Rapamycin prevents cyclophosphamide-induced ovarian follicular loss and potentially inhibits tumour proliferation in a breast cancer xenograft mouse model.

STUDY QUESTION: To what extent and via what mechanism does the concomitant administration of rapamycin (a follicle activation pathway inhibitor and antitumour agent) and cyclophosphamide (a highly toxic ovarian anticancer agent) prevent cyclophosphamide-induced ovarian reserve loss and inhibit tumour proliferation in a breast cancer xenograft mouse model? SUMMARY ANSWER: Daily concomitant administration of rapamycin and a cyclic regimen of cyclophosphamide, which has sufficient antitumour effects as a single agent, suppressed cyclophosphamide-induced primordial follicle loss by inhibiting primordial follicle activation in a breast cancer xenograft mouse model, suggesting the potential of an additive inhibitory effect against tumour proliferation. WHAT IS KNOWN ALREADY: Cyclophosphamide stimulates primordial follicles by activating the mammalian target of the rapamycin (mTOR) pathway, resulting in the accumulation of primary follicles, most of which undergo apoptosis. Rapamycin, an mTOR inhibitor, regulates primordial follicle activation and exhibits potential inhibitory effects against breast cancer cell proliferation. STUDY DESIGN, SIZE, DURATION: To assess ovarian follicular apoptosis, 3 weeks after administering breast cancer cells, 8-week-old mice were randomized into three treatment groups: control, cyclophosphamide, and cyclophosphamide + rapamycin (Cy + Rap) (n = 5 or 6 mice/group). Mice were treated with rapamycin or vehicle control for 1 week, followed by a single dose of cyclophosphamide or vehicle control. Subsequently, the ovaries were resected 24 h after cyclophosphamide administration (short-term treatment groups). To evaluate follicle abundance and the mTOR pathway in ovaries, as well as the antitumour effects and impact on the mTOR pathway in tumours, 8-week-old xenograft breast cancer transplanted mice were randomized into three treatment groups: vehicle control, Cy, and Cy + Rap (n = 6 or 7 mice/group). Rapamycin (5 mg/kg) or the vehicle was administered daily for 29 days. Cyclophosphamide (120 mg/kg) or the vehicle was administered thrice weekly (long-term treatment groups). The tumour diameter was measured weekly. Seven days after the last cyclophosphamide treatment, the ovaries were harvested, fixed, and sectioned (for follicle counting) or frozen (for further analysis). Similarly, the tumours were resected and fixed or frozen. PARTICIPANTS/MATERIALS, SETTING, METHODS: Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) was performed to examine ovarian follicular apoptosis in the short-term treatment groups. All subsequent experiments were conducted in the long-term treatment groups. Tumour growth was evaluated using the tumour volume index. The tumour volume index indicates the relative volume, compared to the volume 3 weeks after tumour cell injection (at treatment initiation) set to 100%. Tumour cell proliferation was evaluated by Ki-67 immunostaining. Activation of the mTOR pathway in tumours was assessed using the protein extracts from tumours and analysed by western blotting. Haematoxylin and eosin staining of ovaries was used to perform differential follicle counts for primordial, primary, secondary, antral, and atretic follicles. Activation of the mTOR pathway in ovaries was assessed using protein extracts from whole ovaries and analysed by western blotting. Localization of mTOR pathway activation within ovaries was assessed by performing anti-phospho-S6 kinase (downstream of mTOR pathway) immunohistochemistry. MAIN RESULTS AND THE ROLE OF CHANCE: Ovaries of the short-term treatment groups were resected 24 h after cyclophosphamide administration and subjected to TUNEL staining of apoptotic cells. No TUNEL-positive primordial follicles were detected in the control, Cy, and Cy + Rap groups. Conversely, many granulosa cells of growing follicles were TUNEL positive in the Cy group but negative in the control and Cy + Rap groups. All subsequent experimental results were obtained from the long-term treatment groups. The tumour volume index stabilized at a mean of 160-200% in the Cy group and 130% in the Cy + Rap group throughout the treatment period. In contrast, tumours in the vehicle control group grew continuously with a mean tumour volume index of 600%, significantly greater than that of the two treatment groups. Based on the western blot analysis of tumours, the mTOR pathway was activated in the vehicle control group and downregulated in the Cy + Rap group when compared with the control and Cy groups. Ki-67 immunostaining of tumours showed significant inhibition of cell proliferation in the Cy + Rap group when compared with that in the control and Cy groups. The ovarian follicle count revealed that the Cy group had significantly fewer primordial follicles (P < 0.001) than the control group, whereas the Cy + Rap group had significantly higher number of primordial follicles (P < 0.001, 2.5 times) than the Cy group. The ratio of primary to primordial follicles was twice as high in the Cy group than in the control group; however, no significant difference was observed between the control group and the Cy + Rap group. Western blot analysis of ovaries revealed that the mTOR pathway was activated by cyclophosphamide and inhibited by rapamycin. The phospho-S6 kinase (pS6K)-positive primordial follicle rate was 2.7 times higher in the Cy group than in the control group. However, this effect was suppressed to a level similar to the control group in the Cy + Rap group. LARGE SCALE DATA: None. LIMITATIONS, REASONS FOR CAUTION: The combinatorial treatment of breast cancer tumours with rapamycin and cyclophosphamide elicited inhibitory effects on cell proliferative potential compared to cyclophosphamide monotherapy. However, no statistically significant additive effect was observed on tumour volume. Thus, the beneficial antitumour effect afforded by rapamycin administration on breast cancer could not be definitively proven. Although rapamycin has ovarian-protective effects, it does not fully counteract the ovarian toxicity of cyclophosphamide. Nevertheless, rapamycin is advantageous as an ovarian protective agent as it can be used in combination with other ovarian protective agents, such as hormonal therapy. Hence, in combination with other agents, mTOR inhibitors may be sufficiently ovario-protective against high-dose and cyclic cyclophosphamide regimens. WIDER IMPLICATIONS OF THE FINDINGS: Compared with a cyclic cyclophosphamide regimen that replicates human clinical practice under breast cancer-bearing conditions, the combination with rapamycin mitigates the ovarian follicle loss of cyclophosphamide without interfering with the anticipated antitumour effects. Hence, rapamycin may represent a new non-invasive treatment option for cyclophosphamide-induced ovarian dysfunction in breast cancer patients. STUDY FUNDING/COMPETING INTEREST(S): This work was not financially supported. The authors declare that they have no conflict of interest.

