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Objectives: The clinical use of less-invasive devices that calculate the cardiac output from arterial pressure waveform is increasing. The authors aimed to evaluate the accuracy and characteristics of the systemic vascular resistance index (SVRI) of the cardiac index measured by 2 less-invasive devices, fourth-generation FloTrac (CI FT ) and LiDCOrapid (CI LR ), compared with the intermittent thermodilution technique, using a pulmonary artery catheter (CI TD )., Design: This was a prospective observational study., Setting: This study was conducted at a single university hospital., Participants: Twenty-nine adult patients undergoing elective cardiac surgery., Interventions: Elective cardiac surgery was used as an intervention., Measurements and Main Results: Hemodynamic parameters, CI FT , CI LR , and CI TD , were measured after the induction of general anesthesia, at the start of cardiopulmonary bypass, after completion of weaning from cardiopulmonary bypass, 30 minutes after weaning, and at sternal closure (135 measurements in total). The CI FT and CI LR had moderate correlations with CI TD (r = 0.62 and 0.58, respectively). Compared with CI TD, CI FT, and CI LR had a bias of -0.73 and -0.61 L/min/m 2 , limit of agreement of -2.14-to-0.68 L/min/m 2 and -2.42-to-1.20 L/min/m 2 , and percentage error of 39.9% and 51.2%, respectively. Subgroup analysis for evaluating SVRI characteristics showed that the percentage errors of CI FT and CI LR were 33.9% and 54.5% in low SVRI (<1,200 dyne×s/cm 5 /m), 37.6% and 47.9% in moderate SVRI (1,200-1,800 dyne×s/cm 5 /m), 49.3% and 50.6% in high SVRI (>1,800 dyne·s/cm 5 /m 2 ), respectively., Conclusions: The accuracy of CI FT or CI LR was not clinically acceptable for cardiac surgery. Fourth-generation FloTrac was unreliable in high SVRI. LiDCOrapid was inaccurate across a broad range of SVRI, and minimally affected by SVRI., Competing Interests: Conflict of Interest Y. Takei reports grants from the Japan Society for the Promotion of Science, received during the conduct of the study; grants from the Japan Agency for Medical Research and Development and Japanese Society of Anesthesiologists, received outside the submitted work. H. Toyama reports grants from the Japan Society for the Promotion of Science, received outside the submitted work. M. Yamauchi reports grants from the Merit Medical, Eisai Co., Philips Japan Ltd., Shionogi, Japan Society for the Promotion of Science, and Japan Agency for Medical Research and Development, received outside the submitted work. All authors have read the journal's authorship agreement and policy on disclosure of potential conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The use of total laparoscopic hysterectomy is increasing. However, as with conventional abdominal hysterectomy, vaginal bacteria-related postoperative complications need to be managed in total laparoscopic hysterectomy. Therefore, we started to combine metronidazole vaginal tablets with intravenous administration of cephem antibiotics immediately before starting surgery to reduce complications. To evaluate the effect of this combination, and to determine the risk factors for these complications, we retrospectively collected medical records from our hospital and performed a multivariate analysis., Methods: We reviewed the medical records of 520 patients who underwent total laparoscopic hysterectomy from 1 January 2015 to 31 December 2021. Among these cases, we identified 16 cases as having vaginal bacteria-related postoperative complications, defined as needing more than one additional day for treatment of postoperative complications, namely postoperative infection (10 cases) and vaginal dehiscence (6 cases). First, we evaluate the effect of metronidazole vaginal tablets by dividing the patients into two groups according to whether metronidazole vaginal tablets were used, and comparing the vaginal bacteria-related postoperative complication rates and other indices. Second, we performed a multivariate logistic regression analysis to assess the influence of each of 17 representative factors, including patient characteristics and symptoms, uterus and leiomyoma sizes, concomitant procedures such as laparoscopic cystectomy and pelvic lymphadenectomy, and others., Results: In the multivariate analysis of the 520 cases, we confirmed that the use of metronidazole vaginal tablets could reduce the vaginal bacteria-related postoperative complications rate by more than half (odds ratio, 0.36). In addition to metronidazole vaginal tablets use, concomitant laparoscopic cystectomy and blood transfusion were associated with significant increases in the vaginal bacteria-related postoperative complication rate., Conclusions: The effect of the addition of metronidazole vaginal tablets to pre- and postsurgical treatment on the reduction of vaginal bacteria-related postoperative complications was confirmed. This easy, safe, and low-cost method may improve the management of total laparoscopic hysterectomy., (© 2023. The Author(s).)

