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Background: We previously demonstrated the applicability of the concept of "platinum sensitivity" in recurrent endometrial cancer. Although immune checkpoint inhibitors have been widely incorporated into endometrial cancer treatment, the debate continues regarding treatment options in patients with recurrent endometrial cancer who have previously received platinum-based chemotherapy. In this study, we assessed the duration of response to secondary platinum-based treatment using pooled data from the SGSG-012/GOTIC-004/Intergroup study. Methods: Among the 279 participants in the SGSG-012/GOTIC-004/Intergroup study wherein platinum-based chemotherapy was re-administered for managing recurrent endometrial cancer between January 2005 and December 2009, 130 (47%) responded to chemotherapy. We compared the relationship between platinum-free interval and duration of secondary platinum-based treatment using pooled data. Results: In 40 patients (31%), the duration of response to secondary platinum-based treatment exceeded the platinum-free interval. The duration of response to secondary platinum-based treatment exceeded 12 months in 51 patients (39%) [platinum-free interval: < 12 months, 14/48 (29%); 12–23 months, 18/43 (42%); 24–35 months, 8/19 (42%); ≥ 36 months, 11/20 (55%)]. In particular, in eight patients (6%), the duration of response to secondary platinum-based treatment exceeded 36 months [platinum-free interval: < 12 months, 3/48 (6%); 12–23 months, 0/19 (0%); 24–35 months, 2/19 (11%); ≥ 36 months, 3/20 (15%)]. Conclusions: Re-administration of platinum-based chemotherapy for recurrent endometrial cancer may result in a long-term response exceeding the platinum-free interval in some patients. Even in the current situation, where immune checkpoint inhibitors have been introduced, re-administration of platinum-based chemotherapy is worth considering. [ABSTRACT FROM AUTHOR]

The active form of vitamin D3, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], is a principal regulator of calcium homeostasis through activation of the vitamin D receptor (VDR). Previous studies have shown that 2α-(3-hydroxypropyl)-1,25D3 (O1C3) and 2α-(3-hydroxypropoxy)-1,25D3 (O2C3), vitamin D derivatives resistant to inactivation enzymes, can activate VDR, induce leukemic cell differentiation, and increase blood calcium levels in rats more effectively than 1,25(OH)2D3. In this study, to further investigate the usefulness of 2α-substituted vitamin D derivatives, we examined the effects of O2C3, O1C3, and their derivatives on VDR activity in cells and mouse tissues and on osteoblast differentiation of dedifferentiated fat (DFAT) cells, a cell type with potential therapeutic application in regenerative medicine. In cell culture experiments using kidney-derived HEK293 cells, intestinal mucosa-derived CaCO2 cells, and osteoblast-derived MG63 cells, and in mouse experiments, O2C2, O2C3, O1C3, and O1C4 had a weaker effect than or equivalent effect to 1,25(OH)2D3 in VDR transactivation and induction of the VDR target gene CYP24A1, but they enhanced osteoblast differentiation in DFAT cells equally to or more effectively than 1,25(OH)2D3. In long-term treatment with the compound without the medium change (7 days), the derivatives enhanced osteoblast differentiation more effectively than 1,25(OH)2D3. O2C3 and O1C3 were more stable than 1,25(OH)2D3 in DFAT cell culture. These results indicate that 2α-substituted vitamin D derivatives, such as inactivation-resistant O2C3 and O1C3, are more effective than 1,25(OH)2D3 in osteoblast differentiation of DFAT cells, suggesting potential roles in regenerative medicine with DFAT cells and other multipotent cells. [ABSTRACT FROM AUTHOR]

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: We evaluated the feasibility of neoadjuvant chemotherapy, followed by debulking surgery, for clinically diagnosed FIGO stage IVb endometrial cancer (protocol number: JGOG2046). Methods: The experimental treatment consisted of 3 cycles of paclitaxel (180 mg/m2) plus carboplatin (AUC5) followed by debulking surgery, including total abdominal hysterectomy, bilateral salpingo-oophorectomy, and 3 cycles of adjuvant chemotherapy. Patients were considered as eligible if they were pathologically diagnosed as primary endometrial cancer, and had both endometrial tumor and distant metastasis confirmed by imaging examinations. The primary endpoint was the incidence of patients who completed debulking surgery after the neoadjuvant chemotherapy. Results: While 51 patients were enrolled from 23 hospitals, the final study cohort consisted of 49 patients with a mean age of 59.0 years. Although the response ratio of the neoadjuvant chemotherapy was 65.3% (95% CI 50.4–78.3%), 67.3% (95% confidence interval (CI) 52.5–80.1%) underwent debulking surgery after the neoadjuvant chemotherapy and 59.2% (95% CI 45.2–71.8%) completed the protocol treatment including 3 courses of adjuvant chemotherapy. The median disease-free survival time was 9.1 months (95% CI 6.5–11.9), while the median overall survival time was 23.2 months (95% CI 11.9–27.8). A patient with sigmoid colon cancer and another with cervical cancer were included in this study. Conclusions: Neoadjuvant chemotherapy followed by debulking surgery was a feasible and acceptable treatment for metastatic endometrial cancer. (225 words). [ABSTRACT FROM AUTHOR]

Purpose: To investigate the clinical significance of programmed cell death ligand 1 (PD-L1) expression in ovarian clear cell carcinoma (CCC). Materials and methods: Patients with CCC who underwent primary surgery at our hospital between 1984 and 2014 were enrolled in this study. PD-L1 and mismatch repair (MMR) protein expression in tumor cells, tumor-infiltrating lymphocytes (TILs), including cluster of differentiation (CD) 8, CD4, forkhead box P3 (FOXP3), programmed cell death 1 (PD-1), and BAF250a, were evaluated using immunohistochemistry. The association between PD-L1 expression, clinicopathological features, prognosis, and expression of several proteins was investigated. Results: Of the 125 patients with CCC, 17 had negative PD-L1 and 108 had positive PD-L1. Patients with positive PD-L1 expression showed a lower response to chemotherapy (p = 0.01). In addition, patients with positive PD-L1 showed worse progression-free survival (PFS, p = 0.01) and overall survival (OS, p = 0.01) than that in patients with negative PD-L1 expression. Multivariate analyses for PFS and OS showed that PD-L1 expression was an independent prognostic factor for PFS (hazard ratio [HR] 7.81, p < 0.01) and OS (HR 12.90, p < 0.01). PD-L1 expression was not associated with the expression of several TILs or proteins. Conclusion: The expression of PD-L1 was related to a lower response to chemotherapy and worse prognosis in CCC. These results may be useful for the development of new treatments. [ABSTRACT FROM AUTHOR]

