Recommendations from the International Consensus Conference on Anemia Management in Surgical Patients (ICCAMS)

Background: Perioperative anemia has been associated with increased risk of red blood cell transfusion and increased morbidity and mortality following surgery. The optimal approach to the diagnosis and management of perioperative anemia is not fully established. Objective: To develop consensus recommendations for anemia management in surgical patients. Methods: An international expert panel reviewed the current evidence and developed recommendations using modified RAND Delphi methodology. Results: The panel recommends that all patients be screened for anemia prior to surgery. Appropriate therapy for anemia should be guided by an accurate diagnosis of the etiology. The need to proceed with surgery in some patients with anemia is expected to persist. However, early identification and effective treatment of anemia has the potential to reduce the risks associated with surgery and improve clinical outcomes. As with preoperative anemia, postoperative anemia should be treated in the perioperative period. Conclusions: Early identification and effective treatment of anemia has the potential to improve clinical outcomes in surgical patients

The role of human papillomavirus (HPV)-related molecular markers in cervical neoplasia, with emphasis on p-21 activated kinase type 1 (PAK 1)

Since high-risk Human Papillomavirus (HPV) plays a critical role in cervical carcinogenesis, it is essential to improve our understandings on the role of HPV-related molecular markers in cervical neoplasia. The aim of this study was to investigate the expression and prognostic significance of selected HPV-related markers, including HPV16/18 E2 binding sites (E2BS) methylation, Pak 1, c-FLIP, Notch 1 and Brd4 expressions, as well as the potential functions of Pak 1 in cervical neoplasia. First, the differential expressions of these markers among clinical samples of normal cervical epithelium, low-grade and high-grade cervical intraepithelial neoplasia (CINs) and cervical cancer were studied. Methylation status of E2BS 1, 2 and 4 was determined by pyrosequencing. Expressions of the target proteins were assessed by immunohistochemistry. Both HPV16/18 E2BS 1&2 and E2BS4 methylation progressively increased from normal cervix through CINs to cancer. More importantly, HPV16 E2BS1&2 (for transcriptional repression of E6/E7 oncoproteins) became more heavily methylated than E2BS4 (for transcriptional activation of E6/E7) in cervical cancer, favouring the differential binding of E2 protein to E2BS4. Pak 1, c-FLIP, Notch 1 and Brd4 were all overexpressed in cervical cancer. Their expressions increased progressively from normal cervix to low-grade +/- high-grade CINs. Pak 1 and c-FLIP expression was positively correlated with HPV18 E6 and HPV16 E7 expression respectively. Notch 1 expression was inversely correlated with HPV16 E7 and HPV18 E6 expressions. Brd4 expression was positively correlated with HPV16 E2 and inversely correlated with HPV16 E7 expressions. The prognostic significance of the molecular markers was investigated by correlation with clinical parameters. Heavier methylation at E2BS1&2 relative to E2BS4 was associated with better overall and disease-free survival in cervical cancer patients. HPV16 E2BS1&2 hypermethylation, weak cytoplasmic Brd4 expression, strong c-FLIP or Notch 1 expression were associated with higher risk of recurrent abnormal smears after treatment of CINs. The role of Pak 1 in cervical cancer was further explored by comparing its functions between cervical cancer cell lines with and without transient knock-down of Pak 1 by siRNAs. It was demonstrated that the significant functions of Pak 1 in cervical cancer were on promoting cell proliferation and inhibiting apoptosis. Transient HPV16 E6 inhibition showed no effect on total / phosphorylated Pak 1 expressions. Lastly, the function of Pak 1 on the regulation of cervical cancer cell radiosensitivity was also investigated. Pak 1 inhibition increased cell sensitivity in response to irradiation by enhancing apoptosis and inhibiting cell proliferation. Conclusively, differential methylation status at HPV16/18 E2BS, as well as Pak 1, c-FLIP, Notch 1 and Brd4 proteins contribute to cervical carcinogenesis, and are potential prognostic markers in cervical cancer and CIN patients. Pak 1 inhibitor may be a potential adjunctive agent to improve radiotherapy.published_or_final_versionObstetrics and GynaecologyDoctoralDoctor of Philosoph

Imprinting genes in gestational trophoblastic diseases

published_or_final_versionMedical SciencesMasterMaster of Medical Science

High incidence of somatic mitochondrial DNA mutations in human ovarian carcinomas

To investigate the potential role of somatic mitochondrial DNA (mtDNA) mutations in tumorigenesis, the occurrence of mutations in mtDNA of ovarian carcinomas was studied. We sequenced the D-loop region of mtDNA of 15 primary ovarian carcinomas and their matched normal controls. Somatic mtDNA mutations were detected in 20% (3 of 15) tumor samples carrying single or multiple changes. Complete sequence analysis of the mtDNA genomes of another 10 pairs of primary ovarian carcinomas and control tissues revealed somatic mtDNA mutations in 60% (6 of 10) of tumor samples. Most of these mutations were homoplasmic, and most were T→C or G→A transitions, but one represented a differential length within a run of identical C residues. A region of mtDNA sequence including the 16S and 12S rRNA genes, the D-loop and the cytochrome b gene, may represent the zone of preferred mtDNA mutation in ovarian cancer. The high incidence of mtDNA mutations found in ovarian carcinomas and other human cancers suggests that genetic instability of mtDNA might play a significant role in tumori-genesis.link_to_subscribed_fulltex

Diagnostic Performance of Risk of Malignancy Algorithm (ROMA), Risk of Malignancy Index (RMI) and Expert Ultrasound Assessment in a Pelvic Mass Classified as Inconclusive by International Ovarian Tumour Analysis (IOTA) Simple Rules

The accurate prediction of malignancy for a pelvic mass detected on ultrasound allows for appropriate referral to specialised care. IOTA simple rules are one of the best methods but are inconclusive in 25% of cases, where subjective assessment by an expert sonographer is recommended but may not always be available. In the present paper, we evaluate the methods for assessing the nature of a pelvic mass, including IOTA with subjective assessment by expert ultrasound, RMI and ROMA. In particular, we investigate whether ROMA can replace expert ultrasound when IOTA is inconclusive. This prospective study involves one cancer centre and three general units. Women scheduled for an operation for a pelvic mass underwent a pelvic ultrasound pre-operatively. The final histology was obtained from the operative sample. The sensitivity, specificity and accuracy for each method were compared with the McNemar test. Of the 690 women included in the study, 171 (25%) had an inconclusive IOTA. In this group, expert ultrasound was more sensitive in diagnosing a malignant mass compared to ROMA (81% vs. 63%, p = 0.009) with no significant difference in the specificity or accuracy. All assessment methods involving IOTA had similar accuracies and were more accurate than RMI or ROMA alone. In conclusion, when IOTA was inconclusive, assessment by expert ultrasound was more sensitive than ROMA, with similar specificity