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Abstract Background This paper reports on results of a health system strengthening implementation research initiative conducted the Upper East Region of northern Ghana. Transformative interventions to accelerate and strengthen the health delivery were implemented that included empowering community leaders and members to actively participate in health delivery, strengthening the referral systems through the provision of community transport systems, providing basic medical equipment to community clinics, and improving the skills of critical health staff through training. Methods A mixed method design was used to evaluate the impact of the interventions. A quantitative evaluation employed a flexible research design to test the effects of various component activities of the project. To assess impact, a pre-versus–post randomized cluster survey design was used. Qualitative research was conducted with focus group data and individual in depth interviews to gauge the views of various stakeholders associated with the implementation process. Results After intervention, significant improvements in key maternal and child health indicators such as antenatal and postnatal care coverage were observed and increases in the proportion of deliveries occurring in health facilities and assisted by skilled health personnel relative to pre-intervention conditions. There was also increased uptake of oral rehydration salts (ORS) for treatment of childhood diarrhoea, as well as marked reductions in the incidence of upper respiratory infections (URI). Conclusions A pre-and post-evaluation of impact suggests that the programme had a strong positive impact on the functioning of primary health care. Findings are consistent with the proposition that the coverage and content of the Ghana Community-based Health Planning and Services programme was improved by program interventions and induced discernable changes in key indicators of health system performance.

Objective: This study aimed to determine risk factors associated with the failure of uterine artery ligation at its origin following development of the retroperitoneal space (UALr) and evaluated its efficacy in decreasing estimated blood loss (EBL) during single-port total laparoscopic hysterectomy (SP-TLH). Materials and methods: This study includes patient data collected prospectively from May 1st, 2013 to establish a registry for single-port surgery. Data for the present study were collected retrospectively from May 1st, 2013 to August 30th, 2016. Patients who underwent SP-TLH for a symptomatic benign disease. When bilateral UALr was performed successfully, the case was classified as part of the UALr success group. When only unilateral UALr was completed or UALr failed, the case was classified as part of the failure group. We compared patients’ baseline characteristics and surgical outcomes between the two groups. Results: Bilateral UALr was successfully performed in 155 cases and failed in 64 patients. Body Mass Index (BMI) was significantly different between the two groups (24.1 kg/m2 vs. 22.86 kg/m2, p = 0.025). A BMI higher than 23.6 kg/m2 was a risk factor for UALr failure in a multivariate analysis (odds ratio = 2.42, p = 0.004). EBL was significantly lower in the UALr success group compared to the UALr failure group (100 [100.0–200.0] vs. 200 [100.0–250.0], p

ObjectiveBRCA mutational status is important in the management of ovarian cancer, but there is a lack of evidence supporting genetic testing in Asian populations. This study was performed to investigate the prevalence and prognostic outcomes of BRCA1/2 mutation and variant of unknown significance (VUS) in Korean patients diagnosed with epithelial ovarian cancer (EOC).MethodsAmong patients newly diagnosed with EOC between January 2007 and January 2017, those tested for germline BRCA1/2 mutation were studied, regardless of family history. Overall survival (OS) and progression-free survival (PFS) were compared between the patients with and without BRCA1/2 mutation and VUS.ResultsA total of 313 patients underwent BRCA testing: 88 patients had a BRCA1/2 mutation and 48 patients had a BRCA1/2 VUS (28.1% and 15.3%, respectively). There were no significant associations between BRCA1/2 mutation, BRCA1/2 wild-type, or BRCA1/2 VUS with age at diagnosis, histologic distribution, or residual disease status after primary cytoreductive surgery. BRCA1 mutation, including BRCA1 VUS, showed no difference in PFS or OS compared to BRCA1 wild-type. In contrast, BRCA2 mutation showed longer PFS than that of BRCA2 wild-type (P=0.04) or BRCA2 VUS (P=0.02). BRCA2 mutation, including BRCA2 VUS, did not show any difference in OS compared to BRCA2 wild-type.ConclusionBRCA mutation and BRCA VUS had similar clinical characteristics and survival outcomes, except that BRCA2 mutation showed better PFS. The results of this study will help to understand the prognostic significance of BRCA mutation and VUS in Korean patients.

