Computer-assisted intraoperative 3D-navigation for liver surgery: a prospective randomized-controlled pilot study.

BACKGROUND Liver surgery is the standard of care for primary and many secondary liver tumors. Due to variability and complexity in liver anatomy preoperative imaging is necessary to determine resectability and for planning the surgical strategy. In the last few years, computer-assisted resection planning has been introduced in liver surgery. Aim of this trial was the evaluation of computer-assisted three-dimensional (3D)-navigation for liver surgery. METHODS This study was a prospective randomized-controlled pilot trial and patients were randomized in navigated or non-navigated group. Primary end point was the quotient of intraoperative resected volume and planned resection volume. Secondary end points included operation time, resection margin and postoperative complications. 3D reconstructions were performed with MeVis Distant Services (MeVis AG, Bremen, Germany). The navigation system CAS-One Liver (CAScination AG, Bern, Switzerland) was used for intraoperative computer-assisted 3D-navigation. RESULTS The data of 16 patients with 20 liver tumors were used in this analysis. Of these, 8 liver tumors were resected with the utilization of intraoperative navigation. Two postoperative complications were classified grade IIIa or higher. There was no difference in duration of operation (189 vs. 180 min, P=0.970), rate of postoperative complications (n=1 vs. n=1, P=0.696) and length of hospital stay (9 vs. 7 days, P=0.368) between the two groups. Minimal resection margin (0.15 vs. 0.40 cm, P=0.384) and quotient of planned to intraoperative resection volume (0.94 vs. 1.11, P=0.305) were also similar. CONCLUSIONS Intraoperative navigation is a technology that can be safely used during liver resection. Surgical accuracy is not yet superior to the current standard of intraoperative orientation. Further technological advances with suitable deformation algorithms and augmented reality systems will enable a further improvement of the technical feasibility

Impact of plastic-related compounds on the gene expression signature of HepG2 cells transfected with CYP3A4

The presence of plastic and microplastic within the oceans as well as in marine flora and fauna have caused a multitude of problems that have been the topic of numerous investigations for many years. However, their impact on human health remains largely unknown. Such plastic and microplastic particles have been detected in blood and placenta, underlining their ability to enter the human body. Plastics also contain other compounds, such as plasticizers, antioxidants, or dyes, whose impact on human health is currently being studied. Critical enzymes within the metabolism of endogenous molecules, especially of xenobiotics, are the cytochrome P450 monooxygenases (CYPs). Although their importance in maintaining cellular balance has been confirmed, their interactions with plastics and related products are poorly understood. In this study, the possible relationship between different plastic-related compounds and CYP3A4 as one of the most important CYPs was analyzed using hepatic cells overexpressing this enzyme. Beginning with virtual compound screening and molecular docking of more than 1000 plastic-related compounds, several candidates were identified to interact with CYP3A4. In a second step, RNA-sequencing was used to study in detail the transcriptome-wide gene expression levels affected by the selected compounds. Three candidate molecules ((2,2′-methylenebis(6-tert-butyl-4-methylphenol), 1,1-bis(3,5-di-tert-butyl-2-hydroxyphenyl)ethane, and 2,2′-methylenebis(6-cyclohexyl-4-methylphenol)) had an excellent binding affinity to CYP3A4 in-silico as well as cytotoxic effects and interactions with several metabolic pathways in-vitro. We identified common pathways influenced by all three selected plastic-related compounds. In particular, the suppression of pathways related to mitosis and ‘DNA-templated DNA replication’ which were confirmed by cell cycle analysis and single-cell gel electrophoresis. Furthermore, several mis-regulated metabolic and inflammation-related pathways were identified, suggesting the induction of hepatotoxicity at different levels. These findings imply that these compounds may cause liver problems subsequently affecting the entire organism

Patient-individualized resection planning in liver surgery using 3D print and virtual reality (i-LiVR) : a study protocol for a prospective randomized controlled trial

