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Background: Retained products of conception (RPOC) often cause severe postpartum hemorrhage (PPH) but the clinical significance of RPOC in placenta previa is unclear. This study aimed to investigate the clinical significance of RPOC in women with placenta previa. The primary outcome was to evaluate risk factors of RPOC and the secondary outcome was to consider risk factors of severe PPH. Methods: Singleton pregnant women with placenta previa who underwent cesarean section (CS) and placenta removal during the operation at the National Defense Medical College Hospital between January 2004 and December 2021 were identified. A retrospective analysis was performed to examine the frequency and risk factors of RPOC and the association of RPOC with severe PPH in pregnant women with placenta previa. Results: This study included 335 pregnant women. Among these, 24 (7.2%) pregnant women developed RPOC. Pregnant women with prior CS (Odds Ratio (OR) 5.98; 95% Confidence Interval (CI) 2.35–15.20, p < 0.01), major previa (OR 3.15; 95% CI 1.19–8.32, p < 0.01), and placenta accreta spectrum (PAS) (OR 92.7; 95% CI 18.39–467.22, p < 0.01) were more frequent in the RPOC group. Multivariate analysis revealed that prior CS (OR 10.70; 95% CI 3.47–33.00, p < 0.01,) and PAS (OR 140.32; 95% CI 23.84–825.79, p < 0.01) were risk factors for RPOC. In pregnant women who have placenta previa with RPOC or without RPOC, the ratio of severe PPH were 58.3% and 4.5%, respectively (p < 0.01). Furthermore, the occurrence of prior CS (OR 9.23; 95% CI 4.02–21.20, p < 0.01), major previa (OR 11.35; 95% CI 3.35–38.38, p < 0.01), placenta at the anterior wall (OR 3.44; 95% CI 1.40–8.44, p = 0.01), PAS (OR 16.47; 95% CI 4.66–58.26, p < 0.01), and RPOC (OR 29.70; 95% CI 11.23–78.55, p < 0.01) was more in pregnant women with severe PPH. In the multivariate analysis for severe PPH, prior CS (OR 4.71; 95% CI 1.29–17.13, p = 0.02), major previa (OR 7.50; 95% CI 1.98–28.43, p < 0.01), and RPOC (OR 13.26; 95% CI 3.61–48.63, p < 0.01) were identified as risk factors. Conclusions: Prior CS and PAS were identified as risk factors for RPOC in placenta previa and RPOC is closely associated with severe PPH. Therefore, a new strategy for RPOC in placenta previa is needed. [ABSTRACT FROM AUTHOR]

Background: Mucinous carcinoma (MC) is a histological subtype of ovarian cancer that has a worse prognosis at advanced stages than the most prevalent histological subtype, high-grade serous carcinomas. Invasive patterns have been recognized as prognostic factors for MCs. MCs with infiltrative invasion were more aggressive than those with expansile invasion. MC with an expansile pattern exhibited behavior similar to mucinous borderline tumors (MBT). However, genomic analysis of invasive patterns is insufficient. This study aimed to compare genetic information between groups with MC and infiltrative invasion (Group A) and those with MC with expansile invasion or MBT (Group B). Methods: Ten cases each of MC with infiltrative invasion, MC with expansile invasion, and MBT between 2005 and 2020 were identified. Deoxyribonucleic acid (DNA) extraction from formalin-fixed paraffin-embedded tissues was performed, and cases with DNA fragmentation or the possibility of DNA fragmentation were excluded. Mutant base candidates and tumor mutation burden (TMB) values (mutations/megabase) were calculated. Results: After assessing the quality of purified DNA, seven cases of MC with infiltrative invasion, five cases of MC with expansile invasion, and three cases of MBT were included. More patients in group A experienced recurrence or progression (p < 0.01) and died of disease (p = 0.03). Moreover, the TMB value was statistically higher in group A than in group B (p = 0.049). There were no statistical differences in the incidence of the mutations of KRAS, TP53, and CREBBP. KRAS, TP53, and CREBBP mutations were discovered in 8/15 (53.3%), 6/15 (40.0%), and 5/15 (33.3%) cases, respectively. Conclusions: Genetic analysis revealed that Group A had higher TMB than Group B. Therefore, this result might be useful for future treatment. [ABSTRACT FROM AUTHOR]

