Association between antihypertensive medicine use and risk of ovarian cancer in women aged 50 years and older.

BACKGROUND: Epithelial ovarian cancer (EOC) has few modifiable risk factors. There is evidence that some antihypertensive medicines may have cancer preventive and/or therapeutic actions; therefore, we assessed the associations between use of different antihypertensive medicines and risk of specific EOC histotypes. METHODS: Our nested case-control study of linked administrative health data included 6070 Australian women aged over 50 years diagnosed with EOC from 2004 to 2013, and 30,337 matched controls. We used multivariable conditional logistic regression to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for the association between ever use of each antihypertensive medicine group, including beta-adrenergic blockers, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, diuretics, and alpha blockers, and the risk of EOC overall and separately for the serous, endometrioid, mucinous, clear cell and other histotypes. RESULTS: We found that most antihypertensive medicines were not associated with risk of EOC. However, women who used calcium channel blockers had a reduced risk of serous EOC (OR= 0.89, 95 % CI:0.81,0.98) and use of combination thiazide and potassium-sparing diuretics was associated with an increased risk of endometroid EOC (OR= 2.09, 95 % CI:1.15,3.82). CONCLUSION: Our results provide little support for a chemo-preventive role for most antihypertensives, however, the histotype-specific associations we found warrant further investigation.

Perioperative Beta-Blocker Supply and Survival in Women With Epithelial Ovarian Cancer and a History of Cardiovascular Conditions.

PURPOSE: Surgery for epithelial ovarian cancer (EOC) may activate stress-inflammatory responses that stimulate tumor growth and increase metastatic growth. Animal and in vitro studies have shown that inhibition of the catecholamine-induced inflammatory response via beta-adrenergic receptor blockade has antitumor potential in EOC. However, observational studies have reported mixed results. We assessed whether beta-blocker (BB) use at the time of primary ovarian cancer surgery was associated with improved survival in a large population-based study. MATERIALS AND METHODS: Using linked administrative data, a population-based cohort of 3,844 Australian women age 50 years or older with a history of cardiovascular conditions who underwent surgery for EOC was followed for survival outcomes. The average treatment effect of selective BB (SBB) and nonselective BB (NSBB) supply at the time of surgery on survival was estimated from a causal inference perspective using covariate-balanced inverse probability of treatment weights with flexible parametric survival models that allowed for time-varying survival effects. RESULTS: Around the time of surgery, 560 (14.5%) women were supplied a SBB and 67 (1.7%) were supplied a NSBB. At 2 years postsurgery, the survival proportion was 80% (95% CI, 68 to 88) for women dispensed NSBBs at surgery compared with 69% (95% CI, 67 to 70) for women not supplied NSBBs. The survival advantage appeared to extend to at least 8 years postsurgery. No association was observed for women dispensed a SBB around the time of surgery. CONCLUSION: Perioperative supply of NSBBs appeared to confer a survival advantage for women age over 50 years with a history of cardiovascular conditions. Long-term clinical trials are required to confirm these findings.

Nitrogen-based Bisphosphonate Use and Ovarian Cancer Risk in Women Aged 50 Years and Older.

BACKGROUND: There are few readily modifiable risk factors for epithelial ovarian cancer; preclinical studies suggest bisphosphonates could have chemopreventive actions. Our study aimed to assess the association between use of nitrogen-based bisphosphonate medicine and risk of epithelial ovarian cancer, overall and by histotype. METHODS: We conducted a case-control study nested within a large, linked administrative dataset including all Australian women enrolled for Medicare, Australia's universal health insurance scheme, between July 2002 and December 2013. We included all women with epithelial ovarian cancer diagnosed at age 50 years and older between July 1, 2004, and December 31, 2013 (n = 9367) and randomly selected up to 5 controls per case, individually matched to cases by age, state of residence, area-level socioeconomic status, and remoteness of residence category (n = 46 830). We used prescription records to ascertain use of nitrogen-based bisphosphonates (ever use and duration of use), raloxifene, and other osteoporosis medicines (no nitrogen-based bisphosphonates, strontium and denosumab). We calculated adjusted odds ratios (OR) and 95% confidence intervals (CI) using conditional logistic regression. RESULTS: Ever use of nitrogen-based bisphosphonates was associated with a reduced risk of epithelial ovarian cancer compared with no use (OR = 0.81, 95% CI = 0.75 to 0.88). There was a reduced risk of endometrioid (OR = 0.51, 95% CI = 0.33 to 0.79) and serous histotypes (OR = 0.84, 95% CI = 0.75 to 0.93) but no association with the mucinous or clear cell histotypes. CONCLUSION: Use of nitrogen-based bisphosphonates was associated with a reduced risk of endometrioid and serous ovarian cancer. This suggests the potential for use for prevention, although validation of our findings is required.

