Potential efficacy of weekly low-dose administration of bevacizumab as a combination therapy for platinum-resistant ovarian carcinoma: a retrospective analysis.

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.

The worsening impact of programmed cell death ligand 1 in ovarian clear cell carcinomas.

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.

Criteria for placenta accreta spectrum in the International Federation of Gynaecology and Obstetrics classification, and topographic invasion area are associated with massive hemorrhage in patients with placenta previa.

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.

The use of magnetic resonance imaging to predict placenta previa with placenta accreta spectrum.

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.

Placenta previa may acquire invasive nature by factors associated with epithelial-mesenchymal transition and matrix metalloproteinases.

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.

Comparison of clinical behavior between mucinous ovarian carcinoma with infiltrative and expansile invasion and high-grade serous ovarian carcinoma: a retrospective analysis.

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.

Clinical significance of CD8-positive lymphocytes on tumor cell clusters of ascites cell block in ovarian high-grade serous carcinoma.

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.

Clear cell borderline tumor without fibromatous component: Pathological and literature review and report of two cases.

The aim of the present study was to examine the clinical outcome of ovarian clear cell borderline tumor (CCBT) through pathological review for cases with clear cell carcinoma (CCC) and CCBT between 1984 and 2015 who received surgery at the National Defense Medical College Hospital using 2020 World Health Organization (WHO) criteria. In addition to the definition of CCBT in 2020 WHO criteria, clear cell with atypia of the glandular epithelium without fibromatous component was added to the diagnostic criteria of CCBT. Two cases with CCBT were identified through review in the current study. There were no cases that changed from the initial CCBT diagnosis that were included in the current study. Case 1 was a 43-year-old woman who received total hysterectomy, bilateral salpingo-oophorectomy and partial omentectomy. Pathologically, cysts were lined by cuboidal, hobnail and clear cells with eosinophilic cytoplasm and moderate nuclear atypia without the fibromatous component. These cells were adjacent to atypical endometriosis and non-atypical endometriosis, and the patient was diagnosed with CCBT. She exhibited no evidence of the disease for 37 months following surgery. Case 2 was a 42-year-old woman who received left salpingo-oophorectomy, partial omentectomy and pelvic lymphadenectomy. The tumor exhibited a cyst (80 mm) and nodular component. Pathologically, the tumor cells were lined by hobnail cells with mild atypia and eosinophilic cytoplasm without the fibromatous component. This patient was diagnosed with CCBT and exhibited no evidence of disease for 20 months following surgery. CCBT without fibromatous component is a rare and non-aggressive histological subtype. Additionally, regardless of fibromatous component, CCBT was able to be diagnosed.

Prognostic similarity between ovarian mucinous carcinoma with expansile invasion and ovarian mucinous borderline tumor: A retrospective analysis.

ABSTRACT: There is a similarity of histological features and survival between ovarian mucinous carcinoma (MC) with expansile invasion and ovarian mucinous borderline tumor (MBT). The aim of this study was to compare the clinical outcomes of MC with expansile invasion with those of MBT based on the 2020 World Health Organization (WHO) criteria.A pathological review was performed on patients with MC, ovarian MBT, and seromucinous borderline tumors that underwent surgery at our hospital between 1984 and 2019. Clinicopathological features were compared retrospectively between MC with expansile invasion and MBT.Among 83 cases of MC, 85 cases of MBT, and 12 cases of seromucinous borderline tumor, 25 MC cases with expansile invasion and 98 MBT cases were included through review. MC cases with expansile invasion were diagnosed with advanced International Federation of Gynecology and Obstetrics (FIGO) stages more frequently (P = .02) than that of MBT cases. In addition, patients with MC with expansile invasion received adjuvant chemotherapy more often (P < .01) than that of patients with MBT. There were no statistically significant differences in recurrence rate (P = .10) between MC with expansile invasion and MBT. Progression-free survival (PFS) was worse in MC cases with expansile invasion than that in MBT cases (P = .01). However, a multivariate analysis for PFS showed that histological subtype, FIGO stage, and adjuvant chemotherapy were not an independent prognostic factor.The prognostic outcome of MC with expansile invasion might mimic those of MBT. These results showed ovarian borderline tumor treatment could be applied to MC treatment.

