Richard W. Lieberman

Domain-Specific Image Analysis for Cervical Neoplasia Detection Based on Conditional Random Fields

This paper presents a domain-specific automated image analysis framework for the detection of pre-cancerous and cancerous lesions of the uterine cervix. Our proposed framework departs from previous methods in that we include domain-specific diagnostic features in a probabilistic manner using conditional random fields. Likewise, we provide a novel window-based performance assessment scheme for 2D image analysis which addresses the intrinsic problem of image misalignment. Image regions corresponding to different tissue types are indentified for the extraction of domain-specific anatomical features. The unique optical properties of each tissue type and the diagnostic relationships between neighboring regions are incorporated in the proposed conditional random field model. The validity of our method is examined using clinical data from 48 patients, and its diagnostic potential is demonstrated by a performance comparison with expert colposcopy annotations, using histopathology as the ground truth. The proposed automated diagnostic approach can support or potentially replace conventional colposcopy, allow tissue specimen sampling to be performed in a more objective manner, and lower the number of cervical cancer cases in developing countries by providing a cost effective screening solution in low-resource settings.

Assessment of "fresh" versus "macerated" as accurate markers of time since intrauterine fetal demise in low-income countries.

To compare provider assessment of fetal maceration with death‐to‐delivery interval to evaluate the reliability of appearance as a proxy for time of death.

Placental histology and neutrophil extracellular traps in lupus and pre-eclampsia pregnancies

Objective Systemic lupus erythematosus (SLE) is associated with increased risk of adverse pregnancy outcomes, including pre-eclampsia, particularly in association with antiphospholipid antibody syndrome (APS). While significant placental abnormalities are expected in pre-eclampsia, less is known about how lupus activity and APS in pregnancy affect the placenta. We describe placental pathology from a population of lupus pregnancies, several of which were complicated by APS-related thromboses, in which pre-eclampsia and other complications developed. We performed standard histopathological placental review and quantified neutrophils and neutrophil extracellular traps (NETs) in the intervillous space, given the recognised association of NETs with lupus, APS and pre-eclampsia. Methods Pre-eclampsia, SLE and control placentas were scored for histological features, and neutrophils were quantified on H&E and immunohistochemical staining for the granular protein myeloperoxidase. NETs were identified by extracellular myeloperoxidase staining in the setting of decondensed nuclei. Non-parametric analysis was used to evaluate differences in netting and intact neutrophils between groups, with Kruskal–Wallis testing for associations between histological findings and neutrophils. Results Placentas were evaluated from 35 pregnancies: 10 controls, 11 pre-eclampsia, 4 SLE+pre-eclampsia and 10 SLE, including one complicated by catastrophic APS and one complicated by hepatic and splenic vein thromboses during pregnancy. Intrauterine growth restriction and oligohydramnios were observed in lupus cases but not controls. Significantly more NETs were found infiltrating placental intervillous spaces in pre-eclampsia, SLE+pre-eclampsia and all 10 SLE non-pre-eclampsia cases. The ratio of NETs to total neutrophils was significantly increased in all case groups compared with controls. When present, NETs were associated with maternal vasculitis, laminar decidual necrosis, maternal–fetal interface haemorrhage and non-occlusive fetal thrombotic vasculopathy. Conclusions In this pilot study of placental tissue from lupus pregnancies, outcomes were more complicated, particularly if associated with APS. Placental tissue revealed marked inflammatory and vascular changes that were essentially indistinguishable from placental tissue of pre-eclampsia pregnancies.

Cost-effectiveness of pap smear screening for vaginal cancer after total hysterectomy for benign disease.

Objective To examine the cost effectiveness of Papanicolaou screening for cancer after total hysterectomy for benign disease. Materials and methods Decision analysis including Markov modeling applied to women aged 40 or older with a history of total hysterectomy for benign disease. We derived expected discounted costs and life expectancy. Results Maximum gain in life expectancy between no screening and any screening strategy was approximately 3 weeks. Cost effectiveness in dollars per life-year gained was > or =

Examining the relationship between positive mid-gestational fetal fibronectin assays and histological evidence of acute placental inflammation

143,875 more than no screening for strategies starting at age 50, and over

A rare case of vulvar endometriosis in an adolescent girl.

12 million for aged 40 or more screening strategy. None of the sensitivity analyses caused the incremental cost effectiveness of any strategy to come to less than

Comparison of Microscopic Examination and Human Papillomavirus DNA Subtyping in Vulvar Lesions of Premenarchal Girls

100,000 per life year gained compared with no screening. Conclusions Despite significant costs for any strategy, Pap smear screening after total hysterectomy for benign disease provides essentially no gain in life expectancy. In absence of risks for genital cancer, such screening is not cost effective.

