The Correlation between Sex Hormone-Binding Globulin and Clinical Characteristics According to Anti-Müllerian Hormone in Women with Regular Menstrual Cycles: A Prospective Study.

BACKGROUND: Polycystic ovarian syndrome (PCOS) can be diagnosed when the anti-Müllerian hormone (AMH) levels are high, but in clinic, women who do not meet the diagnosis of PCOS but have elevated AMH levels are often seen. This study aimed to compare the differences in menstrual cycle patterns and hormone levels in women with regular menstrual cycles, but not PCOS, by dividing them into high and low AMH groups. MATERIAL AND METHODS: This multicenter prospective study included 68 healthy women. Participants with regular menstrual cycles were divided into two groups according to their AMH levels. The main outcome measures were menstrual cycle pattern, body mass index, and hormone levels (thyroid stimulating hormone, prolactin, testosterone, sex hormone-binding globulin, and free androgen index), which were compared between the groups according to AMH levels. The ovulation was assessed by performing pelvic ultrasound, and by assessing the hormone levels of the luteinizing hormone and progesterone. RESULTS: The criteria for determining normal and high AMH levels were based on previous literatures. The participants were divided into normal (39 people) and high (29 people) AMH group. No differences were found in age or BMI between the two groups, and no other differences were observed in TSH, prolactin, testosterone, or free androgen index. However, the high AMH group had significantly higher SHBG levels than the normal group (normal group: 65.46 ± 25.78 nmol/L; high group: 87.08 ± 45.05 nmol/L) (p = 0.025). CONCLUSIONS: This study is the first to analyze the association between SHBG and AMH levels in women with regular menstrual cycles. Elevated AMH levels are associated with increased levels of SHBG levels.

Diagnostic Clues for Women with Acute Surgical Abdomen Associated with Ruptured Endometrioma.

(1) Background: An investigation of the preoperative diagnostic clues used to identify ruptured endometrioma by comparing the ruptured and unruptured states in patients who underwent laparoscopic operations due to endometrioma. (2) Methods: Patients with ruptured endometriomas (14 patients) and unruptured endometriomas (60 patients) were included, and clinical symptoms, laboratory findings, and radiological findings were analyzed. (3) Results: There were no significant differences in age, parity, last menstrual cycle days, or median size of endometrioma between two groups (group A: ruptured; group B: unruptured). The median serum level of CA 125 was 345.1 U/mL in group A and 49.8 U/mL in group B (p = 0.000). The median serum levels of CA 19-9 in group A and B were 46.0 U/mL and 19.1 U/mL, respectively (p = 0.005). The median serum level of CRP in group A was 1.2 g/dL, whereas it was 0.3 in group B (p = 0.000). ROC analysis showed that the optimal CA 125 cutoff value was 100.9 U/mL; the optimal CA 19-9 cutoff value was 27.7 U/mL; and the optimal CRP cutoff value was 1.0 g/dL. (4) Conclusions: Ruptured endometrioma can be diagnosed preoperatively using a combination of clinical symptoms, laboratory findings, and radiological findings. If a physician suspects a ruptured endometrioma, surgery should be performed to ensure optimal prognosis.

Pretreatment CT differential diagnosis of tuberculous peritonitis from peritoneal carcinomatosis of advanced epithelial ovarian cancer.

Delayed diagnosis of female genital tuberculosis (FGTB) can lead to inappropriate treatment and unnecessary surgical procedures rather than standard anti-TB medication. We tried to evaluate the use of computed tomography (CT) imaging to differentiate TB peritonitis from peritoneal carcinomatosis of advanced epithelial ovarian cancer (AEOC). We investigated women who underwent CT to distinguish between TB peritonitis and peritoneal carcinomatosis of AEOC. We evaluated various CT imaging features to identify differences between the two diseases. In addition, we performed univariate and multivariate logistic regression analyses to identify the independent imaging parameters associated with TB peritonitis and evaluated the diagnostic performance of the combined imaging parameters. We also performed the histopathological analysis of the available salpinx specimens of TB peritonitis. We included 25 women with TB peritonitis and 34 women with peritoneal carcinomatosis of AEOC. A multivariate analysis of the discriminant CT imaging features between the two diseases revealed that changes in fallopian tubes and peritoneal micronodules were independent parameters associated with TB peritonitis (p ≤ 0.012). Combining the two imaging parameters showed an area under the receiver operating characteristic curve of 0.855, a sensitivity of 88.0%, and a specificity of 67.7% for differentiating TB peritonitis from peritoneal carcinomatosis. Furthermore, changes in fallopian tubes were correlated with histopathological abnormalities in salpinx specimens. Pretreatment CT evaluation with useful imaging features could help differentiate TB peritonitis from peritoneal carcinomatosis of AEOC.