Background and Aim: Portopulmonary hypertension (PoPH) is a complication associated with portal hypertension. Since the epidemiological study in Japan was limited, this study aimed to investigate the characteristics, treatment patterns, and prognosis of PoPH patients in real‐world data. Methods: The characteristics and treatment patterns of PoPH (n = 386) and portal hypertension without pulmonary arterial hypertension (portal hypertension w/o PAH) (n = 96 463) were analyzed based on the Medical Data Vision (MDV) dataset from April 2008 to September 2020. Survival‐time analyses of emergency hospitalization and mortality were also conducted between matched pair cohorts of PoPH (n = 210) and portal hypertension w/o PAH (n = 840). Results: Among 386 PoPH patients, the Child–Pugh classification of PoPH group comprised patients with Class A (59 [15.3%]), B (109 [28.2%]), and C (42 [10.9%]), and missing (176 [45.6%]). Regarding the feature of PoPH group, the proportion of primary biliary cholangitis (PBC) (13.7%) and splenomegaly (9.8%) was higher compared with portal hypertension w/o PAH group. The survival time of all‐cause hospitalization in PoPH group was shorter than portal hypertension w/o PAH group in matched pair cohort (P < 0.001 by log‐rank test). Of PoPH patients, the frequency of PAH‐specific medicine usage within 90 days was monotherapy of 79 patients (20.5%), combination therapy of 64 patients (16.6%), and PAH‐specific medicine usage of 243 patients (63.0%). Conclusion: This was the first study demonstrating that high proportion of PBC and splenomegaly and a greater risk of hospitalization were observed in PoPH patients based on the analysis using administrative claim database. [ABSTRACT FROM AUTHOR]

Superficial angiomyxoma (SA) is a benign tumor characterized by extensive myxoid stroma, numerous small blood vessels, sparse spindle-shaped fibroblastic cells, and inflammatory cell infiltrate. Oral cavity SA is extremely rare and typically presents as a painless, slow growth. We experienced SA in the mandibular gingiva that is rapidly growing. The patient was a 15-year-old female whose chief complaint was a painless mass in the lingual gingiva of the mandible that increased in size over 1 month. An excisional biopsy was performed under local anesthesia. According to histopathological examination, the mass was diagnosed as SA. The patient experienced recurrence twice because of positive margins. The second recurrent lesion, including periosteum, was resected, and no recurrence has been observed for 1 year. The cause of rapid growth was attributed to edematous changes due to tongue habit or traumatic stimuli. As this case exhibited repeated local recurrence, careful follow-up is required. [ABSTRACT FROM AUTHOR]

Active vitamin D form 1α,25-dihydroxtvitamin D3 (1,25(OH)2D3) plays pivotal roles in calcium homeostasis and osteogenesis via its transcription regulation effect via binding to vitamin D receptor (VDR). Mutated VDR often causes hereditary vitamin D-dependent rickets (VDDR) type II, and patients with VDDR-II are hardly responsive to physiological doses of 1,25(OH)D3. Current therapeutic approaches, including high doses of oral calcium and supraphysiologic doses of 1,25(OH)2D3, have limited success and fail to improve the quality of life of affected patients. Thus, various vitamin D analogues have been developed as therapeutic options. In our previous study, we generated genetically modified rats with mutated Vdr(R270L), an ortholog of human VDR(R274L) isolated from the patients with VDDR-II. The significant reduced affinity toward 1,25(OH)2D3 of rat Vdr(R270L) enabled us to evaluate biological activities of exogenous VDR ligand without 1α-hydroxy group such as 25(OH)D3. In this study, 2α-[2-(tetrazol-2-yl)ethyl]-1α,25(OH)2D3 (AH-1) exerted much higher affinity for Vdr(R270L) in in vitro ligand binding assay than both 25(OH)D3 and 1,25(OH)2D3. A robust osteogenic activity of AH-1 was observed in Vdr(R270L) rats. Only a 40-fold lower dose of AH-1 than that of 25(OH)D3 was effective in ameliorating rickets symptoms in Vdr(R270L) rats. Therefore, AH-1 may be promising for the therapy of VDDR-II with VDR(R274L). [ABSTRACT FROM AUTHOR]

Background: The clinical significance of CD8‐positive (CD8+) lymphocytes on tumor cell clusters of ascites cell blocks in patients with ovarian high‐grade serous carcinoma (HGSC) was investigated. Methods: Among HGSC patients who underwent surgery from January 2014 to December 2019, 38 patients with ascites cell block were selected. Using these cell blocks and primary ovarian tumor tissue, the presence of CD8+ lymphocytes and the expression of PD‐L1 were examined immunohistochemically. Tumor cell clusters were defined as cell clumps consisting of more than 10 malignant cells in cell block. Cases with at least one CD8+ lymphocyte in tumor cell cluster were defined as positive CD8+ lymphocytes (Group A); others were defined as negative CD8+ lymphocytes (Group B). The tumor tissue CD8+ lymphocytes were counted mechanically. Clinicopathological features were retrospectively compared between the two groups. Results: In total, 38 cases were identified: 25 (65.8%) in Group A and 13 (34.2%) in Group B. More cases in Group A were positive for CD4 (p < 0.01), PD‐L1 (p = 0.02), FoxP3 (p = 0.02) and had a higher number of CD8+ lymphocytes in the tissue (p = 0.03). Patients in Group A had better progression‐free survival (p < 0.01) and overall survival (p = 0.04). In multivariate analysis, Group A was an independent prognostic factor for both progression‐free survival (hazard ratio, 0.24; p < 0.01) and overall survival (hazard ratio, 0.21; p = 0.03). Conclusion: The presence of CD8+ lymphocytes in tumor cell clusters of ascites was associated with the status of immune reaction in the tissue and prognosis in patients with HGSC and might be useful information of the immune‐associated therapy. [ABSTRACT FROM AUTHOR]

