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Aim: The role of germline testing in prostate cancer is evolving and knowledge of an individual's genetic profile may be used to guide not only an assessment of their familial risk but also have prognostic and therapeutic implications. Although international guidelines have incorporated recommendations for germline testing in prostate cancer, there is little Australian data to guide referrals. The aim of this study is to review the frequency of relevant pathogenic mutations in an Australian center, their associated clinical factors and clinical impact., Methods: We conducted a single-center retrospective review of men with prostate cancer that undertook prospective germline testing using a targeted next generation sequencing panel., Results: Results for 100 men were analyzed. Median age at diagnosis was 62 years (range 43-84); 92% had metastatic disease at referral. A pathogenic mutation was confirmed in 9%, a likely pathogenic variant in 2% and a variant of uncertain significance in 15%. Age ≤60 years was associated with an increased risk for a pathogenic germline variant (P = 0.0096). Two of the nine (22%) with pathogenic variants went on to receive targeted treatment., Conclusions: In this single center study, the incidence of germline mutations in genes associated with DNA-repair was consistent with rates seen previously published international series of men with metastatic disease. A pathogenic variant was only seen in one patient >60 years of age and no man referred solely on the basis of age or high-risk localized disease had a relevant finding., (© 2019 John Wiley & Sons Australia, Ltd.)

While familial adenomatous polyposis accounts for approximately 1% of all colorectal cancer, the genetic cause underlying the development of multiple colonic adenomas remains unsolved in many patients. Adenomatous polyposis syndromes can be divided into: familial adenomatous polyposis, MUTYH-associated polyposis, polymerase proofreading associated polyposis and the recently described NTHL1-associated polyposis (NAP). NAP is characterised by recessive inheritance, attenuated adenomatous polyposis, colonic cancer(s) and possible extracolonic malignancies. To date, 11 cases have been reported as having germline homozygous or compound heterozygous mutations in the base excision repair gene NTHL1. Here we present a further case of a 65-year-old male with a history of adenomatous polyposis and bladder cancer, who has a previously described homozygous nonsense variant in the NTHL1 gene. This case is consistent with the emerging phenotype previously described of multiple colorectal adenomas and at least one primary tumour, adding to the small but growing body of literature about NAP.

Objective: To identify patient safety measurement tools in use in Australian public hospitals and to determine barriers to their use., Design: Structured survey, conducted between 4 March and 19 May 2005, designed to identify tools, and to assess current use of, levels of satisfaction with, and barriers to use of tools for measuring the domains and subdomains of: organisational capacity to provide safe health care; patient safety incidents; and clinical performance., Participants and Setting: Hospital executives, managers and clinicians from a nationwide random sample of Australian public hospitals stratified by state and hospital peer grouping., Main Outcome Measures: Tools used by hospitals within the three domains and their subdomains; patient safety tools and processes identified by individuals at these hospitals; satisfaction with the tools; and barriers to their use., Results: Eighty-two of 167 invited hospitals (49%) responded. The survey ascertained a comprehensive list of patient safety measurement tools that are in current use for measuring all patient safety domains. Overall, there was a focus on use of processes rather than quantitative measurement tools. Approximately half the 182 individual respondents from participating hospitals reported satisfaction with existing tools. The main reported barriers were lack of integrated supportive systems, resource constraints and inadequate access to robust measurement tools validated in the Australian context. Measurement of organisational capacity was reported by 50 (61%), of patient safety incidents by 81 (99%) and of clinical performance by 81 (99%)., Conclusion: Australian public hospitals are measuring the safety of their health care, with some variation in measurement of patient safety domains and their subdomains. Improved access to robust tools may support future standardisation of measurement for improvement.

