Effects of Vitamin D Supplementation on Telomere Length: An Analysis of Data from the Randomised Controlled D-Health Trial.

OBJECTIVES: Observational studies have suggested that a higher 25-hydroxyvitamin D concentration may be associated with longer telomere length; however, this has not been investigated in randomised controlled trials. We conducted an ancillary study within a randomised, double-blind, placebo-controlled trial of monthly vitamin D (the D-Health Trial) for the prevention of all-cause mortality, conducted from 2014 to 2020, to assess the effect of vitamin D supplementation on telomere length (measured as the telomere to single copy gene (T/S) ratio). DESIGN, SETTING, PARTICIPANTS, AND INTERVENTION: Participants were Australians aged 60-84 years and we randomly selected 1,519 D-Health participants (vitamin D: n=744; placebo: n=775) for this analysis. We used quantitative polymerase chain reaction to measure the relative telomere length (T/S ratio) at 4 or 5 years after randomisation. We compared the mean T/S ratio between the vitamin D and placebo groups to assess the effect of vitamin D supplementation on relative telomere length, using a linear regression model with adjustment for age, sex, and state which were used to stratify the randomisation. RESULTS: The mean T/S ratio was 0.70 for both groups (standard deviation 0.18 and 0.16 for the vitamin D and placebo groups respectively). The adjusted mean difference (vitamin D minus placebo) was -0.001 (95% CI -0.02 to 0.02). There was no effect modification by age, sex, body mass index, or predicted baseline 25-hydroxyvitamin D concentration. CONCLUSION: In conclusion, routinely supplementing older adults, who are largely vitamin D replete, with monthly doses of vitamin D is unlikely to influence telomere length.

Healthcare Costs Before and After Diagnosis of Cancer of Unknown Primary Versus Ovarian Cancer in Australia.

BACKGROUND: Little is known about the healthcare resource usage and costs for patients with cancer of unknown primary (CUP). OBJECTIVE: The aim of this study was to describe and quantify healthcare resource use and costs in Australia, 6 months prior to and after a diagnosis of CUP, and compare to those of women with ovarian cancer. METHODS: Individual-level data combining baseline surveys, clinical records and Medicare Benefits Schedule (MBS) claim records were analysed for 149 patients with CUP and 480 patients with ovarian cancer from two prospective cohort studies. MBS data were aggregated for the period 6 months prior to diagnosis date and 6 months after diagnosis. Data included doctor consultations, pathology, diagnostics, therapeutic procedures, imaging, allied health and medicines. Generalised linear models were used to evaluate the cost differences between CUP and ovarian cancer using gamma family and log link functions. Models were adjusted for age, employment, marital status, surgery, chemotherapy and number of comorbidities. RESULTS: The mean healthcare costs in the 6 months prior to diagnosis of CUP were Australian (AU) $3903 versus AU$1327 for ovarian cancer (adjusted cost ratio 2.94, 95% confidence interval [CI] 2.08-4.15). Mean healthcare costs 6 months post-diagnosis were higher for patients with CUP versus ovarian cancer (AU$20,339 vs AU$13,819, adjusted cost ratio 1.47, 95% CI 1.13-1.92). Higher costs for patients with CUP were driven by imaging (AU$1937 vs AU$1387), procedures (AU$5403 vs AU$2702) and prescribed medicines for all conditions (AU$10,111 vs AU$6717). CONCLUSIONS: Pre-diagnosis costs for patients with CUP are nearly triple those for ovarian cancer. Six months after diagnosis, healthcare costs for CUP remained higher than for ovarian cancer due to imaging, procedures and medicines.

Evaluating the impact of dose reductions and delays on progression-free survival in women with ovarian cancer treated with either three-weekly or dose-dense carboplatin and paclitaxel regimens in the national prospective OPAL cohort study.