Background: Tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) may be useful prognostic indicators in endometrial cancer. However, standardized assessment methods and the prognostic roles of these cells in different stage groups are unclear.Methods: Formalin-fixed paraffin-embedded tissue samples of 107 endometrioid-type endometrial carcinomas (EECs) comprising 60 stage IB and 47 stage IIIC or IVB cases were evaluated. CD3+ TILs, CD8+ TILs, CD68+ TAMs, and CD163+ TAMs were detected by immunohistochemistry, and their densities were evaluated by semiquantitative and quantitative methods. TILs within tumor epithelial cell nests (E-TILs) and those within the stroma at the invasive front (S-TILs) were evaluated separately for CD3+ and CD8+ cells. The "TIL score" was defined as the sum of semiquantitative scores of CD3+ E-TILs, CD3+ S-TILs, CD8+ E-TILs, and CD8+ S-TILs. For TAMs, the area of CD68+ and CD163+ cells in the invasive margin were semiquantitatively and quantitatively evaluated. Clinicopathological and prognostic implications of TILs and TAMs in stage IB and IIIC/IVB EECs were examined by Cox univariate and multivariate analyses.Results: By Cox univariate analyses, semiquantitatively low CD3+ E-TILs, low CD8+ E-TILs, and low "TIL score" were significantly correlated with worse prognosis in stage IB patients (P = 0.011, 0.040, and 0.039, respectively). Likewise, low CD3+ E-TILs and low CD8+ E-TILs, by both semiquantitative (P = 0.011 and 0.0051) and quantitative evaluations (P < 0.0001, and P = 0.0015) and low "TIL score" (P = 0.020) were significantly correlated with worse prognosis in stage IIIC/IVB patients. By Cox multivariate analyses, semiquantitatively low CD3+ E-TILs and low CD8+ E-TILs, low "TIL score", and quantitatively low CD3+ E-TILs and low CD8+ E-TILs were independent worse prognostic factors in stage IIIC/IVB (P = 0.0011, 0.0053, 0.012, < 0.0001, and < 0.0001, respectively). CD68+ or CD163+ TAMs were not correlated with prognosis in any patients.Conclusions: Both semiquantitatively and quantitatively low E-TILs, are correlated with worse prognosis in both early and advanced stage patients with EECs. In particular, CD3+ E-TILs and CD8+ E-TILs are potentially useful prognostic markers in patients with EEC regardless of the stage. [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: The aim of this study was to evaluate the clinicopathological factors and prognosis of mucinous carcinoma (MC) with infiltrative invasion, MC with expansile invasion, and high-grade serous carcinoma (HGSC). Methods: Cases of MC and HGSC between 1984 and 2019 were identified. The clinicopathological factors and prognosis of MC with infiltrative invasion or expansile invasion and HGSC were retrospectively compared. Although our present study included cases in our previous studies, we extended observational period when analysis was performed. Accordingly, our study added increased cases and survival analysis was newly conducted. Results: After pathological review, 27 cases of MC with infiltrative invasion, 25 cases of MC with expansile invasion, and 219 cases of HGSC were included. MC had a better prognosis in terms of progression-free survival (PFS, p < 0.01) and overall survival (OS, p < 0.01) than HGSC for all International Federation of Gynecology and Obstetrics (FIGO) stages; however, multivariate analysis did not show statistical differences in PFS and OS. There were no statistically significant differences in PFS and OS for all FIGO stages between MC with infiltrative invasion and HGSC. However, in cases with FIGO stages II to IV, MC with infiltrative invasion had worse PFS (p < 0.01) and OS (p < 0.01) than HGSC. In univariate analysis, MC with infiltrative invasion was a worse prognostic factor for PFS (hazard ratio [HR] 2.83, p < 0.01) and OS (HR 3.83, p < 0.01) than HGSC. Compared with HGSC, MC with expansile invasion had better PFS (p < 0.01) and OS (p < 0.01). Multivariate analysis demonstrated that MC with expansile invasion was a better prognostic factor for PFS (HR 0.17, p < 0.01) and OS (HR 0.18, p = 0.03) than HGSC. Conclusions: Compared to the prognosis of HGSC, that of MC was different according to the invasive pattern and FIGO stage. Therefore, future study may be needed to consider this association. [ABSTRACT FROM AUTHOR]

Background: In ovarian mucinous carcinoma, invasive pattern is the important factor but there were less reposts to investigate it. The aim of this study was to examine the association between prognosis and invasive patterns of ovarian mucinous carcinoma and to investigate the biomarkers of the diagnosis and prognosis immunochemically. Patients with ovarian mucinous carcinoma at our institution between 1984 and 2018 were identified. A pathological review was conducted using the 2020 World Health Organization criteria. The prognosis of infiltrative invasion and expansile invasion of ovarian mucinous carcinoma were retrospectively compared. In addition, immunohistochemical staining was conducted for all cases, and the immunohistochemical differences between the two invasive patterns were compared. Results: After the pathological review, 25 cases with infiltrative invasion and 24 cases with expansile invasion were included. Ovarian mucinous carcinoma with infiltrative invasion showed significantly worse progression-free survival (PFS, p < 0.01) and overall survival (OS, p < 0.01) than those with expansile invasion. Multivariate analysis demonstrated that the pattern of infiltrative invasion was a worse prognostic factor for PFS (hazard ratio 9.01, p < 0.01) and OS (hazard ratio 17.56, p < 0.01). Immunohistochemically, cytokeratin (CK) 5/6 (p = 0.01), cluster of differentiation (CD) 24 (p = 0.02), and epithelial growth factor receptor (EGFR) (p < 0.01) were statistically related to infiltrative invasion. The PFS (p = 0.04) and OS (p = 0.02) of cases with EGFR-positive OMC were worse than those with negative OMC. Conclusions: Infiltrative invasion was observed to be a prognostic factor showing worse outcomes for ovarian mucinous carcinoma compared to expansile infiltration. CK5/6, CD24, and EGFR might be biomarkers of the diagnosis. [ABSTRACT FROM AUTHOR]

We aimed to investigate the resuscitative efficacy of hemoglobin vesicles (HbVs) as a red blood cell (RBC) substitute for the initial treatment of severe postpartum hemorrhage (PPH). Twenty-five pregnant rabbits underwent cesarean section; uncontrolled hemorrhage was induced by transecting the right uterine artery to establish a severe PPH model. During the first 30 min, all rabbits were administered 6% hydroxyethyl starch (HES) of an equivalent volume to the hemorrhage every 5 min. Thereafter, they received any of the following three isovolemic fluids for resuscitation every 5 min: RBCs with platelet-poor plasma (RBC/PPP) (n = 8), 6% HES (n = 7), or HbVs with 25% human serum albumin (n = 10). After surgical hemostasis at 60 min, survival was monitored until 12 h. No rabbits receiving only HES infusion survived beyond 6 h, whereas all rabbits receiving RBC/PPP transfusion survived. The rabbits receiving HbV infusion showed significantly higher mean arterial pressure and hemoglobin levels than the HES-receiving rabbits, and 8 of 10 rabbits survived for 6 h. The HbV group showed significantly higher survival than the HES group but worse survival than the RBC/PPP group. In conclusion, HbV infusion for severe PPH effectively prevents lethal hemorrhagic shock in a pregnant rabbit model. [ABSTRACT FROM AUTHOR]

