Role of lymph node yield and lymph node ratio in predicting outcomes in non-metastatic colorectal cancer.

Background: Lymph node yield (LNY) of 12 or more in resection of colorectal cancer is recommended in current international guidelines. Although a low LNY (less than 12) is associated with poorer outcome in some studies, its prognostic value is unclear in patients with early-stage colorectal or rectal cancer with a complete pathological response following neoadjuvant therapy. Lymph node ratio (LNR), which reflects the proportion of positive to total nodes obtained, may be more accurate in predicting outcome in stage III colorectal cancer. This study aimed to identify factors correlating with LNY and evaluate the prognostic role of LNY and LNR in colorectal cancer. Methods: An observational study was performed on patients with colorectal cancer treated at three hospitals in Melbourne, Australia, from January 2010 to March 2016. Association of LNY and LNR with clinical variables was analysed using linear regression. Disease-free (DFS) and overall (OS) survival were investigated with Cox regression and Kaplan-Meier survival analyses. Results: Some 1585 resections were analysed. Median follow-up was 27·1 (range 0·1-71) months. Median LNY was 16 (range 0-86), and was lower for rectal cancers, decreased with increasing age, and increased with increasing stage. High LNY (12 or more) was associated with better DFS in colorectal cancer. Subgroup analysis indicated that low LNY was associated with poorer DFS and OS in stage III colonic cancer, but had no effect on DFS and OS in rectal cancer (stages I-III). Higher LNR was predictive of poorer DFS and OS. Conclusion: Low LNY (less than 12) was predictive of poor DFS in stage III colonic cancer, but was not a factor for stage I or II colonic disease or any rectal cancer. LNR was a predictive factor in DFS and OS in stage III colonic cancer, but influenced DFS only in rectal cancer.

New vertebral fractures after vertebroplasty: 2-year results from a randomised controlled trial.

UNLABELLED: A randomised controlled trial of vertebroplasty (VP) versus placebo assessed the effect of VP on the risk of further vertebral fractures. While no statistically significant between-group differences for new or progressed fracture risk at 12 and 24 months were observed, we observed a consistent trend towards higher risk of any type of fracture in the group undergoing VP. Our analysis was underpowered, and further adequately powered studies are needed to be able to draw firm conclusions about further vertebral risk with vertebroplasty. PURPOSE: This study seeks to assess the effect of VP on the risk of further radiologically apparent vertebral fracture within two years of the procedure. METHODS: We conducted a randomised placebo-controlled trial of VP in people with acute osteoporotic vertebral fracture. Eligible participants were randomly assigned to VP (n = 38) or placebo (n = 40). Cement volume and leakage were recorded for the VP group. Plain thoracolumbar radiographs were taken at baseline, 12 and 24 months. Two independent radiologists assessed these for new and progressed fractures at the same, adjacent and non-adjacent levels. RESULTS: At 12 and 24 months, radiographs were available for 45 (58 %) and 47 (60 %) participants, respectively. There were no between-group differences for new or progressed fractures: 32 and 40 in the VP group after 12 and 24 months compared with 21 and 33 in the placebo group (hazard ratio (HR) 1.80, 95 % confidence interval (CI) 0.82 to 3.94). Similar results were seen when considering only adjacent (HR (95 % CI) 2.30 (0.57 to 9.29)) and non-adjacent (HR (95 % CI) 1.45 (0.55 to 3.81) levels. In all comparisons, there was a consistent trend towards higher risk of any type of fracture in the group undergoing VP. Within the VP group, fracture risk was unrelated to total (HR (95 % CI) 0.91 (0.71 to 1.17)) or relative (HR (95 % CI) 1.31 (0.15 to 11.48)) cement volume or cement leakage (HR (95 % CI) 1.20 (0.63 to 2.31)). CONCLUSION: For patients undergoing VP, our study did not demonstrate significant increases in subsequent fracture risk beyond that experienced by those with vertebral fractures who did not undergo the procedure. However, because of the non-significant numerical increases observed, studies with adequate power are needed to draw definite conclusions about fracture risk.

Risk factors for herpes zoster in rheumatoid arthritis patients: the role of tumour necrosis factor-α inhibitors.

