Heterogeneous treatment effect of dose-dense paclitaxel plus carboplatin therapy for advanced ovarian cancer.

A Japanese clinical trial (JGOG3016) showed that dose-dense weekly paclitaxel in combination with carboplatin extensively prolonged overall survival (OS) in patients with advanced ovarian cancer. However, in other clinical trials, dose-dense paclitaxel regimens were not superior to triweekly paclitaxel regimens. In this study, causal tree analysis was applied to explore subpopulations with different treatment effects of dose-dense paclitaxel in a data-driven approach. The 587 participants with stage II-IV ovarian cancer in the JGOG3016 trial were used for model development. The primary endpoint was treatment effect in terms of 3-year OS in patients receiving dose-dense vs. conventional paclitaxel therapies. In patients <50 years, the 3-year OS was similar in both groups; however, it was higher in the dose-dense group in patients ≥50 years. Dose-dense paclitaxel showed strong positive treatment effects in patients ≥50 years with stage II/III disease, BMI <23 kg/m2, non-CC/MC, and residual tumor ≥1 cm. In contrast, although there was no significant difference in OS; the 3-year OS rate was 23% lower in dose-dense paclitaxel than conventional paclitaxel in patients ≥60 years with stage IV cancer. Patients in this group had a particularly lower performance status than other groups. Our causal tree analysis suggested that poor prognosis groups represented by residual tumor tissue ≥1 cm benefit from dose-dense paclitaxel, whereas elderly patients with advanced disease and low-performance status are negatively impacted by dose-dense paclitaxel. These subpopulations will be of interest to future validation studies. Personalized treatments based on clinical features are expected to improve advanced ovarian cancer prognosis.

Vaginal Transmission of Cancer from Mothers with Cervical Cancer to Infants.

Two cases of pediatric lung cancer (in 23-month-old and 6-year-old boys) resulting from mother-to-infant transmission of uterine cervical tumors were incidentally detected during routine next-generation sequencing of paired samples of tumor and normal tissue. Spontaneous regression of some lesions in the first child and slow growth of the tumor mass in the second child suggested the existence of alloimmune responses against the transmitted tumors. Immune checkpoint inhibitor therapy with nivolumab led to a strong regression of all remaining tumors in the first child. (Funded by the Japan Agency for Medical Research and Development and others; TOP-GEAR UMIN Clinical Trials Registry number, UMIN000011141.).

Prognostic significance of adjuvant chemotherapy in stage I-II endometrial carcinoma patients who underwent lymphadenectomy.

BACKGROUND: Endometrial carcinoma, the most common gynecologic carcinoma, has an excellent prognosis post-surgery when diagnosed early. The role of postoperative adjuvant chemotherapy in stages I-II endometrial carcinoma remains controversial. This study assesses the efficacy of adjuvant chemotherapy in improving prognosis for these patients. METHODS: A retrospective analysis was conducted on 1223 stage I-II endometrial carcinoma patients who underwent surgical treatment including total hysterectomy, bilateral salpingo-oophorectomy, and lymph-node biopsy or dissection across four Jikei University School of Medicine-affiliated facilities between 2001 and 2018. Patients were divided into low intermediate risk (LIR) and high intermediate risk (HIR) groups based on recurrence risk. Propensity score matching adjusted for various covariates was used to compare progression-free survival (PFS) and overall survival (OS) between patients who received adjuvant chemotherapy and those who did not. RESULTS: The study included 443 eligible patients, with 288 in the LIR group and 155 in the HIR group. Post propensity score matching, no significant difference in PFS or OS was observed between the observation and adjuvant chemotherapy groups within both risk categories. Notably, the 5-year OS for LIR was 97.6% in the observation group and 96.7% in the chemotherapy group; for HIR, the 5-year OS was similarly high with no significant difference. CONCLUSIONS: The findings suggest that postoperative adjuvant chemotherapy does not significantly contribute to the improvement of recurrence or prognosis in patients with stage I-II endometrial carcinoma who are categorized outside the low-risk group and have no lymph-node metastasis.

Therapeutic effect of dose-dense paclitaxel plus carboplatin with or without bevacizumab for Japanese patients with epithelial ovarian cancer.

