A radiomics-based model to classify the etiology of liver cirrhosis using gadoxetic acid-enhanced MRI

The implementation of radiomics in radiology is gaining interest due to its wide range of applications. To develop a radiomics-based model for classifying the etiology of liver cirrhosis using gadoxetic acid-enhanced MRI, 248 patients with a known etiology of liver cirrhosis who underwent 306 gadoxetic acid-enhanced MRI examinations were included in the analysis. MRI examinations were classified into 6 groups according to the etiology of liver cirrhosis: alcoholic cirrhosis, viral hepatitis, cholestatic liver disease, nonalcoholic steatohepatitis (NASH), autoimmune hepatitis, and other. MRI examinations were randomized into training and testing subsets. Radiomics features were extracted from regions of interest segmented in the hepatobiliary phase images. The fivefold cross-validated models (2-dimensional-(2D) and 3-dimensional-(3D) based) differentiating cholestatic cirrhosis from noncholestatic etiologies had the best accuracy (87.5%, 85.6%), sensitivity (97.6%, 95.6%), predictive value (0.883, 0.877), and area under curve (AUC) (0.960, 0.910). The AUC was larger in the 2D-model for viral hepatitis, cholestatic cirrhosis, and NASH-associated cirrhosis (P-value of 0.05, 0.05, 0.87, respectively). In alcoholic cirrhosis, the AUC for the 3D model was larger (P=0.01). The overall intra-class correlation coefficient (ICC) estimates and their 95% confident intervals (CI) for all features combined was 0.68 (CI 0.56-0.87) for 2D and 0.71 (CI 0.61-0.93) for 3D measurements suggesting moderate reliability. Radiomics-based analysis of hepatobiliary phase images of gadoxetic acid-enhanced MRI may be a promising noninvasive method for identifying the etiology of liver cirrhosis with better performance of the 2D- compared with the 3D-generated models

Systemic Chemotherapy Including Ramucirumab in Combination With Pressurized Intra-Peritoneal Aerosol Chemotherapy Is a Safe Treatment Option for Peritoneal Metastasis of Gastric Cancer

Background: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a laparoscopic technique for local chemotherapy. It has been used for treatment of peritoneal metastasis of gastric cancer (PM GC) in combination with systemic therapy. VEGFR2 antagonist ramucirumab is a second-line therapy for GC, and has been suspected to cause wound healing disorders. Methods: This is a retrospective single center cohort study of patients with PM GC, who received PIPAC treatment in combination with systemic chemotherapy with and without ramucirumab. Data on patients' characteristics and their perioperative courses were collected and complication rates were compared with regard to preoperative use of ramucirumab and time between last dose of systemic therapy and PIPAC treatment. Results: Fifty patients underwent 90 PIPAC treatments for PM GC in 3 years. Overall postoperative morbidity was 11% with 6% severe complications. The mean interval between systemic therapy and PIPAC was 20 days. Neither the length of interval nor the use of ramucirumab had an effect on complication rates. Conclusion: Our study suggests that addition of ramucirumab to pre-PIPAC systemic therapy, irrespective of the length of the treatment-free interval before PIPAC, does not increase the risk of postoperative complications and is therefore a safe option for treatment of PM GC

Hepatocellular adenomas: is there additional value in using Gd-EOB-enhanced MRI for subtype differentiation?

