Prior Thrombectomy Does Not Affect the Surgical Complication Rate of Decompressive Hemicraniectomy in Patients with Malignant Ischemic Stroke.

BACKGROUND: Even though mechanical recanalization techniques have dramatically improved acute stroke care since the pivotal trials of decompressive hemicraniectomy for malignant courses of ischemic stroke, decompressive hemicraniectomy remains a mainstay of malignant stroke treatment. However, it is still unclear whether prior thrombectomy, which in most cases is associated with application of antiplatelets and/or anticoagulants, affects the surgical complication rate of decompressive hemicraniectomy and whether conclusions derived from prior trials of decompressive hemicraniectomy are still valid in times of modern stroke care. METHODS: A total of 103 consecutive patients who received a decompressive hemicraniectomy for malignant middle cerebral artery infarction were evaluated in this retrospective cohort study. Surgical and functional outcomes of patients who had received mechanical recanalization before surgery (thrombectomy group, n = 49) and of patients who had not received mechanical recanalization (medical group, n = 54) were compared. RESULTS: The baseline characteristics of the two groups did significantly differ regarding preoperative systemic thrombolysis (63.3% in the thrombectomy group vs. 18.5% in the medical group, p < 0.001), the rate of hemorrhagic transformation (44.9% vs. 24.1%, p = 0.04) and the preoperative Glasgow Coma Score (median of 7 in the thrombectomy group vs. 12 in the medical group, p = 0.04) were similar to those of prior randomized controlled trials of decompressive hemicraniectomy. There was no significant difference in the rates of surgical complications (10.2% in the thrombectomy group vs. 11.1% in the medical group), revision surgery within the first 30 days after surgery (4.1% vs. 5.6%, respectively), and functional outcome (median modified Rankin Score of 4 at 5 and 14 months in both groups) between the two groups. CONCLUSIONS: A prior mechanical recanalization with possibly associated systemic thrombolysis does not affect the early surgical complication rate and the functional outcome after decompressive hemicraniectomy for malignant ischemic stroke. Patient characteristics have not changed significantly since the introduction of mechanical recanalization; therefore, the results from former large randomized controlled trials are still valid in the modern era of stroke care.

High-performance cavity-dumped Q-switched Alexandrite laser CW diode-pumped in double-pass configuration.

We present a high-performance Alexandrite laser for LIDAR applications with repetition rates up to 20 kHz in cavity-dumped Q-switched operation continuous-wave diode-pumped in the red spectral region. With a double-pass pump configuration, short pulses with 2.8 ns duration at repetition frequencies ranging from 1 kHz to 20 kHz could be demonstrated. At 5 kHz a - to our knowledge - record pulse energy of over 500 µJ could be achieved at 755 nm in TEM00. Furthermore, a stability measurement at an energy of around 350 µJ with 5 kHz showed no degradation over 150 Mega-shots. The influence of the crystal temperature on the laser performance is also investigated, first in continuous-wave and secondly in cavity-dumped Q-switched operation.

Three-dimensional nanothermometry below the diffraction limit.

Lanthanide-doped nanothermometers are used to measure temperature through changes in their emission characteristic with sensitivities of up to a few %/K. In contrast to their sensitivity, their spatial resolution, which is of critical importance for various applications, has not been thoroughly studied and optimized. We numerically investigated the improvement in spatial resolution of nanothermometers with a stimulated emission depletion microscopy approach. Fundamental relationships between spatial and temperature resolution were identified by using different beam parameters for the excitation and depletion beams. Our simulations predict contactless temperature measurement below the diffraction limit with temperature resolution of ±1.25K. We further studied the influence of sample thickness and position on both temperature and spatial resolution and showed the potential of three-dimensional measurements.

Cerebrovascular Autoregulation Monitoring in the Management of Adult Severe Traumatic Brain Injury: A Delphi Consensus of Clinicians.