BACKGROUND: Evidence regarding chemosensitivity to different therapeutic regimens in epithelial ovarian cancer (EOC) remains limited. This study aimed to investigate EOC implementation in daily clinical practice and reveal favorable regimens for EOC among Japanese patients. METHODS: We retrospectively collected clinical data of patients newly diagnosed with EOC from 2012 to 2021 at our affiliated institutions. We evaluated overall survival (OS) and progression-free survival (PFS) of conventional paclitaxel plus carboplatin (TC) vs. dose-dense TC (ddTC) according to the eligibility of GOG262 and JGOG3016 and those with bevacizumab (BEV) vs. without BEV based on GOG218. Further, we evaluated OS and PFS of ddTC and ddTC + BEV to TC + BEV among patients with stage III/IV. RESULTS: The ddTC group (n = 402) demonstrated longer PFS and OS than the TC group (n = 165) (adjusted hazard ratios [aHRs] [95% confidential intervals (CIs)]: 0.69 [0.55-0.88] and 0.67 [0.50-0.90], respectively). The group with BEV (n = 158) demonstrated a longer PFS than those without BEV (n = 296) (0.74 [0.57-0.95]), but not for OS (0.84 [0.60-1.17]). The ddTC and ddTC + BEV groups (n = 259 and 117) demonstrated no statistically significant differences in PFS and OS than the TC + BEV group (n = 75) (1.09 [0.79-1.50] and 0.74 [0.52-1.08] for PFS and 0.89 [0.59-1.34] and 0.73 [0.50-1.05] for OS, respectively). CONCLUSION: Our study may indicate ddTC, BEV, and their combination regimen as the promising first-line chemotherapy option among Japanese patients with advanced EOC.

Phase II study of gemcitabine, cisplatin, and bevacizumab for first recurrent and refractory ovarian clear cell carcinoma Kansai Clinical Oncology Group-G1601.

Patients with advanced ovarian clear cell carcinoma (CCC) have a poor prognosis in the absence of an effective standard treatment. Combination therapy with gemcitabine, cisplatin, and bevacizumab (GPBev) is promising for ovarian CCC. Thus, we conducted a multi-institutional, phase II trial in Japan to examine the efficacy and safety of GPBev for CCC. This is the first study on the use of GPBev for CCC. Eighteen patients (median age, 56.5 years) with pathologically confirmed first recurrent or refractory CCC and having evaluable regions, as assessed using RECIST, were recruited between January 2017 and May 2019. Gemcitabine (1000 mg/m 2 ), cisplatin (40 mg/m 2 ), and bevacizumab (10 mg/kg) were administered intravenously on days 1 and 15, every 28 days, for 6-10 cycles, until disease progression or intolerable toxicity. The primary endpoint was overall response rate (ORR). The secondary endpoints included disease control rate (DCR) and adverse events (AEs). Fifteen patients (83.3%) completed 6-10 cycles of treatment; three patients (two with AEs and one with progressive disease) did not. The ORR was 61.1% [complete response (CR) 3 and partial response (PR) 8] and DCR was 88.9% (CR 3, PR 8, and stable disease 5). Grade 3 and 4 hematological AEs were observed in 16.7 and 5.6% of the patients, respectively. Nonhematological AEs of grades 3 and 4 were observed in 27.8 and 5.6% of the patients, respectively. GPBev is a promising therapy for CCC owing to the high ORR and acceptable toxicity for the first recurrence and refractory CCC.

Evaluation of non-hematologic toxicity in patients with cervical cancer after Type 3 radical hysterectomy followed by concurrent chemoradiotherapy: a retrospective study.

OBJECTIVE: To investigate the safety of concurrent chemoradiotherapy after Type 3 radical hysterectomy, focusing on non-hematologic toxicity. METHODS: Between January 2010 and December 2017, 236 patients diagnosed with cervical cancer Stages IB1-II (FIGO2008) and who had undergone Type 3 radical hysterectomy at the Jikei Medical University School-related four hospitals were included. Of these 236 patients, 134 had undergone adjuvant concurrent chemoradiotherapy after Type 3 radical hysterectomy (radical hysterectomy + concurrent chemoradiotherapy group), and 102 received no adjuvant therapy after Type 3 radical hysterectomy (radical hysterectomy group). The frequency of non-hematologic toxicities, especially lymphedema, pelvic infection, renal dysfunction, ileus and diarrhea, was investigated in the radical hysterectomy + concurrent chemoradiotherapy and radical hysterectomy groups using univariate and multivariate analyses. In these analyses, age, extent of lymph node dissection and preoperative clinical stage were included as risk factors for five complications. The risk factors for grade ≤ 2 adverse events were statistically evaluated. RESULTS: The frequency of lower extremity lymphedema (22 vs. 10%), renal dysfunction (13 vs. 3%), and diarrhea (13 vs. 0%) was significantly higher in the radical hysterectomy + CRRT group than that in the radical hysterectomy group. Logistic regression analysis revealed that adjuvant concurrent chemoradiotherapy significantly affected the occurrence of grade ≥ 2 lymphedema (P < 0.01) and renal dysfunction (P < 0.01). CONCLUSIONS: Concurrent chemoradiotherapy after Type 3 radical hysterectomy is associated with a higher incidence of renal dysfunction, lower extremity lymphedema and diarrhea. A more appropriate adjuvant therapy needs to be established.

