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Background The effect of bacterobilia on morbidity after pancreatoduodenectomy remains unclear. The aim of this study was to examine the influence of positive intraoperative bile cultures and perioperative antibiotic prophylaxis on morbidity measured using the Comprehensive Complication Index, a weighted composite of postoperative complications. Methods Intraoperative bile cultures of 182 patients who underwent pancreatoduodenectomy were obtained. We examined the effect of intraoperative bile cultures and perioperative antibiotic prophylaxis on the Comprehensive Complication Index and the occurrence of postoperative complications. To this aim, we performed general linear models controlling for relevant demographic and perioperative factors. Results Positive (versus negative) intraoperative bile cultures were associated with a higher mean Comprehensive Complication Index (25.34 vs 16.81, P = .025). The mean Comprehensive Complication Index differed significantly between individuals with positive intraoperative bile cultures and bacterial strains not covered by perioperative antibiotic prophylaxis (26.2) versus positive intraoperative bile cultures and bacterial strains sensitive to perioperative antibiotic prophylaxis (22.7) (P = .045). Positive (versus negative) intraoperative bile cultures were associated with 4.75 times (95% confidence interval: 1.74–13.00, P = .002) greater odds of wound infections. The odds of wound infection were 1.93 times (95% confidence interval: .47–8.04) greater in those with positive intraoperative bile cultures and adequate perioperative antibiotic prophylaxis and 6.14 times (95% confidence interval: 2.17–17.35) greater in those with positive intraoperative bile cultures and inadequate perioperative antibiotic prophylaxis (versus negative intraoperative bile cultures) (P = .001). Conclusion Bacterobilia is associated with a significant increase in Comprehensive Complication Index and wound infections after pancreatoduodenectomy, which may be reduced by administration of a specific perioperative antibiotic prophylaxis. Acquisition of bile cultures sampled through the external conduit of patients with preoperative biliary drainage could help in selecting a specific perioperative antibiotic prophylaxis and patients with bile duct stents might benefit from broad spectrum perioperative antibiotic prophylaxis.

OBJECTIVES In the Dutch National colorectal cancer (CRC) screening program, patients with a positive faecal immunochemical test (FIT) are referred for a colonoscopy. In a small proportion, because of contraindications, a computed tomographic colonography (CTC) is performed to rule out advanced neoplasia. The aim of our study is to evaluate the intra- and extra-colonic yield of CTC and its clinical implications. MATERIALS AND METHODS In this retrospective cohort study, all FIT positive patients who underwent primary (instead of colonoscopy) or secondary CTC (after incomplete colonoscopy) between January 2014 and January 2018 were included. Relevant intra-colonic lesions on CTC were defined as lesions suspected for CRC or >10 mm. Relevant extra-colonic findings were defined as E3 and E4 using the E-RADS classification. RESULTS Of the 268 included patients, 66 (24.6%) were suspected to have CRC or 10 mm + lesion on CTC and 56 of them (84.8%) underwent an additional endoscopy. Another 20 patients with

Objectives: The present study compares the utility of eight different tests of vigilance and sustained attention in the neuropsychological examination of adults with Attention-deficit/hyperactivity disorder (ADHD).Methods: Thirty-one adults diagnosed with ADHD performed eight tests for vigilance and sustained attention, spread over three assessment days.Results: Adults with ADHD showed cognitive impairments in most tests and test variables, even though their sensitivity differed greatly. No specific type of test variable stands out to be the most sensitive, and no evidence for a differential deterioration of performance over time was observed.Conclusion: This study underscores the role of vigilance and sustained attention tests in the assessment of adult ADHD. It is further concluded that summary scores over the entire test duration are sufficient, but that all variables of a test should be considered. Finally, we hypothesize that reassessment on a different day may benefit a more accurate clinical assessment of adults with ADHD, in order to adequately take intraindividual fluctuations and limitations regarding test reliability into account.

Tumor cell heterogeneity in colorectal cancers within the same genetic background is a well-described phenomenon. In this work, we investigate the role of hematopoietic pre-B-cell leukemia transcription factor (PBX)-interacting protein (HPIP/PBXIP1) in tumor cell subpopulations with differential Wingless-related integration site (WNT) activity as well as its potential associations with epithelial-mesenchymal transition (EMT) and clinical associations in colorectal cancer. We used in situ analyses to identify immunohistochemical expression of PBXIP1 in normal and colorectal cancer tissues and biostatistical approaches to determine its function and regulatory correlations. Clinical associations were analyzed in a case control collection of metastatic and non-metastatic colon cancers and gene expression data sets of colorectal cancers with recorded clinical follow-up data. PBXIP1 was expressed in single epithelial cells from tumor-free colon crypts as well as in tumor cells with high WNT activity. Colorectal cancer cells close to the invasive edge seemed to possess higher PBXIP1 levels indicative of associations with EMT, whereas stromal cells in the tumor microenvironment appeared mostly negative. PBXIP1 expression was associated with local metastasis to lymph nodes as well as distant metastasis to secondary organs in a case-control collection consisting of 91 cases with or without distant metastasis. Furthermore, high expression of PBXIP1 in The Cancer Genome Atlas (TCGA) data set was associated with worse overall survival in colon cancer. PBXIP1 might serve as a novel histological prognostic and regulatory indicator for EMT processes in colorectal cancer that seems to correlate with cancer cell subtypes of high baseline WNT activity.

In cancer patients, surgical removal of the primary tumor is one of the major steps within a multimodal therapy concept toward eliminating the disease and limiting further progression. In this respect, surgical trauma can have potent effects on the patient's immune system. Intraoperative blood loss associated with major surgical trauma leads to reduced blood flow, regional hypoxia, metabolic, and microenvironmental alterations stimulating an inflammatory response characterized by the release of pro-inflammatory cytokines (i.e., TNF-α, IL-6) and acute-phase proteins. The inflammatory state is accompanied by and intertwined with a counter-regulatory anti-inflammatory response reflected in the rise of anti-inflammatory cytokines (i.e., transforming growth factor-β) and prostaglandins (i.e., prostaglandin E2) which can lead to a depression of cell-mediated immunity and systemic immunosuppression. This results in a highly vulnerable state with concurrent expression of pro- and anti-inflammatory cytokines alternately predominating. The immunosuppressive state is characterized by a reduced antigen-presentation capacity of macrophages, alterations in lymphocyte proliferation, and activation as well as a shift of the Th1/Th2 (T helper cells 1 and 2) balance toward Th2 and a decrease in natural killer cell activity. The severity of the immunosuppression thereby correlates with the extent and the duration of the surgical procedure. Growing evidence suggests that the immunosuppressive state following hemorrhage and surgical trauma might not only be a risk factor for postoperative complications but also facilitate tumor proliferation, metastatic growth, and recurrence. This article provides an overview of the cascade of events and underlying mechanisms resulting in immunosuppression and describes the impact of hemorrhage and major surgical trauma on tumor growth and recurrence. Attempts to control for perioperative inflammation thereby reducing the adverse effects of postoperative immunosuppression could have positive effects on tumor growth, metastasis formation, and recurrence.

Major depressive disorder (MDD) is a severe disease of unknown pathogenesis that will affect ∼10% of people during their lifetime. Therapy for MDD requires prolonged treatment and often fails, predicating a need for novel treatment strategies. Here, we report increased ceramide levels in the blood plasma of MDD patients and in murine stress-induced models of MDD. These blood plasma ceramide levels correlated with the severity of MDD in human patients and were independent of age, sex, or body mass index. In addition, intravenous injection of anti-ceramide antibodies or neutral ceramidase rapidly abrogated stress-induced MDD, and intravenous injection of blood plasma from mice with MDD induced depression-like behavior in untreated mice, which was abrogated by ex vivo preincubation of the plasma with anti-ceramide antibodies or ceramidase. Mechanistically, we demonstrate that ceramide accumulated in endothelial cells of the hippocampus of stressed mice, evidenced by the quantitative measurement of ceramide in purified hippocampus endothelial cells. We found ceramide inhibited the activity of phospholipase D (PLD) in endothelial cells in vitro and in the hippocampus in vivo and thereby decreased phosphatidic acid in the hippocampus. Finally, we show intravenous injection of PLD or phosphatidic acid abrogated MDD, indicating the significance of this pathway in MDD pathogenesis. Our data indicate that ceramide controls PLD activity and phosphatidic acid formation in hippocampal endothelial cells and thereby mediates MDD. We propose that neutralization of plasma ceramide could represent a rapid-acting targeted treatment for MDD. CA Gulbins

