Masayuki Takemori

MR detection of degenerating uterine leiomyomas

Objective Gonadotropin-releasing hormone (GnRH) analogues have been advocated for the conservative management of uterine leiomyoma. These drugs induce a hypoestrogenic state and affect undegenerated myoma cells. Therefore, we evaluated the usefulness of MRI for distinguishing undegenerated and degenerated leiomyomas. Materials and Methods Twenty lesions were studied in 16 patients with surgically resected leiomyoma. A 1.5 T unit was used to obtain T1− and T2-weighted images and Gd-DTPA-enhanced T1-weighted images. Signal intensity maps were made for each pulse sequence, and detailed histological maps were also made in the same plane as the MR images. Then the MR maps were compared with the histological maps of the resected specimens. Results Interstitial edema, the initial sign of degeneration, was detected as a high signal intensity region on T2-weighted images and showed enhancement with Gd-DTPA. Hyaline degeneration could not be distinguished from smooth muscle whorls on T1− and T2-weighted images. However, undegenerated leiomyoma could be distinguished from hyaline degeneration, because the former was slightly enhanced by Gd-DTPA but the latter was not. Conclusion These findings showed that Gd-DTPA-enhanced MRI can distinguish undegenerated leiomyomas from degenerated leiomyomas and suggest that MRI may be useful for predicting the response of this tumor to GnRH analogue therapy.

Photodynamic Therapy for Cervical Intraepithelial Neoplasia

Objectives: Photodynamic therapy (PDT) is a minimally invasive treatment for cervical intraepithelial neoplasia (CIN). We report the effectiveness of PDT in 105 cases of CIN. Methods: All patients received photofrin (PHE) 2 mg/kg intravenously and, 48–60 h later, phototherapy was performed using the Excimer dye laser or a YAG-OPO laser with an irradiation dose of 100 J/cm2 using 630 nm wavelength. Results: Mild photosensitivity occurred in 48% (50/105) of patients. The complete response (CR) rate was 90% (94/105) at 3 months following treatment. In the remaining 11 patients, 5 patients had CIN1, 2 patients had CIN2, and 4 patients had mild cytologic findings. However, in 9 of these 11 patients, CR was achieved 6 months after PDT. In 69 patients, human papilloma virus (HPV) typing was performed before and after PDT therapy. Pre-treatment, 64 of 69 patients (93%), were HPV-positive including 30 cases of high-risk HPV (43%). Testing performed 3, 6 and 12 months following PDT revealed no HPV-DNA in 75% (52/69), 74% (48/65) and 72% (41/57) of patients. At present, the median follow-up period is 636 days (90–2,232 days). In 3 patients, recurrence requiring surgical treatment was identified at 646, 717 and 895 days after PDT. Conclusions: PDT is an effective and minimally invasive treatment for CIN, which also appears to eradicate HPV infection.

Eradication and reinfection of human papillomavirus after photodynamic therapy for cervical intraepithelial neoplasia.

AbstractBackground. Photodynamic therapy (PDT) has been proven to be a promising therapeutic modality for selected dysplasias and malignancies in a variety of organs. We assessed the effectiveness of PDT for treating cervical intraepithelial neoplasia (CIN) by cytological and histological examinations and investigated its impact on human papillomavirus (HPV) infection. Methods. A series of 31 patients with CIN (2 with CIN2, 29 with CIN3) were given polyhematoporphyrin ether/ester (PHE) 2 mg/kg IV. After 60 h their cervices were exposed to a 630-nm YAG-OPO laser. HPV-DNA extracted from cervical smears was amplified by the polymerase chain reaction and typed for HPV using restriction fragment length polymorphism. Results. At 3 months after PDT, cytology and directed biopsy of the cervix revealed regression of the disease in 28 [complete remission (CR) rate 90%] of 31 patients, and HPV-DNA could be no longer detected in the cervical smears of 22 (76%) of 29 HPV-positive patients. After 12 months, all 31 patients had achieved a CR on biopsy, although HPV-DNA was still present in the cervical smears of 6 patients. The types of HPV-DNA detected 12 months after PDT were different from those seen before PDT in each of the 6 patients, suggesting that they might be reinfected with other HPV types after PDT. Conclusion. PDT is effective not only in improving the cytological and histological measures when treating CIN but also for eradicating cervical HPV.

Immunohistochemical expression of gastric mucin and p53 in minimal deviation adenocarcinoma of the uterine cervix.

Comparative immunostaining with antibodies against gastric mucin and p53 was performed on 6 cases of minimal deviation adenocarcinoma (MDA) of the uterine cervix. The MDAs consisted of predominant areas of glands lined by extremely well-differentiated tall columnar epithelial cells with little cytological atypia and minor foci of less well-differentiated glandular epithelium with a minor degree of nuclear atypia. Immunostaining for gastric mucin with a monoclonal antibody HIK1083 revealed that all the tumors areas of typical MDA were partly immunoreactive for HIK1083, but the coexisting less well-differentiated glands were essentially negative. Four MDAs focally contained cells with p53 positive nuclei that were located exclusively in the less well-differentiated cells that lacked gastric mucin. In the pelvic lymph nodes in 2 cases, most of the metastatic tumor was less differentiated and a positive reaction for HIK1083 was observed only in small foci of typical MDA. No significant overexpression of p53 was observed in the metastases. Immunohistochemical expression of gastric mucin and p53 may be related to the histological differentiation of MDA, and detection of p53 overexpression may help to identify critical steps in the local progression of MDA.