AIM: To determine whether exposure to tumour necrosis factor (TNF)-α inhibitors increases the risk of herpes zoster (HZ) among people with rheumatoid arthritis (RA). METHODS: We performed a cohort study of people with RA participating in the Australian Rheumatology Association Database. We identified self-reported cases of HZ and verified using medical records. For the primary analysis, we only included doctor-verified cases. For TNF-α inhibitor exposed groups, we excluded HZ episodes that occurred before TNF-α inhibitor initiation, and for the control group we excluded HZ episodes that occurred prior to 2000 or RA diagnosis. The risk of HZ among participants exposed versus not exposed to TNF-α inhibitors was compared using Cox proportional hazards models including significant covariates affecting the risk. Adjusted hazard ratios (HR) were calculated for TNF inhibitors as a class and for individual agents. RESULTS: Among 2157 active RA participants, there were 442 self-reported cases of HZ. From 346 responses from doctors, 249 cases were verified and four were false positives (false positive rate 1.6%). Crude incidence of verified HZ in the entire RA cohort was 15.9/1000 person-years (95% confidence interval (CI): 13.5-18.8). An increased risk of HZ was found for all TNF-α inhibitors combined (fully adjusted HR 1.71; 95% CI: 1.00-2.92) and adalimumab (fully adjusted HR 2.33; 95% CI: 1.22-4.45), but in the fully adjusted model was not increased with etanercept (fully adjusted HR 1.65; 95% CI: 0.90-3.03). No increased risk was found with infliximab (HR 1.29; 95% CI: 0.37-4.47). CONCLUSIONS: TNF-α inhibitors are associated with an increased risk of HZ in people with RA compared with those who have not been exposed.

How receptive are patients to medical students in Australian hospitals? A cross-sectional survey of a public and a private hospital.

BACKGROUND: Medical student numbers in Australian universities have more than doubled since 2000. There are concerns about the ability for existing clinical training sites to accommodate this increase in student numbers, and there have been calls to increase training in private hospitals. The receptiveness of patients in private hospitals will influence the success of such placements. AIMS: We aimed to evaluate whether patients in a private hospital are as receptive to medical students as patients in a public hospital. METHODS: Cross-sectional survey of patients conducted at a private and a public teaching hospital in Melbourne, Australia. Main outcome measures were willingness to allow a medical student to participate in an interview, physical examination and procedures (electrocardiogram, venepuncture and digital rectal examination), and patient attitudes towards medical students as assessed by a series of 20 attitude statements and a summative attitude score. RESULTS: Patients at the private hospital were more willing than patients at the public hospital to allow a medical student to take their history unsupervised (112/146, 76.7% vs 90/141, 63.8%; P = 0.02). The distribution of patient willingness did not otherwise differ between hospitals for physical examination or procedures. There was no difference in the mean attitude score between hospitals (15.3 ± 0.8 private vs 15.4 ± 1.2 public, P = 0.38), and responses differed between hospitals for only four of the 20 attitude statements. CONCLUSIONS: Our findings suggest that patients in a private hospital are at least as receptive to medical students as patients in a public hospital.

The rate of abdominoperineal resections for rectal cancer in the state of Victoria, Australia: a population-based study.

PURPOSE: The aim of this study was to document a population-based rate of abdominoperineal resections for adenocarcinoma of the rectum in the state of Victoria, Australia. It also determined whether surgeon caseload or specialist colorectal training affects this rate. METHODS: All resections for adenocarcinoma of the rectum (International Classification of Diseases for Oncology, 3rd edition C20) that were performed in Victoria in the year 2005 were included. Procedures for rectosigmoid or colon cancer were excluded. The sample was taken from the Victorian Cancer Registry. The rate of abdominoperineal resections was calculated by dividing the total number of abdominoperineal resections by the total number of procedures for rectal cancer. Mixed-effects logistic regression was used to estimate the odds ratio for surgeon caseload and specialist colorectal training. RESULTS: There were 582 resections available for analysis. Patients were mostly males (66%) and over 60 years of age (67.7%). The overall rate of abdominoperineal resection was 23.4%. The rate of abdominoperineal resections for low rectal cancers was lower (42.8%) among surgeons who had specialist colorectal training compared with those who did not (60.6%) (OR = 2.06; 95% CI, 1.24-3.42). CONCLUSION: The rate of abdominoperineal resection in Victoria for 2005 was 23.4%. Patients with low rectal cancer operated on by surgeons who had had specialist colorectal training were significantly less likely to undergo an abdominoperineal resection compared with patients undergoing an operation by surgeons who did not have specialist colorectal training.

