Kumio Yamamoto

Clinical Predictors in the Natural History of Uterine Leiomyoma: Preliminary Study

This study was conducted to examine the correlation between uterine vascularity and natural history of uterine leiomyoma. Seventy women with leiomyoma participated in this study. Measurements of uterine and leiomyoma volume, as well as blood flow characteristics of the main uterine artery and leiomyoma arteries, were made every 3 months for 1 year. Leiomyoma arteries could be detected in 52 (51.5%) of 101 leiomyomas. Leiomyoma volume increased in 24 (46.2%) of 52 leiomyomas with leiomyoma artery. However, the leiomyoma volume increased in only three (6.1%) of 49 leiomyomas without leiomyoma artery. No difference was found between the pulsatility index of the leiomyoma artery in the group with increased size and in the group with stable size. This study shows the vascularity of leiomyoma to be useful as a predictor of leiomyoma growth.

Differences between Occidental and Oriental postmenopausal women in cutoff level of endometrial thickness for endometrial cancer screening by vaginal scan

Abstract The findings of this study suggest that the mean endometrial thickness and the cutoff thickness for detection of endometrial cancer in Occidental and Oriental postmenopausal women may differ.

Alteration of G2 Cell Cycle Regulators Occurs during Carcinogenesis of the Endometrium

Objectives: In this study, we examined the alteration of the G2 pathway in endometrial hyperplasia (EH) and endometrioid-type endometrial cancer (EC), and analyzed the relationship between the G2 pathway status and the p53 pathway status. Methods: A total of 103 cases (proliferative phase of the endometrium: 20, EH: 22, and endometrioid-type EC: 61 (I: 39, II: 5, III: 15, recurrence: 2)) were included in this study. We examined the ATM, chk2, CDC25C, cdc2, and cyclin B1 protein expression by immunohistochemistry. In 55 cases (EH: 15; EC: 40), we analyzed chk2 mutations by RT-PCR-SSCP. Results: There were no chk2 mutations in endometrial disease. Elevated or reduced expression rates of ATM, chk2, CDC25C, cdc2 and cyclin B1 were 4.5% (1/22), 0%, 0%, 0% and 4.5% (1/22) in EH and 3.3% (2/61), 4.9% (3/61), 13.1% (8/61), 9.8% (6/61) and 9.8% (6/61) in EC. Alteration of the G2 pathway was higher in EC (32.8%; 20/61) than in EH (9.1%; 2/22; p = 0.047). The G2 pathway was significantly higher in the altered p53 pathway group (48.4%; 15/31) than in the normal p53 pathway group (16.7%; 5/30) in EC (p = 0.0134). The altered p53 pathway tended to be related with the cdc2/cyclin B1 status (p = 0.0529). Conclusions: Alteration of the G2 pathway is thought to occur during carcinogenesis of the endometrium.

Preoperative diagnosis of a rudimentary uterine horn

Two cases of rudimentary uterine horn were able to be diagnosed prior to operation. The case of rudimentary horn with cavity non-communicating to unicornuate uterus was easy to diagnose. Transabdominal ultrasonography and computed tomography (CT) demonstrated the uterus to have binodular structure and two uterine lumina. However, the case with pregnancy was difficult to diagnose. In this case, thick myometrium could be seen by ultrasonography to enclose the sac. In both cases hysterosalpingography revealed unicornuate uterus.

Malignant rhabdoid tumour of the uterine cervix

A 36 year old nulliparous woman presented with abnormal vaginal bleeding for the previous month. She had a 7cm solid mass in the uterine cervix. The tumour was ®rm, oval and pigmented. Computed tomography and magnetic resonance imaging showed a solid mass and no evidence of metastasis. A cervical smear showed polygonal malignant cells with pigmentation (Fig. 1). The presumptive diagnosis was malignant melanoma. She underwent a total abdominal hysterectomy, but no evidence of metastatic disease was found. Following surgery, she had post-operative chemotherapy consisting of carboplatin, etoposide and ifosfamide: etoposide 100mg/m per day for three days at weeks 0, 3, 9, 12, 18, and 21. carboplatin 400mg/m at weeks 0, 3, 9, 12, 18, and 21, and ifosfamide 1.5g/m per day for ®ve days at weeks 6, 15, and 24. The woman was well and without disease 38 months after her operation. The tumour was ®rm, oval and pigmented and arose from posterior lip of cervix (Fig. 2). The majority of the tumour was composed of sheets of round or polygonal cells containing single, spherical eosinophilic cytoplasmic inclusions that sometimes compressed the nucleus. The nucleus was prominent and vesicular (Fig. 3). Masson-Fontana and haemosiderin staining revealed the pigment as haemosiderin (Fig. 4). Immunohistochemistry demonstrated that the eosinophilic cytoplasmic inclusions reacted strongly with anti-vimentin and were negative for cytokeratin, desmin, myoglobin, CD34, EMA, S100-protein and HMB45. Electron microscopy showed intermediate ®laments in the cytoplasm; however, typical paranuclear aggregates of intermediate ®laments arranged in concentric whorls were not present (Fig. 5). No junctional complexes, basal lamina, microvilli, melanosomes, premelanosomes or myo®lament arrays were identi®ed. The ®ndings were consistent in a malignant rhabdoid tumour.