A Simple Clinical Tool for Stratifying Risk of Clinically Significant CKD after Nephrectomy: Development and Multinational Validation.

BACKGROUND: Clinically significant CKD following surgery for kidney cancer is associated with increased morbidity and mortality, but identifying patients at increased CKD risk remains difficult. Simple methods to stratify risk of clinically significant CKD after nephrectomy are needed. METHODS: To develop a tool for stratifying patients' risk of CKD arising after surgery for kidney cancer, we tested models in a population-based cohort of 699 patients with kidney cancer in Queensland, Australia (2012-2013). We validated these models in a population-based cohort of 423 patients from Victoria, Australia, and in patient cohorts from single centers in Queensland, Scotland, and England. Eligible patients had two functioning kidneys and a preoperative eGFR ≥60 ml/min per 1.73 m2. The main outcome was incident eGFR <45 ml/min per 1.73 m2 at 12 months postnephrectomy. We used prespecified predictors-age ≥65 years old, diabetes mellitus, preoperative eGFR, and nephrectomy type (partial/radical)-to fit logistic regression models and grouped patients according to degree of risk of clinically significant CKD (negligible, low, moderate, or high risk). RESULTS: Absolute risks of stage 3b or higher CKD were <2%, 3% to 14%, 21% to 26%, and 46% to 69% across the four strata of negligible, low, moderate, and high risk, respectively. The negative predictive value of the negligible risk category was 98.9% for clinically significant CKD. The c statistic for this score ranged from 0.84 to 0.88 across derivation and validation cohorts. CONCLUSIONS: Our simple scoring system can reproducibly stratify postnephrectomy CKD risk on the basis of readily available parameters. This clinical tool's quantitative assessment of CKD risk may be weighed against other considerations when planning management of kidney tumors and help inform shared decision making between clinicians and patients.

Tumor size and postoperative kidney function following radical nephrectomy.

Background: Chronic kidney disease (CKD) following nephrectomy for kidney tumors is common, and both patient and tumor characteristics may affect postoperative kidney function. Several studies have reported that surgery for large tumors is associated with a lower likelihood of postoperative CKD, but others have reported CKD to be more common before surgery in patients with large tumors. Objective: The aim of this study was to clarify inconsistencies in the literature regarding the prognostic significance of tumor size for postoperative kidney function. Study design and setting: We analyzed data from 944 kidney cancer patients managed with radical nephrectomy between January 2012 and December 2013, and 242 living kidney donors who underwent surgery between January 2011 and December 2014 in the Australian states of Queensland and Victoria. Multivariable logistic regression was used to assess the primary outcome of CKD upstaging. Structural equation modeling was used to evaluate causal models, to delineate the influence of patient and tumor characteristics on postoperative kidney function. Results: We determined that a significant interaction between age and tumor size (P=0.03) led to the observed inverse association between large tumor size and CKD upstaging, and was accentuated by other forms of selection bias. Subgrouping patients by age and tumor size demonstrated that all patients aged ≥65 years were at increased risk of CKD upstaging, regardless of tumor size. Risk of CKD upstaging was comparable between age-matched living donors and kidney cancer patients. Conclusion: Larger tumors are unlikely to confer a protective effect with respect to postoperative kidney function. The reason for the previously reported inconsistency is likely a combination of the analytical approach and selection bias.

Incident Chronic Kidney Disease After Radical Nephrectomy for Renal Cell Carcinoma.