BACKGROUND: Several methods have been proposed to measure cerebrovascular autoregulation (CA) in traumatic brain injury (TBI), but the lack of a gold standard and the absence of prospective clinical data on risks, impact on care and outcomes of implementation of CA-guided management lead to uncertainty. AIM: To formulate statements using a Delphi consensus approach employing a group of expert clinicians, that reflect current knowledge of CA, aspects that can be implemented in TBI management and CA research priorities. METHODS: A group of 25 international academic experts with clinical expertise in the management of adult severe TBI patients participated in this consensus process. Seventy-seven statements and multiple-choice questions were submitted to the group in two online surveys, followed by a face-to-face meeting and a third online survey. Participants received feedback on average scores and the rationale for resubmission or rephrasing of statements. Consensus on a statement was defined as agreement of more than 75% of participants. RESULTS: Consensus amongst participants was achieved on the importance of CA status in adult severe TBI pathophysiology, the dynamic non-binary nature of CA impairment, its association with outcome and the inadvisability of employing universal and absolute cerebral perfusion pressure targets. Consensus could not be reached on the accuracy, reliability and validation of any current CA assessment method. There was also no consensus on how to implement CA information in clinical management protocols, reflecting insufficient clinical evidence. CONCLUSION: The Delphi process resulted in 25 consensus statements addressing the pathophysiology of impaired CA, and its impact on cerebral perfusion pressure targets and outcome. A research agenda was proposed emphasizing the need for better validated CA assessment methods as well as the focused investigation of the application of CA-guided management in clinical care using prospective safety, feasibility and efficacy studies.

Chondrocalcinosis is associated with increased knee joint degeneration over 4 years: data from the Osteoarthritis Initiative.

OBJECTIVE: To determine if presence of calcium-containing crystals (CaC) is associated with increased knee joint degeneration over 4 years and assess if total number of CaCs deposited is a useful measure of disease burden. DESIGN: Seventy subjects with CaCs in right knees at baseline were selected from the Osteoarthritis Initiative and matched to 70 subjects without evidence of CaCs. T1-weighted gradient-echo sequences were used to confirm presence of CaCs and count the numbers of distinct circumscribed CaCs. Morphological abnormalities were assessed at baseline and 4-year follow-up using the modified semi-quantitative Whole-Organ Magnetic Resonance Imaging Score (WORMS). Linear regression models were used to analyze the associations between presence of CaCs at baseline and changes in WORMS and to analyze the associations between numbers of circumscribed CaCs at baseline and changes in WORMS. RESULTS: Presence of CaCs was associated with increased cartilage degeneration in the patella (coefficient: 0.33; 95% confidence interval (CI): 0.04-0.63), the medial femur (coefficient: 0.51; 95% CI: 0.18-0.83), the lateral tibia (coefficient: 0.36; 95% CI: 0.01-0.71) as well as the medial and lateral meniscus (coefficient: 0.38; 95% CI: 0.00-0.75 and coefficient: 0.72; 95% CI: 0.12-1.32). Knees with higher numbers of CaCs had increased cartilage degeneration in the patella and medial femur (coefficient: 0.09; 95% CI: 0.05-0.14; P < 0.001 and coefficient: 0.08; 95% CI: 0.02-0.14; P = 0.005). CONCLUSIONS: CaCs were associated with increased cartilage and meniscus degeneration over a period of 4 years. Assessing the number of CaC depositions may be useful to evaluate risk of onset and worsening of degenerative disease.

Experimental and numerical study of interlock requirements for high-power EYDFAs.

