Acceptability and feasibility of telehealth outpatient video-link consultations: A national cross-sectional survey of surgeons prior to the COVID-19 pandemic.

OBJECTIVE: This study explored use and perceived barriers to the use of post-operative video-link telehealth among a sample of Australian surgeons shortly before the COVID-19 pandemic. METHODS: During 2019-2020, a survey was mailed to RACS or RANZCOG Fellows. DESIGN: Cross-sectional survey. SETTING AND PARTICIPANTS: A total of 907 surgeons practising in Australia completed the survey. MAIN OUTCOME MEASURES: The study-specific survey assessed telehealth use in the last 3 months and the perceived barriers and enablers to the use of post-operative teleconsultations, across the domains: quality of care; convenience and efficiency; legal/regulatory issues; financial issues and technological issues. RESULTS: Twenty-five percent of eligible surgeons returned the survey, with n = 763 pre-pandemic responses included in analyses. Approximately one-quarter (26%) of surgeons had used telehealth post-operatively with patients in the last 3 months. The most frequently endorsed barriers to use related to quality of care: 'I cannot undertake a patient examination' and 'I cannot provide the same level of care as during an in-person consultation'; and convenience and efficiency: 'Teleconsultations are more difficult to arrange'. Surgeons who had recently used telehealth were less likely to endorse most barriers. Younger age, awareness of Medicare telehealth reimbursement and working in neurosurgery, urology, paediatric surgery and plastic and reconstructive surgery (compared to general surgery) were associated with recent telehealth use by surgeons. CONCLUSIONS: Some surgeons' perceived barriers to telehealth pre-COVID may be overcome by COVID-19-related telehealth uptake and familiarisation. However, many barriers will need to be addressed to ensure that telehealth adoption is sustained beyond the pandemic.

Gaps in patient-centered follow-up cancer care: a cross sectional study.

Objective There are published guidelines on the care that should be provided to cancer patients upon finishing treatment (i.e. follow-up care). Gaps in care may arise where patients' reported experiences of care do not align with guideline recommendations. The aim of this study was to explore whether oncology patients report gaps in patient-centered follow-up care. Methods This study was a cross-sectional survey of adult cancer patients receiving follow-up care within four outpatient oncology clinics. Patients were approached in clinic waiting rooms and asked to complete an electronic survey. The survey examined patients' self-report of receiving six aspects of follow-up care. Results A total of 239 participants completed the survey (study consent rate = 83%). Only 49% of participants received all six items of care. Patients reported high rates of being told who to contact if they have any questions or concerns (95%); who to contact if signs or symptoms occur (91%); and what to expect in their follow-up care (90%). A lower proportion of patients indicated they were informed about the role of their GP after treatment has finished (79%); what symptoms or signs might suggest the cancer had returned (74%); or were given a written care plan (71%). Conclusions: The study highlights that there is a gap between some aspects of optimal patient-centered care, and the actual care received by patients. Health care providers and researchers should consider how to improve follow-up care experiences to ensure best practice cancer care delivery during this important stage in cancer survivorship.

The System for Patient Assessment of Cancer Experiences (SPACE): a cross-sectional study examining feasibility and acceptability.

BACKGROUND: Continuous quality improvement in cancer care relies on the collection of accurate data on the quality of care provided. It is suggested that such an approach should: (i) measure the patient's care experience throughout the cancer trajectory; (ii) use items and response scales that measure concrete and specific aspects of care; (iii) minimise recall bias; (iv) minimise the burden placed on patients for providing data; (v) minimise administrative burden; and (vi) collect actionable data. The System for Patient Assessment of Cancer Experiences (SPACE) was developed to meet these objectives. This study describes the feasibility and acceptability of the SPACE in a sample of oncology outpatients. METHODS: The SPACE was examined in four medical oncology centres. Adult patients were approached by a research assistant prior to their scheduled consultation. Consenting participants completed the SPACE on a computer tablet. Items were tailored to the patient's cancer treatment phase. RESULTS: Of the eligible participants, 1143 consented (83%) and 1056 completed the survey (92%). The average time taken to complete the survey was 6 min 28 s. A large proportion of the sample indicated that the survey was acceptable (88-93% across three acceptability items). CONCLUSION: This study demonstrates that the SPACE can be feasibly administered each time a patient comes to the oncology unit and is acceptable to patients. The SPACE could be used to quantify the care experiences which patients receive during their cancer care. The resulting data could be used to set benchmarks and improve the performance of cancer clinics.

