Quantifizierung von Komplikationen und Stichkanalmetastasen nach CT-gesteuerter Hochdosis-Brachytherapie im Afterloadingverfahren

Hintergrund und Fragestellung: Die CT-gesteuerte Brachytherapie im Afterloadingverfahren (CT-HDRBT) ist eine minimal- invasive Therapieoption für verschiedene Tumorentitäten. Das Verfahren wird seit mehr als 15 Jahren mit etwa 250 Interventionen jährlich an unserem Zentrum durchgeführt. Es erfolgt eine CT- gesteuerte Punktion der Zielläsion und deren Bestrahlung mit einer Iridium192 Quelle. Komplikationen können durch die Punktion selbst, sowie durch die Bestrahlung auftreten. Außerdem besteht die Gefahr einer Tumorzellverschleppung entlang des Stichkanals. Der Zweck dieser Studie ist eine Quantifizierung der aufgetretenen Komplikationen und der Rate der Stichkanalmetastasen. Methoden: Das Patientenkollektiv umfasst 1106 Patienten, die sich im Zeitraum von 2006 bis 2017 an unserem Zentrum einer CT-HDRBT unterzogen haben. Die notwendigen Informationen konnten der elektronischen Patientenakten sowie der durchgeführten Bildgebung entnommen werden. Die Überprüfung der Stichkanalmetastasen wurde durch einen Radiologen mit mehrjähriger Erfahrung auf diesem Gebiet durchgeführt. Es erfolgte eine deskriptive und explorative Analyse der Ergebnisse. Resultate: In der großen Mehrheit der Interventionen traten keine Komplikationen auf (84.8%). Geringe Komplikationen, ohne Notwendigkeit einer Behandlung, wurden in 9.7% der Interventionen registriert, schwerwiegende Komplikationen mit Notwendigkeit einer Therapie in 5.6% der Fälle. Am häufigsten kam es zu Blutungen (inklusive Hämatomen, 5,6%), Infektionen (2,6%) und verlängerten postinterventionellen Schmerzen (1,9%). Ein Risikofaktor für das Auftreten von Komplikationen ist der summierte Gesamtdurchmesser der behandelten Läsionen (Odds Ratio 1,010; p=0,001). Patienten mit BDA entwickeln häufiger Infektionen (Odds Ratio 9,198; p= 0,001). Stichkanalmetastasen wurden in 1.4% der Interventionen gefunden (insgesamt 14 Fälle) nach einer medianen Follow-Up Zeit von 6 Monaten. Ein Risikofaktor für das Auftreten von Stichkanalmetastasen ist die Anzahl der verwendeten Katheter pro Läsion (Odds Ratio 2,024; p=0,004). Schlussfolgerung: Die CT-gesteuerte Brachytherapie ist eine sichere, minimal-invasive Behandlungsoption für Patienten mit verschiedenen Tumorentitäten. Ein Risikofaktor für postinterventionelle Komplikationen ist der summierte Gesamtdurchmesser der behandelten Läsionen. Patienten mit BDA entwickeln häufiger Infektionen. Eine Tumorzellverschleppung ist möglich, sie tritt jedoch sehr selten auf. Das Risiko einer Stichkanalmetastasierung nimmt mit Anzahl der verwendeten Katheter pro Läsion zu.Background and Purpose: Our center has about 15 years of experience with computed tomography-guided high-dose-rate brachytherapy (CT-HDRBT) and currently performs nearly 250 interventions per year. It is a minimally invasive therapeutic option for the local ablation of unresectable tumors. Patients undergo CT-guided placement of an applicator and CT-HDRBT with iridium192. Procedural complications are related to puncture and radiation. Furthermore, puncturing of the tumor and subsequent applicator retraction has the potential risk of tumor seeding along the puncture track. The purpose of this study therefore is to quantify complications and tumor seeding rates in patients undergoing CT-HDRBT. Methods: We retrospectively analyzed 1106 patients treated with CT-HDRBT at our center between 2006 and 2017. Information on complications was retrieved from electronic patient histories and imaging data. Complications were categorized by time of appearance, need for treatment, and other factors. Tumor seeding along former puncture tracks was assessed by an interventional radiologist with more than 15 years of experience in the field using imaging data and patient history. Statistical analysis was performed. Results: The vast majority of interventions were performed without any complications (84.8%). Minor complications not requiring treatment were recorded in 9.7 % of interventions, and major complications requiring treatment in 5.6%. Bleedings including hematomas (5.6%), infections (2.6%), and prolonged pain (1.9%) were the most common complications. A potential risk factor for complications is the summarized diameter of all treated lesions (odds ratio 1.010; p= 0.001). Patients with biliodigestive anastomosis (BDA) were more likely to develop infections (odds ratio 9.198; p= 0.001). Tumor seeding along puncture tracks was found in 1.4% of interventions (14 cases) after a mean of 6 months. A risk factor for seeding was the number of catheters used per lesion (odds ratio 2.024; p=0.004). Conclusion: CT-HDRBT is a safe minimally invasive treatment option for patients with various tumor entities. Tumor seeding along puncture tracks is possible but rare. A risk factor for seeding is the number of catheters inserted per lesion. Patients with BDA are more likely to develop infections, and the summarized lesion diameter is a risk factor for complications