OBJECTIVES: To determine the impact of chemotherapy dose reductions and dose delays on progression-free survival (PFS) in women with ovarian cancer receiving first line chemotherapy in a real world prospective cohort study. METHODS: Patients with newly diagnosed epithelial ovarian (or peritoneal, fallopian tube) cancer enrolled in a national Australian prospective study, OPAL, who commenced three-weekly carboplatin (AUC 5 or 6) and paclitaxel 175 mg/m2 (CP) or carboplatin (AUC 5 or 6) and dose-dense weekly paclitaxel 80 mg/m2 (DD-CP) were eligible. Primary endpoint was PFS. RESULTS: 634 evaluable patients, 309 commenced CP and 325 DD-CP. Patient's age was similar in the two groups (median 62 years, range 21-79). All planned chemotherapy doses were completed by 66% vs 40% (p < 0.001) in the CP and DD-CP groups respectively. There was at least one treatment delay in 28% vs 58% (p < 0.001) in the CP and DD-CP groups, respectively, and 29% vs 49% (p < 0.001), respectively, required at least a 15% dose reduction for either carboplatin or paclitaxel. Median PFS was 29.2 [22.9, 43.8] and 21.5 [19.4, 23.1] months in the CP and DD-CP groups respectively. Adjusting for age, histology and FIGO stage PFS did not differ between treatment groups. Median PFS was similar in patients irrespective of dose reduction or dose delay. CONCLUSION: Patients receiving DD-CP required more dose reductions and delays due to haematological toxicities and lower completion rates than CP without significant difference in median PFS between CP and DD-CP. Median PFS was similar in patients irrespective of dose reduction or dose delay.

Dietary inflammatory index, risk and survival among women with endometrial cancer.

PURPOSE: Chronic inflammation has been implicated in endometrial carcinogenesis yet the impact of potentially modifiable exposures that might affect inflammation, like diet, has been understudied. This study examined the association between the dietary inflammatory index (DII®), a literature-derived tool to assess the inflammatory potential of diet, and risk of developing, and survival after a diagnosis of endometrial cancer (EC). METHODS: This study included data from 1,287 women with EC and 1,435 population controls who participated in the Australian National Endometrial Cancer Study. Energy-adjusted DII (E-DII) scores were calculated from pre-diagnostic dietary intake obtained using a semi-quantitative food frequency questionnaire. Logistic regression was used to assess the association between E-DII scores and risk of EC and proportional-hazards models were used for survival analyses. RESULTS: Higher E-DII scores, reflecting a more pro-inflammatory diet, were not associated with risk of EC [adjusted odds ratio (OR) 0.98, 95% CI 0.77-1.24, p-trend = 0.7]. However, in stratified analyses, higher E-DII scores were associated with increased risk of EC among very obese (BMI 35 + kg/m2) women (OR 1.60, 95% CI 0.80-3.21, p-trend = 0.049, p-interaction = 0.045). After a median follow-up of 7.2 years there were 160 deaths, of which 110 (69%) were from EC. We found no association between E-DII score and survival. CONCLUSION: Greater inflammatory potential of pre-diagnostic diet was not associated with EC risk or survival. Secondary stratified analysis suggested greater inflammatory potential may be associated with EC risk in very obese women.

Correction to: The association between the inflammatory potential of diet and risk of developing, and survival following, a diagnosis of ovarian cancer.

In the original publication of this article on page 6, paragraph "Discussion", line 4, 'In a U.S. population-based case-control study (n = 493 cases) Peres et al., reported a non-significant association between DII score and risk of developing ovarian cancer of similar magnitude (OR DII scoreQ4 vs. Q1 1.35, 95% CI 0.93-1.97) [20]'. It should read as 'In a U.S. population-based case-control study (n = 493 cases) Peres et al., reported a significant association between DII score and risk of developing ovarian cancer (OR DII scoreQ4 vs. Q1 1.72, 95% CI 1.18-2.51) [20]'.

The association between the inflammatory potential of diet and risk of developing, and survival following, a diagnosis of ovarian cancer.

PURPOSE: Inflammation has been implicated in ovarian carcinogenesis. This study evaluated two dietary indices: the Dietary Inflammatory Index (DII®) and the Empirical Dietary Inflammatory Pattern (EDIP), in relation to risk of developing, and survival following, a diagnosis of ovarian cancer. METHODS: Data came from the Australian Ovarian Cancer Study (1375 cases, 1415 population controls). DII and EDIP scores were computed from dietary information obtained using a semiquantitative food-frequency questionnaire. Logistic regression was used to assess the association between DII and EDIP scores and risk of ovarian cancer and proportional hazards models were used for survival analysis. RESULTS: A high DII score, reflecting a more pro-inflammatory diet, was associated with a modest increased risk of ovarian cancer [odds ratio (OR) DII scoreQ4 vs.Q1 = 1.31, 95% CI 1.06-1.63, ptrend = 0.014]. Likewise a high EDIP score was associated with an increase in risk of ovarian cancer [OR EDIP scoreQ4 vs.Q1 = 1.39, 95% confidence interval (CI) 1.12-1.73, ptrend = 0.002]. We found no association between DII or EDIP score and overall or ovarian cancer-specific survival. CONCLUSION: In conclusion, our results suggest that a pro-inflammatory diet modestly increases the risk of developing ovarian cancer.

