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Australia has transitioned to primary Human Papillomavirus (HPV) screening; however, high-risk HPV (hrHPV)-negative high-grade squamous intraepithelial lesions and adenocarcinoma in situ have been reported. HPV in situ hybridisation (ISH) testing has been proposed to reclassify these cases. This study identified hrHPV-negative lesions and assessed HPV-ISH. A total of 89 of 1468 patients (6.06%) had hrHPV-negative lesions, and HPV-ISH revealed five (5.75%) reclassified positive cases. No demographical differences were found between groups. Current population-level screening is effective. HPV-ISH was not effective for reclassification. This small, significant population requires further study to assess the phenomenon and augment detection given the implications of misidentification., (© 2024 Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Background: Opportunistic bilateral salpingectomy during benign gynaecologic surgery is advocated as a risk-reducing strategy due to the inverse association of epithelial ovarian cancers observed in epidemiological studies in a low-risk setting. Currently, no formal guidance exists for permanent surgical contraception at time of caesarean section in Australia., Aims: Our aim was to survey Fellows of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) regarding bilateral salpingectomy compared to other procedures offered for permanent contraception at the time of caesarean section., Materials and Methods: An online survey was utilised to collect clinician demographics, opinions, barriers, and justifications in regard to options of permanent surgical contraception at time of caesarean section., Results: Bilateral salpingectomy was identified as the most effective method of permanent contraception at time of caesarean section. However, only 62% of respondents offer the procedure as a method of permanent contraception. The two most common reasons for clinicians to offer bilateral salpingectomy at time of caesarean section were evidence suggesting a link between the fallopian tube and gynaecological cancer (80%) and efficacy as a permanent form of contraception (16%). The primary barrier identified by 51% of respondents was perceived increased risk of surgical complications, followed by reasoning that it would not allow the possibility of future tubal reversal., Conclusion: This study identifies diverse opinions on surgical approach to permanent contraception at time of caesarean section and offered by clinicians of RANZCOG. Further research is required to establish safety profiles and short- and long-term risks of bilateral salpingectomy., (© 2023 Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Objective: Adenocarcinoma in situ (AIS) of the cervix is a precursor to cervical adenocarcinoma. When AIS is detected by cervical screening an excision biopsy is mandatory to exclude invasion. We aimed to compare margins status, specimen size and fragmentation after loop electrosurgical excision procedure (LEEP) and 'cold knife cone biopsy' (CKC)., Methods: The EXCISE Trial was an investigator-initiated, multicenter, open-label, parallel-group, phase 2, randomized study. Patients were enrolled at seven hospitals in Australia and New Zealand. We randomly assigned women aged ≥18 to ≤45 years with screen detected AIS to LEEP or CKC. Co-primary endpoints were margin status, specimen size and fragmentation. Analysis was by intention-to-treat., Results: Between August 2, 2017 and September 6, 2019, 40 patients were randomly assigned 2:1 to LEEP or CKC. Margin status was evaluable in 36 cases. The proportion of patients with involved margins did not differ between groups. 25 of 26 LEEP and all 14 CKC biopsies were excised as single specimens (p = 1·00). There were no differences in specimen dimensions. Patients in the CKC group had more post-operative complications (64.3% compared to 15.4% for LEEP p = ·00). There were no differences in grade three complications (p = ·65)., Conclusions: LEEP was not associated with a greater likelihood of positive margins, specimen fragmentation or smaller excision compared to CKC when performed according to a standardized protocol. However, the study was not powered to establish non-inferiority of LEEP and a definitive phase 3 trial to compare margin status and rates of treatment failure after LEEP and CKC is warranted., Competing Interests: Declaration of Competing Interest PAC and CDHW have received honoraria from Seqirus unrelated to this work. MRS has received grants from Astellas, Amgen, Astra Zeneca, Bayer, Bionomics, Bristol-Meyers-Squibb, Celgene, Medivation, Merck Sharp & Dohme, Pfizer, Roche, Sanofi, Specialised Therapeutics and Tilray unrelated to this work. All other authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Little is known about the delivery of surgical services and outcomes for women with ovarian cancer across New South Wales (NSW)., Aim: The study objective was to provide a descriptive analysis of the proportion of women who had surgery for ovarian cancer in NSW in specialist gynaecological oncology hospitals and compare outcomes for women attending specialist and non-specialist services in NSW., Materials and Methods: This study is a retrospective analysis of women with primary ovarian, fallopian tube or peritoneal cancer from 2009 to 2012. Data were analysed from the NSW Cancer Registry, NSW Admitted Patient Data Collection and Register of Births Deaths and Marriages. Treating hospitals were characterised as public specialist, public non-specialist and private. Morbidity and mortality outcomes are reported., Results: The study included 1106 women. Fifty-seven hospitals performed surgery: seven public specialist, 27 private and 23 public non-specialist hospitals. The highest proportion of surgery was performed in public specialist hospitals (61%). There was considerable variation in the utilisation of public specialist hospitals between local health districts. There was no significant difference in outcomes related to the type of hospital where surgery was performed., Conclusions: Although the majority of women are having surgery in a specialist gynaecological oncology public hospital across NSW, many are not. Women living in regional and remote NSW were less likely to have their surgery in a specialist hospital. This is the first step in understanding where women in NSW are currently receiving their surgical care, as well as the outcomes related to this., (© 2020 Commonwealth of Australia. Australian and New Zealand Journal of Obstetrics and Gynaecology © 2020 The Royal Australian and New Zealand College of Obstetricians and Gynecologists.)

