Surgery (Austin & Northern Health) - Research Publications

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    Distress and unmet needs during treatment and quality of life in early cancer survivorship: A longitudinal study of haematological cancer patients
    Oberoi, DV ; White, VM ; Seymour, JF ; Prince, HM ; Harrison, S ; Jefford, M ; Winship, I ; Hill, DJ ; Bolton, D ; Millar, J ; Doo, NW ; Kay, A ; Giles, G (WILEY, 2017-11)
    OBJECTIVE: To examine the influence of anxiety, depression and unmet supportive care needs on future quality of life (QoL) in multiple myeloma (MM) and diffuse large B-cell lymphoma (DLBCL) patients. METHODS: Multiple myeloma and DLBCL patients recruited through the population-based Victorian Cancer Registry. Data were collected through two telephone interviews: (T1) on average 7 months postdiagnosis, (T2) average 8 months later. QoL was examined at T2 using the Functional Assessment of Cancer Therapy (FACT-G) scale. The Hospital Anxiety and Depression Scale measured anxiety and depression, and the Supportive Care Needs Survey measured unmet needs at T1. Multivariate linear regression examined associations between QoL subscales (physical, emotional, social and functional well-being and overall QoL) and T1 anxiety, depression and unmet needs. RESULTS: Except physical well-being, all other QoL subscales and overall QoL were significantly associated with T1 anxiety. All QoL subscales and overall QoL were significantly associated with T1 depression. Only patient care needs were associated with physical and social well-being and overall QoL. CONCLUSION: Anxiety, depression and patient care unmet needs during treatment are associated with diminished physical and emotional well-being in the following months. Psychological distress and unmet supportive care needs experienced during treatment should be addressed to maximise future QoL.
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    Trends in the surgical management of stage 1 renal cell carcinoma: findings from a population-based study
    White, V ; Marco, DJT ; Bolton, D ; Davis, ID ; Jefford, M ; Hill, D ; Prince, HM ; Millar, JL ; Winship, IM ; Coory, M ; Giles, GG (WILEY, 2017-11)
    OBJECTIVES: To determine whether the use of nephron-sparing surgery (NSS) for treatment of stage 1 renal cell carcinoma (RCC) changed between 2009 and the end of 2013 in Australia. PATIENTS AND METHODS: All adult cases of RCC diagnosed in 2009, 2012 and 2013 were identified through the population-based Victorian Cancer Registry. For each identified patient, trained data-abstractors attended treating hospitals or clinician rooms to extract tumour and treatment data through medical record review. Multivariable logistic regression analyses were carried out to examine the significance of change in use of NSS over time, after adjusting for potential confounders. RESULTS: A total of 1 836 patients with RCC were identified. Of these, the proportion of cases with stage 1 tumours was 64% in 2009, 66% in 2012 and 69% in 2013. For T1a tumours, the proportion of patients residing in metropolitan areas receiving NSS increased from 43% in 2009 to 58% in 2012 (P < 0.05), and 69% in 2013 (P < 0.05). For patients residing in non-metropolitan areas, the proportion receiving NSS increased from 27% in 2009 to 49% in 2012, and 61% in 2013 (P < 0.01). Univariable logistic regression showed patients with moderate (odds ratio [OR] 0.57, 95% confidence interval [CI] 0.35-0.94) or severe comorbidities (OR 0.58, 95% CI 0.33-0.99), residing in non-metropolitan areas (OR 0.65, 95% CI 0.47-0.90), were less likely to be treated by NSS, while those attending high-volume hospitals (≥30 cases/year: OR 1.79, 95% CI 1.21-2.65) and those with higher socio-economic status (OR 1.45, 95% CI 1.02-2.07) were more likely to be treated by NSS. In multivariable analyses, patients with T1a tumours in 2012 (OR 2.00, 95% CI 1.34-2.97) and 2013 (OR 3.15, 95% CI 2.13-4.68) were more likely to be treated by NSS than those in 2009. For T1b tumours, use of NSS increased from 8% in 2009 to 20% in 2013 (P < 0.05). CONCLUSION: This population-based study of the management of T1 renal tumours in Australia found that the use of NSS increased over the period 2009 to 2013. Between 2009 and 2013 clinical practice for the treatment of small renal tumours in Australia has increasingly conformed to international guidelines.
