Standardisierte Kontrastmittelsonographie (CEUS) in der klinischen Akut- und Notfallmedizin sowie Intensivmedizin (CEUS-Akut)

Die Anaesthesiologie -     

Patterns in metabolite profile are associated with risk of more aggressive prostate cancer: A prospective study of 3,057 matched case–control sets from EPIC

Metabolomics may reveal novel insights into the etiology of prostate cancer, for which few risk factors are established. We investigated the association between patterns in baseline plasma metabolite profile and subsequent prostate cancer risk, using data from 3,057 matched case–control sets from the European Prospective Investigation into Cancer and Nutrition (EPIC). We measured 119 metabolite concentrations in plasma samples, collected on average 9.4 years before diagnosis, by mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates Life Sciences AG). Metabolite patterns were identified using treelet transform, a statistical method for identification of groups of correlated metabolites. Associations of metabolite patterns with prostate cancer risk (OR_1SD) were estimated by conditional logistic regression. Supplementary analyses were conducted for metabolite patterns derived using principal component analysis and for individual metabolites. Men with metabolite profiles characterized by higher concentrations of either phosphatidylcholines or hydroxysphingomyelins (OR_1SD = 0.77, 95% confidence interval 0.66–0.89), acylcarnitines C18:1 and C18:2, glutamate, ornithine and taurine (OR_1SD = 0.72, 0.57–0.90), or lysophosphatidylcholines (OR_1SD = 0.81, 0.69–0.95) had lower risk of advanced stage prostate cancer at diagnosis, with no evidence of heterogeneity by follow-up time. Similar associations were observed for the two former patterns with aggressive disease risk (the more aggressive subset of advanced stage), while the latter pattern was inversely related to risk of prostate cancer death (OR_1SD = 0.77, 0.61–0.96). No associations were observed for prostate cancer overall or less aggressive tumor subtypes. In conclusion, metabolite patterns may be related to lower risk of more aggressive prostate tumors and prostate cancer death, and might be relevant to etiology of advanced stage prostate cancer.     

Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow-up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m²: HR = 1.94, 95% CI: 1.25–3.03) and women (HR = 2.66, 95% CI: 1.15–6.19); however, adjustment for waist-to-hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99–6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52–4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35–14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76–18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14–0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32–0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04–3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.     

Theoretical potential for endometrial cancer prevention through primary risk factor modification: Estimates from the EPIC cohort

Endometrial cancer (EC) incidence rates vary ~10-fold worldwide, in part due to variation in EC risk factor profiles. Using an EC risk model previously developed in the European EPIC cohort, we evaluated the prevention potential of modified EC risk factor patterns and whether differences in EC incidence between a European population and low-risk countries can be explained by differences in these patterns. Predicted EC incidence rates were estimated over 10 years of follow-up for the cohort before and after modifying risk factor profiles. Risk factors considered were: body mass index (BMI, kg/m²), use of postmenopausal hormone therapy (HT) and oral contraceptives (OC) (potentially modifiable); and, parity, ages at first birth, menarche and menopause (environmentally conditioned, but not readily modifiable). Modeled alterations in BMI (to all ≤23 kg/m²) and HT use (to all non-HT users) profiles resulted in a 30% reduction in predicted EC incidence rates; individually, longer duration of OC use (to all ≥10 years) resulted in a 42.5% reduction. Modeled changes in not readily modifiable exposures (i.e., those not contributing to prevention potential) resulted in ≤24.6% reduction in predicted EC incidence. Women in the lowest decile of a risk score based on the evaluated exposures had risk similar to a low risk countries; however, this was driven by relatively long use of OCs (median = 23 years). Our findings support avoidance of overweight BMI and of HT use as prevention strategies for EC in a European population; OC use must be considered in the context of benefits and risks.     

Exogenous hormone use and cutaneous melanoma risk in women: The European Prospective Investigation into Cancer and Nutrition

Evidence suggests an influence of sex hormones on cutaneous melanoma risk, but epidemiologic findings are conflicting. We examined the associations between use of oral contraceptives (OCs) and menopausal hormone therapy (MHT) and melanoma risk in women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Information on exogenous hormone use at baseline was derived from country-specific self-administered questionnaires. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over 1992–2015, 1,696 melanoma cases were identified among 334,483 women, whereof 770 cases among 134,758 postmenopausal women. There was a positive, borderline-significant association between OC use and melanoma risk (HR = 1.12, 95% CI = 1.00–1.26), with no detected heterogeneity across countries (p_homogeneity = 0.42). This risk increased linearly with duration of use (p_trend = 0.01). Among postmenopausal women, ever use of MHT was associated with a nonsignificant increase in melanoma risk overall (HR = 1.14, 95% CI = 0.97–1.43), which was heterogeneous across countries (p_homogeneity = 0.05). Our findings do not support a strong and direct association between exogenous hormone use and melanoma risk. In order to better understand these relations, further research should be performed using prospectively collected data including detailed information on types of hormone, and on sun exposure, which may act as an important confounder or effect modifier on these relations.     