Growth inhibition by fusidic acid in cervical, thyroid, and breast carcinoma cell lines.

OBJECTIVE: We investigated the effects of fusidic acid (FA) on human cervical, thyroid, and breast carcinoma cell lines to determine the potential usefulness of FA in cancer treatment. METHODS: Six cancer cell lines (cervical cancer: Caski, HeLa; thyroid cancer: 8505C, TPC1; and breast cancer: MCF-7, MDA-MB-231) were treated with FA. Furthermore the changes in cell growth, cell cycle duration, and extent of apoptosis were analyzed. RESULTS: After FA treatment, the cancer cells showed a decrease in growth rate. In the cell death assay, the cell populations were similar in each cell type after treatment with FA, indicating that growth inhibition by FA was not related to the induction of apoptosis. FA induced cell cycle arrest at a dose that inhibited growth rate, which varied in different cell types. G0/G1 phase arrest occurs in breast cancer, S phase arrest in 8505C thyroid cancer, and G2/M phase arrest in cervical cancer. These results indicate that FA reduces growth rates by inducing cell cycle arrest. CONCLUSION: FA treatment can interfere with cell proliferation by inducing cell cycle arrest in human cervical, thyroid, and breast carcinoma cell lines. Thus, FA can be useful in treating human cervical, thyroid, and breast carcinomas.

Laparoscopic systemic restaging surgery for women with unexpected uterine malignancy.

OBJECTIVE: We investigated the feasibility of laparoscopic restaging surgery in patients with unexpected uterine cancer. METHODS: This retrospective study included eight patients who underwent laparoscopic restaging surgery for Iran University uterine cancer after a prior hysterectomy or myomectomy. RESULTS: The median age of the patients and their body mass index were 55 years (range, 44-78) and 23.8 kg/m2 (range, 20.75- 31.89), respectively. The median interval between the prior hysterectomy and the restaging surgery was 21 days (range, 10-35). The median operating time and time for the return of bowel activity were 325 minutes (range, 200-475) and 35 hours (range, 18-50), respectively. The median numbers of harvested pelvic and para-aortic lymph nodes were 17.5 (range, 14-29) and 20.5 (range, 7-36), respectively. In seven of the eight patients, uterine extraction was performed with vaginal or electronic morcellation. The final International Federation of Gynecology and Obstetrics stage was IA in all patients. Intraoperative and postoperative complications did not occur in any of the patients, except for the need for transfusion. Patient 4 had synchronous primary cancer (stage IA) of the endometrium and left ovary. Two of the eight patients with clear cell carcinoma received chemotherapy, and none received radiotherapy. All patients survived without disease recurrence. CONCLUSION: Restaging surgery might be necessary for highly selective patients with unexpected uterine malignancies. This would be an alternative surgical modality for complete staging and planning tailored adjuvant treatments. However, lymphadenectomy might not be performed in patients with early uterine cancer.

Conditional relative survival of patients with endometrial cancer: a Korean National Cancer Registry study.