Genetic characteristics of platinum-sensitive ovarian clear cell carcinoma.

OBJECTIVE: Most ovarian clear cell carcinomas are resistant to platinum-based chemotherapy, while a small subset shows a positive response. The aim of this study was to clarify the clinical, pathological and genetic characteristics of platinum-sensitive ovarian clear cell carcinomas. METHODS: The study included 53 patients with stage III-IV ovarian clear cell carcinoma who had residual tumours after primary surgery and received platinum-based therapy between 2009 and 2018. A retrospective examination of platinum sensitivity was performed using the criterion of ≥6 months from the last day of first-line platinum therapy until recurrence/progression. Cases determined to be platinum-sensitive were subjected to immunohistochemical staining, genomic analyses using target sequencing (i.e. NCC Oncopanel) and homologous recombination deficiency (myChoice® HRD Plus) assays. RESULTS: Of the 53 stage III-IV ovarian clear cell carcinoma cases, 11 (21%) were platinum-sensitive. These cases showed better progression-free and overall survival than platinum-resistant cases (hazard ratio = 0.16, P < 0.001). Among the seven sensitive cases whose tumour tissues were available for molecular profiling, five were pure ovarian clear cell carcinoma based on pathological and genetic features, whereas the remaining two cases were re-diagnosed as high-grade serous ovarian carcinoma. The pure ovarian clear cell carcinomas lacked BRCA1 and BRCA2 mutations, consistent with the absence of the homologous recombination deficiency phenotype, whereas two cases (40%) had ATM mutations. By contrast, the two high-grade serous ovarian carcinoma cases had BRCA1 or BRCA2 mutations associated with the homologous recombination deficiency phenotype. CONCLUSION: The subset of platinum-sensitive ovarian clear cell carcinomas includes a majority with pure ovarian clear cell carcinoma features that lack the homologous recombination deficiency phenotype.

Re-thinking the prognostic significance of positive peritoneal cytology in endometrial cancer.

BACKGROUND: Whether abnormal peritoneal cytology (PC) is an independent prognostic factor in endometrial cancer (EC) remains controversial. This study aimed to re-think the prognostic significance of PC in not only all EC patients but also in various subgroups with similar clinicopathological and biological characteristics. METHODS: EC patients who underwent primary surgery of at least a hysterectomy and were pathologically diagnosed with EC in four hospitals affiliated with the Jikei University School of Medicine were retrospectively reviewed. The prognostic significance of PC was evaluated with univariate and multivariate analyses in the entire cohort and subgroups stratified by surgical stages (early/advanced stages), tumor types (types 1/2), and risk classifications (low/intermediate/high). RESULTS: Of 1963 EC cases, 1616 met the inclusion criteria. Positive PC was identified as an adverse prognostic factor in analyses of all EC cases and in all subgroup analyses stratified by surgical stages and tumor types. In survival curve comparisons, the progression-free survival (PFS) and disease-specific survival in early-stage patients with positive PC were clearly located between those of stage II patients with negative PC and stage III patients. In the subgroup analyses stratified by risk classification in early-stage EC, positive PC was related to poorer PFS in the intermediate- and high-risk groups but not in the low-risk group. CONCLUSION: PC status was an independent prognostic factor of EC in all stages and tumor types. Early PC-positive cases, except for the low-risk group, may be recommended for upstaging and should be carefully managed compared with PC-negative cases.

Analysis of risk factors for patients with early-stage cervical cancer: A study of 374 patients.