The genetic predisposition Peutz-Jeghers Syndrome (PJS) has been shown to be associated with mutations in the serine threonine kinase 11 (STK11) gene but only a proportion of probands have been shown to harbour changes in the gene. The remaining patients were proposed to be either associated with a second PJS gene or they harboured more cryptic mutations within the STK11 gene itself. With the introduction of the multiplex ligation probe amplification (MLPA) assay, large sequence losses or gains can be more readily identified. In this report we have screened 33 PJS patients from unrelated families, employing a combination of denaturing high-performance liquid chromatography, direct DNA sequencing and the MLPA assay to identify deleterious changes in the STK11 gene. The results revealed that 24 (73%) of patients diagnosed with PJS-harboured pathogenic mutations in the STK11 gene, including 10 (36%) with exonic or whole-gene deletions. No phenotypic differences were identified in patients harbouring large deletions in the STK11 gene compared to patients harbouring missense or nonsense mutations. Mutation analysis in PJS should include techniques such as MLPA to identify large exonic or whole-gene deletions and rearrangements. The high proportion of families with identifiable mutations in the STK11 gene using this range of techniques suggests that most, if not all PJS, is attributable to mutations in the STK11 gene, perhaps including as yet undiscovered changes in promoter or enhancer sequences or other cryptic changes.

Background: Changing consumer expectations, particularly in the area of informed consent, coupled with a history of an unanticipated rise in adverse events following the introduction of some new interventional procedures, have produced a need for the more formal evaluation of such procedures before their introduction into a health-care facility. Moreover, a need exists to ensure that the outcomes of such procedures are monitored. Descriptions of such formal evaluation processes were lacking before 2000. The experience of a large regional health service with the implementation of a brief but comprehensive evaluation process for the introduction of new interventional procedures is described., Methods: A policy outlining the approval and monitoring processes, including a simple, 15-point checklist, was developed in consultation with clinicians and managers and was implemented in 2000. The experience with this policy between January 2001 and December 2004 (inclusive) is described., Results: Twenty-nine applications for the introduction of new procedures, from a range of clinical disciplines, were submitted and approved. Some required significant modification, particularly in the areas of clinical risk description and other data required to facilitate the provision of informed consent., Conclusions: Innovation can be protected and encouraged by processes that allow for appropriate scrutiny of the benefits and requirements for the successful introduction of new interventional procedures. The approach described has since been used as the basis for the New South Wales Health Department statewide policy on this matter and as a model policy by the Royal Australasian College of Surgeons.

Background: The evidence for a relationship between patient outcomes and clinician and hospital volume is increasing. The National Colorectal Cancer Care Survey was undertaken to determine the management patterns in Australia for individuals newly diagnosed with colorectal cancer in a 3 month period in the year 2000., Methods: All new cases of colorectal cancer registered at each Australian State Cancer Registry were entered into the survey. This generated a questionnaire that was sent to the treating surgeon. Chi-squared tests and logistic regression analyses were used to determine levels of statistical significance., Results: Of 2,383 surgical questionnaires generated, 2,015 (85%) were completed. The majority (58%) of surgeons treated one or two patients with colorectal cancer over the 3 months of the survey. There was variation across surgeon cohorts for preoperative measures including the use of deep vein thrombosis prophylaxis. Patients seen by low volume surgeons were most likely to be given a permanent stoma (P < 0.0001). Patients with rectal cancer who were operated on by high volume surgeons were significantly more likely to receive a colonic pouch (P < 0.0001)., Conclusion: This nationwide population-based survey of the treatment of colorectal cancer patients suggests that the delivery of care by surgeons (the majority) who treat patients with rectal cancer infrequently should be evaluated.

The MYH gene has recently been shown to be associated with a recessive form of colorectal adenomatous polyposis. Two common mutations in the MYH gene have been identified that lend themselves to rapid screening. We have examined a series of 302 individuals comprising 120 control subjects, 120 patients diagnosed with adenomatous polyposis but without germline mutations in the APC gene and 62 patients diagnosed with familial adenomatous polyposis all harbouring confirmed causative APC germline mutations. The results reveal that MYH accounts for 16 percent of polyposis patients without germline mutations in the APC gene and that it does not appear to be a modifier gene in FAP patients diagnosed with APC germline mutations., ((c) 2005 Wiley-Liss, Inc.)