In this work, we studied the interlock requirements in a seed failure scenario for Er3+:Yb3+ doped fiber amplifiers (EYDFAs) pumped with high intensities in the MWcm-2 range at 9XX nm. We fed a time-dependent FEM-tool with the data from backwards directed amplified spontaneous emission (ASE) transients of different commercially available core-pumped single-mode fibers. In the FEM-tool, the Er3+:Yb3+ system is defined as a bi-directional energy transfer process and described by the corresponding rate equations. The power evolution of the pump, seed, and ASE signal is computed by differential equations taking into account the transient population densities of the relevant energy levels. With the model, we computed the temporal evolution of the corresponding energy levels after a seeder failure to take place within tens to hundreds of µs and calculated the associated gain. The fibers under test provide a critical total gain of 30 dB after ∼ 80 µs within the Yb3+ band and after ∼300 µs within the Er3+ band. This time decreases with increasing pump power and doping concentration. The results can be extrapolated to high-power cladding-pumped EYDFAs to meet the challenging requirements of engineering-level systems.

[Suicidality in adolescents with therapy refractory internalising behaviour]. / Suïcidaliteit bij adolescenten met therapieresistente internaliserende problematiek.

BACKGROUND: Suicidality in adolescence is increasingly becoming a societal problem, especially because there remains a small group of patients in which treatment effectiveness is small. Existing formal guidelines often are of limited value in this group that often shows complex comorbidity.
AIM: To contribute to the diagnostic and aetiological perspective in order to better understand therapy refractory internalising behaviour.
METHOD: Integration of several scientific theoretical concepts into a holistic model.
RESULTS: Evidence shows that suicidality should be considered within a broader scope of therapy refractory internalising behaviour. Important underpinnings comprise a partially overprotective parenting style, disturbed attachment processes and social anxiety. Internalising and externalising behaviour problems are viewed as expressions of avoidance behaviour. Furthermore, we discuss important implications for treatment.
CONCLUSION: Applying an aetiological model for therapy refractory internalising behaviour may help to increase efficacy of treatment. Thus, transdiagnostic treatment can be offered, being less dependent on specific dsm-classifications. Focus of treatment is on restoration of basic trust between the youngster and his parents, and on ending avoidance behaviour that is based on social anxiety.

Initial Characterization of Transgenic Mice Overexpressing Human Histamine H2 Receptors.

In an integrative approach, we studied the role of histamine H2 receptors in the mouse heart. We noted that histamine, added cumulatively to the organ bath, failed to affect the force of contraction in left atrial preparations and did not change spontaneous heart rate in right atrial preparations from wild-type mice. By contrast, in the same preparations from mice that overexpressed the human H2 receptor in a cardiac-specific way, histamine exerted concentration- and time-dependent positive inotropic and positive chronotropic effects. Messenger RNA of the human H2 receptor was only detected in transgenic mice. Likewise, immunohistology and autoradiography only gave signals in transgenic but not in wild-type cardiac preparations. Similarly, a positive inotropic and positive chronotropic effect was observed with histamine in echocardiography of living transgenic mice and isolated perfused hearts (Langendorff preparation). Phosphorylation of phospholamban was increased in atrial and ventricular preparations from transgenic mice, but not in wild-type animals. The effects of histamine were mimicked by dimaprit and amthamine and antagonized by cimetidine. In summary, we generated a new model to study the physiologic and pathophysiologic cardiac role of the human H2 receptor.

3D bone-shape changes and their correlations with cartilage T1ρ and T2 relaxation times and patient-reported outcomes over 3-years after ACL reconstruction.

