Hideaki Yahata

Multicenter Phase II Study of Fertility-Sparing Treatment With Medroxyprogesterone Acetate for Endometrial Carcinoma and Atypical Hyperplasia in Young Women

PURPOSE To assess the efficacy of fertility-sparing treatment using medroxyprogesterone acetate (MPA) for endometrial carcinoma (EC) and atypical endometrial hyperplasia (AH) in young women. PATIENTS AND METHODS This multicenter prospective study was carried out at 16 institutions in Japan. Twenty-eight patients having EC at presumed stage IA and 17 patients with AH at younger than 40 years of age were enrolled. All patients were given a daily oral dose of 600 mg of MPA with low-dose aspirin. This treatment continued for 26 weeks, as long as the patients responded. Histologic change of endometrial tissue was assessed at 8 and 16 weeks of treatment. Either estrogen-progestin therapy or fertility treatment was provided for the responders after MPA therapy. The primary end point was a pathologic complete response (CR) rate. Toxicity, pregnancy rate, and progression-free interval were secondary end points. RESULTS CR was found in 55% of EC cases and 82% of AH cases. The overall CR rate was 67%. Neither therapeutic death nor irreversible toxicities were observed; however, two patients had grade 3 body weight gain, and one patient had grade 3 liver dysfunction. During the 3-year follow-up period, 12 pregnancies and seven normal deliveries were achieved after MPA therapy. Fourteen recurrences were found in 30 patients (47%) between 7 and 36 months. CONCLUSION The efficacy of fertility-sparing treatment with a high-dose of MPA for EC and AH was proven by this prospective trial. Even in responders, however, close follow-up is required because of the substantial rate of recurrence.

Increased nuclear localization of transcription factor YB-1 in acquired cisplatin-resistant ovarian cancer

Abstract Purpose. Nuclear expression of Y box-binding protein (YB-1), a member of the DNA-binding protein family, was recently reported to have a much higher concentration in cisplatin-resistant cancer cell lines than in their drug-sensitive parental counterparts, suggesting the ability to induce cisplatin resistance. Ovarian cancer has been generally treated with cisplatin-based chemotherapy and often recurs due to acquired cisplatin resistance. The aim of our study is to elucidate the association between nuclear YB-1 and cisplatin resistance in human ovarian cancer using cultured cell lines and surgical specimens. Methods. Intracellular YB-1 localization was examined by Western blot analysis for both cisplatin sensitive and resistant human ovarian cancer cell lines. Moreover, 35 pairs of surgical specimens derived from primary and matched recurrent ovarian cancers of the same patient were evaluated for their nuclear YB-1 expression by immunohistochemical staining. Results. Western blot analysis for nuclear and cytoplasmic extracts indicated that cisplatin-resistant cells showed much higher nuclear YB-1 expression than sensitive parental cells. Immunohistochemical analysis showed that ten paired cases turned from negative nuclear YB-1 in primary lesions to positive nuclear YB-1 in recurrent lesions, whereas only two paired cases showed a reverse turn from positive to negative. Conclusions. The expression of YB-1 in the nucleus seems to be associated with acquired cisplatin resistance in ovarian cancers. Nuclear YB-1 might be a useful predictive marker indicating cisplatin sensitivity and/or a target molecule to treat recurring ovarian cancers by cisplatin-based second-line chemotherapy.

Uterine artery embolization along with the administration of methotrexate for cervical ectopic pregnancy: technical and clinical outcomes.

OBJECTIVE The objective of our study was to evaluate the technical and clinical outcomes of uterine artery embolization (UAE) along with the administration of methotrexate (MTX) for cervical ectopic pregnancy with vaginal bleeding as an alternative nonsurgical treatment to control bleeding and preserve fertility. MATERIALS AND METHODS Eight patients (age range, 24-37 years; mean age, 30.1 years) with cervical ectopic pregnancy were treated with UAE using gelatin sponge particles to control vaginal bleeding. In seven patients, the administration of MTX was performed before, after, or before and after UAE. The follow-up periods after UAE ranged from 4 to 46 months (median, 8 months). We evaluated the UAE technique, clinical outcomes, complications, and fertility. RESULTS In all patients, UAE could control active vaginal bleeding on gynecologic examination. In six patients, the cervical ectopic pregnancy was dramatically resolved. In the other two patients presenting with both fetal heartbeat before UAE and persistent high HCG levels, active vaginal rebleeding was observed. The rebleeding was successfully controlled by a second UAE procedure. No major complication related to UAE was detected. The uterus could be preserved in all patients. In seven patients, normal menses resumed within 2 months after UAE. In only one patient, amenorrhea continued 8 months after UAE. In all three patients who could be followed for 2 years or more, three had subsequent successful natural pregnancies, and two patients had live births. CONCLUSION UAE along with the administration of MTX is effective in treating cervical ectopic pregnancy with vaginal bleeding while allowing the preservation of fertility.

