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Introduction: Chorioamnionitis, a perinatal condition caused by fetal membrane inflammation, results in preterm birth, neonatal sepsis, necrotizing enterocolitis, and brain disease in infants. However, predicting maternal and fetal prognoses is challenging. We aimed to assess the relationship between fetal infection induced by severe chorioamnionitis or morbidity and the expression levels　of serum miR-4535, miR-1915-5p, and miR-191-5p levels, which are promising biomarkers for chorioamnionitis, in pregnant women with chorioamnionitis., Methods: We collectedserum and amniotic fluid samples from 40 pregnant women with preterm labor and analyzed miR-4535, miR-1915-5p, and miR-191-5p expressions. We calculated the area under the curve (AUC) and Youden index to examine the diagnostic accuracy of infection-induced fetal morbidity., Results: The serum miR-4535 and miR-191-5p levels were significantly higher in patients with severe chorioamnionitis than in those with chorionitis or sub-chorionitis ( P = 0.001 and 0.003, respectively). The AUC of miR-4535 and miR-191-5p (0.864 and 0.836, respectively) indicated their good diagnostic accuracy for severe chorioamnionitis. Significant correlations were observed between serum and amniotic fluid miR-4535 expression ( P = 0.011) and serum miR-4535 and miR-191-5p expressions. miR-4535 AUC accurately predicted elevated neonatal immunoglobulin M level (AUC = 0.922) and infection-induced fetal morbidity (AUC = 0.805)., Conclusion: Serum miR-4535 and miR-191-5p are associated with infection-induced severe chorioamnionitis and fetal morbidity and maternal infection, respectively., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. The Ethics Committee of the Fukuoka University Hospital (Fukuoka, Japan) and the National Hospital Organization Saga National Hospital (Saga, Japan) issued approval 15-2-08 and 27–4, respectively. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: D. Urushiyama received funding from JSPS KAKENHI (nos. 18K16822, 22K16890), the Seiichi Imai Memorial Foundation (no. 200536), foundation juridical person Kaibara Morikazu Medical Science Promotion Foundation grants, and Perinatal Clinical Research Consortium Committee of the Japanese Society of Perinatal and Neonatal Medicine. S. Miyamoto received funding from JSPS KAKENHI (no. 18K09242), Central Research Institute of Fukuoka University (no. 197011), Center for Advanced Molecular Medicine, Fukuoka University from the Ministry of Education, Culture, Sports, Science and Technology (Tokyo, Japan), and Kakihara Science and Technology Foundation (no. 18381). C. Kiyoshima received funding from Kakihara Science and Technology Foundation (no. 210349). Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ishida et al.)

Obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) syndrome is a rare group of disorders that affects women at all stages of life. These disorders can elicit symptoms such as menstrual molimina and dysmenorrhea during puberty; miscarriage, premature birth, and infertility during childbearing age; and purulent discharge during menopause and old age. In this study, we report our experience with OHVIRA syndrome, which was diagnosed during childbearing age when the patient showed signs of infection during pregnancy. The patient was a 28-year-old female diagnosed with OHVIRA syndrome during pregnancy who had previously undergone a cesarean section. Despite having a normal prenatal period, the patient experienced lower abdominal pain at 27 weeks gestation, prompting urgent hospitalization. Clinical signs suggested chorioamnionitis; however, the amniocentesis results were negative. Computed tomography and magnetic resonance imaging demonstrated unilateral renal agenesis and a duplicated uterus, characteristics of OHVIRA syndrome, in addition to a uterine infection on the non-pregnant side. Antibiotic treatment enabled the pregnancy to continue until an emergency cesarean section was performed at 31 weeks. Surgery confirmed OHVIRA syndrome with incomplete obstruction. This case highlights the challenges that can arise during the perinatal period due to a partially obstructed duplicated uterus. It emphasizes the importance of performing ultrasonographic renal evaluations when assessing uterine malformations, as this can aid in early detection and effective management of women's health, especially during the perinatal period. Despite its rarity, it is crucial for healthcare providers to be aware of OHVIRA syndrome during clinical interventions., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Hirakawa et al.)

