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Abstract Background Histological analysis has revealed the need for new treatment techniques for epithelial ovarian cancer. Immune checkpoint inhibitors may be a new therapeutic strategy for ovarian clear cell carcinoma (OCCC). Lymphocyte-activation gene 3 (LAG-3), an immune checkpoint, is a poor prognostic factor and a new therapeutic target for several malignancies. In this study, we demonstrated the correlation between LAG-3 expression and the clinicopathological features of OCCC. We evaluated LAG-3 expression in tumor-infiltrating lymphocytes (TILs) via immunohistochemical analysis using tissue microarrays containing surgically resected specimens from 171 patients with OCCC. Results The number of LAG-3-positive cases was 48 (28.1%), whereas the number of LAG-3-negative cases was 123 (71.9%). LAG-3 expression significantly increased in patients with advanced stages (P = 0.036) and recurrence (P = 0.012); however, its expression did not correlate with age (P = 0.613), residual tumor (P = 0.156), or death (P = 0.086). Using the Kaplan − Meier method, LAG-3 expression was found to be correlated with poor overall survival (P = 0.020) and progression-free survival (P = 0.019). Multivariate analysis revealed LAG-3 expression (hazard ratio [HR] = 1.86; 95% confidence interval [CI], 1.00 − 3.44, P = 0.049) and residual tumor (HR = 9.71; 95% CI, 5.13 − 18.52, P

Abstract Background To investigate the role of adenosine monophosphate (AMP)-activated protein kinase (AMPK) on the production of interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1, prostaglandin E2 and F2α induced by IL-1β in endometrial stromal cells (ESCs) following treatment with 5-aminoimidazole-4- carboxamide ribonucleoside (AICAR). Methods Endometrial specimens were obtained and cultured. We examined the effects of IL-1β, IL-1 ra and AICAR on the production of IL-8, MCP-1, PGE2 and PGF2α in human ESCs. The phosphorylations of AMPK, IκB, 4EBP-1, p70S6K and S6 ribosomal protein were analyzed by Western immunoblotting. Results Following stimulation by IL-1β, the production of IL-8, MCP-1, PGE2 and PGF2α showed significant increases, and these increases were suppressed by AICAR. The expression of cyclooxygenase-2 (COX-2) induced by IL-1β and suppressed by AICAR. The phosphorylation of IκB, 4EBP-1, p70S6K and S6 ribosomal protein were inhibited via an AMPK-dependent signal transduction. Conclusions The production of IL-8, MCP-1, PGE2 and PGF2α induced by IL-1β in ESCs were involved in the negative regulatory mechanisms of AMPK. The substances that activate AMPK may be promising agents for the treatment of pathological problems such as dysmenorrhea.

Abstract Objectives To clarify characteristic angiographic features and clinical efficacy of selective transarterial embolization (TAE) of retained placenta with abnormal vaginal bleeding. Methods The study cohort comprised 22 patients (mean age, 33.5 years; range, 22–24 years) who underwent selective TAE for retained placenta with abnormal bleeding between January 2018 and December 2020 at our institution. Angiographic images were reviewed by two certified radiologists with consensus. Medical records were reviewed to evaluate the efficacy of TAE. Angiographic features of retained placenta, technical success (disappearance of abnormal findings on angiography), complications, clinical outcomes (hemostatic effects and recurrent bleeding) were evaluated. Results Pelvic angiography showed a dilated vascular channel mimicking arteriovenous fistulas or an aneurysm contiguous with dilated uterine arteries in the mid-arterial–capillary phase in 20 patients; it showed contrast brush in the remaining two patients. TAE technical success was achieved in all patients. No major complications were observed in any patients. Fifteen patients were followed up with expectant management after TAE; all but one patient showed no re-bleeding during the follow-up period (mean follow-up interval, 3.4 months; range, 1–17 months). One patient showed minor rebleeding, which resolved spontaneously. Seven patients underwent scheduled hysteroscopic resection within 1 week after TAE, and no excessive bleeding was observed during or after the surgical procedure in all seven patients. Conclusions The characteristic angiographic feature of retained placenta is “dilated vascular channel that mimic low flow AVM.” TAE is a safe and effective treatment to manage retained placenta with abnormal bleeding.

