Development of information dissemination methods that contribute to improving maternal and child healthcare using social networking sites: a community-based cross-sectional study in Japan.

BACKGROUND: In recent years, feelings of isolation among mothers caring for small children has become a significant social issue in Japan. The purpose of this study is to develop a message to alleviate their loneliness, to evaluate the impact of social networking sites (SNS) for delivering such messages, and to propose means of more effective information transmission to promote health for mothers raising small children. METHODS: Our study was conducted in two stages, first an interview and then a cross-sectional study of the mothers involving a questionnaire survey. The interview was targeted two public-health nurses caring for mothers. Based on these interviews, we developed six messages intended to alleviate the mothers' sense of loneliness, which were vetted by seven mothers. The second stage was to conduct a questionnaire survey of mothers both before and after our selected message as advertisement on Instagram and analyzed the effect. The surveys were collected during routine child health check-ups in the City of Takatsuki, Japan. RESULTS: From the six draft messages created based on interviews with public health nurses, we selected the message that most relieves the feeling of loneliness of the mothers who are raising small children. The survey questionnaire was taken by 494 mothers prior to our posting of Instagram advertisements (ads), and afterwards by 419 mothers. The percentage of mothers feeling loneliness tended to decrease after reading the messages (before ads.:8.1%, after ads.:5.8%). 8.6% of the mothers (36/419) remembered seeing the Instagram ads. Mothers with financial anxiety were significantly more likely to have remembered seeing the Instagram ads (p < 0.01). CONCLUSIONS: Our results indicate that usefulness of SNS messaging for mothers raising small children may reduce their feeling of loneliness. Among the SNS, disseminating child-rearing information on Instagram may be more effective for people with financial instability.

CD70 antibody-drug conjugate: A potential novel therapeutic agent for ovarian cancer.

This study aimed to investigate the cytotoxicity of a cluster of differentiation 70 antibody-drug conjugate (CD70-ADC) against ovarian cancer in in vitro and in vivo xenograft models. CD70 expression was assessed in clinical samples by immunohistochemical analysis. Western blotting and fluorescence-activated cell sorting analyses were used to determine CD70 expression in the ovarian cancer cell lines A2780 and SKOV3, and in the cisplatin-resistant ovarian cancer cell lines A2780cisR and SKOV3cisR. CD70 expression after cisplatin exposure was determined in A2780 cells transfected with mock- or nuclear factor (NF)-κB-p65-small interfering RNA. We developed an ADC with an anti-CD70 monoclonal antibody linked to monomethyl auristatin F and investigated its cytotoxic effect. We examined 63 ovarian cancer clinical samples; 43 (68.3%) of them expressed CD70. Among patients with advanced stage disease (n = 50), those who received neoadjuvant chemotherapy were more likely to exhibit high CD70 expression compared to those who did not (55.6% [15/27] vs 17.4% [4/23], P < .01). CD70 expression was confirmed in A2780cisR, SKOV3, and SKOV3cisR cells. Notably, CD70 expression was induced after cisplatin treatment in A2780 mock cells but not in A2780-NF-κB-p65-silenced cells. CD70-ADC was cytotoxic to A2780cisR, SKOV3, and SKOV3cisR cells, with IC50 values ranging from 0.104 to 0.341 nmol/L. In A2780cisR and SKOV3cisR xenograft models, tumor growth in CD70-ADC treated mice was significantly inhibited compared to that in the control-ADC treated mice (A2780cisR: 32.0 vs 1639.0 mm3 , P < .01; SKOV3cisR: 232.2 vs 584.9 mm3 , P < .01). Platinum treatment induced CD70 expression in ovarian cancer cells. CD70-ADC may have potential therapeutic implications in the treatment of CD70 expressing ovarian cancer.

Surgical and oncologic outcomes of hyperthermic intraperitoneal chemotherapy for uterine leiomyosarcoma: A systematic review of literature.