Background/aim: Age-related decline in the number of ovulations and ovum quality are major causes of female infertility, and stem cells have been reported to be effective in tissue regeneration. However, current therapeutic modalities are inadequate. This study investigated the effects of adipose-derived mesenchymal stem cells (ASCs) on ovarian functions in aged mice., Materials and Methods: Following the characterization of ASCs using flow cytometry, the effects of ASCs on the number of ovulations, fertilization rate, and blastocyst-formation rate were investigated. In addition, the number of ovarian follicles and serum anti-Müllerian hormone (AMH) levels were examined. ASCs marked with Kusabira Orange were used to examine the location after cell administration. The quality of ovulated oocytes was analyzed using next-generation RNA sequencing., Results: ASCs showed characteristics of mesenchymal stem cells and were distributed to various organs, including the ovarian stroma. The transplantation resulted in increased number of oocytes and ovulation in the ovaries and increased AMH values. Genetic analysis revealed improved oocyte quality and increased fertilization and blastocyst-formation rates., Conclusion: ASC therapy may be effective in improving fertility in older women., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Many countries, including Japan, are experiencing declining birth rates. Assisted reproductive technologies have consistently demonstrated good results in resolving infertility. Although the development of fertilized eggs into blastocysts has been recognized as a crucial step in assisted reproductive technologies, the involved mechanisms are currently unclear. Here, we established a new culture system for the in vitro development of fertilized eggs into blastocysts. In the Transwell culture system, the rate of blastocysts hatching from fertilized eggs cultured with adipose-derived stem cells (ASCs) was significantly higher than that of blastocysts cultured only with fertilized eggs. Gene ontology analysis revealed that the developed blastocysts displayed essential gene expression patterns in mature blastocysts. Additionally, when cultured with 3rd-passage ASCs, the developed blastocysts expressed the core genes for blastocyst maturation and antioxidant properties compared to those cultured only with fertilized eggs or cultured with 20th-passage ASCs. These results suggest that the Transwell culture system may imitate the in vivo tubal culture state for fertilized eggs. Exosomes derived from stem cells with stemness potential play a powerful role in the development of blastocysts from fertilized eggs. Additionally, the exosomes expressed specific microRNAs; therefore, the Transwell culture system resulted in a higher rate of pregnancy. In future, the extraction of their own extracellular vesicles from the culture medium might contribute to the development of novel assisted reproductive technologies.

Background: Implantation failure due to thin endometrium has emerged as a major cause of infertility. In this study, we aimed to assess the safety and preliminary efficacy of adipose tissue-derived regenerative cells (ADRCs), a source of adipose-derived stem cells, in infertility patients with implantation failure., Methods: Five infertile women with implantation failure despite artificial reproductive technology were enrolled in this study and treated with ADRCs via the intrauterine route. The primary outcome was the incidence of adverse events. Additional outcomes were endometrial thickness after ADRC treatment and pregnancy success after embryo transfer., Results: There were no adverse events in any patient. There was no elevation of white blood cell count, C-reactive protein, or D-dimer levels. There was a significant difference in endometrial thickness in the secretory phase before versus after intrauterine transplantation of ADRCs (3.8 ± 1.3 mm versus 8.8 ± 2.8 mm, respectively; p<0.05). A gestational sac and fetal heartbeat were detected on transvaginal ultrasound in two of five patients., Conclusion: Intrauterine infusion of autologous ADRCs is a simple and safe procedure that may ameliorate the endometrial microenvironment in infertile women with implantation failure., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Yotsumoto et al.)

Background The current challenge is how to improve the management of postpartum hemorrhage (PPH) to reduce the maternal mortality rate further. This study aimed to investigate whether a combined specific obstetric history and ultrasonographic findings can improve the predictive accuracy of retained products of conception (RPOC) with severe PPH. Methods This retrospective study included 56 patients who were diagnosed with RPOC. We extracted the following clinical data: obstetric history of second-trimester miscarriage, the time at which there was clinical suspicion of RPOC after the previous pregnancy (TIME), grayscale ultrasonographic finding (RPOC long-axis length [SIZE]), and color Doppler ultrasonographic finding based on the Gutenberg classification (RPOC hypervascularity). In this study, we defined cases requiring blood transfusion therapy or transcatheter arterial embolization as severe PPH. The patients were divided into two groups according to the presence or absence of severe PPH. The predictors of severe PPH were evaluated using logistic regression models. Model A comprised a combination of second-trimester miscarriage and TIME, Model B comprised a combination of Model A and long-axis SIZE, and Model C comprised a combination of Model B and RPOC hypervascularity. Results The multivariable analysis showed that long-axis SIZE was the only significant predictor of severe PPH (odds ratio [OR], 10.38; 95% confidence interval [CI], 2.06-63.86) independent of second-trimester miscarriage, TIME, and RPOC hypervascularity. The c-statistic was higher in Model C (OR, 0.863; 95% CI, 0.731-0.936) than in Model A (OR, 0.723; 95% CI, 0.551-0.847) and Model B (OR, 0.834; 95% CI, 0.677-0.923). Conclusion Combining a specific obstetric history (second-trimester miscarriage and TIME) and ultrasonographic findings (long-axis SIZE and RPOC hypervascularity) improves the predictive accuracy of RPOC with severe PPH. This prediction model may be a useful clinical screening tool for RPOC with severe PPH., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Kurakazu et al.)