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    Age at diagnosis and the surgical management of small renal carcinomas: findings from a cross-sectional population-based study
    White, VM ; Marco, DJT ; Bolton, D ; Papa, N ; Neale, RE ; Coory, M ; Davis, ID ; Wood, S ; Giles, GG ; Jordan, SJ (WILEY, 2018-11)
    OBJECTIVES: To describe the use of partial nephrectomy (PN) for patients with stage T1a renal cell carcinoma (RCC) by age group (<65 and ≥65 years) in two Australian states. MATERIALS AND METHODS: All adults diagnosed with RCC in 2012 and 2013 were identified through population-based cancer registries in the Australian states of Queensland and Victoria. For each patient, research assistants extracted patient, tumour and treatment data from medical records. Percentages of patients treated by PN were determined for the two age groups. Multivariable logistic regression analyses examined factors associated with PN. Clinicians treating RCC were sent surveys to assess attitudes towards PN. RESULTS: Data were collected on 956 patients (Victoria: n = 548; Queensland: n = 404) with stage T1a RCC. Of those undergoing surgery (n = 865), PN was more common for those aged <65 years (61%) than for those aged ≥65 years (44%), with this difference significant after adjusting for patient, tumour (odds ratio 0.50, 95% confidence interval 0.36-0.70). There were significant interactions between age and treatment centre volume (P < 0.05) and residential state (P < 0.05). PN was less likely for younger patients treated at lower-volume hospitals (<24 patients a year) but hospital volume was not associated with PN for older patients. PN was less likely for older patients in Queensland than Victoria. In multivariable analyses, age was not related to laparoscopic surgery. Queensland clinicians were less likely than those from Victoria to agree that PN was the treatment of choice for most T1aN0M0 tumours (P < 0.001). CONCLUSIONS: In Australia, patients aged > 65 years with small renal cancers were less likely to be treated by PN than younger patients. The variation in the surgical procedure used to treat older T1a RCC patients by state and hospital volume indicates that better evidence is needed to direct practice in this area.
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    Predictors of new-onset chronic kidney disease in patients managed surgically for T1a renal cell carcinoma: An Australian population-based analysis
    Ahn, T ; Ellis, RJ ; White, VM ; Bolton, DM ; Coory, MD ; Davis, ID ; Francis, RS ; Giles, GG ; Gobe, GC ; Hawley, CM ; Johnson, DW ; Marco, DJT ; McStea, M ; Neale, RE ; Pascoe, EM ; Wood, ST ; Jordan, SJ (WILEY, 2018-06-01)
    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.
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    Circulating concentrations of B group vitamins and urothelial cell carcinoma
    Bassett, JK ; Brinkman, MT ; Dugue, P-A ; Ueland, PM ; Midttun, O ; Ulvik, A ; Bolton, D ; Southey, MC ; English, DR ; Milne, RL ; Hodge, AM ; Giles, GG (WILEY, 2019-04-15)
    B-group vitamins, as components of the one carbon metabolism pathway, are involved in DNA synthesis, repair and methylation. Our aim was to investigate associations between circulating plasma levels of B vitamins and urothelial cell carcinoma (UCC). We conducted a nested case-control study of UCC within the Melbourne Collaborative Cohort Study. B vitamins were measured in pre-diagnostic plasma samples. Conditional logistic regression was used to estimate odds ratios (OR) for UCC risk associated with circulating B vitamins in 363 matched cases and controls. In a case-only analysis (N = 390), hazard ratios (HR) for overall survival associated with plasma B vitamins were estimated using Cox regression. There were no strong associations between UCC risk and pre-diagnostic levels of plasma B vitamins. No heterogeneity in UCC risk was observed by subtype (invasive or superficial), sex, smoking status or alcohol intake. There was no heterogeneity by country of birth for most B vitamins, except for folate (p-homogeneity = 0.03). In UCC cases, there were no strong associations between plasma B vitamins and overall survival. We found no associations between pre-diagnostic plasma concentrations of B-group vitamins and UCC risk or survival.