Purpose: To differentiate subtypes of hepatocellular adenoma (HCA) based on enhancement characteristics in gadoxetic acid (Gd-EOB) magnetic resonance imaging (MRI). Materials and methods: Forty-eight patients with 79 histopathologically proven HCAs who underwent Gd-EOB-enhanced MRI were enrolled (standard of reference: surgical resection). Two blinded radiologists performed quantitative measurements (lesion-to-liver enhancement) and evaluated qualitative imaging features. Inter-reader variability was tested. Advanced texture analysis was used to evaluate lesion heterogeneity three-dimensionally. Results: Overall, there were 19 (24%) hepatocyte nuclear factor (HNF)-1a-mutated (HHCAs), 37 (47%) inflammatory (IHCAs), 5 (6.5%) b-catenin-activated (bHCA), and 18 (22.5%) unclassified (UHCAs) adenomas. In the hepatobiliary phase (HBP), 49.5% (39/79) of all adenomas were rated as hypointense and 50.5% (40/79) as significantly enhancing (defined as > 25% intralesional GD-EOB uptake). 82.5% (33/40) of significantly enhancing adenomas were IHCAs, while only 4% (1/40) were in the HHCA subgroup (p < 0.001). When Gd-EOB uptake behavior was considered in conjunction with established MRI features (binary regression model), the area under the curve (AUC) increased from 0.785 to 0.953 for differentiation of IHCA (atoll sign + hyperintensity), from 0.859 to 0.903 for bHCA (scar + hyperintensity), and from 0.899 to 0.957 for HHCA (steatosis + hypointensity). Three-dimensional region of interest (3D ROI) analysis showed significantly increased voxel heterogeneity for IHCAs (p = 0.038). Conclusion: Gd-EOB MRI is of added value for subtype differentiation of HCAs and reliably identifies the typical heterogeneous HBP uptake of IHCAs. Diagnostic accuracy can be improved significantly by the combined analysis of established morphologic MR appearances and intralesional Gd-EOB uptake. Key points: •Gd-EOB-enhanced MRI is of added value for subtype differentiation of HCA. •IHCA and HHCA can be identified reliably based on their typical Gd-EOB uptake patterns, and accuracy increases significantly when additionally taking established MR appearances into account. •The small numbers of bHCAs and UHCAs remain the source of diagnostic uncertainty

Effects of Artificial Intelligence-Derived Body Composition on Kidney Graft and Patient Survival in the Eurotransplant Senior Program

The Eurotransplant Senior Program allocates kidneys to elderly transplant patients. The aim of this retrospective study is to investigate the use of computed tomography (CT) body composition using artificial intelligence (AI)-based tissue segmentation to predict patient and kidney transplant survival. Body composition at the third lumbar vertebra level was analyzed in 42 kidney transplant recipients. Cox regression analysis of 1-year, 3-year and 5-year patient survival, 1-year, 3-year and 5-year censored kidney transplant survival, and 1-year, 3-year and 5-year uncensored kidney transplant survival was performed. First, the body mass index (BMI), psoas muscle index (PMI), skeletal muscle index (SMI), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) served as independent variates. Second, the cut-off values for sarcopenia and obesity served as independent variates. The 1-year uncensored and censored kidney transplant survival was influenced by reduced PMI (p = 0.02 and p = 0.03, respectively) and reduced SMI (p = 0.01 and p = 0.03, respectively); 3-year uncensored kidney transplant survival was influenced by increased VAT (p = 0.04); and 3-year censored kidney transplant survival was influenced by reduced SMI (p = 0.05). Additionally, sarcopenia influenced 1-year uncensored kidney transplant survival (p = 0.05), whereas obesity influenced 3-year and 5-year uncensored kidney transplant survival. In summary, AI-based body composition analysis may aid in predicting short- and long-term kidney transplant survival

HBP-enhancing hepatocellular adenomas and how to discriminate them from FNH in Gd-EOB MRI

BackgroundRecent studies provide evidence that hepatocellular adenomas (HCAs) frequently take up gadoxetic acid (Gd-EOB) during the hepatobiliary phase (HBP). The purpose of our study was to investigate how to differentiate between Gd-EOB-enhancing HCAs and focal nodular hyperplasias (FNHs). We therefore retrospectively included 40 HCAs classified as HBP Gd-EOB-enhancing lesions from a sample of 100 histopathologically proven HCAs in 65 patients. These enhancing HCAs were matched retrospectively with 28 FNH lesions (standard of reference: surgical resection). Two readers (experienced abdominal radiologists blinded to clinical data) reviewed the images evaluating morphologic features and subjectively scoring Gd-EOB uptake (25-50%, 50-75% and 75-100%) for each lesion. Quantitative lesion-to-liver enhancement was measured in arterial, portal venous (PV), transitional and HBP. Additionally, multivariate regression analyses were performed. ResultsSubjective scoring of intralesional Gd-EOB uptake showed the highest discriminatory accuracies (AUC: 0.848 (R#1); 0.920 (R#2)-p0.05). ConclusionEven in HBP-enhancing HCA, characterization of Gd-EOB uptake was found to provide the strongest discriminatory power in differentiating HCA from FNH. Furthermore, a lobulated appearance and a central scar are more frequently seen in FNH than in HCA