Background/aim: Ultrafine bubbles (UFBs) have been extensively researched owing to their promising physical and biological properties. However, determining the lifespan or ideal concentration of UFBs for various biological events is challenging. This study aimed to determine the maximum concentration and longest lifespan of UFBs and to verify the validity of UFBs for assessing cell properties., Materials and Methods: A generator system (HMB-H0150+P001, TOSSLEC Corporation Limited, Kyoto, Japan) generated UFBs using various gases. The size and concentration of UFBs in ultrapure water and cell culture medium were measured through a nanoparticle tracking analysis method., Results: The UFB concentration increased when the generator operated in a time dependent manner. The mean size of UFBs was approximately 120 nm. In the UFB lifespan, the concentration decreased by approximately 30% within the first two weeks of generation and was stable for up to 6 months. The UFB size increased by approximately 20% within the first two weeks of generation and demonstrated minor changes until the 6th month. The number of cells differed significantly with various concentrations of nitrogen gas UFBs., Conclusion: The generator system can generate UFBs with multiple concentrations within a suitable temperature. Consequently, the solution containing UFBs could be widely acceptable in cell culture systems., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: This study aimed to evaluate the learning curve and perioperative outcomes of robot-assisted hysterectomy (RAH)., Patients and Methods: We retrospectively analyzed data from 45 patients who underwent RAH using the da Vinci Xi surgical system. The learning curve was evaluated using the cumulative summation method. Demographic data and various perioperative parameters, including total operative time, docking time, and console time, were obtained from the medical records., Results: Cumulative summation analysis indicated that proficiency regarding hysterectomy time was reached after 33 cases. There were two unique phases of the learning curve for console time: the introduction phase identified by the bottom point in the curve, and the proficient phase, identified by an upward line after the bottom point in the curve. There were no significant differences between the two phases in terms of patient age and body mass index. Total operative time, docking time, and console time were significantly decreased in the proficient phase compared with those in the introduction phase. There was a significant reduction in blood loss during operation in the proficient phase. The perioperative complication rates were 12.1% in the introduction phase and 0% in the proficient phase (p=0.5606). No blood transfusion or conversion to laparotomy was required in either phase., Conclusion: The introduction and proficient phases identified by cumulative summation analysis demonstrated progressive improvement of surgical performance in surgeons carrying out RAH., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Endometriosis, which exhibits enigmatic pathological features such as stromal fibrosis and proliferation of ectopic epithelial cells, is known as a refractory disease. Mesenchymal stem cells modulate the fibrosis in stromal tissues through their trophic and immunomodulatory properties. To investigate the potential of stem cells in treating endometriosis, we examined the secondary morphology and molecular alterations in endometriosis-like lesions after the administration of adipose tissue-derived stem cells (ASCs) to an experimental murine model of endometriosis. The infused ASCs were found integrated in the endometriosis-like lesions. Accompanied by the suppression of stromal fibrosis and proliferation of endometriotic epithelial cells, the infusion of ASCs with stemness potential (early passage of ASCs) suppressed the growth of endometriosis-like lesions and inhibited the expression of pro-inflammatory and pro-fibrotic cytokines, whereas no significant attenuation of endometriosis-like lesions occurred after the infusion of ASCs without stemness potential (late passage of ASCs). Accordingly, the trophic and immunomodulatory properties of ASCs may regulate fibrosis in endometriosis-like lesions, suggesting that regenerative medicine could be recognized as an innovative treatment for patients with endometriosis through the accumulation of evidence of preclinical efficacy., (© 2022. The Author(s).)

Intra-amniotic infection (IAI) is a major cause of preterm birth with a poor perinatal prognosis. We aimed to determine whether analyzing vaginal microbiota can evaluate the risk of chorioamnionitis (CAM) in preterm labor cases. Vaginal discharge samples were collected from 83 pregnant women admitted for preterm labor. Based on Blanc's classification, the participants were divided into CAM (stage ≥ II; n = 46) and non-CAM (stage ≤ I; n = 37) groups. The 16S rDNA amplicons (V1-V2) from vaginal samples were sequenced and analyzed. Using a random forest algorithm, the bacterial species associated with CAM were identified, and a predictive CAM (PCAM) scoring method was developed. The α diversity was significantly higher in the CAM than in the non-CAM group (P < 0.001). The area under the curve was 0.849 (95% confidence interval 0.765-0.934) using the PCAM score. Among patients at < 35 weeks of gestation, the PCAM group (n = 22) had a significantly shorter extended gestational period than the non-PCAM group (n = 25; P = 0.022). Multivariate analysis revealed a significant difference in the frequency of developmental disorders in 3-year-old infants (PCAM, 28%, non-PCAM, 4%; P = 0.022). Analyzing vaginal microbiota can evaluate the risk of IAI. Future studies should establish appropriate interventions for IAI high-risk patients to improve perinatal prognosis., (© 2021. The Author(s).)