Background: Acute puerperal uterine inversion is rare but may cause massive postpartum blood loss due to uterine atony. Therefore, these patients must be diagnosed, and uterine replacement must be performed as soon as possible. However, in some cases, active bleeding due to uterine atony becomes uncontrollable, even though the uterine inversion itself is treated. In these cases, additional treatments, including surgical procedures, are needed., Case Presentation: A 41-year-old Japanese woman, gravida 1, para 0, was hospitalized for labor induction at 40 weeks and 3 days of gestational age. She had a vacuum-assisted delivery after 3 days of oxytocin administration, but acute uterine inversion occurred. Although replacement of the inverted uterus was successful by manual repositioning and Bakri balloon tamponade insertion, massive postpartum hemorrhage caused by uterine atony became uncontrollable. In this situation, since disseminated intravascular coagulation had developed, we used uterine artery embolization to stop the bleeding. After detecting the pseudo-aneurysmal sac and tortuous vessels of the right uterine artery, transcatheter right-sided uterine artery embolization was performed. Thirteen days after uterine artery embolization, she was discharged with no complications., Conclusions: In cases of disseminated intravascular coagulation caused by massive postpartum bleeding, uterine artery embolization may often be selected. In our case, since we performed angiography to detect the main bleeding site, the hemorrhage could be stopped with unilateral uterine artery embolization alone, without hysterectomy., (© 2022. The Author(s).)

Pregnancy in a noncommunicating rudimentary horn is extremely rare but can cause serious clinical complications, such as uterine rupture. The standard treatment is excision of the rudimentary horn, and recently, in some cases, laparoscopic resection has been performed in the first trimester of gestation. Herein, we present a case of noncommunicating rudimentary horn pregnancy (NCRHP), which was diagnosed by magnetic resonance imaging at 6 weeks of gestation and treated by laparoscopic surgery. However, we have also found some rare cases in which patients could obtain live newborn babies. Since management is affected by the different levels of obstetric medical care and diagnostic tools, we also performed a review and analysis of NCRHP. A PubMed search yielded 103 cases reported in the English literature. Correct diagnosis and laparoscopic treatment were achieved more frequently in developed countries, especially in the first trimester of gestation. On the other hand, symptoms, including abdominal pain and hypovolemic shock, tended to occur in the second trimester of gestation. This period was also found to be a risk factor for uterine rupture. Among 18 patients at the third trimester of gestation, 13 obtained live neonatal infants. Therefore, detailed information about this disease is crucial for proper treatments., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Gynecology and Minimally Invasive Therapy.)