OBJECTIVE: The purpose of this study was to estimate 5-year conditional relative survival (5Y CRS) rates of endometrial cancer (EC) in Korea accounting for time already survived. Subgroup-specific estimates stratified by various patient characteristics were also presented. METHODS: Using the data from the Korean Central Cancer Registry, 5Y CRS rates were calculated in patients who were diagnosed with EC between 1998 and 2017. The CRS rates were presented by year of diagnosis, age at diagnosis, histology, cancer stage, and treatment received. RESULTS: The 5-year relative survival rate at the time of diagnosis was 89.0% for all cases. The probability of surviving an additional 5 years (i.e., 5Y CRS), if the patient survived 1, 2, 3, 4, and 5 years after diagnosis was 91.8%, 94.1%, 95.6%, 96.5%, and 97.3%, respectively. Patients with poor initial prognoses, i.e., those who were older, had non-endometrioid histology, and high stage, showed the largest improvements in 5Y CRS, reaching >90% for most subgroups, except those with serous histology (88.4%) and distant stage (77.7%). Patients aged ≥70 years had the highest probability of death in the 1st and 2nd years after diagnosis (13.8 and 11.0%), but the conditional probability of death in the 3rd, 4th, and 5th years declined rapidly to 7.3%, 4.5%, and 3.7%, respectively. CONCLUSION: The CRS rates for patients with EC improved with increased time elapsed from diagnosis. The greatest improvements in 5Y CRS were observed among patients who were older, those with non-endometrioid histology, and those with more advanced disease.

Trends in incidence and survival of patients with vulvar cancer in an Asian country: Analysis of the Korean Central Cancer Registry 1999-2018.

OBJECTIVE: To report 20-year trends in incidence and survival of vulvar cancer in Korea. METHODS: Using data from the Korean Central Cancer Registry, age-standardized incidence rates (ASRs) and annual percentage changes (APCs) were calculated. Net survival (NS) was estimated by the Pohar-Perme method, and conditional net survival (CNS) was calculated. RESULTS: A total of 2221 patients was diagnosed with vulvar cancer during the 1999-2018 period, with an ASR of 0.32 per 100,000 person-years. Among the cases, 51.4% were squamous cell carcinoma (SqCC), 21.3% were Paget disease, and 8.6% were basal cell carcinoma (BCC). There was an increase in incidence for all vulvar cancer (APC 2.4%, 95% CI 1.8-3.0). However, although BCC (APC 7.0%, 95% CI 3.3-10.8) and Paget disease (APC 5.9%, 95% CI 4.2-7.6) increased, SqCC did not (APC 0.2%, 95% CI -0.8-1.2). There was an increase in incidence in all age groups. The 5Y NS was 74.0% overall, and it did not improve significantly during the study period. The 5Y CNS of vulvar cancer increased continuously with time survived: from 74.0% (71.4-76.4) at baseline to 98.1% (95% CI, 85.4-99.8) at 5 years after diagnosis. CONCLUSIONS: The incidence of vulvar cancer in Korea showed a different pattern from those in the US and Europe: SqCC incidence was relatively low and remained stable, but the incidence of BCC and Paget's disease increased. Survival did not improve in the past two decades. Patients can be considered cured after surviving for 5 years.

Conditional Relative Survival of Ovarian Cancer: A Korean National Cancer Registry Study.

OBJECTIVE: Conditional relative survival (CRS) rates, which take into account changes in prognosis over time, are useful estimates for survivors and their clinicians as they make medical and personal decisions. We aimed to present the 5-year relative conditional survival probabilities of patients diagnosed with ovarian cancer from 1997-2016. METHODS: This nationwide retrospective cohort study used data from the Korean Central Cancer Registry. Patients diagnosed with ovarian cancer between 1997 and 2016 were included. CRS rates were calculated stratified by age at diagnosis, cancer stage, histology, treatment received, year of diagnosis, and social deprivation index. RESULTS: The 5-year relative survival rate at the time of diagnosis was 61.1% for all cases. The probability of surviving an additional 5 years, conditioned on having already survived 1, 2, 3, 4, and 5 years after diagnosis was 65.0, 69.5, 74.6, 79.3, and 83.9%, respectively. Patients with poorer initial survival estimates (older, distant stage, serous histology) generally showed the largest increases in CRS over time. The probability of death was highest in the first year after diagnosis (11.8%), and the conditional probability of death in the 2nd, 3rd, 4th, and 5th years declined to 9.4%, 7.9%, 6.1%, and 5.2%, respectively. CONCLUSION: CRS rates for patients with ovarian cancer increased with each year they survived, but this did not reach the level of 'no excess mortality' even 5 years after diagnosis. The largest improvements in CRS were observed in patients with poorer initial prognoses. Our findings provide updated prognosis to ovarian cancer survivors and clinicians.