BACKGROUND: Chronic kidney disease (CKD) after surgery for kidney cancer is common, and is associated with increased morbidity and mortality. This study aimed to identify factors associated with incident CKD in patients managed with radical nephrectomy. PATIENTS AND METHODS: All patients diagnosed with renal cell carcinoma between January 2012 and December 2013 were ascertained from state-based cancer registries in Queensland and Victoria. Information on patient, tumor, and health service characteristics was obtained via chart review. Multivariable logistic regression was used to evaluate exposures associated with incident CKD (estimated glomerular filtration rate [eGFR] <60 mL per minute per 1.73 m2) at 12 months after nephrectomy. RESULTS: Older age (adjusted odds ratio [aOR] per 5-year increase, 1.5; 95% confidence interval [CI], 1.4-1.6), male sex (aOR, 1.4; 95% CI, 1.0-2.0), obese compared with not obese (aOR, 1.8; 95% CI, 1.2-2.7), rural compared with urban place of residence (aOR, 1.8; 95% CI, 1.1-3.0) were associated with a higher risk of incident CKD. Lower preoperative eGFR was also associated with a higher risk of incident CKD. Management in private compared with public hospitals was also associated with a higher risk of CKD (aOR, 1.6; 95% CI, 1.2-2.2). Factors related to tumor size and cancer severity were also associated with worse postoperative kidney function, although it is likely this was a consequence of selection bias. CONCLUSION: Patient characteristics have the strongest associations with incident CKD after radical nephrectomy. Potential risk factors were reasonably similar to recognized CKD risk factors for the general population. Patients who undergo nephrectomy who have CKD risk factors might benefit from ongoing postoperative screening for deterioration of kidney function.

Predictors of new-onset chronic kidney disease in patients managed surgically for T1a renal cell carcinoma: An Australian population-based analysis.

BACKGROUND: New-onset chronic kidney disease (CKD) following surgical management of kidney tumors is common. This study evaluated risk factors for new-onset CKD after nephrectomy for T1a renal cell carcinoma (RCC) in an Australian population-based cohort. METHODS: There were 551 RCC patients from the Australian states of Queensland and Victoria included in this study. The primary outcome was new-onset CKD (eGFR <60 mL/min per 1.73 m2 ) and the secondary outcome was new-onset moderate-severe CKD (<45 mL/min per 1.73 m2 ). Multivariable logistic regression was used to evaluate associations between patient, tumor and health-service characteristics and these outcomes. RESULTS: Forty percent (219/551) of patients developed new-onset CKD, and 12% (68/551) experienced new-onset moderate-severe CKD. Risk factors for new-onset CKD were age, lower preoperative eGFR, tumor size >20 mm, radical nephrectomy, lower hospital caseloads (<20 cases/year), and rural place of residence. The associations between rural place of residence and low center volume were a consequence of higher radical nephrectomy rates. CONCLUSION: Risk factors for CKD after nephrectomy generally relate to worse baseline health, or likelihood of undergoing radical nephrectomy. Surgeons in rural centres and hospitals with low caseloads may benefit from formalized integration with specialist centers for continued professional development and case-conferencing, to assist in management decisions.

Cost savings for elective laparoscopic resection compared with open resection for colorectal cancer in a region of high uptake.

BACKGROUND: Previous cost analyses of laparoscopic resection for colorectal cancer (CRC) reported slightly higher or similar costs to those of open resection. These analyses were based on randomised controlled trials when the laparoscopic approach was newly adopted. This study compared costs for laparoscopic versus open resection in a region of high uptake where adoption is mature. METHODS: Hospital cost data were obtained for elective resections for CRC that occurred between June 2009 and June 2011 in public hospitals in Queensland, Australia. The primary outcome was total cost and secondary outcomes were length-of-stay, operating time, and ICU admission. Multivariate least-squares regression was used to adjust for potential confounders: age, sex, comorbidities, procedure, and hospital volume. RESULTS: The crude mean cost for laparoscopic resection was euro 20,036 compared with that for open resection of euro 22,780 (difference = euro 2,744). Patients who underwent laparoscopic resection (744/1,397; 53 %) were slightly younger and had fewer comorbidities (decreasing costs) but more had rectal surgery (increasing costs). The adjusted mean cost for laparoscopic resection was euro 20,396 compared with euro 22,442 for open resection (difference = euro 2,054). Compared with open resection, when adjusted for potential confounders, laparoscopic resection resulted in similar operating time (216 vs. 214 min), shorter length-of-stay (difference = -1.1 days, 95 % CI -1.9, -0.3), and shorter admission to ICU (difference = -7.3 h, 95 % CI -11.9, -2.7). CONCLUSIONS: This non-randomised study in a region of high uptake found a similar operating time and lower cost for laparoscopic resection for CRC compared with those of open resection due to a shorter length-of-stay and shorter time in ICU. Laparoscopic resection for CRC saves money when the procedure is widely adopted and surgeons are experienced in the technique.

Australia is continuing to make progress against cancer, but the regional and remote disadvantage remains.