Combining Transarterial Radioembolization (TARE) and CT-Guided High-Dose-Rate Interstitial Brachytherapy (CT-HDRBT): A Retrospective Analysis of Advanced Primary and Secondary Liver Tumor Treatment

Purpose: Treatment of patients with primary and secondary liver tumors remains challenging. This study analyzes the efficacy and safety of transarterial radioembolization (TARE) combined with CT-guided high-dose-rate interstitial brachytherapy (CT-HDRBT) for the treatment of primary and secondary liver tumors. Patients and Methods: A total of 77 patients (30 female) with various liver malignancies were treated. Primary endpoints were median overall survival (OS) and time to untreatable progression (TTUP). Additionally, subgroup analyses were performed in consideration of diagnosis and procedure sequence. Median OS and TTUP prediction were estimated using Kaplan-Meier analysis and hazard ratios (HR) were calculated using a multivariate Cox proportional hazard model. Results: A total of 115 CT-HDRBT and 96 TARE procedures were performed with Purpose: Treatment of patients with primary and secondary liver tumors remains challenging. This study analyzes the efficacy and safety of transarterial radioembolization (TARE) combined with CT-guided high-dose-rate interstitial brachytherapy (CT-HDRBT) for the treatment of primary and secondary liver tumors. Patients and methods: A total of 77 patients (30 female) with various liver malignancies were treated. Primary endpoints were median overall survival (OS) and time to untreatable progression (TTUP). Additionally, subgroup analyses were performed in consideration of diagnosis and procedure sequence. Median OS and TTUP prediction were estimated using Kaplan-Meier analysis and hazard ratios (HR) were calculated using a multivariate Cox proportional hazard model. Results: A total of 115 CT-HDRBT and 96 TARE procedures were performed with no significant complications recorded. Median OS and TTUP were 29.8 (95% CI 18.1-41.4) and 23.8 (95% CI 9.6-37.9) months. Median OS for hepatocellular carcinoma (HCC)-, cholangiocarcinoma carcinoma (CCA) and colorectal cancer (CRC) patients was 29.8, 29.6 and 34.4 months. Patients starting with TARE had a median OS of 26.0 (95% CI 14.5-37.5) compared to 33.7 (95% CI 21.6-45.8) months for patients starting with CT-HDRBT. Hazard ratio of 1.094 per month was shown for patients starting with CT-HDRBT. Conclusion: Combining TARE and CT-HDRBT is effective and safe for the treatment of advanced stage primary and secondary liver tumors. Our data indicate that early TARE during the disease progression may have a positive effect on survival.no significant complications recorded. Median OS and TTUP were 29.8 (95% CI 18.1-41.4) and 23.8 (95% CI 9.6-37.9) months. Median OS for hepatocellular carcinoma (HCC)-, cholangiocarcinoma carcinoma (CCA) and colorectal cancer (CRC) patients was 29.8, 29.6 and 34.4 months. Patients starting with TARE had a median OS of 26.0 (95% CI 14.5-37.5) compared to 33.7 (95% CI 21.6-45.8) months for patients starting with CT-HDRBT. Hazard ratio of 1.094 per month was shown for patients starting with CT-HDRBT. Conclusion: Combining TARE and CT-HDRBT is effective and safe for the treatment of advanced stage primary and secondary liver tumors. Our data indicate that early TARE during the disease progression may have a positive effect on survival

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways

The Crowdsourced Replication Initiative: Investigating Immigration and Social Policy Preferences. Executive Report.

In an era of mass migration, social scientists, populist parties and social movements raise concerns over the future of immigration-destination societies. What impacts does this have on policy and social solidarity? Comparative cross-national research, relying mostly on secondary data, has findings in different directions. There is a threat of selective model reporting and lack of replicability. The heterogeneity of countries obscures attempts to clearly define data-generating models. P-hacking and HARKing lurk among standard research practices in this area.This project employs crowdsourcing to address these issues. It draws on replication, deliberation, meta-analysis and harnessing the power of many minds at once. The Crowdsourced Replication Initiative carries two main goals, (a) to better investigate the linkage between immigration and social policy preferences across countries, and (b) to develop crowdsourcing as a social science method. The Executive Report provides short reviews of the area of social policy preferences and immigration, and the methods and impetus behind crowdsourcing plus a description of the entire project. Three main areas of findings will appear in three papers, that are registered as PAPs or in process