Background: The presence of uterine endometrial polyps is associated with not only abnormal uterine bleeding but also infertility, so the use of hysteroscopic polypectomy has been increasing. This operation is considered to increase cost-effectiveness when performed prior to infertility treatments. However, there are typical problems to consider, including the possibility of spontaneous regression of the polyp and the duration of complete endometrial wound healing after surgery. Meaningless interventions must be avoided, when possible. Therefore, data acquisition and analysis of various findings obtained from surgery have become important for improving treatment procedures and patient selection. To estimate the spontaneous regression rates and contributions of multiple factors to uterine endometrial polyps during the waiting period (approximately 2-3 months) before hysteroscopic polypectomy, we performed a multivariate analysis of data from the records in our hospital., Methods: The medical records of 450 cases from September 2014 to April 2021 in our hospital were retrospectively reviewed under the approval of our Institutional Review Board. We included all cases of hysteroscopic polypectomy with postoperative pathological diagnosis. We defined cases as having a "spontaneously regressed polyp" when the target polyp was not detected by postoperative pathological examination. We extracted data on the following ten factors: "Advanced age" (≥ 42 years), "Small polyp" (< 10 mm), "High body mass index" (≥ 25 kg/m 2 ), "Nulliparity," "Single polyp," "Infertility," "Hypermenorrhea," "Abnormal bleeding," "No symptom," and "Hormonal drug use." We also classified cases into five groups according to the size of the polyp (≤ 4.9 mm, 5.0-9.9 mm, 10.0-14.9 mm, 15.0-19.9 mm, and ≥ 20.0 mm) and determined the frequency of spontaneously regressed polyp in each group., Results: After exclusion of cases with insufficient data or other diseases, such as submucosal leiomyoma, 424 cases were analyzed. Among them, 28 spontaneously regressed polyps were identified, and the highest frequency of spontaneously regressed polyp was detected among the cases with polyps measuring 5.0-9.9 mm (16.4%). On multivariate analysis of the ten factors, "Small polyp" and "Hormonal drug use" were found to significantly impact the frequency of spontaneously regressed polyp., Conclusions: On the basis of the factors identified in this analysis, the indications for observation or medical therapy adapted to small polyps might be expanded., (© 2021. The Author(s).)

Background: The application of laparoscopic surgeries has been increasing, and various uterine diseases in addition to leiomyoma/adenomyoma have become indications for total laparoscopic hysterectomy (TLH). Therefore, data acquisition and analysis of TLH procedures, including TLH for rare uterine diseases, have become important for improving surgical procedures and patient selection. To determine the prevalence of and risk factors for the occurrence of intraoperative and postoperative complications of TLH, we performed a multivariate analysis of the records in our hospital., Methods: We retrospectively reviewed the medical records of 323 patients who underwent TLH for the treatment of leiomyoma/adenomyoma (278 cases), low-grade (pre)malignant uterine tumours (40 cases) and other rare uterine diseases (5 cases) from January 1, 2015, to December 31, 2019. Of the rare uterine diseases, one case of caesarean scar pregnancy for which TLH was performed is introduced as a case report. To assess the effects of 11 representative factors, including patient characteristics, uterus and leiomyoma sizes, indications for TLH and others, we performed a multivariate logistic regression analysis., Results: Among the 323 cases, 20 intraoperative complications and 15 postoperative complications were reported. In the multivariate analysis, "ovarian tumour" and "heavy uterus" were positively associated and "nulliparity" was negatively associated with intraoperative complications. There were no significant risk factors for postoperative complications. The only risk factor for operative complications directly related to the resected uterus was "heavy uterus". Therefore, we could perform TLH relatively safely for patients with other indications besides leiomyoma/adenomyoma., Conclusions: Considering the factors detected in this analysis, the indications for TLH may be expanded. Owing to the increase in TLH for indications other than leiomyoma/adenomyoma, a more accurate determination of the treatment approach can be achieved.

Background: To determine the prevalence of and risk factors for malignant transformation of ovarian endometrioma during dienogest therapy, which is very rare, we examined multiple cases of malignant transformation of ovarian endometrioma during dienogest therapy and performed a multivariate analysis of the records in our hospital., Methods: The medical records of 174 patients who underwent DNGT for the treatment of OMA from June 1, 2011, to May 31, 2018, were reviewed retrospectively with the approval of the Human Ethical Committee of the University of Teikyo Hospital. And we provided one representative case of MT with obtaining written informed consent. To assess the effects of six representative factors, including advanced age, parity, surgical history, and endometrial cyst characteristics (including 3 factors), on the possibility of malignant transformation, we performed a multivariate logistic regression analysis., Results: Of the 174 cases, 4 were diagnosed with malignant transformation, and these cases are reported. In the multivariate analysis, advanced age (P = 0.0064), nullipara (P = 0.0322), and enlargement (P = 0.0079) showed significant differences for malignant transformation occurrence. All 4 malignant transformation cases were among the 19 patients who had all of these 3 factors., Conclusions: For a more accurate determination of the treatment approach, a larger sample size will be needed to determine the risk factors for malignant transformation during dienogest therapy.