PURPOSE: (1) To identify bone-shape changes from baseline to 3-years after anterior cruciate ligament reconstruction (ACLR). (2) to assess association between changes in bone-shape from baseline to 6-months and changes in cartilage matrix and patient functions and symptoms from baseline to 3-years after ACLR. METHODS: Bilateral knees of 30 patients with unilateral ACL injuries were scanned at baseline, 6-months, 1-, 2-, and 3-years after ACLR. Bilateral knees of 13 controls were scanned at baseline, 1- and 3-years. Mean T1ρ and T2 values of each cartilage compartment were computed. Bone shape was quantified using statistical shape modeling (SSM) and 3D-MRI. Patient functions and symptoms were evaluated using Knee Injury and Osteoarthritis Outcome Score (KOOS). RESULTS: Statistically significant changes were observed in Femur 2 (medial femoral condyle [MF] shape), Femur 6 (intercondylar notch width), Tibia 1 (tibia plateau area), and Tibia 7 (medial tibia slope) over 3-years after ACLR. Statistically significant differences were observed between injured and control knees in several modes. Statistically significant correlations were found between changes in bone shape (ΔFemur 6, ΔFemur 8 [trochlea inclination and MF height], ΔTibia 1) from baseline to 6-months and that of cartilage T1ρ and T2 and KOOS from baseline to 3-years after ACLR. CONCLUSION: Bone shape remodeling occurs after ACLR, and early bone shape changes (within 6 months) correlated with cartilage matrix and patient outcomes at 3-years after ACLR. Bone shape can be a promising imaging biomarker that stratifies patients at high risk for post-traumatic osteoarthritis (PTOA).

[Malignant tumors of the skull base]. / Maligne Tumoren der Schädelbasis.

Malignant skull base tumors consist of a heterogeneous group of malignancies that can be divided into primary and secondary (metastatic) skull base tumors. In addition, according their anatomical location, they can be further divided into tumors of the anterior, middle, or posterior cranial fossa. Although malignant skull base tumors do not rigorously respect anatomical borders, their anatomical occurrence can potentially be helpful for possible differential diagnosis. This article is focused on the most common malignant tumors of the skull base and their imaging and clinical presentations.

Forewarning of hypotensive events using a Bayesian artificial neural network in neurocritical care.

Traumatically brain injured (TBI) patients are at risk from secondary insults. Arterial hypotension, critically low blood pressure, is one of the most dangerous secondary insults and is related to poor outcome in patients. The overall aim of this study was to get proof of the concept that advanced statistical techniques (machine learning) are methods that are able to provide early warning of impending hypotensive events before they occur during neuro-critical care. A Bayesian artificial neural network (BANN) model predicting episodes of hypotension was developed using data from 104 patients selected from the BrainIT multi-center database. Arterial hypotension events were recorded and defined using the Edinburgh University Secondary Insult Grades (EUSIG) physiological adverse event scoring system. The BANN was trained on a random selection of 50% of the available patients (n = 52) and validated on the remaining cohort. A multi-center prospective pilot study (Phase 1, n = 30) was then conducted with the system running live in the clinical environment, followed by a second validation pilot study (Phase 2, n = 49). From these prospectively collected data, a final evaluation study was done on 69 of these patients with 10 patients excluded from the Phase 2 study because of insufficient or invalid data. Each data collection phase was a prospective non-interventional observational study conducted in a live clinical setting to test the data collection systems and the model performance. No prediction information was available to the clinical teams during a patient's stay in the ICU. The final cohort (n = 69), using a decision threshold of 0.4, and including false positive checks, gave a sensitivity of 39.3% (95% CI 32.9-46.1) and a specificity of 91.5% (95% CI 89.0-93.7). Using a decision threshold of 0.3, and false positive correction, gave a sensitivity of 46.6% (95% CI 40.1-53.2) and specificity of 85.6% (95% CI 82.3-88.8). With a decision threshold of 0.3, > 15 min warning of patient instability can be achieved. We have shown, using advanced machine learning techniques running in a live neuro-critical care environment, that it would be possible to give neurointensive teams early warning of potential hypotensive events before they emerge, allowing closer monitoring and earlier clinical assessment in an attempt to prevent the onset of hypotension. The multi-centre clinical infrastructure developed to support the clinical studies provides a solid base for further collaborative research on data quality, false positive correction and the display of early warning data in a clinical setting.

Longitudinal changes in MR T1ρ/T2 signal of meniscus and its association with cartilage T1p/T2 in ACL-injured patients.

