ROCK and PDE-5 Inhibitors for the Treatment of Dementia: Literature Review and Meta-Analysis.

Dementia is a disease in which memory, thought, and behavior-related disorders progress gradually due to brain damage caused by injury or disease. It is mainly caused by Alzheimer's disease or vascular dementia and several other risk factors, including genetic factors. It is difficult to treat as its incidence continues to increase worldwide. Many studies have been performed concerning the treatment of this condition. Rho-associated kinase (ROCK) and phosphodiesterase-5 (PDE-5) are attracting attention as pharmacological treatments to improve the symptoms. This review discusses how ROCK and PDE-5 affect Alzheimer's disease, vascular restructuring, and exacerbation of neuroinflammation, and how their inhibition helps improve cognitive function. In addition, the results of the animal behavior analysis experiments utilizing the Morris water maze were compared through meta-analysis to analyze the effects of ROCK inhibitors and PDE-5 inhibitors on cognitive function. According to the selection criteria, 997 publications on ROCK and 1772 publications on PDE-5 were screened, and conclusions were drawn through meta-analysis. Both inhibitors showed good improvement in cognitive function tests, and what is expected of the synergy effect of the two drugs was confirmed in this review.

Evaluation of the distance from the anterior cervicovaginal junction to the anterior peritoneal reflection for anterior colpotomy during vaginal hysterectomy in Korean women.

ABSTRACT: This study aimed to know the distance of the cervicovaginal junction (CVJ) to the anterior peritoneal reflection (APR) as measured in surgical specimens, and assess the distance between the CVJ and APR to ensure safe anterior colpotomy for vaginal hysterectomy among Korean women.Patients who underwent vaginal hysterectomy were included in the analysis. According to the presence of pelvic organ prolapse or menopausal status, the distance from the CVJ to the APR was assessed preoperatively through transvaginal ultrasonography (TV-US), as well as intraoperatively using surgical specimens. The intraclass correlation coefficient was used to determine the reliability between 2 measurements.In total, 171 patients were included. The median distance from the CVJ to the APR measured on TV-US was 19.8 (3.3-41.3) mm. Meanwhile, the median distance from the CVJ to the APR measured using the surgical specimen was 26.0 (12.0-55.0) mm. The intraclass correlation coefficient for the absolute agreement between 2 measurements was 0.353 (95% confidence interval: 0.002-0.570; P < .001), which is indicative of poor reliability. The median distance from the CVJ to the APR measured using the surgical specimen did not differ significantly between the 2 groups according to pelvic organ prolapse (26.0 [12.0-55.0] vs 27.5 [17.0-55.0] mm, P = .076] and menopausal status (27.0 [15.0-55.0] vs 26.0 [12.0-55.0] mm, P = .237).TV-US does not an accurately measure the dissection plane length from the CVJ to the APR during anterior colpotomy. During vaginal hysterectomy, the median distance from the CVJ to the APR measured using the surgical specimen was 26 (12.0-55.0) mm, which can help decrease surgical complications.

Optimal duration of fertility-sparing hormonal treatment for early-stage endometrioid endometrial cancer.

OBJECTIVES: To analyze the oncologic outcomes of long-term fertility-sparing treatment (FST) in patients with early-stage endometrial cancer (EC) and to determine the optimal duration of FST that would not hamper survival outcomes. METHODS: Patients undergoing FST for presumed stage IA, grade 1 EC between 2005 and 2018 were retrospectively analyzed. Oncologic outcomes were compared between the group with ≤6 months of FST and the group with >6 months of FST. Segmented regression analysis was used to estimate the dynamic changes in cumulative complete response (CR) rates according to FST duration. RESULTS: A total of 122 patients received oral progestin, with concurrent levonorgestrel-releasing intrauterine device use in 108 (88.5%) and 105 (86.1%) achieved CR with a median time to achieve CR of 10 (3-42) months. Of the patients not achieving CR at 6 months of FST, 95.1% (78/82) continued further FST. The overall CR rate (88.9% [32/36] vs. 84.9% [73/86], P = 0.436] was not significantly different between the groups with ≤6 and > 6 months of FST. The changes in cumulative CR rates were significantly different between the two segments divided by 15 months from the initial FST (P = 0.0015, segmented regression analysis). The overall progressive disease (PD) rate was 3.3% (4/122), and PD was first detected during 9-12 months of FST. CONCLUSION: Patients not achieving CR and not showing PD at 6 months of FST could continue further FST. If disease progression is excluded, 15 months of FST can be considered as the cutoff for the optimal FST duration.

