Safety of immune checkpoint inhibitors in patients aged over 80 years: a retrospective cohort study.

BACKGROUND: Immuno-oncology (IO) drugs are essential for treating various cancer types; however, safety concerns persist in older patients. Although the incidence of immune-related adverse events (irAEs) is similar among age groups, higher rates of hospitalization or discontinuation of IO therapy have been reported in older patients. Limited research exists on IO drug safety and risk factors in older adults. Our investigation aimed to assess the incidence of irAEs and identify the potential risk factors associated with their development. METHODS: This retrospective analysis reviewed the clinical data extracted from the medical records of patients aged > 80 years who underwent IO treatment at our institution. Univariate and multivariate analyses were performed to assess the incidence of irAEs. RESULTS: Our study included 181 patients (median age: 82 years, range: 80-94), mostly men (73%), with a performance status of 0-1 in 87% of the cases; 64% received IO monotherapy. irAEs occurred in 35% of patients, contributing to IO therapy discontinuation in 19%. Our analysis highlighted increased body mass index, eosinophil counts, and albumin levels in patients with irAEs. Eosinophil count emerged as a significant risk factor for any grade irAEs, particularly Grade 3 or higher, with a cutoff of 118 (/µL). The group with eosinophil counts > 118 had a higher frequency of irAEs, and Grade 3 or higher events than the group with counts ≤ 118. CONCLUSION: IO therapy is a safe treatment option for patients > 80 years old. Furthermore, patients with elevated eosinophil counts at treatment initiation should be cautiously managed.

Emergency right lower lobectomy for severe pulmonary abscess in a pregnant woman at the 25th week of gestation: a case report.

BACKGROUND: Pulmonary abscess is a severe infection commonly seen in patients with chronic obstructive pulmonary disease, interstitial pneumonia, immune deficiency disease, drug-induced immunocompromised state, and congenital pulmonary disease. The treatment strategy in pregnant women with a pulmonary abscess is considered challenging since adverse effects on the fetus must be avoided to ensure safe delivery. CASE PRESENTATION: A 34-year-old female patient at 24 weeks of gestation (G2P1) was admitted to the Department of Obstetrics and Gynecology due to sudden right chest pain. The patient had no significant medical history, including congenital anomalies, and no history of drug addiction or smoking. Laboratory data indicated high levels of inflammation (white blood cell 12,000/µL, C-reactive protein 16.0 mg/dL), and computed tomography demonstrated a large intrapulmonary cyst located in the middle of the right lower lobe, with some fluid collection. As the patient had no medical history of congenital pulmonary anomalies, she was initially diagnosed with a pulmonary cyst infection and treated with intravenous antibiotics. However, the infection did not resolve for over a week, and a spike in fever developed after admission. There was no definitive evidence concerning the risk of preterm delivery and fetal abortion during non-obstetric surgery. However, to control the severely infected pulmonary abscess that was refractory to antibiotics and obtain a pathological diagnosis while saving the life of both the mother and fetus, we elected to perform an emergent right lower lobectomy by open thoracotomy with a fissureless maneuver after receiving informed consent. Postoperatively, the infection gradually improved, and the patient was discharged on the 16th postoperative day without any major complications in the mother or fetus. Although she later experienced coronavirus disease-19 at 29 weeks of gestation, a boy was born at 40th weeks of gestation without any complications. Pathologically, no infectious agents, malignancies, or congenital anomalies other than lung abscesses associated with the pulmonary infarction were observed. The mother and child were healthy 1 year postoperatively. CONCLUSIONS: We experienced a rare case of a pulmonary abscess in a pregnant woman who needed an emergent right lower lobectomy to control the severe infection and obtain a correct pathological diagnosis. Under cooperation from an obstetrician and anesthesiologist, emergency pulmonary resection can be performed safely for serious abscess formation even for pregnant women who have several months left until delivery.

Changes in the conflicting nongenomic effects of progesterone in rat myometrium during pregnancy.