A New Model to Improve the Prediction of Prognosis of Endometrial Carcinoma by Combining Traditional Classification With the Presence of Tumor-infiltrating Lymphocytes.

BACKGROUND/AIM: We aimed to predict the prognosis of endometrial carcinoma by combining traditional histological classification with the status of tumor-infiltrating lymphocytes (TILs). PATIENTS AND METHODS: All patients with endometrial carcinoma, treated at our hospital, were classified into four categories-Category I: Type I positive for TILs; category II: type I negative for TILs; category III: type II positive for TILs; and category IV: type II negative for TILs. Prognoses were compared across all the categories. Positivity for TILs was defined as a continuously formed thick zone of TILs at the invasive front. RESULTS: Multivariate analyses of progression-free and overall survival indicated that category classification was an independent prognostic factor, with hazard ratios of 3.127, 3.483, and 8.459 for progression-free survival, and 3.444, 4.374, and 11.058 for OS for patients in categories II, III, and IV, respectively. CONCLUSION: Combining traditional histological classification with TIL status might better predict prognosis of endometrial carcinoma.

Applicability of ultrasonography for detection of marginal sinus placenta previa.

ABSTRACT: This study aimed to examine whether marginal sinus placenta previa, defined as when the marginal sinus just reaches the internal cervical os and placental parenchyma might be >2 cm from the internal cervical os, can be diagnosed using ultrasonography (US). We identified the placenta previa cases that underwent both US and magnetic resonance imaging (MRI) between April 2010 and December 2018 at our institution. The diagnostic discrepancies for marginal sinus placenta previa between US and MRI were examined retrospectively. Of the 183 cases of placenta previa, 28 (15.3%) cases were diagnosed as marginal sinus placenta previa using MRI. Among them, 18 cases (64.3%) could also be diagnosed using US. The sensitivity and specificity of the diagnosis of marginal sinus placenta previa using US were 64.3% and 92.9%, respectively. A change in US diagnosis occurred in 10 (35.7%) cases, all of which were diagnosed with low-lying placenta previa or marginal placenta previa and did not develop any serious miserable obstetrical outcomes. In conclusion, the diagnostic accuracy of US for detecting marginal sinus placenta previa was not significant. MRI examination may be required to accurately categorize the types of placenta previa.

Survival and biomarker analysis for ovarian mucinous carcinoma according to invasive patterns: retrospective analysis and review literature.

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.

Significance of mesothelin and CA125 expression in endometrial carcinoma: a retrospective analysis.

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.

Psoas muscle index at the fifth lumbar vertebra as a predictor of survival in epithelial ovarian cancers.

Almost a quarter of a century has passed since the term sarcopenia was defined. Sarcopenia is recognized as a poor prognostic factor in a variety of cancer types. In ovarian cancer, it remains controversial whether sarcopenia affects prognosis and how it should be evaluated. The present study aimed to evaluate the association between the volume of the psoas major muscle and survival in patients with epithelial ovarian cancer. Medical charts of patients with epithelial ovarian cancer who received first-line chemotherapy with paclitaxel and carboplatin at the National Defense Medical College Hospital (Tokorozawa, Japan) between April 2010 and January 2015 were retrospectively reviewed. The bilateral psoas major muscle areas at the fifth lumbar vertebra were measured using computed tomography images. The Institutional Review Board at National Defense Medical College Hospital (Tokorozawa, Japan) approved the study protocol. A total of 72 patients with epithelial ovarian cancer who received combination therapy with paclitaxel and carboplatin were identified and enrolled. The median psoas muscle index (PMI; psoas muscle major cross-sectional area divided by height squared) was 5.4 cm2/m2 (range, 3.3-10.0). Patients with higher PMI had significantly improved overall survival (OS) compared with those with lower PMI [log-rank test P=0.014; hazard ratio (HR), 2.61; 95% confidence interval (CI), 1.21-6.06]. Multivariate analysis for OS revealed that lower PMI was an independent unfavorable prognostic factor (HR, 3.87; 95% CI, 1.37-12.1; P=0.0098). The volume of psoas major muscle mass could be a potential biomarker for prognosis in patients with epithelial ovarian cancer.

Diagnostic efficacy of ascites cell block for ovarian clear cell carcinoma.