Bildgebende Verfahren zur Optimierung der prä- und postoperativen Versorgung der Abdomen- und Viszeralchirurgie

In der Behandlung von onkologischen Erkrankungen in der Abdominal- und Viszeralchirurgie ist die enge interdisziplinäre Zusammenarbeit zwischen Radiologie und Chirurgie eine Voraussetzung für eine zeitgerechte individualisierte und hochspezialisierte Versorgung. Die ständige Verbesserung in der präoperativen Diagnostik sowie in der postoperativen Verlaufsbildgebung dient hierbei, diese Zusammenarbeit fortlaufend zu optimieren. In Originalarbeit 1 wurde die Kontrastmittel-unterstützte Sonographie (CEUS) als erweiternde Diagnostik hinsichtlich ihres Zusatznutzens bei fokalen Leberläsionen in Fällen untersucht, wo schnittbildgebende Verfahren wie die CT und die MRT zu keiner eindeutigen Diagnose kamen. Hierzu konnte die CEUS bei 146 Patient*innen bei der Unterscheidung von Läsionen als maligne oder benigne eine AUC von 0.95 und einer Sensitivität von 92% (95%-KI, 79-97) und Sensitivität von 98% (95%-KI, 93-99) erreichen. Auch bei der korrekten Charakterisierung der einzelnen Entitäten schnitt die CEUS gut ab. Aus den gewonnenen Ergebnissen schlussfolgern wir, dass bei dignitätsunklaren fokalen Leberläsionen ohne eindeutige Diagnose in der Schnittbildgebung die CEUS als erweiternde bildgebende Modalität mit hoher diagnostischer Aussagekraft, ob eine Läsion benigne oder maligne ist, einen Zusatznutzen erbringt. In Originalarbeit 2 wurden bildmorphologische Kriterien hinsichtlich der Unterscheidung zwischen Gd-EOB-enhancenden hepatozellulären Adenomen (HCAs) und fokal nodulären Hyperplasien FNHs untersucht. Insgesamt konnten hierzu aus 65 Patient*innen mit insgesamt 100 histopathologisch bestätigten HCAs, 40 Läsionen eingeschlossen werden, während bei 28 Patient*innen jeweils eine resezierte FNH als Läsion miteingeschlossen werden konnte. Hierzu ordneten zwei Reader den Gd-EOB- Uptake subjektiv in 25% Schritten ein (25-50%, 50-75% und 75-100). Weiter wurden das Lesion-to-Liver-Enhancement in allen KM-Phasen quantifiziert und konventionelle MR-Features ausgewertet. Das Scoring des Gd-EOB-Uptakes zeigte die höchste diagnostische Genauigkeit. Darüber hinaus zeigten nur das Feature Lobulation und das Vorhandensein einer zentralen Narbe zumindest bei einem der zwei Reader eine AUC>0.750. Den Einfluss des Gd-EOB-Uptakes als wichtigster Diskriminationsfaktor wurde durch die multivariate Analyse bestätigt. Die quantitativen KM-Analysen kamen dementsprechend ebenfalls zu einem signifikanten Ergebnis, was die Charakterisierung mit hepatobiliärem KM weiterhin als bestes bildmorphologisches Kriterium bestätigt. In Originalarbeit 3 wurde das PoSSe-MRT-Protokoll (Postoperative-Single- Sequence) hinsichtlich der Detektion von Flüssigkeitskollektionen und Verhalten nach hepatobiliärer und Pankreaschirurgie im Rahmen einer prospektiven Studie untersucht. Hierzu konnten insgesamt 46 Patient*innen eingeschlossen werden. Sonographisch konnten bei 41% (21/46) der Patient*innen Verhalte oder Flüssigkeitskollektionen detektiert werden, während im MRT bei allen 46 Patient*innen Verhalte beschrieben worden waren. Basierend auf dem MRT wurde bei 54% (25/46) eine Drainage vorgeschlagen, von denen bei 84% (21/25) die Drainage letztendlich indiziert und gelegt worden war (Sensitivität: 100% / Spezifität: 84%). Somit sind ultraschnelle MRT-Protokolle wie das PoSSe-Protokoll zur Detektion von Flüssigkeitskollektionen und Verhalten im klinischen Alltag geeignet, um als Grundlage von Therapieentscheidungen