OBJECTIVE: To evaluate the longitudinal changes in meniscal T1ρ/T2 signal post-reconstruction in patients with acute anterior cruciate ligament (ACL) injury and to investigate the association with T1ρ/T2 signal in articular knee cartilage. METHOD: In this prospective study, knees of 37 patients with ACL-injury and reconstruction in addition to 13 healthy controls were scanned using magnetic resonance imaging (MRI) T1ρ/T2 mapping. Quantitative analysis of the meniscus was performed in the anterior/posterior horns of lateral/medial meniscus fourteen sub-compartments of cartilage spanning the medial/lateral area of the tibia and femoral condyles. Meniscus T1ρ/T2 signals were compared between injured, contralateral and control knees at baseline, 6-months, 1-year and 2-years using t-tests for cross-sectional comparisons and a mixed model for longitudinal comparisons. Pearson-partial correlations between meniscal and cartilage T1ρ/T2 were evaluated. RESULTS: There was a significant decrease of T1ρ/T2 signal in the posterior horn of lateral meniscus (PHLAT) of injured knees during a 2-year period. In the posterior horn of medial meniscus (PHMED), T1ρ/T2 signal of injured knees was significantly elevated at all time points post-reconstruction compared to contralateral and control knees. Within injured knees, PHMED T1ρ/T2 signal showed significant positive correlations with medial tibia (MT) cartilage T1ρ/T2 signal at all time points. CONCLUSION: A significant decrease in PHLAT T1ρ/T2 signal by 2-years suggests potential tissue recovery after ACL-injury. Elevated T1ρ/T2 signal in the PHMED of injured knees at 2-years correlating with knee cartilage T1ρ/T2 signal elevations suggests involvement of the PHMED in subacute cartilage degeneration after ACL-injury and reconstruction.

Associations between molecular biomarkers and MR-based cartilage composition and knee joint morphology: data from the Osteoarthritis Initiative.

OBJECTIVE: The purpose of this study was to assess the associations between serum/urine biomarkers for osteoarthritis and magnetic resonance (MR) imaging measures of cartilage composition and joint structure (cartilage, meniscus, and bone marrow), using MR imaging data from the Osteoarthritis Initiative (OAI). DESIGN: 141 subjects with Kellgren Lawrence (KL) grades 0-3 in the right knee and with available serum/urine biomarker assays were selected from the OAI. Cartilage magnetic resonance imaging (MRI) T2 measurements were performed in the medial femur, lateral femur, medial tibia, lateral tibia, and patella compartments. Compartment-specific knee morphologic grading [whole-organ magnetic resonance imaging score (WORMS)] in the cartilage, meniscus, and bone marrow was also performed. We focused on associations of serum hyaluronan (sHA), serum cartilage oligomeric matrix protein (sCOMP), serum matrix metalloproteinase-3 (sMMP3), and Urine Carboxy-Terminal Telepeptides of Type II Collagen (uCtX-II)) with MRI parameters (T2, WORMS), assessed using partial correlations adjusted for age, gender, body mass index (BMI), KL grade in both knees, and diabetes status. RESULTS: Higher levels of sHA, sMMP3 and sCOMP were correlated (P < 0.05) with T2 of the lateral femur (r = 0.18 to 0.32) and lateral tibia (r = 0.17 to 0.23), and with average T2 of all knee regions (r = 0.23). uCTXII was correlated with patellar T2 (r = 0.19, P = 0.04). Among the morphologic measures, sHA and sMMP3 was positively correlated (r = 0.17 to 0.21, P < 0.05) with meniscal damage. CONCLUSIONS: This study suggests weak, but statistically significant, correlations between serum biomarkers of OA (sHA, sCOMP, and sMMP3) and MRI T2 measures of cartilage extra-cellular matrix degeneration.

Type 2 diabetes patients have accelerated cartilage matrix degeneration compared to diabetes free controls: data from the Osteoarthritis Initiative.