Sarcopenia as a Predictor of Prognosis in Early Stage Ovarian Cancer.

BACKGROUND: To identify sarcopenia as a predictive prognostic factor of ovarian cancer in terms of survival outcome in patients with early-stage ovarian cancer. METHODS: Data of Konkuk University Medical Center from March 2002 to December 2017 were reviewed retrospectively. Eighty-two patients who underwent surgery due to early-stage (International Federation of Gynecology and Obstetrics stage I/II) ovarian cancer and had computed tomography (CT) images taken at the initial diagnosis were included. The initial CT scan images were analyzed with SliceOmatic software (TomoVision). A sarcopenia cutoff value was defined as a skeletal muscle index of ≤ 38.7 cm²/m². Overall survival (OS) times were compared according to the existence of sarcopenia, and subgroup analyses were performed. RESULTS: A Kaplan-Meier analysis showed a significant survival disadvantage for patients with early-stage ovarian cancer when they had sarcopenia (P < 0.001; log-rank test). Sarcopenia remained a significant prognostic factor for OS in early-stage ovarian cancer, in a Cox proportional hazards model regression analysis (HR, 21.9; 95% CI, 2.0-199.9; P = 0.006). CONCLUSION: This study demonstrated that sarcopenia was predictive of OS in patients with early-stage ovarian cancer. Further prospective studies with a larger number of patients are warranted to determine the extent to which sarcopenia can be used as a prognostic factor in ovarian cancer.

Effect of adjuvant therapy on the risk of recurrence in early-stage leiomyosarcoma: A meta-analysis.

OBJECTIVES: To assess the effect of adjuvant chemotherapy (AC) or radiotherapy (AR) on the risk of recurrence in surgically treated patients with early-stage uterine leiomyosarcoma (uLMS). METHODS: We searched the PubMed, EMBASE, and MEDLINE, and Cochrane databases for publications up to March 2019, which compared patients with early-stage uLMS who received AC or AR with those who did not. The primary endpoint was recurrence rate. Random- or fixed-effects models were used for pooled estimates of the effect of adjuvant treatments on recurrence rates. Subgroup analyses were conducted based on study design, surgical staging, AC regimen (gemcitabine/docetaxel regimen), and type of AR. RESULTS: Three randomized trials and 9 observational studies (9 studies for AC vs. observation, n = 496; 9 studies for AR vs. observation, n = 425) were included. The meta-analysis indicated that AC did not decrease the risk of recurrence compared with observation (odds ratio [OR] = 0.65, 95% confidence interval [CI] = 0.37-1.15, P = 0.14; P = 0.09 and I2 = 42.1). Similarly, AR did not decrease the risk of recurrence compared with observation (OR = 1.11, 95% CI = 0.56-2.21, P = 0.76; P = 0.10 and I2 = 40.4). Meta-regression analyses revealed no significant association between median follow-up time and recurrence. In subgroup analyses (study design, surgical staging, gemcitabine/docetaxel regimen, type of AR), neither AC nor AR decreased the risk of recurrence significantly. CONCLUSION: AC, including gemcitabine/docetaxel regimen, or AR did not reduce the recurrence rate in patients with early-stage uLMS.

Pregnancy and oncologic outcomes after fertility-sparing management for early stage endometrioid endometrial cancer.