Comparison of postoperative adjuvant platinum-based chemotherapy and no further therapy after radical surgery in intermediate-risk early-stage cervical cancer.

OBJECTIVE: To identify a relatively high-risk population in postoperative intermediate-risk cervical cancer and evaluate the effect of platinum-based adjuvant chemotherapy (CT). METHODS: We retrospectively reviewed the medical records of patients with stage IA2-IIA cervical cancer who had been treated with radical hysterectomy and pelvic lymphadenectomy and classified as the intermediate-risk group for recurrence by postoperative pathological examination from January 2007 to December 2018 at 3 medical centers in Japan. First, patients with intermediate-risk were stratified by histological type and the number of intermediate-risk factors (IRF; large tumor diameter, lymph vascular space invasion, and deep cervical stromal invasion) and then divided into 2 groups: high and low-risk population (estimated 5-year recurrence-free survival [RFS] rate with no further therapy [NFT] <90% and ≥90%, respectively). Second, the efficacy of CT for the high-risk population was evaluated by comparing RFS and overall survival (OS) between the patients receiving CT and those with NFT. RESULTS: In total, 133 patients were included in the analysis. Among patients with squamous cell carcinoma (SCC) with all IRF or those with non-SCC with 2 to 3 IRF, the 5-year estimated RFS was <90% when treated with NFT. In this population, adjuvant CT was significantly superior to NFT regarding RFS (log-rank, p=0.014), although there was no statistical difference in OS. CONCLUSION: Patients with SCC with all 3 IRFs and those with non-SCC with 2 to 3 IRFs were at high risk for recurrence. Adjuvant CT is a valid treatment option for these populations.