Predicting pathogenic germline variants (PGVs) in breast cancer patients is important for selecting optimal therapeutics and implementing risk reduction strategies. However, PGV risk factors and the performance of prediction methods in the Japanese population remain unclear. We investigated clinicopathological risk factors using the Tyrer-Cuzick (TC) breast cancer risk evaluation tool to predict BRCA PGVs in unselected Japanese breast cancer patients (n = 1,995). Eleven breast cancer susceptibility genes were analyzed using target-capture sequencing in a previous study; the PGV prevalence in BRCA1, BRCA2, and PALB2 was 0.75%, 3.1%, and 0.45%, respectively. Significant associations were found between the presence of BRCA PGVs and early disease onset, number of familial cancer cases (up to third-degree relatives), triple-negative breast cancer patients under the age of 60, and ovarian cancer history (all P < .0001). In total, 816 patients (40.9%) satisfied the National Comprehensive Cancer Network (NCCN) guidelines for recommending multigene testing. The sensitivity and specificity of the NCCN criteria for discriminating PGV carriers from noncarriers were 71.3% and 60.7%, respectively. The TC model showed good discrimination for predicting BRCA PGVs (area under the curve, 0.75; 95% confidence interval, 0.69-0.81). Furthermore, use of the TC model with an optimized cutoff of TC score ≥0.16% in addition to the NCCN guidelines improved the predictive efficiency for high-risk groups (sensitivity, 77.2%; specificity, 54.8%; about 11 genes). Given the influence of ethnic differences on prediction, we consider that further studies are warranted to elucidate the role of environmental and genetic factors for realizing precise prediction., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: This study was performed to investigate the clinical significance of miR-4535 and miR-1915-5p in severe chorioamnionitis., Materials & Methods: Amniotic fluid samples from 37 patients with severe chorioamnionitis were subjected to miRNA array analysis and ddPCR™. Diagnostic values were assessed using the receiver operating characteristic curve. The patients were separated into three groups according to Blanc's criteria., Results: The expression of miR-4535 and miR-1915-5p was significantly correlated with the copy number of 16S rDNA, had extremely high diagnostic accuracy for severe chorioamnionitis, and was linked to maternal and fetal inflammation., Conclusion: miR-4535 and miR-1915-5p serve as promising biomarkers for the diagnosis of severe chorioamnionitis., Competing Interests: Financial & competing interests disclosure This work was supported in part by the Grant-in-Aid for Scientific Research (C) (grant number 18K09242) and Young Scientists (C) (grant numbers 18K16822, 19K18714 and 20K18179); the Central Research Institute of Fukuoka University (grant number 197011); The Center for Advanced Molecular Medicine; the Fukuoka University from the Ministry of Education, Culture, Sports, Science and Technology (Tokyo, Japan); the Grant-in-Aid from the Kakihara Science and Technology Foundation (Fukuoka, Japan) (grant numbers 18381 to S Miyamoto and 190412 to K Miyata). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript., (© 2021 Chihiro Kiyoshima.)

Aim: Embryo implantation and subsequent pregnancy depends on endometrial thickness. To investigate potential fertility strategies for women with thin endometrium, we explored the efficacy of adipose tissue-derived regenerative cells (ADRCs) on thin endometrium and embryo implantation in a mouse model. Materials & methods: ADRCs isolated from mouse subcutaneous fat were characterized by flow cytometry. Endometrium thickness, endometrial fibrosis, embryo implantation and angiogenesis factors were evaluated in uterine cavities of ethanol-induced thin endometrium mice with ADRC transplantation. Results: ADRCs included adipose-derived stem cells and some blood vessel component cells. ADRCs improved endometrial thickness, endometrial fibrosis and embryo implantation and augmented vascular endothelial growth factor expression in the mouse uterine. Conclusion: ADRCs may be a useful therapeutic strategy to improve fertility of women with thin endometrium.