Background: Bevacizumab (Bev) plays the central role of the adjuvant therapy for patients with ovarian carcinoma. The aim of our study was to examine whether differences in the administration of Bev influence the prognosis of patients.Methods: Patients with ovarian carcinoma who received treatment at two hospitals between 1999 and 2020 were identified. Patients treated with weekly low-dose administration of Bev (100 mg Bev on days 1 and 8 and 200 mg Bev on day 15, monthly) at one hospital (group A) and those with monthly high-dose administration of Bev (15 mg/kg of Bev on day 1, monthly) at another hospital (group B) were retrospectively compared.Results: Among the total patients, 44 were assigned to group A and 33 were assigned to group B. More patients in group A had advanced disease (p = 0.03) and a lower dose of Bev at the first time during the first cycle administration (p < 0.01) than in group B. Progression-free survival (PFS) was better in group A than in group B (p < 0.01). Multivariate analysis revealed that group A was a better prognostic factor for PFS (hazard ratio 0.53, p = 0.03). Stable duration was longer in group A than in group B (p < 0.01). The incidences of adverse effects, including hematological toxicities such as neutropenia (p = 0.01) and nonhematological toxicities such as hypertension (p < 0.01), intestinal obstruction (p < 0.01), and thromboembolic events (p < 0.01), were lower in group A than in group B.Conclusions: Weekly low-dose administration of Bev might improve prognosis and decrease the frequency of adverse effects associated with this drug although the prospective study was needed to get corroboration. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the association between clinicopathologic factors, mesothelin, and cancer antigen (CA) 125 in endometrial carcinoma. Methods: Between 1989 and 2017, patients with endometrial carcinoma who underwent total hysterectomy and bilateral salpingo-oophorectomy at our hospital were identified. The association between either or both immunochemical expression of mesothelin and CA125 and clinicopathological features were retrospectively examined. Results: Among 485 patients, 171 were positive for mesothelin, 368 were positive for CA125, and 167 were positive for mesothelin and CA125. The expression of mesothelin and CA125 was positively correlated (p < 0.01). More patients with mesothelin expression showed myometrial invasion of more than 50% (p = 0.028) and positive lymphovascular invasion (p = 0.027). Similarly, more patients with co-expression of mesothelin and CA125 had myometrial invasion of more than 50% (p = 0.016) and positive lymphovascular invasion (p = 0.02). Patients with mesothelin expression and co-expression of mesothelin and CA125 demonstrated worse progression-free survival (PFS) and overall survival (OS). In the multivariate analysis, mesothelin expression and co-expression were poor prognostic factors for PFS (mesothelin expression: hazard ratio [HR] = 2.14, p < 0.01; co-expression: HR = 2.19, p < 0.01) and OS (mesothelin expression: HR = 2.18, p < 0.01; co-expression: HR = 2.22, p < 0.01). Conclusions: Mesothelin expression and co-expression might be associated with tumor aggressiveness and poor prognosis in patients with endometrial carcinoma. Persons with mesothelin-expressing endometrial cancers present a particularly high medical unmet need. [ABSTRACT FROM AUTHOR]

Objective: The pretreatment neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) have been reported to be useful as markers for prognostic factors and metastasis in several cancers. The aim of this study was to identify the predictor of lymph node (LN) metastasis by pretreatment NLR and PLR in patients with endometrial cancer. Methods: Medical charts of the patients with endometrial cancers that received primary surgery at our hospital between 2007 and 2013 were retrospectively analyzed. The cutoff value was calculated from the receiver operating characteristics (ROC) curve. Clinicopathological parameters including inflammatory markers were evaluated for LN metastasis using multiple logistic regression analysis. Results: Among 197 patients enrolled in the study, LN metastasis was observed in 25 patients (13%). ROC curves demonstrated that the best cutoff value of NLR for predicting LN metastasis was 2.18 and that of PLR was 206. In univariate analysis, several pathological factors, NLR, and PLR were identified as predictors of LN metastasis. In multiple logistic regression analysis, lymphovascular invasion and NLR were found to be significantly correlated with LN metastasis (p = 0.002, 0.039). Conclusion: A higher pretreatment NLR was identified as a predictor of LN metastasis in endometrial cancers. Although further study is needed to confirm the results, NLR could be a candidate clinical marker for detection of LN metastasis. [ABSTRACT FROM AUTHOR]

