Preoperative biliary drainage for periampullary tumors causing obstructive jaundice; DRainage vs. (direct) OPeration (DROP-trial)

BACKGROUND: Surgery in patients with obstructive jaundice caused by a periampullary (pancreas, papilla, distal bile duct) tumor is associated with a higher risk of postoperative complications than in non-jaundiced patients. Preoperative biliary drainage was introduced in an attempt to improve the general condition and thus reduce postoperative morbidity and mortality. Early studies showed a reduction in morbidity. However, more recently the focus has shifted towards the negative effects of drainage, such as an increase of infectious complications. Whether biliary drainage should always be performed in jaundiced patients remains controversial. The randomized controlled multicenter DROP-trial (DRainage vs. Operation) was conceived to compare the outcome of a 'preoperative biliary drainage strategy' (standard strategy) with that of an 'early-surgery' strategy, with respect to the incidence of severe complications (primary-outcome measure), hospital stay, number of invasive diagnostic tests, costs, and quality of life. METHODS/DESIGN: Patients with obstructive jaundice due to a periampullary tumor, eligible for exploration after staging with CT scan, and scheduled to undergo a "curative" resection, will be randomized to either "early surgical treatment" (within one week) or "preoperative biliary drainage" (for 4 weeks) and subsequent surgical treatment (standard treatment). Primary outcome measure is the percentage of severe complications up to 90 days after surgery. The sample size calculation is based on the equivalence design for the primary outcome measure. If equivalence is found, the comparison of the secondary outcomes will be essential in selecting the preferred strategy. Based on a 40% complication rate for early surgical treatment and 48% for preoperative drainage, equivalence is taken to be demonstrated if the percentage of severe complications with early surgical treatment is not more than 10% higher compared to standard treatment: preoperative biliary drainage. Accounting for a 10% dropout, 105 patients are needed in each arm resulting in a study population of 210 (alpha = 0.95, beta = 0.8). DISCUSSION: The DROP-trial is a randomized controlled multicenter trial that will provide evidence whether or not preoperative biliary drainage is to be performed in patients with obstructive jaundice due to a periampullary tumor

The cardiovascular risk profile of middle-aged women with polycystic ovary syndrome

Contains fulltext : 220851.pdf (Publisher’s version ) (Open Access)OBJECTIVES: Contradictory results have been reported regarding the association between polycystic ovary syndrome (PCOS) and cardiovascular disease (CVD). We assessed the cardiometabolic phenotype and prevalence of CVD in middle-aged women with PCOS, compared with age-matched controls from the general population, and estimated 10-year CVD risk and cardiovascular health score. DESIGN: A cross-sectional study. PARTICIPANTS: 200 women aged >45 with PCOS, and 200 age-matched controls. MEASUREMENTS: Anthropometrics, insulin, lipid levels, prevalence of metabolic syndrome and type II diabetes. Ten-year Framingham risk score and the cardiovascular health score were calculated, and carotid intima-media thickness (cIMT) was measured. RESULTS: Mean age was 50.5 years (SD = 5.5) in women with PCOS and 51.0 years (SD = 5.2) in controls. Increased waist circumference, body mass index and hypertension were more often observed in women with PCOS (P < .001). In women with PCOS, the prevalence of type II diabetes and metabolic syndrome was not significantly increased and lipid levels were not different from controls. cIMT was lower in women with PCOS (P < .001). Calculated cardiovascular health and 10-year CVD risk were similar in women with PCOS and controls. CONCLUSIONS: Middle-aged women with PCOS exhibit only a moderately unfavourable cardiometabolic profile compared to age-matched controls, even though they present with an increased BMI and waist circumference. Furthermore, we found no evidence for increased (10-year) CVD risk or more severe atherosclerosis compared with controls from the general population. Long-term follow-up of women with PCOS is necessary to provide a definitive answer concerning long-term risk for CVD

Spontaneous splenic rupture during Pringle maneuver in liver surgery

During liver resection clamping of the hepato-duodenal ligament (the Pringle maneuver) is performed to reduce intraoperative blood-loss. During this maneuver acute portal hypertension may lead to spontaneous splenic rupture requiring rapid splenectomy in order to control blood loss. We present 2 case of patients with hemorrhage from the spleen during clamping for liver surgery. A review of the literature with an emphasis on the pathophysiology of splenic hemorrhage is presented

