Yoshihito Ichikawa

Malignant transformation of ovarian endometriosis.

One hundred forty-seven cases of ovarian endometriosis, encountered from 1976 to 1999 at Tsukuba University Hospital, were studied to clarify the incidence of malignant transformation. There were 18 cases (12.2%) of atypical endometriosis, among which we found a case (5.6%) of ovarian cancer arising from endometriosis not diagnosed before surgery. This is accounted for 0.7% of all ovarian endometriosis cases. Because the incidence was equal to that of the previous reports, it is most likely that the malignant change in ovarian endometriosis occurred in 0.7% of this disease.

Inactivation of p16/CDKN2 and p15/MTS2 is associated with prognosis and response to chemotherapy in ovarian cancer

To define the involvement of p16/CDKN2 and p15/MTS2 tumor‐suppressor genes for response to chemotherapy in primary epithelial ovarian cancer, we analyzed alterations of the gene in 45 patients who were treated with primary cytoreductive surgery followed by 6 courses of cis‐diamminedichloroplatinum (II) (cisplatin)‐based combination chemotherapy. Homozygous deletion of p16/CDKN2 and p15/MTS2 genes was found in 8 (18%) and 15 (33%) cases, respectively. Response to the chemotherapy was confirmed by finding at second surgery after the chemotherapy in 26 patients, resulting in 17 responders and 9 nonresponders. The abundance of gene deletion in nonresponders (56%) was significantly higher (p = 0.0463) when compared to that in responders (18%). Moreover, the deletion of genes was a significant poor prognostic factor (p = 0.0441) in advanced ovarian cancer. These results suggest that deletion of p16/CDKN2 and/or p15/MTS2 is a potential indicator for poor chemotherapy response and adverse prognosis in ovarian cancer patients.

Inactivation of p16/CDKN2 and p15/MTS2 genes in different histological types and clinical stages of primary ovarian tumors.

To define the involvement of p16/CDKN2 and p15/MTS2 inactivation in ovarian tumorigenesis and the association of these inactivation events with histological types and clinical stages of ovarian tumors, we analyzed homozygous deletion and somatic mutation of p16/CDKN2 and p15/MTS2 genes, as well as hypermethylation of the 5′‐CpG island of the p16/CDKN2 gene, in 49 primary ovarian tumors and 6 ovarian carcinoma cell lines. We found homozygous deletions of p16/CDKN2 and p15/MTS2 in 6 (12%) and 5 (10%) primary tumors, respectively. Somatic mutation of p16/CDKN2 was found in only I primary tumor, but mutation of p15/MTS2 was not detected in any sample. None of the 28 primary tumors or 6 cell lines was hypermethylated at the 5′‐CpG island of p16/CDKN2. The incidence of inactivation of p16/CDKN2 in primary tumors was significantly higher in the advanced stages (7 of 29) than in the early stages (0 of 14). Seven of 9 alterations in p16/CDKN2 and p15/MTS2 were observed in serous (3 of 12), endometrioid (3 of 9) and clear‐cell (1 of 4) carcinomas. However, only normal sequences of these genes were detected in mucinous carcinomas. Loss of heterozygosity (LOH) at the IFNA locus was detected in 1 of 19 (5%) tumors, but no change at the D95171 locus was observed in 17 tumors. These results suggest that: (i) homozygous deletion is the main mechanism of inactivation of p16/CDKN2 and p15/MTS2 in ovarian tumorigenesis; (ii) inactivation of p16/CDKN2 and p15/MTS2 may be the histological type‐specific events involved in ovarian tumorigenesis; and (iii) inactivation of p16/CDKN2 is potentially involved in the progression of ovarian tumors in advanced stages.

Ultrasound diagnosis of uterine arteriovenous fistula associated with placental site trophoblastic tumor

We report a case of a woman with abnormal vaginal bleeding who had a placental site trophoblastic tumor (PSTT) detected following hysterectomy. Surgery was performed because of a large uterine arteriovenous fistula detected by transvaginal color and pulsed Doppler sonography. Color Doppler sonography revealed a lacunar‐type lesion with a marked increase in uterine vascularity, and pulsed Doppler sonography demonstrated a low resistance index. This vascular pattern indicated the formation of blood lacunae and arteriovenous shunts caused by PSTT within the uterine myometrium. This is the first report to describe the ultrasound findings in a case of PSTT complicated by a uterine arteriovenous fistula. Copyright

A thickened or indistinct junctional zone on T2-weighted MR images in patients with endometrial carcinoma: pathologic consideration based on microcirculation