OBJECTIVE: To examine the perioperative and survival outcomes in women with disseminated peritoneal uterine leiomyosarcoma (uLMS) who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: A comprehensive systematic review of literature was conducted using multiple public search engines, PubMed, Scopus, and the Cochrane Library, in compliance with the PRISMA guidelines. Women with disseminated peritoneal uLMS treated with CRS-HIPEC were analyzed. Perioperative morbidity and mortality rate as well as oncologic outcomes related to CRS-HIPEC were assessed. RESULTS: Ten studies met the inclusion criteria from 2004 to 2020, including 8 case series (n=28) and 2 original articles (n=47). Of the 75 patients, 68 (90.7%) were women with uLMS whereas 7 women were non-uLMS. Of these, 64 (85.3%) had recurrent disease, and 39 (52.0%) received chemotherapy or radiotherapy prior to CRS-HIPEC. The perioperative mortality rate was 4.0% (intraoperative 1.3%, and postoperative 2.7%), and postoperative complications (grade ≥3) rate ranged 21.4-22.2%. With regard to HIPEC regimens (n=75), cisplatin was most frequently used (n=55, 73.3%) followed by melphalan (n=17, 22.7%) and others (n=3, 4.0%). Among the two observational studies, the median overall survival after CRS-HIPEC treatment was 29.5-37 months. In one limited comparative effectiveness study (n=13), albeit statistically non-significant CRS-HIPEC was associated with higher progression-free survival versus CRS alone (3-year rates, 71.4% versus 0%, P=0.10). When the HIPEC regimens were compared, melphalan use was associated with decreased uLMS-related mortality compared to a cisplatin-based regimen, but the association was not statistically significant (hazard ratio 0.35, 95% confidence interval 0.04-3.05, P=0.35). CONCLUSION: Effectiveness of CRS-HIPEC for disseminated peritoneal uLMS is yet to be determined. As interpretation of the available data on survival is limited due to small sample sizes or the lack of an active comparator, further study is warranted to examine the safety and survival effect of CRS-HIPEC in disseminated peritoneal uLMS.

Uterine carcinosarcoma: Contemporary clinical summary, molecular updates, and future research opportunity.

Uterine carcinosarcoma (UCS) is a biphasic aggressive high-grade endometrial cancer in which the sarcoma element has de-differentiated from the carcinoma element. UCS is considered a rare tumor, but its incidence has gradually increased in recent years (annual percent change from 2000 to 2016 1.7%, 95% confidence interval 1.2-2.2) as has the proportion of UCS among endometrial cancer, exceeding 5% in recent years. UCS typically affects the elderly, but in recent decades patients became younger. Notably, a stage-shift has occurred in recent years with increasing nodal metastasis and decreasing distant metastasis. The concept of sarcoma dominance may be new in UCS, and a sarcomatous element >50% of the uterine tumor is associated with decreased survival. Multimodal treatment is the mainstay of UCS. Lymphadenectomy, chemotherapy, and brachytherapy have increased in the past few decades, but survival outcomes remain dismal: the median survival is less than two years, and the 5-year overall survival rate has not changed in decades (31.9% in 1975 to 33.8% in 2012). Carboplatin/paclitaxel adjuvant chemotherapy improves progression-free survival compared with ifosfamide/paclitaxel, particularly in stages III-IV disease (GOG-261 trial). Twenty-six clinical trials previously examined therapeutic effectiveness in recurrent/metastatic UCS. The median response rate and progression-free survival were 37.5% and 5.9 months, respectively, after first-line therapy, but after later therapies, the outcomes were far worse (5.5% and 1.8 months, respectively). One significant discovery was that epithelial-mesenchymal transition (EMT) plays a pivotal role in the pathogenesis of sarcomatous dedifferentiation in UCS and that heterologous sarcoma is associated with a higher EMT signature compared with homologous sarcoma. Furthermore, next-generation sequencing has revealed that UCS tumors are serous-like and that common somatic mutations include those in TP53, PIK3CA, FBXW7, PTEN, and ARID1A. This contemporary review highlights recent clinical and molecular updates in UCS. A possible therapeutic target of EMT in UCS is also discussed.

CD70 antibody-drug conjugate as a potential therapeutic agent for uterine leiomyosarcoma.