Endometrial carcinoma is one of the most common gynecological cancers. MicroRNA-21 (miR-21) is the most consistently overexpressed miRNA in almost all human cancer types, and it might be a useful clinical biomarker and therapeutic target. However, its precise localization and significance in endometrial carcinoma have not been clarified. This study aimed to examine miR-21 expression in endometrial carcinoma and reveal its clinicopathological importance. We investigated miR-21 expression by in situ hybridization (ISH) using locked nucleic acid (LNA)-modified probes in 230 endometrial carcinoma patients. We evaluated miR-21 expression in cancer cells and stroma separately. High miR-21 expression in cancer cells was significantly associated with higher histological grade and lymph node metastasis. In Kaplan–Meier analysis, high miR-21 expression in cancer cells was significantly associated with poor progression-free survival. In particular, in endometrioid carcinoma, high miR-21 expression in cancer cells was an independent prognostic factor associated with poor progression-free survival, as well as older age and higher International Federation of Gynecology and Obstetrics (FIGO) stage. [ABSTRACT FROM AUTHOR]

Introduction: Placenta previa with placenta accreta spectrum (PAS) is a life-threatening disease that results in massive hemorrhage. The clinical and histologic criteria of PAS were adopted according to the International Federation of Gynaecology and Obstetrics (FIGO) classification. We aimed to investigate whether FIGO criteria and topography were associated with maternal complications in patients with placenta previa.Material and Methods: Patients with placenta previa who underwent cesarean section at our institution between January 2003 and December 2019 were identified. First, they were divided based on FIGO classification, as follows: Group A, with clinical criteria; Group B, with histologic criteria; and Group C: without clinical or histologic criteria. Next, cases with PAS were classified according to the topographic invasion area, as follows: type 1, upper posterior bladder; type 2, lower posterior bladder; type 3, parametrium; type 4, posterior lower uterine segment. Predictive factors for massive hemorrhage were retrospectively analyzed.Results: Among the 350 patients, 24 (6.9%) were classified as Group A, 16 (4.6%) as Group B and 310 (88.5%) as Group C. Regarding maternal history and hemostatic procedures, there were no significant factors other than hysterectomy (p < .01) in Groups A and B. The volume of blood loss in both Groups A and B was greater than in Group C (p < .01). The rates of uterine artery embolization and blood transfusion were higher in Groups A and B than in Group C (p < .01). In addition, there were no significant factors other than hysterectomy between Groups A and B. In the multivariate analysis for massive hemorrhage, Group A (odds ratio: 2.73, p = .04) and Group B (odds ratio: 12.69, p < .01) were identified as independent predictive factors. In addition, massive hemorrhage was closely related to the lower posterior bladder and parametrial invasion in both Groups A and B.Conclusions: Both clinical and histologic criteria for PAS in the FIGO classification were associated with massive hemorrhage. Diagnosing clinical PAS using the FIGO classification, additional hemostatic procedures might be necessary according to the topographic invasion area. [ABSTRACT FROM AUTHOR]

The standard treatment for maxillary sinus cancer is surgery; however, surgery for advanced cases often leads to significant aesthetic and functional disability. Combination treatment (induction chemotherapy) with paclitaxel, carboplatin and cetuximab (PCE) can be effective in head and neck cancer. The present study describes the case of a patient with advanced maxillary sinus cancer that was successfully treated using the PCE regimen. A 69-year-old man presented to the Department of Dentistry and Oral Surgery, Hokuto Hospital (Obihiro, Japan) with left buccal swelling and an irregular mass on the left maxillary gingiva. The lesion filled the ethmoid and maxillary sinus, and destroyed the pterygoid process. Numerous lymph node metastases were suspected in the bilateral cervical region. The patient was diagnosed with left maxillary sinus cancer T4aN2cM0 and treated with PCE. The size of the tumor was markedly reduced after the initial treatment. After six cycles of PCE, bioradiotherapy (BRT; 66 Gy/33 Fr) was performed for the remaining lesion, and a complete response was achieved. Ten months after BRT, the tumor recurred in the anterior wall of the left maxillary sinus, which was treated by partial maxillary resection and split-thickness skin grafting. No local or cervical recurrence was observed 2 years after the surgery. These findings suggested that PCE could be considered as the first step for the treatment of highly advanced malignant tumors in the head and neck. [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]

Aim: To investigate the differences in epithelial‐mesenchymal transition (EMT)‐ and matrix metalloproteinases (MMP)‐related factors among placenta previa with and without placenta accreta spectrum (PAS) (n = 69), and normal placenta (n = 51). Methods: The women diagnosed with placenta previa with or without PAS, and normal placentas, who delivered at our institution between 2006 and 2016, were enrolled. The difference of EMT‐related factors' expression by immunochemical analysis in chorionic villi and decidual cells between the normal placenta and placenta previa with or without PAS were evaluated. Results: In chorionic villi of placenta previa with and without PAS, E‐cadherin expression decreased, while that of ZEB1, SNAIL2 and MMP‐9 increased than that in normal placenta. In decidual cells of placenta previa with and without PAS, expression of vimentin, ZEB1 and MMP‐9 increased than that in normal placenta. In placenta previa with and without PAS, there was strong co‐expression of ZEB1 and vimentin in chorionic villi, of ZEB1 and MMP‐2 or MMP‐9 in decidual cells, and of SNAIL2 and vimentin or MMP‐9 in both chorionic villi and decidual cell. Vimentin expression in both chorionic villi and decidual cells was higher in placenta previa with PAS (n = 18) than in placenta previa without PAS (n = 51). MMP‐2 expression in decidual cells was higher in placenta previa with PAS than in placenta previa without PAS. Conclusion: This study revealed that EMT‐ and MMP‐associated factors may be related to placenta previa with and without PAS. Furthermore, placenta previa without PAS may acquire invasive nature. [ABSTRACT FROM AUTHOR]