AIMS: Although the functions of progesterone in the myometrium are well-established, the nongenomic effects of progesterone in pregnant myometrial contractions are still unclear. Therefore, this study aimed to investigate changes in the nongenomic effects of progesterone during pregnancy. MAIN METHODS: Myometrial strips were obtained from non-pregnant, pregnant, and postpartum rats, and the nongenomic effects of progesterone in the myometrium during pregnancy were examined. Additionally, the influence of actinomycin D and cycloheximide and the effects of Org OD-02-0 (a specific membrane progesterone receptor (mPR) agonist) in the myometrium were investigated. Moreover, DNA microarray and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to identify genes involved in progesterone-induced effects in the myometrium. KEY FINDINGS: Progesterone did not cause rhythmic contractions in non-pregnant myometrium but induced rhythmic contractions in pregnant myometrium, with the effects peaking at 20 d + 8 h of pregnancy. However, myometrial contractions decreased after delivery and were restored to non-pregnant levels at 7 d postpartum. Additionally, progesterone stably inhibited high KCl-induced myometrial contractions during pregnancy. Moreover, the nongenomic effects of progesterone were unaffected by actinomycin D or cycloheximide, and Org OD-02-0 effectively mimicked these effects. DNA microarray analysis and qRT-PCR revealed a significant increase in mPRß gene expression during pregnancy. However, mPRα, mPRγ, mPRδ, and mPRε expression levels remained unchanged. SIGNIFICANCE: The stimulatory nongenomic effect of progesterone, which was inducible and mPRß-dependent during pregnancy, may be involved in parturition. The inhibitory effect, which was constitutive and depended on other mPRs, may be involved in pregnancy maintenance.

Successful pneumovaginoscopic surgery for recurrent abscess of OHVIRA syndrome, preventing further recurrence and subsequent pregnancy.

INTRODUCTION: OHVIRA syndrome is a rare congenital anomaly of Müllerian duct development characterized by uterine didelphys, obstructed hemivagina, and ipsilateral renal agenesis. The primary treatment is surgical excision of the obstructed hemivaginal septum and hematometrial drainage. In recent years, minimally invasive approaches such as hysteroscopic or vaginoscopic septum resection have been reported. Furthermore, we originally developed some novel pneumovaginoscopic gynecologic surgeries for years using a device that consists of a cylinder that fits into the vagina and a lid that mounts multiple ports, allowing the vagina to be dilated with carbon dioxide gas, similar to a single-port laparoscope. MATERIALS AND SURGICAL TECHNIQUE: We report a successful pneumovaginoscopic surgery for a complicated recurrent abscess in a patient with OHVIRA syndrome. Conventional surgery was performed with a single forceps in a liquid, as in cystoscopy or hysteroscopy. However, this new surgery allowed multiple forceps in a gas, as in laparoscopy. So pus and blood were aspirated and washed away without leaking into the abdominal cavity via fallopian tubes. The surgical smoke generated by thermal coagulation also aspirated to clean the field of vision immediately. And thick, complicated abscesses were drained successfully. The patient conceived through IVF with ICSI and delivered safely at full term. DISCUSSION: Pneumovaginoscopy could benefit complex vaginal surgery cases, such as abscess formation in patients with OHVIRA syndrome.

Pneumovaginoscopy-assisted radical hysterectomy for early-stage cervical cancer: a novel bidirectional approach for tumor spillage prevention and R0 resection.

OBJECTIVE: This study evaluated the feasibility and outcomes of pneumovaginoscopy-assisted radical hysterectomy (PVRH) for cervical cancer up to stage IIA using a bidirectional fascia-oriented and nerve-sparing surgical approach. METHODS: This retrospective observational cohort study examined the operative outcomes and prognoses of patients who underwent PVRH (n=59) for up to stage IIA cervical cancer. The basic procedure was Kyoto B2 (Viper Type II nerve-sparing) radical hysterectomy and pelvic lymphadenectomy through simultaneous vaginal and abdominal (open or laparoscopic) approaches. In all cases, pneumovaginoscopy (PV) was used to create a vaginal cuff and dissect the paracolpium and paracervical endopelvic fascia to minimize nerve damage. RESULTS: Thirty-eight (64.4%) patients had stage IB1 cancer. Seven (11.9%) had vaginal invasion (stage IIA1, n=4; IIA2, n=3). The abdominal approach was open in 38 cases and laparoscopic in 21. Adjuvant therapy was administered to 24 patients (41%); one patient received concurrent chemoradiotherapy for gastric-type adenocarcinoma. There were three (6.1%) intraoperative complications (CO2 gas embolism [n=1], sigmoid colon musculosa injury [n=1], and ureteral injury [n=1]) and 8 (14%) postoperative complications (lymphedema with cellulitis [n=4], vaginal cuff dehiscence [n=1], sub-ileus [n=1], symptomatic lymphocyst [n=l], and ureterovaginal fistula [n=1]). The median urination recovery period was 3 days. Microscopic R0 was achieved in all cases. The median follow-up was 44.5 (2-122) months, and no recurrence occurred. CONCLUSION: PVRH is a new fascia-oriented and nerve-sparing surgery for early-stage cervical cancer. Further, it has favorable operative outcomes and good prognoses, similar to those of adjacent pelvic surgery such as trans-anal total mesorectal excision and radical prostatectomy.