25 years of experience with transjugular intrahepatic portosystemic shunt (TIPS): changes in patient selection and procedural aspects

Background: TIPS is an established treatment for portal hypertension. The aim was to analyze how patient selection for TIPS implantation and procedural aspects have changed over 25 years. Routinely collected demographic, clinical, laboratory, and procedural data of 835 patients treated with TIPS in a single center were used. Time trends over the observational period from 1993 to 2018 were retrospectively analyzed. Descriptive statistical analysis was performed. Results: The most common indication for TIPS implantation has changed significantly from secondary prevention of variceal hemorrhage in the early years to treatment of recurrent ascites. During the observation period, increasingly more severely ill patients became TIPS candidates. There was little change in MELD scores over this period (in total median 13.00; IQR 10.00-18.00). The proportion of patients with Child-Pugh C cirrhosis increased. The most frequent underlying diseases in total were alcohol-related liver disease (66.5%) and viral hepatitis (11.9%). However, shares of cryptogenic liver cirrhosis, autoimmune hepatitis, and NASH increased over time. The proportion of patients post liver transplant also increased. While bare metal stents were standard in the past, use of covered stents increased. The success rate of TIPS (defined by successful implantation and a decrease in the portosystemic pressure gradient <= 12 mmHg) increased significantly over time. The total success rate according to this definition was 84.9%. Conclusion: The results of our analysis reflect technical developments in TIPS, especially in terms of stent material and gains in clinical experience, particularly regarding indications and patient selection for TIPS implantation

Diagnostic Value of Initial Chest CT Findings for the Need of ICU Treatment/Intubation in Patients with COVID-19

Computed tomography (CT) plays an important role in the diagnosis of COVID-19. The aim of this study was to evaluate a simple, semi-quantitative method that can be used for identifying patients in need of subsequent intensive care unit (ICU) treatment and intubation. We retrospectively analyzed the initial CT scans of 28 patients who tested positive for SARS-CoV-2 at our Level-I center. The extent of lung involvement on CT was classified both subjectively and with a simple semi-quantitative method measuring the affected area at three lung levels. Competing risks Cox regression was used to identify factors associated with the time to ICU admission and intubation. Their potential diagnostic ability was assessed with receiver operating characteristic (ROC)/area under the ROC curves (AUC) analysis. A 10% increase in the affected lung parenchyma area increased the instantaneous risk of intubation (hazard ratio (HR) = 2.00) and the instantaneous risk of ICU admission (HR 1.73). The semi-quantitative measurement outperformed the subjective assessment diagnostic ability (AUC = 85.6% for ICU treatment, 71.9% for intubation). This simple measurement of the involved lung area in initial CT scans of COVID-19 patients may allow early identification of patients in need of ICU treatment/intubation and thus help make optimal use of limited ICU/ventilation resources in hospitals

CT-Based Risk Stratification for Intensive Care Need and Survival in COVID-19 Patients—A Simple Solution

We evaluated a simple semi-quantitative (SSQ) method for determining pulmonary involvement in computed tomography (CT) scans of COVID-19 patients. The extent of lung involvement in the first available CT was assessed with the SSQ method and subjectively. We identified risk factors for the need of invasive ventilation, intensive care unit (ICU) admission and for time to death after infection. Additionally, the diagnostic performance of both methods was evaluated. With the SSQ method, a 10% increase in the affected lung area was found to significantly increase the risk for need of ICU treatment with an odds ratio (OR) of 1.68 and for invasive ventilation with an OR of 1.35. Male sex, age, and pre-existing chronic lung disease were also associated with higher risks. A larger affected lung area was associated with a higher instantaneous risk of dying (hazard ratio (HR) of 1.11) independently of other risk factors. SSQ measurement was slightly superior to the subjective approach with an AUC of 73.5% for need of ICU treatment and 72.7% for invasive ventilation. SSQ assessment of the affected lung in the first available CT scans of COVID-19 patients may support early identification of those with higher risks for need of ICU treatment, invasive ventilation, or death