Objective To assess the perioperative and long-term outcome following pulmonary resection in patients with metachronous metastasis of pancreatic ductal adenocarcinoma (PDAC). Background Most patients with PDAC relapse or develop tumor spread to secondary organs. Currently, it remains unclear how to proceed with pulmonary metastasis in the metachronous setting. In particular, the role of surgery remains controversial. Methods Data of patients with pulmonary metachronous metastasis after PDAC collected from 2003 to 2015 in databases of two high-volume pancreatic cancer centers were retrospectively analyzed. Clinical and pathological aspects of primary PDAC as well as the perioperative and long-term outcome following pulmonary metastasectomy (PM) was evaluated, respectively. Patients with synchronous liver metastasis or metastasis to other secondary organs were excluded. Univariate survival analysis was performed. Results We identified 15 patients undergoing pulmonary resection for suspected metastasis after primary pancreatic resection. Operative and histopathologic evaluation revealed resectable pancreatic pulmonary metastasis in 11 patients (73.3%). The median disease-free survival (DFS) and overall survival (OS) after PM diagnosis was 18 months and 26 months, respectively. The median time to metachronous metastasis (TMM) was 17 months [3–64 months]. Perioperative morbidity was low with only one readmission (8.3%). There was no perioperative mortality. Patients who developed pulmonary metastasis later than 17 months after primary surgery showed better OS compared to those who did earlier (32.2 vs. 14.75 months, p = 0.025). In addition, patients with high-grade tumors had worse survival (12.4 vs. 31 months, p = 0.02). Elevated serum CEA levels or CA 19-9 levels were also not associated with shortened OS. Conclusions This study suggests that pulmonary metastasectomy after PDAC is safe and effective. Patients with extended DFS after primary pancreatic surgery as well as favorable tumor grading seem to particularly benefit from pulmonary surgery.

Although primary tumor sidedness (PTS) has a known prognostic role in sporadic colorectal cancer (CRC), its role in Inflammatory Bowel Disease related CRC (IBD-CRC) is largely unknown. Thus, we aimed to evaluate the prognostic role of PTS in patients with IBD-CRC.All eligible patients with surgically treated, non-metastatic IBD-CRC were retrospectively identified from institutional databases at ten European and Asian academic centers. Long term endpoints included recurrence-free (RFS) and overall survival (OS). Multivariable Cox proportional hazard regression as well as propensity score analyses were performed to evaluate whether PTS was significantly associated with RFS and OS.A total of 213 patients were included in the analysis, of which 32.4% had right-sided (RS) tumors and 67.6% had left-sided (LS) tumors. PTS was not associated with OS and RFS even on univariable analysis (5-year OS for RS vs LS tumors was 68.0% vs 77.3%, respectively, p = 0.31; 5-year RFS for RS vs LS tumors was 62.8% vs 65.4%, respectively, p = 0.51). Similarly, PTS was not associated with OS and RFS on propensity score matched analysis (5-year OS for RS vs LS tumors was 82.9% vs 91.3%, p = 0.79; 5-year RFS for RS vs LS tumors was 85.1% vs 81.5%, p = 0.69). These results were maintained when OS and RFS were calculated in patients with RS vs LS tumors after excluding patients with rectal tumors (5-year OS for RS vs LS tumors was 68.0% vs 77.2%, respectively, p = 0.38; 5-year RFS for RS vs LS tumors was 62.8% vs 59.2%, respectively, p = 0.98).In contrast to sporadic CRC, PTS does not appear to have a prognostic role in IBD-CRC.

Background Molecular differences in colorectal cancer (CRC) are associated with the metastatic route. Patient survival is mainly driven by metastatic spread thus it is imperative to understand its key drivers to develop biomarkers for risk stratification, follow-up protocols and personalized therapy. Thus, this study aimed to identify genes associated with the metastatic route in CRC. Material and methods CRC patients resected at our clinic from 2005 to 2014 and with a minimum 5-year follow-up were included in this analysis and grouped into CRC with hepatic (HEP), peritoneal (PER) or without distant metastases (M0), and HEP/PER. Firstly, tumor RNA of 6 patients each was isolated by microdissection from formalin-fixed paraffin-embedded specimens and analyzed by a NanoString analysis. Subsequently, these results were validated with immunohistochemistry and correlated to clinicopathological parameters in a larger collective of CRC patients (HEP n = 51, PER n = 44, M0 n = 47, HEP/PER n = 28). Results Compared to M0, HEP tumors showed 20 differentially expressed genes associated with epithelial-mesenchymal transition (EMT) and angiogenesis. Compared to M0, PER tumors had 18 differentially expressed genes. The finding of different gene signatures was supported by the multidimensional principal component clustering analysis. Tumor perforation did not influence the metastatic route. CIB1 was homogenously and significantly overexpressed in HEP compared to M0 (p p Conclusion Gene expression analysis revealed that CIB1 is significantly overexpressed in CRC leading to liver metastases compared to M0 and PER. Thus, the present results suggest that CIB1 may play a crucial role for hematogenous spread to the liver but not for peritoneal carcinomatosis. Consequently, CIB1 seems to be a promising prognostic marker and a potential tool for future targeted therapies as well as early diagnostics and follow-up.

Introduction Partial pancreatoduodenectomy (PD) is the treatment of choice for various benign and malignant tumours of the pancreatic head or the periampullary region. For reconstruction of the gastrointestinal passage, two stomach preserving PD variants exist: pylorus preservation (ppPD), or pylorus resection (prPD) with preservation of the stomach. In pancreatic surgery, delayed gastric emptying (DGE) remains a serious complication after PD with an incidence varying between 4.5% and 45%, potentially delaying hospital discharge or further treatment, e.g. adjuvant chemotherapy. Evidence is lacking to assess which variant of PD entails fewer postoperative DGE. Methods and analysis The protocol of a large-scale, multicentre, pragmatic, two-arm parallel-group, registry-based randomised controlled trial (rRCT) using a two-stage group-sequential design is presented. This patient-blind rRCT aims to demonstrate the superiority of prPD over ppPD with respect to the overall incidence of DGE within 30 days after index surgery in a German real-world setting. A total of 984 adults undergoing elective PD for any indication will be randomised in a 1:1 ratio. Patients will be recruited at about 30 hospitals being members of the StuDoQ|Pancreas registry established by the German Society of General and Visceral Surgery (DGAV). The postoperative follow-up for each patient will be 30 days. The primary analysis will follow an intention-to-treat approach and applies a binary logistic random intercepts model. Secondary perioperative outcomes include overall severe morbidity (Clavien-Dindo-classification), blood loss, 30-day all-cause mortality, postoperative hospital stay, and operation time. Complication rates and adverse events will be closely monitored. Ethics and dissemination This protocol was approved by the leading ethics committee of the Medical Faculty of the Ludwig-Maximilians-Universitat, Munich (reference no. 19-221). The results will be published in a peer-reviewed journal and presented at international conferences. Study findings will also be disseminated via the website (http://www.dgav.de/studoq/pylorespres/). Trial registration number DRKS-ID: DRKS00018842 (https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00018842, prospectively registered on 24-Oct-2019) ARTICLE SUMMARY Strengths and limitations of this study ▪This will be the first large-scale, surgical registry-based randomised controlled trial (rRCT) in Germany. ▪Patients will be blinded to the allocated and actually performed treatment. ▪The active control intervention will be pylorus preserving pancreatoduodenectomy (PD), currently the surgical standard treatment of tumours of the pancreatic head and periampullary region. ▪Synthesizing evidences from RCTs for this comparative effectiveness research question (preserving vs. resecting PD) is inconclusive with respect to delayed gastric emptying (DGE), a common post-operative complication. ▪The rRCT approach combines the advantages of a prospective (adaptive two-stage) 2-arm parallel-group RCT and the German multicentre StuDoQ|Pancreas registry as platform for patient enrolment, allocation and data collection, with the aim of improving the evidence-based surgical techniques for PD.