BACKGROUND: Uterine leiomyosarcoma is a rare and aggressive gynecologic malignancy originating in the myometrium of the uterine corpus that tends to recur even after complete surgical excision. Current therapeutic agents have only modest effects on uterine leiomyosarcoma. Although antibodies and antibody-drug conjugates have been recognized as useful targeted therapies for other cancers, no study has yet evaluated the effects of this approach on uterine leiomyosarcoma. OBJECTIVE: This study aimed to examine the activity of tumoral CD70 in uterine leiomyosarcoma and assess the antitumor activity of CD70-antibody-drug conjugate treatment in uterine leiomyosarcoma. STUDY DESIGN: Target membrane proteins were screened by profiling and comparing membrane protein expression in 3 uterine leiomyosarcoma cell lines (SK-UT-1, SK-LMS-1, and SKN) and normal uterine myometrium cells using the isobaric tags for relative and absolute quantitation labeling method. Western blotting, fluorescence-activated cell sorting analyses, and immunohistochemistry were used to examine CD70 expression in the membrane proteins in uterine leiomyosarcoma cell lines and clinical samples. We developed an antibody-drug conjugate with a monoclonal antibody of the target membrane protein linked to monomethyl auristatin F and investigated its antitumor effects against uterine leiomyosarcoma (in vitro, in vivo, and in patient-derived xenograft models). RESULTS: CD70 was identified as a specific antigen highly expressed in uterine leiomyosarcoma cell lines. Of the 3 uterine leiomyosarcoma cell lines, CD70 expression was confirmed in SK-LMS-1 cells by western blotting and fluorescence-activated cell sorting analysis. CD70 overexpression was observed in 19 of 21 (90.5%) tumor specimens from women with uterine leiomyosarcoma. To generate CD70-antibody-drug conjugate, anti-CD70 monoclonal antibody was conjugated with a novel derivative of monomethyl auristatin F. CD70-antibody-drug conjugate showed significant antitumor effects on SK-LMS-1 cells (half maximal inhibitory concentration, 0.120 nM) and no antitumor effects on CD70-negative uterine leiomyosarcoma cells. CD70-antibody-drug conjugate significantly inhibited tumor growth in the SK-LMS-1 xenograft mouse model (tumor volume, 129.8 vs 285.5 mm3; relative reduction, 54.5%; P<.001) and patient-derived xenograft mouse model (tumor volume, 128.1 vs 837.7 mm3; relative reduction, 84.7%; P<.001). CONCLUSION: Uterine leiomyosarcoma tumors highly express CD70 and targeted therapy with CD70-antibody-drug conjugate may have a potential therapeutic implication in the treatment of uterine leiomyosarcoma.

Clinico-pathological significance of suspicious peritoneal cytology in endometrial cancer.

BACKGROUND AND OBJECTIVES: Suspicious peritoneal cytology refers to the result of peritoneal cytology testing that is insufficient in either quality or quantity for a definitive diagnosis of malignancy. This study examined characteristics and survival outcomes related to suspicious peritoneal cytology in endometrial cancer. METHODS: A population-based retrospective study by querying the National Cancer Institute's Surveillance, Epidemiology, and End Results Program was conducted. A total of 41,229 women with Stage I-III endometrial cancer who had peritoneal cytologic sampling at hysterectomy from 2010 to 2016 were examined. A Cox proportional hazard regression model and a competing risk analysis with Fine-Gray model were fitted to assess survival outcome related to suspicious peritoneal cytology. RESULTS: Suspicious peritoneal cytology was seen in 702 (1.7%) cases. In multivariable models, suspicious peritoneal cytology was associated with increased risk of endometrial cancer mortality (subdistribution-hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.29-2.20, p < 0.001) and all-cause mortality (adjusted-HR: 1.55, 95% CI: 1.27-1.90, p < 0.001) compared with negative peritoneal cytology. Sensitivity analysis demonstrated that suspicious peritoneal cytology had discrete overall survival improvement compared with malignant peritoneal cytology in a propensity score weighting model (HR: 0.85, 95% CI: 0.72-0.99, p = 0.049). CONCLUSION: Our study suggests that suspicious peritoneal cytology may be a prognostic factor for decreased survival in endometrial cancer.

A questionnaire survey on a feeling of loneliness of the mothers raising children.

AIM: A feeling of isolation childcare mothers' face is a serious social problem in Japan because the relationships with mothers and local communities have grown sparser. The purpose of this study was to clarify the feelings of isolation of mothers during childcare and the factors related to it. METHODS: We conducted a questionnaire survey in Yao City, Osaka. We mailed out a questionnaire survey of 1293 mothers with infants who had either a 4-month or 42-month routine health checkup during the period from September to December of 2018. RESULTS: There was no association between "feeling lonely while raising my child" and the absence of "people who helped raise my children." On the other hand, it was found that the mothers' inner feelings, such as "I wasn't satisfied with my childcare environment" (OR: 2.55, 95% CI: 1.32-4.91, p = 0.0052) or "I lacked confidence in my own childcare abilities" (OR: 6.21, 95% CI: 4.31-8.95, p < 0.0001), were associated with their sense of loneliness. CONCLUSIONS: Mothers' "sense of loneliness" was shown to be best correlated with their dissatisfaction with the environment of their childcare and with their lack of confidence in raising their own children.