Demons syndrome is defined by hydrothorax and ascites associated with a benign genital tumor that resolves after resection of the tumor. However, Demons syndrome with pericardial effusion has never been reported. Intensive care unit–acquired weakness is a neurological sequela to sepsis/systemic inflammatory response syndrome, or multi-organ failure. A 47-year-old, nulligravid, Japanese woman, was transferred to our hospital for refractory heart failure and a ruptured ovarian tumor. She had an 11-cm left ovarian tumor with ascites, hydrothorax, and pericardial effusion; she was intubated for pulmonary hypertension and admitted to the intensive care unit for septic shock. Four days later, a left salpingo-oophorectomy was performed for Demons syndrome with pericardial effusion. The histological diagnosis indicated a serous cystadenoma with fibrotic changes. Following surgery, ventilator weaning was delayed due to intensive care unit–acquired weakness. The association between Demons syndrome and pericardial effusion should be recognized to ensure early treatment and for preventing sequalae from the disease.

Although parasitic leiomyoma could be spontaneous or iatrogenic in origin, port-site implantation of parasitic leiomyoma is an iatrogenic benign sequela of laparoscopic surgery. A 30-year-old, primigravida Japanese woman was referred after unresponsiveness to preoperative gonadotropin-releasing hormone for intramural fibroids. Magnetic resonance imaging showed multiple intramural fibroids and left ovarian endometrioma with no malignant features. Laparoscopic myomectomy with power morcellation and ovarian cystectomy were performed, followed by treatment with a combined oral contraceptive. Seven years after the primary surgery, she underwent abdominal myomectomy for a port-site, and peritoneal recurrence of the leiomyoma and intramural leiomyomas was detected. Microscopic examination revealed that resected specimens from the port-site demonstrated leiomyoma with lesser cell density and more prominent hyalinization than those from the uterus. Therefore, clinicians should counsel patients regarding the risks and benefits of laparoscopy with morcellation versus laparotomy. Further development of techniques for uterine tissues extraction is warranted.

Objective: Although uterine didelphys per se is not associated with an impaired ability to conceive, the association between uterine anomalies and gestational trophoblastic neoplasia (GTN) remains unclear. The management of chemotherapy-resistant GTN in women with uterine didelphys raises a new issue regarding whether to perform a hemi-hysterectomy. Case report: A 23-year-old, gravida 1, para 0 Japanese woman was referred with a failed intermittent cervical dilatation for hematometra. Four years previously, she developed a GTN Stage III, score 5. As two cycles of chemotherapy with methotrexate (MTX) and one cycle of EMA-CO (etoposide, MTX, actinomycin D, cyclophosphamide and vincristine) did not result in remission, we performed an abdominal hemi-hysterectomy. After a canalization procedure and cervicoplasty were performed, the patient conceived naturally and prematurely delivered by cesarean section twice. Conclusion: A hemi-hysterectomy should be considered for fertility preservation when GTN develops on either side of a didelphic uterus and adjuvant chemotherapy does not result in remission. Keywords: Adjuvant chemotherapy, Fertility preservation, Gestational trophoblastic disease, Hysterectomy, Anomalies

Minimally invasive surgery (MIS) is performed for various human cancers, among which robot-assisted surgery is widely used in the United States, Europe, and other countries. Presently, the total number of robot-assisted surgeries in gynecology exceeds that in urology and any other clinical department. Our group began using robot-assisted surgery for early-stage uterine corpus cancer as from November 2017 and has already performed 40 robot-assisted operations. For this study, we examined the cases of 35 patients, excluding 3 in whom lymphadenectomy was not performed and 2 who underwent additional vaginal wall plasty. Compared with the first 20 cases, the latter 15 had reduced bleeding and shorter operation times. No serious complications were observed in the whole cohort, but infections, including urinary tract infections and peritonitis, were common among the first 20 patients. Although robot-assisted surgery is considered more advantageous for obese patients than laparoscopic and open surgery, we found no significant differences in bleeding, surgical time, or the number of resected lymph nodes between obese patients (Body Mass Index (BMI) ≥30) and other patients in this present study. Robot-assisted surgery is expected to be more widely used, and further technical improvements are needed. [ABSTRACT FROM AUTHOR]