Objectives Osteoporotic fractures of the pelvis (OFP) are an increasing issue in orthopedics. Current classification systems (CS) are mostly CT-based and complex and offer only moderate to substantial inter-rater reliability (interRR) and intra-rater reliability (intraRR). MRI is thus gaining importance as a complement. This study aimed to develop a simple and reliable CT- and MRI-based CS for OFP. Methods A structured iterative procedure was conducted to reach a consensus among German-speaking spinal and pelvic trauma experts over 5 years. As a result, the proposed OF-Pelvis CS was developed. To assess its reliability, 28 experienced trauma and orthopedic surgeons categorized 25 anonymized cases using X-ray, CT, and MRI scans twice via online surveys. A period of 4 weeks separated the completion of the first from the second survey, and the cases were presented in an altered order. While 13 of the raters were also involved in developing the CS (developing raters (DR)), 15 user raters (UR) were not deeply involved in the development process. To assess the interRR of the OF-Pelvis categories, Fleiss’ kappa (κF) was calculated for each survey. The intraRR for both surveys was calculated for each rater using Kendall’s tau (τK). The presence of a modifier was calculated with κF for interRR and Cohen’s kappa (κC) for intraRR. Results The OF-Pelvis consists of five subgroups and three modifiers. Instability increases from subgroups 1 (OF1) to 5 (OF5) and by a given modifier. The three modifiers can be assigned alone or in combination. In both surveys, the interRR for subgroups was substantial: κF = 0.764 (Survey 1) and κF = 0.790 (Survey 2). The interRR of the DR and UR was nearly on par (κF Survey 1/Survey 2: DR 0.776/0.813; UR 0.748/0.766). The agreement for each of the five subgroups was also strong (κF min.–max. Survey 1/Survey 2: 0.708–0.827/0.747–0.852). The existence of at least one modifier was rated with substantial agreement (κF Survey 1/Survey 2: 0.646/0.629). The intraRR for subgroups showed almost perfect agreement (τK = 0.894, DR: τK = 0.901, UR: τK = 0.889). The modifier had an intraRR of κC = 0.684 (DR: κC = 0.723, UR: κC = 0.651), which is also considered substantial. Conclusion The OF-Pelvis is a reliable tool to categorize OFP with substantial interRR and almost perfect intraRR. The similar reliabilities between experienced DRs and URs demonstrate that the training status of the user is not important. However, it may be a reliable basis for an indication of the treatment score.

The heterozygous human Klotho KL-VS haplotype has been associated with improved cognitive performance but results are inconsistent. Here we assessed Klotho KL-VS haplotype and cognition using data from the third examination of the population-based Heinz Nixdorf Recall Study. We analyzed cognition tests (immediate and delayed word list, Trail-Making Test [TMT] part A and B, Maze test, interference condition of the Stroop color-word test, verbal fluency) and their associations with Klotho KL-VS haplotype. The Klotho KL-VS haplotype is classified by the V-allele at SNP rs9536314 (F352V) and the S-allele at SNP rs9527025 (C370S). Heterozygotes for the KL-VS haplotype were compared with non-carriers. Analyses were performed in 1812 subjects (55–87 years). We found consistent but only slightly lower performance in heterozygous carriers of the KL-VS haplotype in all tasks with Z-scores ranging between Z = − 0.042 (verbal fluency) and − 0.17 (TMT part A). Differences between carriers and non-carriers were similar for men and women for all tests but TMT part B (interaction contrast = 8.4 s (95% CI − 2.3; 19.1)). While cognition declined with age, we found an effect modification by age (55–65 years, 66–75 years, > 75 years). In the 66–75 years KL-VS heterozygous age group, lower performance was seen in memory, visual attention and motor speed. Contrary to our hypothesis, heterozygous carriers of the KL-VS haplotype did not show enhanced performance in cognitive tests in our study.

Summary Aims Classifications of occluding vasculopathies (except vasculitis [1]) may exhibit some difficulties. Firstly, classifications may follow different principles, e.g. clinicopathologic findings, etiology or pathogenesis. Secondly, authors may not distinguish between vasculitis and occluding vasculopathies. Thirdly, occluding vasculopathies are systemic diseases. Organ‐specific variations make morphologic findings difficult to compare. Moreover, subtle changes are recognized in the skin, but may be invisible in other organs. Our aim was to use the skin and subcutis as a tool and clinicopathological correlation as the basic process for classification. Methods and results We first differentiate in the skin between small and medium vessel occluding vasculopathies. Here we focus on medium vessel‐occluding vasculopathies. In the second step we differentiate the vessel subtypes. In the final step, we differentiate according to the time point of the coagulation/reorganization process and the involved inflammatory cells/stromal features. By applying the same procedure to the various entities and visualizing the findings in the style of bar codes, the overlaps and differences in the clinical picture as well as the histopathology become more apparent. Conclusions Occluding vasculopathies are often not separate entities, but reaction patterns and epiphenomena. Distinguishing them from vasculitides is crucial because of the differences in pathogenesis, therapeutic approach and prognosis.

Background Inguinal hernia repair, gallbladder removal, and knee- and hip replacements are the most commonly performed surgical procedures, but all are subject to practice variation and variable patient-reported outcomes. Shared decision-making (SDM) has the potential to reduce surgery rates and increase patient satisfaction. This study aims to evaluate the effectiveness of an SDM strategy with online decision aids for surgical and orthopaedic practice in terms of impact on surgery rates, patient-reported outcomes, and cost-effectiveness. Methods The E-valuAID-study is designed as a multicentre, non-randomized stepped-wedge study in patients with an inguinal hernia, gallstones, knee or hip osteoarthritis in six surgical and six orthopaedic departments. The primary outcome is the surgery rate before and after implementation of the SDM strategy. Secondary outcomes are patient-reported outcomes and cost-effectiveness. Patients in the usual care cluster prior to implementation of the SDM strategy will be treated in accordance with the best available clinical evidence, physician’s knowledge and preference and the patient’s preference. The intervention consists of the implementation of the SDM strategy and provision of disease-specific online decision aids. Decision aids will be provided to the patients before the consultation in which treatment decision is made. During this consultation, treatment preferences are discussed, and the final treatment decision is confirmed. Surgery rates will be extracted from hospital files. Secondary outcomes will be evaluated using questionnaires, at baseline, 3 and 6 months. Discussion The E-valuAID-study will examine the cost-effectiveness of an SDM strategy with online decision aids in patients with an inguinal hernia, gallstones, knee or hip osteoarthritis. This study will show whether decision aids reduce operation rates while improving patient-reported outcomes. We hypothesize that the SDM strategy will lead to lower surgery rates, better patient-reported outcomes, and be cost-effective. Trial registration: The Netherlands Trial Register, Trial NL8318, registered 22 January 2020. URL: https://www.trialregister.nl/trial/8318.

Brain vascular damage accumulate in aging and often manifest as white matter hyperintensities (WMHs) on MRI. Despite increased interest in automated methods to segment WMHs, a gold standard has not been achieved and their longitudinal reproducibility has been poorly investigated. The aim of present work is to evaluate accuracy and reproducibility of two freely available segmentation algorithms. A harmonized MRI protocol was implemented in 3T-scanners across 13 European sites, each scanning five volunteers twice (test-retest) using 2D-FLAIR. Automated segmentation was performed using Lesion segmentation tool algorithms (LST): the Lesion growth algorithm (LGA) in SPM8 and 12 and the Lesion prediction algorithm (LPA). To assess reproducibility, we applied the LST longitudinal pipeline to the LGA and LPA outputs for both the test and retest scans. We evaluated volumetric and spatial accuracy comparing LGA and LPA with manual tracing, and for reproducibility the test versus retest. Median volume difference between automated WMH and manual segmentations (mL) was −0.22[IQR = 0.50] for LGA-SPM8, −0.12[0.57] for LGA-SPM12, −0.09[0.53] for LPA, while the spatial accuracy (Dice Coefficient) was 0.29[0.31], 0.33[0.26] and 0.41[0.23], respectively. The reproducibility analysis showed a median reproducibility error of 20%[IQR = 41] for LGA-SPM8, 14% [31] for LGA-SPM12 and 10% [27] with the LPA cross-sectional pipeline. Applying the LST longitudinal pipeline, the reproducibility errors were considerably reduced (LGA: 0%[IQR = 0], p < 0.001; LPA: 0% [3], p < 0.001) compared to those derived using the cross-sectional algorithms. The DC using the longitudinal pipeline was excellent (median = 1) for LGA [IQR = 0] and LPA [0.02]. LST algorithms showed moderate accuracy and good reproducibility. Therefore, it can be used as a reliable cross-sectional and longitudinal tool in multi-site studies.