Effectiveness of an articulating laparoscopic needle holder for cesarean scar defect repair.

AIM: To evaluate the efficacy of an articulating laparoscopic needle holder in laparoscopic surgery for cesarean scar defect. METHODS: We performed a retrospective case-control study at the Shiga University of Medical Science. Patients who underwent laparoscopic uterine scar repair were divided into an articulating laparoscopic needle holder (ArtiSential®) group and a rigid needle holder (conventional) group to compare the suture and total operative times. Uterine myometrial suturing involves a double-layer interrupted suture, including a modified Gambee suture for the first layer. We measured the residual myometrial thickness using magnetic resonance imaging preoperatively and at 3 months postoperatively. RESULTS: Both groups comprised 10 patients each. The time per stitch for the first and second layers was significantly shorter in the ArtiSential group than in the conventional group (median 208 s vs. 403 s, p < 0.0001 and median 17 s vs. 29 s; p < 0.0001, respectively). The total operating time was significantly shorter in the ArtiSential group (mean 188 min vs. 240 min, p = 0.0015). The postoperative residual myometrial thickness (mean 9.1 mm in the ArtiSential group and 9.6 mm in the conventional group) was significantly higher than the preoperative residual myometrial thickness (mean 1.6 mm in the ArtiSential group and 1.6 mm in the conventional group) (p < 0.0001 in both groups). CONCLUSIONS: An articulating needle holder is useful in laparoscopic surgery for cesarean scar defect, especially when a modified Gambee suture is required.

Cases of pleural effusion possibly due to clinical pleuroperitoneal communication in the perioperative period of emergency gynecologic surgery: Case series and literature review.

Pleuroperitoneal communication poses a respiratory failure risk due to pleural fluid accumulation with thoracic migration of ascites. Here, we discuss the following cases: Case 1: A woman was diagnosed with a ruptured ovarian tumor with right pleural fluid and ascites, without respiratory failure. Ovarian cystectomy was performed with inadequate removal of ascites. Postoperatively, respiratory failure occurred, and thoracentesis detected pleural fluid resembling ascites. Case 2: A woman was diagnosed with a ruptured ectopic pregnancy with right pleural fluid and ascites without respiratory failure. A diagnosis of clinical pleuroperitoneal communication was considered based on computed tomography findings. During laparoscopic salpingectomy, high-pressure ventilation was performed to push the pleural fluid back into the abdominal cavity; a negative-pressure drain was inserted, and the ascites was completely removed. Postoperative radiography revealed the absence of pleural fluid. Therefore, a preoperative diagnosis of clinical pleuroperitoneal communication and appropriate intraoperative techniques can prevent postoperative respiratory failure.

Locally advanced endometrial cancer with multiple immune-related adverse events coinciding with the complete response to radiotherapy after immune checkpoint inhibitor therapy: A case report.

We report a case of a 70-year-old female patient with locally advanced endometrial cancer with primary empty sella who developed multiple immune-related adverse events (irAEs), including hypopituitarism coinciding with the complete response to radiotherapy after receiving immune checkpoint inhibitors. A computed tomography scan acquired after a traffic accident led to the discovery of endometrial cancer that had invaded the vulva and primary empty sella. Following adriamycin and cisplatin, pembrolizumab was administered for three cycles. No irAEs were observed during treatment, but the tumor was progressive. The patient underwent radiotherapy for the residual tumor. Four months after the last dose of pembrolizumab, hypopituitarism caused secondary adrenal insufficiency, primary hypothyroidism, and pseudogout at the end of radiotherapy. The tumor later achieved a complete response. In conclusion, radiotherapy after immune checkpoint inhibitor (ICI) therapy is expected to have an antitumor effect by stimulating tumor-specific immunity. However, proper management of irAEs is necessary. Patients with primary empty sella may be prone to pituitary insufficiency induced by ICIs.