Dose-dense (DD) chemotherapy is a treatment option for patients with high-risk premenopausal breast cancer. Pegfilgrastim may be administered as prophylaxis against the development of febrile neutropenia and enables the continuation of the DD schedule; however, it is associated with adverse effects, including bone and muscle pain and fatigue. We herein describe our experience with pegfilgrastim administration alongside DD chemotherapy in a patient with breast cancer. A 29-year-old female patient was diagnosed with locally advanced breast cancer during lactation. The patient was diagnosed with cT2N1M0, stage IIB triple-negative breast cancer and underwent four cycles of DD chemotherapy with epirubicin plus cyclophosphamide, followed by four cycles of docetaxel (DTX) every 2 weeks preoperatively, with 3.6 mg pegfilgrastim administered subcutaneously on day 3 of each cycle. The absolute neutrophil count (ANC) was 2,700, 8,400, 11,100, 13,300 and 15,000/mm 3 on day 1 of each cycle. The patient experienced fatigue after each pegfilgrastim injection and was considered to be a high responder to pegfilgrastim. Therefore, 1.8 mg pegfilgrastim on day 3 of the first DD-DTX cycle was recommended. On day 1 of the second cycle, the ANC was 13,090/mm 3 . The patient experienced less fatigue after the administration of 1.8 mg pegfilgrastim, but there was a significant decline in her performance status. As there is currently no evidence of pegfilgrastim dose reduction to below 1.8 mg, pegfilgrastim was omitted on day 3. On day 14, the patient developed viral enteritis, fever (38°C), and an ANC of 297/mm 3 . Therefore, the third cycle was postponed. After 1 week, the patient's ANC recovered to 2,480/mm 3 and she was administered the third cycle with 3.6 mg pegfilgrastim on day 3. Between January 2015 and March 2018, a total of 55 patients with breast cancer received chemotherapy with pegfilgrastim at the Shiga General Hospital. No patients other than the one presented herein experienced leukocytosis during chemotherapy. Although this was a rare complication, a dose of 1.8 mg pegfilgrastim was effective in palliating the patient's symptoms and preventing DD chemotherapy discontinuation.

Background: Radiotherapy is an effective local control therapy for breast cancer. Locoregional control is associated with distant metastasis risk and survival after surgery., Aim: We aimed to evaluate whether Japanese standard postoperative radiotherapy after surgery correlates with disease-free survival (DFS) and overall survival and clarify the characteristics of patients who benefit from it., Method and Results: This retrospective study included 626 operable breast cancer patients. Tumor characteristics and survival outcomes were compared between patients who received radiotherapy and those who did not. Cox proportional hazard analysis was used to analyze prognostic factors for DFS and perform subgroup analysis. Propensity score matching was used to evaluate the efficacy of radiotherapy using a logistic regression model in patients who received radiotherapy or did not. The median follow-up duration after diagnosis of breast cancer was 63 months. DFS and overall survival were better in the irradiated group (P= .002 and P = .001, respectively). Radiotherapy was more effective for estrogen receptor (ER)-positive disease and for early breast cancer without lymph node metastasis. Multivariate analysis revealed that radiotherapy was a dependent risk factor for recurrence or metastasis., Conclusion: Radiotherapy prevents distant metastasis and recurrence in early breast cancer patients. In particular, ER-positive, node-negative patients benefit from Japanese standard tangent field radiation., (© 2019 Wiley Periodicals, Inc.)

Background/aim: Initial treatment of endometrial cancer with surgery and platinum and taxane-based chemotherapy is often successful, but it remains unclear as to whether certain types of the disease relapse. The aim of this study was to identify the clinical features of recurrence in patients without residual tumour in endometrial cancer., Patients and Methods: Clinical features, histological type, and time to recurrence were analyzed in 640 endometrial cancer patients without residual tumours., Results: Of 640 patients, 517 were type I and 123 were type II. For type I, early recurrent (ER) disease and late recurrent (LR) disease were noted in 80 and 8 patients, respectively, and 97.5% of ER occurred within 2 years. After recurrence, 76.2% of ER and 50% of LR patients died. In type II, ER and LR were noted in 41 and 1 patients, respectively, and 97.6% of ER occurred within 2 years, of which 75.6% died after recurrence. One LR case died of disease., Conclusion: Most patients recurred within 2 years irrespective of clinical stage or type., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Abnormalities in the number of vessels can be found for both the umbilical artery and vein. We sometimes encounter cases of a decreased number of umbilical cord vessels, such as a single umbilical artery. In contrast, there may be an increase from three to four vessels within the umbilical cord. A supernumerary umbilical vein is particularly very rare, and it is generally found in combination with congenital anomalies. We report a case of a partial supernumerary umbilical vein., Case Presentation: The previous pregnancy of a 37-year-old healthy Japanese woman (gravida 2, para 1) had been uncomplicated, and the resulting child was alive and well. Prenatal examination at 36 weeks of gestation revealed the coexistence of a four-vessel part and a normal three-vessel part of the umbilical cord. A healthy female neonate weighing 2726 g was born at 38 weeks of gestation. The umbilical cord measured 40 cm in length; the four-vessel part continued to a distance of 18 cm from the surface of the infant's body, and the remaining umbilical cord comprised three vessels. On histological examination, the fetal side of the umbilical cord had two arteries and two veins, and the placental side had two arteries and one vein. Isolated supernumerary umbilical veins tend to be overlooked. We consider that it is important to evaluate the number of umbilical cord vessels in the second trimester using ultrasound combined with color Doppler in at least three sites: the insertion sites on both the fetal abdomen and placenta, and the free loop of the umbilical cord., Conclusions: Prenatal diagnosis of isolated supernumerary umbilical cord vessels tends to be overlooked. However, supernumerary vessels of the umbilical can be associated with fetal congenital anomalies. The number of vessels within the umbilical cord must be examined because the detection of such abnormalities may lead to the prenatal diagnosis of other congenital anomalies.