Aim: Our objective was to determine the preoperative factors associated with difficulty in total laparoscopic hysterectomy (TLH)., Methods: This retrospective clinical study included 157 patients who underwent TLH for leiomyoma or adenomyosis between 2009 and 2013. All patients underwent magnetic resonance imaging (MRI) before surgery. We categorized patients as 'difficult' if the operation time was > 243 min, if total blood loss was > 500 mL, or if conversion to laparotomy was necessary. Preoperative information, including MRI findings, was compared between the difficult and 'other' patients. Stepwise logistic regression analysis was used to control for covariates that were significant on univariate analysis (P < 0.05)., Results: The presence of an endometrioma, a previous cesarean section (CS), a wide uterus, and a high body mass index were independent risk factors for being a difficult patient. For adenomyosis patients, the presence of an endometrioma, a prior CS, subtype II adenomyosis, and high body mass index were independent risk factors for being a difficult patient. For leiomyoma patients, the presence of an endometrioma, a prior CS, and having at least seven leiomyomas were independent risk factors for being a difficult patient. All laparotomy conversion patients had multiple risk factors., Conclusion: We have elucidated the factors associated with difficult TLH patients using patients' background and preoperative MRI findings. Awareness of these predictive factors may enable surgeons to prepare for the operation, minimize complications, or choose another more appropriate route of hysterectomy than TLH., (© 2017 Japan Society of Obstetrics and Gynecology.)

Adenomyosis is a common disorder in premenopausal women that causes dysmenorrhea, pelvic pain and menorrhagia. Considering that adenomyosis is an estrogen-dependent disease, the medical treatment is based on this hormone. Effective and well-tolerated medical treatments for symptomatic adenomyosis are needed. Dienogest, an oral progestin, has been extensively investigated in the treatment of endometriosis. In this report, we present the results on the efficacy and safety of dienogest in the treatment of symptomatic adenomyosis. Seventeen patients with symptomatic adenomyosis were included in this study, of which 15 continued dienogest for up to 24 weeks. Dienogest significantly reduced adenomyosis-associated pelvic pain as well as serum CA-125 and CA19-9 levels. It also demonstrated a modest suppression of estradiol (>50 pg/ mL), which is consistent with the findings of other reports. During treatment, five patients experienced worsening anemia because of metrorrhagia, which is the most frequent adverse effect associated with dienogest. This report suggests that dienogest is an effective and well-tolerated therapy for symptomatic adenomyosis.

Large cell neuroendocrine carcinoma (LCNEC) is well-reported to result in unfavorable prognoses in many organ cancers while being rarely reported in gynecologic cancer, especially ovarian and endometrial cancers. Here we report a case of ovarian cancer with LCNEC which spread to distant organs within 1 year of primary surgery despite the fact that the post-surgical stage was Ia. The case received platinum-based chemotherapy as an adjuvant therapy after her curative surgery. However, LCNEC in the case was resistant to the chemotherapy. In our review of published works, ovarian cancer cases with LCNEC show poor prognoses regardless of adjuvant chemotherapy following complete resection. Median overall survival was 10 months in stage I cases. Development of chemotherapy sensitive for LCNEC is needed.

Aim: The aim of this study was to review diagnostic/therapeutic strategies of umbilical endometriosis managed in our department and evaluate the effectiveness of these strategies., Methods: Medical records for patients with diagnosis of endometriosis managed from 1999 through 2011 in the University of Tokyo Hospital were retrospectively reviewed. Cases with diagnosis of umbilical endometriosis were identified. Clinical information of age, gravida, parity, histories of surgery and oral contraceptive (OC), management for the disease prior to the first visit, symptoms, patients' desire for pregnancy, diagnostic/therapeutic methods and prognosis were reviewed and summarized., Results: During the period, 2530 patients with diagnosis of endometriosis were identified. Seven patients had diagnosis of umbilical endometriosis, giving an incidence of 0.29% of all endometriosis cases and 5.6% of extragenital endometriosis cases. A definitive diagnosis was made by histological examination following a biopsy (two cases) or a resection (three cases). A clinical diagnosis was made by empirical treatment with OC (one case) or dienogest (one case). With regard to therapy, three patients chose expectant management and did not require therapeutic intervention. Three patients began OC and symptoms were well controlled in all patients. One patient who wished to conceive chose a wide resection followed by umbilical reconstruction. She became pregnant afterwards and recurrence was not reported., Conclusion: There are various options of diagnostic/therapeutic strategies, such as empirical treatments and OC that can provide individualized management of umbilical endometriosis, congruent with the severity of patient symptoms, age and desire for pregnancy., (© 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.)