Abstract Background Gynecologic malignancy is one of the leading causes of mortality in female adults worldwide. Comprehensive genomic analysis has revealed a list of molecular aberrations that are essential to tumorigenesis, progression, and metastasis of gynecologic tumors. However, targeting such alterations has frequently led to treatment failures due to underlying genomic complexity and simultaneous activation of various tumor cell survival pathway molecules. A compilation of molecular characterization of tumors with pharmacological drug response is the next step toward clinical application of patient-tailored treatment regimens. Results Toward this goal, we establish a library of 139 gynecologic tumors including epithelial ovarian cancers (EOCs), cervical, endometrial tumors, and uterine sarcomas that are genomically and/or pharmacologically annotated and explore dynamic pharmacogenomic associations against 37 molecularly targeted drugs. We discover lineage-specific drug sensitivities based on subcategorization of gynecologic tumors and identify TP53 mutation as a molecular determinant that elicits therapeutic response to poly (ADP-Ribose) polymerase (PARP) inhibitor. We further identify transcriptome expression of inhibitor of DNA biding 2 (ID2) as a potential predictive biomarker for treatment response to olaparib. Conclusions Together, our results demonstrate the potential utility of rapid drug screening combined with genomic profiling for precision treatment of gynecologic cancers.

Objective: To compare laparoscopic surgery to laparotomy for harvesting para-aortic lymph nodes in presumed stage I–II, high-risk endometrial cancer patients.Methods: Patients with histologically proven endometrial cancer, presumed stage I-II with high-risk tumor features who had undergone hysterectomy, bilateral salpingoophorectomy, or pelvic and para-aortic lymphadenectomy by either laparoscopy or laparotomy in Samsung Medical Center from 2005 to 2017 were retrospectively investigated. The primary outcome was para-aortic lymph node count. Secondary outcomes were pelvic lymph node count, perioperative events, and postoperative complications.Results: A total of 90 patients was included (35 for laparotomy, 55 for laparoscopy) for analysis. The mean (±SD) para-aortic lymph node count was 10.66 (±7.596) for laparotomy and 10.35 (±5.848) for laparoscopy (p = 0.827). Mean pelvic node count was 16.8 (±6.310) in the laparotomy group and 16.13 (±7.626) in the laparoscopy group (p = 0.664). Lower estimated blood loss was shown in the laparoscopy group. There was no difference in perioperative outcome between the groups. Additional multivariate analysis showed that survival outcome was not affected by surgical methods in presumed stage I-II, high-risk endometrial cancer patients.Conclusions: Study results demonstrate comparable para-aortic lymph node count with less blood loss in laparoscopy over laparotomy. In women with presumed stage I-II, high-risk endometrial cancer, laparoscopy is a valid treatment modality.

Malignant melanoma of the genital tract is a rare disease that is usually diagnosed by chance. When a definite diagnosis is delayed, the prognosis is very poor without standardized treatment. Herein, we describe a 40-year-old patient who presented with a history of bloody vaginal discharge for 7 months. Gynecological examination showed an exophytic, hard and pigmented cervical mass involving the upper vagina. The patient was diagnosed with cervical melanoma after a punch biopsy and underwent a radical hysterectomy, upper vaginectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy. After surgeries, the patient underwent 2-cycles of adjuvant immunotherapy with pembrolizumab, but died within 8 months. In this report, treatment with pembrolizumab after radical surgery was not effective for this patient who had a primary cervical melanoma that metastasized to bone and lung tissue. We do not know why pembrolizumab was ineffective for this patient, but there are several possible explanations; further research is needed.