Feasibility of a complex optimized process for the treatment of patients receiving hip and knee endoprostheses in most different settings in Germany : results from the PROMISE Trial

Background: While there is evidence on the effectiveness of optimized treatment processes for patients receiving hip and knee endoprostheses, feasibility in various settings has not been adequately investigated. The multicenter PROMISE Trial (Process optimization by interdisciplinary and cross-sectoral care using the example of patients with hip and knee prostheses) was set up to fill this gap. Methods: A complex optimized process was implemented in three German hospitals offering different levels of care and five cooperating rehabilitation centers. For the feasibility question, data on 19 parameters characterizing the defined process were collected. The extent of cross-sectoral collaboration was a special focus. Results: The data show, for almost all parameters in all facilities, an implementation rate of more than 80% with missing data below 5%, n = 1887 study participants. A total of 96.8% attended a rehabilitation program, and for 29.2% rehabilitation took place in a PROMISE-collaborating facility. Conclusions: Adherence to the defined and well-documented process was very high in all three organizationally very different hospitals, so that feasibility is given and transferability of the concept can be assumed. An exception was the targeted integration of rehabilitation into the treatment process. The goal of cross-sectoral networking could only be partially achieved

Submillisievert chest CT in patients with COVID-19 - experiences of a German Level-I center

Purpose: Computed tomography (CT) is used for initial diagnosis and therapy monitoring of patients with coronavirus disease 2019 (COVID-19). As patients of all ages are affected, radiation dose is a concern. While follow-up CT examinations lead to high cumulative radiation doses, the ALARA principle states that the applied dose should be as low as possible while maintaining adequate image quality. The aim of this study was to evaluate parameter settings for two commonly used CT scanners to ensure sufficient image quality/diagnostic confidence at a submillisievert dose. Materials and methods: We retrospectively analyzed 36 proven COVID-19 cases examined on two different scanners. Image quality was evaluated objectively as signal-to-noise ratio (SNR)/contrast-to-noise ratio (CNR) measurement and subjectively by two experienced, independent readers using 3-point Likert scales. CT dose index volume (CTDIvol) and dose-length product (DLP) were extracted from dose reports, and effective dose was calculated. Results: With the tested parameter settings we achieved effective doses below 1 mSv (median 0.5 mSv, IQR: 0.2 mSv, range: 0.3−0.9 mSv) in all 36 patients. Thirty-four patients had typical COVID-19 findings. Both readers were confident regarding the typical COVID-19 CT-characteristics in all cases (3 ± 0). Objective image quality parameters were: SNRnormal lung: 17.0 ± 5.9, CNRGGO/normal lung: 7.5 ± 5.0, and CNRconsolidation/normal lung: 15.3 ± 6.1. Conclusion: With the tested parameters, we achieved applied doses in the submillisievert range, on two different CT scanners without sacrificing diagnostic confidence regarding COVID-19 findings

Complement in Renal Disease as a Potential Contributor to Arterial Hypertension

Objective: Complement deposition is prevalent in kidney biopsies of patients with arterial hypertension and hypertensive nephropathy, but an association of hypertension and complement deposition or involvement of complement in the pathogenesis of hypertensive nephropathy has not been shown to date. Methods: In this study, we analyzed complement C1q and C3c deposition in a rat model of overload and hypertension by subtotal nephrectomy (SNX) and in archival human renal biopsies from 217 patients with known hypertension and 91 control patients with no history of hypertension using semiquantitative scoring of C1q and C3c immunohistochemistry and correlation with parameters of renal function. To address whether complement was only passively deposited or actively expressed by renal cells, C1q and C3 mRNA expression were additionally analyzed. Results: Glomerular C1q and C3c complement deposition were significantly higher in kidneys of hypertensive SNX rats and hypertensive compared to nonhypertensive patients. Mean arterial blood pressure (BP) in SNX rats correlated well with the amount of glomerular C1q and C3c deposition and with left ventricular weight, as an indirect parameter of high BP. Quantitative mRNA analysis showed that C3 was not only deposited but also actively produced by glomerular cells of hypertensive SNX rats and in human renal biopsies. Of note, in patients CKD-stage correlated significantly with the intensity of glomerular C3c staining, but not with that of C1q. Conclusion: Renal complement deposition correlated with experimental hypertension as well as the presence of hypertension in a variety of renal diseases. To answer the question, if and how exactly renal complement is causative for the pathogenesis of arterial hypertension in men, further studies are needed

A 68 ka precipitation record from the hyperarid core of the Atacama Desert in northern Chile