Prevalence, definition, and etiology of cesarean scar defect and treatment of cesarean scar disorder: A narrative review.

Background: Cesarean scar defects (CSD) are caused by cesarean sections and cause various symptoms. Although there has been no previous consensus on the name of this condition for a long time, it has been named cesarean scar disorder (CSDi). Methods: This review summarizes the definition, prevalence, and etiology of CSD, as well as the pathophysiology and treatment of CSDi. We focused on surgical therapy and examined the effects and procedures of laparoscopy, hysteroscopy, and transvaginal surgery. Main findings: The definition of CSD was proposed as an anechoic lesion with a depth of at least 2 mm because of the varied prevalence, owing to the lack of consensus. CSD incidence depends on the number of times, procedure, and situation of cesarean sections. Histopathological findings in CSD are fibrosis and adenomyosis, and chronic inflammation in the uterine and pelvic cavities decreases fertility in women with CSDi. Although the surgical procedures are not standardized, laparoscopic, hysteroscopic, and transvaginal surgeries are effective. Conclusion: The cause and pathology of CSDi are becoming clear. However, there is variability in the prevalence and treatment strategies. Therefore, it is necessary to conduct further studies using the same definitions.

The efficacy of adjuvant chemotherapy on the survival of early stage endometrial cancer.

OBJECTIVE: No consensus exists on the adjuvant chemotherapy for the International Federation of Gynecology and Obstetrics (FIGO) Stage I-II endometrial cancer with risk factors for recurrence. This study evaluated adjuvant chemotherapy's efficacy in improving these patients' survival. STUDY DESIGN: We conducted a retrospective chart review of patients with FIGO Stage I-II endometrial cancer with recurrence risk factors. The patients received no adjuvant therapy at the National Cancer Center Hospital (NCCH) but received platinum-based chemotherapy at Shiga University of Medical Science (SUMS). RESULTS: Six hundred thirty-eight patients with endometrial cancer were identified. Of these, 118 met the inclusion criteria, 321 were excluded from NCCH, while 49 met the inclusion criteria, and 150 were excluded from SUMS. Multivariate analyses of age, surgery, para-aortic lymphadenectomy, omentectomy, histological type, myometrial invasion, cervical stromal invasion, and adjuvant therapy revealed that in patients aged > 60 years with type II histology, the outer half of myometrial invasion, cervical stromal invasion, and positive peritoneal cytology had significantly worse recurrence-free survival (RFS) rates, and patients aged > 60 years with type II histology, outer half of myometrial invasion, and positive peritoneal cytology had significantly worse overall survival (OS) rates. Patients that received adjuvant chemotherapy showed equivalent effects on RFS (hazard ratio [HR] = 2.13; 95% confidence interval [CI] = 0.82-5.53) and worse on OS ([HR = 5.20; 95 %CI = 1.26-21.50) than patients who did not. CONCLUSION: This study did not show that adjuvant chemotherapy for FIGO Stages I-II endometrial cancer with recurrence risk factors has survival benefit. Further large-scale studies are necessary to validate our findings.

Indication Criteria of Hysteroscopic Surgery for Secondary Infertility due to Symptomatic Cesarean Scar Defect Based on Clinical Outcomes: A Retrospective Cohort Study.

