A Longitudinal Study of Thrombosis and Bleeding Outcomes With Thromboprophylaxis in Pregnant Women at Intermediate and High Risk of VTE.

BACKGROUND: The efficacy and safety of thromboprophylaxis in pregnancy at intermediate to high risk of venous thrombo-embolism (VTE) is an area of ongoing research. AIM: This study aimed to assess thrombosis and bleeding outcomes associated with thromboprophylaxis in women at risk of VTE. METHODS: A cohort of 129 pregnancies, who received thromboprophylaxis for the prevention of VTE, were identified from a specialist obstetric clinic in Johannesburg, South Africa. Intermediate-risk pregnancies, with medical comorbidities or multiple low risks, were managed with fixed low-dose enoxaparin antepartum and for a median (interquartile range) of 4 (4) weeks postpartum. High-risk pregnancies, with a history of previous VTE, were managed with anti-Xa adjusted enoxaparin antepartum and for a median of 6 (0) weeks postpartum. Pregnancy-related VTE was objectively confirmed. Major bleeding, clinically relevant nonmajor bleeding (CRNMB) and minor bleeding were defined according to the International Society on Thrombosis and Hemostasis Scientific Subcommittee. RESULTS: Venous thrombo-embolism occurred antepartum in 1.4% (95% CI: 0.04-7.7) of intermediate and 3.4% (95% CI: 0.4-11.7) of high-risk pregnancies. Bleeding events occurred in 7.1% (95% CI: 2.4-15.9) of intermediate and 8.5% (95% CI: 2.8-18.7) of high-risk pregnancies. Of these bleeding events, 3.1% (95% CI: 1.0-8.0) were classified as major bleeding. On univariate analysis, no independent predictors of bleeding were identified. CONCLUSION: The rates of thrombosis and bleeding in this predominantly African population were consistent with similar studies and can be used to inform pregnant women of the benefits of anticoagulation and the risks of potential bleeding.

Detection of human papillomavirus in large cell neuroendocrine carcinoma of the uterine cervix: a study of 12 cases.

AIM: To investigate the role of human papillomavirus (HPV) in large cell neuroendocrine carcinoma (LCNEC) of the uterine cervix. METHODS: Twelve archival, immunohistochemically and/or electron microscopically confirmed cases of cervical LCNEC were studied. Non-isotopic in situ hybridisation (NISH) was performed on the formalin fixed, paraffin wax embedded biopsies using digoxigenin labelled probes to HPV types 6, 11, 16, 18, 31, and 33. The tumours were then subjected to polymerase chain reaction (PCR) analysis using GP5+/GP6+ consensus primers to the HPV L1 gene, in addition to type specific primers to the E6 and E6/E7 genes. RESULTS: HPV-16 was detected by NISH and/or PCR in seven of the 12 carcinomas. Two additional tumours were HPV-18 positive by NISH and/or PCR. HPV DNA was not detected in the three remaining cases. CONCLUSION: Integration of high risk HPV, in particular type 16 and to a lesser extent type 18, is associated with this uncommon variant of cervical carcinoma.

Large-cell neuroendocrine carcinoma of the uterine cervix--a clinicopathological study of five cases.

OBJECTIVE: The present study describes 5 cases of large-cell neuroendocrine carcinoma (LCNEC) of the uterine cervix, evaluating their clinical features and pathological profiles. METHODS: Clinical data were obtained from the patients' clinical files at the combined gynaecological-oncology unit of Johannesburg Hospital and the University of the Witwatersrand Medical School, Johannesburg, South Africa. A histopathological diagnosis was obtained after biopsy material from all 5 patients was examined microscopically and subjected to immunohistochemical staining with MNF116 (pankeratin) synaptophysin and chromagranin A, all of which are neuroendocrine markers. Two patients received pelvic radiotherapy only. None of the 5 patients in this series received chemotherapy or underwent surgery. RESULTS: All 5 patients were adult females, with an average age of 57.3 years. The majority were multiparous, with the most common presenting complaint being vaginal bleeding. Three of the 5 patients presented with advanced-stage cervical carcinoma, with evidence of metastases in 2 of them. Treatment responses and long-term survival in our series proved to be disappointing as 3 of the 5 patients died in less than 6 months. On histopathological examination, all 5 tumours showed features of a high-grade poorly differentiated malignant neoplasm with ulceration and extensive tumour necrosis including trabecular and organoid growth patterns. All 5 neoplasms also showed strong immunoreactivity for MNF116, while their endocrine nature was confirmed by staining for synaptophysin in all cases. None of the tumours showed positive straining for chromagranin A. CONCLUSIONS: LCNECs are rare tumours and distinct from other neoplasms of the uterine cervix. The results of this study reaffirm the biologically aggressive nature of this uncommon tumour and its very unfavourable prognosis.