Objective: To investigate a new role of interleukin (IL)-17A in endometriosis., Design: Laboratory study., Setting: University hospital., Patient(s): Patients with ovarian endometrioma undergoing laparoscopy or laparotomy., Intervention(s): Primary culture of endometrioma stromal cells (EoSCs) was stimulated with IL-17A. Sections of endometrioma tissue were immunostained with antibodies for IL-17A, growth-regulated oncogene-α (Gro-α), and elastase, a marker of neutrophils. They were also examined with immunofluorescent double staining for IL-17A and myeloperoxidase, another marker of neutrophils., Main Outcome Measure(s): Concentration of Gro-α was measured using a specific ELISA. Neutrophil chemotaxis was measured with Boyden chamber method. Immunostained sections were examined under microscope., Result(s): Interleukin-17A increased the secretion of Gro-α from EoSCs dose-dependently. The conditioned medium of EoSCs stimulated with IL-17A attracted more neutrophils than that of EoSCs stimulated with vehicle, and the increase was inhibited by the addition of Gro-α-neutralizing antibody. On immunostaining, IL-17A and Gro-α were detected in similar areas of the stroma beneath the epithelium, where Gro-α was detected in cells with a stromal cell appearance whereas IL-17A was detected in neutrophils as determined by detection of elastase. Fluorescent immunostaining corroborated that myeloperoxidase-positive neutrophils were also positive for IL-17A., Conclusion(s): It is suggested that IL-17A produced by neutrophils stimulates Gro-α secretion from EoSCs, thereby recruiting more neutrophils and inducing perpetuating inflammation in endometriosis., (Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Problem: Preeclampsia is a pregnancy disorder characterized by systemic inflammation. High mobility group box 1 (HMGB1) is a molecule known to act as a 'danger signal' by participating in various inflammatory processes, but data in regard to preeclampsia are sparse. The aim of this study was to analyze placental and serum HMGB1 levels in normal pregnancy and preeclampsia., Method of Study: Sera were collected from women with preeclampsia soon after the manifestation of the disease and before commencing any medication. Placental samples were collected immediately after delivery. Expressed isoforms of HMGB1 (28- and 30-kDa) in the placenta were evaluated by Western blot analysis. Serum HMGB1 concentrations were measured using enzyme-linked immunosorbent assays (ELISA)., Results: Two isoforms of HMGB1 are expressed by the human placenta. The 28- and 30-kDa HMGB1 isoforms were expressed highly in preeclamptic placental tissue; however, compared with normotensive control tissue, differences in detected expression levels did not reach statistical significance. No significant difference was observed in serum HMGB1 levels between control and preeclampsia., Conclusion: Inflammation provoked by HMGB1 is likely to be involved in the proinflammatory process in preeclamptic placenta. Further studies are needed to elucidate the precise role of HMGB1 in preeclampsia., (© 2011 John Wiley & Sons A/S.)

