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Biomedical subjects

F Flam

Publications and source records attributed to F Flam.

At least 19 recordsLinked to original sources

Hysteroscopy provides proof of trophoblastic tumors in three cases with negative color Doppler images.

Color Doppler sonography has replaced pelvic arteriography as well as real-time ultrasound in the assessment of patients with gestational trophoblastic disease. In about 25% of patients in whom human chorionic gonadotropin (hCG) levels are suggestive of trophoblastic disease, there will be no evidence of abnormal vessels in the uterus. In these cases it is assumed that hCG was produced by metastatic lesions. We present here three cases in which color Doppler examination was negative and where myometrial biopsies containing tumor were obtained by means of hysteroscopy. The fact that color Doppler, in its present form, does not detect small areas of trophoblastic tumor might also have implications for other kinds of tumors. Knowledge of the exact microscopic diagnosis in molar patients with persistent disease may have an impact on management.

Adult

Subcutaneous metastasis from an ovarian carcinoma disappeared following tamoxifen therapy.

In a 78-year-old woman who had been treated for a breast cancer, a subcutaneous metastasis was diagnosed. This metastasis disappeared following a 3-months' treatment with tamoxifen. Only then was the primary tumour found to be ovarian carcinoma rather than a mammary one. This and other reports indicate that hormonal agents may also be considered as a third line of treatment in ovarian carcinoma.

Aged

Bilateral tubal pregnancy following in vitro fertilization and transfer of two embryos.

A case of simultaneous bilateral tubal pregnancy after IVF-ET treatment is presented. This condition occurred despite the fact that only two embryos were transferred. Due to misinterpretation of repeated sonographic images, the diagnosis was delayed, and laparatomy with bilateral salpingectomy was not performed until 57 days had passed from the day of ET. Although there is a substantial risk of ectopic pregnancy following IVF-ET, this risk should be reduced as the number of embryos transferred per cycle decreases. This is, to the best of our knowledge, the first report of bilateral tubal pregnancies following the transfer of only two embryos.

Adult

Endometrial stromal sarcoma diagnosed by operative hysteroscopy.

A 33 year old, para-2 woman had a 'submucous myoma' diagnosed in the uterine fundus during a diagnostic hysteroscopy because of dysfunctional bleeding. After pretreatment with a gonadotrophin-releasing hormone (GnRH) agonist for 3 months, the myoma was resected through a resectoscope. Histological examination showed features of low-grade stromal sarcoma although no complete diagnostic certainty was reached. Due to the age of the patient and her wish to preserve fertility, it was decided not to perform extensive surgery but to perform hysteroscopy again in a follow-up visit after 3 months. Since the myoma had by this time recurred in the same place, it was decided to perform a total abdominal hysterectomy. The subsequent histopathological examination confirmed the growth of a low-grade stromal sarcoma. Following this diagnosis, the ovaries were removed laparoscopically and were found to be free of tumour.

Adult

Allele-specific in situ hybridization (ASISH) analysis: a novel technique which resolves differential allelic usage of H19 within the same cell lineage during human placental development.

Precursory studies of H19 transcription during human foetal development have demonstrated maternally derived monoallelic expression. Analyses in extra-embryonic tissues, however, have been more equivocal, with discernible levels of expression of the paternal allele of H19 documented in the first trimester placenta. By refining the in situ hybridization technique we have developed an assay to enable the functional imprinting status of H19 to be determined at the cellular level. This assay involves the use of oligonucleotide DNA probes that are able to discriminate between allelic RNA transcripts containing sequence polymorphisms. Biallelic expression of H19 is confined to a subpopulation of cells of the trophoblast lineage, the extravillous cytotrophoblast, while the mesenchymal stroma cells maintain the imprinted pattern of monoallelic expression of H19 throughout placental development. This data demonstrates that the low level of paternal H19 expression previously detected in normal human placenta is not due to a random loss of functional imprinting, but appears to result from a developmentally regulated cell type-specific activation of the paternal allele. In addition, biallelic expression of H19 does not seem to affect the functional imprinting of the insulin-like growth factor II gene, which is monoallelically expressed at relatively high levels in the extra-villous cytotrophoblasts. These results imply that the allelic usage of these two genes in normal human placental development may not be directly analogous to the situation previously documented in the mouse embryo.

Alleles

Hysteroscopy in gestational trophoblastic diseases.

Hysteroscopic evaluations were performed in eight women with gestational trophoblastic diseases. Seven of the eight patients had abnormal hysteroscopic findings and biopsies were obtained from the endometrium and adjacent myometrium. Five patients had histopathological proof of tumour. This preliminary report shows the feasibility of the method. The potential risks involved are discussed. A correct histopathological diagnosis in patients evaluated for gestational trophoblastic diseases may be useful in order to tailor the treatment.