OBJECTIVE: To measure progress, over the past decade, in reducing the disadvantage in cancer death rates among people living in regional and remote areas of Australia. DESIGN: Analysis of routinely collected death certificate and corresponding population data from the Australian Bureau of Statistics. SETTING: Population-based, Australia-wide comparison of mortality rates in regional and remote areas compared with metropolitan areas from 1 January 2001 to 31 December 2010. MAIN OUTCOME MEASURES: Absolute and relative excess of cancer deaths in regional and remote areas. RESULTS: The number of excess cancer deaths in regional and remote areas from 2001 to 2010 was 8878 (95% CI, 8187-9572). For men, the age-standardised mortality ratios (comparing regional and remote areas with metropolitan areas) showed no evidence of improvement, from 1.08 in 1997-2000 to 1.11 in 2006-2010. For women, they increased from 1.01 in 1997-2000 to 1.07 in 2006-2010. The age-standardised cancer death rate in regional and remote areas (annual percentage change [APC], - 0.6%; 95% CI, - 0.8% to - 0.4%) is decreasing more slowly than in metropolitan areas (APC, - 1.1%; 95% CI, - 1.3% to - 1.0%). CONCLUSIONS: The regional and remote disadvantage for cancer deaths has been recognised as a problem for more than two decades, yet we have made little progress. This is not surprising - we have not invested in research into solutions. The benefits of laboratory and clinical research to identify innovative cancer treatments will not be fully realised across the entire Australian population unless we also invest in health systems and policy research.

Has the association between hysterectomy and ovarian cancer changed over time? A systematic review and meta-analysis.

Until recently most studies suggested that hysterectomy with ovarian conservation was associated with a decreased risk of ovarian cancer. However, several recent studies have reported modestly increased risks of ovarian cancer following hysterectomy. Given that as many as 35% of women will have a hysterectomy, the nature of the association requires clarification. We conducted a systematic review and meta-analysis of the published literature on the relationship between hysterectomy and ovarian cancer to investigate whether there has been a temporal change in the association. Twenty observational studies that have reported a quantitative assessment of the association between hysterectomy and risk of histologically-confirmed ovarian cancer were included in the meta-analysis. The overall relative risk (RR) estimate was 0.81 (95% confidence interval (CI) 0.72-0.92) suggesting hysterectomy decreases the risk of ovarian cancer. However, there was significant heterogeneity in the results (I(2) = 74%). Our exploration of sources of heterogeneity and metaregression showed that median year of cancer diagnosis of included cases explained most of the heterogeneity relative risk (RR = 0.70 (95% CI 0.65-0.76) for median year diagnosis pre 2000; RR = 1.18 (95% CI 1.06-1.31) for post 2000). This study shows that there has been a temporal shift in the association between hysterectomy and risk of ovarian cancer. One explanation may be the trend away from hysterectomy in younger women. Other speculative possibilities include the decline in oophorectomy rates and the use of oestrogen-only hormone replacement therapy in hysterectomised women. Until further evidence becomes available, clinicians should not advise women that a hysterectomy without salpingo-oophorectomy will favourably influence their future risk of ovarian cancer.

A study of head and neck cancer treatment and survival among indigenous and non-indigenous people in Queensland, Australia, 1998 to 2004.

BACKGROUND: Overall, Indigenous Australians with cancer are diagnosed with more advanced disease, receive less cancer treatment and have poorer cancer survival than non-Indigenous Australians. The prognosis for Indigenous people with specific cancers varies however, and their prognosis for cancers of the head and neck is largely unknown. We therefore have compared clinical characteristics, treatment and survival between Indigenous and non-Indigenous people diagnosed with head and neck cancer in Queensland, Australia. METHODS: Rates were based on a cohort of Indigenous people (n = 67), treated in public hospitals between 1998 and 2004 and frequency-matched on age and location to non-Indigenous cases (n = 62) also treated in the public health system. Data were obtained from hospital records and the National Death Index. We used Pearson's Chi-squared analysis to compare categorical data (proportions) and Cox proportional hazard models to assess survival differences. RESULTS: There were no significant differences in socioeconomic status, stage at diagnosis or number and severity of comorbidities between Indigenous and non-Indigenous patients, although Indigenous patients were more likely to have diabetes. Indigenous people were significantly less likely to receive any cancer treatment (75% vs. 95%, P = 0.005) and, when cancer stage, socioeconomic status, comorbidities and cancer treatment were taken into account, they experienced greater risk of death from head and neck cancer (HR 1.88, 1.10, 3.22) and from all other causes (HR 5.83, 95% CI 1.09, 31.04). CONCLUSION: These findings show for the first time that Indigenous Australians with head and neck cancer receive less cancer treatment and suggest survival disparity could be reduced if treatment uptake was improved. There is a need for a greater understanding of the reasons for such treatment and survival disparities, including the impact of the poorer overall health on cancer outcomes for Indigenous Australians.