Objective: To examine the effects of interleukin (IL)-17F on the secretion of IL-8 and the gene expression of cyclooxygenase 2 (COX2) in endometriotic stromal cells., Design: In vitro experimental study using human samples., Setting: University hospital., Patient(s): Endometriotic tissues were obtained from women with ovarian endometriomas undergoing laparoscopic surgery., Intervention(s): Endometriotic stromal cells (ESCs) were cultured with IL-17F., Main Outcome Measure(s): Concentrations of IL-8 were measured by a specific ELISA, and messenger RNA levels of IL-8 and COX2 were measured by real-time reverse transcription-polymerase chain reaction (PCR)., Result(s): IL-17F increased the secretion of IL-8 from ESCs, and the effect was inhibited by antibodies for IL-17 receptor A and IL-17 receptor C. Tumor necrosis factor α (TNF-α) synergistically enhanced IL-17F-induced increase in IL-8 secretion from ESCs. The IL-17F increased the gene expression of IL-8 and COX2 in ESCs., Conclusion(s): These findings suggest that IL-17F may stimulate the development of endometriosis by up-regulation of IL-8 and COX2., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Proteinase-activated receptor 2 (PAR2) is a G-protein-coupled receptor that is activated by several serine proteases. PAR2 activation in endometriotic stromal cells (ESCs) has been implicated in the development of endometriosis but the regulatory mechanism of PAR2 expression in ESC is unknown. Our objective was to study the mechanism by which PAR2 expression may be regulated in endometriotic lesions., Methods: Primary cultures of ESCs were treated with transforming growth factor-β (TGF-β) 1, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and the expression of PAR2 was examined by real-time quantitative PCR. ESCs pretreated with or without TGF-β1 were treated with PAR2 agonist peptide (PAR2AP) and the secretion of the pro-endometriotic cytokine, IL-6, was measured using a specific enzyme-linked immunosorbent assay. Effects of TGF-β type 1 inhibitor, SB431542, and PAR2 small interfering RNA (siRNA) on the TGF-β1 stimulation of PAR2 gene expression and PAR2AP-induced IL-6 secretion were also evaluated. To study intracellular signaling, effects of inhibitors of mitogen-activated protein kinases (MAPKs) and phosphoinositide 3-kinase (PI3K) and of Smad4 siRNA on the TGF-β1-induced PAR2 gene expression were studied., Results: Only TGF-β1, but neither TNF-α nor IL-1β, increased gene expression of PAR2. Activation of PAR2 with PAR2AP increased the secretion of IL-6 from ESCs. As expected, TGF-β1 pretreatment dose-dependently enhanced the PAR2AP-induced increase in IL-6 secretion from ESCs. Treatment of ESCs with the TGF-β type 1 inhibitor, SB431542, inhibited both TGF-β1-stimulation of PAR2 gene expression and PAR2AP-induced IL-6 secretion. Transfection of ESCs with PAR2 siRNA produced a similar inhibition of IL-6 secretion. The TGF-β1-induced increase in PAR2 gene expression was repressed by inhibition of p38 MAPK, p42/44 MAPK or PI3K, but not by knockdown of Smad4 expression., Conclusions: In view of significant roles of PAR2 and IL-6 in endometriosis, the TGF-β1-induced increase in PAR2 expression may be an elaborate mechanism that augments the progression of the disease.

Fucoidan is a complex of sulfated polysaccharides derived from non-mammalian origin such as marine brown algae and induces cytokine expression. We investigated the effect of fucoidan on concanavalin A (Con A)-induced liver injury in mice. Liver injury was induced by an intravenous injection of Con A (18.5mg/kg). Various doses of fucoidan (1-30mg/kg) were intravenously administered 30min before Con A injection. The plasma alanine aminotransferase (ALT) and several cytokines levels were determined, and hepatic histological changes were also assessed. The effect of fucoidan administration by itself on induction of interleukin (IL)-10 in plasma and liver tissue was investigated. Con A administration induced an elevation of plasma ALT level, and fucoidan administration dose-dependently prevented the Con A-induced elevation of plasma ALT. Con A administration increased plasma TNF-alpha and IFN-gamma levels, and fucoidan pretreatment significantly inhibited these alterations and increased plasma IL-10 level. The inhibitory effect of fucoidan on Con A-induced liver injury and production of proinflammatory cytokines were reversed by anti-mouse IL-10 antibody pretreatment. Fucoidan induced the IL-10 production in plasma and liver tissue. These findings suggest that fucoidan prevents Con A-induced liver injury by mediating the endogenous IL-10 production and the inhibition of proinflammatory cytokine in mice.