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    Dietary intake of nutrients involved in one-carbon metabolism and risk of urothelial cell carcinoma: A prospective cohort study
    Dugue, P-A ; Brinkman, MT ; Hodge, AM ; Bassett, JK ; Bolton, D ; Longano, A ; Hopper, JL ; Southey, MC ; English, DR ; Milne, RL ; Giles, GG (WILEY, 2018-07-15)
    Nutrients involved in one-carbon metabolism may play a role in carcinogenesis through DNA replication, repair and methylation mechanisms. Most studies on urothelial cell carcinoma (UCC) have focused on folate. We sought to examine the association between B-group vitamins and methionine intake and UCC risk, overall and by subtype, and to test whether these associations are different for population subgroups whose nutritional status may be compromised. We followed participants in the Melbourne Collaborative Cohort Study (N = 41,513) for over 20 years and observed 500 UCC cases (89% originating in the bladder; superficial: 279, invasive: 221). Energy-adjusted dietary intakes of B vitamins (B1, B2, B3, B5, B6, B8, B9 and B12) and methionine were estimated from a 121-item food frequency questionnaire administered at baseline (1990-1994), using the residuals method. We used Cox regression models to compute hazard ratios (HRs) of UCC risk per standard deviation (SD) of log-transformed nutrient intakes and 95% confidence intervals, adjusted for potential confounders. We investigated associations by tumor subtype, and tested interactions with sex, country of birth, smoking and alcohol drinking. The risk of UCC appeared not to be associated with intake of B-group vitamins or methionine, and findings were consistent across tumor subtypes and across demographic and lifestyle characteristics of the participants. A potential interaction between vitamin B1 and alcohol drinking was observed (all participants: HR per 1 SD = 0.99 (0.91-1.09), never drinkers: HR = 0.81 (0.69-0.97), p-interaction = 0.02), which needs to be confirmed by other studies. Our findings do not indicate that dietary intake of nutrients involved in one-carbon metabolism are associated with UCC risk.
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    Rare germline genetic variants and risk of aggressive prostate cancer
    Nguyen-Dumont, T ; MacInnis, RJ ; Steen, JA ; Theys, D ; Tsimiklis, H ; Hammet, F ; Mahmoodi, M ; Pope, BJ ; Park, DJ ; Mahmood, K ; Severi, G ; Bolton, D ; Milne, RL ; Giles, GG ; Southey, MC (WILEY, 2020-10-15)
    Few genetic risk factors have been demonstrated to be specifically associated with aggressive prostate cancer (PrCa). Here, we report a case-case study of PrCa comparing the prevalence of germline pathogenic/likely pathogenic (P/LP) genetic variants in 787 men with aggressive disease and 769 with nonaggressive disease. Overall, we observed P/LP variants in 11.4% of men with aggressive PrCa and 9.8% of men with nonaggressive PrCa (two-tailed Fisher's exact tests, P = .28). The proportion of BRCA2 and ATM P/LP variant carriers in men with aggressive PrCa exceeded that observed in men with nonaggressive PrCa; 18/787 carriers (2.3%) and 4/769 carriers (0.5%), P = .004, and 14/787 carriers (0.02%) and 5/769 carriers (0.01%), P = .06, respectively. Our findings contribute to the extensive international effort to interpret the genetic variation identified in genes included on gene-panel tests, for which there is currently an insufficient evidence-base for clinical translation in the context of PrCa risk.
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    Detection of infectious organisms in archival prostate cancer tissues
    Yow, MA ; Tabrizi, SN ; Severi, G ; Bolton, DM ; Pedersen, J ; Longano, A ; Garland, SM ; Southey, MC ; Giles, GG (BIOMED CENTRAL LTD, 2014-08-09)
    BACKGROUND: Seroepidemiological studies have reported associations between exposure to sexually transmitted organisms and prostate cancer risk. This study sought DNA evidence of candidate organisms in archival prostate cancer tissues with the aim of assessing if a subset of these cancers show any association with common genital infections. METHODS: 221 archival paraffin-embedded tissue blocks representing 128 histopathologically confirmed prostate cancers comprising 52 "aggressive" (Gleason score ≥ 7) and 76 "non-aggressive" (Gleason score ≤ 6) TURP or radical prostatectomy specimens were examined, as well as unaffected adjacent tissue when available. Representative tissue sections were subjected to DNA extraction, quality tested and screened by PCR for HSV-1, HSV-2, XMRV, BKV, HPV, Chlamydia trachomatis, Ureaplasma parvum, Ureaplasma urealyticum, Mycoplasma genitalium, and Trichomonas vaginalis. RESULTS: 195 of 221 DNA samples representing 49 "aggressive" and 66 "non-aggressive" prostate cancer cases were suitable for analysis after DNA quality assessment. Overall, 12.2% (6/49) aggressive and 7.6% (5/66) non-aggressive cases were positive for any of the candidate organisms. Mycoplasma genitalium DNA was detected in 4/66 non-aggressive, 5/49 aggressive cancers and in one cancer-unaffected adjacent tissue block of an aggressive case. Ureaplasma urealyticum DNA was detected in 0/66 non-aggressive and 1/49 aggressive cancers and HSV DNA in 1/66 non-aggressive and 0/49 aggressive cancers. This study did not detect BKV, XMRV, T. vaginalis, U. parvum, C. trachomatis or HPV DNA. CONCLUSIONS: The low prevalence of detectable microbial DNA makes it unlikely that persistent infection by the selected candidate microorganisms contribute to prostate cancer risk, regardless of tumour phenotype.