AIM: This study aimed to identify the postoperative histological features affecting the prognosis of patients with early-stage cervical cancer who underwent open radical hysterectomy. METHODS: This retrospective study enrolled 374 patients with pT1a, 1b1 and 2a1 early-stage cervical cancer who underwent open radical hysterectomy between 2001 and 2018. Survival outcomes were analyzed by Kaplan-Meier method and compared with log-rank test. Using the Cox proportional hazards regression test, we conducted a multivariate analysis for disease-free survival and overall survival. RESULTS: Others histology, including other epithelial tumors and neuroendocrine tumors, had a significantly worse prognosis in both disease-free survival and overall survival than those of squamous cell carcinoma and adenocarcinoma (hazard ratio, 4.37 and 11.76; P = 0.006 and P = 0.002, respectively), along with lymph node metastasis (hazard ratio, 2.99 and 7.03; P = 0.009 and P = 0.001, respectively). CONCLUSION: Others histology including adenosquamous carcinoma had a poor prognosis in early-stage cervical cancer as with high-risk factors.

Long term outcomes from lymphatic venous anastomosis after total hysterectomy to prevent postoperative lymphedema in lower limb.

BACKGROUND: Lymphedema in lower limb is one of major postoperative complications followed by a total hysterectomy with lymph node dissection. The objective of this report is to examine a long-term result of lymphaticovenous anastomosis procedure as a preventive surgery. METHODS: Sixteen patients with endometrial cancer underwent an abdominal hysterectomy with a bilateral salpingo-oophorectomy. Just after pelvic lymph node dissection, either end-to-end or sleeve anastomosis utilizing venules and suprainguinal lymph vessels was performed. During the observation period from 4 to 13 years, the symptom of lymphedema in lower extremities has been assessed. RESULTS: Among 16 patients, 1 presented postoperative lymphedema grade 3 (CTCAE (Common Terminology Criteria for Adverse Events) Ver. 4.0, 10025233) in lower limb, and a second surgery at 7 years after the first one was required. Other 6 patients showed non-severe symptoms of lymphedema, diagnosed as grade 1. The rest 9 patients did not show any symptoms of postoperative lymphedema in a long term (up to 13 years). CONCLUSION: From the long term outcomes of our 16 cases, we propose that a direct lymphaticovenous microsurgery immediately after a hysterectomy with lymphadenectomy of external inguinal lymph node is one of the appropriate therapeutic choices to prevent severe lymphedema in lower limb.

Prognostic impact of interleukin-6 expression in stage I ovarian clear cell carcinoma.

OBJECTIVE: Ovarian clear cell carcinoma (OCCC) frequently presents at an early stage. In stage I OCCC, the prognosis differs according to substage. In particular, predictive biomarkers and new treatment strategies are needed for stage IC2/IC3 disease. We investigated tumor biology and prognostic factors for stage I OCCC from a clinicopathological perspective, including the expression of ARID1A and IL-6, which are considered critical for OCCC carcinogenesis. METHODS: A retrospective cohort study of 192 patients with stage I OCCC treated at a single institution was performed. We calculated overall survival (OS) with respect to 12 clinicopathological parameters that included the unique and diverse histological features of OCCC. RESULTS: The estimated 5-year OS rate in patients with all stage I OCCC was 88.9% during a median of 91months of follow-up. The multivariate analysis indicated that substage classification and IL-6 expression status were associated with poor OS (p=0.010 and p=0.027, respectively). Loss of ARID1A expression had no impact on survival; however, it was associated with substage (p=0.001), capsule rupture status (p=0.011), and ascites cytology (p=0.016). No clear association was found between ARID1A and IL-6 expressions. Histological findings, including the presence of endometriosis, adenofibroma, architectural pattern, and tumor cell type, showed no prognostic effects. CONCLUSIONS: Both substage classification and IL-6 expression status may be independent prognostic factors in stage I OCCC. Therefore, IL-6 molecular stratification may be crucial in optimizing therapeutic strategies for early stage OCCC to improve survival.

Antitumor effects of interleukin-6 (IL-6)/interleukin-6 receptor (IL-6R) signaling pathway inhibition in clear cell carcinoma of the ovary.