Editorial zur Ausgabe „Fall verstehen: Diagnostik und Psychotherapie“

Psychotherapie Forum -     

Risk factors for colorectal cancer in man induce aberrant crypt foci in rats: Preliminary findings

Epidemiological studies have demonstrated clear associations between specific dietary and environmental risk factors and incidence of colorectal cancer, but the mechanisms responsible for these associations are not known. An animal model could facilitate such an understanding. Both genotoxic and nongenotoxic carcinogens induce aberrant crypt foci (ACF) in the colons of F344 rats. F344 rats were provided with diets that contained putative risk factors for CRC: low calcium and low vitamin D, high iron, high fructose, and decreased light (UV) exposure or a control diet for 14 wk. The rats were then assessed with biochemical measures and by topological examination for evidence of colon abnormalities. Circulating ionized calcium was decreased from 2.85 to 1.69 mmol/L, and ACF were increased from 0.7 to 13.6 lesions/colon (both P < 0.001). Rats exposed to the multiple environmental conditions associated with colon cancer, developed ACF similar to the heterogeneous or ill-defined ACF in the human colon. Heterogeneous ACF are the most frequently seen in humans and are also seen in rats shortly after exposure to the non-genotoxic colon carcinogen, dextransulfate sodium. The rodent model could be used to assess the pathways from diet and environment to colon cancer and to provide guidance for clinical studies.     

Similar risk of complete revision for infection with single-dose versus multiple-dose antibiotic prophylaxis in primary arthroplasty of the hip and knee: results of an observational cohort study in the Dutch Arthroplasty Register in 242,179 patients

Background and purpose — The optimal type and duration of antibiotic prophylaxis for primary arthroplasty of the hip and knee are subject to debate. We compared the risk of complete revision (obtained by a 1- or 2-stage procedure) for periprosthetic joint infection (PJI) after primary total hip or knee arthroplasty between patients receiving a single dose of prophylactic antibiotics and patients receiving multiple doses of antibiotics for prevention of PJI.Patients and methods — A cohort of 130,712 primary total hip and 111,467 knee arthroplasties performed between 2011 and 2015 in the Netherlands was analyzed. We linked data from the Dutch arthroplasty register to a survey collected across all Dutch institutions on hospital-level antibiotic prophylaxis policy. We used restricted cubic spline Poisson models adjusted for hospital clustering to compare the risk of revision for infection according to type and duration of antibiotic prophylaxis received.Results — For total hip arthroplasties, the rates of revision for infection were 31/10,000 person-years (95% CI 28–35), 39 (25–59), and 23 (15–34) in the groups that received multiple doses of cefazolin, multiple doses of cefuroxime, and a single dose of cefazolin, respectively. The rates for knee arthroplasties were 27/10,000 person-years (95% CI 24–31), 40 (24–62), and 24 (16–36). Similar risk of complete revision for infection among antibiotic prophylaxis regimens was found when adjusting for confounders.Interpretation — In a large observational cohort we found no apparent association between the type or duration of antibiotic prophylaxis and the risk of complete revision for infection. This does question whether there is any advantage to the use of prolonged antibiotic prophylaxis beyond a single dose.

Annually around 1 million patients receive a total hip or total knee prosthesis in the United States and over 190,000 hip and knee replacements are performed in England and Wales (Maradit et al. 2015, National Joint Registry for England and Wales 2018). The incidences of prosthetic replacement of the hip and knee are expected to increase (Kurtz et al. 2014). Prosthetic joint infection (PJI) following total hip or knee arthroplasty and the treatment thereof are catastrophic for patients and pose tremendous costs to healthcare systems (Poultsides et al. 2010, Zmistowski et al. 2013, Moore et al. 2015). Perioperative antibiotic prophylaxis remains an effective method of reducing the risk of PJI (Illingworth et al. 2013, Thornley et al. 2015). The type and duration of antibiotic prophylaxis are subject to debate.Both single-dose and multiple-dose antibiotic prophylaxis regimens have been advocated with comparable results (Thornley et al. 2015, Tan et al. 2019). The recommendations provided by the Second International Consensus Meeting of the MusculoSkeletal Infection Society (MSIS) and the European Bone and Joint Infection Society (EBJIS) advise that antibiotic prophylaxis should be administered 30–60 minutes before incision and discontinued within 24 hours after surgery (Hansen et al. 2014, Parvizi and Gehrke 2018). Large variation in prophylaxis regimens has been observed in the United Kingdom (Hickson et al. 2015). The Dutch national orthopedic association advises administration of antibiotic prophylaxis using a first- or second-generation cephalosporin starting 30–60 minutes preoperatively and discontinuing the antibiotic prophylaxis within 24 hours (Swierstra et al. 2009, Nederlandse Orthopaedische Vereniging 2018). The World Health Organization and, in the USA, the Centers for Disease Control and Prevention (CDC) recommend against the use of postoperative continuation of antibiotic prophylaxis and advocate for a single dose of antibiotics delivered preoperatively (Berrios-Torres et al. 2017). This recommendation is vehemently challenged by the American Association of Hip and Knee Surgeons and the International Consensus Meeting, which encourage their members to proceed with the current common practice of multiple-dose antibiotic prophylaxis protocols until more evidence is available (Yates 2018).We compared the risk of complete revision for infection in the 1st year following primary hip and knee arthroplasty according to the perioperatively administered antibiotic prophylaxis regimen by using data from the Dutch Arthroplasty Register (LROI).