PURPOSE: Osteoarthritis (OA) and diabetes mellitus (DM) share common risk factors with a potential underlying relationship between both diseases. The purpose of this study was to investigate the longitudinal effects of DM on cartilage deterioration over 24-months with MR-based T2 relaxation time measurements. METHODS: From the Osteoarthritis Initiative (OAI) cohort 196 diabetics were matched in small sets for age, sex, BMI and Kellgren-Lawrence score with 196 non-diabetic controls. Knee cartilage semi-automatic segmentation was performed on 2D multi-slice multi-echo spin-echo sequences. Texture of cartilage T2 maps was obtained via grey level co-occurrence matrix analysis. Linear regression analysis was used to compare cross-sectional and changes in T2 and texture parameters between the groups. RESULTS: Both study groups were similar in age (63.3 vs 63.0 years, P = 0.70), BMI (30.9 vs 31.2 kg/m2, P = 0.52), sex (female 53.6% vs 54.1%, P = 0.92) and KL score distribution (P = 0.97). In diabetics, except for the patella, all compartments showed a significantly higher increase in mean T2 values when compared to non-diabetic controls. Global T2 values increased almost twice as much; 1.77ms vs 0.98ms (0.79ms [CI: 0.39,1.19]) (P < 0.001). Additionally, global T2 values showed a significantly higher increase in the bone layer (P = 0.006), and in a separate analysis of the texture parameters, diabetics also showed consistently higher texture values (P < 0.05), indicating a more disordered cartilage composition. CONCLUSION: Cartilage T2 values in diabetics show a faster increase with a consistently more heterogeneous cartilage texture composition. DM seems to be a risk factor for developing early OA with an accelerated degeneration of the articular cartilage in the knee.

Current treatment procedures for civilian gunshot wounds.

INTRODUCTION: This work provides an overview of the incidence of gunshot wounds during peace conditions in a civilian population and aims to assess the principles of their treatment. METHOD: We evaluated a total of 104 patients with gunshot wounds with an average age of 38.7 years (range 1871). 84 men (80.8%) and 20 women (19.2%) were involved. The head was affected 7 times (6.7%). Out of those, penetrating injury occurred only once (1.0%). The throat was hit three times (2.9%). The chest was injured 15 times (14.4%), penetrating injury at this site was observed in 10 cases (9.6%). In five cases the lungs were affected and the heart once. Gastric injury occurred 13 times, penetration into the peritoneal cavity occurred seven times (6.7%). The intestine was injured five times, the liver three times and the gall-bladder once. Limb injury was present in 66 (63.5%) cases and in 19 of those, the injury was associated with a fracture. In 50 cases (48.1%), the patient was attacked by another person. 45 patients (43.3%) injured themselves unintentionally, five patients (4.8%) were injured in a suicidal attempt and four (3.8%) were accidentally shot by someone else. The weapons used were: pistol in 57 (54.8%) cases, air rifle in 20 cases (19.2%), a rifle in 10 cases (9.6%), two patients (1.9%) were injured with a detonator and one (1.0%) with an assault rifle. In 14 cases (13.5%), the type of firearm used was not established. RESULTS: Surgical treatment was indicated in all cases. The first step was always a thorough wound irrigation. Single surgical treatment was performed in 48 cases (46.2%) while the other 56 patients (53.8%) required multiple surgeries. Specialized surgical procedures were performed in a total of 30 cases: seven laparotomies, five thoracotomies, five fracture stabilizations using external fixator, four amputations of limbs, two intramedullary osteosyntheses, two stabilizations with the use of Kirchner wires, two vascular surgeries, one craniotomy and one suture of a peripheral nerve. Complications of healing were not frequent: wound infection was observed in two cases (1.9%), wound dehiscence in one case (1.0%), osteomyelitis in two cases (1.9%), nonunion of the fracture (1.0 %) occurred once and in one case (1.0%), pulmonary embolism was diagnosed which was not fatal. CONCLUSION: Consistent debridement, fasciotomy, and complete drainage of the wound are only indicated in deep gunshot wounds. A surgical revision of the abdominal cavity is indicated for all penetrating abdominal gunshot injuries. The watch-and-wait approach with surgical wound management and hospitalization is only allowed for unambiguously non-penetrating abdominal injuries. Complications of gunshot wound healing in civilian settings are not common and are most often infectious. Key words: gunshot wound - civilian settings surgical treatment.