A pilot study of repeated 5-aminolevulinic acid photodynamic therapy for cervical intraepithelial neoplasia by a newly developed intravaginal irradiation system.

The pilot study was performed to assess the usefulness of a newly developed patientand physician-friendly intravaginal irradiation system for photodynamic therapy with 5-aminolevulinic acid (5-ALA PDT) for cervical intraepithelial neoplasia (CIN). We used an intravaginal balloon applicator to make the cervix upright and to adjust the position and direction of the laser source in the vagina, resulting in minimal patient discomfort and minimal effort required by the physician during irradiation. Ten outpatients of CIN2 or 3 with high-risk human papillomavirus (HPV) infection without a history of HPV vaccination were treated by 5-ALA PDT. Each patient underwent PDT four times every two weeks. Nine patients showed pathological improvement, and the HPV clearance rate was 80%, and no recurrence was observed at two-years follow-up. Serum anti-HPV16 antibodies were detected in seven patients, and the antibody levels of three patients were high, equivalent to those acquired after HPV vaccination. Our newly developed irradiation system enabled easy repeat 5-ALA PDT in the outpatient clinic resulting in the improvement of CIN lesions and HPV clearance. Our results also suggested that repeated 5-ALA PDT might enhance HPV antibody production in CIN patients.

Fertility-sparing radical resection of juvenile clear cell adenocarcinoma of the cervix by pneumovaginal endoscopic surgery.

Vaginoscopy has been mainly used diagnostically due to the lack of adequate equipment for performing complicated surgeries (Johary et al., 2015). However, herein, we report therapeutic vaginal endoscopic surgery (pneumovaginoscopy) for secondary malignant vaginal tumors using the vNOTES technique and devices (Kita et al., 2021, Yokoe et al., 2022). To our knowledge, this report and surgical video demonstrate the first case of successful fertility-sparing R0 tumor resection of a rare primary cervical clear cell adenocarcinoma using pneumovaginoscopy. A 12-year-old girl was referred to our outpatient clinic with a chief complaint of a genital tumor and possible clear cell carcinoma on biopsy. There was no history of diethylstilbestrol exposure. MRI and CT images suggested a polypoid cervical tumor without metastatic lesions. Therefore, we performed therapeutic pneumovaginoscopic surgery with diagnostic laparoscopy and hysteroscopy. The cervical tumor was resected completely, and hysteroscopy and laparoscopy revealed no abnormalities. The total surgical time was 123 min, and the blood loss volume was minimal. R0 resection was achieved microscopically. Postoperatively, we performed a partial cervical resection around the first surgical scar to confirm no residual tumor. There were no postoperative complications, and a 2-year follow-up revealed no recurrence. The standard treatment for early-stage cervical cancer (IA2-IB1) remains radical hysterectomy with pelvic lymphadenectomy. However, fertility-sparing minimally invasive surgery has recently been introduced for clear cell adenocarcinoma of the cervix (Su et al., 2020). Our report supports the possibility of this minimally invasive surgery under exceptional conditions. This study was approved by the ethics committee of Kansai Medical University. Written and signed informed consent was obtained from the patient's legal guardian.

R0 resection of vaginal stump recurrence of gynecologic malignancy by bi-directional endoscopic approach: A case series of four patients.