Introduction: A disturbed sense of self is frequently discussed as an etiological factor for delusion symptoms in psychosis. Phenomenological approaches to psychopathology posit that lacking the sense that the self is localized within one’s bodily boundaries (disembodiment) is one of the core features of the disturbed self in psychosis. The present study examines this idea by experimentally manipulating the sense of bodily boundaries. Methods: Seventy-three patients with psychosis were randomly assigned to either a 10-min, guided self-massage in the experimental group (EG) to enhance the sense of bodily boundaries or a control group (CG), which massaged a fabric ring. Effects on an implicit measure (jumping to conclusion bias; JTC) and an explicit measure (Brief State Paranoia Checklist; BSPC) of delusion processes were assessed. The JTC measures the tendency to make a decision with little evidence available, and the BSPC explicitly measures the approval of paranoid beliefs. Results: Patients in the EG showed a lower JTC (M = 4.11 draws before decision) than the CG (M = 2.43; Cohen’s d = 0.64). No significant difference in the BSPC was observed. Discussion/Conclusion: Our results indicate that enhancing the sense of body boundaries through a self-massage can reduce an implicit bias associated with delusional ideation and correspondingly support the idea that disembodiment might be a relevant factor in the formation of psychotic symptoms.

A 38-year-old woman presented for 18F-FDG PET/CT after multiple intra-abdominal surgical resections of a rare recurrent perivascular epithelioid cell tumor of the gastrointestinal tract. A solitary pelvic metastasis was detected, but surprisingly exhibited neither increased glucose consumption nor contrast enhancement on CT. Follow-up 18F-FDG PET/CT staging in the further disease course revealed multiple abdominal metastases, now, however, with markedly increased 18F-FDG uptake and intraoperatively correlating widespread peritoneal sarcomatosis. This case gives preliminary insight into monitoring of disease progression in metastatic perivascular epithelioid cell tumor, although the underlying pathophysiological bases for varying 18F-FDG uptake in PET/CT are not yet fully understood.

Background: The jumping to conclusions bias (JTC) is considered to be an important causal factor in theoretical models for the formation and maintenance of delusions. However, recent meta-analytic findings show a rather equivocal pattern of results regarding associations between JTC and delusions. Thus, the present study aims to investigate in a large sample whether the JTC-bias is more pronounced in patients with psychotic disorders in comparison to controls and whether the JTC bias is associated with a more severe delusional conviction, persecutory delusions, and positive symptoms in general.Methods: Patients with psychotic disorders (n = 300) enrolled in a therapy trial and healthy controls (n = 51) conducted a variant of the beads task (fish task) as a measure for the JTC-bias at the start of the trial. Further, clinical interviews were used to assess patients’ delusional severity and delusional conviction. Results: There were no statistically significant differences between patients with psychotic disorders (with 53% displaying the JTC-bias) and controls (41%). Furthermore, there were no statistically significant correlations between JTC measures and persecutory delusions, delusional conviction, and positive symptoms.Conclusions: We found no differences in JTC between patients with psychotic disorders and healthy controls, which is in part in line with meta-analytic findings using a wide range of JTC task variants. Interestingly, patients with psychotic disorders displayed JTC rates commonly found in the literature, while healthy control subjects showed an unexpectedly high level of JTC. The task variant we used in the present study (fish task) is discussed as a potential reason for our results, as it may induce a more deliberative reasoning style in controls as compared to the traditional beads task. Furthermore, possible implications for the measurement of the JTC-bias, in general, are discussed.Trial Registration: ISRCTN29242879 (isrctn.com), date of registration: April 12th 2006, retrospectively registered

Background: The amygdala and the hippocampus are two limbic structures that play a critical role in cognition and behavior, however their manual segmentation and that of their smaller nuclei/subfields in multicenter datasets is time consuming and difficult due to the low contrast of standard MRI. Here, we assessed the reliability of the automated segmentation of amygdalar nuclei and hippocampal subfields across sites and vendors using FreeSurfer in two independent cohorts of older and younger healthy adults.Methods: Sixty-five healthy older (cohort 1) and 68 younger subjects (cohort 2), from the PharmaCog and CoRR consortia, underwent repeated 3D-T1 MRI (interval 1-90 days). Segmentation was performed using FreeSurfer v6.0. Reliability was assessed using volume reproducibility error (epsilon) and spatial overlapping coefficient (DICE) between test and retest session.Results: Significant MRI site and vendor effects (p 0.43, p 0.80).Conclusion: Our results support the use of volumetric measures of larger amygdalar nuclei and hippocampal subfields in multisite MRI studies. These measures could be useful for disease tracking and assessment of efficacy in drug trials.

BACKGROUND Side effects of the immunosuppressive therapy after solid organ transplantation are well known. Recently, significant benefits were shown for mTOR-Is with respect to certain viral infections in comparison with CNIs. However, reported total incidences of infections under mTOR-Is vs CNIs are usually not different. This raises the question to additional differences between these immunosuppressants regarding development and incidence of infections. METHODS The current literature was searched for prospective randomized controlled trials in renal transplantation. There were 954 trials screened of which 19 could be included (9861 pts.). The 1-year incidence of infections, patient and graft survival were assessed in meta-analyses. RESULTS Meta-analysis on 1-year incidence of infections showed a significant benefit of an mTOR-I based therapy when combined with a CNI vs CNI-based therapy alone (OR 0.76). There was no difference between mTOR-I w/o CNI and CNI therapy (OR 0.97). For pneumonia, a significant disadvantage was seen only for mTOR-I monotherapy compared to CNI's (OR 2.09). The incidence of CMV infections was significantly reduced under mTOR-I therapy (combination with CNI: OR 0.30; mTOR w/o CNI: OR: 0.46). There was no significant difference between mTOR-I and CNI therapy with respect to patient survival (mTOR-I w/o CNI vs CNI: OR 1.22; mTOR-I with CNI vs CNI: OR 0.86). Graft survival was negatively affected by mTOR-I monotherapy (OR 1.52) but not when combined with a CNI (OR 0.97). CONCLUSION Following renal transplantation the incidence of infections is lower when mTOR-Is are combined with a CNI compared to a standard CNI therapy. Pneumonia occurs more often under mTOR-I w/o CNI.

Myeloid-derived suppressor cells (MDSCs) are one of the main suppressive cell population of the immune system. They play a pivotal role in the establishment of the tumor microenvironment (TME). In the context of cancers or other pathological conditions, MDSCs can differentiate, expand, and migrate in large quantities during circulation, inhibiting the cytotoxic functions of T cells and NK cells. This process is regulated by ROS, iNOS/NO, arginase-1, and multiple soluble cytokines. The definition of MDSCs and their phenotypes in humans are not as well represented as in other organisms such as mice, owing to the absence of the cognate molecule. However, a comprehensive understanding of the differences between different species and subsets will be beneficial for clarifying the immunosuppressive properties and potential clinical values of these cells during tumor progression. Recently, experimental evidence and clinical investigations have demonstrated that MDSCs have a close relationship with poor prognosis and drug resistance, which is considered to be a leading marker for practical applications and therapeutic methods. In this review, we summarize the remarkable position of MDSCs in solid tumors, explain their classifications in different models, and introduce new treatment approaches to target MDSCs to better understand the advancement of new approaches to cancer treatment.

ObjectiveIt is difficult to predict the presence of histological risk factors for lymph node metastasis (LNM) before endoscopic treatment of T1 colorectal cancer (CRC). Therefore, endoscopic therapy is propagated to obtain adequate histological staging. We examined whether secondary surgery following endoscopic resection of high-risk T1 CRC does not have a negative effect on patients' outcomes compared with primary surgery.DesignPatients with T1 CRC with one or more histological risk factors for LNM (high risk) and treated with primary or secondary surgery between 2000 and 2014 in 13 hospitals were identified in the Netherlands Cancer Registry. Additional data were collected from hospital records, endoscopy, radiology and pathology reports. A propensity score analysis was performed using inverse probability weighting (IPW) to correct for confounding by indication.Results602 patients were eligible for analysis (263 primary; 339 secondary surgery). Overall, 34 recurrences were observed (5.6%). After adjusting with IPW, no differences were observed between primary and secondary surgery for the presence of LNM (OR 0.97; 95% CI 0.49 to 1.93; p=0.940) and recurrence during follow-up (HR 0.97; 95% CI 0.41 to 2.34; p=0.954). Further adjusting for lymphovascular invasion, depth of invasion and number of retrieved lymph nodes did not alter this outcome.ConclusionsOur data do not support an increased risk of LNM or recurrence after secondary surgery compared with primary surgery. Therefore, an attempt for an en-bloc resection of a possible T1 CRC without evident signs of deep invasion seems justified in order to prevent surgery of low-risk T1 CRC in a significant proportion of patients.