Influence of mRNA expression of epiregulin and amphiregulin on outcome of patients with metastatic colorectal cancer treated with 5-FU/LV plus irinotecan or irinotecan plus oxaliplatin as first-line treatment (FIRE 1-trial).

Our aim was to investigate the impact of EREG and AREG mRNA expression (by RT-qPCR) in patients with metastatic colorectal cancer (mCRC). In addition, epidermal growth factor receptor (EGFR) expression (by immunohistochemistry) as well as RAS-and PIK3CA-mutations (by pyrosequencing) were assessed. Tumors of 208 mCRC patients receiving 5-fluorouracil/leucovorin plus irinotecan (FUFIRI) or irinotecan plus oxaliplatin (mIROX) within the FIRE-1 trial were analyzed for mutations. Molecular characteristics were correlated with response, progression-free survival (PFS), overall survival (OS). mRNA expression was evaluated using ROC-analysis in 192 tumors (AREG high n = 31 vs. low n = 161; EREG high n = 89 vs. low n = 103). High versus low AREG expression was associated with PFS of 10.0 versus 8.0 months (HR = 0.62, 95% CI: 0.402-0.940, p = 0.03) and OS of 24.6 versus 18.7 months (HR = 0.72, 95% CI: 0.476-1.078, p = 0.11). High versus low EREG expression correlated with prolonged PFS (9.4 vs. 6.8 months, HR = 0.62, 95% CI: 0.460-0.846, p = 0.002) and OS (25.8 vs. 15.5 months, HR = 0.48, 95% CI: 0.351-0.657, p < 0.001). The positive prognostic effect of high EREG expression was confirmed in a multivariate analysis and was neither affected by EGFR expression nor by mutations of RAS- and PIK3CA-genes. EREG expression appears as an independent prognostic marker in patients with mCRC receiving first-line irinotecan-based chemotherapy.

Should ALPPS be Used for Liver Resection in Intermediate-Stage HCC?

BACKGROUND: Extended liver resections in patients with hepatocellular carcinoma (HCC) are problematic due to hepatitis, fibrosis, and cirrhosis. Associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) has been promoted as a novel method to induce hypertrophy for patients with extensive colorectal liver metastases, but outcomes in HCC have not been well investigated. METHODS: All patients registered in the international ALPPS Registry ( www.alpps.org ) from 2010 to 2015 were studied. Hypertrophy of the future liver remnant, perioperative morbidity and mortality, age, overall survival, and other parameters were compared between patients with HCC and patients with colorectal liver metastases (CRLM). RESULTS: The study compared 35 patients with HCC and 225 patients with CRLM. The majority of patients undergoing ALPPS for HCC fall into the intermediate-stage category of the Barcelona clinic algorithm. In this study, hypertrophy was rapid and extensive for the HCC patients, albeit lower than for the CRLM patients (47 vs. 76 %; p < 0.002). Hypertrophy showed a linear negative correlation with the degrees of fibrosis. The 90-day mortality for ALPPS used to treat HCC was almost fivefold higher than for CRLM (31 vs. 7 %; p < 0.001). Multivariate analysis showed that patients older than 61 years had a significantly reduced overall survival (p < 0.004). CONCLUSION: The ALPPS approach induces a considerable hypertrophic response in HCC patients and allows resection of intermediate-stage HCC, albeit at the cost of a 31 % perioperative mortality rate. The use of ALPPS for HCC remains prohibitive for most patients and should be performed only for a highly selected patient population younger than 60 years with low-grade fibrosis.

Validating new diagnostic imaging criteria for primary progressive aphasia via anatomical likelihood estimation meta-analyses.