Introduction: Massive hemorrhage due to placenta previa with placenta accreta spectrum is associated with high maternal mortality and morbidity. Therefore, accurate prediction of placenta previa with placenta accreta spectrum is essential; magnetic resonance imaging (MRI) is a useful tool for this purpose. This study investigated novel predictors of anterior and posterior placenta previa with placenta accreta spectrum using MRI. Material and methods: This was a retrospective study at a tertiary obstetrics hospital in Japan. The singleton patients with placenta previa who were scanned with MRI prenatally and had a cesarean section at our institution between 2007 and 2018 were included. The prediction of anterior and posterior placenta previa with placenta accreta spectrum was evaluated using four MRI findings: heterogeneous signals in the placenta, dark T2‐weighted intraplacental bands, myometrial thinning or interruption, and focal uterine bulging. The prediction of posterior placenta previa with placenta accreta spectrum was performed using the quantification of cervical varicosities, which were defined as the ratio of the distance between the minimum distance from the most dorsal cervical varicosities (a) to the deciduous and amniotic placenta (b) on a sagittal image. Results: Among 202 patients, 14 (6.9%) patients were pathologically diagnosed as having placenta accreta spectrum. Further, 38 (18.8%) patients had anterior placenta previa and 164 (81.2%) patients had posterior placenta previa. When anterior placenta previa with placenta accreta spectrum was predicted using at least one of the four MRI findings, the sensitivity and specificity of the anterior placenta previa with placenta accreta spectrum were 87.5% and 86.7%, respectively. In contrast, the sensitivity and specificity of posterior placenta previa with placenta accreta spectrum were 42.9% and 96.2%, respectively. But when the A/B ratio was set at 0.20, the sensitivity and specificity of the prediction for posterior placenta previa with placenta accreta spectrum using cervical varicosities were 100.0% and 89.2%, respectively. Conclusions: The findings of MRI to predict the anterior placenta previa with placenta accreta spectrum were different from posterior placenta previa. The cervical varicosities may be useful in predicting posterior placenta previa with placenta accreta spectrum. [ABSTRACT FROM AUTHOR]

The expression of L-type amino acid transporter 1 (LAT1) has been described to play essential roles in cancer cell growth and survival. To determine the significance of LAT1 in the prognosis of endometrial endometrioid carcinoma, we investigated LAT1 expression in 353 endometrioid carcinoma patients by immunohistochemical analysis using tissue microarray. The tumors in which stained tumor cells made up more than 25% of the tumor were graded as high expression. High expression of LAT1 was detected in 29 (8.2%) of patients. The ratio of high LAT1 expression did not significantly differ by age (< 60 vs. ≥ 60), FIGO stage (stage I/II vs. III/IV), histological grade (grade 1 vs. grade 2/3), or lymph node metastasis (positive vs. negative). However, high LAT1 expression in endometrioid carcinoma was associated with a poorer progression-free survival and overall survival, as per the results of the log-rank test (P = 0.0263 and 0.0404, respectively). Cox univariate and multivariate analyses revealed that high LAT1 expression is an independent marker of poor progression-free survival (hazard ratio = 2.598, P = 0.0137), in addition to a higher age (≥ 60 years vs. < 60 years), FIGO stage (stage III/IV vs. I/II), and histological grade (grade 2/3 vs. grade 1). In conclusion, we demonstrate that LAT1 is associated with a poor prognosis of endometrioid carcinoma of the uterine corpus. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate the association between changes in the levels of vascular endothelial growth factors (VEGFs) after treatment with bevacizumab and gemcitabine (Bev-Gem) and the clinical outcome.Methods: Platinum-resistant ovarian cancer patients treated with Bev-Gem therapy at our hospital between 2014 and 2018 were identified. Serum VEGF levels at the first and second treatment cycle were measured by ELISA. All patients were categorized into two groups-patients with > 50% decrease in serum VEGF-A levels (Group A) and patients with < 50% decrease serum VEGF-A levels (Group B). The association between clinical outcome and serum VEGF levels was investigated between the two groups.Results: Among 18 patients, 10 were in Group A and 8 in Group B. Group A exhibited a lower response rate (0% vs.75% p < 0.01) and clinical benefit rate (60% vs.100% p = 0.02) than Group B. The median serum VEGF-A level of Group A before the first cycle of Bev-Gem therapy was higher than that in Group B (61.2 vs. 3.7 pg/mL, p < 0.01). Group A exhibited worse PFS (7 vs., 10 months, p < 0.01) and OS (17 vs. 26 months, p = 0.04) than Group B. There were more patients with > 10% increase in serum VEGF-B levels in Group A than in Group B (p < 0.01).Conclusion: The rapid decrease in VEGF-A levels and the resultant increase in serum VEGF-B levels might be associated with an unfavorable clinical outcome. Large-scale studies are needed to further examine these results. [ABSTRACT FROM AUTHOR]

The article discusses the process of implant-supported restoration for restoring lost tissue with artificial appliances. The procedure involves placing an alloplastic material, similar in shape to a root of a tooth into the alveolar bone and bone resorption that takes place after tooth loss. Corrent implant placement and correct implant position and angulation are required in making appropriate occlusal relationships amid the resorption of the buccal plate and the lingual displacement of the edentulous mandibular alveolar ridge. Patients who have undergone the restoration are advised to receive oral hygiene instructions and proper professional plaque control.

Purpose: To compare the efficacy, safety, and tolerability profiles of pegylated liposomal doxorubicin and carboplatin (PLDC) with those of gemcitabine and carboplatin (GC) for the treatment of patients with platinum-sensitive recurrent ovarian cancer. Methods: Ovarian cancer patients with recurrence > 6 months after first-line platinum and taxane-based therapies were randomly assigned to PLDC [pegylated liposomal doxorubicin 30 mg/m2 plus carboplatin area under the curve (AUC) 5 mg/mL/min on day 1] every 4 weeks or GC (gemcitabine 1000 mg/m2 on days 1 and 8 plus carboplatin AUC 4 mg/mL/min on day 1) every 3 weeks for at least 6 cycles. The primary endpoint was progression-free survival, and overall response rate, overall survival, toxicity, and dose administration were secondary endpoints. Results: One-hundred patients (49 PLDC; 51 GC) were randomly assigned. Over a median follow-up of 24 months, the median progression-free survival was 12.0 months (95% CI 9.2–15.0) for PLDC and 9.8 months (8.9–12.3) for GC [HR 0.69 (0.455–1.047)] with a difference of 2.2 months. The response rate was 57.1% (41.0–72.3) for PLDC and 56.4% (39.6–72.2) for GC. No obvious differences in toxicity (G3/4) were noted between arms. The median relative dose intensity of planned dose per week was 88.9% for pegylated liposomal doxorubicin and 53.1% for gemcitabine (p < 0.0001). Conclusions: PLDC and GC are both good treatment candidates for platinum-sensitive recurrent ovarian cancer patients; however, the dose intensity was lower for GC than for PLDC. PLDC had a more favorable risk–benefit profile than that of GC for patients. [ABSTRACT FROM AUTHOR]