Preferences for models of peer support in the digital era: A cross-sectional survey of people with cancer.

OBJECTIVE: Many people with cancer report an unmet need for peer support, yet participation rates are low. This study examined cancer patients' preferences for participating in peer support, and the characteristics associated with having or wanting to participate in peer support. METHODS: Adult cancer patients were recruited from outpatient oncology clinics at 5 hospitals in Australia. Participants were invited to self-complete 2 questionnaires: one at recruitment assessing their demographic and cancer characteristics, and another 4 weeks later assessing their preferences for participating in cancer-related peer support. RESULTS: The peer support questionnaire was completed by 177/273 (65%) of participants. Most (59%, n = 104) had or wanted to participate in peer support. More than half reported that it was important the people they connected with had the same cancer treatment (56%, n = 99) or type of cancer (53%, n = 94) as themselves. Half had or wanted to participate in 1-to-1 peer support (52%, n = 92). Half had or wanted to connect with peers face-to-face (53%, n = 93). Only 13% (n = 23) were receptive to connecting with peers over the internet. Being aged ≤65 years was significantly associated (OR = 2.3; 95% CI: 1.1-5.1) with reporting a preference for participating in peer support. CONCLUSIONS: Cancer patients are interested in participating in peer support, particularly those who are younger. Despite the digital era, traditional forms of peer support continue to be important in supporting people with cancer. Greater understanding of the barriers to cancer patients' involvement in potentially low cost and high reach web-based models of peer support is required.

Using the Health Belief Model to explore why women decide for or against the removal of their ovaries to reduce their risk of developing cancer.

BACKGROUND: Women at an increased risk of ovarian cancer often have to decide for or against the surgical removal of their healthy ovaries to reduce their cancer risk. This decision can be extremely difficult. Despite this, there is a lack of guidance on how to best support women in making this decision. Research that is guided by theoretical frameworks is needed to help inform clinical practice. We explored the decision-making process of women who are at an increased risk of developing ovarian cancer and had to decide for or against the removal of their ovaries. METHODS: A qualitative study of 18 semi-structured interviews with women who have attended a cancer treatment centre or cancer counselling and information service in New South Wales, Australia. Data collection and analysis were informed by the Health Belief Model (HBM). Data was analysed using qualitative content analysis. RESULTS: The paper describes women's decision making with the help of the four constructs of the HBM: perceived susceptibility, perceived severity, perceived benefits, and perceived barriers. The more anxious and susceptible women felt about getting ovarian cancer, the more likely they were to have an oophorectomy. Women's anxiety was often fuelled by witnessing family members suffer or die from cancer. Women considered a number of barriers and potential benefits to having the surgery but based their decision on "gut feeling" and experiential factors, rather than statistical risk assessment. Age, menopausal status and family commitments seemed to influence but not determine women's decisions on oophorectomy. Women reported a lack of decision support and appreciated if their doctor explained their treatment choice, provided personalised information, involved their general practitioner in the decision-making process and offered a second consultation to follow-up on any questions women might have. CONCLUSIONS: These findings suggest that deciding on whether to have an oophorectomy is a highly personal decision which can be described with the help of the HBM. The results also highlight the need for tailored decision support which could help improve doctor-patient-communication and patient-centred care related to risk reducing surgery in women at an increased risk of ovarian cancer.

Consumer input into health care: Time for a new active and comprehensive model of consumer involvement.

BACKGROUND: To ensure the provision of patient-centred health care, it is essential that consumers are actively involved in the process of determining and implementing health-care quality improvements. However, common strategies used to involve consumers in quality improvements, such as consumer membership on committees and collection of patient feedback via surveys, are ineffective and have a number of limitations, including: limited representativeness; tokenism; a lack of reliable and valid patient feedback data; infrequent assessment of patient feedback; delays in acquiring feedback; and how collected feedback is used to drive health-care improvements. OBJECTIVES: We propose a new active model of consumer engagement that aims to overcome these limitations. This model involves the following: (i) the development of a new measure of consumer perceptions; (ii) low cost and frequent electronic data collection of patient views of quality improvements; (iii) efficient feedback to the health-care decision makers; and (iv) active involvement of consumers that fosters power to influence health system changes.

