Osamu Ishiko

Transmission of symptomatic parvovirus B19 infection by fibrin sealant used during surgery

Human parvovirus B19 infection has been shown to be transmissible by blood and blood products and to result in transient aplastic crisis in patients with rapid red cell turnover. We report three cases of iatrogenic parvovirus B19 infection resulting from the use of the same batch of fibrin sealant under operation. Fibrin sealant, which is a typical haemostatic agent produced from blood, has been used during surgery. Human parvovirus is resistant to existing virus‐inactivating techniques, suggesting that infection may occur from blood products contaminated with it. Use of recombinant products for these proteins may thus be necessary.

Outcomes of fertility-sparing surgery for stage I epithelial ovarian cancer: a proposal for patient selection.

PURPOSE The objective of this study was to assess clinical outcomes and fertility in patients treated conservatively for unilateral stage I invasive epithelial ovarian cancer (EOC). PATIENTS AND METHODS A multi-institutional retrospective investigation was undertaken to identify patients with unilateral stage I EOC treated with fertility-sparing surgery. Favorable histology was defined as grade 1 or grade 2 adenocarcinoma, excluding clear cell histology. RESULTS A total of 211 patients (stage IA, n = 126; stage IC, n = 85) were identified from 30 institutions. Median duration of follow-up was 78 months. Five-year overall survival and recurrence-free survival were 100% [corrected] and 97.8% for stage IA and favorable histology (n = 108), 100% and 100% for stage IA and clear cell histology (n = 15), 100% and 33.3% for stage IA and grade 3 (n = 3), 96.9% and 92.1% for stage IC and favorable histology (n = 67), 93.3% and 66.0% for stage IC and clear cell histology (n = 15), and 66.7% and 66.7% for stage IC and grade 3 (n = 3). Forty-five (53.6%) of 84 patients who were nulliparous at fertility-sparing surgery and married at the time of investigation gave birth to 56 healthy children. CONCLUSION Our data confirm that fertility-sparing surgery is a safe treatment for stage IA patients with favorable histology and suggest that stage IA patients with clear cell histology and stage IC patients with favorable histology can be candidates for fertility-sparing surgery followed by adjuvant chemotherapy.

A high-frequency polymorphism in exon 6 of the CD45 tyrosine phosphatase gene (PTPRC) resulting in altered isoform expression

CD45 (leukocyte common) antigen is a hemopoietic cell-specific tyrosine phosphatase essential for antigen receptor-mediated signaling in lymphocytes. The molecule undergoes complex alternative splicing in the extracellular domain, and different patterns of CD45 splicing are associated with distinct functions. Lack of CD45 leads to severe combined immunodeficiency, and alterations of CD45 splicing, because of a polymorphism in exon 4, have been associated with altered immune function. Here we describe a polymorphism in exon 6 (A138G) of the gene encoding CD45 that interferes with alternative splicing. The polymorphism results in an amino acid substitution of Thr-47 to Ala in exon 6, a potential O- and N-linked glycosylation site. This exon 6 A138G variant is present at a frequency of 23.7% in the Japanese population but is absent in Caucasoids. Peripheral blood T cells from individuals carrying the A138G variant show a significant decrease in the proportion of cells expressing the A, B, and C CD45 isoforms and a high frequency of CD45R0+ cells. These phenotypic alterations in the A138G carriers may lead to changes in ligand binding, homodimerization of CD45, and altered immune responses, suggesting the involvement of natural selection in controlling the A138G carrier frequency.

The urinary incontinence score in the diagnosis of female urinary incontinence.

Objective: Our purpose was to determine whether the urinary incontinence (UI) score is significantly useful in evaluating the clinical status of UI. Method: The questionnaire was administered to 198 UI patients (27–73 years of age) diagnosed by conventional procedures. It consisted of 15 questions, and the answers were assigned points divided into a stress score (s‐s) and urge score (u‐s) according to severity. Results: The patients were classified into a stress incontinence group (SI; 125 cases), urge incontinence group (URI; 29 cases), mixed incontinence group (MI; 41 cases), and overflow incontinence group (3 cases). Classification by questionnaire yielded 110 SI cases, 31 URI cases, and 46 MI cases, accuracy of 83.2%, 86.2%, and 61.0%, respectively. A significant correlation was observed with s‐s of SI (r=0.669, P<0.001) and u‐s of URI (r=0.583, P<0.005). Conclusion: The UI score will be a simple, clinically effective diagnostic procedure for UI for use by general gynecologists.