Contains fulltext : 191992.pdf (Publisher’s version ) (Closed access) Background: Only 60% of depressed patients respond sufficiently to treatment, so there is a dire need for novel approaches to improve treatment effects. Cognitive Bias Modification (CBM) may be an effective and easily implemented computerized add-on to treatment-as-usual. Therefore, we investigated the effects of a positivity-attention training and a positivity-approach training compared to control trainings. Methods: In a blinded randomized-controlled design, 139 depressed inpatients received either the CBM Attention Dot-Probe Training (DPT) or the CBM Approach-Avoidance Training (AAT), next to treatment as usual. N = 121 finished all four training sessions. Both trainings had an active and a control condition. In both active conditions, patients were trained to preferentially process generally positive pictures over neutral pictures. Depressive symptom severity was assessed before and after CBM, and positivity bias was measured at the start and end of each session. Results: Clinician-rated depressive symptom severity decreased more in patients who received the active condition of the DPT or the AAT compared to patients in the control conditions. Significant change in positivity bias was found for the DPT (not the AAT), but did not mediate the effect of the training on depressive symptoms. Conclusions: The results suggest that both types of CBM (i.e., DPT and AAT) may provide a fitting add-on treatment option for clinical depression. The working mechanisms and optimal dose of CBM trainings, plus their possible combination, should be examined in more detail. 9 p.

Background The objective of this study is to test the conflicting theories concerning the association of negative self and other schemata and paranoid ideation. Methods A risk-based approach, including risk stratification, is used to gain insight into the association of the negative self and other schemata that may be shared by individuals or differentiate between individuals at clinical high risk (CHR) for a first-episode psychosis and those with full-blown psychosis. The dataset includes a sample of individuals at CHR (n = 137) and a sample of individuals with persisting positive symptoms (PPS, n = 211). The CHR sample was subdivided according to a prognostic index yielding 4 CHR sub-classes with increasing risk for transition to psychosis. Results Negative beliefs about the self were associated with paranoid ideation in CHR and a lower risk state. In the highest risk state and full-blown psychosis, there is an association with negative beliefs about others. Conclusion These findings are in line with theories suggesting a switch from a predominantly activated negative self-schema to a malevolent others-schema in association with paranoid ideation along the risk-continuum. However, due to methodological limitations these results should be replicated by future studies.

Immunotherapy has become an established pillar of cancer treatment improving the prognosis of many patients with a broad variety of hematological and solid malignancies. The two main drivers behind this success are checkpoint inhibitors (CPIs) and chimeric antigen receptor (CAR) T cells. This review summarizes seminal findings from clinical and translational studies recently presented or published at important meetings or in top-tier journals, respectively. For checkpoint blockade, current studies focus on combinational approaches, perioperative use, new tumor entities, response prediction, toxicity management and use in special patient populations. Regarding cellular immunotherapy, recent studies confirmed safety and efficacy of CAR T cells in larger cohorts of patients with acute lymphoblastic leukemia or diffuse large B cell lymphoma. Different strategies to translate the striking success of CAR T cells in B cell malignancies to other hematological and solid cancer types are currently under clinical investigation. Regarding the regional distribution of registered clinical immunotherapy trials a shift from PD-1 / PD-L1 trials (mainly performed in the US and Europe) to CAR T cell trials (majority of trials performed in the US and China) can be noted.

Mismatch negativity (MMN) is an electrophysiological index of prediction error processing and recently has been considered an endophenotype marker in schizophrenia. While the prediction error is a core concept in the MMN generation, predictability of deviance occurrence has rarely been assessed in MMN research and in schizophrenia patients. We investigated the MMN to 12% temporally predictable or unpredictable duration decrement deviant stimuli in two runs in 29 healthy controls and 31 schizophrenia patients. We analyzed MMN amplitudes and latencies and its associations with clinical symptoms at electrode Fz. With a stimulus onset asynchronicity of 500 ms in the regular predictable condition, a deviant occurred every 4s while it varied randomly in the unpredictable condition. In the random condition we found diminished MMN amplitudes in patients which normalized in the regular deviance condition, resulting in an analysis of variance main effect of predictability and a predictability x group interaction. Deviance predictability did not affect the MMN of control subjects and we found no relevant results with regard to MMN latencies. Our results indicate that MMN amplitudes in patients normalize to the level of the control subjects in the case of a temporally fixed regular deviant. In schizophrenia patients the detection of deviance is basically intact. However, the temporal uncertainty of deviance occurrence may be of substantial relevance to the highly replicated MMN deficit in schizophrenia patients.

Item does not contain fulltext Colorectal cancer (CRC) screening is capable of reducing CRC-related morbidity and mortality. Colonoscopy is the reference standard to detect CRC, also providing the opportunity to detect and resect its precursor lesions: colorectal polyps. Therefore, colonoscopy is either used as a primary screening tool or as a subsequent procedure after a positive triage test in screening programs based on non-invasive stool testing or sigmoidoscopy. However, in both settings, colonoscopy is not fully protective for the occurrence of post-colonoscopy CRCs (PCCRCs). Because most PCCRCs are the result of colonoscopy-related factors, a high-quality procedure is of paramount importance to assure optimal effectiveness of CRC screening programs. For this reason, at the start of the Dutch fecal immunochemical test (FIT)-based screening program, quality criteria for endoscopists performing colonoscopies in FIT-positive screenees, as well as for endoscopy centers, were defined. In conjunction, an accreditation and auditing system was designed and implemented. In this report, we describe the quality assurance process for endoscopists participating in the Dutch national CRC screening program, including a detailed description of the evidence-based quality criteria. We believe that our experience might serve as an example for colonoscopy quality assurance programs in other CRC screening programs.

In many solid tumors, parasympathetic input is provided by the vagus nerve, which has been shown to modulate tumor growth. However, whether cholinergic signaling directly regulates progression of pancreatic ductal adenocarcinoma (PDAC) has not been defined. Here, we found that subdiaphragmatic vagotomy in LSL-Kras+/G12D;Pdx1-Cre (KC) mice accelerated PDAC development, whereas treatment with the systemic muscarinic agonist bethanechol restored the normal KC phenotype, thereby suppressing the accelerated tumorigenesis caused by vagotomy. In LSL-Kras+/G12D;LSL-Trp53+/R172H;Pdx1-Cre mice with established PDAC, bethanechol significantly extended survival. These effects were mediated in part through CHRM1, which inhibited downstream MAPK/EGFR and PI3K/AKT pathways in PDAC cells. Enhanced cholinergic signaling led to a suppression of the cancer stem cell (CSC) compartment, CD11b+ myeloid cells, TNFα levels, and metastatic growth in the liver. Therefore, these data suggest that cholinergic signaling directly and indirectly suppresses growth of PDAC cells, and therapies that stimulate muscarinic receptors may be useful in the treatment of PDAC. Significance: Subdiaphragmatic vagotomy or Chrm1 knockout accelerates pancreatic tumorigenesis, in part via expansion of the CSC compartment. Systemic administration of a muscarinic agonist suppresses tumorigenesis through MAPK and PI3K/AKT signaling, in early stages of tumor growth and in more advanced, metastatic disease. Therefore, CHRM1 may represent a potentially attractive therapeutic target. Cancer Discov; 8(11); 1458–73. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 1333

Enteroatmospheric fistulas (EAF) are rare but challenging and morbid complications of abdominal surgery and require time- as well as resource-consuming management. Furthermore, they severely affect patients' quality of life. Several treatment modalities for EAF management are described in the literature. We describe 3 consecutive cases of EAF treatment by employing negative pressure wound therapy (NPWT) along with either a special silicone fistula adapter or a Silo-Vac-like system in another case to isolate the fistula from the remaining abdominal wound. Spontaneous fistula closure was achieved in 2 of the 3 cases, and surgical resection of the small bowel segment harbouring EAF opening was possible in a third case after wound conditioning. The rate of fistula closure was 100% (n = 3/3). Compartmentalisation of the contaminated area using NPWT accelerated healing of the open abdominal wound remarkably. In summary, we present a useful tool for the challenging management of EAF and review the literature on different treatment options of EAF available today.