Objective: The clinical significance of lymphocyte infiltration (LI) at the invasive front in endometrial carcinomas (EC) has not been determined. The aim of the current study was to evaluate the association between zone formation of LI at the invasive front of the tumor margin and prognoses of the patients with EC. Methods: All available pathological slides of the enrolled cases were reviewed, and the degree of LI at the invasive front was categorized into 2 groups: strong LI and weak LI. Clinical significance of LI was evaluated retrospectively. Results: A total of 333 cases with EC were enrolled in the study: 225 cases with weak LI and 108 cases with strong LI. Weak LI was more frequently observed in the patients with grade1/2 endometrioid EC. Multivariate analyses for progression-free survival (PFS) and overall survival (OS) revealed that weak LI was identified as an independent worse prognostic factor for OS (p = 0.004) in addition to PFS (p = 0.022). Conclusion: Weak LI at the invasive front of the tumor margin was associated with worse prognoses in EC. Although further studies are needed, it is suggested that LI could be a biomarker of prognoses in EC. [ABSTRACT FROM AUTHOR]

Purpose: To compare a cohort of patients with platinum-resistant recurrent ovarian cancer (PROC) treated with bevacizumab and gemcitabine (Bev-Gem) to that of patients treated only with gemcitabine (Gem).Methods: Between 2011 and 2017, we identified the Bev-Gem and Gem PROC groups. The regimen included 1000 mg/m2 of Gem on days 1, 8, and 15, and 15 mg/m2 of Bev on day 1, every 4 weeks. Progression-free survival (PFS) and overall survival (OS) were calculated from the date of the administration of Bev-Gem or Gem until disease progression or death.Results: The Bev-Gem and Gem groups included 18 and 29 patients, respectively. More patients had advanced stage disease in the Bev-Gem group (p = 0.048); no other characteristics differed between the groups. The response rates [ratio of complete remission (CR) to partial remission (PR)] of Bev-Gem and Gem were 38.9 and 3.4%, respectively (p < 0.01). The clinical benefit rates [combined percentages of CR, PR, and stable disease] of the Bev-Gem and Gem groups were 88.9 and 41.4%, respectively (p = 0.04). PFS and OS of the Bev-Gem group were superior (p < 0.01, p = 0.03, respectively). Bev-Gem was the better prognostic factor of both PFS [hazard ratio (HR) 0.17, p < 0.01] and OS (HR 0.31, p = 0.01). The frequency of hematologic and non-hematologic adverse effects was similar in each group.Conclusion: Bev-Gem regimens improved PFS and OS for PROC. Furthermore, the adverse effects of Bev-Gem were tolerable. Thus, Bev-Gem could be a candidate treatment strategy for PROC. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to prenatally predict placenta accreta in posterior placenta previa using magnetic resonance imaging (MRI).Methods: This retrospective study was approved by the Institutional Review Board of our hospital. We identified 81 patients with singleton pregnancy who had undergone cesarean section due to posterior placenta previa at our hospital between January 2012 and December 2016. We calculated the sensitivity and specificity of several well-known findings, and of cervical varicosities quantified using magnetic resonance imaging, in predicting placenta accreta in posterior placenta previa. To quantify cervical varicosities, we calculated the A/B ratio, where "A" was the minimum distance from the most dorsal cervical varicosity to the deciduous placenta, and "B" was the minimum distance from the most dorsal cervical varicosity to the amniotic placenta. The appropriate cut-off value of the A/B ratio was determined using a receiver operating characteristic (ROC) curve.Results: Three patients (3.7%) were diagnosed as having placenta accreta. The sensitivity and specificity of the well-known findings were 0 and 97.4%, respectively. Furthermore, the A/B ratio ranged from 0.02 to 0.79. ROC curve analysis revealed that the area under the combined placenta accreta and A/B ratio curve was 0.96. When the cutoff value of the A/B ratio was set 0.18, the sensitivity and specificity were 100 and 91%, respectively.Conclusion: It was difficult to diagnose placenta accreta in the posterior placenta previa using the well-known findings. The quantification of cervical varicosities could effectively predict placenta accreta. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effectiveness of routine rapid insertion of a Bakri balloon during cesarean section for placenta previa based on a retrospective control study.Methods: Women with singleton pregnancies who underwent cesarean section for placenta previa at our institution between 2003 and 2016 were enrolled. Between 2015 and 2016, women who routinely underwent balloon tamponade during cesarean section were defined as the balloon group. Between 2003 and 2014, women who underwent no hemostatic procedures except balloon tamponade were defined as the non-balloon group. The clinical outcomes of the two groups were retrospectively analyzed.Results: Of the 266 women with placenta previa, 50 were in the balloon group and 216 were in the non-balloon group. The bleeding amounts were significantly smaller in the balloon group than in the non-balloon group: intraoperative bleeding (991 vs. 1250 g, p < 0.01), postoperative bleeding (62 vs. 150 g, p < 0.01), and total bleeding (1066 vs. 1451 g, p < 0.01). Furthermore, the mean surgical duration was shorter in the balloon group than the non-balloon group (30 vs. 50 min, p < 0.01). In the balloon group, five patients suffered from increasing hemorrhage due to prolapse of the balloon from the uterus after the operation, but the hemorrhage was controlled by balloon re-insertion without additional hemostatic procedures.Conclusions: This study demonstrated that the routine rapid insertion of Bakri balloon tamponade during cesarean section significantly decreased intra- and postoperative hemorrhage and shortened the surgical duration in women with placenta previa. [ABSTRACT FROM AUTHOR]

Purpose: Recently, generic drugs of paclitaxel have been commonly used mainly by economic reasons; however, predictive factors for toxicities are not fully determined. Hypersensitivity reaction (HSR) is one of the most important adverse events in the paclitaxel-based therapy, and sometimes leads to lethal condition. The aim of the study was to identify predictors for HSR in patients treated with paclitaxel-based regimens.Methods: All the patients treated with chemotherapy including paclitaxel at our hospital between 1998 and 2013 were retrospectively evaluated. Clinicopathological factors of the patients that developed HSR and those without HSR were compared, and predictive factors for HSR were identified.Results: Among 414 patients enrolled in the study, 26 patients (6.3%) developed HSR. Multivariate analyses showed that younger age (odds ratio 6.31), a history of allergy (odds ratio 3.79), and short-course premedication (odds ratio 14.1) were identified as predictive factors for HSR. There was no significant difference in the incidence of HSR between original paclitaxel and generic drug. The incidence of HSR was higher as the number of these predictors was accumulated.Conclusions: Three factors were identified as predictive factors for HSR: younger age, a history of allergy, and short-course premedication. Accumulation of these factors increased the incidence of HSR; however, the use of generic drug was not associated HSR in gynecologic cancer patients. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to assess whether hysterectomy with wider resection could improve survival by preventing local recurrence. Methods: Medical charts of the patients with clinical stage I/II endometrial cancers treated at our hospital between 1990 and 2009 were retrospectively analyzed. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS) and adverse effects according to the type of hysterectomy. Results: A total of 247 patients were identified: 46 patients treated with total abdominal hysterectomy (TAH group) and 201 patients with modified radical hysterectomy (mRH group). No significant differences were observed in OS (p = 0.52) and PFS (p = 0.67) between the two groups. Also, there was no significant difference in the distribution of recurrent sites between the two groups. The patients treated with mRH had a longer operation time and more frequently developed severe adverse events, such as blood loss and lymphedema. Conclusion: In our cohorts, there were no significant differences in both PFS and OS according to surgical procedures, and the mRH group more frequently developed severe adverse events. Overall, clinical benefit was not obtained by mRH in patients with clinical stage I/II endometrial carcinomas. [ABSTRACT FROM AUTHOR]