Among epithelial ovarian cancers, clear cell carcinoma of the ovary (CCC) has unique clinical and molecular characteristics that include chemoresistance resulting in poor prognosis. It was shown that CCC recently was characterized by specific upregulation of the IL-6/IL-6R-signal transducer and activator of transcription 3 (Stat3) signaling pathway. In this study, we aim to clarify whether IL-6/IL-6R mediated signaling pathway could have clinical relations with CCC and to evaluate inhibitory effects of the pathway on CCC carcinogenesis. A total of 84 CCC cases collected from primary surgical specimens were evaluated by the immunohistochemical analysis for IL-6R and phosphorylated Stat3 (pStat3), and we found that high IL-6R expression correlated with poor patient survival both by the univariate and multivariate analyses, suggesting that IL-6/IL-6R signaling pathway could be implicated in the progression of CCC. We further investigated the effects of IL-6/IL-6R mediated signaling pathway inhibition either by IL-6R small interfering RNA (siRNA) approach or humanized anti-human IL-6R antibody (tocilizumab) in CCC. Inhibition of endogenous IL-6R including tocilizumab in CCC cells did reduce cell invasion ability and restored their response to cytotoxic reagent. These data suggest that IL-6/IL-6R signaling pathway could act on CCC cells to enhance invasion and chemoresistance and, therefore, targeting IL-6/IL-6R mediated signaling pathway could be a promising therapeutic strategy for CCC.

Evaluation of human epididymis protein 4 (HE4) and Risk of Ovarian Malignancy Algorithm (ROMA) as diagnostic tools of type I and type II epithelial ovarian cancer in Japanese women.

Human epididymis protein 4 (HE4) levels and the Risk of Ovarian Malignancy Algorithm (ROMA) have recently been shown to improve the sensitivity and specificity of epithelial ovarian cancer (EOC) diagnosis. We evaluated HE4 levels and ROMA as diagnostic tools of type I and type II EOC in Japanese women. Women who had a pelvic mass on imaging and were scheduled to undergo surgery were enrolled as ovarian mass patients. Serum levels of carbohydrate antigen 125 (CA125) and HE4 were tested in 319 women (131 benign, 19 borderline, 75 malignant, and 94 healthy controls). CA125, HE4, and ROMA were evaluated for sensitivity and by receiver operating characteristics (ROC) in type I and type II EOC. The results showed that, at 75% specificity, the sensitivity of CA125 and HE4 for type II was 92.1% for both markers and for type I was 51.5% and 78.8%, respectively. The sensitivities of ROMA (type I, 84.8% and type II, 97.4%) were better than those of CA125 and HE4. CA125, HE4, and ROMA were all highly accurate markers for type II. For type I, HE4 and ROMA showed better sensitivity than CA125. ROMA displayed the best diagnostic power for type I and type II including for the early stage of type I. In conclusion, HE4, CA125, and ROMA are valuable markers for type II EOC diagnosis. HE4 and ROMA analyses may improve differentiation between type I EOC and a benign mass. Measurement of combined HE4 and CA125 levels provides a more accurate method for EOC diagnosis.

A retrospective study of dose-dense paclitaxel and carboplatin plus bevacizumab as first-line treatment of advanced epithelial ovarian cancer.

OBJECTIVE: This study compared the effectiveness, safety, and tolerability of dose-dense paclitaxel and carboplatin plus bevacizumab (ddTC+Bev) with ddTC for advanced ovarian cancer. METHODS: We retrospectively analyzed the clinical records of 134 patients who received ddTC+Bev or ddTC as first-line chemotherapy for stage III-IV ovarian cancer. Progression-free survival as primary endpoint of this study was compared using the log-rank test. Cox proportional hazards model and propensity score matching (PSM) were used to analyze prognostic factors, and the frequency of adverse events was examined using the χ² test. RESULTS: We categorized 134 patients in the ddTC+Bev (n=57) and ddTC (n=77) groups who started treatment at four related institutions from November 2013 to December 2017. No patients used poly (ADP-ribose) polymerase inhibitors as the first line maintenance therapy. The progression-free survival (PFS) of the ddTC+Bev group had a significantly better prognosis than that of the ddTC group (hazard ratio [HR]=0.50; 95% confidence interval [CI]=0.32-0.79; p<0.003). Multivariate analysis showed that ddTC+Bev regimen was a prognostic factor. However, intergroup comparison using PSM revealed that the PFS of the ddTC+Bev group had a nonsignificantly better prognosis than that of the ddTC group (HR=0.70; 95% CI=0.41-1.20; p=0.189). Few adverse events above G3 were noted for ddTC+Bev, which were sufficiently tolerable. CONCLUSION: This study could not demonstrate that adding Bev to ddTC improves prognosis. Further studies with more cases are warranted.