Maternal and Fetal Outcomes after Prior Mid-Trimester Uterine Rupture: A Systematic Review with Our Experience.

Background and Objectives: Since spontaneous uterine rupture in the mid-trimester is rare, maternal and fetal outcomes in subsequent pregnancies remain unclear. Therefore, this study aimed to examine the maternal and fetal outcomes of subsequent pregnancies after prior mid-trimester uterine rupture. Materials and Methods: A systematic review using PubMed, the Cochrane Central Register of Controlled Trials, and Scopus until 30 September 2021, was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The studies that clarified the maternal and fetal outcomes after prior mid-trimester uterine rupture and our case (n = 1) were included in the analysis. Results: Among the eligible cases, there were five women with eight subsequent pregnancies after prior mid-trimester uterine rupture. The timing of prior mid-trimester uterine rupture ranged from 15 to 26 weeks of gestation. The gestational age at delivery in subsequent pregnancies was 23-38 gestational weeks. Among the included cases (n = 8), those involving prior mid-trimester uterine rupture appeared to be associated with an increased prevalence of placenta accreta spectrum (PAS) (n = 3, 37.5%) compared with those involving term uterine rupture published in the literature; moreover, one case exhibited recurrent uterine rupture at 23 weeks of gestation (12.5%). No maternal deaths have been reported in subsequent pregnancies following prior mid-trimester uterine rupture. Fetal outcomes were feasible, except for one pregnancy with recurrent mid-trimester uterine rupture at 23 weeks of gestation, whose fetus was alive complicated by cerebral palsy. Conclusions: Our findings suggest that clinicians should be aware of the possibility of PAS and possible uterine rupture in pregnancies after prior mid-trimester uterine rupture. Further case studies are warranted to assess maternal and fetal outcomes in pregnancies following prior mid-trimester prior uterine rupture.

Copper ions are novel therapeutic agents for uterine leiomyosarcoma.

BACKGROUND: Multidrug resistance is a major concern in uterine leiomyosarcoma treatment. Development of effective chemotherapies and management of drug resistance in patients is necessary. The copper efflux transporter adenosine triphosphatase copper transporting beta is a member of the P-type adenosine triphosphatase family and is also known as a strong platinum efflux transporter. Various reports have shown the association between adenosine triphosphatase copper transporting beta and platinum resistance; however, suitable inhibitors or methods for inhibiting platinum efflux via adenosine triphosphatase copper transporting beta are not developed. OBJECTIVE: Our study focused on platinum resistance in uterine leiomyosarcoma. The role of adenosine triphosphatase copper transporting beta in uterine leiomyosarcoma resistance to platinum drugs was investigated both in vitro and in vivo. STUDY DESIGN: Adenosine triphosphatase copper transporting beta expression was investigated by Western blotting and the efficacy of copper sulfate pretreatment and cisplatin administration in adenosine triphosphatase copper transporting beta-expressing cells was investigated both in vitro and in vivo. RESULTS: Western blot analysis of SK-LMS-1 cells (uterine leiomyosarcoma cell line) revealed strong adenosine triphosphatase copper transporting beta expression. A permanent SK-LMS-ATPase copper transporting beta-suppressed cell line (SK-LMS-7B cells) was generated, and cisplatin exhibited a significant antitumor effect in SK-LMS-7B cells, both in vitro (SK-LMS-1 cells, half-maximal inhibitory concentration, 17.2 µM; SK-LMS-7B cells, half-maximal inhibitory concentration, 4.2 µM, P < .01) and in xenografts compared with that in SK-LMS-1 cells (5.8% vs 62.8%, P < .01). Copper sulfate was identified as a preferential inhibitor of platinum efflux via adenosine triphosphatase copper transporting beta. In SK-LMS-1 cells pretreated with 15 µM copper sulfate for 3 hours, the cisplatin half-maximal inhibitory concentration decreased significantly compared with that in untreated cells and resulted in significantly increased intracellular platinum accumulation (1.9 pg/cell vs 8.6 pg/cell, P < .01). The combination of copper sulfate pretreatment with cisplatin administration was also effective in vivo and caused cisplatin to exhibit significantly increased antitumor effects in mice with SK-LMS-1 xenografts (3.1% vs 62.7%, P < .01). CONCLUSION: Our study demonstrates that adenosine triphosphatase copper transporting beta is overexpressed in uterine leiomyosarcoma cells and that copper sulfate, which acts as an inhibitor of platinum efflux via adenosine triphosphatase copper transporting beta, may be a therapeutic agent in the treatment of uterine leiomyosarcoma.