Background: Endometrial cytology by direct intrauterine sampling is the most common test for an initial evaluation of the endometrium in Japan. However, its diagnostic value for endometrial cancer remains unknown. Here, we assess the correlation between cytopathology and histopathology to evaluate the diagnostic value of cytology for endometrial cancer. Methods: Patients with histologically confirmed endometrial cancer and controls with a normal endometrium confirmed by hysterectomy had all undergone preoperative endometrial cytology between 2001 and 2010 at our eight institutions and were retrospectively analyzed. The cytological results were compared by clinical stage, histological type, differentiation, and sampling instrument. Results: We analyzed 1,441 endometrial cancer and 1,361 control cases. Endometrial cytology detected cancer in 1,279 (916 positive and 363 suspicious) cases with a sensitivity (positive plus suspicious cases) of 88.8% and a specificity of 98.5%. The positive rate was high in advanced-stage, nonendometrioid, and undifferentiated cases, but there was no significant difference in sensitivity between these clinical conditions. Conclusion: Endometrial cytology shows a relatively high sensitivity and specificity for endometrial cancer, and neither statistical measure is significantly affected by clinical stage, histological type, differentiation, sample numbers, or sampling instrument. These findings form a superior dataset for evaluating the efficacy of endometrial cytology. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background We conducted a phase III, non-inferiority trial comparing upfront primary debulking surgery (PDS) and interval debulking surgery (IDS) following neoadjuvant chemotherapy (NAC) for stage III/IV ovarian, tubal, and peritoneal cancers (JCOG0602). Two earlier studies, EORTC55971 and CHORUS, demonstrated non-inferior survival of patients treated with NAC. However, they could not evaluate true treatment invasiveness because of adding diagnostic laparotomy or laparoscopy before treatment in over 30% of both arms of EORTC55971 and in 16% of NAC arm of CHORUS. Methods Patients were randomised into the standard arm (PDS followed by eight cycles of paclitaxel and carboplatin [TC]) and NAC arm (four cycles of TC, IDS, and four cycles of TC). In the standard arm, IDS was optional for patients who had undergone suboptimal or incomplete PDS. Treatment invasiveness was compared between arms (UMIN000000523). Results Between November 2006 and October 2011, 301 patients were randomised. In the standard arm, 147/149 underwent PDS and 49 underwent IDS. In the NAC arm, 130/152 underwent IDS. The NAC arm required fewer surgeries (mean 0.86 versus 1.32, p < 0.001) and shorter total operation time (median 273 min versus 341 min, p < 0.001) than the standard arm and required a lower frequency of abdominal organ resection (23.7% versus 37.6%, p = 0.012) or distant metastases resection (3.9% versus 10.7%, p = 0.027). In the NAC arm IDS, blood/ascites loss was smaller (median 787 ml versus 3235 ml, p < 0.001) and albumin transfusion and G3/4 adverse events after surgery in total were less frequent (26.2% versus 58.5%, p < 0.001; 4.6% versus 15.0%, p = 0.005, respectively). Conclusion Our findings demonstrated that NAC treatment is less invasive than standard treatment. NAC treatment may become the new standard treatment for advanced ovarian cancer when non-inferior survival is confirmed in the planned primary analysis in 2017. [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to investigate prognostic factors, including postoperative chemotherapy regimen, for the treatment of ovarian yolk sac tumour (YST), and resulting fertility outcome. Methods A multi-institutional retrospective investigation was undertaken to identify patients with ovarian pure or mixed YST who were treated between 1980 and 2007. Postoperative chemotherapy regimen and other variables were assessed in univariate and multivariate analyses. Additionally, the reproductive safety of the BEP (bleomycin, etoposide and cisplatin) regimen was evaluated. Results There were 211 patients enrolled from 43 institutions. The BEP regimen and a non-BEP regimen were administered to 112 and 99 patients as postoperative chemotherapy, respectively. In univariate and multivariate analyses, age ⩾ 22, alpha-fetoprotein ⩾ 33,000 ng/ml, residual tumours after surgery and non-BEP regimen were independently and significantly associated with poor overall survival (OS). BEP was significantly superior to non-BEP in 5-year OS (93.6% versus 74.6%, P = 0.0004). Reduced-dose BEP (<75% standard-dose bleomycin and < 50% etoposide dose) was significantly associated with poorer 5-year OS compared with standard-dose BEP (89.4% versus 100%, P = 0.02 and 62.5% versus 96.9%, P = 0.0002). All patients who underwent fertility-sparing surgery recovered their menstrual cycles. Sixteen of 23 patients receiving BEP (70.0%) and 13 of 17 patients receiving non-BEP (76.5%) who were nulliparous at fertility-sparing surgery and married at the time of investigation gave birth to 21 and 19 healthy children, respectively. Conclusions The results of the present study suggest that standard-dose BEP should be administered for ovarian YST. BEP is as safe as non-BEP for preserving reproductive function. [ABSTRACT FROM AUTHOR]