Daisuke Miyahara

Postoperative pulmonary embolism including asymptomatic cases in gynecologic oncology.

Introduction: So far, there has been no report addressing the actual rate of asymptomatic pulmonary embolism (PE). The present study was conducted to clarify the incidence and the characteristics of postoperative PE including asymptomatic cases in gynecologic oncology. Methods: A total of 2107 gynecologic surgery cases that were performed from January 1996 to December 2006 at the National Kyushu Cancer Center were included. Pulmonary embolism was diagnosed using a lung scan, multi-detector row computed tomography, or pulmonary angiography. The clinical factors, including prophylaxes, were analyzed by univariate and multivariate analyses. Results: PE was diagnosed in 45 patients (2.14%). Six (13.3%) of the 45 patients had respiratory symptoms or signs, and 16 patients (35.6%) had no symptoms or signs except for a SpO2 level decrease. PE was diagnosed within 4 days after the surgery in 42 patients (93.3%). There were 1 massive, 2 recurrent, and no fatal PEs. A multivariate analysis demonstrated the incidence of PE to be associated with age (odds ratio, 1.957; 95% confidence interval, 1.497-2.559), operation time (1.664; 1.180-2.346), body mass index (2.457; 1.735-3.479), surgical position (2.253; 1.468-3.458), and the use of a perioperative intermittent pneumatic compression device (0.389; 0.229-0.659). Conclusions: A substantial number of postoperative PEs were occult, and identification of high-risk patients and routine SpO2 level monitoring would reduce the diagnostic delay of PE after gynecologic surgery. Increasing age, longer operation time, and obesity were risks. The use of a perioperative intermittent pneumatic compression device in multimodal conditions might thus prevent PE.

MicroRNA-135a-3p as a promising biomarker and nucleic acid therapeutic agent for ovarian cancer

Ovarian cancer is the most lethal gynecologic malignancy. Recently, several molecularly targeted anticancer agents have been developed for ovarian cancer; however, its prognosis remains extremely poor. The development of molecularly targeted therapy, as well as companion diagnostics, is required to improve outcomes for patients with ovarian cancer. In this study, to identify microRNAs (miRNAs) involved in the progression of ovarian cancer we analyzed serum miRNAs in patients with ovarian cancer using miRNA array and quantitative RT‐PCR and examined the anticancer properties of miRNA expression in ovarian cancer cells. In patients with ovarian cancer, high amount of miR‐135a‐3p in serum samples was significantly associated with favorable clinical prognosis. The amount of miR‐135a‐3p was significantly decreased in patients with ovarian cancer compared with patients with ovarian cysts or normal ovaries. In SKOV‐3 and ES‐2 human ovarian cancer cells, enhanced expression of miR‐135a‐3p induced drug sensitivity to cisplatin and paclitaxel and suppressed cell proliferation and xenograft tumor growth. These findings suggest that miR‐135a‐3p may be considered as a biomarker and a therapeutic agent in ovarian cancer.

Monitoring of endometrial K-ras mutation in tamoxifen-treated patients with breast cancer.

Introduction: A high incidence of endometrial K-ras mutations has been reported in tamoxifen (TAM)-treated patients with breast cancer. We examined the changes in the frequency of the endometrial K-ras mutations after the cessation of TAM treatment. Methods: DNA was extracted from fresh cytological or polypectomy samples of the endometrium in 28 patients who had undergone TAM treatment of breast cancer. Mutations were detected by an enriched polymerase chain reaction-enzyme-linked minisequence assay (Sumitomo Metal Industry, Inc, Tokyo, Japan). K-ras codon 12 mutations were monitored in these 28 patients. Results: An initial examination detected endometrial K-ras mutations in 13 of the 28 patients. However, repeated examinations performed after cessation of TAM treatment did not detect endometrial K-ras mutations in any of these 13 patients. No endometrial K-ras mutation has been detected in the repeated examinations performed for these patients for more than 2 years since the cessation of TAM treatment. In addition, the 15 patients who did not have endometrial K-ras mutations in the initial examination did not demonstrate them in repeat examinations. Conclusions: The cessation of TAM treatment may reduce the risk of developing endometrial cancers through K-ras mutations.

Association of Serum HB-EGF Value and Response to Chemotherapy in Patients with Recurrent Ovarian Cancer

Background/Aim: Many anticancer agents including molecularly-targeted drugs have been developed for ovarian cancer. However, the prognosis of recurrent ovarian cancer remains extremely poor. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is reported as a rational target for ovarian cancer therapy. Moreover, serum HB-EGF expression is recognized as a biomarker in patients with primary ovarian cancer. Materials and Methods: We analysed serum samples with recurrent ovarian cancer at the Fukuoka University Hospital from April 2009 to March 2014. To assess the clinical significance of serum HB-EGF in recurrent ovarian cancer, the association between serum HB-EGF levels and prognosis in patients with recurrent ovarian cancer was examined using ELISA. Results: Patients with high serum HB-EGF expression showed a significantly poor response to second-line chemotherapeutic agents compared with patients with low HB-EGF levels. Conclusion: HB-EGF expression in serum may be a potential therapeutic indicator for novel HB-EGF-targeted therapy in recurrent ovarian cancer.

A case of secondary amenorrhea caused by uterine myoma successfully treated by a combined laparoscopic and hysteroscopic approach

Uterine myoma is a common disease. Twenty to 80% of women develop myoma before they reach age 50 years.1,2 Common symptoms of myoma are menorrhagia, abdominal pain, or subfertility. Here, we report a rare case of secondary amenorrhea with cyclic abdominal pain secondary to obstructive myoma. A 43-year-old G1P1 woman presented at our hospital with secondary amenorrhea. She had undergone cesarean section 10 years earlier, and her regular period resumed after several months. However, for the past 3 years, she had had intermittent abdominal pain with amenorrhea. She was 163 cm tall and weighed 50 kg. Pelvic examination revealed a uterus of normal size and no adnexal masses. Transvaginal ultrasonography showed a uterus of normal size with normal endometrial thickness (4 mm), normal ovaries, and no echo-free space. It also revealed a hyperechoic solid mass near a cesarean section scar (Figure 1A). A blood test revealed that she had an elevated carbohydrate antigen-125 level (96.6 U/ mL) and her estradiol and follicle-stimulating hormone levels were 240 pg/mL and 2.3 mIU/mL, respectively. She had no withdrawal bleeding after a progesterone test, but presented with abdominal pain and free fluid in the pouch of Douglas on ultrasound. Magnetic resonance imaging demonstrated an inhomogeneous mass (20 mm 14 mm 8 mm) near a cesarean section scar (Figure 1B). The presumed diagnosis at that time was secondary amenorrhea caused by obstructive myoma. During the next menstrual period, the patient underwent hysteroscopy and laparoscopy under general anesthesia. Laparoscopy indicated that the reproductive organs and any other organs examined were normal in size and appearance. However, it revealed sings of bleeding through the fallopian tubes into the peritoneal cavity, as well as the presence of endometriotic lesions in the peritoneal cavity (Figures 2A and 2B). The endometriotic lesions were vaporized using argon plasma (Figure 2C). Histological confirmation of endometriosis was not performed. Hysteroscopy was performed using a standard 24Fr irrigating monopolar resectoscope. Cervical priming before surgery was not done because she complained of severe pain. The cervix was dilated with a size 10 Hagar dilator. The uterine cavity was irrigated using Uromatic S (Baxter,