Potential role of LMP2 as tumor-suppressor defines new targets for uterine leiomyosarcoma therapy

Although the majority of smooth muscle neoplasms found in the uterus are benign, uterine leiomyosarcoma (LMS) is extremely malignant, with high rates of recurrence and metastasis. We earlier reported that mice with a homozygous deficiency for LMP2, an interferon (IFN)-γ-inducible factor, spontaneously develop uterine LMS. The IFN-γ pathway is important for control of tumor growth and invasion and has been implicated in several cancers. In this study, experiments with human and mouse uterine tissues revealed a defective LMP2 expression in human uterine LMS that was traced to the IFN-γ pathway and the specific effect of JAK-1 somatic mutations on the LMP2 transcriptional activation. Furthermore, analysis of a human uterine LMS cell line clarified the biological significance of LMP2 in malignant myometrium transformation and cell cycle, thus implicating LMP2 as an anti-tumorigenic candidate. This role of LMP2 as a tumor suppressor may lead to new therapeutic targets in human uterine LMS.

Clinical management of atypical polypoid adenomyoma of the uterus. A clinicopathological review of 29 cases.

OBJECTIVE The clinical management of atypical polypoid adenomyoma (APAM) of the uterus remains to be established. We collected APAM cases, reviewed the clinicopathological features, and discussed the clinical management. METHODS Twenty-nine patients with APAM were identified by searching the tumor registry of the Japan Clinical Oncology Group (JCOG). Clinical information and histological specimens were obtained from 13 institutional members of the JCOG, and a central pathological review was performed. RESULTS The mean age of the patients was 38 years (range, 22-58). Squamous metaplasia was present in 19 cases (65.5%), and well-differentiated endometrioid adenocarcinoma coexisted in 5 cases (17.2%). Primary treatment consisted of dilatation and curettage in 9 patients (31.0%), vaginal resection in 2 patients (6.9%), hysteroscopic transcervical resection (TCR) using hysteroscopy in 10 patients (34.5%), and hysterectomy in 8 patients (27.6%). There were recurrences in 5 (23.8%) of the 21 cases in which fertility was preserved, and the recurrent rate was 10% (1/10) in patients those were treated with TCR and 36.4% (4/11) in those the other treatment options were selected. All patients were alive after primary treatment (a mean follow-up period was 39.6 months; range, 1-202). CONCLUSION The clinical outcome of APAM is benign. However, differential diagnosis should be performed because of its histological similarity to invasive endometrial carcinoma and the possibility of coexistence with other endometrial neoplasms. TCR is a recommended diagnostic and treatment option for patients who desire to preserve fertility.

Transcervical microwave myolysis for uterine myomas assisted by transvaginal ultrasonic guidance

Aim:  The effects of transcervical microwave myolysis at 2.45 GHz after microwave endometrial ablation for menorrhagia were examined in patients with myomas.

Vesicovaginal fistula treated with fibrin glue.

We report here a case of vesicovaginal fistula, following radiation therapy and intensive local chemotherapy for recurrent endometrial cancer of the vaginal stump, which was ameliorated with fibrin glue. The procedure temporarily postponed urinary diversion until the recurrence of irreparable fistula more than 4 years after the development of the first vesicovaginal fistula.

Potential role of LMP2 as an anti-oncogenic factor in human uterine leiomyosarcoma: Morphological significance of calponin h1

Uterine leiomyosarcoma (LMS) is a highly metastatic smooth muscle neoplasm for which calponin h1 is suspected to have a biological role as a tumor‐suppressor. We earlier reported that LMP2‐null mice spontaneously develop uterine LMS through malignant transformation of the myometrium, thus implicating this protein as an anti‐tumorigenic candidate as well. In the present study, we show that LMP2 may negatively regulate LMS independently of its role in the proteasome. Moreover, several lines of evidence indicate that although calponin h1 does not directly influence tumorigenesis, it clearly affects LMP2‐induced cellular morphological changes. Modulation of LMP2 may lead to new therapeutic approaches in human uterine LMS.

Adenocarcinoma arising from respiratory ciliated epithelium in mature ovarian cystic teratoma

Abstract Malignant transformation of a mature cystic teratoma of the ovary is rare, that of an adenocarcinoma is extremely rare. A 32-year-old woman was suspected as having a malignant transformation of her mature cystic teratoma of the ovary because the preoperative level of carcinoembryonic antigen (CEA) was extremely high. Resections of her ovarian cysts were performed, and this particular tumor was histopathologically diagnosed as an adenocarcinoma arising from a mature cystic teratoma of the left ovary. Because adenocarcinomas arising from mature cystic teratomas of the ovary are extremely rare, we report this case with a review of some of the literature.