Background A multitude of different diseases—benign and malign—can require surgery of the liver. The liver is an especially challenging organ for resection planning due to its unique and interindividually variable anatomy. This demands a high amount of mental imagination from the surgeon in order to plan accordingly - a skill, which takes years of training to acquire and which is difficult to teach. Since the volume of the functional remnant liver is of great importance, parenchyma sparing resections are favoured. 3D reconstructions of computed tomography imaging enable a more precise understanding of anatomy and facilitate resection planning. The modality of presentation of these 3D models ranges from 2D monitors to 3D prints and virtual reality applications. Methods The presented trial compares three different modes of demonstration of a 3D reconstruction of CT scans of the liver, which are 3D print, a demonstration on a regular computer screen or using a head-mounted virtual reality headset, with the current gold standard of viewing the CT scan on a computer screen. The group size was calculated with n=25 each. Patients with major liver resections in a laparoscopic or open fashion are eligible for inclusion. Main endpoint is the comparison of the quotient between planned resection volume and actual resection volume between these groups. Secondary endpoints include usability for the surgical team as well as patient specifics and perioperative outcome measures and teaching issues. Discussion The described study will give insight in systematic planning of liver resections and the comparison of different demonstration modalities of 3D reconstruction of preoperative CT scans and the preference of technology. Especially teaching of these demanding operations is underrepresented in prior investigations

Prediction of remission and low disease activity in disease-modifying anti-rheumatic drug-refractory patients with rheumatoid arthritis treated with golimumab

OBJECTIVE: To create a tool to predict probability of remission and low disease activity (LDA) in patients with RA being considered for anti-TNF treatment in clinical practice. METHODS: We analysed data from GO-MORE, an open-label, multinational, prospective study in biologic-naïve patients with active RA (DAS28-ESR ⩾3.2) despite DMARD therapy. Patients received 50 mg s.c. golimumab (GLM) once monthly for 6 months. In secondary analyses, regression models were used to determine the best set of baseline factors to predict remission (DAS28-ESR <2.6) at month 6 and LDA (DAS28-ESR ⩽3.2) at month 1. RESULTS: In 3280 efficacy-evaluable patients, of 12 factors included in initial regression models predicting remission or LDA, six were retained in final multivariable models. Greater likelihood of LDA and remission was associated with being male; younger age; lower HAQ, ESR (or CRP) and tender joint count (or swollen joint count) scores; and absence of comorbidities. In models predicting 1-, 3- and 6-month LDA or remission, area under the receiver operating curve was 0.648-0.809 (R(2) = 0.0397-0.1078). The models also predicted 6-month HAQ and EuroQoL-5-dimension scores. A series of matrices were developed to easily show predicted rates of remission and LDA. CONCLUSION: A matrix tool was developed to show predicted GLM treatment outcomes in patients with RA, based on a combination of six baseline characteristics. The tool could help provide practical guidance in selection of candidates for anti-TNF therapy

Long-term weight change and risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Background: The role of obesity and weight change in breast-cancer development is complex and incompletely understood. We investigated long-term weight change and breast-cancer risk by body mass index (BMI) at age 20 years, menopausal status, hormone replacement therapy (HRT) and hormone-receptor status. Methods: Using data on weight collected at three different time points from women who participated in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we investigated the association between weight change from age 20 years until middle adulthood and risk of breast cancer. Results: In total, 150 257 women with a median age of 51 years at cohort entry were followed for an average of 14 years (standard deviation = 3.9) during which 6532 breast-cancer cases occurred. Compared with women with stable weight (+/- 2.5 kg), long-term weight gain >10 kg was positively associated with postmenopausal breast-cancer risk in women who were lean at age 20 [hazard ratio (HR) = 1.42; 95% confidence interval 1.22-1.65] in ever HRT users (HR = 1.23; 1.04-1.44), in never HRT users (HR = 1.40; 1.16-1.68) and in oestrogen-and-progesterone-receptor-positive (ERthornPRthorn) breast cancer (HR = 1.46; 1.15-1.85). Conclusion: Long-term weight gain was positively associated with postmenopausal breast cancer in women who were lean at age 20, both in HRT ever users and non-users, and hormone-receptor-positive breast cancer

Assessment of the EarlyCDT-Lung test as an early biomarker of lung cancer in ever-smokers: A retrospective nested case-control study in two prospective cohorts