[Abstract] The Atacama Desert in northern Chile is one of the driest deserts on Earth. Hyperaridity persists at least since the Miocene and was punctuated by pluvial phases. However, very little is known about the timing, regional spread and intensities of precipitation changes. Here, we present a new precipitation record from a sedimentary sequence recovered in a tectonically blocked endorheic basin that is located in the hyperarid core of the Atacama Desert. The chronostratigraphic framework of the record is given by a multi-disciplinary dating approach, suggesting an age of ca. 68 ka BP for the core base. The sequence consists of three sediment types, whose sedimentological and geochemical characteristics suggest different depositional processes that reflect different degrees in humidity. First, particularly fine-grained sediments with high clastic but low calcium sulfate and carbonate contents reflect a particularly dry climate with only sporadic precipitation events and fluvial supply via channel systems. Second, more coarse-grained sediments with lower clastic and higher calcium sulfate and carbonate contents reflect more moist conditions with stronger precipitation events that lead to fluvial activity not restricted to the channels but involving the slopes and plains in the catchment. Third, normally graded layers with an equally high proportion of calcium sulfate and carbonate reflect occasional high-precipitation events that caused sediment supply also from most distant parts of the catchment via severe flash floods. The sedimentary succession suggests that precipitation changes took place on orbital but also on millennial time scales. Rather moist periods occurred during most of MIS 2, several shorter periods within MIS 3 and parts of MIS 4. Comparison of the findings from the Huara record with selected climate records from continental and marine sites in South America suggests a strong precipitation heterogeneity across the Atacama. This heterogeneity is caused by pronounced differences in the dominating climate patterns and a shift from predominant summer rain in the north to winter rain in the south. Precipitation supply to the Huara clay plan is controlled by the atmospheric circulation rather than the surface temperature of the adjacent ocean

Prognostic Value of Homotypic Cell Internalization by Nonprofessional Phagocytic Cancer Cells

Background. In this study, we investigated the prognostic role of homotypic tumor cell cannibalism in different cancer types. Methods. The phenomenon of one cell being internalized into another, which we refer to as “cell-in-cell event,” was assessed in 416 cases from five head and neck cancer cohorts, as well as one anal and one rectal cancer cohort. The samples were processed into tissue microarrays and immunohistochemically stained for E-cadherin and cleaved caspase-3 to visualize cell membranes and apoptotic cell death. Results. Cell-in-cell events were found in all of the cohorts. The frequency ranged from 0.7 to 17.3 cell-in-cell events per mm2. Hardly any apoptotic cells were found within the cell-in-cell structures, although apoptotic cell rates were about 1.6 to two times as high as cell-in-cell rates of the same tissue sample. High numbers of cell-in-cell events showed adverse effects on patients’ survival in the head and neck and in the rectal cancer cohorts. In multivariate analysis, high frequency was an adverse prognostic factor for overall survival in patients with head and neck cancer (p=0.008). Conclusion. Cell-in-cell events were found to predict patient outcomes in various types of cancer better than apoptosis and proliferation and might therefore be used to guide treatment strategies

Strain specific differences in vitamin D3 response: impact on gut homeostasis

Vitamin D3 regulates a variety of biological processes irrespective of its well-known importance for calcium metabolism. Epidemiological and animal studies indicate a role in immune regulation, intestinal barrier function and microbiome diversity. Here, we analyzed the impact of different vitamin D3- containing diets on C57BL/6 and BALB/c mice, with a particular focus on gut homeostasis and also investigated effects on immune cells in vitro. Weak regulatory effects were detected on murine T cells. By trend, the active vitamin D3 metabolite 1,25-dihydroxyvitamin D3 suppressed IFN, GM-CSF and IL-10 cytokine secretion in T cells of C57BL/6 but not BALB/c mice, respectively. Using different vitamin D3-fortified diets, we found a tissue–specific enrichment of mainly CD11b+ myeloid cells but not T cells in both mouse strains e.g. in spleen and Peyer’s Patches. Mucin Reg3γ and Batf expression, as well as important proteins for gut homeostasis, were significantly suppressed in the small intestine of C57BL76 but not BALB/c mice fed with a high-vitamin D3 containing diet. Differences between both mouse stains were not completely explained by differences in vitamin D3 receptor expression which was strongly expressed in epithelial cells of both strains. Finally, we analyzed gut microbiome and again an impact of vitamin D3 was detected in C57BL76 but not BALB/c. Our data suggest strain-specific differences in vitamin D3 responsiveness under steady state conditions which may have important implications when choosing a murine disease model to study vitamin D3 effects