Background & Aims: Most patients with pedunculated T1 colorectal tumors referred for surgery are not found to have lymph node metastases, and were therefore unnecessarily placed at risk for surgery-associated complications. We aimed to identify histologic factors associated with need for surgery in patients with pedunculated T1 colorectal tumors. Methods: We performed a cohort-nested matched case–control study of 708 patients diagnosed with pedunculated T1 colorectal tumors at 13 hospitals in The Netherlands, from January 1, 2000 through December 31, 2014, followed for a median of 44 months (interquartile range, 20–80 months). We identified 37 patients (5.2%) who required surgery (due to lymph node, intramural, or distant metastases). These patients were matched with patients with pedunculated T1 colorectal tumors without a need for surgery (no metastases, controls, n = 111). Blinded pathologists analyzed specimens from each tumor, stained with H&E. We evaluated associations between histologic factors and patient need for surgery using univariable conditional logistic regression analysis. We used multivariable least absolute shrinkage and selection operator (LASSO; an online version of the LASSO model is available at: http://t1crc.com/calculator/) regression to develop models for identification of patients with tumors requiring surgery, and tested the accuracy of our model by projecting our case–control data toward the entire cohort (708 patients). We compared our model with previously developed strategies to identify high-risk tumors: conventional model 1 (based on poor differentiation, lymphovascular invasion, or Haggitt level 4) and conventional model 2 (based on poor differentiation, lymphovascular invasion, Haggitt level 4, or tumor budding). Results: We identified 5 histologic factors that differentiated cases from controls: lymphovascular invasion, Haggitt level 4 invasion, muscularis mucosae type B (incompletely or completely disrupted), poorly differentiated clusters and tumor budding, which identified patients who required surgery with an area under the curve (AUC) value of 0.83 (95% confidence interval, 0.76–0.90). When we used a clinically plausible predicted probability threshold of ≥4.0%, 67.5% (478 of 708) of patients were predicted to not need surgery. This threshold identified patients who required surgery with 83.8% sensitivity (95% confidence interval, 68.0%–93.8%) and 70.3% specificity (95% confidence interval, 60.9%–78.6%). Conventional models 1 and 2 identified patients who required surgery with lower AUC values (AUC, 0.67; 95% CI, 0.60–0.74; P =.002 and AUC, 0.64; 95% CI, 0.58–0.70; P

To date, few optical imaging systems are available in clinical practice to perform noninvasive measurements transcutaneously. Instead, functional imaging is performed using ionizing radiation or intense magnetic fields in most cases. The applicability of fluorescence imaging (e.g., for the detection of fluorescently labeled objects, such as tumors) is limited due to the restricted tissue penetration of light and the required long exposure time. Thus, the development of highly sensitive and easily manageable instruments is necessary to broaden the utility of optical imaging. To advance these developments, an improved fluorescence imaging system was designed in this study that operates on the principle of noncontact laser-induced fluorescence and enables the detection of fluorescence from deeper tissue layers as well as real-time imaging. The high performance of the developed optical laser scanner results from the combination of specific point illumination, an intensified charge-coupled device (ICCD) detector with a novel light trap, and a filtering strategy. The suitability of the laser scanner was demonstrated in two representative applications and an in vivo evaluation. In addition, a comparison with a planar imaging system was performed. The results show that the exposure time with the developed laser scanner can be reduced to a few milliseconds during measurements with a penetration depth of up to 32 mm. Due to these short exposure times, real-time fluorescence imaging can be easily achieved. The ability to measure fluorescence from deep tissue layers enables clinically relevant applications, such as the detection of fluorescently labeled malignant tumors.

Background. The need for adjuvant chemotherapy after resection of ampullary cancer (PapCa) remains undefined. Recent data suggest that a different epithelial origin of PapCa might be associated with different tumor biology. The aim of the present study was to assess the clinical value of morphologic and immunohistochemic subclassification of PapCa into intestinal-type (IT) and pancreaticobiliary-type (PT) to predict chemotherapy response and overall survival (OS). Methods. Via a prospective database, 112 PapCa were identified, of which 95 could be included in the present study. Those were compared with 206 matching patients with periampullary pancreatic cancer (ie, pancreatic ductal adenocarcinoma, PDAC). ITand PT PapCa were classified morphologically, and tissue microarray was prepared with immunohistochemistry for CK7, CK20, MUC2, CDX2, s-Catenin, and Villin. Multivariate survival analysis was performed. Results. OS of PT patients was less compared with IT patients (25 vs 98 months; P

To determine predictors of failed enhanced recovery after surgery (ERAS) in patients after elective colorectal surgery.A cohort of 55 patients undergoing elective colorectal surgery was monitored prospectively. Perioperative care was based on a previously established protocol for ERAS. Pre-, intra-, and postoperative parameters were analyzed to elicit predictors of ERAS failure. ERAS failure was defined as prolonged hospital stay (7 days). The risk calculator CR-POSSUM was evaluated for its clinical utility.Body mass index (BMI) or the American Society of Anesthesiologists score (ASA) was not associated with ERAS failure on univariate analysis, but patients that failed ERAS were significantly older (64 y vs 54 y ; p = 0.023). Prolonged length of stay (7 days) was also associated with an open approach (p = 0.009), intraoperative nasogastric tube placement (p = 0.005), blood loss500 ml (p = 0.008), stoma formation (p = 0.006) and insertion of more than one intraabdominal drain during surgery (p = 0.005). Postoperative continuation of intravenous fluids (p = 0.027), reinsertion of urinary catheter (p = 0.045) and postoperative ileus (p = 0.020) were also strongly associated with delayed discharge on univariate analysis. After multivariate analysis the preoperative parameters CR-POSSUM score (p = 0.022), increasing BMI (p = 0.014) and preoperative albumin level (p = 0.031) were all independently associated with failure of ERAS.A variety of perioperative factors contribute to failure of ERAS in routine practice. CR-POSSUM can help to identify patients at risk for possible failure of ERAS. This may help to optimize avoidable factors, or accommodate those patients likely to require a longer post-operative stay.

Summary Background There is substantial uncertainty regarding the optimal surgical treatment for chronic pancreatitis. Short-term outcomes have been found to be better after duodenum-preserving pancreatic head resection (DPPHR) than after partial pancreatoduodenectomy. Therefore, we designed the multicentre ChroPac trial to investigate the long-term outcomes of patients with chronic pancreatitis within 24 months after surgery. Methods This randomised, controlled, double-blind, parallel-group, superiority trial was done in 18 hospitals across Europe. Patients with chronic pancreatitis who were planned for elective surgical treatment were randomly assigned to DPPHR or partial pancreatoduodenectomy with a central web-based randomisation tool. The primary endpoint was mean quality of life within 24 months after surgery, measured with the physical functioning scale of the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire. Primary analysis included all patients who underwent one of the assigned procedures; safety analysis included all patients who underwent surgical intervention (categorised into groups as treated). Patients and outcome assessors were masked to group assignment. The trial was registered, ISRCTN38973832. Recruitment was completed on Sept 3, 2013. Findings Between Sept 10, 2009, and Sept 3, 2013, 250 patients were randomly assigned to DPPHR (n=125) or partial pancreatoduodenectomy (n=125), of whom 226 patients (115 in the DPPHR group and 111 in the partial pancreatoduodenectomy group) were analysed. No difference in quality of life was seen between the groups within 24 months after surgery (75·3 [SD 16·4] for partial pancreatoduodenectomy vs 73·0 [16·4] for DPPHR; mean difference −2·3, 95% CI −6·6 to 2·0; p=0·284). The incidence and severity of serious adverse events did not differ between the groups. 70 (64%) of 109 patients in the DPPHR group and 61 (52%) of 117 patients in the partial pancreatoduodenectomy group had at least one serious adverse event, with the most common being reoperations (for reasons other than chronic pancreatitis), gastrointestinal problems, and other surgical morbidity. Interpretation No differences in quality of life after surgery for chronic pancreatitis were seen between the interventions. Results from single-centre trials showing superiority for DPPHR were not confirmed in the multicentre setting. Funding German Research Foundation (DFG).