The EarlyCDT-Lung test is a blood-based autoantibody assay intended to identify high-risk individuals for low-dose computed tomography lung cancer screening. However, there is a paucity of evidence on the performance of the EarlyCDT-Lung test in ever-smokers. We conducted a nested case-control study within two prospective cohorts to evaluate the risk-discriminatory performance of the EarlyCDT-Lung test using prediagnostic blood samples from 154 future lung cancer cases and 154 matched controls. Cases were selected from those who had ever smoked and had a prediagnostic blood sample <3 years prior to diagnosis. Conditional logistic regression was used to estimate the association between EarlyCDT-Lung test results and lung cancer risk. Sensitivity and specificity of the EarlyCDT-Lung test were calculated in all subjects and subgroups based on age, smoking history, lung cancer stage, sample collection time before diagnosis and year of sample collection. The overall lung cancer odds ratios were 0.89 (95% CI: 0.34-2.30) for a moderate risk EarlyCDT-Lung test result and 1.09 (95% CI: 0.48-2.47) for a high-risk test result compared to no significant test result. The overall sensitivity was 8.4% (95% CI: 4.6-14) and overall specificity was 92% (95% CI: 87-96) when considering a high-risk result as positive. Stratified analysis indicated higher sensitivity (17%, 95% CI: 7.2-32.1) in subjects with blood drawn up to 1 year prior to diagnosis. In conclusion, our study does not support a role of the EarlyCDT-Lung test in identifying the high-risk subjects in ever-smokers for lung cancer screening in the EPIC and NSHDS cohorts

Prognostic role of pre-diagnostic circulating inflammatory biomarkers in breast cancer survival: evidence from the EPIC cohort study

Background: Inflammation influences tumour progression and cancer prognosis, but its role preceding breast cancer (BC) and its prognostic implications remain inconclusive. Methods: We studied pre-diagnostic plasma inflammatory biomarkers in 1538 women with BC from the EPIC study. Cox proportional hazards models assessed their relationship with all-cause and BC-specific mortality, adjusting for tumour characteristics and lifestyle factors. Results: Over a 7-year follow-up after diagnosis, 229 women died, 163 from BC. Elevated IL-6 levels were associated with increased all-cause mortality risk (HR1-SD 1.25, 95% CI 1.07–1.47). Among postmenopausal, IL-6 was associated with higher all-cause (HR1-SD 1.41, 95% CI 1.18–1.69) and BC-specific mortality (HR1-SD 1.31, 95% CI 1.03–1.66), (PHeterogeneity (pre/postmenopausal) < 0.05 for both), while IL-10 and TNFα were associated with all-cause mortality only (HR1-SD 1.19, 95% CI 1.02–1.40 and HR1-SD 1.28, 95% CI 1.06–1.56). Among ER+PR+, IL-10 was associated with all-cause and BC-specific mortality (HR1-SD 1.35, 95% CI 1.10–1.65 and HR1-SD 1.42 95% CI 1.08–1.86), while TNF-α was associated with all-cause mortality in HER2- (HR1-SD 1.31, 95% CI 1.07–1.61). An inflammatory score predicted higher all-cause mortality, especially in postmenopausal women (HR1-SD 1.30, 95% CI 1.07–1.58). Conclusions: Higher pre-diagnosis IL-6 levels suggest poorer long-term survival among BC survivors. In postmenopausal survivors, elevated IL-6, IL-10, and TNFα and inflammatory scores seem to predict all-cause mortality

Dietary intake of plant- and animal-derived protein and incident cardiovascular diseases:the pan-European EPIC-CVD case–cohort study