Use of aspirin, other nonsteroidal anti-inflammatory drugs and acetaminophen and risk of endometrial cancer: the Epidemiology of Endometrial Cancer Consortium.

BACKGROUND: Regular use of aspirin has been associated with a reduced risk of cancer at several sites but the data for endometrial cancer are conflicting. Evidence regarding use of other analgesics is limited. PATIENTS AND METHODS: We pooled individual-level data from seven cohort and five case-control studies participating in the Epidemiology of Endometrial Cancer Consortium including 7120 women with endometrial cancer and 16 069 controls. For overall analyses, study-specific odds ratios (ORs) and 95% confidence intervals (CI) were estimated using logistic regression and combined using random-effects meta-analysis; for stratified analyses, we used mixed-effects logistic regression with study as a random effect. RESULTS: At least weekly use of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with an approximately 15% reduced risk of endometrial cancer among both overweight and obese women (OR = 0.86 [95% CI 0.76-0.98] and 0.86 [95% CI 0.76-0.97], respectively, for aspirin; 0.87 [95% CI 0.76-1.00] and 0.84 [0.74-0.96], respectively, for non-aspirin NSAIDs). There was no association among women of normal weight (body mass index < 25 kg/m2, Pheterogeneity = 0.04 for aspirin, Pheterogeneity = 0.003 for NSAIDs). Among overweight and obese women, the inverse association with aspirin was stronger for use 2-6 times/week (OR = 0.81, 95% CI 0.68-0.96) than for daily use (0.91, 0.80-1.03), possibly because a high proportion of daily users use low-dose formulations. There was no clear association with use of acetaminophen. CONCLUSION: Our pooled analysis provides further evidence that use of standard-dose aspirin or other NSAIDs may reduce risk of endometrial cancer among overweight and obese women.

The association between diabetes, comorbidities, body mass index and all-cause and cause-specific mortality among women with endometrial cancer.

OBJECTIVE: Although endometrial cancer (EC) is associated with relatively good survival rates overall, women diagnosed with high-risk subtypes have poor outcomes. We examined the relationship between lifestyle factors and subsequent all-cause, cancer-specific and non-cancer related survival. METHODS: In a cohort of 1359 Australian women diagnosed with incident EC between 2005 and 2007 pre-diagnostic information was collected by interview at recruitment. Clinical and survival information was abstracted from women's medical records, supplemented by linkage to the Australian National Death Index. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific survival (EC death vs. non-EC death) associated with each exposure, overall and by risk group (low-grade endometrioid vs. high-grade endometrioid and non-endometrioid). RESULTS: After a median follow-up of 7.1 years, 179 (13%) women had died, with 123 (69%) deaths from EC. As expected, elevated body mass index (BMI), diabetes and the presence of other co-morbidities were associated with a significantly increased risk of all-cause and non-cancer related death. Women with diabetes had higher cancer-specific mortality rates (HR 2.09, 95% CI 1.31-3.35), particularly those who had were not obese (HR 4.13, 95% CI 2.20-7.76). The presence of ≥2 other co-morbidities (excluding diabetes) was also associated with increased risk of cancer-specific mortality (HR 3.09, 95% CI 1.21-7.89). The patterns were generally similar for women with low-grade and high-grade endometrioid/non-endometrioid EC. CONCLUSION: Our findings demonstrate the importance of diabetes, other co-morbidities and obesity as negative predictors of mortality among women with EC but that the risks differ for cancer-specific and non-cancer related mortality.

The D-Health Trial: A randomized trial of vitamin D for prevention of mortality and cancer.