Histologic correlation between smartphone and coloposcopic findings in patients with abnormal cervical cytology: experiences in a tertiary referral hospital.

BACKGROUND: Smartphones recently have been applied in the medical setting. However, the literature evaluating the utility of smartphones in gynecologic oncology is limited. OBJECTIVE: To evaluate the utility of a smartphone in the detection of uterine cervical lesions in patients with abnormal cervical cytology. STUDY DESIGN: Seventy-five women with abnormal cervical cytology were enrolled. Two doctors independently inspected the uterine cervix by using smartphone or colposcopy. Images were captured using acetic acid, and biopsies were taken as standard-of-care procedures. The diagnostic performance of the smartphone for cervical intraepithelial neoplasm 1 or worse and cervical intraepithelial neoplasm 2 or worse were evaluated, and the kappa value was calculated to determine the chance corrected agreement of the histologic diagnoses based on the smartphone and colposcopic findings. RESULTS: There was a substantial agreement between histologic diagnoses based on the smartphone and colposcopic findings, with a kappa value of 0.67 (95% confidence interval, 0.43-0.90). The sensitivity, specificity, positive predictive value, and negative predictive value of the smartphone in the diagnosis of cervical intraepithelial neoplasm 1 or worse were 0.89 (95% confidence interval, 0.79-0.96), 0.33 (95% confidence interval, 0.08-0.70), 0.91 (95% confidence interval, 0.81-0.97), and 0.30 (95% confidence interval, 0.07-0.65), respectively. The sensitivity, specificity, positive predictive value, and negative predictive value in the diagnosis of cervical intraepithelial neoplasm 2 or worse were 0.92 (95% confidence interval, 0.81-0.98), 0.24 (95% confidence interval, 0.09-0.45), 0.71 (95% confidence interval, 0.58-0.81), and 0.60 (95% confidence interval, 0.26-0.88), respectively. CONCLUSION: We found that there was a substantial agreement between the histologic diagnoses based on the smartphone and colposcopic findings. The smartphone seems to be useful and may be an alternative to colposcopy.

Systematic review on the needle and suture types for uterine compression sutures: a literature review.

BACKGROUND: This study aimed to identify and review associations between the types of sutures used for uterine compression suture (UCS) and its outcomes in postpartum hemorrhage. METHODS: An electronic search using PubMed and Scopus databases was performed. We included the English articles reported from January 1, 1997, to May 31, 2017, using search words or terms regarding the types of suture and needle used for UCSs. We only included studies describing the sutures in the systematic review. RESULTS: We found 196 studies and included 76 (38.8%) in our analysis. We collected data on maternal outcomes for 924 patients and categorized them. Of the 76 studies, suture sizes 0, 1, and 2 were used in 6, 44, and 32 articles, respectively (some studies used multiple sutures). Of the 45 studies mentioning the needles, curved and straight needles were used in 35 and 10, respectively. The results of our review revealed that about 80% of previous articles used Catgut and Polyglactin 910 sutures. Because no studies that compared the efficacy of different size of sutures were identified, we investigated the differences using the cases reported in previous studies mentioned above. In the first analysis, we compared the uterine preservation rate between size 1 and size 2 sutures. We found no significant difference in uterine preservation rate (92.8%: size 1 vs. 94.2%: size 2, p > 0.05) but found significant difference in transfusion rate (62.4% vs. 79.1%, p < 0.01). With the hypothesis that non-transfusion cases were less severe, we excluded these cases from second analysis. Although our second analysis of only Catgut or Polyglactin showed strong selection bias, we observed that uterine preservation rate was significantly higher in cases with size 2 suture than in those with size 1 suture (86.9% vs. 93.5%, p = 0.033). CONCLUSIONS: Our systematic review showed that approximately 80% of cases were treated by Catgut and Polyglactin 910. Due to the heterogeneity of cases included in this review, it is difficult to estimate which suture is better for UCSs. More robust studies are necessary to enable the identification of the superior suture for performing UCSs.

New dedicated blunt straight needles and sutures for uterine compression sutures: a retrospective study and literature review.