Does screening for physical and psychosocial symptoms vary between medical oncology treatment centres?

OBJECTIVE: Our aim is to examine whether provider screening for physical and emotional symptoms, as reported by medical oncology outpatients, varies across medical oncology treatment centres. METHODS: A cross-sectional sample of 716 patients attending the outpatient medical oncology department of six public cancer treatment centres across five Australian states participated. Four patient-report survey items explored how often patients were specifically asked by clinical staff at the treatment centre about their (i) emotional distress (anxiety, distress and depression), (ii) pain, (iii) fatigue and (iv) other physical symptoms (e.g. nausea and constipation). Asking at less than half of all appointments was classified as infrequent screening. RESULTS: No significant associations were found between treatment centre and symptom screening for emotional distress (p = 0.65), pain (p = 0.21), fatigue (p = 0.95) and other physical symptoms (p = 0.40). The proportion of patients who were regularly screened versus infrequently screened was significantly higher for physical symptoms than emotional symptoms (p < 0.001): 36% infrequently screened for emotional distress (range: 33-45%), 15% infrequently screened for pain (range: 9-21%), 16% infrequently screened for fatigue (range: 15-19%) and 11% infrequently screened for other physical symptoms (range: 5-17%). CONCLUSIONS: No significant variation in symptom screening was found across treatment centres. While the majority of patients received recommended care, treatment centres must continue to improve symptom screening rates, particularly for emotional distress. However, screening is only the first step and must be accompanied by the offer of help and provision of help to relieve patient suffering.

Insights into preferences for psycho-oncology services among women with gynecologic cancer following distress screening.

Much attention has been given to implementing routine screening programs in cancer care to improve the management of distress following diagnosis. Although patients might screen positive for distress, several studies have found that most then refuse additional psychosocial support. To inform the development of successful models of distress screening, this qualitative study explored preferences for psychosocial care among 18 women diagnosed with a gynecologic cancer who scored at least 4 on the Distress Thermometer (DT). Participants were recruited from a gynecologic oncology outpatient clinic in Newcastle, Australia, and interviewed. Unanimously, participants felt that completing the DT was an integral part of their cancer care. However, half then refused the referral to see a psychologist. These women typically reported that a referral was not needed, because their rating on the DT reflected transient stressors or physical distress. Many also spoke about their need to cope with the challenges they were facing on their own and the extensive social support they already had in place to help them overcome these challenges. In contrast, women who accepted referral to the psychologist often struggled to cope with several losses they felt had existential and long-term effects. Commonly, these women reported not having the social support they needed, managing several concurrent life stressors, and/or not having the repertoire of coping skills they required to "remain afloat." Findings from this study begin to bridge the gap between clinicians' and patients' expectations of how psychosocial services should be used in response to distress screening.

Preparation for Cancer Treatment: A Cross-Sectional Study Examining Patient Self-Reported Experiences and Correlates.

Given the significant physical and psychosocial side-effects cancer treatment has on individuals, it is important to ensure patients receive adequate preparation prior to treatment. The purpose of this study was to explore, among Australian oncology patients, (i) the self-reported treatment preparation information they received; and (ii) the patient characteristics associated with the treatment preparation information received. Patients in the early stages of cancer treatment were invited to complete a survey exploring their receipt of information about treatment preparation. Items assessed patients' self-report of whether they had received information about the treatment process. A total of 165 participants completed the survey. Patients most frequently reported receiving information about how they might feel physically (94%) and what side effects to watch for (93%). One in five patients reported not receiving information about how to cope with any stress or worry related to treatment. Females reported receiving significantly fewer items of care compared to males (p = 0.0083). This study suggests that while self-reported preparation for cancer treatment is generally high, components of preparation related to psychosocial concerns could be improved. Survey data could be used as a feedback tool for centres to monitor delivery of care.