STUDY OBJECTIVE: Hysteroscopic surgery criteria for patients with cesarean scar defect (CSD) are unclear. Therefore, this study aimed to explore the indication of hysteroscopic surgery for secondary infertility owing to CSD. DESIGN: Retrospective cohort study. SETTING: Single university hospital. PATIENTS: Seventy patients with secondary infertility owing to symptomatic CSD who underwent hysteroscopic surgery under laparoscopy between July 2014 and February 2022 were included. INTERVENTIONS: Clinical data, including basic patient information, preoperative residual myometrial thickness (RMT), and postoperative pregnancy status, were collected from medical records. Patients were divided into postoperative pregnancy and nonpregnancy groups. A receiver operating characteristic curve was drawn, and the optimal cutoff value was calculated based on the area under the curve to predict pregnancy after hysteroscopic surgery. MEASUREMENTS AND MAIN RESULTS: No complications were observed in any cases. Among the 70 patients, 49 patients (70%) became pregnant after hysteroscopic surgery. There was no significant difference in patient characteristics between the pregnancy and nonpregnancy groups. In the receiver operating characteristic curve analysis for patients aged <38 years, the value of the area under the curve was 0.77 (sensitivity, 0.83; specificity, 0.78) when optimal cutoff of RMT was 2.2 mm. There was a significant difference in preoperative RMT between the pregnancy and nonpregnancy groups (3.3 mm and 1.7 mm, respectively) in patients aged <38 years. CONCLUSION: For RMT ≥2.2 mm, hysteroscopic surgery was reasonable for secondary infertility owing to symptomatic CSD, particularly in patients aged <38 years.

Transanal total mesorectal excision for primary rectovaginal carcinosarcoma: A case report and literature review.

We report a case of rectovaginal septum carcinosarcoma successfully treated with surgical excision via transanal total mesorectal excision following platinum-based neoadjuvant chemotherapy. A 48-year-old woman presented with a 3-week defecation pain preceding the visit. Pelvic imaging showed an 8-cm sized lesion in the lower rectovaginal septum. Transvaginal biopsy and immunohistochemical analysis were performed. After three courses of carboplatin-paclitaxel-bevacizumab therapy, the mass reduced by half. Subsequently, laparoscopic excision with transanal total mesorectal excision, and radical hysterectomy were performed. The anus was preserved, and dysuria improved within a month. The final histopathological diagnosis was carcinosarcoma of the rectovaginal septum from an uncertain origin, presumably endometriotic or mesonephric. Twelve months following surgery, solitary liver metastasis was confirmed; however, there was no evidence of local recurrence. Total mesorectal excision following platinum-based neoadjuvant chemotherapy may be an ideal treatment for gynecological malignancies in the rectovaginal septum, especially for large tumors localized deep into the pelvis.

Bovine lactoferrin suppresses inflammatory cytokine expression in endometrial stromal cells in chronic endometritis.

Chronic endometritis (CE) is a type of chronic inflammation in the endometrium that is associated with infertility, which is primarily due to implantation failure. Antibiotics are the most common treatment for CE. However, some patients with CE are resistant to antibiotic treatment, while others refuse this treatment. Therefore, we focused on lactoferrin (Lf), which exhibits antimicrobial and anti-inflammatory properties, and studied its effect on inflammation in endometrial stromal cells (ESCs) from patients with CE. Endometrial tissue was collected from patients with CE, and ESCs were isolated and cultured. When ESCs were cultured with bovine lactoferrin (bLf: 1 mg/mL), the mRNA expression of TNF-α (p < 0.05) and IL-1ß (p < 0.01) was significantly decreased compared with that in cells cultured without bLf. The level of TNF-α protein in the culture medium was significantly decreased (p < 0.01), while that of IL-1ß was also decreased, but not significantly (p < 0.10), when 1 mg/mL of bLf was added to the culture medium. When more inflammation was induced artificially by adding 0.1 ng/mL of TNF-αto ESCs, the addition of bLf (1 mg/mL) to ESCs decreased IL-6 and IL-1ß mRNA expression to levels similar to those in ESCs without TNF-α treatment. Furthermore, it was revealed that the actions of bLf are mediated by the AKT and MAPK intracellular signaling pathways, which are mechanisms by which the increase in TNF-α-induced cytokine expression is suppressed in ESCs. bLf suppresses the expression of inflammatory cytokines in human ESCs and may be a new therapeutic candidate for CE.