Risk of prostate cancer associated with a family history in an era of rapid increase in prostate cancer diagnosis (Australia).

OBJECTIVE: We conducted a case-control study of prostate cancer and familial risk of the disease in Australia between 1994 and 1998, a period during which the incidence of prostate cancer increased dramatically with widespread use of prostate-specific antigen (PSA) testing. METHODS: 1475 cases and 1405 controls were asked about prostate cancer in their first-degree relatives. Odds ratios (OR) were calculated using logistic regression. RESULTS: Cases were more likely to report a family history of prostate cancer than controls (OR 3.0; 95% confidence interval (CI) 2.3-3.9) and cases reporting an affected relative were younger (58.8 versus 60.9 years, p < 0.0001). The OR for an affected first-degree relative increased with increasing number of affected relatives and decreased with increasing age of the case. The OR for more than one affected first-degree relative was 6.9 (95% CI 2.7-18). The OR for an affected brother was 3.9 (95% CI 2.5-6.1) and for an affected father was 2.9 (95% CI 2.1-3.9) but these were not significantly different (p = 0.2). When analyses were repeated including only diagnoses made in relatives prior to 1992, the risks were generally similar except that the OR for an affected brother decreased to 3.1 (95% CI 1.2-3.9). When only relatives' diagnoses made after 1991 were included results were again similar to those for all relatives, although the effect for brothers was greater and the attenuation with age at diagnosis dissipated. CONCLUSIONS: The recent introduction of PSA testing that has resulted in a greater prevalence of apparent prostate cancer, does not appear to have substantially altered familial risks of disease, although effects associated with brothers may be inflated.

Segregation analyses of 1,476 population-based Australian families affected by prostate cancer.

Segregation analyses aim to detect genetic factors that have a major effect on an individual's risk of disease and to describe them in terms of mode of inheritance, age-specific cumulative risk (penetrance), and allele frequency. We conducted single- and two-locus segregation analyses of data from 1,476 men with prostate cancer diagnosed at age <70 years and ascertained through population registries in Melbourne, Sydney, and Perth, Australia, and from their brothers, fathers, and both maternal and paternal lineal uncles. Estimation and model selection were based on asymptotic likelihood theory and were performed through use of the software MENDEL. All two-locus models gave better fits than did single-locus models, even if lineal uncles were excluded or if we censored data (age and disease status) for relatives at 1992, when prostate-specific-antigen testing started to have a major impact on the incidence of prostate cancer in Australia. Among the genetic models that we considered, the best-fitting ones included a dominantly inherited increased risk that was greater, in multiplicative terms, at younger ages, as well as a recessively inherited or X-linked increased risk that was greater, in multiplicative terms, at older ages. The recessive and X-linked effects were strongly confounded, and it was not possible to fit them together. Penetrance to age 80 years was approximately 70% (95% confidence interval [CI] 57%-85%) for the dominant effect and virtually 100% for the recessive and X-linked effects. Approximately 1/30 (95% CI 1/80-1/12) men would carry the dominant risk, and 1/140 (95% CI 1/220-1/90) would carry the recessive risk or 1/200 (95% CI 1/380-1/100) would carry the X-linked risk. Within discussed limitations, these analyses confirm the genetic heterogeneity, of prostate cancer susceptibility, that is becoming evident from linkage analyses, and they may aid future efforts in gene discovery.

Has mortality from melanoma stopped rising in Australia? Analysis of trends between 1931 and 1994.

OBJECTIVE: To describe recent trends in mortality from melanoma in Australia. DESIGN: An analysis of trends in age standardised and age and sex specific mortalities by year of death and median year of birth (cohort). SETTING: Australia. SUBJECTS: All deaths from melanoma registered in Australia between 1931 and 1994. RESULTS: Melanoma mortality rose steadily from 1931 to 1985. From 1959 the annual rate of increase was 6.3% in men and 2.9% in women, resulting in mortalities of 4.82 and 2.51 per 100,000 person years in 1985 and 1989, respectively. Mortalities for both sexes seem to have plateaued from June 1985 onwards. In 1990-4 the rate rose by 3.7% in men to 5.00 per 100,000 and in women it fell by 5.2% to 2.38 per 100,000. The non-significant increase after 1985 in mortality in men was restricted to those aged over 70 years of age, whereas the fall in rates in women was mostly in those aged under 55 years. This pattern was generally reflected in the state trends, though with some variation: rates for women in Queensland had peaked in the late 1970s; while rates for men in New South Wales continued to rise in 1990-4, placing them above those for Queensland. Examination of mortalities specific for age, period, and cohort for Australia as a whole showed several salient features. Rates in men rose steeply in cohorts born before about 1930; were stable in cohorts born between 1930 and 1950; and fell in more recent cohorts. Rates in women showed similar changes but about five years earlier. CONCLUSION: Melanoma mortality in Australia peaked in about 1985 and has now plateaued. On the basis of trends in cohorts it can be expected to fall in coming years.