Vaginal stump recurrence post-hysterectomy for gynecologic malignancies occurs in 2%-3% of cases. Local excision has been recognized as the primary treatment of localized recurrence, in which precise surgical margin is critical. However, R0 resection is not always easy, given the deep and narrow operation field, as well as severe postoperative fibrosis or adhesion of the vaginal stump at times. Here, we report four cases of vaginal stump recurrence of gynecologic malignancies resected by bi-directional (laparoscopic and pneumovaginoscopic) endoscopy to overcome these difficulties. The primary tumors were uterine cancer in two cases and uterine cervical and ovarian cancer in one case each. The mean operating time was 199 (162-235) minutes, blood loss was minimal, and no perioperative complications were observed. Postoperative follow-up (7.0-19.4 months) revealed no recurrence. This combined procedure could be a therapeutic option for localized vaginal stump recurrence.

The Regulators of Human Endometrial Stromal Cell Decidualization.

Several factors are important for implantation and subsequent placentation in the endometrium, including immunity, angiogenesis, extracellular matrix, glucose metabolism, reactive oxidative stress, and hormones. The involvement or abnormality of these factors can impair canonical decidualization. Unusual decidualization can lead to perinatal complications, such as disruption of trophoblast invasion. Drastic changes in the morphology and function of human endometrial stromal cells (hESCs) are important for decidualization of the human endometrium; hESCs are used to induce optimal morphological and functional decidualization in vitro because they contain estrogen and progesterone receptors. In this review, we will focus on the studies that have been conducted on hESC decidualization, including the results from our laboratory.

Small-cell neuroendocrine carcinoma of the cervix accompanied by adenocarcinoma and high-grade squamous intraepithelial lesion.

Few cytological reports have described small-cell neuroendocrine carcinoma (SCNEC) in the female genital tract. In the present study, we describe a cytological case of SCNEC accompanied by adenocarcinoma, as well as high-grade squamous intraepithelial lesion (HSIL). A Japanese woman (42 years old) presented with abnormal genital bleeding. A conventional Papanicolaou smear revealed an inflammatory condition with three neoplastic components: SCNEC as irregular aggregates of neoplastic small round cells with nuclear molding and granular chromatin; adenocarcinoma as columnar cell clusters with peripherally located large nuclei, and HSIL as sheets or clusters of dysplastic basal-type squamous cells with irregular hyperchromatic nuclei. Accordingly, a cytodiagnosis of SCNEC with adenocarcinoma and HSIL was made. Owing to the rarity of cervical SCNEC, cytological diagnosis may be difficult. Due to its aggressive clinical behavior, the presence of an SCNEC component should be verified in any cytodiagnosis of adenocarcinoma or HSIL.

Laparoscopic hemostasis and drainage for postpartum retroperitoneal hematoma complicated with an infection: A case report and surgical video.

Introduction: and importance: Postpartum retroperitoneal hematomas are a potential complication of childbirth. The management of secondary infections of such hematomas has not been fully elucidated. We present a typical case of such management via laparoscopic surgery, and include a surgical video. Case presentation: A woman in her 20s experienced fever and right lower quadrant pain and distension on postpartum day 2. Pelvic examination revealed a hump on the vaginal wall on the right side of the uterine cervix, and ultrasonography revealed a hematoma. Contrast-enhanced computed tomography revealed no active extravasation into the hematoma. Conservative antibiotic treatment was started; however, on postpartum day 6, her pain increased and her C-reactive protein concentration and white blood cell count were high. Magnetic resonance imaging revealed a paravaginal/upper vaginal wall hematoma (80 × 70 × 63 mm) located to the right of the uterus and bladder. Hence, laparoscopic drainage was performed on postpartum day 7. The retroperitoneal hematoma was incised and drained. The source of bleeding was the right vaginal vein, and bleeding was halted via electrocoagulation. The patient's symptoms improved immediately, and the postoperative course was uneventful. Clinical discussion: The laparoscopic approach enabled immediate hemostasis and identification of the source of bleeding. The drainage route was cleaner than would be possible via a vaginal approach, possibly preventing postoperative retrograde re-infection. Conclusion: Laparoscopic surgery for postpartum retroperitoneal hematoma with infection was useful for both drainage and hemostasis.