BACKGROUND: Vitamin D, specifically serum 25(OH)D has been associated with mortality, cancer and multiple other health endpoints in observational studies, but there is a paucity of clinical trial evidence sufficient to determine the safety and effectiveness of population-wide supplementation. We have therefore launched the D-Health Trial, a randomized trial of vitamin D supplementation for prevention of mortality and cancer. Here we report the methods and describe the trial cohort. METHODS: The D-Health Trial is a randomized placebo-controlled trial, with planned intervention for 5years and a further 5years of passive follow-up through linkage with health and death registers. Participants aged 65-84years were recruited from the general population of Australia. The intervention is monthly oral doses of 60,000IU of cholecalciferol or matching placebo. The primary outcome is all-cause mortality. Secondary outcomes are total cancer incidence and colorectal cancer incidence. RESULTS: We recruited 21,315 participants to the trial between February 2014 and May 2015. The participants in the two arms of the trial were well-balanced at baseline. Comparison with Australian population statistics shows that the trial participants were less likely to report being in fair or poor health, to be current smokers or to have diabetes than the Australian population. However, the proportion overweight or with health conditions such as arthritis and angina was similar. CONCLUSIONS: Observational data cannot be considered sufficient to support interventions delivered at a population level. Large-scale randomized trials such as the D-Health Trial are needed to inform public health policy and practice.

Infertility and incident endometrial cancer risk: a pooled analysis from the epidemiology of endometrial cancer consortium (E2C2).

BACKGROUND: Nulliparity is an endometrial cancer risk factor, but whether or not this association is due to infertility is unclear. Although there are many underlying infertility causes, few studies have assessed risk relations by specific causes. METHODS: We conducted a pooled analysis of 8153 cases and 11 713 controls from 2 cohort and 12 case-control studies. All studies provided self-reported infertility and its causes, except for one study that relied on data from national registries. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Nulliparous women had an elevated endometrial cancer risk compared with parous women, even after adjusting for infertility (OR=1.76; 95% CI: 1.59-1.94). Women who reported infertility had an increased risk compared with those without infertility concerns, even after adjusting for nulliparity (OR=1.22; 95% CI: 1.13-1.33). Among women who reported infertility, none of the individual infertility causes were substantially related to endometrial cancer. CONCLUSIONS: Based on mainly self-reported infertility data that used study-specific definitions of infertility, nulliparity and infertility appeared to independently contribute to endometrial cancer risk. Understanding residual endometrial cancer risk related to infertility, its causes and its treatments may benefit from large studies involving detailed data on various infertility parameters.

Dietary folate and related micronutrients, folate-metabolising genes, and ovarian cancer survival.

OBJECTIVE: Folate is essential for DNA synthesis and methylation and is implicated in tumour progression. Few studies have examined its role in ovarian cancer survival. Our objective was to determine relationships between intake of folate, related one-carbon nutrients, single nucleotide polymorphisms (SNPs) in folate-metabolising genes and survival following ovarian cancer diagnosis. METHODS: This analysis included 1270 women with invasive epithelial ovarian cancer diagnosed in 2002-2006. Pre-diagnostic and some post-diagnostic lifestyle, dietary, and sociodemographic information was collected via self-administered questionnaires. DNA samples were genotyped for SNPs in methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR) and methionine synthase reductase (MTRR) genes. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression. RESULTS: Multivariate analyses did not identify associations between higher pre-diagnostic intake of folate, folic acid, vitamins B2, B6, and B12, methionine, betaine or choline and survival overall. In stratified analyses, higher folic acid and folate intake was associated with significantly worse survival among women with mucinous tumours (HRs per 100 µg 1.30 and 1.43, respectively) and smokers (HRs per 100 µg 1.23 and 1.16 respectively). There was also a suggestion that higher supplemental folic acid use post-diagnosis was associated with worse survival (HR per 100 µg 1.03, 95%CI 1.00-1.05). MTHFR SNP rs2066470 was significantly associated with survival (per allele HR 0.81, 95%CI 0.67-0.98). CONCLUSIONS: Our data provide little evidence that folate intake affects ovarian cancer survival. However, combined effects with smoking, and findings within the mucinous subtype and for post-diagnosis folic acid, warrant further investigation.

Physical symptoms, coping styles and quality of life in recurrent ovarian cancer: a prospective population-based study over the last year of life.