The purpose of this study is to investigate the prognostic value of pre-resection serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 after resection of ampullary cancer (AC) in consideration of intestinal (IT) and pancreatobiliary (PT) subtypes. Overall survival (OS) analysis of patients undergoing curative resection of ampullary cancer. Elevated preoperative CEA (P = 0.013) and CA 19-9 levels (P = 0.030) were significant prognostic factors. Subgroup analysis, however, showed both markers having prognostic value only for the IT subgroup. Pre-resection CEA within normal range identified a subgroup of IT patients with an excellent median survival of 145 months. Compared to other AC patients, this low-risk ITCEA − subpopulation was characterized by less frequent advanced pT stages (pT3/pT4, 41 vs. 62%; P = 0.047) and lymph node involvement (pN+, 30 vs. 65%; P = 0.001). OS of this subgroup was significantly better compared to other AC patients (145 vs. 25 months; HR = 3.8; P

Among violent offenders with schizophrenia, there are 2 sub-groups, one with and one without, conduct disorder (CD) and antisocial personality disorder (ASPD), who differ as to treatment response and alterations of brain structure. The present study aimed to determine whether the 2 groups also differ in Theory of Mind and neural activations subsuming this task. Five groups of men were compared: 3 groups of violent offenders-schizophrenia plus CD/ASPD, schizophrenia with no history of antisocial behavior prior to illness onset, and CD/ASPD with no severe mental illness-and 2 groups of non-offenders, one with schizophrenia and one without (H). Participants completed diagnostic interviews, the Psychopathy Checklist Screening Version Interview, the Interpersonal Reactivity Index, authorized access to clinical and criminal files, and underwent functional magnetic resonance imaging while completing an adapted version of the Reading-the-Mind-in-the-Eyes Task (RMET). Relative to H, nonviolent and violent men with schizophrenia and not CD/ASPD performed more poorly on the RMET, while violent offenders with CD/ASPD, both those with and without schizophrenia, performed similarly. The 2 groups of violent offenders with CD/ASPD, both those with and without schizophrenia, relative to the other groups, displayed higher levels of activation in a network of prefrontal and temporal-parietal regions and reduced activation in the amygdala. Relative to men without CD/ASPD, both groups of violent offenders with CD/ASPD displayed a distinct pattern of neural responses during emotional/mental state attribution pointing to distinct and comparatively successful processing of social information.

WOS:000390259700002; International audience; Free water elimination (FWE) in brain diffusion MRI has been shown to improve tissue specificity in human white matter characterization both in health and in disease. Relative to the classical diffusion tensor imaging (DTI) model, FWE is also expected to increase sensitivity to microstructural changes in longitudinal studies. However, it is not clear if these two models differ in their test-retest reproducibility. This study compares a bi-tensor model for FWE with DTI by extending a previous longitudinal-reproducibility 3T multisite study (10 sites, 7 different scanner models) of 50 healthy elderly participants (55-80 years old) scanned in two sessions at least 1 week apart. We computed the reproducibility of commonly used DTI metrics (FA: fractional anisotropy, MD: mean diffusivity, RD: radial diffusivity, and AXD: axial diffusivity), derived either using a DTI model or a FWE model. The DTI metrics were evaluated over 48 white-matter regions of the JHU-ICBM-DTI-81 white-matter labels atlas, and reproducibility errors were assessed. We found that relative to the DTI model, FWE significantly reduced reproducibility errors in most areas tested. In particular, for the FA and MD metrics, there was an average reduction of approximately 1% in the reproducibility error. The reproducibility scores did not significantly differ across sites. This study shows that FWE improves sensitivity and is thus promising for clinical applications, with the potential to identify more subtle changes. The increased reproducibility allows for smaller sample size or shorter trials in studies evaluating biomarkers of disease progression or treatment effects. Hum Brain Mapp 38:12-26, 2017. (c) 2016 Wiley Periodicals, Inc.

T1 colorectal cancer can be mimicked by pseudo-invasion in pedunculated polyps. British guidelines are currently one of the few which recommend diagnostic confirmation of T1 colorectal cancer by a second pathologist. The aim of this study was to provide insights into the accuracy of histological diagnosis of pedunculated T1 colorectal cancer in daily clinical practice. A sample of 128 cases diagnosed as pedunculated T1 colorectal cancer between 2000 and 2014 from 10 Dutch hospitals was selected for histological review. Firstly, two Dutch expert gastrointestinal pathologists reviewed all hematoxylin-eosin stained slides. In 20 cases the diagnosis T1 colorectal cancer was not confirmed (20/128; 16%). The discordant cases were subsequently discussed with a third Dutch gastrointestinal pathologist and a consensus diagnosis was agreed. The revised diagnoses were pseudo-invasion in 10 cases (10/128; 8%), high-grade dysplasia in 4 cases (4/128; 3%), and equivocal in 6 cases (6/128; 5%). To further validate the consensus diagnosis, the discordant cases were reviewed by an independent expert pathologist from the United Kingdom. A total of 39 cases were reviewed blindly including the 20 cases with a revised diagnosis and 19 control cases where the Dutch expert panel agreed with the original reporting pathologists diagnosis. In 19 of the 20 cases with a revised diagnosis the British pathologist agreed that T1 colorectal cancer could not be confirmed. Additionally, amongst the 19 control cases the British pathologist was unable to confirm T1 colorectal cancer in a further 4 cases and was equivocal in 3 cases. In conclusion, both generalist and expert pathologists experience diagnostic difficulty distinguishing pseudo-invasion and high-grade dysplasia from T1 colorectal cancer. In order to prevent overtreatment, review of the histology of pedunculated T1 colorectal cancers by a second pathologist should be considered with discussion of these cases at a multidisciplinary meeting.Modern Pathology advance online publication, 7 October 2016; doi:10.1038/modpathol.2016.165.

Background In patients with stage II colorectal cancer (CRC) the number of surgically retrieved lymph nodes (LNs) is associated with prognosis, resulting in a minimum of 10–12 retrieved LNs being recommended for this stage. Current guidelines do not provide a recommendation regarding LN yield in T1 CRC. Studies evaluating LN yield in T1 CRC suggest that such high LN yields are not feasible in this early stage, and a lower LN yield might be appropriate. We aimed to validate the cut-off of 10 retrieved LNs on risk for recurrent cancer and detection of LN metastasis (LNM) in T1 CRC, and explored whether this number is feasible in clinical practice. Methods Patients diagnosed with T1 CRC and treated with surgical resection between 2000 and 2014 in thirteen participating hospitals were selected from the Netherlands Cancer Registry. Medical records were reviewed to collect additional information. The association between LN yield and recurrence and LNM respectively were analyzed using 10 LNs as cut-off. Propensity score analysis using inverse probability weighting (IPW) was performed to adjust for clinical and histological confounding factors (i.e., age, sex, tumor location, size and morphology, presence of LNM, lymphovascular invasion, depth of submucosal invasion, and grade of differentiation). Results In total, 1017 patients with a median follow-up time of 49.0 months (IQR 19.6–81.5) were included. Four-hundred five patients (39.8%) had a LN yield ≥ 10. Forty-one patients (4.0%) developed recurrence. LN yield ≥ 10 was independently associated with a decreased risk for recurrence (IPW-adjusted HR 0.20; 95% CI 0.06–0.67; P = 0.009). LNM were detected in 84 patients (8.3%). LN yield ≥ 10 was independently associated with increased detection of LNM (IPW-adjusted OR 2.27; 95% CI 1.39–3.69; P = 0.001). Conclusions In this retrospective observational study, retrieving

Objective: Patients with ADHD display a decreased contingent negative variation in Go/NoGo tasks. It is unclear whether the attenuation is due to deficits of executive function or to disorder of motor planning. The readiness potential (RP) recorded during self-initiated movements could cast light on this question. Method: RP was recorded in 25 stably medicated adult ADHD patients and 21 healthy controls matched for age, education, and verbal IQ. Participants also completed neuropsychological tests of executive function. Results: Compared with healthy controls, ADHD patients showed significantly diminished RP peaks and also decreased negativity in preparation of the movement at frontal locations. There were no significant group differences with regard to tests of executive function. Conclusion: In adults with ADHD, deficits of motor organization are also manifest in situations not involving external stimulus processing. The attenuated RP occurred in the absence of executive dysfunction. Results are consistent with partial independence between motor and executive dysfunction in ADHD.