Conditional relative survival of cervical cancer: a Korean National Cancer Registry Study.

OBJECTIVE: Conditional relative survival (CRS) considers changes in prognosis over time and may offer more useful estimates for survivors. We aimed to investigate CRS among patients with cervical cancer stratified by various factors that influence survival probability. METHODS: This nationwide retrospective study used data from the Korean Central Cancer Registry. We included 78,606 patients diagnosed with cervical cancer as their first cancer between January 1, 1996 and December 31, 2015, and who were followed until December 31, 2016. CRS and the conditional probabilities of death for the following 1 year were stratified by age at diagnosis, histology, cancer stage, treatment, year of diagnosis, and social deprivation index. RESULTS: The 5-year relative survival rate at the time of diagnosis was 80.6% for all cases. The probability of surviving an additional 5 years conditioned on having already survived 1, 2, 3, 4, and 5 years after diagnosis was 85.7%, 90.6%, 93.5%, 95.3%, and 94.3%, respectively. Patients with poorer initial survival estimates (older, advanced stage, non-squamous cell histology) generally showed the largest increases in CRS over time. Patients aged ≥70 years had the highest probability of death in the first year after diagnosis (24.5%), but the conditional probability of death in the 2nd, 3rd, 4th, and 5th years declined abruptly to 13.1%, 7.5%, 5.4%, and 3.9%, respectively. CONCLUSIONS: The CRS rates for patients with cervical cancer improved over time, particularly among patients with poorer initial prognoses. Our estimates enable patients to make better informed decisions regarding follow-up care and their personal life.

Increased amounts and stability of telomeric repeat-containing RNA (TERRA) following DNA damage induced by etoposide.

Telomeric repeat-containing RNAs (TERRAs) are long noncoding RNAs transcribed from subtelomeres toward telomeric repeat tracts, which have been implicated in telomere protection and heterochromatin formation. Genotoxic stress leads to upregulation of TERRAs. However, the mechanism of DNA damage-mediated TERRA induction remains elusive. Here, we treated HeLa cells with etoposide, a DNA double-strand break-generating agent, for various times and monitored the levels of TERRAs. Etoposide treatment led to a gradual time-dependent increase in TERRAs. Etoposide-mediated induction was evident in many TERRAs arising from various chromosome loci, including 20q and XpYp. Chromatin immunoprecipitation assays revealed no significant changes in the occupancy of RNA polymerase II at telomeres upon etoposide treatment. Interestingly, TERRAs arising from 20q, XpYp, 10q, and 13q degraded at slower rates in cells treated with etoposide, while degradation rates of TERRAs from many loci tested were nearly identical in both etoposide- and mock-treated cells. Telomere damage occurred from early time points of etoposide treatment, but telomere lengths and abundance of telomeric repeat-binding factor 2 (TRF2) at telomeres remained unchanged. In summary, etoposide treatment led to telomere damage and TERRA accumulation, but telomere lengths and TRF2-mediated telomere integrity were maintained. Etoposide-mediated TERRA accumulation could be attributed partly to RNA stabilization. These findings may provide insight into the post-transcriptional regulation of TERRAs in response to DNA damage.

Clinical characteristics of patients with leiomyoma who undergo surgery after high intensity focused ultrasound (HIFU).