Decreased Fertility in Women with Cesarean Scar Syndrome Is Associated with Chronic Inflammation in the Uterine Cavity.

Chronic inflammation in cesarean scar defect contributes to secondary infertility in women with cesarean scar syndrom; however, it remains unclear about the situation of inflammation in uterine cavity in women with cesarean scar syndrome. This ambidirectional cohort study aimed to explore the effect of inflammation in the uterine cavities of women with cesarean scar syndrome on infertility at a single university hospital. The frequency of chronic endometritis in infertile patients was retrospectively compared between the cesarean scar syndrome group and non-cesarean scar syndrome group. The frequency of endometriosis was also investigated in patients with cesarean scar syndrome who underwent laparoscopy. The level of tumor necrosis factor-α and interleukin-1ß in the uterine cavity was prospectively evaluated in the cesarean scar syndrome group and in women with a history of cesarean section (control group) using an enzyme-linked immunosorbent assay. There was a significant difference in the incidence of chronic endometritis between the cesarean scar syndrome and non-cesarean scar syndrome groups (65.8% and 46.0%, respectively, p = 0.0315). Endometriosis was detected in 51 (70%) patients with laparoscopy. Tumor necrosis factor-α and interleukin-1ß levels in the cesarean scar syndrome group were significantly higher than those in the control group (p = 0.0002 and p = 0.0217, respectively). Our findings suggest that one cause of secondary infertility in women with cesarean scar syndrome is embryo implantation failure-associated chronic endometritis, endometriosis, and chronic inflammation in the uterine cavity.

Retinol dehydrogenase 10 contributes to cancer stemness and intracellular carbohydrate storage in ovarian clear cell carcinomas.

BACKGROUND: Ovarian clear cell carcinomas (OCCCs) have been recurrent and refractory among the present treatments, so novel therapeutics are urgently needed. OBJECTIVE: The present study accumulates the proof of concept to examine the feasibility of RDH10 as a therapeutic target for treating OCCCs. METHODS: Immunohistochemically, RDH10 expression was evaluated in 111 primary epithelial ovarian cancers, including 55 OCCCs, 31 ovarian endometrioid carcinomas and 25 ovarian serous carcinomas. The spherogenecity provoked by RDH10 was evaluated in OCCC cells. To analyze whether RDH10 promotes carbohydrate storage via the vitamin A-gluconeogenesis pathway, phosphoenolpyruvate carboxykinase 1 (PCK1) protein levels and intracellular carbohydrate content were measured in response to modified RDH10 expression. RESULTS: Abundant RDH10 was expressed specifically in OCCCs. RDH10 promoted spherogenecity and intracellular carbohydrate storage via modulation of PCK1 expression in OCCC cells. CONCLUSIONS: In the present study, abundant RDH10 contributed to cancer cell stemness and intracellular carbohydrate storage in OCCCs. RDH10 is a potentially, new therapeutic candidate for treating OCCC cases.

Histopathological evaluation of cesarean scar defect in women with cesarean scar syndrome.

Purpose: To explore the histopathological findings of cesarean scar defect (CSD) and the immunological component in women with cesarean scar syndrome (CSS). Methods: This retrospective study was conducted in a university hospital and a public hospital. A total of 63 patients with secondary infertility due to CSS who underwent laparoscopic resection of the CSD lesion were enrolled (CSS group), and 21 patients who underwent hysterectomy with a history of cesarean section were enrolled as control (non-CSS group). We compared the differences in histopathological findings of CSD lesions by hematoxylin and eosin staining and immunohistochemistry for CD3, CD20, CD56, CD68, CD138, myeloperoxidase, and tryptase between the two groups. Results: The frequency of presence of endometrium on the CSD surface was significantly lower (p = 0.0023) and that of adenomyosis was significantly higher (p = 0.0195) in the CSS group than in the non-CSS group. The number of CD3-, CD20-, CD68-, and tryptase-positive cells was significantly lower in the CSS group than in the non-CSS group; however, the number of CD138-positive cells was significantly higher in the CSS group (p = 0.0042). Conclusions: This study suggested that the absence of endometrium, presence of adenomyosis, and chronic inflammation in CSD contributes to secondary infertility due to CSS.