Ovarian undifferentiated carcinoma resembling giant cell carcinoma of the lung

Giant cell carcinoma (GCC) is a highly aggressive variant of sarcomatoid carcinoma of the lung. To date, however, there have been no reported cases of ovarian carcinoma mainly composed of GCC. Herein is reported the case of a 54‐year‐old Japanese woman with an undifferentiated ovarian carcinoma producing granulocyte colony‐stimulating factor (G‐CSF) and an inflammatory cytokine. Histologically, the tumor was composed of cohesive nests or discohesive pleomorphic mononucleated or multinucleated tumor giant cells, accompanied by inflammatory cell infiltration and emperipolesis. Immunohistochemically, the tumor cells were focally positive for epithelial membrane antigen and cytokeratin 7. Clinically, after the initial surgery, the tumor had rapid regrowth along with the production of G‐CSF and an inflammatory cytokine. Adjuvant chemotherapy was administered but induced severe heart failure and severe neutropenia, probably due to the presence of hypercytokinemia and excess G‐CSF. Upon the appearance of these fatal side‐effects the chemotherapy was immediately discontinued and replaced with radiotherapy. The recognition of this type of ovarian tumor is important for clinical management, because adjuvant chemotherapy is the standard treatment for clinical management of epithelial ovarian cancer.

Prophylactic effect of pemirolast, an antiallergic agent, against hypersensitivity reactions to paclitaxel in patients with ovarian cancer

We have previously shown that sensory nerve peptides contribute to the pathogenesis of pulmonary hypersensitivity reactions (HSRs) to paclitaxel in rats. Moreover, pemirolast, an antiallergic agent, reverses the HSRs to paclitaxel, although the mechanism is considered to result from the blockade of paclitaxel‐induced release of sensory peptides, rather than the inhibition of histamine release. In the present study, we investigated the preventive effect of pemirolast against acute HSRs in a total of 84 patients who undertook postoperative paclitaxel plus carboplatin chemotherapy every 4 weeks for ovarian cancer. Patients were assigned to receive oral lactose (placebo) or pemirolast (10 mg), 2 hr before paclitaxel infusion. All patients received conventional premedication, including oral diphenhydramine, intravenous ranitidine and intravenous dexamethasone, 30 min before paclitaxel infusion. The HSRs that led to the discontinuance of paclitaxel infusion (grade ≥≥2) occurred in 5 of 42 patients in placebo group, whereas none of pemirolast‐treated 42 patients showed any signs of HSRs. Plasma histamine concentrations were not changed after paclitaxel infusion in either group. Our present findings suggest that pemirolast is potentially useful for prophylaxis of paclitaxel‐induced HSRs. In this respect, the use of pemirolast as premedication is expected to be beneficial to the safety management in patients who undergo chemotherapy containing paclitaxel.

1481PDAPREPITANT FOR THE PREVENTION OF CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING WITH A MODERATELY EMETOGENIC CHEMOTHERAPY: A MULTICENTER, PLACEBO-CONTROLLED, DOUBLE-BLIND, RANDOMIZED STUDY IN JAPANESE GYNECOLOGIC PATIENTS RECEIVING PACLITAXEL AND CARBOPLATIN

ABSTRACT Aim: Aprepitant is a new neurokinin-1 receptor antagonist developed as a treatment for chemotherapy-induced nausea and vomiting (CINV). Several reports have shown that aprepitant is very effective for the prevention of CINV with highly emetogenic chemotherapy (HEC) in cisplatin-based regimens. However the efficacy of aprepitant for moderately emetogenic chemotherapy (MEC), such as paclitaxel plus carboplatin (TC), is still unclear. We conducted a multicenter, placebo-controlled, double-blind, randomized study in Japanese gynecologic patients who received a TC regimen. Methods: This phase III, randomized, double-blind study enrolled patients from nine institutions with a diagnosis of ovarian, endometrial, or cervical cancer who were scheduled to receive paclitaxel (175-180mg/m2) and carboplatin (AUC=5-6) for the first time. Patients received aprepitant or placebo with a 5-HT3 antagonist (except palonosetron) and dexamethasone before chemotherapy. Patients recorded nausea and vomiting episodes in a diary. Endpoints were proportions of patients with no vomiting, no significant nausea and complete response ( no vomiting and no rescue medication) for five days after chemotherapy. Results: Of 324 randomized patients, 297 patients (151 in the aprepitant group; 146 in the placebo group) were evaluable for efficacy and toxicity. The percentages of patients with no vomiting (84.8% vs 61.6%, p Conclusions: The combination of aprepitant, a 5-HT3 antagonist, and dexamethasone demonstrated efficacy for CINV prevention with MEC in patients with gynecologic cancer receiving a TC regimen. Disclosure: All authors have declared no conflicts of interest.