Objective: In early-stage endometrial cancer, aggressive histologic types (grade 3 endometrioid, serous, clear cell, carcinosarcomas, undifferentiated, mixed, and other unusual types) are associated with an increased risk of distant metastases and worse survival. However, the optimal adjuvant treatment for these patients remains controversial. The present study investigated the outcomes of different adjuvant treatments in patients with 2023 FIGO stage IIC endometrial cancer. Methods: We retrospectively identified patients with 2023 FIGO stage IIC endometrial cancer who underwent surgery followed by either adjuvant treatment or observation from 2000 to 2020 at two tertiary centers in Korea and Taiwan. Recurrence-free survival (RFS) and overall survival (OS) were evaluated using Kaplan-Meier estimates and Cox proportional-hazards models. We also analyzed recurrence patterns after different adjuvant treatments. Results: A total of 272 patients were identified; 204 received adjuvant treatment postoperatively, whereas 68 only underwent observation. Adjuvant treatment was not associated with improved RFS or OS. Non-endometrioid histologic types (p=0.003) and presence of lymphovascular space invasion (LVSI, p=0.002) were associated with worse RFS, whereas only non-endometrioid histologic types impacted OS (p=0.004). In subgroup analyses, adjuvant treatment improved OS in patients with LVSI (p=0.020) and in patients with both LVSI and grade 3 endometrioid histologic type (p=0.007). We found no difference in locoregional and distant recurrence between patients undergoing adjuvant treatment or observation. Conclusion: In this study, the addition of adjuvant treatment was associated with an OS benefit for patients with LVSI, especially those with grade 3 endometrioid tumors. [ABSTRACT FROM AUTHOR]

Objective: To evaluate feasibility and safety of hysterectomy and adnexal procedures by vaginal natural orifice transluminal endoscopic surgery (vNOTES).Study Design: This is a prospective observational study at a tertiary center and teaching University hospital. We enrolled prospectively 34 patients with benign diseases sequentially.Results: We measured baseline characteristics, surgical data, and pain score (VAS) after surgery. We surveyed before/after surgery. The time of port installation and each stage of surgery was measured. The learning curve was assessed through the graph according to the number of operations using linear and logarithmic regression curve estimation. The complications of surgery were investigated. The median age of the patients was 47.5 years (38–73). Median BMI was 22.4 (18.2–30.0). 20 cases of leiomyoma, four cases of adenomyosis, three cases of uterine prolapse, four cases of endometrial hyperplasia, and three cases of CIN were diagnosed. The median uterine weight was 180.0 g. The median port-installation time was 15.0 min (range, 4–35 min) and median total operation time was 85.5 min (range 43.0–132.0). Complications occurred in three patients. Two cases of bladder injury happened during vesicovaginal space dissection before the installation of the Wound Retractor (WR). One patient underwent transumbilical single-port surgery because of late-onset postoperative bleeding on the 13th postoperative day. The mean postoperative VAS scores were 3.36 immediately after surgery and 3.06, 2.79, and 2.45 at 6, 12, and 24 h after surgery, respectively. In continuous variable analysis, we detected a correlation between port-installation time and postoperative VAS ≥4 (pain score as need for medication). Based on a learning curve, port-installation time and total operation time appeared to reach the proficiency level by the 10th case.Conclusions: Although there were three complications, vNOTES offers advantages to patients and surgeons. More surgical techniques will be developed in vNOTES.