The efficacy of human papillomavirus vaccination in young Japanese girls: the interim results of the OCEAN study.

Human papillomavirus (HPV) vaccine has been used to prevent chronic HPV infection, which accounts for cervical cancer. Japanese Ministry of Health, Labor and Welfare (MHLW) conducted an HPV vaccination campaign in 2010 and the Obstetrical Gynecological Society of Osaka initiated a multicenter, prospective cohort study in Osaka, Japan - OCEAN (Osaka Clinical resEArch of HPV vacciNe) study - to investigate the oncogenic HPV prevalence and the long-term protection rate of HPV vaccine. A total of 2814 participants were enrolled on their visit for HPV vaccination between 12 and 18 years old. Among them, 102 participants received HPV/Pap co-test as primary cancer screening at the age of 20-21. We compared the prevalence in two groups (the vaccinated and the unvaccinated group). HPV infection ratio was significantly lower in the vaccinated group compared to the unvaccinated (12.9% vs. 19.7%; p = .04). In particular, HPV 16 and 18 were not detected in the vaccinated group, while 4.9% of participants in the unvaccinated group were infected (p = .001), suggesting that vaccination provided effective protection against high-risk types of HPV. The cross-protection effect of HPV vaccines was also observed against HPV 31, 45, and 52. Although HPV vaccines were not contributed to the reduction of cervical intraepithelial neoplasia 1 (CIN) (p = .28), CIN2 or worse was not observed in vaccinated group. Our research showed that at the age of 20-21, HPV vaccine inhibited the infection of high-risk HPV and had impacted on the development to CIN2 or worse in Japan.

Matrix Metalloproteinases in Human Decidualized Endometrial Stromal Cells.

Cyclic changes, such as growth, decidualization, shedding, and regeneration, in the human endometrium are regulated by the reciprocal action of female hormones, such as estradiol (E2), and progesterone (P4). Matrix metalloproteases (MMPs) and tissue inhibitors of MMPs (TIMPs) control the invasion of extravillous trophoblast cells after implantation. Several MMPs and TIMPs function in the decidua and endometrial stromal cells (ESCs). Here, we aimed to systematically investigate the changes in MMPs and TIMPs associated with ESC decidualization. We evaluated the expression of 23 MMPs, four TIMPs, and four anti-sense non-coding RNAs from MMP loci. Primary ESC cultures treated with E2 + medroxyprogesterone acetate (MPA), a potent P4 receptor agonist, showed significant down-regulation of MMP3, MMP10, MMP11, MMP12, MMP20, and MMP27 in decidualized ESCs, as assessed by quantitative reverse transcription PCR. Further, MMP15 and MMP19 were significantly upregulated in decidualized ESCs. siRNA-mediated silencing of Heart and Neural Crest Derivatives Expressed 2 (HAND2), a master transcriptional regulator in ESC decidualization, significantly increased MMP15 expression in untreated human ESCs. These results collectively indicate the importance of MMP15 and MMP19 in ESC decidualization and highlight the role of HAND2 in repressing MMP15 transcription, thereby regulating decidualization.

Successful minimally invasive surgery for postpartum retroperitoneal hematoma complicated by an infection: Two case reports.

INTRODUCTION: and importance Postpartum retroperitoneal hematoma is a birth canal injury that is difficult to diagnose because of its invisibility. Secondary infections of these hematomas are rare, and their diagnostic and management strategies have not been fully elucidated. We present two cases of postpartum retroperitoneal hematomas with infection, which were successfully treated with minimally invasive surgery. CASE PRESENTATION: Case 1 was of a 2X-year-old woman who presented with complaints of fever; a provisional diagnosis of chorioamnionitis and Streptococcus pyogenes-induced sepsis was made. Case 2 was of a 3X-year-old woman who underwent uterine artery embolization and manual removal of the placenta for suspected placenta accreta. Both cases were diagnosed with adnexal hematomas, and antibiotic therapy failed in both patients. Therefore, we performed exploratory laparoscopy and made a diagnosis of retroperitoneal hematomas with infection; laparoscopic drainage resulted in rapid resolution of the clinical symptoms and abnormal blood test results. CLINICAL DISCUSSION: Once an abscess develops, antibiotic treatment has a limited effect, and surgical drainage should be performed. Management of retroperitoneal hematomas is difficult, especially when complicated by an infection. CONCLUSION: Minimally invasive procedures involving laparoscopy could be beneficial for the management of postpartum retroperitoneal hematomas complicated by an infection.