Top Priorities for Health Service Improvements Among Australian Oncology Patients.

OBJECTIVE: To determine among a sample of Australian cancer patients receiving outpatient oncology care: 1) the most frequently endorsed general health service improvements selected by patients; 2) for the three most endorsed general health service improvements, the proportion of participants endorsing specific health service changes; and 3) sociodemographic, disease and treatment characteristics associated with the most frequently endorsed general health service improvements. METHODS: A cross-sectional survey was conducted across six outpatient oncology treatment units located in New South Wales, Australia. Patients receiving chemotherapy for any cancer diagnosis at any of six oncology services were recruited. Participants completed an online survey which included the Consumer Preferences Survey. Logistic regression analyses were conducted to identify sociodemographic, disease and treatment characteristics associated with frequently endorsed health service improvements. RESULTS: A total of 879 eligible patients initiated the survey (72% consent rate). Participants selected a median of two health service improvements. The three most wanted improvements were car parking (56%), up-to-date information about treatment or condition progress (19%), and hospital catering (17%). Age was the only characteristic significantly associated with identifying car parking as a needed improvement. CONCLUSION: Achieving high quality cancer care requires understanding of the views and experiences of patients about the quality of care they receive. Car parking and access to information were the two most frequently endorsed general health service changes desired by this sample of participants. PRACTICE IMPLICATION: Future studies could examine whether enacting changes as per patient feedback improves patient perceptions of quality of care, and health outcomes.

Toll-like receptor (TLR) and nucleosome-binding oligomerization domain (NOD) gene polymorphisms and endometrial cancer risk.

BACKGROUND: Endometrial cancer is the most common gynaecological malignancy in women of developed countries. Many risk factors implicated in endometrial cancer trigger inflammatory events; therefore, alterations in immune response may predispose an individual to disease. Toll-like receptors (TLRs) and nucleosome-binding oligomerization domain (NOD) genes are integral to the recognition of pathogens and are highly polymorphic. For these reasons, the aim of the study was to assess the frequency of polymorphic variants in TLR and NOD genes in an Australian endometrial cancer population. METHODS: Ten polymorphisms were genotyped in 191 endometrial cancer cases and 291 controls using real-time PCR: NOD1 (rs2075822, rs2907749, rs2907748), NOD2 (rs5743260, rs2066844, rs2066845), TLR2 (rs5743708), TLR4 (rs4986790) and TLR9 (rs5743836, rs187084). RESULTS: Haplotype analysis revealed that the combination of the variant alleles of the two TLR9 polymorphisms, rs5743836 and rs187084, were protective for endometrial cancer risk: OR 0.11, 95% CI (0.03-0.44), p = 0.002. This result remained highly significant after adjustment for endometrial cancer risk factors and Bonferroni correction for multiple testing. There were no other associations observed for the other polymorphisms in TLR2, TLR4, NOD1 and NOD2. CONCLUSIONS: The variant 'C' allele of rs5743836 causes greater TLR9 transcriptional activity compared to the 'T' allele, therefore, higher TLR9 activity may be related to efficient removal of microbial pathogens within the endometrium. Clearly, the association of these TLR9 polymorphisms and endometrial cancer risk must be further examined in an independent population. The results point towards the importance of examining immune response in endometrial tumourigenesis to understand new pathways that may be implicated in disease.

Polymorphisms in TP53 and MDM2 combined are associated with high grade endometrial cancer.