BACKGROUND: We developed a dedicated blunt straight needle with No. 2 polydioxanone sutures (2-Monodiox®) for uterine compression sutures (UCSs) and aimed to assess the outcomes and complication rates of UCSs for postpartum hemorrhage by comparing with commercially available needle and suture types. METHODS: A retrospective analysis was performed between January 2010 and February 2018. During the study period, two types of commercially available sutures and 2-Monodiox® were used. PubMed, MEDLINE, and Scopus databases were searched for English articles published between January 1997 and May 2017 using search terms related to the suture and needle types for UCSs to discuss the dedicated needles and sutures for UCS. RESULTS: The analysis included 47 cases of UCSs for the uterine body with three suture types (No. 0 polydioxanone, 7 cases; No. 1 poliglecaprone 25, 21 cases; and No. 2 polydioxanone, 19 cases). B-Lynch suture using No. 0 sutures was associated with a significantly lower uterine preservation rate than those with Nos. 1 and 2 sutures (42.9% vs. 95.2 and 89.5%, respectively; p < 0.01). A modified Hayman suture technique was performed using 2-Monodiox® sutures, which achieved a similar uterine preservation rate compared with B-Lynch suture using No. 1 poliglecaprone 25 sutures. No patients developed severe complications. The literature review showed that no dedicated sutures have developed for UCSs. Three dedicated needles for UCSs have been developed, and 2-Monodiox® is the first dedicated blunt straight needle for UCSs. CONCLUSION: Our data showed that No. 0 sutures should not be used for B-Lynch suture. The uterine preservation rate is similar for 2-Monodiox® with modified Hayman suture and No. 1 poliglecaprone 25 sutures with B-Lynch suture, without the occurrence of severe complications.

Anti-glypican-1 antibody-drug conjugate exhibits potent preclinical antitumor activity against glypican-1 positive uterine cervical cancer.

Glypican-1 (GPC1) is highly expressed in solid tumors, especially squamous cell carcinomas (SCCs), and is thought to be associated with disease progression. We explored the use of a GPC1-targeted antibody-drug conjugate (ADC) as a novel treatment for uterine cervical cancer. On immunohistochemical staining, high expression levels of GPC1 were detected in about 50% of uterine cervical cancer tissues and also in a tumor that had relapsed after chemoradiotherapy. Novel anti-GPC1 monoclonal antibodies were developed, and clone 01a033 was selected as the best antibody for targeted delivery of the cytotoxic agent monomethyl auristatin F (MMAF) into GPC1-positive cells. The anti-GPC1 antibody was conjugated with MMAF. On flow cytometry, HeLa and ME180 cervical cancer cells highly expressed GPC1, however, RMG-I ovarian clear cell cancer cell line showed weak expression. The GPC1-ADC was rapidly internalized into GPC1-expressing cells in vitro and was potently cytotoxic to cancer cells highly expressing GPC1. There were no inhibitory effects on cancer cells with low expression of GPC1. In a murine xenograft model, GPC1-ADC also had significant and potent tumor growth inhibition. GPC1-ADC-mediated G2/M phase cell cycle arrest was detected, indicating that the dominant antitumor effect in vivo was MMAF-mediated. The toxicity of GPC-ADC was tolerable within the therapeutic dose range in mice. Our data showed that GPC1-ADC has potential as a promising therapy for uterine cervical cancer.

Predictors for recurrent/persistent high-grade intraepithelial lesions and cervical stenosis after therapeutic conization: a retrospective analysis of 522 cases.

OBJECTIVE: The objective of the study is to identify the risk factors associated with recurrent/persistent disease and cervical stenosis after conization. METHODS: Five hundred twenty-two (522) cases of high-grade intraepithelial lesions treated by conization were retrospectively reviewed. Risk factors associated with recurrent/persistent disease were analyzed by univariate and multivariate analysis using a Cox hazard regression model. Factors that could potentially affect the risk of cervical stenosis were examined by univariate and by multivariate analysis using the χ 2 test and logistic regression, respectively. RESULTS: Recurrent/persistent diseases and cervical stenosis occurred in 4.8% and 5.4% of the patients, respectively. Age ≥46 years [hazard ratio (HR) 3.6, 95% CI 1.36-10.3, p = 0.0092] and surgical margin involvement (HR 13.44, 95% CI 5.07-46.37, p < 0.001) were independent predictors for recurrent/persistent diseases. Age ≥46 years [odds ratio (OR) 4.27, 95% CI 1.88-10.07, p < 0.001] and shortened interval after childbirth to conization (within 12 months) (OR 5.42, 95% CI 1.42-17.41, p = 0.016) were independent risk factors for cervical stenosis. CONCLUSION: Elderly patients (aged ≥46 years) are at high risk of recurrence and cervical stenosis, which may lead to unsatisfactory follow-up. Subsequent hysterectomy is beneficial to patients aged 46 or older with surgical margin involvement. Clinicians should recognize the possibility of cervical stenosis after conization during the breastfeeding period, leading to secondary infertility or hematometra.