Abstract.Thickened or indistinct junctional zone (JZ) is a problematic finding in staging endometrial carcinoma. We studied the incidence, pathological cause of this condition correlated to microcirculation, and the utility of dynamic contrast MRI for differential diagnosis. T2-weighted images were analyzed in 119 cases with endometrial carcinoma. The enhancement of the JZ during the dynamic contrast MRI, histopathological causes, and the density of arterioles in the JZ were retrospectively analyzed in cases with thickened or indistinct JZ. The MRI histopathological correlation of all 31 patients with a thickened or indistinct JZ were analyzed, in which it was corresponded to myometrial cancer invasion only in 22%. The sensitivity of a poor early enhancement pattern on dynamic study for detecting myometrial invasion was 71.4%, the specificity was 100%, and the overall accuracy was 92.5%. Although only weak relationship between the contrast enhancement and the arteriole density was revealed, the arteriole density within the JZ with cancer invasion was significantly decreased. Poor enhancement of JZ in early dynamic phase was correlated with the decreased density of arterioles within the myometrium which was invaded by endometrial carcinoma. Dynamic contrast study should be performed in staging endometrial carcinoma especially when JZ was thickened or indistinct.

Postpartum MR diagnosis of retained placenta accreta

Retained placenta accreta can cause catastrophic postpartum hemorrhage. This study aims to determine whether MR imaging can differentiate retained placenta accreta from postpartum hemorrhage caused by other conditions. Fourteen cases suspicious for retained placenta were examined with MR imaging. Signal intensity, the enhancing pattern of uterine contents, and flow voids within the myometrium were retrospectively studied. As hysterectomy was performed in only two cases, final diagnosis was based on clinical outcome and analysis of uterine contents. Final diagnoses were retained placenta accreta in seven cases, retained normally attached placenta in four, hematoma in two, and placental site trophoblastic tumor (PSTT) in one. All seven cases with placenta accreta had a very hyperintense area on T2-weighted images, showing transient early enhancement. None demonstrated delayed strong enhancement around the hyperintense area. In two cases with retained normally attached placenta and in both with hematomas, there were no hyperintense areas on T2-weighted images. Of these, only one showed transient early enhancement. Flow voids were observed in four cases with placenta accreta, one with normally attached placenta, and the case with PSTT. A markedly hyperintense area on T2-weighted images and transient early enhancement without delayed strong enhancement between the mass and the myometrium can indicate retained placenta accreta.

Complete response to irinotecan hydrochloride and nedaplatin in a patient with advanced ovarian clear cell carcinoma

A 55-year-old multiparous woman was diagnosed with stage IIIc ovarian clear cell carcinoma. Three years after the first surgery and adjuvant chemotherapy with irinotecan hydrochloride and mitomycin C, she developed common iliac lymph node recurrence. Two cycles of chemotherapy with irinotecan hydrochloride and nedaplatin led to a complete response. Surgical resection revealed pathological complete response. The chemosensitivity of ovarian clear cell carcinoma has been reported to be very poor. No standard chemotherapeutic regimens for this carcinoma have been established. The present study is the first report of a pathological complete response in a patient with advanced ovarian clear cell carcinoma. Future studies are needed to confirm the efficacy of this regimen for this carcinoma.

Postpartum choriocarcinoma complicated by brain and lung metastases treated successfully with EMA/CO regimen

A 25 year old woman, who had given birth at 38 weeks in June 1998, was admitted to her local hospital in November 1998 after a sudden right occipital headache. Her symptoms included increased intracranial pressure and a positive urine pregnancy test. Computed tomography of the brain and the chest revealed multiple lesions consistent with brain and lung metastases for choriocarcinoma, therefore she was referred to Tsukuba University Hospital for immediate treatment. Her cervical and endometrial smears were normal. Both transvaginal ultrasonography and magnetic resonance imaging of the pelvis revealed normal findings. However, her serum P-human chorionic gonadotrophin level was 16,256 mIU/mL,. Magnetic resonance imaging of the brain showed a cerebral haemorrhage 3 cm in diameter in the right occipital lobe and multiple small haemorrhages in other areas (Fig. 1 a), which contraindicated surgical resection. Glycerol was administered intravenously to reduce intracranial pressure. Subsequent computed tomography of the chest revealed multiple small masses in the lungs bilaterally and a haemothorax in the right lung (Fig. lb). The World Health Organisation prognostic score was 12, or high risk, and the FIG0 Stage was IVa. An EMA/CO’ treatment regimen was started, consisting of alternate weekly cycles of etoposide (200 mg/m2), methotrexate (300 mg/m’), actinomycinD1 mg/body, cyclophosphamide (600 mg/m2), and vincristine (1.0 mg/m2). Despite the chemotherapy, the haemothorax gradually worsened. Although multiple metastatic tumours were present, due to active bleed-