Comparison of the Anterior Colporrhaphy Procedure and the Marshall-Marchetti-Krantz Operation in the Treatment of Stress Urinary Incontinence among Women

Objective: To compare retrospectively the efficacy of the anterior colporrhaphy procedure (AC) and the Marshall‐Marchetti‐Krantz operation (MMK) in the treatment of stress urinary incontinence (SUI).

Successfully treated abdominal pregnancy causing hemoperitoneum using combined surgical and systemic methotrexate therapy: A case report and review of cases treated at kyushu university hospital

Abdominal pregnancy is a rare condition that accounts for only 1% of all ectopic pregnancies but results in high maternal morbidity and mortality. We present a case of abdominal pregnancy with massive peritoneal bleeding successfully treated using systemic methotrexate (MTX). A 34-year-old woman with amenorrhea for 8 weeks and a positive pregnancy test was referred for evaluation of ectopic pregnancy. Transvaginal ultrasonographic scan showed a gestational sac measuring 25 mm in diameter containing a viable embryo in the cul-de-sac and a considerable amount of free fluid in the patients lower abdomen and pelvis. Laboratory parameters showed that her hemoglobin concentration was 5.8 g/dl and serum human chorionic gonadotropin concentration was 13,195 mIU/ml. Emergency surgery revealed an abdominal pregnancy in the cul-de-sac and a massive intra-abdominal hemorrhage. After a hemostasis procedure, the patient was successfully treated using systemic MTX. We also present the review of abdominal pregnancy cases treated using systemic MTX at our institution over 10 years. Systemic MTX treatment for abdominal pregnancy is safe and effective and makes it possible to avoid the risk of excessive bleeding by surgical resection of the implantation site.

Value of Intraoperative Cytological and Pathological Sentinel Lymph Node Diagnosis in Fertility-Sparing Trachelectomy for Early-Stage Cervical Cancer

Background and Objectives: Trachelectomy, a fertility-sparing surgery for early-stage cervical cancer, can be performed only when there is no extrauterine extension present. Therefore, identifying the sentinel lymph nodes (SLNs) and using them to obtain an intraoperative pathologic diagnosis can provide information on the feasibility and safety of trachelectomy. Our aim was to assess the value of an intraoperative SLN diagnosis. Methods: We retrospectively analyzed the accuracy of intraoperative imprint cytology and frozen-section examination in 201 patients at our institution in whom trachelectomy was planned. Results: All patients could be evaluated for SLNs; a total of 610 SLNs were analyzed. Although the specificity of both imprint cytology and frozen-section examination was 100.0%, the sensitivity was only 58.6 and 65.5%, respectively. The diagnostic sensitivity was higher in 2-mm slices along the short axis than on bisection along the longitudinal axis. Imprint cytology correctly diagnosed 2 patients who had false-negative results on frozen section. The nature of the metastatic foci that caused an intraoperative false-negative diagnosis was either micrometastasis or isolated tumor cells. Conclusions: The accuracy of intraoperative SLN diagnosis requires improvement, especially when small metastatic foci are present.

Uterine Myxoid Leiomyosarcoma with Tumor Embolism Extending into the Right Atrium

Uterine myxoid leiomyosarcoma (MLMS) is an extremely rare variant of uterine leiomyosarcoma; only 56 cases were reported from 1982 to 2013. Uterine MLMS is characterized by a myxoid appearance and highly malignant behavior. We herein report a case involving a 65-year-old woman with uterine MLMS with a large tumor embolism that reached the right atrium. A total abdominal hysterectomy, bilateral salpingooophorectomy, and tumor embolism resection with the use of a heart-lung machine were performed. Epirubicin-ifosfamide chemotherapy in the adjuvant setting led to reductions in both the tumor emboli and peritoneal dissemination. The patient retained a good quality of life for 10 months after the initial surgery. She then developed progressive disease despite treatment with pazopanib. She died of her disease 14 months after the initial surgery. Although complete surgical resection of the tumor is desirable, tumor reduction surgery followed by adjuvant chemotherapy might help to retain a good quality of life. This is the first reported case of a primary uterine MLMS with tumor emboli.