Clinical outcomes of abnormal cervical cytology and human papillomavirus-related lesions in patients with organ transplantation: 11-year experience at a single institution.

OBJECTIVES: The objective of this study is to analyze the clinical outcomes of abnormal cervical cytology and newly diagnosed human papillomavirus (HPV)-related disease after organ transplantation. MATERIALS AND METHODS: Medical records from July 2004 to August 2015 were reviewed, and thirteen patients were identified who had been newly diagnosed with HPV-related disease (cervical intraepithelial neoplasia [CIN] and cervical cancer) after organ transplantation. The median transition time to the aggravation of cervical cytology and the spontaneous regression rate of CIN were evaluated. Clinical outcomes of CIN1 and CIN2 were compared between the general population and patients with organ transplantation. We also reviewed the current literature regarding the incidence of HPV infection, Pap smear abnormality and/or CIN after organ transplantation. RESULTS: The cervical cytology aggravated in nine of the 13 patients (69 %). In seven of the 13 cases (54 %), treatments such as cervical conization, laser vaporization, or radiation therapy, were conducted. HPV-related disease disappeared after treatment in only three of the seven actively treated cases (43 %). In contrast, the lesions persisted in three (43 %) cases after treatment. One patient died from cervical cancer. The spontaneous regression rate of the HPV-related diseases, if left untreated, was 0 %. There was a statistically significant difference in the clinical outcomes of CIN1 and CIN2 between the general population and patients with organ transplantation (p = 0.0026 and 0.0315, respectively; chi-squared test). CONCLUSIONS: HPV-related lesions that are newly diagnosed after organ transplantation do not seem to regress as spontaneously as in the general population. Physicians should recognize the importance of close monitoring and long-term follow-up.

Potential targets for ovarian clear cell carcinoma: a review of updates and future perspectives.

Advances in surgical and medical treatments for ovarian cancer have improved prognoses. Platinum drugs in particular are pivotal for the medical treatment of ovarian cancer. However, previous studies have revealed that some histological subtypes, such as clear cell carcinoma, are resistant to medical treatment, including that with platinum drugs. Consequently, the clinical prognosis of advanced clear cell carcinoma is remarkably inferior, primarily because of its chemoresistant behavior. The prevalence of clear cell carcinoma is approximately 5 % in the West, but in Japan, its prevalence is particularly high, at approximately 25 %. Current medical treatments for advanced clear cell carcinoma are difficult to administer, and they have poor efficacy, warranting the development of novel target-based therapies. In this review, we describe medical treatments for clear cell carcinoma and discuss future prospects for therapy. In particular, we focus on the mechanism of platinum resistance in clear cell carcinoma, including the role of annexin A4, one of the most investigated factors of platinum resistance, as well as the mutant genes and overexpressed proteins such as VEGF, PI3K/AKT/mTOR signaling pathway, ARID1A, hepatocyte nuclear factor-1ß, ZNF217. We also review targeted molecular therapeutics for epithelial ovarian cancer and discuss their role in clear cell carcinoma treatment. We review the drugs targeting angiogenesis (bevacizumab, sorafenib, and pazopanib), growth factors (gefitinib, erlotinib, lapatinib, trastuzumab, and AMG479), and signaling pathways (temsirolimus, dasatinib, and imatinib), and other drugs (oregovomab, volociximab, and iniparib). This current review summarizes and discusses the clinical significance of these factors in ovarian clear cell carcinoma as well as their potential mechanisms of action. It may provide new integrative understanding for future studies on their exact role in ovarian clear cell carcinoma.

Large uterine cervical adenomyoma excised by vaginal approach: case report, images, and literature review.

Uterine adenomyoma is often overlooked, and cervical adenomyoma is extremely rare. Previous reports suggest that a uterine adenomyoma usually occurs in the uterine corpus but rarely in the uterine cervix. Approximately 20 reports of cervical adenomyoma have been published to date. However, cervical adenomyoma has been rarely investigated using magnetic resonance imaging. We encountered a large multicystic tumor in the uterine cervix of a 26-year-old woman that was difficult to diagnose preoperatively. On the basis of cytology, biopsy, and imaging findings, the cervical multicystic tumor measured approximately 13.0 cm. The patient underwent vaginal adenomyomectomy, and the tumor was completely resected. A histologic diagnosis of cervical adenomyoma was made because of proliferation of endocervical glands and the presence of rounded smooth muscle stroma. Awareness of this tumor in the uterine cervix is important for accurate diagnosis and treatment. Herein we present a rare case of a large cervical adenomyoma, with imaging studies, an image of the operation, histologic findings, and a literature review.

