Tomoko Hirakawa

Advanced small cell carcinoma of the uterine cervix treated by neoadjuvant chemotherapy with irinotecan and cisplatin followed by radical surgery

Small cell carcinoma of the uterine cervix is a rare form of cervical cancer characterized by extreme aggressiveness and poor prognosis because of its rapid growth, frequent distant metastases, and resistance to conventional treatment modalities. We report here a case of advanced-stage small cell carcinoma of the uterine cervix treated by neoadjuvant chemotherapy, followed by radical surgery, resulting in locoregional disease control. A 39-year-old Japanese woman was diagnosed as having stage IIIb small cell carcinoma of the uterine cervix. She was treated by neoadjuvant chemotherapy with irinotecan/cisplatin, followed by extended radical hysterectomy with pelvic and paraaortic lymphadenectomy. The patient was further treated by adjuvant chemotherapy with irinotecan/cisplatin. Intrapelvic recurrence has not been detected throughout the postoperative course. However, the patient died with distant metastases of the disease, 27 months following the initial treatment. It has been suggested that neoadjuvant chemotherapy therapy followed by radical surgery is a treatment option for advanced-stage small cell carcinoma of the uterine cervix for the locoregional disease control. Further studies are necessary to obtain information regarding multimodal treatment including sequence, duration, frequency, and type of effective chemotherapy agents to be used in the treatment of small cell carcinoma of the uterine cervix.

Decidualization Differentially Regulates microRNA Expression in Eutopic and Ectopic Endometrial Stromal Cells

Decidualization of the endometrium and endometriosis involves the morphological and biochemical reprogramming of the estrogen-primed proliferative stromal compartment under the continuing influence of progesterone. Here, we evaluated the involvement of microRNA in the decidualization processes of normal endometrial stromal cells (NESCs) and endometriotic cyst stromal cells (ECSCs). In vitro decidualization of NESCs and ECSCs was induced by long-term culture with a combination of 0.5 mmol/L of dibutyryl cyclic adenosine monophosphate and 100 nmol/L of dienogest. We investigated the effect of in vitro decidualization on the microRNA and messenger RNA (mRNA) expression profiles of the NESCs and ECSCs using global microarray techniques and an Ingenuity Pathways Analysis. Decidualization differentially enhanced the miR-30a-5p expression in the NESCs and the miR-210 expression in the ECSCs. The enhanced miR-30a-5p expression in the NESCs correlated with the increased mRNA expression of Krüppel-like factor 9 and period circadian clock 3 as well as the decreased mRNA expression of tolloid-like 1, tolloid-like 2, and paired-like homeodomain 1. The enhanced expression of miR-210 in the ECSCs correlated with the decreased mRNA expression of growth hormone receptor and thymidine kinase 1. Although there is no direct evidence, we speculate that the loss of miR-30a-5p-mediated mechanisms of decidualization and the acquisition of miR-210-mediated mechanisms of decidualization may be involved in the progesterone resistance in endometriosis. Further investigations are necessary to test this speculation.

Arcyriaflavin a, a cyclin D1–cyclin-dependent kinase4 inhibitor, induces apoptosis and inhibits proliferation of human endometriotic stromal cells: a potential therapeutic agent in endometriosis