Hardening of cheese is one of major issues that degrade the quality of Home Meal Replacement (HMR) foods containing cheese such as Cheese-ddukbokki rice cake (CD, stir-fried rice cakes with shredded cheese). The quality of cheese, such as pH, proteolytic, and flavor properties, depends on various lactic acid bacteria (LAB) used in cheese fermentation. The hardening of cheese is also caused by LAB. In this study, various LAB strains were isolated from CD samples that showed rapid hardening. The correlation of LAB with the hardening of cheese was investigated. Seven of the CD samples with different manufacturing dates were collected and tested for hardening properties of cheese. Among them, strong-hardening of cheese was confirmed for two samples and weak-hardening was confirmed for one sample. All LAB in two strong-hardening samples and 40% of LAB in one weak-hardening sample were identified as Latilactobacilluscurvatus. On the other hand, most LAB in normal cheese samples were identified as Leuconostoc mesenteroides and Lactobacillus casei. We prepared cheese samples in which L. curvatus (LC-CD) and L. mesenteroides (LM-CD) were most dominant, respectively. Each CD made of the prepared cheese was subjected to quality test for 50 days at 10 °C. Hardening of cheese with LC-CD dominant appeared at 30 days. However, hardening of cheese with LM-CD dominant did not appear until 50 days. The pH of the LC-CD was 5.18 ± 0.04 at 30 days, lower than that of LM-CD. The proteolytic activity of LC-CD sample was 2993.67 ± 246.17 units/g, higher than that of LM-CD sample (1421.67 ± 174.5 units/g). These results indicate that high acid production and high protease activity of L. curvatus might have caused hardening of cheese.

Objective: To evaluate the impact of 2014 Food and Drug Administration (FDA) warning against power morcellation (PM) on survival outcomes of patients with incidentally found uterine leiomyosarcoma (uLMS) after minimally invasive surgery (MIS). Methods: Patients who underwent hysterectomy or myomectomy via MIS for presumed uterine leiomyoma and were pathologically diagnosed with stage I uLMS between 2003 and 2022 were retrospectively reviewed. Survival outcomes and clinicopathologic factors were compared between the 2 groups of which the initial MIS was performed before and after the FDA statement: pre-FDA vs. post-FDA. Results: Thirty-two women were included: 12 in the pre-FDA group and 20 in the post-FDA group. Median follow-up period was 63.1 months. There were no significant differences in stage, type of surgery, tumor size, mitotic counts, resection margin status, lymphovascular space invasion, additional surgery, and adjuvant treatment between the 2 groups. The frequency of PM decreased in the post-FDA group compared with the pre-FDA group (33.3% vs. 10.0%, p=0.165), while endobag use (16.7% vs. 50.0%, p=0.075) and umbilical knife morcellation (KM) (0.0% vs. 20.0%, p=0.271) increased despite statistical insignificance. Of note, however, vaginal KM was significantly increased between the 2 period (16.7% vs. 65.0%, p=0.012). There was significant difference neither in recurrence-free survival (RFS) (2-year RFS rate, 72.7% and 63.3%; p=0.451) nor in overall survival (p=0.348) between the 2 groups. Conclusion: Despite seemingly decreased use of PM and increase of KM with endobag use for the last 10 years after the FDA warning compared with pre-FDA era, we failed to demonstrate significant survival improvements in patients who were incidentally diagnosed with uLMS after MIS between the 2 periods. [ABSTRACT FROM AUTHOR]