Oncologic outcomes in elderly patients who underwent hysterectomy for endometrial cancer: a multi-institutional survey in Kinki District, Japan.

BACKGROUND: The goal of this study is to assess the oncologic outcomes of elderly patients who underwent hysterectomy for endometrial cancer across three variables: hysterectomy approach, lymph node resection, and adjuvant therapy. METHODS: Hospital records of patients aged ≥ 70 years who underwent hysterectomy for endometrial cancer were obtained from 19 institutions. Patients were categorized into three risk groups: low, intermediate, and high. In each group, disease-free survival and overall survival were compared according to hysterectomy approach, lymph node resection, and adjuvant therapy using Kaplan-Meier method. Cox regression analysis with a 95% confidence interval was performed to estimate relative risk (RR) of death. RESULTS: A total of 1246 patients were included. In the low-risk group, the adjusted RR for death for minimally invasive surgery (MIS) versus laparotomy and lymph node resection versus no lymph node resection were 0.64 (0.24-1.72) and 0.52 (0.24-1.12), respectively. In the intermediate-risk group, the adjusted RR for death for MIS versus laparotomy, lymph node resection versus no lymph node resection, and adjuvant therapy versus no adjuvant therapy were 0.80 (0.36-1.77), 0.60 (0.37-0.98), and 0.89 (0.55-1.46), respectively. In the high-risk group, the adjusted RRs for death for lymph node resection versus no lymph node resection and adjuvant therapy versus no adjuvant therapy were 0.56 (0.37-0.86) and 0.60 (0.38-0.96), respectively. CONCLUSIONS: MIS is not inferior to laparotomy in uterine-confined diseases. Lymph node resection improved the outcome for all disease stages and histological types. In contrast, adjuvant therapy improved the outcomes only in high-risk patients.

The association between chronic deciduitis and preeclampsia.

Chronic deciduitis (CD) is slight inflammation of the decidua found during pregnancy. The cause of preeclampsia is thought to be placental hypoplasia, and various theories have been proposed to explain the detailed mechanism; however, its association with decidual inflammation is unclear. A retrospective case control study was conducted in a single university. Subjects were cases who delivered by cesarean section between January 1, 2013 and June 30, 2020 and whose placentas were pathological assessed. CD was diagnosed by CD138 immunostaining of placental decidua tissue, and the perinatal prognosis and incidences of hypertensive disorder of pregnancy and preeclmpsia were examined according to the presence or absence of CD. A logistic regression analysis was performed to evaluate the association between preeclampsia and 11 explanatory variables (10 patient or perinatal background factors and CD). The study population included 76 patients (non-CD, n = 54; CD, n = 22). The rate of preeclampsia was significantly higher in the CD group (P = 0.0006). Patients with CD gave birth at a significantly earlier gestational age (P=0.040) with a lower birth weight (P = 0.001), and a higher rate of LFD (P = 0.005). The Apgar scores at 1 and 5 min and umbilical artery pH were lower (P = 0.0003, 0.021 and 0.002, respectively) in the CD group. The logistic regression analysis revealed that CD was positively associated with preeclampsia. A retrospective examination of the placenta found that patients with CD had a significantly higher incidence of preeclampsia and CD is considered to be a factor that is associated with poor perinatal outcomes.

A novel surgical treatment for labial adhesion - The combination of Z- and Y-V-plasty: A case report.