OBJECTIVE: We evaluated the clinical characteristics of patients who underwent surgery after high intensity focused ultrasound (HIFU) to treat uterine leiomyoma. METHODS: From June 2016 to September 2017, patients at our hospital who underwent HIFU to treat uterine leiomyoma prior to surgery were enrolled. All patients underwent pelvic magnetic resonance imaging (MRI) before and after HIFU. If 6 months had passed since the last pelvic MRI was performed, imaging was performed again before the operation. RESULTS: A total of 12 patients were analyzed. The median age was 45 (range, 28-51) years. The median body mass index was 24.9 (range, 18.1-29.2) kg/m2. The median size of the leiomyoma was 10.1 (range, 7.8-14.0) cm before HIFU, which changed to 8.75 (range, 5.9-14.8) cm after HIFU. The median size increased to 9.1 (range, 5.9-18.0) cm before the operation. Surgery was planned for several reasons, including an increase in the leiomyoma size (n=6), persistent symptoms (n=4), and newly developed lesion (n=2). The median interval between HIFU and surgery was 7 (range, 3-32) months. Ten of the 12 patients underwent laparoscopic surgery, while the others underwent laparotomy; 6 patients also underwent laparoscopic myomectomy, and 4 underwent hysterectomy. Histopathologic findings showed infarction-type necrosis surrounded by granulation tissue with the infiltration of lymphocytes and macrophages in all patients. CONCLUSION: Treatment of leiomyoma with operative procedures should be considered in selected patients with tumor size greater than 10 cm, multiple tumors, and persistent symptoms after HIFU treatment.

Systemic Laparoscopic Para-Aortic Lymphadenectomy to the Left Renal Vein.

BACKGROUND: No large-scale clinical study has been done to show the standard surgical boundary and efficacy of laparoscopic para-aortic lymphadenectomy (LPAL). OBJECTIVES: Therfore, this study aimed to evaluate the feasibility, efficacy, and standard surgical boundary of LPAL performed up to the left renal vein level in gynecological malignancies. METHODS: Medical records of 333 patients were retrospectively reviewed. All cases had gynecologic malignancies and had an operation including LPAL by a single surgical team between November 2003 and May 2018. RESULTS: Three hundred twenty-six patients underwent LPAL as part of their staging, restaging, or debulking surgery. Seven patients with isolated para-aortic lymph node recurrence underwent a repeat LPAL. The median age and body mass index were 54 years (range, 28-81 years) and 26.0 kg/m2 (range, 20.3-37.2 kg/m2), respectively. The median operating time was 60 minutes (range, 24-135 minutes), and the median number of harvested para-aortic lymph nodes was 12 (range, 6-49). There were 11 cases of complications: 5 of major vessel injuries (3 inferior vena cava, 1 aorta, and 1 common iliac vein), 2 lymphocysts, 2 cases of chylous ascites, a cisterna chyli rupture, and 1 case of ureteric injury. There were 2 conversions to laparotomy: 1 left common iliac vein laceration that needed to be repaired and removal of an enlarged para-aortic lymph node completely. CONCLUSION: It is feasible and efficient to perform LPAL to the left renal vein level for women with gynecologic malignancies by well-trained gynecologic oncology surgeons according to our suggested standard surgical boundary.

Coexisting ovarian and tubal pregnancies on opposite sides after intrauterine insemination: a case report.

BACKGROUND: Ovarian pregnancy is very rare, and contralateral tubal pregnancy coexisting with ovarian pregnancy must be even rarer. CASE PRESENTATION: A 33-year-old Korean nulliparous woman was referred to our hospital because she suffered lower abdominal pain and had missed her periods after controlled ovarian hyperstimulation and intrauterine insemination. We could not identify any normal gestational sac in the endometrium, or specific ectopic pregnancies, on an initial ultrasound scan. However, there was a large hematoma in the cul-de-sac and free fluid in the right paracolic gutter. We decided to perform emergent laparoscopic surgery. We found contralateral tubal and ovarian ectopic pregnancies. CONCLUSION: To the best of our knowledge, this is the first report of a case in which a patient underwent laparoscopic right salpingectomy and left ovarian ectopic mass excision due to contralateral tubal and ovarian ectopic pregnancies after assisted reproductive technology.

Effect of radioactive iodine-induced hypothyroidism on longitudinal bone growth during puberty in immature female rats.