zu dienen. In Originalarbeit 4 wurde ein speziell für Pankreas- und cholangiozelluläre Karzinome (CCC) entwickeltes KM-unterstütztes CT-Split-Bolus-Protokoll (SBP) hinsichtlich der diagnostischen Genauigkeit, Bildqualität und Dosisreduktion mit einem Standard- multiphasischen Protokoll (MPP) im Rahmen einer prospektiven Studie bei 56 Patient*innen verglichen. Das durchschnittliche Dosislängenprodukt DLP (in mGy*cm) war in der SBP-Kohorte signifikant niedriger als in der MPP-Kohorte (p<0.001). In den ROI-Messungen zeigt sich nur für die Aorta und für die Portalvene eine höherer KM- Konzentration, während für die anderen Strukturen kein signifikanter Unterschied beschrieben werden konnte. Jedoch schien das keinen Einfluss auf die subjektive Wahrnehmung der Reader zu haben, die insgesamt sogar das SBP besser bewerteten. Die diagnostische Genauigkeit korrelierte ebenso wie die Interreader- Variabilitäten miteinander. Die Studie liefert den Beweis, dass SBP das Potential besitzen, bei Patient*innen mit Pankreas- und CCC die Strahlenbelastung bei gleichbleibender diagnostischer Genauigkeit und Bildqualität zu reduzieren. In Originalarbeit 5 wurde im Rahmen einer bizentrischen Studie bei 345 Patient*innen untersucht, ob ein positiver (R1)-Resektionsstatus einen Einfluss auf die Lokalisation von hepatischen Rezidiven hat und ob diese das Langzeitüberleben beeinflusst. Hierbei wurden 18% (63/345) der Patient*innen wurden als R1 reseziert. Nach einem medianen Beobachtungszeitraum von 34 Monaten wurde ein hepatisches Rezidiv bei 45% (154/345) der Patient*innen diagnostiziert. Randrezidive wurden hierbei nicht signifikant häufiger bei Patient*innen mit R1- als bei einem R0-Status diagnostiziert (p=0.555). Es zeigt sich das die Lokalisation keinen signifikanten Einfluss auf das Gesamtüberleben zeigte (p=0.436). Ein positiver initialer R1-Resektionsstatus hingegen war unabhängig von der Rezidivlokalisation mit einem schlechteren Gesamtübereben assoziiert (p=0.025). Somit scheint im Gegensatz zur Rezidivlokalisation der R1-Status als robuster Surrogatparameter dienen zu können, um als Entscheidungshilfe bei der chirurgischen Indikations- und Resektionsplanung kolorektaler Lebermetastasen zu dienen. In Originalarbeit 6 wurde im Rahmen einer multizentrischen Studie mit 290 Patient*innen die Prognose und damit assoziierte Parameter der Pneumatosis Intestinalis (PI) und porto-mesentrico-venösen Gases (PMVG) untersucht. Insgesamt betrug die 90d-Mortalität 55,2%. Unterteilt in Patiente*innen mit PI und PI + PMVG konnte hinsichtlich der Mortalität ein signifikanter Unterschied bei Patient*innen mit PMVG beobachtet werden (p<0.001). Patient*innen, die trotz konservativer Therapie über 90 Tage überlebten, wurden als „benigne“/reversible bezeichnet (24,9% (72/290). Als die Prognose beeinträchtigende Faktoren konnten PMVG, COPD, Sepsis und niedrige Thrombozyten identifiziert werden. Wir kamen zu dem Schluss, dass, obwohl die PI mit hohen Mortalitätsraten korreliert, „benigne“ Verläufe existieren und häufiger sind als angenommen. Die zusätzliche Diagnose von PMVG bleibt jedoch ein prognostisch ungünstiges Zeichen. Die im Rahmen dieser Habilitationsschrift vorgestellten Studien liefern den Beleg für das enorme Potential, das moderne bildgebende Techniken in der prä- und postoperativen Diagnostik und Verlaufsbildgebung besitzen. Durch den ständigen Austausch von Radiologie und Chirurgie müssen so immer neue Impulse ausgehen, um die Behandlung der Patient*innen in der Zukunft immer mehr zu individualisieren