Yoriko Tsuji

A randomized study of screening for ovarian cancer: a multicenter study in Japan.

Ovarian cancer is common in women from developed countries. We designed a prospective randomized controlled trial of ovarian cancer screening to establish an improved strategy for the early detection of cancers. Asymptomatic postmenopausal women were randomly assigned between 1985 and 1999 to either an intervention group (n= 41,688) or a control group (n= 40,799) in a ratio of 1:1, with follow-up of mean 9.2 years, in Shizuoka district, Japan. The original intention was to offer women in the intervention group annual screens by gynecological examination (sequential pelvic ultrasound [US] and serum CA125 test). Women with abnormal US findings and/or raised CA125 values were referred for surgical investigation by a gynecological oncologist. In December 2002, the code was broken and the Shizuoka Cohort Study of Ovarian Cancer Screening and Shizuoka Cancer Registry were searched to determine both malignant and nonmalignant diagnoses. Twenty-seven cancers were detected in the 41,688-screened women. Eight more cancers were diagnosed outside the screening program. Detection rates of ovarian cancer were 0.31 per 1000 at the prevalent screen and 0.38–0.74 per 1000 at subsequent screens; they increased with successive screening rounds. Among the 40,779 control women, 32 women developed ovarian cancer. The proportion of stage I ovarian cancer was higher in the screened group (63%) than in the control group (38%), which did not reach statistical significance (P= 0.2285). This is to our knowledge the first prospective randomized report of the ovarian cancer screening. The rise in the detection of early-stage ovarian cancer in asymptomatic postmenopausal women is not significant, but future decisions on screening policy should be informed by further follow-up from this trial.

Clinicopathologic features of ovarian cancer in patients with ovarian endometrioma

Objective:  The purpose of this study was to describe the clinicopathologic features of malignant transformation in patients with ovarian endometrioma, their treatment and outcome in the Kinki region, Japan.

Giant abdominal tumor of the ovary

A giant abdominal tumor can exert a mass effect on surrounding structures. We report here a 34‐year‐old single female who presented with an increased abdominal girth and was subsequently found to have a giant abdominal mass. Large volume aspiration (85 L) at a slow rate (1 L/min) was initially performed before surgical resection to prevent the development of severe clinical hypotension after large volume aspiration. The patient underwent left salpingo‐oophorectomy. Histology revealed a serous cystadenoma of the ovary. Systemic hemodynamics were sequentially measured during the perioperative period. The patient is now well.

Massive ovarian edema in pregnancy after ovulation induction using clomiphene citrate

BackgroundMassive ovarian edema is a benign enlargement of the ovary caused by accumulation of fluid occurring mainly in young women. Most cases are thought to result from venous and lymphatic obstruction.Case reportWe treated a 40-year-old multiparous pregnant woman with massive ovarian edema who had been received clomiphene citrate. She was admitted at 13th week of pregnancy for acute pelvic pain. Left oophorectomy was performed, and pathologic examination disclosed massive ovarian edema. Our report is the first case of massive ovarian edema with pregnancy after ovulation induction using clomiphene citrate.

Two cases of pregnant women with ovarian endometrioma mimicking a malignant ovarian tumor

The detection of an ovarian mass during pregnancy is often a diagnostic challenge. We describe 2 cases of ovarian endometrioma during pregnancy with marked mural nodules on the cyst wall. The sonographic and MR imaging findings mimicked ovarian cancer. Surgical intervention may still be inevitable to exclude the possibility of malignancy.

Inhibition of cell death and induction of G2 arrest accumulation in human ovarian clear cells by HNF-1β transcription factor: chemosensitivity is regulated by checkpoint kinase CHK1.

Objective Appropriate cell cycle checkpoints are essential for the maintenance of normal cells and chemosensitivity of cancer cells. Clear cell adenocarcinoma (CCA) of the ovary is highly resistant to chemotherapy. Hepatocyte nuclear factor-1β (HNF-1β) is known to be overexpressed in CCA, but its role and clinical significance is unclear. We investigated the role of HNF-1β in regulation of the cell cycle in CCA. Methods To clarify the effects of HNF-1β on cell cycle checkpoints, we compared the cell cycle distribution and the expression of key proteins involved in CCA cells in which HNF-1β had been stably knocked down and in vector-control cell lines after treatment with bleomycin. HNF-1β (+) cells were arrested in G2 phase because of DNA damage. Results HNF-1β (−) cells died because of a checkpoint mechanism. G2 arrest of HNF-1β (+) cells resulted from sustained CHK1 activation, a protein that plays a major role in the checkpoint mechanism. HNF-1β (+) cells were treated with a CHK1 inhibitor after bleomycin treatment. Flow cytometric analysis of the cell cycle demonstrated that DNA damage–induced G2-arrested cells were released from the checkpoint and killed by a CHK1 inhibitor. Conclusions The chemoresistance of CCA may be due to aberrant retention of the G2 checkpoint through overexpression of HNF-1β. This is the first study demonstrating cell cycle regulation and chemosensitization by a CHK1 inhibitor in CCA.