Background: This study aimed to examine the clinical significance and risk factors of thromboembolic events (TEEs) in patients with ovarian carcinoma. Methods: Patients with ovarian carcinoma treated at our hospital between 2000 and 2017 were identified. The risk factors of TEEs, including venous TEEs and arterial TEEs, and the association between TEEs and prognosis were investigated. Patients with TEEs were classified into two groups: those with severe TEEs, defined as patients who required urgent treatment for deep vein thrombosis, massive pulmonary embolism, acute myocardial infarction, and symptomatic cerebral infarction, and those with mild TEEs. The risk factors of severe TEEs and the association between severe TEEs and prognosis were investigated. Results: A total of 369 patients were enrolled. Among them, 53 patients (14.4%) were complicated with TEEs. Clear cell carcinoma (CCC) was a greater risk factor of TEEs than serous carcinoma (hazard ratio [HR] = 2.81, p = 0.03). In multivariate analysis for survival, TEEs were a prognostic factor of poor progression-free survival (PFS; HR = 2.90, p < 0.01) and overall survival (OS; HR = 2.89, p < 0.01). Among 53 patients with TEEs, 17 (32.1%) developed severe TEEs. CCC was strongly associated with severe TEEs (HR = 42.6, p = 0.02). Multivariate analysis for survival demonstrated that severe TEEs were a risk factor of worse PFS (HR = 4.34, p < 0.01) and OS (HR = 3.30, p = 0.03). Conclusion: TEEs induced poor prognosis and was associated with CCC. A standard treatment for CCC should be included in the strategy of TEEs. [ABSTRACT FROM AUTHOR]

L-type amino acid transporter 1 (LAT1) is a Na+-independent neutral amino acid transporter that plays a key role in cancer cell growth and survival. To determine the significance of LAT1 in prognosis and resistance to chemotherapy in ovarian carcinoma, we investigated the LAT1 expression in 245 ovarian carcinoma patients by immunohistochemistry using tissue microarray. High expression of LAT1 was detected in 85 (34.7%) patients. The ratio of high expression of LAT1 was significantly high in clear cell carcinoma and low in serous carcinoma compared to other histological types (P < 0.0001). High expression of LAT1 in ovarian carcinoma was associated with poorer prognosis as per log-rank test (P = 0.008). Cox's univariate and multivariate analysis revealed that high expression of LAT1 is an independent marker indicating poor prognosis (hazard ratio = 2.810, P < 0.0001) as well as the FIGO stage III/IV (vs. I/II) and suboptimal surgery. High LAT1 expression was also found to be associated with resistance to chemotherapy (P = 0.016) notably in clear cell carcinoma. In conclusion, we demonstrate that LAT1 is not only associated with poor prognosis of ovarian carcinoma, but also associated with chemoresistance in ovarian carcinoma. [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]

A 44-year-old man with cirrhosis arising from alcohol abuse manifested melena caused by the rupture of esophageal varices. He received endoscopic variceal ligation for the initial hemostasis, followed by endoscopic injection sclerotherapy as an additional consolidation therapy. A CT examination performed at the time of admission revealed collateral veins developing around the ascending colon, in which the feeding and draining vessels were identified as the superior mesenteric vein and the right testicular vein, respectively. Moreover, large nodular varices were observed in the ascending colon during a colonoscopy. To prevent the rupture of the colonic varices, balloon-occluded retrograde transvenous obliteration (B-RTO) was performed through the right testicular vein using a microballoon catheter. A CT examination performed 4 days after the B-RTO procedure revealed the disappearance of blood flow with thrombosis formation in both the colonic varices and the feeding vein. The varices in the ascending colon had completely disappeared when examined during a colonoscopy performed 4 months after the B-RTO procedure. B-RTO is a useful and minimally invasive procedure for the treatment of colonic varices to prevent bleeding. [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]

The activation of JAK2/STAT3 pathway has been reported to have critical roles in several solid tumors. The present study aimed to evaluate the correlation between JAK2/STAT3 activation and clinicopathological parameters in ovarian cancer types. Tissue microarrays made from the patients treated at the National Defense Medical College Hospital between 1984 and 2008 were evaluated using immunohistochemical (IHC) stainings. Medical charts of these patients including IHC results were retrospectively analyzed, and prognostic factors for progression-free survival and overall survival were evaluated. Among 341 enrolled patients, positive expression of p-STAT3 was observed in 95 cases (28%). Positive p-STAT3 was an independent worse prognostic factor for overall survival in all the cases. Additionally, p-STAT3 expression was related with overall survival in patients with clear-cell histology, but not in serous histology. The effect of an inhibitor of STAT3, niclosamide, was evaluated in ovarian clear-cell cancer cells, and niclosamide treatment decreased expression of p-STAT3, leading to increased apoptosis in a dose-dependent manner in vitro. The activation of JAK2/STAT3 pathway had significant impact on survival of ovarian cancers, especially for the cases with clear-cell histology. Although further analyses are needed, suppression of this pathway could be a candidate for the treatment of ovarian cancers. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to retrospectively evaluate the efficacy and toxicity of an irinotecan hydrochloride (CPT) and nedaplatin (N) combination therapy for recurrent and refractory endometrial carcinoma, administered based on UGT1A1 genotype.Methods: Between 2009 and 2017, 21 patients who received CPT-N therapy for recurrent endometrial carcinoma as second- or third-line chemotherapy at our hospital were identified. The CPT-N regimen included 40-70 mg/m2 of CPT-11 on days 1, 8, and 15, and 50 mg/m2 of nedaplatin on day 1, q4 weeks.Results: The median patient age was 63 years. The number of prior chemotherapeutic regimens ranged from 1 to 2. Two patients had prior pelvic irradiation. The response rate [ratio of complete remission (CR) to partial remission (PR)] of CPT-N therapy was 3 of 21 (14.3%), and clinical benefit rate (CBR) [the combined percentages of CR, PR, and stable disease (SD)] was 9 of 21 (42.8%). Toxicities included grade 3 neutropenia [4 (19.0%) cases], grade 3 febrile neutropenia [2 (9.5%) cases], and grade 3 diarrhea [3 (14.3%) cases]; all resolved with conservative treatment. Patients with a wild-type UGT1A1 status received higher doses of CPT-11 (p = 0.048) and had similar RR and CBR compared to those with a UGT1A1*6 and *28 status. There were no significant differences in frequencies of hematological or non-hematological toxicities, regardless of UGT1A1 status.Conclusions: The CPT-N regimen for recurrent and refractory endometrial carcinoma had tolerable side effects and significant efficacy. This regimen is a viable treatment option for endometrial carcinoma. [ABSTRACT FROM AUTHOR]