Few studies have examined the relationship between CSF and structural biomarkers, and cognitive function in MCI. We examined the relationship between cognitive function, hippocampal volume and cerebrospinal fluid (CSF) Aβ42 and tau in 145 patients with MCI. Patients were assessed on cognitive tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB), the Geriatric Depression Scale and the Functional Activities Questionnaire. Hippocampal volume was measured using magnetic resonance imaging (MRI), and CSF markers of Aβ42, tau and p-tau181 were also measured. Worse performance on a wide range of memory and sustained attention tasks were associated with reduced hippocampal volume, higher CSF tau and p-tau181 and increased tau/Aβ42 ratio. Memory tasks were also associated with lower ability to conduct functional activities of daily living, providing a link between AD biomarkers, memory performance and functional outcome. These results suggest that biomarkers of Aβ and tau are strongly related to cognitive performance as assessed by the CANTAB, and have implications for the early detection and characterization of incipient AD.

Theoretical models postulate an important role of attributional style (AS) in the formation and maintenance of persecutory delusions and other positive symptoms of schizophrenia. However, current research has gathered conflicting findings. In a cross-sectional design, patients with persistent positive symptoms of schizophrenia (n = 258) and healthy controls (n = 51) completed a revised version of the Internal, Personal and Situational Attributions Questionnaire (IPSAQ-R) and assessments of psychopathology. In comparison to controls, neither patients with schizophrenia in general nor patients with persecutory delusions (n = 142) in particular presented an externalizing and personalizing AS. Rather, both groups showed a “self-blaming” AS and attributed negative events more toward themselves. Persecutory delusions were independently predicted by a personalizing bias for negative events (beta = 0.197, P = .001) and by depression (beta = 0.152, P = .013), but only 5% of the variance in persecutory delusions could be explained. Cluster analysis of IPSAQ-R scores identified a “personalizing” (n = 70) and a “self-blaming” subgroup (n = 188), with the former showing slightly more pronounced persecutory delusions (P = .021). Results indicate that patients with schizophrenia and patients with persecutory delusions both mostly blamed themselves for negative events. Nevertheless, still a subgroup of patients could be identified who presented a more pronounced personalizing bias and more severe persecutory delusions. Thus, AS in patients with schizophrenia might be less stable but more determined by individual and situational characteristics that need further elucidation.

Decisions are called decisions under uncertainty when either prior information is incomplete or the outcomes of the decision are unclear. Alterations in these processes related to decisions under uncertainty have been linked to delusions. In patients with schizophrenia, the underlying neural networks have only rarely been studied. We aimed to disentangle the neural correlates of decision-making and relate them to neuropsychological and psychopathological parameters in a large sample of patients with schizophrenia and healthy subjects. Fifty-seven patients and fifty-seven healthy volunteers from six centers had to either indicate via button-press from which of two bottles red or blue balls were drawn (decision-making under uncertainty condition), or indicate whether eight red balls had been presented (baseline condition) while BOLD signal was measured with fMRI. Patients based their decisions on less conclusive evidence and had decreased activations in the underlying neural network, comprising of medial and lateral frontal as well as parietal areas, as compared to healthy subjects. While current psychopathology was not correlated with brain activation, positive symptoms led to longer decision latencies in patients. These results suggest that decision-making under uncertainty in schizophrenia is affected by a complex interplay of aberrant neural activation. Furthermore, reduced neuropsychological functioning in patients was related to impaired decision-making and task performance was modulated by distinct positive symptoms.

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ObjectiveThis study evaluated the preresection accuracy of optical diagnosis of T1 colorectal cancer (CRC) in large non-pedunculated colorectal polyps (LNPCPs).DesignIn this multicentre prospective study, endoscopists predicted the histology during colonoscopy in consecutive patients with LNPCPs using a standardised procedure for optical assessment. The presence of morphological features assessed with white light, and vascular and surface pattern with narrow-band imaging (NBI) were recorded, together with the optical diagnosis, the confidence level of prediction and the recommended treatment. A risk score chart was developed and validated using a multivariable mixed effects binary logistic least absolute shrinkage and selection (LASSO) model.ResultsAmong 343 LNPCPs, 47 cancers were found (36 T1 CRCs and 11 ≥T2 CRCs), of which 11 T1 CRCs were superficial invasive T1 CRCs (23.4% of all malignant polyps). Sensitivity and specificity for optical diagnosis of T1 CRC were 78.7% (95% CI 64.3 to 89.3) and 94.2% (95% CI 90.9 to 96.6), and 63.3% (95% CI 43.9 to 80.1) and 99.0% (95% CI 97.1 to 100.0) for optical diagnosis of endoscopically unresectable lesions (ie, ≥T1 CRC with deep invasion), respectively. A LASSO-derived model using white light and NBI features discriminated T1 CRCs from non-invasive polyps with a cross-validation area under the curve (AUC) of 0.85 (95% CI 0.80 to 0.90). This model was validated in a temporal validation set of 100 LNPCPs (AUC of 0.81; 95% CI 0.66 to 0.96).ConclusionOur study provides insights in the preresection accuracy of optical diagnosis of T1 CRC. Sensitivity is still limited, so further studies will show how the risk score chart could be improved and finally used for clinical decision making with regard to the type of endoresection to be used and whether to proceed to surgery instead of endoscopy.Trial registration numberNTR5561.

This study assesses the perioperative course and long-term survival of inflammatory bowel disease (IBD)-associated vs. sporadic colorectal cancer (IBD-CRC vs. SCRC) after elimination of known confounders. Between 1991 and 2007, n = 3,299 patients underwent surgery for CRC at our institution. Thirty-three IBD patients were identified and compared to 165 SCRC using a matched-pair analysis (1:5 scenario). As matching parameters were used: age, gender, Union Internationale Contre le Cancer (UICC) stage, site of primary lesion, and date of surgery. After univariate analysis of the perioperative course, a multivariate survival analysis (Cox) of all patients (n = 198) was performed. Significant differences were shown for preoperative symptoms (p = 0.022), transfusion rate (p = 0.01), ileostomy construction rate (p = 0.001), total complication rate (p = 0.042), and hospital stay (15 vs. 11 days, p

Attributions are constantly assigned in everyday life. A well-known phenomenon is the self-serving bias: that is, people's tendency to attribute positive events to internal causes (themselves) and negative events to external causes (other persons/circumstances). Here, we investigated the neural correlates of the cognitive processes implicated in self-serving attributions using social situations that differed in their emotional saliences. We administered an attributional bias task during fMRI scanning in a large sample of healthy subjects (n = 71). Eighty sentences describing positive or negative social situations were presented, and subjects decided via buttonpress whether the situation had been caused by themselves or by the other person involved. Comparing positive with negative sentences revealed activations of the bilateral posterior cingulate cortex (PCC). Self-attribution correlated with activation of the posterior portion of the precuneus. However, self-attributed positive versus negative sentences showed activation of the anterior portion of the precuneus, and self-attributed negative versus positive sentences demonstrated activation of the bilateral insular cortex. All significant activations were reported with a statistical threshold of p ≤ .001, uncorrected. In addition, a comparison of our fMRI task with data from the Internal, Personal and Situational Attributions Questionnaire, Revised German Version, demonstrated convergent validity. Our findings suggest that the precuneus and the PCC are involved in the evaluation of social events with particular regional specificities: The PCC is activated during emotional evaluation, the posterior precuneus during attributional evaluation, and the anterior precuneus during self-serving processes. Furthermore, we assume that insula activation is a correlate of awareness of personal agency in negative situations.

Item does not contain fulltext Although 'irrational' decision-making has been linked to depression, the contribution of biases in information processing to these findings remains unknown. To investigate the impact of cognitive biases and aberrant processing of facial emotions on social decision-making, we manipulated both context-related and emotion-related information in a modified Ultimatum Game. Unfair offers were (1) paired with different unselected alternatives, establishing the context in which an offer was made, and (2) accompanied by emotional facial expressions of proposers. Responder behavior was assessed in patients with major depressive disorder and healthy controls. In both groups alike, rejection rates were highest following unambiguous signals of unfairness, i.e. an angry proposer face or when an unfair distribution had deliberately been chosen over an equal split. However, depressed patients showed overall higher rejection rates than healthy volunteers, without exhibiting differential processing biases. This suggests that depressed patients were, as healthy individuals, basing their decisions on informative, salient features and differentiating between (i) fair and unfair offers, (ii) alternatives to unfair offers and (iii) proposers' facial emotions. Although more fundamental processes, e.g. reduced reward sensitivity, might underlie increased rejection in depression, the current study provides insight into mechanisms that shape fairness considerations in both depressed and healthy individuals. 6 p.