Background: Human epididymis protein 4 (HE4) has been proposed as a novel biomarker for the diagnosis of epithelial ovarian cancer. Using HE4 and CA125, the risk of malignancy algorithm (ROMA) has been shown to be effective in the stratification of epithelial ovarian cancer risk., Aims: To determine the effectiveness of HE4 and ROMA in the diagnosis of malignancy of women presenting with a complex pelvic mass in an Australian population and to compare it with CA125 and the risk of malignancy index (RMI)., Materials and Methods: Prospective recruitment of women was conducted between October 2012 and March 2014 (n = 50). CA125 and HE4 serum concentrations were collected and stored for subsequent analysis. Sensitivities, specificities, positive predictive values (PPV) and negative predictive values (NPV) were calculated for HE4, CA125, ROMA and the RMI. Receiver operating characteristic (ROC) area under the curves (AUC) were also calculated for comparison., Results: There was a higher HE4 level in women with ovarian cancer compared with women with benign pathology (P = 0.008), and this observation was seen in benign versus stage 1 ovarian cancer women (P = 0.025). HE4 had a better specificity than CA125 for the diagnosis of ovarian cancer in all women (P = 0.022), and this effect was also observed in premenopausal women (P = 0.012). Furthermore, the ROC-AUC for HE4 was superior than CA125 in all women (P = 0.0451). The ROMA algorithm was not inferior to the RMI calculation in this population., Conclusions: In an Australian population, HE4 and ROMA are useful in the diagnosis of epithelial ovarian cancer., (© 2015 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

The simultaneous bilateral rupture of the quadriceps tendon is a rare injury; only occasional reports exist about the bilateral simultaneous rupture of the patellar tendon. Degenerative changes of the tendon due to drugs or diseases lead to the rupture. We describe two cases of simultaneous rupture of the patellar and contralateral quadriceps tendons; only one patient had special risks. We report the management of therapy and the functional results using the Lysholm score and Knee Rating Scale.

Polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic amines (HCAs) ingested with food have repeatedly been suggested to be involved in the malignant transformation of colon epithelial cells. In order to test this hypothesis, HCEC cells (SV40 large T antigen-immortalized human colon epithelial cells) were incubated with a racemic mixture of benzo[c]phenanthrene dihydrodiol epoxides (B[c]PhDE), extremely potent carcinogenic PAH metabolites in vivo, or with 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-OH-PhIP), the N-hydroxylated metabolite of the most abundant HCA in cooked meat. First, it was shown that HCEC cells express sulfotransferase 1A1, which is needed to metabolize N-OH-PhIP to the corresponding N-sulfonyloxy derivative, the direct precursor molecule of genotoxic nitrenium ions. Thereafter, exponentially growing HCEC cells were exposed five times to 0.1 microg (0.37 nmol) B[c]PhDE/ml for 30 min or 0.72 microg (3 nmol) N-OH-PhIP/ml for 24 h. Chemically treated HCEC cells showed an enhanced saturation density and grew faster than the corresponding solvent-treated cell cultures. After five treatment cycles, HCEC(B[c]PhDE) as well as HCEC(N-OH-PhIP) cells lost cell-cell contact inhibition and started piling up and forming foci in the culture flasks. Furthermore, HCEC(B[c]PhDE) and HCEC(N-OH-PhIP) cells were injected i.m. into SCID mice. Within 6 weeks after injection, eight animals out of eight injected with HCEC(B[c]PhDE) or HCEC(N-OH-PhIP) cells developed tumors at the site of injection, thus demonstrating the high tumorigenic potential of the HCEC(B[c]PhDE) and HCEC(N-OH-PhIP) cell cultures. Taken together, we show for the first time that the abovementioned active PAH metabolites as well as N-OH-PhIP are indeed able to malignantly transform human colon epithelial cells in vitro.

Lipolytic products of triglyceride-rich lipoproteins, i.e., free fatty acids, may cause activation and dysfunction of the vascular endothelium. Mechanisms of these effects may include lipid peroxidation. One of the major and biologically active products of peroxidation of n-6 fatty acids, such as linoleic acid or arachidonic acid, is the aldehyde 4-hydroxynonenal (HNE). To study the hypothesis that HNE may be a critical factor in endothelial cell dysfunction caused by free fatty acids, human umbilical endothelial cells (HUVEC) were treated with up to160 microM of linoleic or arachidonic acid. HNE formation was detected by immunocytochemistry in cells treated for 24 h with either fatty acid, but more markedly with arachidonic acid. To study the cellulareffects of HNE, HUVEC were treated with different concentrations of this aldehyde, and several markers of endothelial cell dysfunction were determined. Exposure to HNE for 6 and 9 h resulted in increased cellular oxidative stress. However, short time treatment with HNE did not cause activation of nuclear factor-kappaB (NF-kappaB). In addition, HUVEC exposure to HNE caused a dose-dependent decrease in production of both interleukin-8 (IL-8) and intercellular adhesion molecule-1 (ICAM-1). On the other hand, HNE exerted prominent cytotoxic effects in cultured HUVEC, manifested by morphological changes, diminished cellular viability, and impaired endothelial barrier function. Furthermore, HNE treatment induced apoptosis of HUVEC. These data provide evidence that HNE does not contribute to NF-kappaB-related mechanisms of the inflammatory response in HUVEC, but rather to endothelial dysfunction, cytotoxicity, and apoptotic cell death., (Copyright 1999 Wiley-Liss, Inc.)