OBJECTIVES: Determinants of endometrial cancer grade have not been precisely defined, however, cell cycle control is considered to be integrally involved in endometrial cancer development. TP53 and MDM2 are essential components for cell cycle arrest and apoptosis. Polymorphisms in these genes cause TP53 inactivation and MDM2 over-expression, leading to accumulation of genetic errors. METHODS: One polymorphism in MDM2, rs2279744 (SNP309) and three polymorphisms in TP53 rs1042522 (R72P), rs17878362 and rs1625895 were genotyped in 191 endometrial cancer cases and 291 controls using PCR-based fragment analysis, RFLP analysis and real-time PCR. RESULTS: The results showed no associations of the three TP53 polymorphisms and MDM2 SNP309 alone or in combination with endometrial cancer risk. However, the combination of MDM2 SNP309 and the three TP53 polymorphisms was significantly associated with a higher grade of endometrial cancer (wild-type genotypes versus variant genotypes: OR 4.15, 95% CI 1.82-9.46, p=0.0003). Analysis of family history of breast cancer revealed that the variant genotypes of the three TP53 polymorphisms were significantly related to a higher frequency of family members with breast cancer in comparison to endometrial cancer cases without a family history of breast cancer (wild-type genotypes versus variant genotypes: OR 2.78, 95% CI 1.36-5.67, p=0.004). CONCLUSIONS: The combination of the MDM2 SNP309 and the three TP53 polymorphisms appear to be related to a higher grade of endometrial cancer. The association of the endometrial cancer cases with family history of breast cancer and the three TP53 polymorphisms suggests that this constellation of malignancies may represent a low-risk familial cancer grouping.

Positron emission tomography and granulosa cell tumor recurrence: a report of 2 cases.

Two case reports of women with recurrent granulosa cell tumors identified initially by increasing levels of inhibin. As part of their investigation to assess the extent of the recurrence, an abdominopelvic computed tomography and a positron emission tomography scans were performed. Interestingly, the recurrent tumors were identified on the abdominopelvic computed tomography but not on the positron emission tomography scan. These recurrences were confirmed at surgery, and the histopathologic findings were identical to the original lesion.

Cross-sectional survey to inform the development of a telehealth support model: a feasibility study for women undergoing breast cancer surgery.

BACKGROUND: For patients undergoing breast cancer surgery, the pre- and post-operative periods can be characterised by feelings of fear, anxiety, and uncertainty. Telehealth offers an opportunity to provide perioperative support to surgical patients and overcome some of the barriers to accessing care. AIMS: In order to inform the development of a telehealth support model for women undergoing breast cancer surgery, this feasibility study explored: (a) access and preferences for telehealth; and (b) the proportion of participants who reported problems with unmet information and preparation needs related to surgery, post-operative pain, anxiety, and quality of life. METHODS: Women aged 18-85 years attending for a follow-up appointment within 2 months of undergoing surgery for breast cancer were asked to complete a baseline (T1) and 1-month follow-up (T2) survey. Surveys assessed telehealth access and preferences, preparatory information receipt and preparedness for surgery, and anxiety, pain, and quality of life. RESULTS: Fifty-three T1 (45% consent rate) and 50 T2 surveys were returned. One fifth of the sample (20%) travelled 50 km or more to access surgery. Most participants had access to a device suitable for telehealth (75%); however, only 15% indicated that they would have accepted a teleconsultation with their surgeon post-operatively if this had been offered. The most frequently reported unmet preparatory information needs were information about: how long it would take to recover from the surgery; how other patients had experienced similar surgery; and practical needs such as parking or transport. Approximately one third of the sample reported potentially clinically significant symptoms of anxiety, and less than one in ten women reported moderate levels of pain. CONCLUSIONS: While the majority of women had access to a suitable device and internet connection for telehealth, less than one fifth would have accepted a home-based video-link teleconsultation with their surgeon post-operatively. A small proportion of the sample would have liked more information about aspects of surgery including about managing side effects and anxiety. The key findings in terms of teleconsultation preferences and information and preparation needs from this study will be incorporated into the telehealth support model being developed.

The influence of the Cyclin D1 870 G>A polymorphism as an endometrial cancer risk factor.