OBJECTIVE: The aim of this study was to describe the trajectory of physical symptoms, coping styles and quality of life (QoL) and the relationship between coping and QoL over the last year of life in women with recurrent ovarian cancer. METHODS: The patient cohort were women recruited to the Australian Ovarian Cancer Study who subsequently experienced recurrent, invasive ovarian cancer and completed at least one psychosocial assessment (optimism, minimisation, hopelessness/helplessness, QoL) during the last year of life (n=217). RESULTS: QoL declined sharply from six months before death. Lack of energy was the most prevalent symptom over three measurement periods (67-92%) and also the most severe. Anorexia (36-55%), abdominal swelling (33-58%), nausea (26-47%) and pain (26-43%) all increased in prevalence and severity towards the end of life. Higher optimism (p=0.009), higher minimisation (p=0.003) and lower helplessness/hopelessness (p=0.03) at baseline were significant predictors of subsequent higher QoL. CONCLUSIONS: Progressive deterioration in quality of life may be an indicator of death within about six months and therefore should be an important consideration in decisions about subsequent treatment. Coping styles which independently predicted subsequent changes in QoL could potentially be targeted by interventions to minimise worsening QoL.

Impact of weight change and weight cycling on risk of different subtypes of endometrial cancer.

AIM: Obesity is an established risk factor for endometrial cancer. Associations tend to be stronger for the endometrioid subtype. The role of adult weight change and weight cycling is uncertain. Our study aimed to determine whether there is an association between different adult weight trajectories, weight cycling and risk of endometrial cancer overall, and by subtype. METHODS: We analysed data from the Australian National Endometrial Cancer study, a population-based case-control study that collected self-reported information on height, weight at three time points (age 20, maximum and 1 year prior to diagnosis [recent]), intentional weight loss/regain (weight cycling) from 1398 women with endometrial cancer and 1538 controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression analysis. RESULTS: Relative to women who maintained a stable weight during adulthood, greater weight gain after the age of 20 was associated with increased risk of endometrial cancer (OR for gain 40+kg all subtypes 5.3, 95% CI 3.9-7.3; endometrioid 6.5, 95% CI 4.7-9.0). The strongest associations were observed among women who were continually overweight from the age of 20 (all subtypes OR 3.6, 95% CI 2.6-5.0). Weight cycling was associated with increased risk, particularly among women who had ever been obese (OR 2.9 95% CI 1.8-4.7), with ~3-fold risks seen for both endometrioid and non-endometrioid tumour subtypes. Women who had intentionally lost weight and maintained that weight loss were not at increased risk. CONCLUSION: These results suggest that higher adult weight gain, and perhaps weight cycling, independently increase the risk of endometrial cancer, however women who lost weight and kept that weight off were not at increased risk.

Intake of omega-3 and omega-6 fatty acids and risk of ovarian cancer.

OBJECTIVES: Limited experimental evidence suggests that omega-3 polyunsaturated (n-3) fatty acids inhibit the proliferation of ovarian cancer cells in vitro, whereas omega-6 polyunsaturated (n-6) fatty acids have been shown to promote carcinogenesis, but epidemiological studies to date have been inconclusive. Our aim was to evaluate the role of polyunsaturated fatty acids in ovarian carcinogenesis. METHODS: Participants in the Australian Ovarian Cancer Study (1,366 cases and 1,414 population controls) self-completed risk factor and food frequency questionnaires. Logistic regression models were used to calculate adjusted odds ratio (OR) and 95 % confidence intervals (CI). RESULTS: We found no association between intake of total n-3 fatty acids from foods, or the individual n-3 fatty acids-alpha-linolenic, eicosapentaenoic, docosapentaenoic, docosahexaenoic acids-and ovarian cancer risk. High intake of total n-6 fatty acids was inversely associated with risk (OR for highest vs. lowest category 0.78, 95 % CI 0.60-1.00, p-trend 0.04); however, the association was restricted to n-6 fatty acids from avocado, vegetables, and nuts. Neither higher intake of the individual n-6 fatty acids nor the ratio of n-3 to n-6 fatty acids was associated with ovarian cancer risk. We found no evidence that risk varied by supplement use. CONCLUSIONS: Our data provide no evidence of a protective role for n-3 fatty acids in ovarian carcinogenesis. The benefit, if any, of higher intake of n-6 fatty acids is due to general properties of the food sources, rather than due to the n-6 fatty acids per se.