Feasibility study of paclitaxel plus carboplatin in patients with endometrial cancer: a Japan Kanto Tumor Board study (JKTB trial).

AIM: The optimal chemotherapy regimen for patients with endometrial cancer has not been established. We assessed the feasibility of paclitaxel plus carboplatin (TC) for postoperative chemotherapy in patients with endometrial cancer. MATERIAL AND METHODS: Patients with newly diagnosed endometrial cancer received TC (paclitaxel 180 mg/m(2) , carboplatin AUC6 mg/mL/min) every three weeks. Treatment was continued until disease progression or completion of six cycles. Toxicities were evaluated every cycle according to NCI-CTCAE version 3.0. RESULTS: Sixty patients were registered from December 2005 through November 2006. Forty-four of 60 (73.3%) cases completed all of the planned six cycles. Grades 3 and 4 hematologic toxicities were observed as follows: leukopenia (61.7%), neutropenia (95.0%), anemia (21.7%), and thrombocytopenia (5.0%). There were six patients who dropped out from the protocol by neutropenia. Grade 3 non-hematologic toxicities were observed as follows: nausea (3.3%), vomiting (1.7%), neuropathy (5.0%), myalgia (6.7%) and constipation (1.7%). No grade 4 non-hematologic toxicity was observed. CONCLUSION: This TC regimen is feasible for endometrial cancer patients.

Carcinoma of the fallopian tube: Results of a multi-institutional retrospective analysis of 127 patients with evaluation of staging and prognostic factors.

The aim of this study was to determine the impact of prognostic factors in primary fallopian tube carcinoma (PFTC). All cases of PFTC diagnosed between 1990 and 2010 were retrieved from the files of 6 academic centers. The cases were staged according to a modification of the International Federation of Obstetrics and Gynecology staging system proposed by Alvarado-Cabrero et al (Gynecol Oncol 1999; 72: 367-379). One hundred twenty-seven PFTC cases were identified. The mean age of the patients was 64.2 years. Stage distribution was as follows: 72 (57%), stage I; 19 (15%), stage II; 28 (22%), stage III; and 8 (6.2%), stage IV. Depth of infiltration of the tubal wall was an independent prognostic factor in stage I cases (P < .001). Carcinomas located in the fimbriated end even without invasion had a worse prognosis than did carcinomas involving the tubal portion of the organ. The presence of vascular space invasion correlated with the depth of tubal wall invasion (P = .001) and the presence of lymph node metastases (P = .003). Tumor grade significantly correlated with survival (P < .0001), but histologic type was of marginal significance and only if it was grouped as nonserous/non-clear cell vs serous/clear cell (P = .04). The depth of invasion of the tubal wall and the presence of carcinoma in the fimbriated end even without invasion are important prognostic indicators. The modified International Federation of Obstetrics and Gynecology staging system should be used on a routine basis in all carcinomas of the fallopian tube.

Clinical Features of Borderline Ovarian Seromucinous Tumor.

BACKGROUND/AIM: Ovarian seromucinous tumor is a histological type of ovarian neoplasm. Although seromucinous borderline tumors (BSMT) are associated with endometriosis, the frequency of their occurrence is low, and many aspects of their behavior remain unclear. In this study, we aimed to clarify the clinicopathological factors of BSMT. PATIENTS AND METHODS: We retrospectively reviewed 32 patients with pathologically diagnosed BSMT who underwent surgery at Jikei University Hospital. The survey items were patient characteristics, such as age, initial symptoms, preoperative tumor markers, surgical procedure and stage of surgery, presence of endometriosis, and recurrence. RESULTS: The median age was 45 years. Lower abdominal pain was the most common chief complaint, about one-third of patients were asymptomatic; one-sixth were discovered during follow-up for endometriosis. The majority had a high serum CA19-9 level. Twenty-five patients (78.1%) had unilateral masses, whereas seven patients (21.9%) had bilateral masses. More than 90% of the cases had coexisting endometriosis histologically. Thirty cases (93.8%) were stage I, only two were stage II, and none were stage III or IV. Recurrence was observed in two cases: one was borderline malignant and the other was a carcinoma. CONCLUSION: BSMT is a rare form of borderline malignancy. Its preoperative diagnosis is often difficult because of various clinical findings, but a history of endometriosis and an elevated serum CA19-9 level may aid in some cases.