National trends in the uptake of laparoscopic resection for colorectal cancer, 2000-2008.

OBJECTIVE: To examine the trends in the uptake of laparoscopic resection for colorectal cancer. DESIGN AND SETTING: Retrospective analysis of Australia-wide data on elective resections for colorectal cancer over the 8 financial years 2000-01 to 2007-08, obtained from the National Hospital Morbidity Database. MAIN OUTCOME MEASURES: National trends in annual percentage of colorectal resections for cancer that were conducted laparoscopically for each year, stratified by hospitals conducting a high volume of elective resections (40 or more/year) versus a low volume, and by public versus private hospitals. RESULTS: For all Australian hospitals combined, the percentage of resections for colon cancer conducted laparoscopically increased from 2.4% in 2000-01 to 27.5% in 2007-08. For rectal cancer, this increase was from 1.1% to 21.5%. The largest increases were seen in high-volume private hospitals (colon cancer, 2.7% to 34.1%; rectal cancer, 1.5% to 26.2%), but increases also occurred in high-volume public hospitals (colon cancer, 2.7% to 32.2%; rectal cancer, 0.5% to 20.3%), low-volume private (colon cancer, 3.8% to 27.1%; rectal cancer, 2.4% to 25.5%) and low-volume public (colon cancer, 1.1% to 17.0%; rectal cancer, 0.5% to 13.8%) hospitals. CONCLUSIONS: The use of laparoscopic resection for colorectal cancer has increased throughout Australian hospitals. Our findings provide the data necessary to ensure adequate resource allocation by the appropriate medical bodies to achieve optimal success in the uptake of laparoscopic resection for colorectal cancer in Australia.

Urban-rural differences in prostate cancer outcomes in Australia: what has changed?

OBJECTIVE: To update our previous analysis of trends for prostate-specific antigen (PSA) testing, prostate cancer incidence, radical prostatectomy and prostate cancer mortality to assess whether men in rural and regional areas of Australia now have more equitable access to prostate cancer services, and improved outcomes. DESIGN, SETTING AND PARTICIPANTS: Descriptive study using population-based data for Australian men aged 50-79 years from 1982 to the 2008-09 financial year (depending on data availability for each outcome measure). MAIN OUTCOME MEASURES: Age-standardised rates per 100,000 men and 5-year survival rates. RESULTS: Overall, rates of PSA screening and radical prostatectomy increased, accompanied by reductions in mortality and improvements in survival throughout Australia. Incidence rates were similar for men in urban and rural areas. However, in the last year of data collection, for men in rural areas compared with urban areas, rates of PSA screening (21,267/100,000 v 24,606/100,000; P < 0.01) and radical prostatectomy (182.2/100,000 v 239.2/100,000; P < 0.01) remained lower, mortality remained higher (56.9/100,000 v 45.8/100,000; P < 0.01), and survival outcomes continued to be poorer (5-year relative survival, 87.7% v 91.4%; P < 0.01). CONCLUSIONS: With some limitations, these ecological data demonstrate that the use of diagnostic and treatment services among men living in rural areas of Australia remains lower than among their urban counterparts, their survival and mortality outcomes are poorer, and these differentials are continuing. There is an urgent need to explore further the reasons for these differences and to implement changes so these inequalities can be reduced.

Cancer incidence and mortality in Indigenous Australians in Queensland, 1997-2006.

OBJECTIVE: To examine cancer incidence and mortality in Indigenous Queenslanders. DESIGN, SETTING AND PATIENTS: Assessment of indirectly standardised incidence and mortality ratios for Indigenous Australians in Queensland diagnosed with cancer from 1997 to 2006, compared with the total Queensland population. MAIN OUTCOME MEASURES: Standardised incidence and mortality ratios. RESULTS: Compared with the total Queensland population, Indigenous Queenslanders had a lower overall incidence of cancer (standardised incidence ratio, 0.79; 95% CI, 0.75-0.82), but a higher incidence of some of the more fatal cancer types. Overall cancer mortality was higher (standardised mortality ratio, 1.36; 95% CI, 1.28-1.45) and similar to rates for Indigenous people in other Australian states. CONCLUSION: Cancer rates for Indigenous Queenslanders, a mostly urbanised population, are similar to rates for Indigenous Australians mostly living in remote areas.