Comparison between Transabdominal and Transvaginal Ultrasonography for Identifying Endometrial Malignancies

Transvaginal ultrasound (TVS) is generally considered superior to transabdominal ultrasound (TAS) in the estimation of endometrial abnormalities. A disadvantage of TVS is the limited field of view. The purpose of this study is a comparison between TAS and TVS for endometrial cancer screening. Ninety-one postmenopausal women were included. They were evaluated by TAS, TVS, and endometrial tissue sampling. The mean endometrial thickness estimated by TVS was larger than that obtained by TAS (p < 0.0001). Sensitivity and specificity of TAS were 83.3 and 58.8% and of TVS 100 and 54.1%, respectively. We conclude that TVS might be superior to TAS, especially in patients with a retroflexed uterus.

Preoperative assessment of myometrial invasion of endometrial cancer by MR imaging and intrauterine ultrasonography with a high-frequency probe: preliminary study.

This study was undertaken to assess the capabilities of intrauterine ultrasonography performed while inflating the endometrial cavity with fluid and magnetic resonance imaging as a means to assess the depth of myometrial invasion by endometrial cancer preoperatively. Twenty women with endometrial disorders underwent preoperative intrauterine ultrasonography and magnetic resonance imaging. We introduced the probe and hysteroscope simultaneously into the uterine cavity and observed both the uterine cavity surface and cross‐sectional uterine muscle. We classified the depth of myometrial invasion as none, superficial (less than half of the myometrium), or deep (more than half of the myometrium). The accuracy of magnetic resonance imaging and intrauterine ultrasonography in assessing the depth of myometrial invasion was 85%. In two cases, intrauterine sonography was able to demonstrate superficial myometrial invasion that could not be diagnosed by magnetic resonance imaging. In contrast, intrauterine ultrasonography was unable to diagnose myometrial invasion in two cases in which magnetic resonance imaging could diagnose it. Intrauterine sonography may be useful for estimation of myometrial invasion of endometrial cancer.

Phase I-ii study of neoadjuvant chemoradiotherapy followed by radical surgery in locally advanced cervical cancer

The usefulness of neoadjuvant chemotherapy (NAC) regimens has been reported; however, the effect of NAC for advanced stages (especially stage III-IVA) is thought to be insufficient. We conducted a phase I-II study of neoadjuvant chemoradiotherapy consisting of intra-arterial (i.a.) infusion of carboplatin and intracavitary brachytherapy in patients with locally advanced cervical cancer to achieve the new NAC method. Sixteen eligible patients included those with previously untreated stage IIB, III or IVA cancer with bulky tumor. Brachytherapy using iridium-192 was performed with concurrent i.a. chemotherapy with carboplatin (200, 300 and 400 mg/m2). Treatment was repeated every 4 weeks for a total of two cycles. Both hematologic and non-hematologic toxicities were generally mild. Grade 4 hematologic toxicity was observed in 12.5% and there were no grade III or IV non-hematologic toxicities. The optimal dose of carboplatin was determined to be 400 mg/m2. Among 16 patients, six showed complete response (37.5%) and nine showed partial response (56.3%), for an overall response rate of 93.8%. All 15 responding patients underwent radical surgery with a pelvic lymphadenectomy and postoperative radiotherapy. The combination of brachytherapy and i.a. chemotherapy with carboplatin is a promising regimen for NAC in locally advanced cervical cancer.

Continuous Local Injection of Carboplatin into the Uterine Cervix for Cervical and Endometrial Cancer: Preliminary Study

Platinum compounds are thought to be concentration- and time-dependent, but intravenous (i.v.) administration does not afford prolonged high platinum concentration in tumor tissue. In order to examine the influence of long-term local continuous (LC) injection of carboplatin, a pharmacokinetic study was performed. Twenty-six patients with uterine cancer were included. I.v. administration (11 patients): carboplatin (210 mg) was given i.v. and samples of target tissue were obtained at operation about 2 or 24 h after administration. LC administration (15 patients): the 21-gauge needle was implanted at the uterine cervix, and carboplatin was injected continuously (30 mg/day) for 3, 7 or 14 days using an external pump. The tissue platinum concentration was measured in the pelvic organs. The mean platinum levels at the cervix and vaginal wall in the LC (7 days) group were higher than those in the i.v. (2 h) group (p < 0.01). With LC injection, sustained platinum levels were maintained in the pelvic organs for a long time, with very few side effects. LC injection may be advantageous on the basis of pharmacokinetics.