BackgroundWe previously showed that microRNA-503 (miR-503) transfection into endometriotic cyst stromal cells (ECSCs) induced cell cycle arrest at the G0/G1 phase by suppressing cyclin D1. This finding prompted us to evaluate the potential therapeutic effects of cyclin D1 inhibitors in endometriotic cells. This study aimed to determine whether arcyriaflavin A, a representative inhibitor of cyclin D1–cyclin-dependent kinase 4 (CDK4), is beneficial in the treatment of endometriosis.MethodsECSCs were isolated from the ovarian endometriotic tissues of 32 women. The effects of arcyriaflavin A on cell viability and proliferation, vascular endothelial growth factor A expression, apoptosis, and cell cycle progression were evaluated using a modified methylthiazoletetrazolium assay, enzyme-linked immunosorbent assay (ELISA), Caspase-Glo® 3/7 assay, and flow cytometry.ResultsArcyriaflavin A significantly inhibited cell viability, proliferation, and angiogenesis of ECSCs as assessed using the 5-bromo-2-deoxyuridine (BrdU) and methylthiazoletetrazolium bromide (MTT) assays, and vascular endothelial growth factor (VEGF) ELISA. Arcyriaflavin A induced apoptosis as shown in the Caspase-Glo® 3/7 assay and cell death detection ELISA whilethe cell cycle was arrested at the G0/G1 phase.ConclusionThe findings indicate that cyclin D1–CDK4 inhibitors may be promising candidates for the treatment of endometriosis. This is the first study to demonstrate the potential usefulness of arcyriaflavin A as a therapeutic agent for endometriosis. Further studies of the effects of cyclin D1–CDK4 inhibitors on endometriosis may provide useful information on pathogenesis and treatment.

Functioning Endometrium and Endometrioma in a Patient with Mayer-Rokitanski-Kuster-Hauser Syndrome

Mayer-Rokitanski-Kuster-Hauser (MRKH) syndrome is a rare disease. A 27-year-old woman was admitted for primary amenorrhea and cyclic pelvic pain. Magnetic resonance imaging (MRI) revealed bilateral Müllerian remnants with functioning endometrium and a pelvic mass considered to be an endometriotic cyst. Bilateral Müllerian remnants were removed, and right ovarian cystectomy was performed at laparoscopic surgery. Accurate evaluation before the operation and informed consent are necessary to treat patients with MRKH syndrome.

Cadmium Chloride Induces the Expression of Metallothionein mRNA by Endometrial Stromal Cells and Amnion-Derived (WISH) Cells

Background: Metallothionein (MT) is known to bind to metals with high affinity. The potential for MT-1 mRNA expression in endometrial stromal cells (ESC) and amniotic cells in response to cytokines and cadmium chloride (CdCl2) was evaluated. Methods: Human ESC were cultured and treated with interleukin-1α, 12-O-tetradecanoylphobol 13-acetate (TPA), forskolin, transforming growth factor-β, and CdCl2. Amnion-derived (WISH) cells were also cultured and treated with the same reagents. The levels of MT mRNA were evaluated by Northern blot analysis in ESC and WISH cells. Results: In response to treatment with CdCl2 (0.01–10 µM), the expression of MT mRNA markedly increased in ESC and WISH cells in a dose-dependent manner. On the other hand, the expression of MT mRNA did not increase after treatment with interleukin-1α (1 nM), TPA (10 nM), forskolin (1 µM) or transforming growth factor-β (1 nM) in these cells. Conclusion: These findings indicate that MT expression in ESC and WISH cells is sensitive to the CdCl2 concentration, which is known to be evaluated in cigarette smokers. The present results suggest that increased levels of MT may affect metal metabolism at the feto-maternal interface.

Sclerosing stromal tumor of the ovaries overexpressing vascular endothelial growth factor: two cases

Sclerosing stromal tumor (SST) is histologically benign and accounts for 6% of the tumors derived from the stroma of the ovaries [1]. The patients who are diagnosed with an SST are predominantly in their 20s and 30s, unlike other stromal tumors [2,3]. Clinical imaging by magnetic resonance imaging (MRI) shows high vascularity and a solid part in SSTs. Many cases are suspected as a malignant tumor before surgery, during which, a unilateral ovary is removed without partial preservation. Case 1: A 25-year-old woman, gravida 0, para 0 who reported that she had never had sexual intercourse was admitted with the complaint of irregular and frequent menstruation every 15e30 days. A 10-cm-diameter pelvic mass at the front of the uterus was revealed by transrectal ultrasonography. MRI showed findings suggesting a possible malignant tumor in the right ovary (Figure 1). Gastroscopy and colon fiberoscopy were normal. Enhanced computed tomography showed no enlarged pelvic or para-aortic lymph nodes and no metastasis. The findings related to tumor markers [carbohydrate antigen (CA)-125, CA19-9, CA72-4, and human chorionic gonadotropin) and a hormonal analysis was within normal limits. A right salpingo-oophorectomywasperformedbecause the lesion wasmostly a solid tumor, but edematouswithyellowisheclear liquid (Figure 1). A fresh specimen from the solid part was used to obtain a frozen section, and massive ovarian edema was diagnosed.