The use of nonsteroidal anti-inflammatory drugs and the risk of Barrett's oesophagus.

BACKGROUND: Epidemiological studies have consistently reported inverse associations between nonsteroidal anti-inflammatory drugs (NSAIDs) and oesophageal adenocarcinoma, but few have investigated associations with the precursor lesion, Barrett's oesophagus. AIM: To investigate the relationship between NSAID use and risk of Barrett's oesophagus. METHODS: We conducted a large population-based case-control study that collected information on patterns of intake for aspirin and non-aspirin NSAIDs during the past 5 years and other exposures from 285 patients with nondysplastic Barrett's oesophagus, 108 patients with dysplastic Barrett's oesophagus, and two separate control groups: 313 endoscopy patients with acute inflammatory changes ('inflammation controls') and 644 population controls. We calculated odds ratios (ORs) and 95% CIs using unconditional logistic regression. RESULTS: Use of aspirin was not associated with nondysplastic Barrett's oesophagus when compared with population (OR=1.01, 95% CI 0.71-1.43) or inflammation controls (OR=1.16, 95% CI 0.80-1.68). Whereas we observed significant risk reductions for use of non-aspirin NSAIDs when nondysplastic Barrett's oesophagus cases were compared with population controls (OR=0.69, 95% CI 0.49-0.97), the effect was weaker and nonsignificant when cases were compared with inflammation controls (OR=0.82, 95% CI 0.57-1.18), and no dose-response effects were present in either analysis. We found no evidence that aspirin or non-aspirin NSAID use conferred risk reductions for dysplastic Barrett's oesophagus, regardless of the control series. We excluded effect modification by known risk factors as an explanation for these null findings. CONCLUSIONS: We found little support for an inverse association between use of NSAIDs and Barrett's oesophagus. The question of whether or not these medications prevent the onset of Barrett's oesophagus remains open.

Folate and related micronutrients, folate-metabolising genes and risk of ovarian cancer.

BACKGROUND/OBJECTIVE: Folates are essential for DNA synthesis and methylation, and thus may have a role in carcinogenesis. Limited evidence suggests folate-containing foods might protect against some cancers and may partially mitigate the increased risk of breast cancer associated with alcohol intake, but there is little information regarding ovarian cancer. Our aim was to evaluate the role of folate and related micronutrients, polymorphisms in key folate-metabolising genes and environmental factors in ovarian carcinogenesis. SUBJECTS/METHODS: Participants in the Australian Ovarian Cancer Study (1363 cases, 1414 controls) self-completed risk factor and food-frequency questionnaires. DNA samples (1638 cases, 1278 controls) were genotyped for 49 tag single-nucleotide polymorphisms (SNPs) in the methylene tetrahydrofolate reductase (MTHFR), methionine synthase (MTR) and MTR reductase (MTRR) genes. Logistic regression models were used to generate adjusted odds ratios and 95% confidence intervals. RESULTS: We saw no overall association between the intake of folate, B vitamins or other methyl donors and ovarian cancer risk, although increasing folate from foods was associated with reduced risk among current smokers (P(trend)=0.03) and folic acid intake was associated with borderline significant increased risks among women who consumed ≥1 standard alcoholic drinks/day (odds ratio (OR)=1.64; 95% confidence interval (CI) 1.05-2.54, P(trend)=0.05). Two SNPs (rs7365052, rs7526063) showed borderline significant inverse associations with ovarian cancer risk; both had very low minor allele frequencies. There was little evidence for interaction between genotype and micronutrient intake or for variation between different histological subtypes of ovarian cancer. CONCLUSIONS: Our data provide little evidence to support a protective role for folate in ovarian carcinogenesis but suggest further evaluation of the joint effects of folic acid and alcohol is warranted.

Does pilonidal abscess heal quicker with off-midline incision and drainage?