Introduction: This study was performed to determine whether the combination of maternal blood and amniotic fluid biomarkers can improve the predictive accuracy of histologic chorioamnionitis (HC)., Methods: This retrospective study included 80 singleton pregnant women who were suspected to have intrauterine infection and underwent measurement of two maternal blood biomarkers [maternal white blood cell count (mWBC) and maternal C-reactive protein level (mCRP)] and three amniotic fluid biomarkers [amniotic white blood cell count (aCell), amniotic glucose level (aGlucose), and amniotic lactate dehydrogenase level (aLDH)]. We divided the patients into two groups based on the presence or absence of HC and assessed the predictors of HC using logistic regression models: Model 1, combination of mWBC and mCRP; Model 2, combination of Model 1 and aGlucose; and Model 3, combination of Model 2, aCell, and aLDH., Results: The multivariable analysis showed that aCell was the only significant predictor of HC [odds ratio, 1.24; 95% confidence interval (CI), 1.06-1.68] independent of mWBC, mCRP, aGlucose, and aLDH. The c-statistics were higher in Model 3 (0.803; 95% CI, 0.701-0.905) than Model 1 (0.634; 95% CI, 0.511-0.758) and Model 2 (0.785; 95% CI, 0.684-0.887)., Discussion: We found that the combination of maternal blood and amniotic fluid biomarkers can improve the predictive accuracy of HC. Therefore, our data provide relevant information to support counseling with regard to improving the predictive accuracy of HC in patients with suspected intrauterine infection., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Male breast cancer (MBC) is rare, accounting for only around 1% of all breast cancers. Most MBCs are hormone-driven. Not only the estrogen receptor (ER), but also other steroid hormone receptors, including the androgen receptor (AR) and progesterone receptor (PgR) are expressed in MBC. AR activation in breast cancer cells facilitates downstream gene expression that drives tumorigenesis in a similar manner to ER. AR-mediated signalling works paradoxically in breast cancer and prostate cancer, and cancer cells expressing the AR are endocrine-sensitive., Case Presentation: We describe a case of double cancer of MBC and prostate cancer. A 69-year-old man was referred to our hospital with a lump in his left breast in the 1990s. The patient had cT3N3M0, stage IIIC breast cancer, and underwent a mastectomy and axillary lymph node dissection. Though adjuvant chemotherapy was administered, he experienced pleural metastasis 2 months after the surgery. Two years after the recurrence during endocrine therapy with oral 5-fluorouracil, he complained of frequent urination. Radiological and histological examinations revealed that the patient had cT3N0M0, stage III primary prostate cancer with a prostate-specific antigen (PSA) level of 40.5 ng/mL. Germline mutations in the BRCA1 and BRCA2 genes were not tested. He received multidisciplinary, continuous therapy for both breast and prostate cancer; however, 5 and 3 years after each diagnosis, respectively, he experienced a deep vein thrombosis in his right leg related to the endocrine therapy. Liver metastasis progressed after he stopped breast cancer therapy. However, long-term disease control had been achieved with anti-estrogen therapy for breast cancer and estrogen replacement therapy for prostate cancer., Conclusions: Several studies have shown that estrogen exposure after estrogen depletion likely causes apoptosis of ER-positive breast cancer cells. Our findings indicate that this also applies to the environment in male body. AR dominant signaling prevents breast cancer recurrence and metastasis, especially in MBC patients.