FAST, EXPRESSIVE SE(n) EQUIVARIANT NETWORKS THROUGH WEIGHT-SHARING IN POSITION-ORIENTATION SPACE

Based on the theory of homogeneous spaces we derive geometrically optimal edge attributes to be used within the flexible message-passing framework. We formalize the notion of weight sharing in convolutional networks as the sharing of message functions over point-pairs that should be treated equally. We define equivalence classes of point-pairs that are identical up to a transformation in the group and derive attributes that uniquely identify these classes. Weight sharing is then obtained by conditioning message functions on these attributes. As an application of the theory, we develop an efficient equivariant group convolutional network for processing 3D point clouds. The theory of homogeneous spaces tells us how to do group convolutions with feature maps over the homogeneous space of positions R3, position and orientations R3×S2, and the group SE(3) itself. Among these, R3×S2 is an optimal choice due to the ability to represent directional information, which R3 methods cannot, and it significantly enhances computational efficiency compared to indexing features on the full SE(3) group. We support this claim with state-of-the-art results -in accuracy and speed- on five different benchmarks in 2D and 3D, including interatomic potential energy prediction, trajectory forecasting in N-body systems, and generating molecules via equivariant diffusion models.</p

Immunogenicity of dendritic cells pulsed with CEA peptide or transfected with CEA mRNA for vaccination of colorectal cancer patients

Dendritic cells (DCs) are the professional antigen-presenting cells of the immune system. We have demonstrated that vaccination of autologous ex vivo cultured DCs results in the induction of tumor-specific immune responses in cancer patients, which correlates with clinical response. Optimization of antigen loading is one of the possibilities for further improving the efficacy of DC vaccination. Theoretically, transfection of DCs with RNA encoding a tumor-specific antigen may induce a broader immune response as compared to the most widely used technique of peptide pulsing. In this clinical study, RNA transfection was compared with peptide pulsing as an antigen loading strategy for DC vaccination. Patients with resectable liver metastases of colorectal cancer were vaccinated intravenously and intradermally 3 times weekly with either carcinoembryogenic antigen (CEA)-derived HLA-A2 binding peptide-loaded or CEA mRNA electroporated DCs prior to surgical resection of the metastases. All DCs were loaded with keyhole limpet hemocyanin (KLH) as a control protein. Evaluation of vaccine-induced immune reactivity consisted of T-cell proliferative responses and B-cell antibody responses against KLH in peripheral blood. CEA reactivity was determined in T-cell cultures of biopsies of post-treatment delayed type hypersensitivity skin tests. Sixteen patients were included. All patients showed T-cell responses against KLH upon vaccination. CEA peptide-specific T-cells were detected in 8 out of 11 patients in the peptide group, but in none of the 5 patients in the RNA group. In our study, DC CEA mRNA transfection was not superior to DC CEA peptide pulsing in the induction of a tumor-specific immune response in colorectal cancer patient

Molecular Markers of Prognosis in Canine Cortisol-Secreting Adrenocortical Tumours

Hypercortisolism is caused by a cortisol-secreting adrenocortical tumour (ACT) in approximately 15-20% of cases in dogs. Little is known about which molecular markers are associated with malignant behaviour of canine ACTs. The objective of this study was to identify molecular markers of prognosis, which could be useful to refine prognostic prediction and to identify potential treatment targets. Cortisol-secreting ACTs were included from 40 dogs, of which follow-up information was available. The ACTs were classified as low risk of recurrence tumours (LRT; n = 14) or moderate-high risk of recurrence tumours (MHRT; n = 26), based on the novel histopathological Utrecht score. Normal adrenals (NAs) were included from 11 healthy dogs as reference material. The mRNA expression of 14 candidate genes was analysed in the 40 ACTs and in 11 NAs with quantitative RT-PCR. The genes' expression levels were statistically compared between NAs, LRTs and MHRTs. Univariate and multivariate analyses were performed to determine the association of the genes' expression levels with survival. Seven genes were differentially expressed between NAs and ACTs, of which pituitary tumour-transforming gene-1 (PTTG1) and topoisomerase II alpha (TOP2A) were also differentially expressed between LRTs and MHRTs. In survival analyses, high expression levels of Steroidogenic factor-1 (SF-1), PTTG1 and TOP2A were significantly associated with poor survival. In conclusion, we have identified several genes that are part of the molecular signature of malignancy in canine ACTs. These findings can be used to refine prognostic prediction, but also offer insights for future studies on druggable targets. This article is protected by copyright. All rights reserved

