Publications by authors named "David R Genest"

Objective: To identify clinical characteristics associated with developing persistent gestational trophoblastic neoplasia (GTN) after partial hydatidiform molar pregnancy (PHM).

Study Design: Utilizing the Donald P. Goldstein in patients who developed persistence between 1973 and 1989.

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Objective: To develop human chorionic gonadotropin (hCG) criteria that determine a patient's risk of developing persistent gestational trophoblastic neoplasia (GTN) or achieving remission after partial mole evacuation.

Study Design: We used a database from the New England Trophoblastic Disease Center to analyze hCG levels from 284 women with partial molar pregnancies diagnosed between 1973 and 2003.

Results: An hCG level >199 mIU/mL in the third through eighth week following molar evacuation was associated with at least a 35% risk of GTN.

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Objective: We evaluated the risk of gestational trophoblastic neoplasia (GTN) for women with partial molar pregnancy whose human chorionic gonadotropin (hCG) levels fall spontaneously to undetectable levels using a sensitive hCG assay.

Methods: We analyzed data from the New England Trophoblastic Disease Center to estimate the risk of GTN among 284 women with partial molar pregnancy and at least 6 months of gonadotropin follow-up.

Results: None of the 238 women with complete gonadotropin follow-up and a spontaneous decline in serum hCG levels to undetectable levels subsequently developed GTN (95% confidence interval 0-1.

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The 2001 Bethesda System revision recommends reporting benign-appearing endometrial cells (BAEMC) in all women 40 years or older, not just in postmenopausal women. We studied the influence of this change on clinical practice and the detection of endometrial neoplasia. Women 40 years or older were selected for study if BAEMC were reported on a cervical cytologic specimen.

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Objective: To determine if immunohistochemistry for PHLDA2 (also known as IPL and TSSC3), the product of a paternally imprinted, maternally expressed gene, can be used as a tool in the differential diagnosis of molar gestations.

Study Design: Twenty-five cases (15 complete moles, 5 partial moles and five hydropic abortions) were stained by immunohistochemistry for PHLDA2 and scored (without knowledge of the diagnosis) for positivity in the villous cytotrophoblast and then compared to adjacent sections stained by p57KIP2 immunohistochemistry.

Results: All partial moles and hydropic abortions were positive for PHLDA2 and p57KIP2.

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Hydatidiform moles are pregnancies characterized by abnormal development of both embryonic and extraembryonic tissues and are associated with the misexpression of imprinted genes. The vast majority of complete hydatidiform moles are diploid and androgenetic, whereas partial hydatidiform moles are triploid, with an extra set of chromosomes of paternal origin. Here, we present an unusual complete mole that showed strong expression of two imprinted, maternally transcribed genes, CDKN1C (encoding p57(KIP2)) and PHLDA2 (TSSC3/IPL), both part of a large imprinted gene domain on chromosome 11.

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We present a case of unilateral terminal transverse forearm deficiency with subterminal digit-like nubbins, identified in a fetus from a pregnancy terminated electively in the second trimester because the distal right arm and hand could not be seen by ultrasound and were presumed to be absent. Pathologic evaluation showed distal transverse shortening, tapering to a point in the mid-forearm. Five primitive digital nubbins were present, located just proximal to the tapered point.

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Objective: Osteopontin (OPN) is a glycoprotein of the extracellular matrix that can bind to different types of receptors including integrins and CD44 receptors. Multiple binding affinity enables OPN to play a role in many physiological and pathological processes. OPN contributes to tumorigenesis in several types of cancers.

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Type 3 iodothyronine deiodinase (D3) is the major physiologic inactivator of thyroid hormone. This selenoenzyme, previously identified in human placenta and brain, catalyzes the inner-ring deiodination of T(4) to reverse T(3) and T(3) to 3, 3'-diiodothyronine, both of which are biologically inactive. We analyzed D3 expression in several human adult and fetal tissues by immunohistochemistry and correlated the results with D3 activity assays where possible.