Current Evidence on Vasa Previa without Velamentous Cord Insertion or Placental Morphological Anomalies (Type III Vasa Previa): Systematic Review and Meta-Analysis.

Vasa previa carries a high risk of severe fetal morbidity and mortality due to fetal hemorrhage caused by damage to unprotected fetal cord vessels upon membrane rupture. Vasa previa is generally classified into types I and II. However, some cases are difficult to classify, and some studies have proposed a type III classification. This study aimed to review the current evidence on type III vasa previa. A systematic literature search was conducted, and 11 articles (2011-2022) were included. A systematic review showed that type III vasa previa accounts for 5.7% of vasa previa cases. Thirteen women with type III vasa previa were examined at a patient-level analysis. The median age was 35 (interquartile range [IQR] 31.5-38) years, and approximately 45% were assisted reproductive technology (ART) pregnancies. The median gestational week of delivery was 36 (IQR 34-37) weeks; the antenatal detection rate was 84.6%, and no cases reported neonatal death. The characteristics and obstetric outcomes (rate of ART, antenatal diagnosis, emergent cesarean delivery, gestational age at delivery, and neonatal mortality) were compared between types I and III vasa previa, and all outcomes of interest were similar. The current evidence on type III vasa previa is scanty, and further studies are warranted.

Relationship between Abnormal Placenta and Obstetric Outcomes: A Meta-Analysis.

The placenta has several crucial physiological functions that help maintain a normal pregnancy. Although approximately 2-4% of pregnancies are complicated by abnormal placentas, obstetric outcomes remain understudied. This study aimed to determine the outcomes and prevalence of patients with abnormal placentas by conducting a systematic review of 48 studies published between 1974 and 2022. The cumulative prevalence of circumvallate placenta, succenturiate placenta, multilobed placenta, and placenta membranacea were 1.2%, 1.0%, 0.2%, and 0.004%, respectively. Pregnancies with a circumvallate placenta were associated with an increased rate of emergent cesarean delivery, preterm birth (PTB), and placental abruption compared to those without a circumvallate placenta. The succenturiate lobe of the placenta was associated with a higher rate of emergent cesarean delivery, whereas comparative results were observed in terms of PTB, placental abruption, and placenta previa in comparison to those without a succenturiate lobe of the placenta. A comparator study that examined the outcomes of multilobed placentas found that this data is usually unavailable. Patient-level analysis (n = 15) showed high-rates of abortion (40%), placenta accreta spectrum (40%), and a low term delivery rate (13.3%) in women with placenta membranacea. Although the current evidence is insufficient to draw a robust conclusion, abnormal placentas should be recognized as a high-risk factor for adverse outcomes during pregnancy.

Systematic Review of the Survival Outcomes of Neoadjuvant Chemotherapy in Women with Malignant Ovarian Germ Cell Tumors.

Randomized clinical trials assessing the efficacy of neoadjuvant chemotherapy (NACT) for advanced epithelial ovarian cancer have predominantly included women with high-grade serous carcinomas. The response rate and oncological outcomes of NACT for malignant ovarian germ cell tumors (MOGCT) are poorly understood. This study aimed to examine the effects of NACT on women with MOGCT by conducting a systematic review of four public search engines. Fifteen studies were identified, and a further descriptive analysis was performed for 10 original articles. In those studies, most women were treated with a bleomycin, etoposide, and cisplatin regimen, and one to three cycles were used in most studies. Four studies comparing NACT and primary debulking surgery showed similar complete response rates (n = 2; pooled odds ratio [OR] 0.90, 95% confidence interval [CI] 0.15-5.27), comparable overall survival (n = 3; 87.0-100% versus 70.0-100%), disease-free survival (n = 3; 87.0-100% versus 70.0-100%), recurrence rate (n = 1; OR 3.50, 95%CI 0.38-32.50), and adverse events rate from chemotherapy between the groups. In conclusion, NACT may be considered for the management of MOGCT; however, possible candidates for NACT use and an ideal number of NACT cycles remain unknown. Further studies are warranted to validate the efficacy of NACT in advanced MOGCT patients.