Molecular Markers of Prognosis in Canine Cortisol-Secreting Adrenocortical Tumours

Hypercortisolism is caused by a cortisol-secreting adrenocortical tumour (ACT) in approximately 15-20% of cases in dogs. Little is known about which molecular markers are associated with malignant behaviour of canine ACTs. The objective of this study was to identify molecular markers of prognosis, which could be useful to refine prognostic prediction and to identify potential treatment targets. Cortisol-secreting ACTs were included from 40 dogs, of which follow-up information was available. The ACTs were classified as low risk of recurrence tumours (LRT; n = 14) or moderate-high risk of recurrence tumours (MHRT; n = 26), based on the novel histopathological Utrecht score. Normal adrenals (NAs) were included from 11 healthy dogs as reference material. The mRNA expression of 14 candidate genes was analysed in the 40 ACTs and in 11 NAs with quantitative RT-PCR. The genes' expression levels were statistically compared between NAs, LRTs and MHRTs. Univariate and multivariate analyses were performed to determine the association of the genes' expression levels with survival. Seven genes were differentially expressed between NAs and ACTs, of which pituitary tumour-transforming gene-1 (PTTG1) and topoisomerase II alpha (TOP2A) were also differentially expressed between LRTs and MHRTs. In survival analyses, high expression levels of Steroidogenic factor-1 (SF-1), PTTG1 and TOP2A were significantly associated with poor survival. In conclusion, we have identified several genes that are part of the molecular signature of malignancy in canine ACTs. These findings can be used to refine prognostic prediction, but also offer insights for future studies on druggable targets. This article is protected by copyright. All rights reserved

Improving the Diagnostic Performance of F-18-Fluorodeoxyglucose Positron-Emission Tomography/Computed Tomography in Prosthetic Heart Valve Endocarditis

Background: F-18-Fluorodeoxyglucose (FDG) positron-emission tomography/computed tomography (PET/CT) was recently introduced as a new tool for the diagnosis of prosthetic heart valve endocarditis (PVE). Previous studies reporting a modest diagnostic accuracy may have been hampered by unstandardized image acquisition and assessment, and several confounders, as well. The aim of this study was to improve the diagnostic performance of FDG PET/CT in patients in whom PVE was suspected by identifying and excluding possible confounders, using both visual and standardized quantitative assessments. Methods: In this multicenter study, 160 patients with a prosthetic heart valve (median age, 62 years [43-73]; 68% male; 82 mechanical valves; 62 biological; 9 transcatheter aortic valve replacements; 7 other) who underwent FDG PET/CT for suspicion of PVE, and 77 patients with a PV (median age, 73 years [65-77]; 71% male; 26 mechanical valves; 45 biological; 6 transcatheter aortic valve replacements) who underwent FDG PET/CT for other indications (negative control group), were retrospectively included. Their scans were reassessed by 2 independent observers blinded to all clinical data, both visually and quantitatively on available European Association of Nuclear Medicine Research Ltd-standardized reconstructions. Confounders were identified by use of a logistic regression model and subsequently excluded. Results: Visual assessment of FDG PET/CT had a sensitivity/specificity/positive predictive value/negative predictive value for PVE of 74%/91%/89%/78%, respectively. Low inflammatory activity (C-reactive protein <40 mg/L) at the time of imaging and use of surgical adhesives during prosthetic heart valve implantation were significant confounders, whereas recent valve implantation was not. After the exclusion of patients with significant confounders, diagnostic performance values of the visual assessment increased to 91%/95%/95%/91%. As a semiquantitative measure of FDG uptake, a European Association of Nuclear Medicine Research Ltd-standardized uptake value ratio of 2.0 was a 100% sensitive and 91% specific predictor of PVE. Conclusions: Both visual and quantitative assessments of FDG PET/CT have a high diagnostic accuracy in patients in whom PVE is suspected. FDG PET/CT should be implemented early in the diagnostic workup to prevent the negative confounding effects of low inflammatory activity (eg, attributable to prolonged antibiotic therapy). Recent valve implantation was not a significant predictor of false-positive interpretations, but surgical adhesives used during implantation were