A 78-year-old male patient was referred to the Department of Oral Surgery, Hokuto Hospital (Obihiro, Japan) for painless swelling on the left neck and tongue. Histopathological examination of a biopsy specimen resulted in a diagnosis of squamous cell carcinoma of the tongue. Imaging examinations revealed cervical lymph node metastases on both sides, along with diffuse uptake of 18F-fluorodeoxyglucose (FDG) in the bone marrow of the spine and pelvis. Hematologic tests revealed an increased white blood cell (WBC) count and serum concentrations of granulocyte colony stimulating factor (G-CSF). These findings suggested a G-CSF producing tumor, with fluctuations of WBC count, serum G-CSF concentration, and FDG uptake in the bone marrow, associated with tumor shrinkage and enlargement, an indicator of tumor status. [ABSTRACT FROM AUTHOR]

High-temperature-required protein A2 (HtrA2) is one of the serine proteases related to apoptosis. HtrA2 protein expression has been associated with cisplatin resistance and poor prognosis in ovarian serous adenocarcinoma (SAC). The aim of this study was to understand the influence of HtrA2 on repeated treatment with cisplatin. The change in HtrA2 expression in 31 ovarian cancers was investigated by immunohistochemical analysis, before and after cisplatin-based chemotherapy, and the association between HtrA2 expression after chemotherapy and prognosis was analyzed. The association between the change in HtrA2 and proteins associated with LATS1 in ovarian serous cancer cell lines after repeated treatment with cisplatin was evaluated in vitro. In immunohistochemical analysis, repeated cisplatin treatment induced downregulation of HtrA2 protein expression, before and after cisplatin-based chemotherapy in SAC. Progression-free survival and overall survival of SAC with low expression of HtrA2 were worse than those with high expression. In vitro analysis using cisplatin-sensitive ovarian cancer cell lines, KF28, and cisplatin-resistant cancer cell lines, KFr13, obtained from KF28 by repeated cisplatin treatment, showed that HtrA2 protein expression was lower in KFr13 than in KF28. Furthermore, KFr13 had a higher invasive capacity than KF28. Next, downregulation of HtrA2 transfected with an HtrA2-specific siRNA in KF28 had not only cisplatin resistance, but also more invasive capacity than those with non-specific siRNA. Repeated treatment with cisplatin downregulated the HtrA2 protein, which led to cisplatin resistance and increased invasive capacity. Thus, HtrA2 might be a biomarker of response to cisplatin treatment and prognosis, after cisplatin-based chemotherapy. [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: Low skeletal muscle mass (sarcopenia) has been reported to have an influence on survival and toxicities of chemotherapy in several solid tumors. The impact of sarcopenia on the treatment of ovarian cancers has not been determined. The present study aimed to evaluate correlation between sarcopenia and toxicities of chemotherapy in ovarian cancers.Methods: Medical charts of the ovarian cancer patients that received chemotherapy with paclitaxel and carboplatin at our hospital between 2010 and 2015 were retrospectively reviewed. Muscle areas of bilateral psoas major muscles at the fifth lumbar vertebra were measured using images obtained by computed tomography. The volume of muscle and clinicopathological factors were evaluated for toxicities of chemotherapy. The protocol of the present study was approved by the institutional review board of our institution.Results: A total of 76 patients with ovarian cancers were identified, and enrolled in the present study. Median psoas index (PI, the psoas muscle major cross-sectional area divided by the height squared) was 583 mm2/m2 (range 326-999). The patients with low PI developed peripheral neuropathy more frequently compared with those with high PI (32 vs. 11%; P = 0.047). PI value was not associated with other toxicities such as neutropenia and thrombocytopenia. PI value was associated with grade 2 or higher peripheral neuropathy in univariate analysis (OR = 3.92; 95% CI 1.21-15.32; P = 0.02) and multivariate analysis (OR = 3.93; 95% CI 1.17-15.87; P = 0.03).Conclusions: PI value was significantly associated with peripheral neuropathy induced by combination therapy with paclitaxel and carboplatin in ovarian cancer patients. Although further studies are needed to confirm the results, the volume of skeletal muscle mass could be a potential biomarker to predict toxicities in ovarian cancer patients. [ABSTRACT FROM AUTHOR]

A placental surface cyst is a cystic mass arising from the surface of the placenta. It is seldom complicated by intracystic hemorrhaging and the clinical importance of this kind of case is unclear. Therefore, we present a case of a placental surface cyst with intracystic hemorrhaging. A 29-year-old multiparous woman was diagnosed with multiple placental surface cysts with threatened preterm birth and fetal growth restriction on ultrasonography at 26 gestational weeks (GW). At 31 GW, the hemorrhage was identified inside the cyst. At 32 GW, she presented with placental abruption, and emergency cesarean section was performed. Both the mother and her baby survived. Placental surface cysts up to 77 × 65 mm in diameter containing old hemorrhages were discovered, and pathological examination revealed hemosiderin and fibrin deposition. Pregnancy with a placental surface cyst with intracystic hemorrhaging may have the potential for severe obstetric complications. [ABSTRACT FROM AUTHOR]