Background: The National Colorectal Cancer Care Survey was undertaken to determine the management patterns for individuals newly diagnosed with colorectal cancer in Australia., Methods: Between 1 February and 30 April 2000, all new cases of colorectal cancer registered at each Cancer Registry within Australia were entered into the survey. This generated a questionnaire that was sent to the treating surgeons. Chi-squared and logistic regression analyses were used to determine levels of statistical significance for the various comparisons of interest., Results: Of 2383 surgical questionnaires generated, 2015 (85%) were completed. A total of 1911 patients (95% of those who responded to the questionnaire) had an operation. Of the 86 guidelines for the management of colorectal cancer published by the National Health and Medical Research Council, the survey allowed for comparison between 18 of these, which covered a spectrum of surgical management. Thromboembolic prophylaxis was given to 1843 patients (96.4%) undergoing surgery. Prophylactic antibiotics were commonly used, but there appear to be issues regarding the best regimen to use. Curative resections were carried out in 1563 patients (81.8%), with anterior resections being the most commonly performed procedure. Adjuvant therapy was regularly used, but not all eligible patients were offered such treatment., Conclusion: With the considerable resources required to develop clinical practice guidelines, studies like this are essential to monitor the impact of the guidelines. To ensure that the guidelines are in line with current evidence, regular reviews of the guideline recommendations are required.

Peutz-Jeghers syndrome (PJS) is a rare cancer predisposition, which is characterized by the presence of hamartomatous polyposis and mucocutaneous pigmentation. A significant proportion of both familial and sporadic forms of this disorder are associated with mutations in the STK11 (serine/threonine kinase 11)/LKB1 gene. In this report we present a series of Australian PJS cases, which suggest that mutations in the STK11 gene do not account for many families or patients without a family history. The most likely explanation is either the presence of another susceptibility gene or genetic mosaicism in the non-familial patients.

Up to 20% of colorectal cancers are thought to have a genetic component. Several familial syndromes are known to confer an increased risk for colorectal cancer. Advances in our understanding of these syndromes has improved the care delivered to, and the overall survival of, these patients. Genetic testing has great potential to further improve detection and direct subsequent preventative measures. The diagnosis, management and surveillance issues relating to some of the more commonly encountered syndromes - in particular Familial Adenomatous Polyposis and Hereditary Non-Polyposis Colorectal Cancer - are reviewed.

Objective: To determine attitudes among surgeons in Australia to assisted death, and the proportion of surgeons who have intentionally hastened death with or without an explicit request., Design: Anonymous, cross-sectional, mail-out survey between August and November 1999, Participants: 683 out of 992 eligible general surgeons (68.9% response rate)., Main Outcome Measures: Proportion of respondents answering affirmatively to questions about administering excessive doses of medication with an intention to hasten death., Results: 247 respondents (36.2%; 95% CI, 32.6%-39.9%) reported that, for the purpose of relieving a patient's suffering, they have given drugs in doses that they perceived to be greater than those required to relieve symptoms with the intention of hastening death. More than half of these (139 respondents; 20.4% of all respondents; 95% CI, 17.4%-23.6%) reported that they had never received an unambiguous request for a lethal dose of medication. Of all respondents, only 36 (5.3%; 95% CI, 2.9%-6.1%) reported that they had given a bolus lethal injection, or had provided the means to commit suicide, in response to an unambiguous request., Conclusions: More than a third of surgeons surveyed reported giving drugs with an intention to hasten death, often in the absence of an explicit request. However, in many instances, this may involve the use of an infusion of analgesics or sedatives, and such actions may be difficult to distinguish from accepted palliative care, except on the basis of the doctor's self-reported intention. Legal and moral distinctions based solely on a doctor's intention are problematic.

A postal survey was undertaken to determine the extent of surgical audit in Australian public hospitals in the context of clinical governance. Participants were 88 surgical units from 74 Australian public hospitals in 1998 with more than 70 beds. The main outcome measures were performance of audit, methods used, frequency, documentation and perceived adequacy of resources and comparison of performance with Royal Australasian College of Surgeons requirements for re-certification. The main findings were that most units performed audit, but over two-thirds declared that they had insufficient resources to conduct audit according to College requirements, while a substantial proportion did not comply with other published guidelines for the conduct of audit meetings. The conclusion from this survey is that surgical audit will be unable to play its part in quality initiatives inherent in the clinical governance concept unless appropriately resourced.