Endometrioid adenocarcinoma arising from intestinal endometriosis

Purpose Gastrointestinal involvement of endometriosis may exist in up to 37% of women suffering from endometriosis, but malignant transformation of intestinal endometriosis is extremely rare. In this case report, we present a case of endometrioid adenocarcinoma arising from 2 different large bowel endometriotic sites, with a review of the reported cases of epithelial malignancies developed in gastrointestinal endometriosis. Case A 33-year-old nulligravid Japanese woman was admitted for the evaluation of massive ascites. The patient had undergone a laparoscopic bilateral cystectomy for bilateral endometriomas 8 years before. At laparotomy, we found massive serous ascites, diffuse peritoneal endometriotic lesions, edematous gastrointestinal tract with small surface nodules, stenosis of the sigmoid colon and firm and thick peritoneum. No endometriotic or tumorous lesions were found in the genital tract. The patient underwent a resection of the sigmoid colon, partial resection of the transverse colon, partial omentectomy and multiple biopsies of the peritoneum and ovaries. On the histologic examination, benign endometriosis, atypical hyperplasia and grade 1 endometrioid adenocarcinoma were found to be present in the transverse and sigmoid colon. Subsequently, the patient was treated with chemotherapy consisting of paclitaxel and carboplatin under a diagnosis of endometrioid adenocarcinoma arising in the intestinal endometriosis. The patient is well without evidence of disease 26 months following the surgery. Conclusions The tumors arising from intestinal endometriosis can clinically and pathologically mimic primary neoplasms of the gastrointestinal tract. Recognition of these lesions is important because primary gastrointestinal neoplasms are managed differently from those arising in endometriosis, and these differences may have significant clinical implications.

Retrospective analysis of outcomes of secondary debulking surgery for recurrent epithelial ovarian cancer with favorable prognostic factors

Ovarian cancer is the second most common gynecological malignancy, yet it has the highest case‐fatality ratio of all gynecologic malignancies. Surgery followed by combination platinum‐taxane chemotherapy is the standard approach to the management of primary epithelial ovarian cancer. However, standard treatment of patients with recurrent ovarian cancer remains poorly defined. Secondary cytoreductive surgery (SDS) at the time of relapse has been proposed as a means of improving the prognosis of recurrent ovarian cancer patients with a treatment‐free interval of at least 6 months.

Transfundal Uterine Incision Performed with Prophylactic Common Iliac Artery Balloon Occlusion for Patient with Placenta Previa Totalis

A 37-year-old primigravida at 35 weeks of gestation presented with known anterior wall dominant placenta previa totalis and suspected placenta accreta was successfully treated with transfundal uterine (transverse) incision performed with prophylactic common iliac artery balloon occlusion. This new surgical approach could be an alternative procedure for avoiding excessive blood loss during caesarean delivery.

Ruptured external iliac artery pseudoaneurysm following surgery for ovarian cancer: A case report and literature review

Ruptured pseudoaneurysm following pelvic surgery is a rare and fatal complication. Because of its rarity, existing evidence is limited to a small case series. A 60‐year‐old woman underwent staging laparotomy, including pelvic and para‐aortic lymphadenectomy, for ovarian cancer. On the 11th day, the patient developed a sudden lumbar pain and loss of consciousness, which resulted in a state of shock. She was diagnosed as having a pelvic abscess and ruptured external iliac artery pseudoaneurysm. We performed ligation of the external iliac artery to restrain hemorrhage and femoro‐femoral artery bypass to prevent infection, which saved the patients life. Our study had two findings. First, this is the first reported case of ruptured external iliac artery pseudoaneurysm following surgery for ovarian cancer. Second, treatment of ruptured pseudoaneurysm requires rapid hemostasis, prevention of infection, and revascularization.