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Until recently, the histologic diagnosis of obstetrical and gynecologic neoplasia was based principally on morphologic criteria. However, interobserver reproducibility for entities such as squamous intraepithelial, endometrial, and trophoblastic disease varies widely between observers. This inherent variability in interpretation between individuals has led to wide ranges in diagnostic precision between practices, and in many cases, between recognized experts.

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We address the question as to whether Ureaplasma urealyticum or Mycoplasma hominis, cultured from the placenta of very-low-birthweight (VLBW) infants, are associated with an increased risk of (a) fetal vasculitis and (b) ultrasonographic cerebral white matter echolucency. The sample consisted of 464 VLBW infants for whom (i) the surface of the chorion was cultured for U. urealyticum and M.

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Hydatidiform mole (HM) is an abnormal gestation characterized by trophoblast hyperplasia and overgrowth of placental villi. The genetic basis in the vast majority of cases is an excess of paternal to maternal genomes, suggesting that global misexpression of imprinted genes is the common molecular mechanism underlying the genesis of this condition. Although most complete HM are androgenetic in origin, a rare, frequently familial, biparental variant has been described.

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Objective: To study whether nontriploid partial hydatidiform moles truly exist.

Study Design: We conducted a reevaluation of pathology and ploidy in 19 putative nontriploid partial hydatidiform moles using standardized histologic diagnostic criteria and repeat flow cytometric testing by the Hedley technique.

Results: On review of the 19 moles, 53% (10/19) were diploid nonpartial moles (initially pathologically misclassified), and 37% (7/19) were triploid partial moles (initial ploidy misclassifications).

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Objective: To determine whether the combination of flow cytometry and immunohistochemistry for p57 expression is useful for the pathologic classification of diagnostically challenging hydatidiform moles.

Study Design: Six probable hydatidiform moles that were difficult to classify pathologically were reevaluated by histology, flow cytometry and immunohistochemistry for p57.

Results: In all cases, the pathologic diagnoses were easily resolved: two cases were partial moles (triploid, p57 positive), two cases were early complete moles (diploid, p57 negative), and two cases were twin gestations with normal villi (diploid, p57 positive) admixed with villi from a complete hydatidiform mole (diploid, p57 negative).

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Placental site trophoblastic tumor (PSTT) is the least common form of gestational trophoblastic disease. The tumor represents a neoplastic transformation of intermediate trophoblastic cells that normally play a critical role in implantation. PSTT can occur after a normal pregnancy, spontaneous abortion, termination of pregnancy, ectopic pregnancy or molar pregnancy.

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Objective: To evaluate the clinical outcome and histologic findings of pregnancies in which placental surface cysts were detected on prenatal sonography.

Methods: A computerized search of our obstetric sonographic database from 1988 through 2000 identified 34 cases. Results of pathologic examinations, when performed, were obtained.

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Maternal floor infarction (MFI) is a poorly understood placental lesion reportedly associated with intrauterine growth restriction (IUGR) and recurrence. In this study of MFI and the related placental disorder, massive perivillous fibrin deposition (MFD), semiquantitative histologic criteria for these diagnoses are defined and rates of IUGR and recurrence are assessed. Pathologic slides of 80 placentas diagnosed as MFI or MFD at the Brigham and Women's Hospital (1989-99) were reviewed and reclassified as classic MFI, transmural MFD, borderline MFD, or neither MFI or MFD.

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Objective: This study related morphologic subtype, human papillomavirus status, and a second cytologic examination to the follow-up biopsy-proven high-grade squamous intraepithelial lesion (HSIL; grade II or III cervical intraepithelial neoplasia) after a cytologic diagnosis of atypical squamous cells of undetermined significance (ASCUS).

Study Design: Seven hundred four liquid-based cervical cytology specimens were classified as normal, "ASCUS, favor reactive" (AFR), "ASCUS, not otherwise specified," "ASCUS, favor low-grade squamous intraepithelial lesion," "ASCUS, favor HSIL" (AFHS), low-grade squamous intraepithelial lesion, and HSIL. Human papillomavirus typing used polymerase chain reaction-restriction fragment length polymorphism analysis.

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