-protocol analysis, patients who completed DCV and ASV treatment achieved an SVR12 of 100%. DCV and ASV were well tolerated by the majority of patients. Three patients discontinued treatment due to adverse events (AEs) including dizziness, dyspnea, and neutropenia. The patient with indeterminate NS5A RAV showed viral breakthrough and discontinued treatment. CONCLUSIONS: DCV and ASV combination therapy in chronic hemodialysis patients with HCV infection achieved a high SVR12 rate with few AEs. To maximize the SVR12 rate, it is important to identify candidates by baseline RAV testing. Close monitoring of the safety and tolerability of DCV and ASV may be necessary in HCV-infected patients on hemodialysis. (ClinicalTrials.gov ID NCT02580474)

Polycystic ovarian morphology is associated with primary dysmenorrhea in young Korean women

OBJECTIVE: This study was aimed at identifying a correlation between polycystic ovarian morphology (PCOM) and the severity of primary dysmenorrhea in young Korean women. METHODS: A total of 592 patients who visited a tertiary hospital from March 2008 to March 2015 for dysmenorrhea were examined. After excluding those with secondary causes of menstrual pain (for example, myoma, adenomyosis, endometriosis, and pelvic inflammatory disease), 361 women were recruited and retrospectively analyzed. Severe dysmenorrhea was defined as a visual analog scale (VAS) score ≥6. RESULTS: The mean patient age was 23.0±4.0 years, the average menstrual cycle length was 34.4±23.7 days, and the average pain intensity was VAS 6.7±0.1 at baseline. PCOM was assessed by ultrasound in 54 women (15%). Patients with severe menstrual pain were more likely to have irregular menstrual cycles (P=0.03) and heavy menstrual flow (P=0.01) than those with mild menstrual pain. After adjusting for weight, height, menstrual cycle interval, and menstrual flow in the logistic regression analysis, PCOM (odds ratio [OR], 2.26; 95% confidence interval [CI], 1.05–4.97; P=0.04) and heavy menstrual flow (OR, 1.85; 95% CI, 1.05–3.28; P=0.04) were found to be significant independent factors influencing pain. CONCLUSION: Our study shows that PCOM may have a correlation with the severity of primary dysmenorrhea. Since PCOM may play a role in the development of menstrual pain, patients with PCOM should be under active surveillance with resources for prompt pain management readily available. It may also be necessary to further investigate the molecular mechanisms of pain development in primary dysmenorrhea.

Diagnosis of an indistinct Leydig cell tumor by positron emission tomography-computed tomography

A 51-year-old perimenopausal female patient presented with hirsutism and voice thickening which was started approximately one and a half years ago. Her initial hormone assay revealed elevated plasma testosterone, 5a-dihydrotestosterone, and dehydroepiandrosterone (DHEA) levels and therefore androgen-secreting tumor was first suspected. However, the lesion was inconspicuous on transvaginal sonography, abdominal-pelvic computed tomography (CT) scan, and pelvic magnetic resonance (MRI) imaging. Consequently, 18F-fluorodeoxyglucose (FDG) positron emission tomography-CT was performed, which localized the lesion as a focal FDG uptake within the right adnexa. Total laparoscopic hysterectomy with bilateral salpingo-oophorectomy was performed, and although visible gross mass lesions were not observed intraoperatively, pure Leydig cell tumor was pathologically confirmed within the right ovary. Plasma testosterone, 5a-dihydrotestosterone, and DHEA levels were normalized postoperatively. Clinical signs of virilization were also significantly resolved after 3-months of follow-up.

Updated guideline for clinical evaluation and management of endometriosis

Endometriosis is a common disease in reproductive aged women, and it detrimentally affects patients' quality of life and fertility. Moreover, because of the complexity of the disease itself, proper effective management is difficult. Within this context, this review proposes the guidelines of the Korean Society of Endometriosis and other world leading societies for endometriosis with an emphasis on: diagnosis of endometriosis, treatment for endometriosis associated pain and infertility, management of asymptomatic women, endometriosis associated malignancy, and endometriosis in postmenopausal women. In recent years, the importance of medical treatment as opposed to surgical removal in the management of endometriosis is gaining popularity. Many guidelines recommend empirical treatment without diagnostic laparoscopy and long term use of medication. This is also closely connected to the social trend of late marriage age and childbirth age. Nevertheless, timely surgical interventions and assisted reproductive procedures are still crucial in the management of endometriosis. Because treatment goals differ in each patient's individual situation, possible treatment options may vary and individualized management is also important. Ultimately, a multimodal approach that is tailored to each individual's therapeutic purpose is of paramount importance in the treatment of endometriosis.