Objective: Most of the endometrial carcinomas are detected in early stages and have a better prognosis; however, predictive factors for recurrence have not been determined. Methods: Patients with grade 1 endometrioid carcinoma (EG1) according to the 2014 WHO criteria at FIGO 2009 stage IA that were identified through scanning medical charts were included, and we assessed whether the presence of uterine serous carcinoma (SC) component which comprised less than 5% of the total volume using the ovarian two-tiered grading system could be a recurrent risk factor in these patients. Results: Among 126 cases which met inclusion criteria, 12 cases had SC. SC tumors were divided into 2 groups: SC resembling high-grade serous carcinoma (HGSC) and SC resembling low-grade serous carcinoma (LGSC). Five (3.9%) cases had HGSC and 7 (5.6%) cases had LGSC. Recurrence was observed in 3 of all cases (2.3%): 2 cases with HGSC, and 1 case with LGSC. Regarding several clinicopathological factors, only the presence of SC was associated with recurrence. The sensitivity and specificity to predict recurrence using this system were 100 and 93%, respectively. Conclusion: The identification of SC using the ovarian two-tiered grading system could be an accurate predictor of recurrence in stage IA EG1. [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]

Background: Placenta previa, one of the most severe obstetric complications, carries an increased risk of intraoperative massive hemorrhage. Several risk factors for intraoperative hemorrhage have been identified to date. However, the correlation between birth weight and intraoperative hemorrhage has not been investigated. Here we estimate the correlation between birth weight and the occurrence of intraoperative massive hemorrhage in placenta previa. Materials and Methods: We included all 256 singleton pregnancies delivered via cesarean section at our hospital because of placenta previa between 2003 and 2015. We calculated not only measured birth weights but also standard deviation values according to the Japanese standard growth curve to adjust for differences in gestational age. We assessed the correlation between birth weight and the occurrence of intraoperative massive hemorrhage (>1500 mL blood loss). Receiver operating characteristic curves were constructed to determine the cutoff value of intraoperative massive hemorrhage. Results: Of 256 pregnant women with placenta previa, 96 (38%) developed intraoperative massive hemorrhage. Receiver-operating characteristic curves revealed that the area under the curve of the combination variables between the standard deviation of birth weight and intraoperative massive hemorrhage was 0.71. The cutoff value with a sensitivity of 81.3% and specificity of 55.6% was −0.33 standard deviation. The multivariate analysis revealed that a standard deviation of >−0.33 (odds ratio, 5.88; 95% confidence interval, 3.04–12.00), need for hemostatic procedures (odds ratio, 3.31; 95% confidence interval, 1.79–6.25), and placental adhesion (odds ratio, 12.68; 95% confidence interval, 2.85–92.13) were independent risk of intraoperative massive hemorrhage. Conclusion: In patients with placenta previa, a birth weight >−0.33 standard deviation was a significant risk indicator of massive hemorrhage during cesarean section. Based on this result, further studies are required to investigate whether fetal weight estimated by ultrasonography can predict hemorrhage during cesarean section in patients with placental previa. [ABSTRACT FROM AUTHOR]

Ovarian hyperstimulation syndrome (OHSS) is generally induced by assisted reproduction procedures (Pfeifer et al. [12]). Similar to spontaneous OHSS, there have also been cases of I hyperreactio luteinalis i (HL), which is a rare disease characterised by enlarged ovaries brought on by hCG alterations during pregnancy (Malinowski et al. [8]). Presence and absence of follicle-stimulating hormone receptor mutations provide some insights into spontaneous ovarian hyperstimulation syndrome physiopathology. Ovarian hyperstimulation syndrome (OHSS) in a spontaneous pregnancy with fetal and placental triploidy: information about the general pathophysiology of OHSS. [Extracted from the article]

A 66-year-old male patient with liver cirrhosis because of alcohol intake underwent a Hartmann's procedure for rectal cancer. Four months later, bleeding from the sigmoid stoma occurred and persisted for 2 months. A colonoscopic examination revealed bleeding from stomal varices. Three-dimensional computed tomography (CT) imaging demonstrated the inferior mesenteric vein and left superficial epigastric vein as the feeding and drainage vessels, respectively. Balloon-occluded retrograde transvenous obliteration (B-RTO) through the left epigastric vein was performed using a microballoon catheter inserted from the right femoral vein according to the Seldinger method. A CT examination performed 2 days after the B-RTO procedure revealed that the blood flow had disappeared, with thrombosis formation in both the stomal varices and the feeding vein. No recurrent bleeding from the stoma occurred. B-RTO using a microballoon catheter is useful as a therapeutic procedure for stomal varices to prevent bleeding, since the procedure can be performed with minimal invasion using the Seldinger method. [ABSTRACT FROM AUTHOR]

Aim Irinotecan-induced severe toxicities are possibly related to UGT1A1*6 and *28 genotypes. However, the correlation between UGT1A1 polymorphisms and the risk of toxicities induced by low-dose irinotecan plus platinum combination therapy still remains controversial. This prospective observational study aimed to examine the correlation between UGT1A1 genotypes and clinical outcomes of low-dose irinotecan (median 60 mg/m2, range 25-115 mg/m2) plus platinum in Japanese patients with solid tumors. Methods Toxicity profiles were compared between UGT1A1 SNP heterozygotes (hetero-group) and patients with homozygous SNP profile (*6/*6, *28/*28 and *6/*28). Logistic regression models were used to identify independent risk factors for these toxicities. Results A total of 331 patients were enrolled: 84% with hetero-group and 16% with homo-group. Although the initial irinotecan dose was similar, the dose intensities during the three cycles were significantly lower in the homo-group ( P < 0.01). Grade 3/4 hematological toxicities were significantly more frequent in the homo-group. Multivariable analysis identified UGT1A1 genotype ( P < 0.01) as an independent factor for grade 4 hematological toxicity in the first treatment cycle. Conclusion UGT1A1 genotype has a major impact on the increased risk of severe hematological toxicities, even in low-dose irinotecan regimens. UGT1A1 genotypes are useful biomarkers for predicting severe hematological toxicities in patients treated with irinotecan plus platinum analog. [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]

Refeeding syndrome very rarely develops during pregnancy. A 35-year-old primiparous woman pregnant with twins complained of severe fatigue at 19 weeks’ gestation. She was admitted to our hospital in a malnourished condition because of repeated self-induced vomiting due to anorexia nervosa. Just after hospitalization, she voluntarily increased her caloric intake significantly above the recommended prescribed diet, without medical permission. Nine days later, she developed refeeding syndrome. Electrolyte replacement and calorie restriction were started and her condition gradually improved. The healthy twin babies were born by cesarean section at 36 weeks’ gestation. Acute increases in caloric intake by previously malnourished pregnant women with anorexia nervosa may induce refeeding syndrome. Women with the binge eating/purging subtype of anorexia nervosa may be at additional risk due to alternating phases of starvation and overeating. [ABSTRACT FROM AUTHOR]