Labial adhesion is characterised by complete or partial fusion of the labia minora. It occurs rarely in postmenopausal women. Although various methods have been proposed, there is no established treatment for postmenopausal patients with labial adhesions due to its low prevalence in this age group. Severe cases require surgical intervention, and the postoperative recurrence rate is relatively high at 14-20%. In this study, a novel therapeutic method was designed to treat labial adhesions: a combination of Z- and Y-V-plasty. An 82-year-old woman was diagnosed with severe long labial adhesion during an episode of urinary tract infection. The labia could not be separated manually; hence, Z-plasty was performed on the ventral side and Y-V-plasty on the anal side under general anaesthesia. No recurrence was noted eight months postoperatively. This method is relatively easy and produced the desired therapeutic effect with decreased risk of recurrence. This is a novel approach for postmenopausal patients with severe labial adhesion.

Case of adenomyosis causing the activation of the coagulation system after a complete loss of endometrium following microwave endometrial ablation.

The formation of microbleed and minute tissue necrosis inside adenomyosis after the shedding of endometrial or endometrial-like tissue within the myometrium during menstruation is receiving attention as a new pathological condition of uterine adenomyosis. These formations might greatly affect coagulation and fibrinolysis function. However, these modulations might occur due to indirect effects of massive hemorrhage from the uterus with adenomyosis. We present a case of adenomyosis in which the patient's coagulation system was markedly activated despite the absence of menstruation due to previous microwave endometrial ablation to prevent massive uterine hemorrhage. Although no uterine bleeding was observed at all, the patient's serum levels of thrombin-antithrombin complex and soluble fibrin were abnormally elevated at the time when she complained of lower abdominal pain. As the first such case in the world, the present case is valuable for showing that the coagulation function can be modified by uterine adenomyosis.

Histological diagnostic criterion for chronic endometritis based on the clinical outcome.

BACKGROUND: The diagnostic criteria of chronic endometritis remain controversial in the treatment for infertile patients. METHODS: A prospective observational study was conducted in a single university from June 2014 to September 2017. Patients who underwent single frozen-thawed blastocyst transfer with a hormone replacement cycle after histological examination for the presence of chronic endometritis were enrolled. Four criteria were used to define chronic endometritis according to the number of plasma cells in the same group of patients: 1 or more (≥ 1) plasma cells, 2 or more (≥ 2), 3 or more (≥ 3), or 5 or more (≥ 5) in 10 high-power fields. Pregnancy rates, live birth rates, and miscarriage rates of the non-chronic endometritis and the chronic endometritis groups defined with each criterion were calculated. A logistic regression analysis was performed for live births using eight explanatory variables (seven infertility factors and chronic endometritis). A receiver operating characteristic curve was drawn and the optimal cut-off value was calculated. RESULTS: A total of 69 patients were registered and 53 patients were finally analyzed after exclusion. When the diagnostic criterion was designated as the presence of ≥ 1 plasma cell in the endometrial stroma per 10 high-power fields, the pregnancy rate, live birth rate, and miscarriage rate were 63.0% vs. 30.8%, 51.9% vs. 7.7%, and 17.7% vs. 75% in the non-chronic and chronic endometritis groups, respectively. This criterion resulted in the highest pregnancy and live birth rates among the non-chronic endometritis and the smallest P values for the pregnancy rates, live birth rates, and miscarriage rates between the non-chronic and chronic endometritis groups. In the logistic regression analysis, chronic endometritis was an explanatory variable negatively affecting the objective variable of live birth only when chronic endometritis was diagnosed with ≥ 1 or ≥ 2 plasma cells per 10 high-power fields. The optimal cut-off value was obtained when one or more plasma cells were found in 10 high-power fields (sensitivity 87.5%, specificity 64.9%). CONCLUSIONS: Chronic endometritis should be diagnosed as the presence of ≥ 1 plasma cells in 10 high-power fields. According to this diagnostic criterion, chronic endometritis adversely affected the pregnancy rate and the live birth rate.