Dietary factors and the risk of glioma in adults: results of a case-control study in Melbourne, Australia.

In a population-based case-control study of 416 incident gliomas in adults carried out in Melbourne, Australia, between 1987 and 1991, 409 age-sex-matched case-control pairs (243 male and 166 female) had adequate data available to examine associations between the dietary intake of N-nitroso compounds, N-nitroso precursors, other nutrients including N-nitroso inhibitors, and the risk of glioma. Dietary intakes were based on the reported frequency of consumption of 59 food items. Increased odds ratio (OR) were observed in males who consumed high levels of bacon, corned meats, apples, melons and oil. OR less than unity were observed in men consuming cabbage and cola drinks, and in women who consumed wholegrain bread, pasta, corned meat, bananas, cauliflower, brocoli, cola drinks and nuts. Generally, N-nitroso associations were greater in men and micronutrient associations were greater in women. Elevated OR in men, but not women, were associated with the intake of N-nitroso dimethylamine (NDMA), retinol and vitamin E. The intake of nitrate (largely of vegetable origin) was protective in women but not in men. When analyzed using multiple logistic regression, the association with NDMA intake in males was not modified by dietary micronutrient intakes. In females, beta carotene alone, though not directly associated with risk, modified the effect of NDMA. On balance, this study added only limited support to the N-nitroso hypothesis of glial carcinogenesis.

The incidence of colon, breast and prostate cancer in Italian migrants to Victoria, Australia.

The incidence of cancers of the colon, breast and prostate in Australian and Italian born residents of Victoria, Australia were compared with the incidence of these cancers in Italy. Italian migrants' rates were between those of the Australian born and those from Italian cancer registries. Italian migrants' rates for colon cancer (males 23.1 and females 15.8 per 100,000) differed from rates in Ragusa (males 12.1 and females 10.4 per 100,000) but not from rates in Parma or Varese. The migrants' breast cancer rate was similar to the rate in Ragusans (48.7 vs 46.7) and their prostate cancer rate of 27.3 was higher than all Italian registries. Modelling identified that Italian migrants' rates by age were intermediate to Australian and Italian rates, but indistinguishable from cancer rates in Ragusa, except for colon cancer which demonstrated an interaction with age.

Cervical cancer screening: a comparison of recruitment strategies among older women.

OBJECTIVE: To compare the effectiveness of different recruitment strategies in encouraging older women to have a Papanicolaou (Pap) test. DESIGN: A 2 x 2 factorial study. SETTING: Two rural areas of Victoria, Australia. PARTICIPANTS: A total of 10,620 persons aged between 40 and 69 years and designated as female on electoral lists. INTERVENTIONS: A personal letter of invitation and a community-based campaign of 4 weeks' duration alone and in combination. A control group received no active intervention. OUTCOME MEASURE: The proportion of eligible women having a Pap test report issued by the Victorian Cytology Service during the 12 weeks after the intervention compared with the 12 weeks before the intervention, with an intervening two-week washout period. RESULTS: The odds ratio of an eligible woman being screened during the intervention period relative to the pre-intervention period was 3.00 for women who were exposed to the campaign and sent the letter of invitation (95% confidence interval, 2.38-3.77, P less than 0.001), 1.86 for women who were exposed to the campaign (95% confidence interval, 1.49-2.33, P less than 0.001), 1.61 for women who were sent the letter of invitation (95% confidence interval, 1.34-1.92, P less than 0.001). The baseline was a control group who received no active intervention. CONCLUSIONS: Both personal invitation letters and community-based campaigns are effective in recruiting women for Pap test screening. Combined strategies are more effective than single strategies.