We investigated the incidence of reactive thrombocytosis after maximal cytoreductive surgery in advanced epithelial ovarian cancer (EOC) and its role in patient survival. We retrospectively reviewed the electronic medical records of patients who underwent primary cytoreductive surgery for advanced EOC from 1 January 2012 to 31 December 2017. We analyzed the serum platelet counts at various time points from before surgery, during the peri-operative period, and after each cycle of adjuvant chemotherapy. A total of 474 patients were eligible for the analysis. Among them, 401 patients (84.6%) had FIGO stage III disease status. The most common histology type was serous adenocarcinoma (405 patients, 85.4%). Seventy-nine patients (22.6%) received splenectomy, and optimal cytoreduction was achieved in 326 patients (68.8%). A week after surgery, thrombocytosis was observed in 165 patients (34.8%) in the entire cohort. Higher platelet counts were observed in patients with splenectomy compared with patients without splenectomy. In particular, thrombocytosis on the fifth cycle of adjuvant chemotherapy showed the most significant effects on overall survival in multivariate analysis. In a logistic regression model, splenectomy was significantly attributed to thrombocytosis on the fifth cycle of chemotherapy. Reactive thrombocytosis after primary cytoreductive surgery is associated with poor survival in advanced EOC, particularly when thrombocytosis is observed during adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose Lymph node metastasis (LNM) is the most significant prognostic factor in cervical cancer that was recently incorporated into the International Federation of Gynecology and Obstetrics (FIGO) staging system. This study was performed to evaluate whether the prognostic significance of LNM differs according to disease status. Materials and Methods Patients with FIGO stage IB or higher cervical cancer who had pretreatment computed tomography and/or magnetic resonance imaging studies as well as long-term follow-up were enrolled in this retrospective study. The hazard ratio (HR) of Cox regression was used to determine the prognostic significance of LNM. The HRs were compared between the different tumor groups (based on stage, histology, tumor size, primary treatment, age, parametrium involvement, and lymphovascular space invasion). Results A total of 970 patients treated between January 1999 and December 2007 were included. The pretreatment LNM had prognostic significance in patients with stage IB1/IIA (HR for progression-free survival 2.10, p=0.001; HR for overall survival 1.99, p=0.005). However, the significance gradually decreased or disappeared with advancing stages. Similarly, the prognostic significance of the pretreatment LNM decreased with advancing disease status, including old age, parametrial involvement or lymphovascular space involvement. In contrast, the tumor size was associated with the prognostic significance of LNM with advancing status. The significance of the clinical LNM did not reflect the significance of the clinical stage. In contrast, the tumor size, parametrial involvement, and significance of the pathologic LNM reflected the clinical stage. Conclusion In patients with cervical cancer, pretreatment LNM on imaging has different clinical significance depending on the tumor status. [ABSTRACT FROM AUTHOR]

Purpose We investigated the impact of four types of antihypertensive medications, angiotensin receptor blockers (ARBs), beta blockers (BBs; both selective and non-selective), calcium channel blockers (CCBs), and thiazide diuretics (TDs) on survival outcomes in epithelial ovarian cancer (EOC). Materials and Methods A single-institutional retrospective chart review of 878 patients with EOC was performed. Survival was compared according to use of the four antihypertensive medications during primary treatment. Propensity score matching (ratio 1:3) was performed to control possible associated covariates, such as age, International Federation of Gynecology and Obstetrics stage, residual status after primary debulking surgery, and co-morbidity. Results Among 878 patients, 56 patients (6.4%) were ARB users, 62 (7.1%) were BB users, 107 (12.2%) were CCBs users and 32 (3.6%) used TDs. Median progression-free survival (PFS) for ARB, BB, and CCB users was 37.8, 27.2, and 23.6 months compared with 33.6 months for non-users. ARB was associated with 35% decreased risk of disease progression (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.42 to 0.99; p=0.046) in multivariate analysis. After propensity score matching, median PFS for ARB users was 37.8 months and ARB use remained to be associated with lower recurrence rate in univariate (p=0.035) and multivariate analysis (HR, 0.60; 95% CI, 0.39 to 0.93; p=0.022). Conclusion In this study, ARBs use during primary treatment is associated with lower recurrence in EOC patients. However, CCBs, BBs, and TDs did not show beneficial impact. [ABSTRACT FROM AUTHOR]