Background: Women with polycystic ovary syndrome (PCOS) are generally insulin- resistant and are consequently often treated with metformin. We investigated the effect of metformin and AICAR on the AMP-activated protein kinase (AMPK) pathway. Methods: We evaluated the effects of 5-amino-imidazole-4-carboxyamide-1- beta-D-ribofuranoside (AICAR) and metformin on tumor necrosis factor (TNF)-alpha- stimulated chemokine production in human granulosa cells. The phosphorylations of AMPK, I-kappaB, 4E-BP-1, p70S6K were analyzed by western immunoblotting. Results: AICAR and metformin markedly reduced the IL-8 and GROalpha production induced by TNF-alpha. AICAR and metformin also reduced the TNF-alpha-induced phosphorylation of I-kappaB. The phosphorylations of I-kappaB, 4EBP-1, p70S6K were inhibited via an AMPK-dependent signal transduction. Conclusions: These results suggest that metformin promotes granulosa cell function by reducing a TNF-alpha- and chemokine-mediated inflammatory reaction through an AMPK-dependent pathway. These finding may have implications for metformin's actions during the treatment of PCOS with metformin. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to investigate the role of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in folliculogenesis, and to evaluate the effect of these substances concerning oocyte maturation Methods Follicular fluids (FFs) were aspirated from the women undergoing in IVF-ET. Serum were collected from women in IVF-ET and normal menstrual cycles with informed consents. VEGF and HGF in FFs and serum were measured by ELISA. VEGF and HGF mRNA expression in the follicles were analyzed by reverse transcription and polymerase chain reaction (RT-PCR) Results: The concentrations of VEGF in FFs were higher than those in serum [VEGF; 1909 pg/ml, 516 pg/ml (P < 0.001), HGF; 74.6 ng/ml, 0.83 ng/ml (P < 0.0001)] The levels of HGF in FF were increased correlated with oocyte maturation[immature; 62.9 ng/ml, mature 80.3 ng/ml (P < 0.05)] The levels of VEGF in FF including mature oocytes under 39-yearold-women were significantly decreased compared with these more than 40-year-old-women [less than 39 yrs; 1386.3 pg/ml, more than 40 yrs; 2682.7 pg/ml (P < 0.05)] Conclusion Our data suggest that VEGF and HGF as angiogenic factors may play an important role of follicular growth and development in human preovulatory processes. It is suggested that VEGF and HGF production might be available biochemical markers for oocyte maturation. [ABSTRACT FROM AUTHOR]

Objective IL-8 and GRO-α have been demonstrated to be important modulators of neutrophil-chemotaxis in the inflammation-like mechanism of human ovulation. In this study, we investigated the possible effects of TGF-α and EGF on IL-8 and GRO-α secretion by granulosa cells Methods We used immortalized granulosa cells and granulosalutein cells with informed consents. Confluent cells were placed in serum-free media and treated with the above-mentioned growth factors for 8 hrs. IL-8 and GRO-α were measured in the culture media using an ELISA Results Treatment of immortalized granulosa cells with 10 nM of TGF-α and EGF produced higher levels of IL-8 than untreated cells by 8 hrs (241.8 ± 21.8, 261.4 ± 19.4 pg/ml; control = 125 ± 15 pg/ml; P < 0.0001). On the other hand, the same treatment produced slightly higher levels of GRO-α than untreated cells by 8 hrs. Treatment of granulosa-lutein cells with 1 nM of TGF-α and EGF produced higher levels of IL-8 than untreated cells by 8 h (980.1 ± 51.5, 1134.6 ± 76.2 pg/ml; control = 593.9 ± 30.2 pg/ml; P < 0.0001). Furthermore, the same treatment produced higher level of GRO-α than untreated cells after 8 h (P < 0.0005) Conclusion Given the significant effects of both TGF-α and EGF on IL-8 and GRO-α secretion by granulosa-lutein cells, our data suggest that TGF-α and EGF might play a role in the inflammatory mechanism of human ovulation. [ABSTRACT FROM AUTHOR]

Objective To clarify the role of platelet-activating factor (PAF) in parturition, we have investigated the effect of sex-steroids on the PAF metabolism in the decidua. Methods The decidual macrophages were obtained from human decidua by enzymic digestion, followed by Ficoll-Paque centrifugation. The effects of estrone (E[sub 1]), estradiol (E[sub 2]), estriol (E[sub 3]), progesterone (P[sub 4]), and medroxy progesterone acetate (MPA) on the secretion of a PAF-inactivating enzyme, PAFacetylhydrolase (PAF-AH), by these cells were examined. The enzyme activity was assayed by the method of Miwa et al. This study was approved by our ethical committee. Results E[sub 2] inhibited PAF-AH secretion by decidual macrophages in a dose-dependent manner (IC50:82 ± 7 nM, n = 6). E[sub 3] also inhibited PAF-AH secretion (IC50:4153 ± 297 nM, n = 6); however, the effect was seen only at 50 time's higher concentrations than required for E[sub 2]-induced inhibition (P < 0.001). In contrast to E[sub 2] and E[sub 3], P[sub 4] and MPA increased the PAF-AH secretion by the decidual macrophages (SC50:206 ± 32 nM, 47 ± 3 nM, respectively, n = 6). E1 had no effect on the enzyme secretion. Conclusion Sex-steroids may modulate the concentration of PAF in the decidua via their inhibitory or stimulatory effect on the PAF-AH secretion by decidual macrophages, contributing to the regulation of PAF concentration at the maternal-fetal interface during parturition. [ABSTRACT FROM AUTHOR]