Background: Epidemiological evidence suggests that a potential association between dietary protein intake and cardiovascular disease (CVD) may depend on the protein source, that is, plant- or animal-derived, but past research was limited and inconclusive. Objectives: To evaluate the association of dietary plant- or animal-derived protein consumption with risk of CVD, and its components ischemic heart disease (IHD) and stroke. Methods: This analysis in the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD case–cohort study included 16,244 incident CVD cases (10,784 IHD and 6423 stroke cases) and 15,141 subcohort members from 7 European countries. We investigated the association of estimated dietary protein intake with CVD, IHD, and stroke (total, fatal, and nonfatal) using multivariable-adjusted Prentice-weighted Cox regression. We estimated isocaloric substitutions of replacing fats and carbohydrates with plant- or animal-derived protein and replacing food-specific animal protein with plant protein. Multiplicative interactions between dietary protein and prespecified variables were tested. Results: Neither plant- nor animal-derived protein intake was associated with incident CVD, IHD, or stroke in adjusted analyses without or with macronutrient-specified substitution analyses. Higher plant-derived protein intake was associated with 22% lower total stroke incidence among never smokers [HR 0.78, 95% confidence intervals (CI): 0.62, 0.99], but not among current smokers (HR 1.08, 95% CI: 0.83, 1.40, P-interaction = 0.004). Moreover, higher plant-derived protein (per 3% total energy) when replacing red meat protein (HR 0.52, 95% CI: 0.31, 0.88), processed meat protein (HR 0.39, 95% CI: 0.17, 0.90), and dairy protein (HR 0.54, 95% CI: 0.30, 0.98) was associated with lower incidence of fatal stroke.Conclusion: Plant- or animal-derived protein intake was not associated with overall CVD. However, the association of plant-derived protein consumption with lower total stroke incidence among nonsmokers, and with lower incidence of fatal stroke highlights the importance of investigating CVD subtypes and potential interactions. These observations warrant further investigation in diverse populations with varying macronutrient intakes and dietary patterns.</p

Reproductive and hormonal factors and risk of renal cell carcinoma among women in the European Prospective Investigation into Cancer and Nutrition

PurposeThe incidence of small intestinal cancer (SIC) is increasing, however, its aetiology remains unclear due to a lack of data from large-scale prospective cohorts. We examined modifiable risk factors in relation to SIC overall and by histological subtype.MethodsWe analysed 450,107 participants enrolled in the European Prospective Investigation into Cancer and Nutrition cohort. Cox proportional hazards models were used to estimate univariable and multivariable hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsDuring an average of 14.1 years of follow-up, 160 incident SICs (62 carcinoids, 51 adenocarcinomas) were identified. Whilst univariable models revealed a positive association for current versus never smokers and SIC (HR, 95% CI: 1.77, 1.21-2.60), this association attenuated in multivariable models. In energy-adjusted models, there was an inverse association across vegetable intake tertiles for SIC overall (HRT3vsT1, 95% CI: 0.48, 0.32-0.71, p-trend: < 0.001) and for carcinoids (HRT3vsT1, 95% CI: 0.44, 0.24-0.82, p-trend: 0.01); however, these attenuated in multivariable models. Total fat was also inversely associated with total SIC and both subtypes but only in the second tertile (SIC univariable HRT2vsT1, 95% CI: 0.57, 0.38-0.84; SIC multivariable HRT2vsT1, 95% CI: 0.55, 0.37-0.81). Physical activity, intake of alcohol, red or processed meat, dairy products, or fibre were not associated with SIC.ConclusionThese exploratory analyses found limited evidence for a role of modifiable risk factors in SIC aetiology. However, sample size was limited, particularly for histologic subtypes; therefore, larger studies are needed to delineate these associations and robustly identify risk factors for SIC

Reproductive and hormonal factors and risk of renal cell carcinoma among women in the European Prospective Investigation into Cancer and Nutrition

Background - Renal cell carcinoma (RCC) is twice as common among men compared with women, and hormonal factors have been suggested to partially explain this difference. There is currently little evidence on the roles of reproductive and hormonal risk factors in RCC aetiology. Materials & Methods - We investigated associations of age at menarche and age at menopause, pregnancy-related factors, hysterectomy and ovariectomy and exogenous hormone use with RCC risk among 298,042 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Results - During 15 years of follow-up, 438 RCC cases were identified. Parous women had higher rates of RCC compared with nulliparous women (HR = 1.71, 95% CI 1.18, 2.46), and women who were older at age of first pregnancy had lower rates of RCC (30 years + vs. Conclusion - Our results suggest that parity and reproductive organ surgeries may play a role in RCC aetiology