OBJECTIVE: Hormonal management is an alternative treatment for preserving fertility in patients with presumed early stage endometrioid endometrial cancer. This study aimed to define the pregnancy and oncologic outcomes and factors of successful conception after hormone therapy for endometrioid endometrial cancer. METHODS: We retrospectively analyzed patients presumed to have stage IA, grade 1-2 endometrioid endometrial cancer who underwent fertility-sparing treatment. Concurrent medroxyprogesterone and levonorgestrel-release intra-uterine devices were used for treatment. The pregnancy outcomes and oncologic outcomes were compared between the pregnant and non-pregnant groups. RESULTS: Seventy-one patients presumed to have stage IA, grade 1-2 endometrioid endometrial cancer had complete remission, and 49 of them tried to conceive. Twenty-two (44.9%) patients became pregnant; the total number of pregnancies was 30. These pregnancies resulted in seven abortions (23.3%), one pre-term birth (3.3%), and 20 full-term births (66.6%). The total live birth rate was 66.6 % (20/30). The median duration of hormonal treatment was 11.9 months (range 4-49) and 12.0 months (range 3-35) in the pregnant and non-pregnant groups, respectively. On multivariate analysis, age, body mass index, treatment duration, medroxyprogesterone dose, and number of dilatation and curettage biopsies were not significantly associated with pregnancy failure, but the association with grade (OR 6.2, 95% CI 1.0 to 38.9; P<0.05) was statistically significant. The median disease-free survival duration was 26 months (range 20-38) and 12 months (range 4-48) in the pregnant and non-pregnant groups, respectively (P<0.05, log-rank test). CONCLUSIONS: A lower grade might be a positive factor for future pregnancy. Moreover, successful pregnancy might be a factor in preventing recurrence.

Incarceration of early gravid uterus with adenomyosis and myoma: report of two patients managed with uterine reduction.

Although gravid uterine incarceration is typically diagnosed during the early second trimester, we encountered two unusual cases in early pregnancy. A 34-year-old multiparous woman with adenomyosis presented at 7 + 2 weeks of gestation with increased urinary frequency and a sensation of incomplete bladder emptying. The uterine incarceration was successfully reduced by manual reduction and pessary insertion, and she delivered a normal infant at term. In the second case, a 31-year-old nulliparous woman with a large myoma complained of dysuria, acute urinary retention, and intense back pain at 6 weeks of gestation. Manual reduction was successful in the knee-chest position. Subsequent pessary insertion failed; however, a slight reduction in pain was achieved. After a week, the fetus spontaneously aborted. In summary, gravid uterine incarceration is a rare but potentially fatal condition for the fetus, and a suspicion of this condition in patients with urinary symptoms, especially urinary retention and pelvic pain, is important in the early gestation period.

Contributions and Limitations of National Cervical Cancer Screening Program in Korea: A Retrospective Observational Study.

PURPOSE: The purpose of this study was to evaluate the contributions and limitations of the cervical cancer screening test with accuracy in Korea. METHODS: This was a retrospective observational study. The study population consisted of all participants who underwent cervical cancer screening test from 2009 to 2014. The data were obtained from National Health Information Database (NHID) which represents medical use records of most Koreans. As the indices for contributions and limitations of the screening test, crude detection rate, incidence rate of interval cancer, sensitivity, specificity, and positive predictive value were used. RESULTS: The crude detection rate of screening test per 100,000 participants increased from 100.7 in 2009 to 102.1 in 2014. The incidence rate of interval cancer per 100,000 negatives decreased from 13.0 in 2009 to 10.2 in 2014. The sensitivities of screening test were 88.7% in 2009 and 91.2% in 2014, and the specificities were 98.5% in 2009 and 97.7% in 2014. The positive predictive value of screening decreased from 6.2% in 2009 to 4.3% in 2014. CONCLUSION: The Korean national cervical cancer screening program has improved in accuracy and has contributed to detection of early stage of cervical cancer over the years. Along with efforts to promote participation in cancer screening programs, quality control over the screening program should be enhanced.

Impact of adjuvant hysterectomy on prognosis in patients with locally advanced cervical cancer treated with concurrent chemoradiotherapy: a meta-analysis.