Semantic Image Analysis for Cervical Neoplasia Detection

Abstract Aims: Both acute placental inflammation and positive mid-gestational cervico-vaginal fetal fibronectin assays have been independently correlated with preterm delivery. We conducted this study to examine the relationship between positive mid-gestational fetal fibronectin (fFN) assays and histological evidence of acute placental inflammation at delivery among women presenting with symptomatic preterm labor. Methods: This retrospective chart review included women who underwent cervico-vaginal fFN testing for preterm contractions between 24–34 weeks gestation and also had placental histological analysis after delivery. Women with a multiple gestation, cerclage, preterm premature rupture of membranes, intercourse or vaginal bleeding within 24 h before the assay were excluded. The primary outcome was histological evidence of acute placental inflammation defined as acute chorioamnionitis, acute deciduitis, funisitis, or microabscess formation. Results: Of 82 women who met all study inclusion criteria, 45% were fFN positive. Women with positive assays were no more likely to have histological evidence of acute inflammation noted at birth than women with negative assays (45% vs. 26%, P=0.07). The assay had a sensitivity of 58.6%, specificity of 62.3%, positive predictive value of 46.0%, and negative predictive value of 73.3% for predicting acute inflammation at delivery. Conclusions: No association exists between positive fetal fibronectin assays and acute histologic placental inflammation at birth.

A stratified randomized double-blind phase II trial of celecoxib for treating patients with cervical intraepithelial neoplasia: The potential predictive value of VEGF serum levels: An NRG Oncology/Gynecologic Oncology Group study

OBJECTIVE To describe a case of vulvar endometriosis in a teenager after a history of vulvar ulcers in the same location. DESIGN Case report. SETTING University medical center. PATIENT(S) A 13-year-old girl with a history of vulvar ulcers. MAIN OUTCOME MEASURE(S) None RESULT(S) A 13-yr-old female presented with painful, open vulvar ulcerations on the inner side of her labia minora. Biopsy revealed dermatitis with ulceration. One year later she noted an ulcer and blood in her undergarments. Biopsy results were consistent with endometriosis. Five years later, the lesions persisted and bled during menses. A bilateral labial excision was performed. Pathology again revealed endometriosis. CONCLUSION(S) Vulvar endometriosis is extremely unusual. This rare case of vulvar endometriosis in the same location as a previous vulvar ulcer is most likely due to ectopic transplantation of endometrial cells during a menstrual cycle. Excision is considered definitive treatment.

Enhancing colposcopy with polarized light

STUDY OBJECTIVE The purpose of this study is to compare the microscopic examination and human papillomavirus (HPV) DNA subtyping of vulvar specimens from premenarchal girls clinically diagnosed with condyloma to determine whether DNA subtyping aids in the diagnostic process. DESIGN A retrospective chart review was performed on all premenarchal girls who underwent surgical treatment of clinically diagnosed condyloma between 1993 and 1999 at the University of Michigan Medical Center by the Pediatric and Adolescent Gynecology Service. Tissue was sent for pathologic evaluation and in 10 patients the specimens also underwent DNA subtyping. One patient had prior DNA subtyping. All the other lesions were surgically ablated. The microscopic slides were reviewed by a single pathologist blinded to the study. SETTING The study was performed in a tertiary care university hospital. PARTICIPANTS The study group included 11 premenarchal girls with an average age of 2.3 yr. MAIN OUTCOME MEASURES The charts were reviewed for previous HPV treatment, maternal history of HPV, history of sexual abuse, microscopic diagnosis, and HPV DNA subtyping. RESULTS Four patients had prior surgical treatment and two patients had undergone prior medical treatment. The microscopic diagnosis was condyloma in 8 patients, chronic dermatitis in 2 patients, and 1 patient had VIN 2-3. All 11 specimens tested positive for HPV DNA, 10 specimens contained at least one of the low-risk subtypes (6, 11, 42, 43, 44), and 1 tested positive for low-risk as well as intermediate/high-risk HPV subtypes (16, 18, 31, 33, 35, 45, 51, 52, 56). CONCLUSIONS Although all the patients with a clinical diagnosis of condyloma tested positive for HPV DNA, only 9 of 11 were definitely diagnosed with HPV-related pathology by microscopic examination. Therefore, in premenarchal patients with verrucous lesions in the anogenital area, microscopic evaluation alone may be inadequate as a confirmatory test when a positive clinical diagnosis has been made, and HPV DNA subtyping should be considered to avoid confusion with the diagnosis.