Recently, diagnostic clinical and imaging criteria for primary progressive aphasia (PPA) have been revised by an international consortium (Gorno-Tempini et al. Neurology 2011;76:1006-14). The aim of this study was to validate the specificity of the new imaging criteria and investigate whether different imaging modalities [magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET)] require different diagnostic subtype-specific imaging criteria. Anatomical likelihood estimation meta-analyses were conducted for PPA subtypes across a large cohort of 396 patients: firstly, across MRI studies for each of the three PPA subtypes followed by conjunction and subtraction analyses to investigate the specificity, and, secondly, by comparing results across MRI vs. FDG-PET studies in semantic dementia and progressive nonfluent aphasia. Semantic dementia showed atrophy in temporal, fusiform, parahippocampal gyri, hippocampus, and amygdala, progressive nonfluent aphasia in left putamen, insula, middle/superior temporal, precentral, and frontal gyri, logopenic progressive aphasia in middle/superior temporal, supramarginal, and dorsal posterior cingulate gyri. Results of the disease-specific meta-analyses across MRI studies were disjunct. Similarly, atrophic and hypometabolic brain networks were regionally dissociated in both semantic dementia and progressive nonfluent aphasia. In conclusion, meta-analyses support the specificity of new diagnostic imaging criteria for PPA and suggest that they should be specified for each imaging modality separately.

[Prognostic biomarkers for metastatic colorectal cancer]. / Prognostische Biomarker für das metastasierte kolorektale Karzinom.

In colorectal cancer (CRC) distant metastases essentially determine the overall survival and prognosis. Biomarkers that correlate with the presence of distant metastases are therefore of great clinical importance for risk stratification and clinical treatment decisions. As part of the habilitation project various prognostic biomarkers were analyzed and correlated with the occurrence of distant metastases and different patterns of distant spread in CRC. It could be demonstrated that CRC with microsatellite instability (MSI), as detected by a loss of hMLH1 protein expression, have a very low risk of distant metastases. In contrast, microsatellite stable (MSS) CRC (with positive hMLH1 expression) with concurrent activation of the Wnt-beta catenin signaling pathway and strong expression of the cancer stem cell marker CD133, exhibit a very high risk for liver metastases. From these observations a two-step immunohistochemical algorithm based on three immunohistochemical stains could be derived, allowing CRC to be classified according to the risk of distant metastases. Further studies demonstrated that a deregulation of the Wnt-beta catenin signaling pathway and the expression of cancer stem cell markers, such as CD133 and CD44 correlated with hematogenous metastasis to the liver but not with peritoneal carcinomatosis or hematogenous metastasis to the central nervous system (CNS). Finally, in CRC patients with CNS metastases, increased rates of mutations in the mitogen-activated protein kinases (MAPK) pathway (KRAS and BRAF mutations) in combination with a low beta catenin expression could be detected. It can be concluded from these results that for CRC with different patterns of distant spread alternative molecular mechanisms must play a role.

[Frequency, Cause, and Awareness of Pulmonary Embolism in Oncologic Patients]. / Die Lungenarterienembolie bei onkologischen Erkrankungen: Häufigkeit, Ursachen und Wahrnehmung.

The frequency of pulmonary embolism (PE) in oncologic patients ranges from 1.1 % to 7.3 % depending on whether not only symptomatic findings but also incidental and initially overseen events are considered. The frequency of PE is tumor-specific. Most frequently PE occurs in patients with malignancy of the ovary (25 %), pancreas, brain, uterus, and multiple myeloma. Most rarely is PE found in patients with malignancy of the testis (< 1 %).The tumor-specific frequency shows that the association of malignancy and PE is not equally true for alle malignancies. A number of arguments that support the above association are also valid in non-oncologic patients.The awareness of the diagnosing radiologist and the thrombus mass decide whether or not an unexpected PE is detected. An increased awareness is suggested in patients with malignancies with high PE frequency and in patients with advanced oncologic disease.