OBJECTIVE: Few data exist regarding adjuvant hysterectomy (AH) in locally advanced cervical cancer (LACC) patients treated with chemoradiotherapy. We investigated the effect of AH on prognosis in LACC patients, through meta-analysis. METHODS: EMBASE and MEDLINE databases and the Cochrane Library were searched for published studies comparing LACC patients who received AH after chemoradiotherapy with those who did not, through April 2016. Endpoints were mortality and recurrence rates. For pooled estimates of the effect of AH on mortality/recurrence, random- or fixed-effects meta-analytical models were used. RESULTS: Two randomized trials and six observational studies (AH following chemoradiotherapy, 630 patients; chemoradiotherapy, 585 patients) met our search criteria. Fixed-effects model-based meta-analysis indicated no significant difference in mortality between the groups (odds ratio [OR]=1.01; 95% confidence interval [CI]=0.58-1.78; p=0.968) with low cross-study heterogeneity (p=0.73 and I²=0.0). This pattern was observed in subgroup analysis for study design, radiation type, response after chemoradiotherapy, and hysterectomy type. The pooled OR for AH and recurrence was 0.59 (95% CI=0.44-0.79; p<0.05) with low cross-study heterogeneity (p=0.29 and I²=17.8), favoring the AH group. However, this pattern was not observed in the subgroup analysis for the randomized trials. There was no evidence of publication bias. CONCLUSION: In this meta-analysis, AH following chemoradiotherapy did not improve survival in patients with LACC, although it seemed to reduce the risk of recurrence. Concerning the significant morbidity of AH after chemoradiotherapy, routine use of AH should be avoided.

Uterine rupture in pregnancies following myomectomy: A multicenter case series.

OBJECTIVE: The purpose of this case series was to retrospectively examine records of cases with uterine rupture in pregnancies following myomectomy and to describe the clinical features and pregnancy outcomes. METHODS: This study was conducted as a multicenter case series. The patient databases at 7 tertiary hospitals were queried. Records of patients with a diagnosis of uterine rupture in the pregnancy following myomectomy between January 2012 and December 2014 were retrospectively collected. The uterine rupture cases enrolled in this study were defined as follows: through-and-through uterine rupture or tear of the uterine muscle and serosa, occurrence from 24+0 to 41+6 weeks' gestation, singleton pregnancy, and previous laparoscopic myomectomy (LSM) or laparotomic myomectomy (LTM) status. RESULTS: Fourteen pregnant women experienced uterine rupture during their pregnancy after LSM or LTM. Preterm delivery of less than 34 weeks' gestation occurred in 5 cases, while intrauterine fetal death occurred in 3, and 3 cases had fetal distress. Of the 14 uterine rupture cases, none occurred during labor. All mothers survived and had no sequelae, unlike the perinatal outcomes, although they were receiving blood transfusion or treatment for uterine artery embolization because of uterine atony or massive hemorrhage. CONCLUSION: In women of childbearing age who are scheduled to undergo LTM or LSM, the potential risk of uterine rupture on subsequent pregnancy should be explained before surgery. Pregnancy in women after myomectomy should be carefully observed, and they should be adequately counseled during this period.

Transvaginal Versus Conventional Laparoscopy for Ovarian Dermoid Cysts: A Matched Cohort Study.

OBJECTIVE: To compare transvaginal versus conventional laparoscopy for dermoid cysts. STUDY DESIGN: We retrospectively analyzed all con-secutive patients with dermoid cysts who underwent transvaginal (n = 219) or conventional (n = 245) laparoscopy from 2007-2013 at our institution. Each group of patients was matched (1:1 ratio) for age, body mass index, previous surgical history, cyst diameter, bilaterality, and cystectomy/oophorectomy. Surgical outcomes were compared between the 2 groups. RESULTS: Overall, 165 pairs were matched. Operating times (expressed as median [interquartile range]) (64 [49-88] vs. 70 [54-93] minutes, p = 0.011), estimated blood loss (100 [70-200] vs. 90 [70-130] mL, p = 0.245), and postoperative hospital stay (1 [1-1] vs. 1 [1-2] days, p = 0.029) were similar between groups. Postsurgical pain scores after 3 (expressed as mean [standard deviation]) (3.52 [1.27] vs. 3.94 [1.05], p < 0.001), 8 (2.88 [0.92] vs. 3.60 [1.01], p < 0.001), and 16 (2.81 [0.97] vs. 3.38 [0.93], p = 0.005) hours were similar but statistically significant between groups. Perioperative complications occurred in 2 and 4 patients in the transvaginal and conventional groups, respectively. CONCLUSION: Transvaginal laparoscopy shows feasibility and efficacy similar to those of conventional laparoscopy for management of dermoid cysts.