BACKGROUND: Cyclin D1 is integral for the G1 to S phase of the cell cycle as it regulates cellular proliferation. A polymorphism in cyclin D1, 870 G>A, causes overexpression and supports uncontrollable cellular growth. This polymorphism has been associated with an increased risk of developing many cancers, including endometrial cancer. METHODS: The 870 G>A polymorphisms (rs605965) in the cyclin D1 gene was genotyped in an Australian endometrial cancer case-control population including 191 cases and 291 controls using real-time PCR analysis. Genotype analysis was performed using chi-squared (chi2) statistics and odds ratios were calculated using unconditional logistic regression, adjusting for potential endometrial cancer risk factors. RESULTS: Women homozygous for the variant cyclin D1 870 AA genotype showed a trend for an increased risk of developing endometrial cancer compared to those with the wild-type GG genotype, however this result was not statistically significant (OR 1.692 95% CI (0.939-3.049), p = 0.080). Moreover, the 870 G>A polymorphism was significantly associated with family history of colorectal cancer. Endometrial cancer patients with the homozygous variant AA genotype had a higher frequency of family members with colorectal cancer in comparison to endometrial cancer patients with the GG and combination of GG and GA genotypes (GG versus AA; OR 2.951, 95% CI (1.026-8.491), p = 0.045, and GG+GA versus AA; OR 2.265, 95% CI (1.048-4.894), p = 0.038, respectively). CONCLUSION: These results suggest that the cyclin D1 870 G>A polymorphism is possibly involved in the development of endometrial cancer. A more complex relationship was observed between this polymorphism and familial colorectal cancer.

Expression of renin-angiotensin system (RAS) components in endometrial cancer.

A dysfunctional endometrial renin-angiotensin system (RAS) could aid the growth and spread of endometrial cancer. To determine if the RAS is altered in endometrial cancer, we measured RAS gene expression and protein levels in 30 human formalin-fixed, paraffin-embedded (FFPE) endometrioid carcinomas and their adjacent endometrium. All components of the RAS were expressed in most tumours and in adjacent endometrium; mRNA levels of (pro)renin receptor (ATP6AP2), angiotensin II type 1 receptor (AGTR1), angiotensin-converting enzyme (ACE1) and angiotensin-converting enzyme 2 (ACE2) mRNA levels were greater in tumour tissue than adjacent non-cancerous endometrium (P = 0.023, 0.008, 0.004 and 0.046, respectively). Prorenin, ATP6AP2, AGTR1, AGTR2 and ACE2 proteins were abundantly expressed in both cancerous and adjacent non-cancerous endometrium. Staining was most intense in cancerous glandular epithelium. One potential target of the endometrial RAS, transforming growth factor beta-1 (TGFB1), which is essential for epithelial-to-mesenchymal transition, was also upregulated in endometrial cancer tissue (P = 0.001). Interestingly, TGFB1 was strongly correlated with RAS expression and was upregulated in tumour tissue. This study is the first to characterise the mRNA and protein expression of all RAS components in cancerous and adjacent non-cancerous endometrium. The greater expression of ATP6AP2, AGTR1 and ACE1, key elements of the pro-angiogenic/proliferative arm of the RAS, suggests that the RAS plays a role in the growth and spread of endometrial cancer. Therefore, existing drugs that inhibit the RAS and which are used to treat hypertension may have potential as treatments for endometrial cancer.

Prognostic importance of preoperative CA-125 in International Federation of Gynecology and Obstetrics stage I epithelial ovarian cancer: an Australian multicenter study.

PURPOSE: To evaluate the prognostic significance of preoperative CA-125 levels on overall survival of patients with International Federation of Gynecology and Obstetrics (FIGO) stage I epithelial ovarian cancer (EOC). PATIENTS AND METHODS: Data from 518 patients with FIGO stage I EOC treated in seven gynecologic oncology centers throughout Australia between 1990 and 2002 were analyzed. Patients with borderline tumors and nonepithelial ovarian carcinomas were excluded, as were women in whom CA-125 had not been determined preoperatively. Preoperative CA-125 levels were studied in surgically staged and incompletely staged patients and compared with prognostic factors, such as substage, grade, and histologic type. Multivariate Cox models were calculated. RESULTS: CA-125 levels more than 30 U/mL were associated with higher grade, substage 1B and 1C, nonmucinous histologic type, and older age. In univariate analysis, higher histologic grade, the absence of surgical staging, and preoperative CA-125 levels more than 30 U/mL were associated with impaired survival. Multivariate analysis identified histologic grade, preoperative CA-125, and surgical staging as independent predictors for survival. In the subgroup of completely surgically staged patients, the 5-year overall survival rate was 82% (95% CI, 76% to 88%) for patients with CA-125 levels more than 30 U/mL and 95% (95% CI, 90% to 99%) for patients with CA-125 levels of 30 U/mL or less (P = .028). In the group of incompletely staged patients, the 5-year survival rates were similar for patients with elevated and normal serum CA-125 levels. CONCLUSION: Complete surgical staging, histologic grade, and preoperative serum CA-125 levels are independent prognostic factors and should be included in the decision making for chemotherapy.