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    Increased prostate cancer specific mortality following radical prostatectomy in men presenting with voiding symptoms-A whole of population study
    Ta, AD ; Papa, NP ; Lawrentschuk, N ; Millar, JL ; Syme, R ; Giles, GG ; Bolton, DM (ELSEVIER INC, 2015-09)
    BACKGROUND: Whole of population studies reporting long-term outcomes following radical prostatectomy (RP) are scarce. We aimed to evaluate the long-term outcomes in men with prostate cancer (PC) treated with RP in a whole of population cohort. A secondary objective was to evaluate the influence of mode of presentation on PC specific mortality (PCSM). METHODS: A prospective database of all cases of RP performed in Victoria, Australia between 1995 and 2000 was established within the Victorian Cancer Registry. Specimen histopathology reports and prostate-specific antigen (PSA) values were obtained by record linkage to pathology laboratories. Mode of presentation was recorded as either PSA screened (PSA testing offered in absence of voiding symptoms) or symptomatic (diagnosis of PC following presentation with voiding symptoms). Multivariate Cox and competing risk regression models were fitted to analyze all-cause mortality, biochemical recurrence, and PCSM. RESULTS: Between 1995 and 2000, 2,154 men underwent RP in Victoria. During median follow up of 10.2 years (range 0.26-13.5 years), 74 men died from PC. In addition to Gleason score and pathological stage, symptomatic presentation was associated with PCSM. After adjusting for stage and PSA, no difference in PCSM was found between men with Gleason score ≤ 6 and Gleason score 3 + 4 = 7. Men with Gleason score 4 + 3 had significantly greater cumulative incidence of PCSM compared with men with Gleason score 3 + 4. CONCLUSIONS: Primary Gleason pattern in Gleason 7 PC is an important prognosticator of survival. Our findings suggest that concomitant voiding symptoms should be considered in the work-up and treatment of PC.
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    Genome-wide measures of DNA methylation in peripheral blood and the risk of urothelial cell carcinoma: a prospective nested case-control study
    Dugue, P-A ; Brinkman, MT ; Milne, RL ; Wong, EM ; FitzGerald, LM ; Bassett, JK ; Joo, JE ; Jung, C-H ; Makalic, E ; Schmidt, DF ; Park, DJ ; Chung, J ; Ta, AD ; Bolton, DM ; Lonie, A ; Longano, A ; Hopper, JL ; Severi, G ; Saffery, R ; English, DR ; Southey, MC ; Giles, GG (SPRINGERNATURE, 2016-09)
    BACKGROUND: Global DNA methylation has been reported to be associated with urothelial cell carcinoma (UCC) by studies using blood samples collected at diagnosis. Using the Illumina HumanMethylation450 assay, we derived genome-wide measures of blood DNA methylation and assessed them for their prospective association with UCC risk. METHODS: We used 439 case-control pairs from the Melbourne Collaborative Cohort Study matched on age, sex, country of birth, DNA sample type, and collection period. Conditional logistic regression was used to compute odds ratios (OR) of UCC risk per s.d. of each genome-wide measure of DNA methylation and 95% confidence intervals (CIs), adjusted for potential confounders. We also investigated associations by disease subtype, sex, smoking, and time since blood collection. RESULTS: The risk of superficial UCC was decreased for individuals with higher levels of our genome-wide DNA methylation measure (OR=0.71, 95% CI: 0.54-0.94; P=0.02). This association was particularly strong for current smokers at sample collection (OR=0.47, 95% CI: 0.27-0.83). Intermediate levels of our genome-wide measure were associated with decreased risk of invasive UCC. Some variation was observed between UCC subtypes and the location and regulatory function of the CpGs included in the genome-wide measures of methylation. CONCLUSIONS: Higher levels of our genome-wide DNA methylation measure were associated with decreased risk of superficial UCC and intermediate levels were associated with reduced risk of invasive disease. These findings require replication by other prospective studies.