Background: Lumpectomy is a standard surgery for breast cancer; however, it results in breast deformity, especially after radiation therapy. Wider surgical margin correlates lower local recurrence rate. However, bigger defect brings worse cosmetic outcome. The use of a simple filler for the defect is expected. We aimed to improve the cosmetic outcome by using an absorbable Vicryl mesh for breast reconstruction immediately post-lumpectomy., Methods: One sheet of Vicryl woven mesh was prepared for insertion, washed the cavity with natural saline, and placed into the space. The cosmetic outcome was scored for the size, shape, scar, and softness of the breast. The size, shape, color, and position of the nipple-areola complex were also scored. Adverse events were collected retrospectively., Results: From April 2008 to October 2014, 24 female patients received immediate Vicryl mesh insertion. A lumpectomy only group was recruited for cosmetic analysis. All patients received postsurgical radiotherapy. The mean cosmetic assessment score was 8.0 and 9.1 of 12 for the Vicryl mesh group and lumpectomy only group, respectively (P = 0.17). Sixteen patients had adverse events such as erythema at approximately 2 weeks post-surgery. No significant differences were shown except adverse events between two groups. No patient has had local recurrence thus far., Conclusion: Immediate Vicryl mesh insertion leads to significantly increased incidence of postoperative complications and delay in commencement of adjuvant radiotherapy. Furthermore, the cosmetic outcomes are not superior to that of no reconstruction. The development of superior biomaterials is anticipated for breast reconstruction after lumpectomy., (Copyright © 2017. Published by Elsevier Taiwan LLC.)

Background/aim: Many anticancer agents including molecularly-targeted drugs have been developed for ovarian cancer. However, the prognosis of recurrent ovarian cancer remains extremely poor. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is reported as a rational target for ovarian cancer therapy. Moreover, serum HB-EGF expression is recognized as a biomarker in patients with primary ovarian cancer., Materials and Methods: We analysed serum samples with recurrent ovarian cancer at the Fukuoka University Hospital from April 2009 to March 2014. To assess the clinical significance of serum HB-EGF in recurrent ovarian cancer, the association between serum HB-EGF levels and prognosis in patients with recurrent ovarian cancer was examined using ELISA., Results: Patients with high serum HB-EGF expression showed a significantly poor response to second-line chemotherapeutic agents compared with patients with low HB-EGF levels., Conclusion: HB-EGF expression in serum may be a potential therapeutic indicator for novel HB-EGF-targeted therapy in recurrent ovarian cancer., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The prognosis of patients with metastatic or recurrent breast cancer (MBC) is improving as novel treatments are developed. The present study compared the clinical characteristics of patients with MBC with or without a complete clinical response (cCR) and identified the survival-associated factors. This was a retrospective study, which included 171 patients treated for MBC between 2011 and 2017 at the Shiga Medical Center for Adults. Neutrophil to lymphocytes ratios (NLRs) were determined in blood samples. The median follow-up period following diagnosis of MBC was 44 months (range, 0-217 months). A total of 32 patients (18.7%) achieved a cCR. Compared with the non-cCR group, the cCR group had significantly fewer metastases or recurrences (P<0.001), significantly fewer visceral metastases (P<0.001), a significantly lower NLR (P<0.001) and were diagnosed with primary breast cancer at a significantly earlier stage (P=0.003). Prognosis was significantly improved in the cCR group compared with the non-cCR group (P<0.001) and a high NLR (≥19) independently predicted worse survival in a multivariate analysis (P=0.0218; hazard ratio, 1.75; 95% confidence interval, 1.09-2.85). In conclusion, the present study determined that achieving a cCR and having a low NLR are important for the long-term survival of patients with MBC.

Background: As the aging population grows, the number of elderly breast cancer patients has rapidly increased especially in Japan; a suitable treatment for elderly patients, considering chronic comorbidities and treatment tolerance, is urgently needed., Methods: In this retrospective study, 286 elderly breast cancer patients were investigated. Tumor characteristics and survival outcome were compared between 70-79-year-old and ≥ 80-year-old groups. Disease-free survival, overall survival, and breast cancer-specific survival were compared, and the effect of variables was analyzed statistically. For resectable cases, prognoses were compared based on treatment (standard therapy or undertreated)., Results: Tumor characteristics were similar between groups, but the Ki-67 labeling index tended to be higher in older patients. Elderly patients with resectable cancer tended to be undertreated. During the median 59-month follow-up period, overall survival was significantly worse in the ≥80-year-old than in the 70-79-year-old group (p < 0.001), but disease-free and breast cancer-specific survivals were equivalent. Recurrence or death event hazard rates tended to be lower in patients receiving standard treatment., Conclusions: Standard multidisciplinary treatment for breast cancer prevents recurrence and metastasis and tends to extend breast cancer-specific survival even in elderly patients.