Thyroid cancer in children, the most common endocrine malignancy, shows aggressive behavior and has a high recurrence rate after surgical ablation. Radioactive iodine (RAI) treatment is the most effective primary modality for medical ablation of juvenile thyroid cancer, and leads to intentional hypothyroidism. Although several negative impacts of hypothyroidism have been reported in children in response to other antithyroid agents, the combined effects of RAI exposure and hypothyroidism, on growing bones specifically, are unknown. In this study, we investigated the effect of RAI-induced hypothyroidism on the long bones during the pubertal growth spurt using immature female rats. Female Sprague-Dawley rats were randomly divided into a control group, and an RAI-treated group fed with RAI (0.37 MBq/g body weight) twice via gavage. After 4 weeks, we observed a significantly-reduced serum free thyroxine level in the RAI group. The latter group also displayed decreased body weight gain compared to the control. In addition, the lengths of long bones, such as the leg bones and vertebral column, as well as bone mineral content, were reduced in the RAI-treated animals. Our results confirm the negative impacts of RAI-induced thyroid deficiency during puberty on longitudinal bone growth and bone mineralization.

Encountering the Accessory Polar Renal Artery during Laparoscopic Para-Aortic Lymphadenectomy.

A 60-year-old Korean woman underwent laparoscopic bilateral salpingo-oophorectomy and was confirmed to have high-grade serous carcinoma of both ovaries with a huge omental cake, extensive agglutinated intra-abdominal metastatic masses, extensive serosa invasion of the intestines, and mesenterial deposits. She underwent 3 cycles of neoadjuvant chemotherapy followed by laparoscopic interval debulking surgery, including hysterectomy, pelvic and para-aortic lymphadenectomy, appendectomy, partial peritonectomy, and omentectomy. We encountered the right accessory polar renal artery (APRA) during the surgery and carefully preserved the right APRA from the abdominal aorta to the right kidney (Fig. 1). Postoperative computed tomography angiography showed an intact right APRA and normal-appearing kidney (Fig. 2). The patient had adjuvant chemotherapy and is alive without disease recurrence. Because APRA is a functional end artery, it is important to preserve it during surgery to prevent ischemic damage and renal failure [1]. It is very important for the gynecologic-oncologist to have knowledge of the retroperitoneal vascular anatomy, experience in laparoscopic surgery, and an accurate surgical technique to avoid vascular injury during laparoscopic para-aortic lymphadenectomy.

Preoperative diagnostic clues to ovarian pregnancy: retrospective chart review of women with ovarian and tubal pregnancy.

OBJECTIVE: To analyze the preoperative diagnostic clues to ovarian pregnancy (OP). METHODS: This study conducted a retrospective chart review of 23 patients with OP and 46 patients with tubal pregnancy (TP) from October 1, 2003 to September 31, 2016 in Hanyang University Hospital. RESULTS: There were no significant differences in demographic and clinical characteristics between the two groups. The presence of an ectopic gestational sac and hemoperitoneum was significantly higher in the TP group (13.0% vs. 95.7%, P=0.000; 13.0% vs. 54.3%, P=0.001, respectively) in preoperative ultrasonogram. The OP group had more ruptured ectopic gestational sacs than the TP group (73.9% vs. 45.7%, P=0.039) in surgical findings. CONCLUSION: For the patients in whom a gestational sac is not detected in the uterus or the fallopian tubes, it is important to be aware of the possibility of OP and rupture of an ovarian gestational sac to promote early diagnosis and surgical intervention.

Variable TERRA abundance and stability in cervical cancer cells.

Telomeres are transcribed into long non-coding RNA, referred to as telomeric repeat-containing RNA (TERRA), which plays important roles in maintaining telomere integrity and heterochromatin formation. TERRA has been well characterized in HeLa cells, a type of cervical cancer cell. However, TERRA abundance and stability have not been examined in other cervical cancer cells, at least to the best of our knowledge. Thus, in this study, we measured TERRA levels and stability, as well as telomere length in 6 cervical cancer cell lines, HeLa, SiHa, CaSki, HeLa S3, C-33A and SNU-17. We also examined the association between the TERRA level and its stability and telomere length. We found that the TERRA level was several fold greater in the SiHa, CaSki, HeLa S3, C-33A and SNU-17 cells, than in the HeLa cells. An RNA stability assay of actinomycin D-treated cells revealed that TERRA had a short half-life of ~4 h in HeLa cells, which was consistent with previous studies, but was more stable with a longer half-life (>8 h) in the other 5 cell lines. Telomere length varied from 4 to 9 kb in the cells and did not correlate significantly with the TERRA level. On the whole, our data indicate that TERRA abundance and stability vary between different types of cervical cancer cells. TERRA degrades rapidly in HeLa cells, but is maintained stably in other cervical cancer cells that accumulate higher levels of TERRA. TERRA abundance is associated with the stability of RNA in cervical cancer cells, but is unlikely associated with telomere length.