Gynaecological cancer surgery.

Cancers of the female genital tract account for a significant proportion of cancers in women. Surgery plays a major role in the management of these patients. As a single modality, it provides definitive treatment for early-stage cancers and contributes to the management of patients with advanced cancers as part of multimodality treatment. Surgery can involve relatively simple procedures, such as wide local excision for microinvasive lesions of the vulva. However, for more advanced cancers, such as metastatic ovarian cancer, surgery can be very complex indeed, at times requiring resection of non-gynaecological organs, such as small or large bowel. Extensive surgical training and experience is needed to successfully manage patients with these challenging conditions, and this has resulted in the development of the subspecialty of gynaecological oncology. This chapter discusses the place of surgery in the treatment of individual gynaecological cancers.

Renin-angiotensin system gene polymorphisms and endometrial cancer.

Endometrial cancer (EC) is the most common gynaecological malignancy and its incidence is increasing. Dysregulation of the endometrial renin-angiotensin system (RAS) could predispose to EC; therefore, we studied the prevalence of RAS single nucleotide polymorphisms (SNPs) in Australian women with EC. SNPs assessed were AGT M235T (rs699); AGTR1 A1166C (rs5186); ACE A240T and T93C (rs4291, rs4292) and ATP6AP2 (rs2968915). They were identified using TaqMan SNP Genotyping Assays. The C allele of the AGTR1 SNP (rs5186) was more prevalent in women with EC (odds ratio (OR) 1.7, 95% confidence interval (CI) (1.2-2.3), P=0.002). The CC genotype of this SNP is associated with upregulation of the angiotensin II type 1 receptor (AGTR1). The G allele of AGT rs699, which is associated with higher angiotensinogen (AGT) levels, was less prevalent in women with EC (OR 0.54, 95% CI (0.39-0.74), P<0.001) compared with controls. AGT and AGT formed by removal of angiotensin I (des(Ang I)AGT) are both anti-angiogenic. In women with EC who had had hormone replacement therapy (HRT), the prevalence of the AGTR1 SNP (rs5186) and the ACE SNPs (rs4291 and rs4292) was greater than in women who had no record of HRT; SNP rs4291 is associated with increased plasma ACE activity. These data suggest there is an interaction between genotype, oestrogen replacement therapy and EC. In conclusion, the prevalence of two SNPs that enhance RAS activity was different in women with EC compared with healthy controls. These genetic factors may interact with obesity and hyperoestrogenism, predisposing ageing, obese women to EC.

Targeted next-generation sequencing of 22 mismatch repair genes identifies Lynch syndrome families.

Causative germline mutations in mismatch repair (MMR) genes can only be identified in ~50% of families with a clinical diagnosis of the inherited colorectal cancer (CRC) syndrome hereditary nonpolyposis colorectal cancer (HNPCC)/Lynch syndrome (LS). Identification of these patients are critical as they are at substantially increased risk of developing multiple primary tumors, mainly colorectal and endometrial cancer (EC), occurring at a young age. This demonstrates the need to develop new and/or more thorough mutation detection approaches. Next-generation sequencing (NGS) was used to screen 22 genes involved in the DNA MMR pathway in constitutional DNA from 14 HNPCC and 12 sporadic EC patients, plus 2 positive controls. Several softwares were used for analysis and functional annotation. We identified 5 exonic indel variants, 42 exonic nonsynonymous single-nucleotide variants (SNVs) and 1 intronic variant of significance. Three of these variants were class 5 (pathogenic) or class 4 (likely pathogenic), 5 were class 3 (uncertain clinical relevance) and 40 were classified as variants of unknown clinical significance. In conclusion, we have identified two LS families from the sporadic EC patients, one without a family history of cancer, supporting the notion for universal MMR screening of EC patients. In addition, we have detected three novel class 3 variants in EC cases. We have, in addition discovered a polygenic interaction which is the most likely cause of cancer development in a HNPCC patient that could explain previous inconsistent results reported on an intronic EXO1 variant.