Background: Human epidermal growth factor receptor 2 (HER2) -positive breast cancers tend to be more aggressive and more likely to recur than HER2-negative breast cancers. However, novel anti-HER2 therapies have dramatically improved the prognosis of patients with HER2-positive breast cancer., Case Report: We review the cases of 4 women with metastatic breast cancer who achieved clinical complete response (cCR) and terminated their systemic therapy. Two patients had de novo metastatic disease and two patients experienced relapse after adjuvant therapy. All patients achieved cCR using multidisciplinary therapy, experienced prolonged complete remission, and subsequently terminated their systemic therapy without experiencing secondary recurrence., Conclusion: There is no evidence that systemic therapy can be safely terminated after a specific time period, although adverse events (e.g., cardiotoxicity) and unnecessary treatment should be avoided. Thus, it is possible that select patients may be suitable for termination of systemic therapy after they have achieved a prolonged period of cCR., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Chondrolipoma of the breast is a very rare tumor whose histogenesis remains obscure. We report two cases (56-year-old and 43-year-old women) and present the results of an immunohistochemical study which strongly suggests that this tumor is a variant of myofibroblastoma. The tumors predominantly consisted of lipoma-like, mature adipose tissue, and many islands of hyaline cartilage. A proliferation of spindle cells associated with the deposition of collagen fibers was also seen. On immunohistochemical examination, spindle cells showed cytoplasmic reactivity for vimentin, desmin, bcl-2, and α-smooth muscle actin, as well as nuclear reactivity for estrogen receptor (ER) and progesterone receptor (PgR). Chondrocytes were immunoreactive for ER, PgR, S-100 protein, and Sox9. The nuclei of adipocytes, chondrocytes, and spindle cells were not immunoreactive for Rb (retinoblastoma) protein. The immunoreactivity of spindle cells for muscle markers indicates myofibroblastic differentiation, and the lack of the nuclear expression of Rb protein suggests the close relationship of this tumor with myofibroblastoma and spindle cell lipoma. The immunoreactivity of chondrocytes for ER and PgR suggests that they are derived from metaplasia of hormone-sensitive spindle cells. These findings support the concept that chondrolipoma of the breast could be a lipomatous variant of myofibroblastoma associated with cartilaginous metaplasia and that it should be added to members of the "13q/Rb family of tumors."

Mucinous breast carcinoma (MBC) is relatively rare, accounting for <10% of all breast cancers in women. These tumors are usually slow-growing and exhibit less aggressive characteristics compared with other types of breast cancer. Between 1989 and 2016, 55 patients underwent surgery for MBC at the Shiga Medical Center for Adults (Moriyama, Japan). The 10-year disease-free survival (DFS) and overall survival rates were 94.5 and 100.0%, respectively. Specifically, the 10-year DFS rates of pure MBC (PMBC) and mixed MBC were 97.7 and 83.3%, respectively. We herein report the case of a sizeable mucinous carcinoma causing rupture of the skin and bleeding due to tumor pressure. Palliative surgery was performed in order to remove the bleeding source after a total of 5 months of preoperative endocrine-based therapy. In conclusion, palliative surgery improved the patient's quality of life and may be a viable option for PMBC patients. The aim of the present study was to review the characteristics and management of these tumors, particularly in elderly patients.

Chorioamnionitis (CAM), an inflammation of the foetal membranes due to infection, is associated with preterm birth and poor perinatal prognosis. The present study aimed to determine whether CAM can be diagnosed prior to delivery based on the bacterial composition of the amniotic fluid (AF). AF samples from 79 patients were classified according to placental inflammation: Stage III (n = 32), CAM; Stage II (n = 27), chorionitis; Stage 0-I (n = 20), sub-chorionitis or no neutrophil infiltration; and normal AF in early pregnancy (n = 18). Absolute quantification and sequencing of 16S rDNA showed that in Stage III, the 16S rDNA copy number was significantly higher and the α-diversity index lower than those in the other groups. In principal coordinate analysis, Stage III formed a separate cluster from Stage 0-I, normal AF, and blank. Forty samples were classified as positive for microbiomic CAM (miCAM) defined by the presence of 11 bacterial species that were found to be significantly associated with CAM and some parameters of perinatal prognosis. The diagnostic accuracy for CAM according to miCAM was: sensitivity, approximately 94%, and specificity, 79-87%. Our findings indicate the possibility of predicting CAM prior to delivery based on the AF microbiome profile.

Ovarian cancer is the most lethal malignancy among gynaecological cancers. Although many anticancer agents have been developed for the treatment of ovarian cancer, it continues to have an extremely poor prognosis. Heparin-binding epidermal growth factor-like grown factor (HB-EGF) has been reported to be a rational therapeutic target for ovarian cancer. Here, we evaluated the clinical significance of serum HB-EGF by examining the association between prognosis and serum HB-EGF levels in patients with primary ovarian cancer. We found that high serum HB-EGF concentrations were significantly associated with poor prognosis in a combined cohort of patients with all stages of ovarian cancer, as well as in a subset of patients with advanced disease. In addition, serum HB-EGF levels increased as the cancer advanced. These data suggest that serum HB-EGF may be a target for the design of novel therapies for ovarian cancer., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)