Peri-pubertal high caffeine exposure increases ovarian estradiol production in immature rats.

Chronic caffeine consumption exerts a negligible effect on the reproductive organs of normal adult females, but it is not known whether this is also true for children and adolescents. Here, we investigated the effects of high caffeine exposure on sexual maturation and ovarian estradiol production in immature female rats. Immature female SD rats were divided into controls and caffeine groups fed 120 and 180mg/kg/day for 4 or 8 weeks. There was a significant delay in vaginal opening in the caffeine-fed groups. In addition, serum estradiol levels were elevated in the caffeine-fed animals after 2 and 4 weeks of exposure. Estradiol secretion as well as aromatase expression also increased significantly in the ovarian cells in response to caffeine. These results demonstrate that peripubertal exposure to high caffeine increases estradiol production in the ovary; this may disturb the coordinated regulation of the hypothalamo-pituitary-ovarian axis, thereby interfering with sexual maturation.

Longitudinal bone growth is impaired by direct involvement of caffeine with chondrocyte differentiation in the growth plate.

We showed previously that caffeine adversely affects longitudinal bone growth and disrupts the histomorphometry of the growth plate during the pubertal growth spurt. However, little attention has been paid to the direct effects of caffeine on chondrocytes. Here, we investigated the direct effects of caffeine on chondrocytes of the growth plate in vivo and in vitro using a rapidly growing young rat model, and determined whether they were related to the adenosine receptor signaling pathway. A total of 15 male rats (21 days old) were divided randomly into three groups: a control group and two groups fed caffeine via gavage with 120 and 180 mg kg-1  day-1 for 4 weeks. After sacrifice, the tibia processed for the analysis of the long bone growth and proliferation of chondrocytes using tetracycline and BrdU incorporation, respectively. Caffeine-fed animals showed decreases in matrix mineralization and proliferation rate of growth plate chondrocytes compared with the control. To evaluate whether caffeine directly affects chondrocyte proliferation and chondrogenic differentiation, primary rat chondrocytes were isolated from the growth plates and cultured in either the presence or absence of caffeine at concentrations of 0.1-1 mm, followed by determination of the cellular proliferation or expression profiles of cellular differentiation markers. Caffeine caused significant decreases in extracellular matrix production, mineralization, and alkaline phosphatase activity, accompanied with decreases in gene expression of the cartilage-specific matrix proteins such as aggrecan, type II collagen and type X. Our results clearly demonstrate that caffeine is capable of interfering with cartilage induction by directly inhibiting the synthetic activity and orderly expression of marker genes relevant to chondrocyte maturation. In addition, we found that the adenosine type 1 receptor signaling pathway may be partly involved in the detrimental effects of caffeine on chondrogenic differentiation, specifically matrix production and mineralization, as evidenced by attenuation of the inhibitory effects of caffeine by blockade of this receptor. Thus, our study provides novel information on the integration of caffeine and adenosine receptor signaling during chondrocyte maturation, extending our understanding of the effect of caffeine at a cellular level on chondrocytes of the growth plate.

Surgical manual of the Korean Gynecologic Oncology Group: ovarian, tubal, and peritoneal cancers.

The Surgery Treatment Modality Committee of the Korean Gynecologic Oncology Group has determined to develop a surgical manual to facilitate clinical trials and to improve communication between investigators by standardizing and precisely describing operating procedures. The literature on anatomic terminology, identification of surgical components, and surgical techniques were reviewed and discussed in depth to develop a surgical manual for gynecologic oncology. The surgical procedures provided here represent the minimum requirements for participating in a clinical trial. These procedures should be described in the operation record form, and the pathologic findings obtained from the procedures should be recorded in the pathologic report form. Here, we describe surgical procedure for ovarian, fallopian tubal, and peritoneal cancers.