Long-term survival in patients with clear cell adenocarcinoma of ovary treated with irinotecan hydrochloride plus cisplatin therapy as first-line chemotherapy.

AIM: Several previous reports showed that irinotecan hydrochloride plus cisplatin (CPT-P) was a candidate first-line chemotherapy regimen for clear cell adenocarcinoma of the ovary (CCC). However, long-term survival in CCC patients treated with CPT-P as first-line chemotherapy remains to be determined. The aim of the present study was to evaluate the long-term results of CPT-P as first-line chemotherapy for CCC. MATERIAL AND METHODS: We performed a retrospective review of 31 patients with CCC who were treated with CPT-P between 1996 and 2004. RESULTS: The median follow-up period was 91 months. The estimated 8-year overall survival (OS) rate in all patients was 64.5%, while the rate in 18 stage I, 21 stage I/II, and 10 stage III/IV patients was 88.9%, 85.7%, and 20.0%, respectively. The estimated 8-year OS rate in patients with pT1/pT2 disease was 87.0%, while the 3-year OS rate in patients with pT3 disease was 0%. Univariate analysis using the log-rank test revealed that Eastern Cooperative Oncology Group performance-status 1, pT3 stage, and presence of residual disease (stage II-IV) were significantly correlated with shortened patient survival. Multiple regression analysis revealed that pT3 predicted worse OS in patients with CCC than pT1 (P<0.001) or pT2 disease (P < 0.005). CONCLUSION: The long-term results suggest CPT-P as a candidate in first-line chemotherapy for CCC in not only stage I, but also in optimally debulked stage II-IV patients with pT1/pT2 disease.

Pilot study of CD147 protein expression in epithelial ovarian cancer using monoclonal antibody 12C3.

AIM: CD147 is a membrane glycoprotein that is expressed in various cancer cells and is involved in tumor invasion and metastasis by inducing stromal fibroblastic cells to produce matrix metalloproteinases. This study was carried out to evaluate the correlation between CD147 expression and various clinicopathologic parameters, including histological grade and prognosis in a small sample set of human ovarian cancer patients. MATERIAL AND METHODS: Paraffin-embedded surgical tissue samples from 25 patients with ovarian serous and endometrioid adenocarcinoma were stained with anti-CD147 antibody (monoclonal antibody 12C3: MoAb 12C3) for immunohistochemical analysis. RESULTS: CD147 protein was expressed in 84.0% (21 of 25 cases) of cancerous lesions, but not in normal lesions. CD147 expression by ovarian cancer cells was inversely correlated with overall survival. There was no correlation between CD147 expression and histological grade. CONCLUSIONS: These results suggest that measurement of CD147 expression may enhance the understanding of the pathophysiology of epithelial ovarian cancer.

Efficacy of edoxaban for the treatment of gynecological cancer-associated venous thromboembolism: analysis of Japanese real-world data.

OBJECTIVE: Direct oral anticoagulants (DOACs) are increasingly being used for the treatment of cancer-associated venous thromboembolism (CAT). However, there is limited evidence of the efficacy of DOACs for the treatment of gynecological CAT. Thus, this study aimed to investigate the efficacy and safety of edoxaban for the treatment of gynecological CAT using Japanese real-world data. METHODS: We reviewed the medical records of patients with 371 gynecological cancer who received edoxaban or vitamin K antagonist (VKA) between January 2011 and December 2018. RESULTS: Altogether, 211 and 160 patients were treated with edoxaban and VKA, respectively. Fourteen patients (6.8%) in the edoxaban group and 22 (13.8%) in the VKA group showed recurrence of venous thromboembolism (VTE). Cumulative VTE recurrence was not significantly different between the 2 groups (p=0.340). Adverse events occurred in 15 (7.1%) and 11 (6.9%) patients in the edoxaban and VKA groups, respectively (p=0.697). Subgroup analysis of the edoxaban and VKA groups according to different tumor types, including ovarian, endometrial, and cervical cancer, showed equivalent outcomes in terms of VTE recurrence and adverse events. Patients without pulmonary embolism (PE) were mostly omitted from initial unfractionated heparin (UFH) therapy prior to administration of edoxaban. However, this did not increase the recurrence of VTE. CONCLUSION: This study confirmed that edoxaban is effective and safe for the treatment of gynecological CAT. This finding was consistent for different types of gynecological cancer. Additionally, initial UFH therapy prior to the administration of edoxaban may be unnecessary for patients without PE.