Prevalence of Ovarian Cancer among Women with a CA125 Level of 35 U/ml or Less

Background: The optimal upper limit of the normal range for CA125 in ovarian cancer screening is unknown. We investigated the prevalence of ovarian cancer among women in the Shizuoka Cohort Study on Ovarian Cancer Screening (SCSOCS) trial who had an abnormal ultrasound (US) and a CA125 level of 35 U/ml or less. Methods: Of 48,027 women enrolled in the SCSOCS trial, 40,801 women never had a CA125 level of more than 35 U/ml, and underwent transvaginal US. Results: Among the 40,801 women (age range 45–85 years), 4,859 women had an abnormal transvaginal US examination (category 1 [simple morphology], 4,741 women, and category 2 [complex morphology], 118 women). Of the 4,859 women, 981 (912 with the category 1 and 69 with the category 2) had a surgery. Of the 981 women, ovarian cancer was diagnosed in 8 (0.815%), and 5 of these 8 cancers (63%) were in stage I. The prevalence of ovarian cancer with abnormal US was 0.207% among women with a CA125 level of up to 15 U/ml, 0.488% among those with values of 15–20 U/ml, 0.685% among those with values of 20–25 U/ml, 2.04% among those with values of 25–30 U/ml, and 6.12% among those with values of 30–35 U/ml. Conclusions: Surgery-detected ovarian cancer is not rare among women with CA125 levels of 35 U/ml or less – levels generally thought to be in the normal range.

Bikunin suppresses expression of pro-inflammatory cytokines induced by lipopolysaccharide in neutrophils.

Activated neutrophils contribute to the development of preterm delivery. Because of its ability to suppress inflammation, bikunin, a Kunitz-type protease inhibitor, is currently in clinical trials. To investigate the molecular mechanism of this inhibition, we analyzed the effect of bikunin on pro-inflammatory cytokine production and nuclear factor-kappaB (NF-κB) activation in mouse neutrophils stimulated by lipopolysaccharide (LPS), an inflammatory inducer. Here, we show that bikunin: (i) blocks LPS-induced secretion of pro-inflammatory cytokines, including TNF-α and IL-1β, in a dose-dependent manner; (ii) has an inhibitory effect on cytokine production at a concentration of 0.2 µM, reaching 65% inhibition at the highest doses of bikunin tested (5 µM); (iii) has the suppressive capacity of ERK1/2 and p38 signaling pathways; and (iv) inhibited sequentially the LPS-induced phosphorylation of IκB-α, degradation of IκB-α, and nuclear translocation of NF-κB. When the MAPK data are analyzed, a significant decrease in phosphorylation is not seen at 0.2 µM bikunin but is at 1.0 µM dosing. Bikunin can inhibit LPS-induced neutrophil activation and cytokine release, although it is unlikely that it works primarily through the inhibition of MAPK phosphorylation. These data suggest that such effects are important in vivo and play a major contributory role in abrogation of neutrophil-mediated inflammatory responses, such as preterm delivery.

Late onset of pulmonary embolism caused by lymphocyst following pelvic lymphadenectomy.

Herein is reported a case of late‐onset pulmonary embolism following pelvic surgery, despite prophylactic measures in the perioperative period. Twenty‐six days after hysterectomy and pelvic lymphadenectomy for endometrial carcinoma, an 83‐year‐old woman developed a pulmonary embolism. This was caused by pelvic lymphocyst, which, in turn, led to chronic compression of the right external iliac vein. This case strongly suggests that prolonged postoperative thromboembolic prophylaxis should be considered in elderly patients undergoing lymphocyst following pelvic surgery.

Malignancy and Thrombosis

The association between cancer and an increased incidence of venous thromboembolism (VTE; Trousseau syndrome) is well characterized. This chapter reviews the pertinent literature related to VTE in patients with malignancy and the impact and scope of cancer-associated thrombosis, possible risk factors, etiology, pathogenesis, current practice patterns, and future directions.