BACKGROUND: Ascites cytology is important for determining the stage and treatment methods for ovarian clear cell carcinoma (CCC) as defined by the 2014 International Federation of Obstetrics and Gynecology classification. METHODS: Patients with CCC who underwent surgery at our hospital between January 2012 and December 2019 and who received cytodiagnosis of their ascites using Papanicolaou (Pap) and May-Grünwald-Giemsa (MGG) staining, and cell block methods were identified. The cell block technique was performed using hematoxylin-eosin (H&E) staining and immunohistochemical staining for hepatocyte nuclear factor-1ß (HNF-1ß), estrogen receptor (ER), progesterone receptor (PR), and Wilms tumor-1 (WT-1). Cancer cells of CCC were defined as tumor cells that were positive for HNF-1ß and negative for ER, PR, and WT-1. The diagnostic accuracy of ascites cytology using Pap and MGG staining and cell block methods was examined. RESULTS: Based on cytological data, our study included 17 patients: seven (41.1%) with malignant (MAL) ascites, eight (47.1%) with negative for malignancy (NFM), and two (11.8%) with atypia of undetermined significance (AUS) because of a few atypical cells based on Pap and MGG staining. Malignant cells diagnosed by cell blocks were detected in 7/7 patients with MAL ascites based on PAP and MGG staining, 2/8 (25.0%) patients with NFM, and 1/2 (50%) patients with AUS. CONCLUSION: These findings show that the cell block method combined with the immunohistochemical investigation may be useful for increasing the diagnostic accuracy of malignant cells in CCC.

Rapid decrease in serum VEGF-A levels may be a worse prognostic biomarker for patients with platinum-resistant recurrent ovarian cancer treated with bevacizumab and gemcitabine.

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.

Co-Expression of Mesothelin and CA125 Is Associated with the Poor Prognosis of Endometrial Serous Carcinoma and Mixed Carcinomas Including Serous Carcinoma.

The aim of this study was to investigate the association between the clinicopathologic factors and either expression or co-expression of mesothelin and cancer antigen (CA) 125 in endometrial serous carcinoma and mixed carcinomas including serous carcinoma. Between 1990 and 2017, patients with endometrial serous carcinoma and mixed carcinoma including serous carcinoma treated by total hysterectomy and bilateral salpingo-oophorectomy at our hospital were identified. The association between either expression or co-expression of mesothelin and CA125 was evaluated by immunochemical analysis and the clinico-pathological features were retrospectively examined. Among the 40 patients included, 19, 31, and 18 patients exhibited single positive mesothelin, single positive CA125, and positive co-expression, respectively. The expression of mesothelin and CA125 was observed to be positively associated (p = 0.021). There was no significant association of age and FIGO stage with individual mesothelin or CA125 expression or their co-expression. Overall survival (OS), but not progression-free survivals (PFS), of only mesothelin-positive patients was worse (p = 0.024). Hence, OS and PFS of patients with positive co-expression were worse (PFS: p = 0.043, OS: p = 0.012). In multivariate analysis, single mesothelin expression and single CA125 expression did not lead to worse prognosis. However, positive co-expression was the worst prognostic factor for OS (hazard ratio: 3.32, p = 0.039). Co-expression of mesothelin and CA125 may accurately predict OS in endometrial serous carcinoma and mixed carcinomas including serous carcinoma. Further studies should examine this relationship.

Ovarian Seromucinous Borderline Tumors Are Histologically Different from Mucinous Borderline Tumors.

AIM: To examine the clinicopathological features of ovarian seromucinous borderline tumors (SMBTs) and compare them with those of mucinous borderline/atypical proliferative mucinous tumors (MB/APMTs). PATIENTS AND METHODS: Patients with SMBT between 2014 and 2018 and those with MB/APMT between 1988 and 2018 who underwent surgery at our Institution were identified. Pathological review was conducted using the 2014 World Health Organization criteria. Clinical features were compared retrospectively between SMBT and MB/APMT. RESULTS: In total, 11 (12.9%) patients with SMBT and 74 (87.1%) patients with MB/APMT were included in our study. The diagnosis of six patients with SMBT and 73 patients with MB/APMT was not revised on review. SMBT was diagnosed at a younger age (p=0.04), was of smaller size (p<0.01) and bilateral (p=0.03), coexisted with endometriosis (p<0.01), and more frequently recurred than MB/APMT (p=0.04). CONCLUSION: SMBT might be more aggressive than MB/APMT.