Production and Secretion of hCG and hCG Subunits by Trophoblastic Tissue

Advanced techniques have brought great success in purification and characterization of glycoprotein hormones. The human glycoprotein hormones, such as luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), and human chorionic gonadotropin (hCG) are all composed of a protein core derived from two non-identical alpha and beta subunits, with branched carbohydrate side chains radically attached to asparagine, serines, and/or threonine. In contrast to the essentially identical or nearly identical amino acid sequence among the α-subunits, the biological properties of native hormones are greatly contributed by the β-subunit (which also carries specific antigenic sites) and are structurally unique for each species. Antisera generated to the β-subunit of hCG discriminate comparatively well between hLH and hCG, while most of those derived from intact hormones do not (Amir, 1972).

Ovarian thecoma with ascites and high serum levels of CA125

Abstract We report a 34-year-old woman with an ovarian thecoma and ascites who exhibited high serum levels of CA125. Measuring serum tumor markers and imaging are two important diagnostic tools for malignant ovarian tumors. In the present case, a preoperative diagnosis of benign ovarian tumor could not be made due to the elevation of CA125 (895 U/ml) and nonspecific MRI findings.

Clinical evaluation of MRI in the diagnosis of borderline ovarian tumors

Objective. To evaluate the clinical potential of contrast‐enhanced MRI with Gd‐DTPA (gadopentetate dimeglumine) in the diagnosis of borderline ovarian tumors.

Carcinosarcoma of the Uterus: Magnetic Resonance Imaging

We report the magnetic resonance imaging (MRI) findings with a paramagnetic enhancement agent (gadopentetate dimeglumine (Gd-DTPA)) in a 70-year-old woman with carcinosarcoma of the uterus. In the present patient, the polypoid portion histologically most abundant in the sarcomatous component was strongly enhanced by Gd-DTPA and was clearly demonstrated with high signal intensities on contrast-enhanced T1-weighted images. We suggest that MRI with Gd-DTPA may be clinically useful for detection of carcinosarcoma, and that any patient having endometrial carcinoma with the polypoid portion, which is more strongly enhanced by Gd-DTPA within the tumor, may be suspected of carcinosarcoma.

Enzyme Immunoassay of Urinary β-Core Fragment of Human Chorionic Gonadotropin as a Tumor Marker for Ovarian Cancer

Human chorionic gonadotropin (hCG), a glycoprotein hormone composed of two nonidentical α- and β-subunits, is normally produced by trophoblasts. Serum and urine from some patients with nontrophoblastic tumors are found to contain similar immunoactivity to the β-subunit of hCG and this phenomenon has been recognized as an ectopic hCGβ production (1). Elevated levels of ectopic hCGβ are detected more frequently in urine than in serum. Recent studies have shown that urinary ectopic hCGβ mainly represents hCGβ-core fragment (β-CF) (2). Urinary β-CF consists of residues 6-40 disulfide bridged to residues 55-92 of the β-subunit of hCG (3,4), suggesting that it may be a degradative product of hCGβ. Such partial identity of the amino acid sequence between intact hCG, free hCGβ, and β-CF makes their specific measurements difficult. The existence of two more antigenic sites unique to hCGβ has been demonstrated. The one domain locates in the β-core portion and the other in COOH- terminal region of the β-subunit of hCG Fig. 1). By selecting appropriate pairs of antibodies to construct sandwich enzyme immunoassays (EIAs), it is possible to design methods that measure either intact hCG, free hCGβ, or β-CF Table 1). By using this EIA, the authors assessed the clinical usefulness of urinary β-CF as a tumor marker for nontrophoblastic tumors (5,6). Here, the authors describe the methods to measure urinary β-CF in patients with ovarian cancer. Fig. 1. Two antigenic sites: the first domain is located in the β-core portion and the second domain is located in the COOH-terminal region of the β-subunit of hCG. Table 1 Specificities and Sensitivities of Enzyme-Immunoassays Specific for Intact hCG(EIA-1), Free hCGβ(EIA-2), and β-CF(EIA-3) First antibody Second antibody Cross-reactivity (%) Sensitivity Intact Free Assay Code Epitope Code Epitope Specificity (ng/ml) hCG hCGβ β-CF EIA-1 No.277(MoAb) β-CTP No.224(MoAb) hcGa Intact hCG 0.01 100 15 1.0 EIA-2 No.209(MoAb) hCGβ No.115(PoAb) β-core Free hCGβ 0.01 1.9 100 1.9 EIA-3 No.229(MoAb) β-core No.105(PoAb) β-core β-CF 0.01 3.3 100 100 MoAb: monoclonal antibody. PoAb: polyclonal antibody.

Ovarian Dysgerminoma with Massive Metastases to Para-Aortic Lymph Nodes

We report on a 15-year-old female with left ovarian dysgerminoma accompanied by massive swelling of the para-aortic lymph nodes which was clearly demonstrated by preoperative magnetic resonance imaging (MRI). Metastasis to the para-aortic lymph nodes from dysgerminoma was confirmed by biopsies obtained during surgery. No study has previously reported dysgerminoma with massive para-aortic lymph node metastases clearly demonstrated by MRI. These preoperative MRI findings are presented here. The patient received six cycles of cisplatin-based combination chemotherapy with the BEP regimen (bleomycin, etoposide and cisplatin) after conservative surgery, and no residual para-aortic lymph nodes were detected by MRI or CT after the chemotherapy.