Transcriptional regulation of LGALS9 by HAND2 and FOXO1 in human endometrial stromal cells in women with regular cycles.

Uterine natural killer cells are regulated via surface inhibitory receptors for IL15 and galectin-9 (LGALS9) secreted by endometrial stromal cells (ESCs). However, the mechanism that regulates LGALS9 mRNA levels in ESCs is unclear. The aim of this study is to clarify the transcriptional regulation of LGALS9 in ESCs. Here, LGALS9 mRNA expression levels significantly decreased in the endometrial tissue in the early- to mid-secretory phase, and recovered in the mid- to late-secretory phase, compared to that in the proliferative phase. In ESCs, LGALS9 mRNA expression significantly decreased following estradiol + medroxyprogesterone acetate treatment for 1 day and increased after 12 days compared to that in the control. The transcriptional activity of the LGALS9 upstream region was upregulated by heart and neural crest derivatives expressed 2 (HAND2) and downregulated by forkhead box O1 (FOXO1). In ESCs, HAND2 expression significantly increased throughout the 12 days treatment with steroid hormones, whereas FOXO1 expression significantly increased on Day 1, reached a plateau, and significantly increased again after 6 days of treatment. Levels of FOXO1 phosphorylation (pFOXO1) remained unchanged after a 3-day treatment of ESCs with steroid hormones, but significantly increased following a 12-day treatment. pFOXO1 could not bind to the DNA and was thus unable to directly suppress LGALS9 transcription. Therefore, expression level of HAND2 and phosphorylation status of FOXO1 may determine LGALS9 mRNA expression. This study provides a novel molecular mechanism underlying the transcriptional regulation of LGALS9 mRNA in ESCs, which could be valuable in the treatment of diseases associated with decidualization failure.

Conflicting Nongenomic Effects of Progesterone in the Myometrium of Pregnant Rats.

Recently, it has been suggested that progesterone affects the contractile activity of pregnant myometrium via nongenomic pathways; therefore, we aimed to clarify whether progesterone causes and/or inhibits pregnant myometrial contractions via nongenomic pathways. Our in vitro experiments using myometrial strips obtained from rats at 20 days of gestation revealed that progesterone caused myometrial contractions in a concentration- and time-dependent manner at concentrations up to 5 × 10-7 M; however, this effect decreased at concentrations higher than 5 × 10-5 M. Similarly, progesterone enhanced oxytocin-induced contractions up to 5 × 10-7 M and inhibited contractions at concentrations higher than 5 × 10-5 M. Conversely, progesterone did not enhance high-KCl-induced contractions but inhibited contractions in a concentration- and time-dependent manner at concentrations higher than 5 × 10-7 M. We also found that RU486 did not affect progesterone-induced contractions or the progesterone-induced inhibition of high-KCl-induced contractions; however, progesterone-induced contractions were blocked by calcium-free phosphate saline solution, verapamil, and nifedipine. In addition, FPL64176, an activator of L-type voltage-dependent calcium channels, enhanced high-KCl-induced contractions and rescued the decrease in high-KCl-induced contractions caused by progesterone. Together, these results suggest that progesterone exerts conflicting nongenomic effects on the contractions of pregnant myometrium via putative L-type voltage-dependent calcium channels.

Resection of vaginal recurrence of granulosa cell tumor by pneumovaginal endoscopic surgery.