Biopsy

Choriocarcinoma in the term placenta: a difficult diagnosis.

Although choriocarcinoma following a term pregnancy is an uncommon disease, it is important to identify these patients early. The time interval between delivery and onset of treatment is a crucial factor influencing prognosis. We present a case where the woman was delivered of a stillborn infant and histological examination of the placenta at first did not reveal the true diagnosis of choriocarcinoma. Due to persistent vaginal bleeding curettage was performed 11 weeks later establishing choriocarcinoma. In this particular case it was then possible to review the original material and to confirm the diagnosis in this specimen. The case is extraordinary since the placenta harbouring the primary tumour had been macroscopically and microscopically described and the material could be reviewed. Secondly the case underlines the diagnostic difficulties when examining a mature placenta.

Adult

Paternally derived H19 is differentially expressed in malignant and nonmalignant trophoblast.

The paternal allele of the H19 gene has been shown to be transcriptionally inactive in the developing human embryo. Using reverse transcription PCR and RNase protection assays, we demonstrate that expression of H19 is predominantly, but not exclusively, from the maternal allele in the human placenta. In situ hybridization analysis shows strong expression of the H19 gene in eight complete hydatidiform moles, hyperplastic tissues consisting of trophoblasts which contain only paternally derived genetic material, indicating that H19 is not functionally imprinted in this tissue. H19, a putative growth suppressor, is oppositely imprinted to the neighboring insulin-like growth factor II (IGF2) gene and an up-regulation of IGF2 expression has been linked previously to a down-regulation of H19 expression in the progression to Wilms' tumor. Two cases of complete hydatidiform mole which progressed to choriocarcinoma show high levels of expression of both H19 and IGF2. The choriocarcinomas which developed from these complete hydatidiform moles showed similar expression of IGF2 but a decreased number of H19-positive cells, which may reflect selection for cells expressing IGF2 and against those expressing H19 in this tissue.

Alleles

Management of uterine perforations in connection with legal abortions.

The incidence of uterine perforation while performing legal abortions was evaluated in the Stockholm area. Among 84,850 legal abortions performed during 1982-1992 there were 145 cases of uterine perforation, 0.17%. In about half of these cases an immediate exploration of the abdomen was decided upon and in 18 patients there were significant bleeding and/or lacerations to organs situated in the pelvis. No case of intestinal perforation was encountered. It is likely that many of these injuries would have healed just as well unattended. Based on this study, the authors advocate a conservative approach in dealing with uterine perforation in connection with vacuum aspiration for legal abortion.

Abortion, Legal

Value of uterine artery Doppler in endometrial cancer.

Twenty-seven women with endometrial cancer were studied with Doppler ultrasound coupled with a vaginal probe. Pulsatility index of the flow velocity of the uterine artery was recorded and compared to that of a control group. The subjects and the controls did not differ in blood flow measurements. There was no correlation between severity of disease and flow velocimetry values. Eleven of the patients underwent brachytherapy prior to surgery. Administration of brachytherapy resulted in a decrease of the peripheral resistance. The results of this study indicate that Doppler velocimetry of the uterine artery is not a valuable tool in discriminating between malignant and benign endometrium.

Adenocarcinoma

Decreased expression of Ras GTPase activating protein in human trophoblastic tumors.

The normally developing placenta undergoes extensive but regulated noninvasive cellular proliferation. Various proto-oncogenes and growth factors have been associated with the regulation of trophoblastic placental growth. Activation of some oncogenes and altered expression of growth factors have been demonstrated in trophoblastic tumors (hydatidiform mole and choriocarcinoma). The ras proto-oncogene plays a key role in the signal transduction cascade of activated growth factors, and is known to be activated or overexpressed in multiple tumor types. Ras GTPase activating protein (RasGAP), a major down-regulator of ras activity, is present at high levels in placenta. To assess the role that Ras-GAP plays in the development of trophoblastic tumors, we performed immunohistochemical analyses with anti RasGAP antibodies of normal placentas, hydatidiform moles, invasive moles, and malignant choriocarcinomas. Normal placentas and noninvasive hydatidiform mole displayed intense positive staining confined to trophoblasts, whereas no staining was observed in the trophoblasts of invasive moles or choriocarcinomas. Thus, there was an inverse correlation between expression levels of RasGAP protein and the invasive potential and malignant phenotype in human trophoblastic tumors. The data indicate that RasGAP may play a regulatory role in trophoblast proliferation and that abolishing its activity may be associated with malignant transformation of these cells.

Cell Transformation, Neoplastic