BACKGROUND: No clinical trials have been done to guide the surgeon in the optimal technique of draining a pilonidal abscess. The aim of our study was to investigate whether the location of the incision influences wound healing. METHODS: Electronic records from the surgical database at our 200-bed district general hospital were reviewed for operative technique (midline vs. lateral) for patients who underwent incision and drainage for acute pilonidal abscess between January 2003 and February 2010. These patients were admitted from the Emergency Department with a pilonidal abscess, underwent operative drainage, and returned for follow-up. The main outcome measure was wound healing time. RESULTS: Two hundred and forty-three pilonidal abscesses were drained, 134 with a lateral and 74 with a midline incision. All patients underwent simple longitudinal incision. No patient underwent de-roofing, marsupialisation, or closure. Forty-eight patients with midline drainage who returned for follow-up were matched for gender, age, and microbiology culture results with patients who underwent lateral drainage. Almost all were drained under general anesthesia with a median postoperative stay of 1 day. The overall length of follow-up was the same in both groups (P = 0.13). Abscesses that did not heal were followed-up for the same period of time irrespective of incision type (P = 0.48). Abscesses that healed after midline incision took approximately 3 weeks longer than those drained via a lateral incision (P = 0.02). Our study has limitations since it was a retrospective study that did not capture patients whose abscess drained spontaneously or were drained in the emergency department. CONCLUSIONS: Pilonidal abscess should be drained away from the midline.

Carbohydrate intake, glycemic load, glycemic index, and risk of ovarian cancer.

BACKGROUND: Our objective was to determine the relationship between dietary glycemic load (GL), glycemic index (GI), carbohydrate intake, and ovarian cancer risk in a population-based case-control study. PATIENTS AND METHODS: A self-administered questionnaire was used to collect data on demographic and lifestyle factors, and a food frequency questionnaire was used to collect dietary information from 1366 women with ovarian cancer and 1414 population controls. RESULTS: GL was positively associated with ovarian cancer. The adjusted odds ratio (OR) for the highest versus the lowest quartile of intake was 1.24 [95% confidence interval (CI) 1.00-1.55, P for trend = 0.03]. Fiber intake was inversely associated with risk. The OR comparing women in the highest fiber-intake group with those in the lowest was 0.78 (95% CI 0.62-0.98, P for trend = 0.11). We found no association between GI, carbohydrate intake, and ovarian cancer. In analyses stratified by body mass index, the risk estimates for GL, carbohydrate, and sugar were higher among overweight/obese women; however, the interaction term was only significant for sugar (P for interaction = 0.004). CONCLUSIONS: Our results suggest that diets with a high GL may increase the risk of ovarian cancer, particularly among overweight/obese women, and a high intake of fiber may provide modest protection.

Gastro-oesophageal reflux symptoms and the risks of oesophageal cancer: are the effects modified by smoking, NSAIDs or acid suppressants?

OBJECTIVE: To measure the extent to which risks of oesophageal cancers associated with gastro-oesophageal reflux (GOR) are modified by common factors including smoking, non-steroidal anti-inflammatory drugs (NSAIDs) and acid suppressant medications. DESIGN AND SETTING: Population-based case-control study. PARTICIPANTS: Cases were patients with oesophageal (OAC; n = 365) or gastro-oesophageal junction (GOJAC; n = 426) adenocarcinomas, or squamous cell carcinomas (OSCC; n = 303). Controls were sampled from a population register (n = 1580). MAIN OUTCOME MEASURE: Odds ratio and 95% confidence interval. RESULTS: Frequent (at least weekly) symptoms of GOR were associated with significant 6.4-fold, 4.6-fold and 2.2-fold increased risks of OAC, GOJAC and OSCC, respectively. Under models examining effects of combined exposure, patients with frequent GOR symptoms who were also heavy smokers had markedly higher OAC risks (OR = 12.3, 95% CI 6.3 to 24.0) than those with frequent GOR who did not smoke (OR = 6.8, 95% CI 3.6 to 12.9). Similar patterns were observed for GOJAC and OSCC. Among people with frequent GOR symptoms, regular use of aspirin/NSAIDs was associated with almost two-thirds lower OAC risks (OR = 4.8, 95% CI 2.5 to 9.2) than non-users (13.9, 95% CI 6.5 to 30.0). In contrast, among those with frequent GOR symptoms, users of acid suppressants had similar OAC risks (OR 7.8, 95% CI 5.2 to 11.8) to non-users (OR 5.3, 95% CI 3.2 to 9.0). CONCLUSIONS: People experiencing frequent GOR symptoms have markedly increased risks of OAC and GOJAC, and this effect may be greater amongst smokers. Use of aspirin and NSAIDs, but not acid suppressants, significantly reduced the risks of oesophageal cancers associated with GOR.