Vaginal surgery is a classic and unique gynecologic procedure. However, the operation field is narrow, which may make surgery difficult to perform. While vaginoscopy or vaginal endoscopy could be the solution of choice, they are mainly used for diagnosis due to the lack of adequate equipment to perform complicated surgery (Johary et al., 2015). Laparoscopy, especially single-port surgery, has been introduced in gynecologic surgery, and excellent equipment has been developed to perform complex surgical procedures through narrow inlets. And vaginal endoscopy using such single-port surgery devices, so-called vaginal natural orifice transluminal endoscopic surgery (vNOTES), has recently been introduced in the gynecologic field (Li and Hua, 2019 Aug) and allows the easier performance of endoscopic surgery through the vagina for ovarian cystectomy (Baekelandt, 2018 Feb 1), salpingo-oophorectomy (Baekelandt et al., 2018) and hysterectomy (Housmans et al., xxxx) for benign pathology. However, vNOTES has been used mainly as an alternative laparoscopic pathway to reduce abdominal wounds or bypass transabdominal approaches into the abdominal cavity. This report including the surgical video demonstrates the first case, to our knowledge, of successful tumor resection of a rare vaginal recurrence of ovarian granulosa cell tumor (Fujita et al., 2015 May, Levin et al., 2018) by pneumovaginoscopy using single-port surgery devices. A 39-year-old woman with an adult-type ovarian granulosa cell tumor had undergone left salpingo-oophorectomy. At 23 years after surgery, a recurrent mass was detected in her left vaginal wall. The patient had no history of pregnancy, and her vagina was too narrow to secure a good field of operation. Therefore, we underwent pneumovaginoscopic surgery. The total operating time was 88 min, and the blood loss volume was minimal. Complete tumor clearance (R0 resection) was achieved microscopically. There were no postoperative complications, and a one-year follow-up revealed no recurrence. Institutional Review Board approval was obtained through our local Ethics Committee of Kansai Medical University (#2019208).

Cigarette Smoke Extract Activates Hypoxia-Inducible Factors in a Reactive Oxygen Species-Dependent Manner in Stroma Cells from Human Endometrium.

Cigarette smoking (CS) is a major contributing factor in the development of a large number of fatal and debilitating disorders, including degenerative diseases and cancers. Smoking and passive smoking also affect the establishment and maintenance of pregnancy. However, to the best of our knowledge, the effects of smoking on the human endometrium remain poorly understood. In this study, we investigated the regulatory mechanism underlying CS-induced hypoxia-inducible factor (HIF)-1α activation using primary human endometrial stromal cells and an immortalized cell line (KC02-44D). We found that the CS extract (CSE) increased reactive oxygen species levels and stimulated HIF-1α protein stabilization in endometrial stromal cells, and that CS-induced HIF-1α-dependent gene expression under non-hypoxic conditions in a concentration- and time-dependent manner. Additionally, we revealed the upregulated expression of a hypoxia-induced gene set following the CSE treatment, even under normoxic conditions. These results indicated that HIF-1α might play an important role in CS-exposure-induced cellular stress, inflammation, and endometrial remodeling.

Exposure to cigarette smoke affects endometrial maturation including angiogenesis and decidualization.

PURPOSE: To elucidate the effects of cigarette smoking on human endometrial maturation for reproductive function, the authors examined the in vitro effects of cigarette smoke extract (CSE) on angiogenesis and decidualization in primary human endometrial stromal cells (ESCs). METHODS: Endometrial stromal cells were cultured with CSE and/or estradiol-17ß (E2) and medroxyprogesterone acetate (MPA). The mRNA, protein levels, and protein secretion of the angiogenic factors and decidual specific factors were assessed using real-time polymerase chain reaction, Western blot analysis, and enzyme-linked immunosorbent assay, respectively. Decidualization was also monitored by the changes in cellular morphology. RESULTS: Endometrial stromal cell proliferation substantially decreased after dose-dependent treatments with CSE at concentrations above 1%, whereas cell death was induced at treatment concentrations above 1% CSE. Treatments above 0.025% CSE led to increased vascular endothelial growth factor mRNA through hypoxia-inducible factor-1α accumulation. CSE concentrations at 0.01% and 0.025% increased the prolactin expression levels after treatment with E2 and MPA, whereas 0.1% and 0.25% CSE concentrations suppressed prolactin. Similar tendencies were observed in cellular morphology and other decidual specific factors. CONCLUSION: These results suggest that exposure to cigarette smoke affects endometrial appropriate maturation including the processes of angiogenesis and decidualization in the reproductive system.