Objective: The objective of the study is to compare the intra- and post-operative outcomes of laparoendoscopic single-site surgery (LESS) and conventional laparoscopic surgery (CLS) in mature cystic teratoma (MCT) of the ovary. Methods: We reviewed 254 patients who underwent surgery (cystectomy) for ovarian MCT from March 1, 2014, to August 31, 2016. During the study period, 216 patients underwent LESS and 38 patients underwent CLS. The outcome measures included operation time, estimated blood loss, changing hemoglobin (Hb) level, postoperative pain, and complications. Statistical analysis was performed using SPSS 24. Results: There was no statistically significant difference in age, body mass index, sexual experience, cyst size, operative time, adhesiolysis, preoperative Hb, Hb changes, postoperative pain scores (visual analog scale), hospital days, and complications between the two groups. In emergent situation, the frequency of CLS was high as three cases (7.9%) versus one case (0.5%, P = 0.007) with LESS. As the year progressed, the frequency of LESS increased. There were one case of re-operation for bleeding control and transfusion, one case of postoperative peritonitis and transfusion, and one case of postoperative transfusion in LESS. During LESS, additional port(s) was/were created in 13 cases (6.0%, P = 0.249). Conclusions: LESS is not inferior to CLS in MCT surgery, and LESS is useful for the surgery of MCT. Our study demonstrates that LESS confers feasibility, convenience, and safety regarding cystectomy of MCT. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to determine possible prognostic factors in patients with uterine leiomyosarcoma (LMS). Methods This study retrospectively investigated 48 patients with uterine LMS treated in Samsung Medical Center between 2008 and 2017. To analyze the prognostic significance of factors for recurrence-free survival (RFS), overall survival (OS), and survival after recurrence, the log-rank test and Cox proportional hazards model were used for univariate and multivariate analysis. Results Of the 48 patients, twenty-nine patients (60.4%) experienced recurrence and 16 patients (33.3%) died within a median follow-up period of 20 months (range, 3-99months). On multivariate analysis, older age, presence of residual tumor after surgery, lower mitotic count, and history of adjuvant radiotherapy at first treatment were significantly associated with better RFS. Presence of residual tumor after surgery and severe nuclear atypia were associated with poor OS. In analysis of survival after recurrence, hematogenous recurrence, severe nuclear atypia, and presence of residual tumor at primary surgery were significantly associated with worse prognosis. Notably, residual tumor status at primary surgery was associated with RFS, OS, and survival after recurrence. Conclusions We demonstrated possible prognostic factors for RFS, OS, and survival after recurrence for patients with LMS. These results may provide useful information for patients with LMS. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the anti-cancer effects of tetraarsenic hexoxide (TAO, As4O6) in cervical cancer cell lines and in a series of patient-derived xenograft (PDX) mouse models. Methods: Human cervical cancer cell lines, including HeLa, SiHa and CaSki, and human umbilical vein endothelial cells (HUVECs), were used to evaluate the anti-cancer activity of TAO. Cellular proliferation, apoptosis, and enzyme-linked immunosorbent assay (ELISA) for matrix metallopeptidase 2 (MMP-2) and 9 (MMP-9) were assessed. The tumor weights of the PDXs that were given TAO were measured. The PDXs included primary squamous cell carcinoma, primary adenocarcinoma, recurrent squamous cell carcinoma, and recurrent adenocarcinoma. Results: TAO significantly decreased cellular proliferation and increased apoptosis in cervical cancer cell lines and HUVEC. The functional studies on the cytotoxicity of TAO revealed that it inhibited the activation of Akt and vascular endothelial growth factor receptor 2 (VEGFR2). It also decreased the concentrations of MMP-2 in both cervical cancer cell lines and HUVECs. Active caspase-3 and p62 were both increased by the treatment of TAO, indicating increased rates of apoptosis and decreased rates of autophagy, respectively. In vivo studies with PDXs revealed that TAO significantly decreased tumor weight for both primary squamous cell carcinoma and adenocarcinoma of the cervix. However, this anti-cancer effect was not seen in PDXs with recurrent cancers. Nevertheless, the combination of TAO with cisplatin significantly decreased tumor weight in PDX models for both primary and recurrent cancers. Conclusions: TAO exerted inhibitory effects on angiogenesis, cellular migration, and autophagy, and it showed stimulatory effects on apoptosis. Overall, it demonstrated anti-cancer effects in animal models for human cervical cancer.